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.

ObjectiveTo investigate the effect and mechanism of Yishen Tongluo prescription in protecting mice from oxidative stress injury in diabetic kidney disease （DKD） via the nuclear factor erythroid 2-related factor 2 （Nrf2）/heme oxygenase-1 （HO-1）/NAD（P）H quinone oxidoreductase 1 （NQO1） signaling pathway. MethodsSpecific pathogen-free （SPF） male C57BL/6 mice were assigned into a control group （n=10） and a modeling group （n=50）. The DKD model was established by intraperitoneal injection of streptozotocin. The mice in the modeling group were randomized into a model group， a semaglutide （40 μg·kg^-1） group， and high-， medium-， and low-dose （18.2， 9.1， 4.55 g·kg^-1， respectively） Yishen Tongluo prescription groups， with 10 mice in each group. The treatment lasted for 12 weeks. Blood glucose and 24-h urine protein levels were measured， and the kidney index （KI） was calculated. Serum levels of creatinine （SCr）， blood urea nitrogen （BUN）， alanine aminotransferase （ALT）， and aspartate aminotransferase （AST） were assessed. The pathological changes in the renal tissue were evaluated by hematoxylin-eosin， periodic acid-Schiff， periodic acid-silver methenamine， and Masson’s trichrome staining. Enzyme-linked immunosorbent assay kits were used to measure the levels of β2-microglobulin （β2-MG）， neutrophil gelatinase-associated lipocalin （NGAL）， kidney injury molecule-1 （KIM-1）， liver fatty acid-binding protein （L-FABP）， nitric oxide synthase （NOS）， glutathione （GSH）， total antioxidant capacity （T-AOC）， and 8-hydroxy-2'-deoxyguanosine （8-OHdG）. Immunohistochemical staining was performed to examine the expression of Kelch-like ECH-associated protein 1 （Keap1） and malondialdehyde （MDA）. Real-time fluorescence quantitative polymerase chain reaction (Real-time PCR） and Western blot were employed to determine the mRNA and protein levels， respectively， of factors in the Nrf2/HO-1/NQO1 signaling pathway. ResultsCompared with the control group， the DKD model group showed rises in blood glucose， 24-h urine protein， KI， SCr， BUN， and ALT levels， along with glomerular hypertrophy， renal tubular dilation， thickened basement membrane， mesangial expansion， and collagen deposition. Additionally， the model group showed elevated levels of β2-MG， NGAL， KIM-1， L-FABP， NOS， and 8-OHdG， lowered levels of GSH and T-AOC， up-regulated expression of MDA and Keap1， and down-regulated expression of Nrf2， HO-1， NQO1， and glutamate-cysteine ligase catalytic subunit （GCLC） （P<0.05）. Compared with the model group， the semaglutide group and the medium- and high-dose Yishen Tongluo prescription groups showed reductions in blood glucose， 24-h urine protein， KI， SCr， BUN， and ALT levels， along with alleviated pathological injuries in the renal tissue. In addition， the three groups showed lowered levels of β2-MG， NGAL， KIM-1， L-FABP， NOS， and 8-OHdG， elevated levels of GSH and T-AOC， down-regulated expression of MDA and Keap1， and up-regulated expression of Nrf2， HO-1， NQO1， and GCLC （P<0.05）. ConclusionYishen Tongluo prescription exerts renoprotective effects in the mouse model of DKD by modulating the Nrf2/HO-1/NQO1 signaling pathway， mitigating oxidative stress， and reducing renal tubular injuries.

