ObjectiveTo investigate the therapeutic efficacy of Qizhi Tongluo granules on proteinuria in membranous nephropathy （MN） and its potential protective effects and underlying mechanism against endoplasmic reticulum stress. MethodsAfter 70 Sprague-Dawley （SD） rats were adaptively fed for one week， the MN rat model was established by injecting cationic bovine serum albumin （C-BSA） into the tail vein. Rats were divided into the normal group， model group， low-dose Qizhi Tongluo granules group （2.43 g·kg^-1）， medium-dose group （4.86 g·kg^-1）， high-dose group （9.72 g·kg^-1）， and benazepril group （0.01 g·kg^-1）， with 10 rats in each group. Treatment was administered for four weeks. The 24-hour urinary total protein （UTP） content， as well as the levels of reactive oxygen species （ROS）， malondialdehyde （MDA）， and glutathione peroxidase （GPX） in renal tissues， were measured. Renal pathological changes were assessed using immunoglobulin G （IgG） staining， periodic acid-silver methenamine （PASM） staining， and transmission electron microscopy （TEM）. The localization and expression levels of glucose-regulated protein 78 （GRP78）， phosphorylated inositol-requiring enzyme 1α （p-IRE1α）， phosphorylated protein kinase R-like endoplasmic reticulum kinase （p-PERK）， activating transcription factor 4 （ATF4）， nuclear factor erythroid 2-related factor 2 （Nrf2）， and 2'-5' oligoadenylate synthetase-like protein 1 （OASL1） in rat kidneys were detected by immunohistochemistry （IHC）. The mRNA and protein expression levels of Nrf2， thioredoxin 1 （Trx1）， thioredoxin-interacting protein （TXNIP）， and OASL1 in rat kidneys were measured using real-time quantitative polymerase chain reaction （Real-time PCR） and Western blot analysis. ResultsCompared with the normal group， UTP levels were significantly increased in the model rats （P<0.05）， with obvious renal pathological damage. GPX content levels were significantly decreased in renal tissue （P<0.05）， while ROS and MDA content levels were significantly increased （P<0.05）. The expression of GRP78， p-IRE1α， p-PERK， and ATF4 proteins was significantly increased in the kidneys （P<0.05）， while the mRNA and protein expression levels of Trx1 and Nrf2 were significantly decreased （P<0.05）. The mRNA and protein expression levels of TXNIP and OASL1 were significantly increased （P<0.05）. Compared with the model group， the UTP levels of rats in the Qizhi Tongluo granules groups and the benazepril group decreased to varying degrees （P<0.05）， and renal pathological damage was significantly alleviated. The GPX content in renal tissue was significantly increased （P<0.05）， while the ROS and MDA levels were significantly decreased （P<0.05）. The expression of GRP78， p-IRE1α， p-PERK， and ATF4 proteins in the kidney was significantly decreased （P<0.05）. The mRNA and protein expression levels of Trx1 and Nrf2 were significantly increased （P<0.05）， while the mRNA and protein expression levels of TXNIP and OASL1 were significantly decreased （P<0.05）. ConclusionQizhi Tongluo granules alleviates proteinuria in MN rats by modulating the Nrf2/OASL1 signaling pathway in renal tissues to reduce endoplasmic reticulum stress， which represents its underlying mechanism.

Chronic visceral pain is a persistent and debilitating condition arising from dysfunction or sensitization of the visceral organs and their associated nervous pathways. Increasing evidence suggests that imbalances in central nervous system function play an essential role in the progression of visceral pain, but the exact mechanisms underlying the neural circuitry and molecular targets remain largely unexplored. In the present study, the ventral tegmental area (VTA) was shown to mediate visceral pain in mice. Visceral pain stimulation increased c-Fos expression and Ca²⁺ activity of glutamatergic VTA neurons, and optogenetic modulation of glutamatergic VTA neurons altered visceral pain. In particular, the upregulation of NMDA receptor 2A (NR2A) subunits within the VTA resulted in visceral pain in mice. Administration of a selective NR2A inhibitor decreased the number of visceral pain-induced c-Fos positive neurons and attenuated visceral pain. Pharmacology combined with chemogenetics further demonstrated that glutamatergic VTA neurons regulated visceral pain behaviors based on NR2A. In summary, our findings demonstrated that the upregulation of NR2A in glutamatergic VTA neurons plays a critical role in visceral pain. These insights provide a foundation for further comprehension of the neural circuits and molecular targets involved in chronic visceral pain and may pave the way for targeted therapies in chronic visceral pain.
Animals ; Male ; Visceral Pain/metabolism* ; Up-Regulation/physiology* ; Ventral Tegmental Area/metabolism* ; Receptors, N-Methyl-D-Aspartate/antagonists & inhibitors* ; Neurons/drug effects* ; Mice, Inbred C57BL ; Mice ; Proto-Oncogene Proteins c-fos/metabolism* ; Chronic Pain/metabolism* ; Glutamic Acid/metabolism*

