Objective: To investigate the mechanism of Yishen Tongluo Formula in ameliorating renal pyroptosis in diabetic nephropathy mice by regulating the toll-like receptor 4 (TLR4)/myeloid differentiation factor 88 (MyD88)/nuclear factor-κB (NF-κB) signaling pathway. Methods: Sixty C57BL/6 male mice were randomly divided into control (10 mice) and intervention groups (50 mice) using random number table method. The diabetes nephropathy model was established by intraperitoneally injecting streptozotocin(50 mg/kg). After modeling, the intervention group was further divided into model, semaglutide (40 μg/kg), and high-, medium-, and low-dose Yishen Tongluo Formula groups (15.6, 7.8, and 3.9 g/kg, respectively) using random number table method. The high-, medium-, and low-dose Yishen Tongluo Formula groups were administered corresponding doses of medication by gavage, the semaglutide group received a subcutaneous injection of semaglutide injection, and the control group and model groups were administered distilled water by gavage for 12 consecutive weeks. Random blood glucose levels of mice in each group were monitored, and the 24-h urinary protein content was measured using biochemical method every 4 weeks; after treatment, the serum creatinine and urea nitrogen levels were measured using biochemical method. The weight of the kidneys was measured, and the renal index was calculated. Hematoxylin and eosin, periodic acid-Schiff, periodic Schiff-methenamine, and Masson staining were used to observe the pathological changes in renal tissue. An enzyme-linked immunosorbent assay was used to detect urinary β2-microglobulin (β2-MG), neutrophil gelatinase-associated lipocalin (NGAL), and kidney injury molecule-1 (KIM-1) levels. Western blotting and real-time fluorescence PCR were used to detect the relative protein and mRNA expression levels of nucleotide-binding domain leucine-rich repeat and pyrin domain-containing receptor 3 (NLRP3), Caspase-1, gasdermin D (GSDMD), interleukin-1β (IL-1β), and interleukin-18 (IL-18) in renal tissue. Immunohistochemistry was used to detect the proportion of protein staining area of the TLR4, MyD88, and NF-κB in renal tissue. Results: Compared with the control group, the random blood glucose, 24-h urinary protein, serum creatinine, urea nitrogen, and renal index of the model group increased, and the urine β2-MG, NGAL, and KIM-1 levels increased. The relative protein and mRNA expression levels of NLRP3, Caspase-1, GSDMD, IL-1β, and IL-18 in renal tissue increased, and the proportion of TLR4, MyD88, and NF-κB protein positive staining areas increased (P<0.05). Pathological changes such as glomerular hypertrophy were observed in the renal tissue of the model group. Compared with the model group, the Yishen Tongluo Formula high-dose group showed a decrease in random blood glucose after 12 weeks of treatment (P<0.05). The Yishen Tongluo Formula high- and medium-dose groups showed a decrease in 24-h urinary protein, creatinine, urea nitrogen, and renal index, as well as decreased β2-MG, NGAL, and KIM-1 levels. NLRP3, Caspase-1, GSDMD, IL-1 β, and IL-18 relative protein and mRNA expression levels were also reduced, and the proportion of TLR4, MyD88, and NF-κB protein positive staining areas was reduced (P<0.05). Pathological damage to renal tissue was ameliorated. Conclusion Yishen Tongluo Formula may exert protective renal effects by inhibiting renal pyroptosis and alleviating tubular interstitial injury in diabetic nephropathy mice by regulating the TLR4/MyD88/NF-κB signaling pathway.