Background Automotive repair workers are exposed to a wide variety of volatile organic compounds (VOCs) during painting operations, which poses significant health risks. Biomonitoring can directly reflect the internal body burden of these compounds. Therefore, it is essential to develop an analytical method for simultaneous determination of VOCs in the urine of automotive spray painting workers. Objective To establish a static headspace gas chromatography-mass spectrometry (GC-MS) method for simultaneously determining 22 VOCs in the urine of spray painting workers in automotive repair enterprises. Methods An automatic headspace sampler was used for the pretreatment of urine samples. The headspace conditions as well as the chromatographic and mass spectrometric conditions of static headspace GC-MS were optimized. The separation of 22 VOCs was achieved by optimizing the temperature program. Sensitivity was enhanced by optimizing the quantitative ions. The signal response of VOCs was improved by optimizing the headspace equilibrium temperature, equilibrium time, and the amount of inorganic salt added. The method's detection limit, lower limit of quantification, accuracy, precision, and stability were tested using blank urine samples spiked with standards. Additionally, the method was applied to examine 40 urine samples collected from painting workers in automotive repair enterprises in Tianjin. Results In this study, the headspace equilibrium temperature was set at 80 ℃, the equilibrium time was 30 min, and the salt addition amount was 2.0 g. A DB-624ms chromatographic column was selected for the separation of 22 VOCs. The initial temperature of heating program was 50 ℃, maintained for 15 min, and then increased to 85 ℃ at a heating rate of 10 ℃·min⁻¹ for 10 min, followed by increasing to 90 ℃ at a heating rate of 5 ℃·min⁻¹ for 20 min. The single ion monitoring (SIM) mode was chosen for the quantitative analysis of the 22 VOCs. The method demonstrated good linearity for determining 22 target analytes in the urine of spray painting workers, with correlation coefficients all above 0.990. The lower limits of quantification (LOQ) for the components ranged from 0.4 to 3.8 μg·L⁻¹. The spiked recovery rates of the samples were between 80.1% and 112.1%, and the relative standard deviations (RSD) ranged from 1.5% to 9.7%. All target analytes could be stored at 4 ℃ for 5 d and at −20 ℃ for 7 d. This method was applied to evaluate urine samples from 40 spray painting workers in automotive repair enterprises in Tianjin. The positive rate of butyl acetate was 37.5%. The positive rate of xylene was 32.5%. The positive rate of toluene was 30.0%. The positive rate of isopropanol was 25.0%. The concentration range of the detected substances was from −1. Conclusion The established simultaneous determination protocol of 22 VOCs by static headspace- GC-MS is characterized by its simplicity, high sensitivity, excellent selectivity, and high accuracy. It is suitable for urine samples of spray painting workers in automotive repair industry.

Background Currently, incidents of organic solvent poisoning are occurring frequently. Rapidly and accurately qualitative and quantitative analysis of toxic substances is crucial for the treatment of affected individuals. In recent years, many biomarker assays with good specificity and high sensitivity have been developed for the detection of exposure to organic solvents, but they cannot meet the demand for real-time and fast detection. Objective To establish a paper spray mass spectrometry method for direct and rapid detection of four organic compound metabolites (toluene diamine, 2,5-hexanedione, hippuric acid, and methylhippuric acid) in the urine of occupational populations. Methods Toluene diamine and 2,5-hexanedione were analyzed using positive ion mode, while hippuric acid and methylhippuric acid were analyzed using negative ion mode. The ion transfer tube temperature was 275 °C. The ion transfer tube voltage was 35 V. For positive ion mode, the scan range was 50-150 m/z. For negative ion mode, the scan range was 150-250 m/z. The distance from the paper substrate tip to the mass spectrometry inlet was 8 mm. The applied voltage was 3.5 kV. The spray solvent was methanol/water (90:10). The spray solvent volume was 15 μL. Under the optimized experimental conditions, both external standard and internal standard methods were used for quantitative analysis. Limit of detection, limit of quantification, accuracy, and precision of the proposed method were determined by spiking blank urine samples. To evaluate the feasibility of the method, the established approach was compared with current national standard detection methods or methods described in the literature. All methods were used to analyze 40 urine samples collected from occupationally exposed individuals (20 exposed to n-hexane and 20 exposed to toluene and xylene). Results The four biomarkers showed good linearity within their respective measurement ranges and the correlation coefficients were higher than 0.9990. The limits of detection of the method were in the range of 0.00027 to 0.020 μg·mL⁻¹, and the limits of quantification were in the range of 0.0009 to 0.067 μg·mL⁻¹. The spiked recoveries at low, medium, and high concentrations ranged from 96.5% to 106.9%, with relative standard deviations (RSDs) between 5.6% and 9.7%. When applying the method to 40 urine samples from occupationally exposed individuals, the detection rates for toluene diamine, 2,5-hexanedione, hippuric acid, and methylhippuric acid were 0%, 45%, 20%, and 37.5%, respectively. For biomarkers detected by both this method and the reference methods, the detection values were generally consistent. The analysis time per sample was approximately 1-2 min using paper spray mass spectrometry, compared to 1-2 h for reference methods. Conclusion The paper spray mass spectrometry method established in this study for detecting four organic compound metabolites in urine is characterized by its simplicity, rapidity, efficiency, and high accuracy. It can obtain results within 1-2 min, which significantly improves the timeliness of detection. It is suitable for direct and rapid screening of four organic compound metabolites in urine, and can provide technical support for the diagnosis and treatment of organic solution poisoning.