Objective To develop a refined printer management system based on the PDCA cycle,aiming to improve both operational cost efficiency and medical service quality through full-process management.Methods A total of 400 printers in use at the Third Affiliated Hospital of Sun Yat-sen University(Zhaoqing Hospital)were included from June 2024 to May 2025.The period from June to November 2024 was designated as the pre-refinement phase(under conventional management),while December 2024 to May 2025 served as the post-refinement phase(under PDCA-based refined management).A fishbone diagram was used to identify root causes of previous management inefficiencies,and targeted measures were developed and implemented.Outcomes were compared between the two phases.Results After implementing the PDCA cycle,the average equipment utiliza-tion rate increased by 5.41％,indicating optimized resource allocation.The average page yield per drum increased by 3.51％,reflecting improved consumable efficiency and reduced operational costs.The incidence of driver failures decreased by 34.71％,and operational issues dropped by 7.25％,demonstrating enhanced device reliability and system stability.Consultation-related work orders increased by 78.68％,and routine maintenance tasks rose by 30.62％,signaling a shift from reactive repairs to pro-active preventive maintenance.Conclusion The PDCA-based refined management model effectively enhances printer operational efficiency,reduces resource waste,and improves device reliability.This approach reinforces a patient-centered service philosophy by increasing the accuracy and efficiency of medical documentation output,thereby supporting safer and more efficient healthcare delivery.

Objective:To evaluate the efficacy and safety of immunotherapy combined with chemotherapy as conversion therapy for initially unresectable locally advanced esophageal squamous cell carcinoma.Methods:This retrospective case series study analyzed clinical and pathological data of 32 patients with initially unresectable locally advanced esophageal squamous cell carcinoma who received immunotherapy combined with chemotherapy at the Department of Thoracic Surgery, the Fourth Hospital of Hebei Medical University, from June 2020 to December 2024. The cohort included 27 males and 5 females, with an age ( M(IQR)) of 61(9)years (range:46 to 73 years). Five patients were diagnosed with stage Ⅲ, 27 with stage ⅣA. All patients received PD-1 inhibitor sintilimab combined with nedaplatin and albumin-bound paclitaxel. Radiological evaluations were performed every two cycles, the multidisciplinary team evaluation was conducted to determine conversion to resectable status, and patients with successful conversion underwent radical esophagectomy. Follow-up was conducted via telephone or outpatient visits every 3 to 6 months after the last treatment. The primary endpoint was R0 resection rate, secondary endpoints included objective response rate (ORR), pathological complete response (pCR) rate, major pathological response (MPR) rate, event-free survival (EFS), disease-free survival (DFS) in patients with R0 resection, overall survival (OS) and safety. Kaplan-Meier method was used to plot survival curves and estimate median EFS, DFS, OS rates and their 95% CI. The 95% CI for ORR, pCR rate, MPR rate, and downstaging rate were calculated using the Clopper-Pearson method. Results:The median treatment cycle of 2(1) (range:2 to 8). As of June 2025, the median follow-up was 32.5(13.5)months (range:6.4 to 59.1 months). Among the 32 patients, 9 experienced progression or recurrence, including 2 with liver and lymph node metastases, 2 with lung metastases, 2 with thoracic vertebral metastases, and 3 with mediastinal lymph node metastases. After conversion therapy, 29 patients underwent surgery, achieving an R0 resection rate of 84.4% (95% CI:67.2% to 94.7%), a pCR rate of 27.6% (95% CI:12.7% to 47.2%), and an MPR rate of 55.2% (95% CI:35.7% to 73.6%). Grade 3 or higher surgical complications occurred in 6.9%(2/29) of patients, and grade 3 or higher treatment-related adverse events were observed in 15.6%(5/29). Among the 32 patients, the ORR was 56.3% (95% CI:37.7% to 73.6%),the 3-year EFS rate and OS rate was 59.4% (95% CI:40.8% to 86.4%) and 59.7% (95% CI:40.0% to 89.0%) respectively. Conclusion:Immunotherapy combined with chemotherapy demonstrates high conversion rates and favorable safety in the conversion therapy of initially unresectable locally advanced esophageal squamous cell carcinoma, representing a promising treatment strategy.