Objective:To evaluate the safety, feasibility, and technical advantages of the domestic Jingfeng single-port robotic surgical system in transoral and transaxillary approach surgeries for multisite diseases. Methods:A retrospective analysis was conducted on the clinical data of 6 patients who underwent Jingfeng SP1000 single-port robotic-assisted surgery at our hospital from June 2025 to July 2025. They were divided into the transoral robotic surgery group（4cases） and the transaxillary approach thyroid cancer radical resection group（2cases） based on surgical approaches. The transoral robotic surgery group included extended resection of right tonsillar cancer with cervical lymph node dissection, epiglottic cyst resection, extended resection of right pyriform sinus cancer with cervical lymph node dissection, and surgery for epiglottic cyst and obstructive sleep apnea（OSA）. For each case, parameters including operative time, intraoperative blood loss, perioperative complications, robotic operation performance, and postoperative recovery were recorded. Results:All 6 surgeries were successfully completed without conversion to open surgery or system failure. In the transoral robotic surgery group, the mean robotic operation time was（60.00±34.88） minutes, and the mean intraoperative blood loss was 20.00（5.75，20.00）mL. In the transaxillary robotic surgery group, the robotic operation time was respectively 60.00 and 40.00 minutes, and the intraoperative blood loss was 10.00 and 5.00 mL, respectively. One case of minor perioperative complication（in the flap dissection area） occurred, with no severe complications reported. All patients recovered smoothly after surgery, with a median follow-up of 1.9 months showing no residual lesions, recurrence, or functional impairment. Conclusion:This case series confirms the safety and feasibility of the domestic Jingfeng single-port robot in transoral and axillary approach surgeries in oropharyngeal-head and neck surgery. Its single-port design reduces trauma and the risk of robotic arm collision, adapts to minimally invasive needs, and its domestic production attribute lowers costs to facilitate popularization, providing a new option for such patients.
Humans ; Robotic Surgical Procedures/methods* ; Retrospective Studies ; Operative Time ; Middle Aged ; Male ; Female ; Neck/surgery* ; Sleep Apnea, Obstructive/surgery* ; Adult ; Head and Neck Neoplasms/surgery* ; Oropharynx/surgery* ; Oropharyngeal Neoplasms/surgery*

Objective: To explore the cross sectional and longitudinal associations between 24 hour movement behaviors and physical fitness in preschool children, and to adopt the method of equal time substitution analysis to evaluate the impact of time redistribution of different activity behaviors on physical fitness scores,so as to provide a scientific basis for promoting the health of preschool children. Methods: A total of 193 preschool children aged 3-6 years were selected from three Shanghai districts (Jing an, Baoshan, Jiading) from October to December 2023 by the stratified cluster random sampling method. The 24 hour movement behaviors were monitored via 7 day accelerometry, and physical fitness was measured according to the National Physical Fitness Measurement Standards (Revised 2023, preschool section). From October to December 2024, the follow up of physical fitness among preschool children used the same testing method. The comparison between groups was conducted by t-test. Compositional regression analyses evaluated the relationship of 24 hour movement behaviors and physical fitness among preschool children. Results: At baseline, moderate to vigorous physical activity (MVPA) time was significantly higher in boys [(84.10±25.78)min/d] than in girls [( 70.44± 25.98)min/d]; the composite physical fitness score was significantly higher in boys (71.65±8.69) than in girls (68.84±9.89), and the differences were statistically significant ( t =3.65, 2.10, both P <0.01). After adjusting for gender, age and body mass index, the results of component multiple linear regression analysis showed that MVPA time proportion was positively correlated with the composite physical fitness score at baseline among preschool children ( β =6.61), but was negatively correlated with two legged continuous hopping time at 1 year ( β =-1.12) (both P <0.05). Light physical activity (LPA) time proportion was negatively correlated with walking on the balance beam time at 1 year ( β =-4.44), and sedentary behavior (SB) time proportion was negatively correlated with the composite score of physical fitness at baseline ( β =-6.55) (both P <0.05). Isotemporal substitution analysis revealed that replacing 10 minutes of sleep (SP), SB, and LPA with MVPA increased the baseline physical fitness composite score by 0.750, 0.689 and 0.575 units, respectively; at 1 year follow up, the composite score increased by 1.440, 1.419 and 1.430 units, respectively (all P <0.05). Conversely, replacing MVPA with 10 minutes of SP, SB, and LPA,resulted in decreases in baseline physical fitness composite scores of 0.836, 0.777 and 0.669 units, and reductions of 1.613, 1.592 and 1.598 units at 1 year follow up (all P < 0.05 ). Conclusions Preschool children s 24 hour movement behaviors, especially MVPA, are closely related to physical health. Implementing appropriate strategies to increase physical activity and reduce sedentary time may improve the physical fitness of preschoolers.