The objective of this study is to map the global scientific competitive landscape in the field of artificial intelligence (AI) medical devices using scientific data. A bibliometric analysis was conducted using the Web of Science Core Collection to examine global research trends in AI-based medical devices. As of the end of 2023, a total of 55 147 relevant publications were identified worldwide, with 76.6% published between 2018 and 2024. Research in this field has primarily focused on AI-assisted medical image and physiological signal analysis. At the national level, China (17 991 publications) and the United States (14 032 publications) lead in output. China has shown a rapid increase in publication volume, with its 2023 output exceeding twice that of the U.S.; however, the U.S. maintains a higher average citation per paper (China: 16.29; U.S.: 35.99). At the institutional level, seven Chinese institutions and three U.S. institutions rank among the global top ten in terms of publication volume. At the researcher level, prominent contributors include Acharya U Rajendra, Rueckert Daniel and Tian Jie, who have extensively explored AI-assisted medical imaging. Some researchers have specialized in specific imaging applications, such as Yang Xiaofeng (AI-assisted precision radiotherapy for tumors) and Shen Dinggang (brain imaging analysis). Others, including Gao Xiaorong and Ming Dong, focus on AI-assisted physiological signal analysis. The results confirm the rapid global development of AI in the medical device field, with "AI + imaging" emerging as the most mature direction. China and the U.S. maintain absolute leadership in this area-China slightly leads in publication volume, while the U.S., having started earlier, demonstrates higher research quality. Both countries host a large number of active research teams in this domain.
Artificial Intelligence ; Bibliometrics ; Humans ; China ; Equipment and Supplies ; United States ; Biomedical Research

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 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*

Demyelination and remyelination play key roles in spinal cord injury (SCI), affecting the recovery of motor and sensory functions. Research in rodent models is extensive, but the study of these processes in non-human primates is limited. Therefore, our goal was to thoroughly study the histological features of demyelination and remyelination after contusion injury of the cervical spinal cord in Macaca fascicularis. In a previous study, we created an SCI model in M. fascicularis by controlling the contusion displacement. We used Eriochrome Cyanine staining, immunohistochemical analysis, and toluidine blue staining to evaluate demyelination and remyelination. The results showed demyelination ipsilateral to the injury epicenter both rostrally and caudally, the former mainly impacting sensory pathways, while the latter primarily affected motor pathways. Toluidine blue staining showed myelin loss and axonal distension at the injury site. Schwann cell-derived myelin sheaths were only found at the center, while thinner myelin sheaths from oligodendrocytes were seen at the center and surrounding areas. Our study showed that long-lasting demyelination occurs in the spinal cord of M. fascicularis after SCI, with oligodendrocytes and Schwann cells playing a significant role in myelin sheath formation at the injury site.
Animals ; Spinal Cord Injuries/physiopathology* ; Demyelinating Diseases/etiology* ; Remyelination/physiology* ; Macaca fascicularis ; Disease Models, Animal ; Myelin Sheath/pathology* ; Oligodendroglia/pathology* ; Schwann Cells/pathology* ; Female ; Spinal Cord/pathology* ; Axons/pathology*