OBJECTIVE To study the safety of Shuangshu decoction in rats and its efficacy in improving functional dyspepsia （FD） in rats. METHODS In safety test， 40 rats were divided into blank control group， Shuangshu decoction low-dose， medium- dose and high-dose groups [108， 216， 324 g/（kg·d）， calculated by raw medicine， the same applies below]； they were given relevant medicine intragastrically， for continuous 14 days. The mortality and toxic reactions of rats were recorded， and the organ indexes of the liver， kidney， spleen， lung and heart of rats were calculated； the pathological morphological changes in the liver， kidney， spleen， lung， heart， stomach， duodenum， and colon were observed to evaluate the acute toxicity of Shuangshu decoction. Another 40 rats were grouped and administered in the same way for 30 consecutive days. The mortality and toxic reactions of the rats were recorded， and the corresponding organ indexes were calculated. The pathological morphological changes in the corresponding organs were observed， and blood routine and serum biochemical indicators were measured， in order to assess the subacute toxicity of Shuangshu decoction. In pharmacodynamic experiments: 50 rats were divided into blank control group， model group， and Shuangshu decoction low-， medium-， and high-dose groups （9.45， 18.9， 37.8 g/kg）， with 10 rats in each group. Except for blank control group， rats in all other groups were used to establish the FD rat model by subcutaneous injection of loperamide （3.5 mg/kg）. Rats in each group were administered the corresponding drug solution/normal saline intragastrically， once a day， for 14 consecutive days. After the last medication， fecal moisture content， intestinal propulsion rate， gastric emptying rate and serum level of motilin were all detected， and interstitial cell of Cajal （ICC） ultrastructure of rats was observed in colon tissue. RESULTS The safety experiments showed that no death occurred in each dose group， and no significant difference was found in organ coefficient， routine blood and serum biological index， compared to blank control group （P＞0.05）； no abnormality was found in organ appearance and pathological sections. The results of the pharmacodynamic experiments showed that， compared with the blank control group， the fecal moisture content， gastric emptying rate， intestinal propulsion rate， and serum motilin levels in the model group were significantly decreased （P＜0.05）； in the colonic tissue， the mitochondria in the ICC exhibited severe swelling with the disappearance of cristae， and the endoplasmic reticulum was dilated. Compared with model group， the rats in Shuangshu decoction high-dose group showed significant increases in the above quantitative indicators （P＜ 0.05）； additionally， there was a large number of mitochondria in the ICC of the colonic tissue， with clear cristae and regular arrangement. CONCLUSIONS Shuangshu decoction is safe and has a beneficial improving effect on FD rats； its mechanism of action may be related to the regulation of gastrointestinal hormone expression to promote gastric emptying and intestinal propulsion， as well as the repair of mitochondrial structure in ICCs to restore gastrointestinal function.

OBJECTIVES: Intracranial aneurysm (IA) has an insidious onset, and once ruptured, it carries high rates of mortality and disability. Cardiometabolic factors may be associated with the formation and rupture of IA. This study aims to summarize the application of Mendelian randomization (MR) methods in research on cardiometabolic factors and IA, providing insights for further elucidation of IA etiology and pathogenesis. METHODS: Literature about MR-based IA studies published up to February 21, 2024, was retrieved from PubMed, Embase, Web of Science, CNKI, and Wanfang. Two researchers independently performed literature screening, data extraction, and quality assessment. A narrative synthesis approach was used to conduct a qualitative systematic review of the included studies. RESULTS: A total of 11 MR-based studies on IA published between 2017 to 2024 were included, of which 4 were rated as high quality. These studies investigated the associations between blood pressure, blood lipids, blood glucose, obesity-related indicators, and inflammatory cytokines with IA and its subtypes, though issues of duplication were noted. Four MR studies based on the same European population but using different instrumental variable selection criteria, as well as another MR study in a different European cohort, consistently identified blood pressure as a risk factor for IA and its subtypes. Findings for blood lipids, blood glucose, obesity-related indicators, and inflammatory cytokines were inconsistent across MR studies. CONCLUSIONS Blood pressure appears to increase the risk of IA and its subtypes. Associations between other cardiometabolic factors and IA/subtypes require further in-depth investigation. Given the inherent limitations of MR studies, causal inferences should be made cautiously in combination with other lines of evidence.
Humans ; Mendelian Randomization Analysis ; Intracranial Aneurysm/etiology* ; Risk Factors ; Blood Pressure ; Blood Glucose ; Obesity/complications* ; Cardiometabolic Risk Factors ; Lipids/blood*

Objective:To explore the clinical efficacy of "four-step" aortic valve anatomic repair for bicuspid aortic valve(BAV) with aortic regurgitation(AR).Methods:From August 2021 to November 2024, a total of 298 consecutive patients with BAV-AR underwent aortic valve anatomic repair(AVr) in Shanghai Zhongshan Hospital Fudan University, 266 males and 32 females, with age of 39(29.5, 48.5) years. All patients underwent " four-step" three-dimensional anatomic repair of the aortic annulus and leaflets, 129(43.3%) patients via upper mini-sternotomy and 169(56.7%) patients via conventional median sternotomy, with the main steps including: (1) deep dissecting and annuloplasty of the virtual basal ring(VBR); (2) symmetrical repairing of leaflets; (3) replacement or remodeling of the sinus of Valsalva; (4) annuloplasty of the sinotubular junction(STJ). Basal and perioperative data were retrospectively collected, and statistical analysis was performed in conjunction with follow-up data.Results:All patients successfully underwent anatomical repair without transferring to valve replacement during operation. Among them, 43 patients underwent aortic root reimplantation technique(Reimplantation group), while 255 patients underwent modified aortic root sleeve remodeling technique(Sleeve group). The median cardiopulmonary bypass time for the Reimplantation and Sleeve groups were 154(134, 169) minutes and 111(95, 129) minutes, respectively( P<0.05); the median aortic cross-clamp time were 112(100, 131) minutes and 80(67, 94) minutes, respectively( P<0.05). Preoperative TEE showed 35 patients(81.4%) and 229 patients(89.8%) with moderate and severe AR in Reimplantation and Sleeve groups, respectively. Postoperative TEE showed 41 patients(95.3%) with no/trace AR and 2 patients(4.7%) with central mild AR in Reimplantation group, while 212 patients(83.1%) with no/trace AR and 43 patients(16.9%) with central mild AR in Sleeve group. Follow-up was completed in all patients, with a median follow-up of 12.9(4.7, 21.2) months. Echocardiography was obtained in 271 patients(90.9%) at the latest follow-up, including no/trace AR in 167 patients(56.0%), mild AR in 89 patients(29.9%), moderate AR in 14 patients(4.7%), and severe AR in 1 patient(0.3%). Conclusion:Aortic valve anatomic repair by standardized "four-step" approach is safe and reproducible. Satisfied short- and mid-term outcome have obtained in selected BAV-AR patients.

Objectives:To evaluate the safety and feasibility of endovascular aortic repair without contrast agent under branch artery guidewire marking(FLARE technique).Methods:The clinical data of 7 patients who underwent contrast-free endovascular aortic repair with branch artery guidewire marking in Fuwai Hospital from 2024 to 2025 were retrospectively analyzed.The criteria for patient selection included renal insufficiency,history of contrast agent allergy,high risk of high-pressure angiography due to extensive calcification of the aortic arch,and patients'strong personal wishes,all patients merited with anatomically friendly and anchored area criteria.The patients were evaluated by preoperative computed tomography or color Doppler ultrasound,and the occlusive stent anchor point was located by branch artery guidewire marking combined with bone marking during surgery.The primary endpoints were early stage of postoperative renal function changes(comparison of preoperative and postoperative serum creatinine)and surgical technique success rate,and the secondary endpoints included the incidence of internal leakage,re-intervention rates,and incidence of aneurysm and kidney-related adverse events during follow-up.Results:Among the seven patients who underwent endovascular aortic repair without contrast using a branch artery guidewire,four were male,with an average age of(72.0±5.9)years.Six of these patients had infrarenal abdominal aortic aneurysms,two of them with bilateral renal artery severe stenosis and renal insufficiency underwent renal artery stenting combined with endovascular aortic repair,one patient had isolated chronic renal insufficiency,one had a history of iodine contrast skin allergy,and the remaining two cases wished this surgery option.The seventh patient had a penetrating ulcer in the aortic arch and descending aorta,along with extensive thrombosis and calcification in the ascending aorta,aortic arch and descending aorta.All the patients achieved surgical technique success.No iodine contrast agent was used during the procedure for endovascular aortic repair.In patients with chronic renal insufficiency and renal artery stenosis before surgery,serum creatinine levels were significantly improved after surgery.All patients did not need hemodialysis,there was no allergic reaction,and no graft-related or perioperative complications.The average follow-up was(5.8±3.0)months,all patients recovered well without re-intervention or complications.The creatinine levels did not fluctuate significantly after surgery.Conclusions:Branch artery guidewire marked contrast-free aortic endovascular repair may be a safe and feasible treatment option in selected patients,especially in patients with contraindications to contrast agents.