ObjectiveTo explore the effect of Qingre Huayu Jianpi prescription （QHJ） on colitis-associated colorectal cancer （CAC） in mice， and its related mechanism. MethodC57BL/6 mice were randomly divided into four groups including the normal， model， QHJ low-dose （QHJ-L， 10 g·kg^-1）， and QHJ high-dose （QHJ-H， 40 g·kg^-1） groups. Azoxymethane （AOM） and dextran sodium sulfate （DSS） were combined to chemically build a CAC mouse model for 14 weeks. Each drug group was given intragastrically from the 5^th week to the 14^th week， once per day. An equal volume of water was fed to the normal and model groups. The mouse survival rate， colon length， weight， and pathological alterations were assessed. The protein expressions of Wnt-3a protein signaling （Wnt3a）， β-catenin， Non-phosphor-β-catenin （Non-p-β-catenin）， and cholesterol-binding glycoproteins 133 （CD133） were detected by Western blot. The localization and expression of the cluster of differentiation （CD） 80 and CD11 antigen-like family member B （CD11b） were detected by immunohistochemistry （IHC）. The colon organoids derived from CAC mice were isolated and cultured to detect the expression of Wnt signaling pathway-related proteins. ResultThe survival rate of the CAC mice was improved by QHJ treatment and the number of colon tumors was inhibited significantly. Compared with those in the normal group， the expression levels of Wnt3a， β-catenin， Non-p-β-catenin， and CD133 in colon tissues in the model group were significantly increased （P<0.05， P<0.01）. Compared with those in the model group， the levels of Wnt3a and β-catenin in the QHJ-L group were significantly decreased （P<0.01）， and the protein levels of Wnt3a， β-catenin， Non-p-β-catenin， and CD133 in the QHJ-H group were significantly decreased （P<0.05， P<0.01）. Meanwhile， the expression level of CD11b in the model group was significantly increased compared with that in the normal group while the CD80 level was significantly decreased （P<0.05， P<0.01）. Compared with those in the model group， CD11b in QHJ-L and QHJ-H groups was significantly decreased， and CD80 was significantly increased（P<0.05， P<0.01）. The expressions of Non-p-β-catenin and CD133 in colonic organoids of CAC model mice were significantly increased， while QHJ treatment could inhibit the expressions of Non-p-β-catenin and CD133 in colonic organoids （P<0.01）. ConclusionQHJ could inhibit the inflammation-cancer development in CAC mice， the mechanism of which might be related to regulating the microenvironment and inhibiting the over-activation of Wnt signaling.

ObjectiveTo comprehensively assess the clinical value of Duliang soft capsules in the treatment of migraine with wind-cold blood stasis syndrome， and to provide guidance for national medical decision-making， clinical drug promotion， and pharmaceutical services. MethodThe evaluation of Duliang soft capsules' clinical value was conducted in accordance with the Guidelines for the Management of Comprehensive Clinical Evaluation of Drugs （Trial Version， 2021） using a combination of qualitative and quantitative methods. Utilizing the CSC v2.0 software， this study conducted a comprehensive clinical evaluation of Duliang soft capsules across the "6+1" dimensions， including safety pre- and post-market launch， effectiveness in treating migraine， economy （cost-effectiveness）， and innovation， suitability， accessibility， and traditional Chinese medicine （TCM） characteristics in both its technology and clinical applications. ResultSafety： Duliang soft capsules were found to have good safety based on evidence from known adverse reactions （spontaneous reporting system （SRS） data， literature data， etc.）， pre-marketing toxicological research， and post-marketing drug monitoring. Effectiveness： A meta-analysis indicated that the combination of Duliang soft capsules and western medicine was more effective than Western medicine alone in the treatment of migraine. The product's effectiveness was rated as "Best" based on the quality and value of the evidence. Economy： Duliang soft capsules are moderately priced and categorized as a Type B medical insurance product. Economic research indicated that the combination of Western medicine and Duliang soft capsules was more cost-effective than Western medicine alone. The product's economy was rated as "Better". Innovation： Duliang soft capsules， with Angelicae Dahuricae Radix and Chuanxiong Rhizoma as the main components， hold one invention patent and have been awarded the China Patent Excellence Award. The pharmaceutical company has introduced innovative extraction （CO₂ supercritical extraction technology） and formulation （soft capsule） processes. The product's innovation was rated as "Better". Suitability： A questionnaire survey on Duliang soft capsules showed that it was well-suited for both patients and healthcare professionals. The product received a comprehensive assessment of suitability through the "Evaluation of Chinese Patent Medicine Information Services". The product's suitability was rated as "Best". Accessibility： Duliang soft capsules are moderately priced， making them accessible and affordable. The product's accessibility was rated as "Good" based on evidence from these three aspects. TCM characteristics： The formulation of Duliang soft capsules can be traced back to WANG Qiu's Selected Formulas from the Praiseworthy Studio （Shi Zhai Bai Yi Xuan Fang） from the Song Dynasty， and it was documented in ZHANG Jiebin's The Complete Works of Zhang Jing-yue （Jing Yue Quan Shu） as "Duliangwan". The product has been extensively studied with over 2000 clinical cases since its market launch， and its TCM characteristics were rated as outstanding with sufficient evidence. ConclusionThe comprehensive clinical value evaluation of Duliang soft capsules demonstrated its high effectiveness， suitability， and accessibility， and outstanding TCM characteristics. The product's safety， economy， and innovation received good ratings. In summary， Duliang soft capsules exhibited significant clinical value and outstanding TCM characteristics， the evidence was sufficient， and the result was confirmed， providing crucial references for clinical decision-making and pharmaceutical management.