Intricate and complex interactions between tumor cells and tumor microenvironment(TME)are essential driving factors in tumor development and metastasis.In recent years,modulation of TME to reverse tumor progression has garnered significant attention as a therapeutic strategy.For precise and targeted tumor treatment,there is an urgent need for accurate and effective TME tar-get molecules and relevant prediction model.Fibronectin,a protein with multiple domains in extracellular matrix(ECM),plays a cru-cial role in physiological and pathological processes.Particularly,Fibronectin extra domain B(FN-EDB)in fibronectin is pivotal in regulating interaction between ECM and cells.During active tissue remodeling processes,especially in angiogenesis,FN-EDB expres-sion tends to increase.Studies have indicated that FN-EDB is involved in regulating various key aspects of tumorigenesis,including promoting tumor cell invasion and metastasis,influencing development of immune evasion mechanisms,enhancing tumor angiogene-sis,and contributing to development of chemoresistance.Therefore,targeting FN-EDB as a potential therapeutic target for cancer treat-ment and developing relevant therapeutic drugs hold significant importance and promising clinical prospects.This article reviews roles of FN-EDB in TME in recent years and research progress on tumor immunotherapy targeting this molecule,with aim of providing new insights and strategies for cancer treatment.

Acute liver failure (ALF) is a life-threatening condition associated with macrophage-mediated inflammatory responses. Effective therapies and drugs are still lacking to date. Here, we reveal that a derivative of xanthohumol, CAM12203, alleviates lipopolysaccharide (LPS) + d-galactosamine (D-GalN)-induced ALF through limiting macrophage-mediated inflammation, with the most significant impact on interleukin-1β (IL-1β) transcription. Through biotin labeling-mediated pull-down and LC-MS/MS analysis, diacylglycerol kinase ζ (DGKζ), a lipid-metabolizing kinase, is identified as the direct target of CAM12203. Mechanistically, DGKζ is induced in macrophages upon inflammatory stimuli and is upregulated observed on clinical liver failure samples. Its product phosphatidic acid (PA) boosts phospholipase C (PLC)-inositol 1,4,5-trisphosphate (IP₃)-Ca²⁺ signaling and subsequent janus kinase 2 (JAK2)-signal transducer and activator of transcription 3 (STAT3) cascade, ultimately promoting IL-1β production and liver failure. DGKζ knockdown/ablation or inhibition significantly impairs the DGKζ-STAT3-IL-1β pathway along with ALF progression. Finally, CAM12203 is confirmed to be a new DGKζ inhibitor and acts against inflammation in a DGKζ-reliant manner. Taken together, CAM12203 inhibits IL-1β transcription in macrophages by binding to DGKζ and blocking the DGKζ-STAT3 axis, thereby exerting an ameliorative effect on ALF. These results not only highlight CAM12203 as a promising lead compound for ALF treatment, but also define DGKζ as a novel therapeutic target.

Anxiety disorder is a major symptom of autism spectrum disorder (ASD) with a comorbidity rate of ~40%. However, the neural mechanisms of the emergence of anxiety in ASD remain unclear. In our study, we found that hyperactivity of basolateral amygdala (BLA) pyramidal neurons (PNs) in Shank3 InsG3680 knock-in (InsG3680^+/+) mice is involved in the development of anxiety. Electrophysiological results also showed increased excitatory input and decreased inhibitory input in BLA PNs. Chemogenetic inhibition of the excitability of PNs in the BLA rescued the anxiety phenotype of InsG3680^+/+ mice. Further study found that the diminished control of the BLA by medial prefrontal cortex (mPFC) and optogenetic activation of the mPFC-BLA pathway also had a rescue effect, which increased the feedforward inhibition of the BLA. Taken together, our results suggest that hyperactivity of the BLA and alteration of the mPFC-BLA circuitry are involved in anxiety in InsG3680^+/+ mice.
Animals ; Prefrontal Cortex/metabolism* ; Basolateral Nuclear Complex/metabolism* ; Mice ; Anxiety/metabolism* ; Nerve Tissue Proteins/genetics* ; Male ; Gene Knock-In Techniques ; Pyramidal Cells/physiology* ; Mice, Transgenic ; Neural Pathways/physiopathology* ; Mice, Inbred C57BL ; Microfilament Proteins