Background:Colorectal cancer(CRC)is a major cause of cancer death worldwide,and about 30%to 35%of CRC arises from the serrated pathway.Aims:To analyze the clinicopathological and histomorphological characteristics of colorectal superficially serrated adenoma(SuSA),and to investigate the malignant transformation potential of SuSA and further elucidate the role of RSPO2 and RSPO3 in its carcinogenic mechanism.Methods:A total of 169 serrated colorectal lesions confirmed pathologically and fulfilling the inclusion criteria were collected from Shanxi Bethune Hospital from February 2019 to May 2023.Among them,there were 84 cases of SuSA,23 sessile serrated lesions(SSL),32 traditional serrated adenomas(TSA),and 30 hyperplastic polyps(HP).Thirty-nine cases of tubular adenoma(TA),32 CRC,and 33 normal colorectal mucosal tissues were served as controls.The clinicopathological and histomorphological parameters were collected and recorded.Immunohistochemical staining was used to detect the protein expressions of RSPO2,RSPO3,p53,MLH1 and β-catenin.Results:Patients with SuSA were male predominance,with a mean age of 51.89 years.The average diameter of the lesions was 0.20 cm,predominantly located in the left colon and rectum,and frequently complicated with other polyps/adenomas.The histomorphological features of SuSA were as follows:the glandular necks and crypt bases exhibited straight tubular structure with low-grade dysplasia;the superficial layer demonstrated a serrated architecture,with or without dysplasia,and contained a variable number of goblet cells.Immunohistochemically,there were no statistically significant differences in RSPO2,RSPO3,and p53 expressions between SuSA and TSA(all P>0.05).A strong positive correlation was observed between RSPO2 and RSPO3 in colorectal lesions,excluding HP.Expressions of MLH1 and β-catenin showed no statistically significant differences between SuSA and other colorectal lesions(all P>0.05).Conclusions:SuSAs are more common in males,occur mostly in the left colon and rectum,and are often associated with other polyps/adenomas.They might be precursors of KRAS-mutated TSA and microsatellite stable CRC with high malignant potential.RSPO2 and RSPO3 might play an important role in the carcinogenesis of SuSA.

Objective To explore the effect of step frequency-controlled walking exercise on vascular endothelial injury in postmenopausal patients with essential hypertension.Methods According to the screening criteria,postmenopausal women aged 55～60 years with essential hypertension and age-matched healthy women with normal blood pressure were recruited.The hypertensive patients were fur-ther divided into an exercise training group(ET)(n=23)that received step frequency-based walking intervention,and a positive control group(PC)(n=23)without exercise intervention.The normotensive healthy subjects were assigned to a negative control group(NC)(n=23).The exercise training lasted 45 to 60 minutes every other day,at least three times a week,for 12 weeks.Before and after the in-tervention,the following parameters were measured:morphological indices[body fat percentage and waist-to-hip ratio(WHR)],blood pressure indicators[systolic blood pressure(SBP)and diastolic blood pressure(SDP)],lipid metabolism markers consisting of the total cholesterol(TC),triglycerides(TG),low-density lipoprotein cholesterol(LDL-c),and high-density lipoprotein cholesterol,and vascular en-dothelial injury parameters such as endothelial microparticles(EMPs),high-sensitivity C-reactive pro-tein(hs-CRP),and superoxide dismutase(SOD).Results After the intervention,the ET group exhibit-ed significant improvements compared to baseline(P<0.05).Specifically,reductions were observed in body fat percentage,WHR,SBP,TC,TG,LDL-c,EMPs,and hs-CRP(P<0.05).Meanwhile,HDL-c and SOD levels increased significantly(P<0.05).Most of the above indicators demonstrated sig-nificant improvements in the ET group compared to the PC group after the intervention(P<0.05).Con-clusion A 12-week step frequency-controlled walking exercise at moderate intensity improves body com-position,SBP,lipid metabolism,and vascular endothelial function in postmenopausal patients with hy-pertension,suggesting its potentialto reduce cardiovascular risk in this population.

Steroid-induced osteonecrosis of the femoral head(SNOFH)is a prevalent challenging condition in orthopedics,characterized by a high disability rate and intricate pathophysiological mechanisms including diminished an-giogenesis and impaired osteogenic function.The concept of osteogenesis-angiogenesis coupling involves the interplay be-tween osteoblasts and angiogenesis.Restoring the blood supply to bone tissue,boosting bone cell activity,and facilitating bone regeneration are crucial for the recovery of SNOFH patients.Research has demonstrated the significant role of mi-croRNAs(miRNAs)in the coordination of osteogenesis and angiogenesis.MiRNAs have the ability to concurrently regu-late multiple target genes and signaling pathways associated with osteogenesis and angiogenesis,effectively stimulating the regeneration of bones and blood vessels.By considering the interaction of multiple miRNAs and their target genes,the de-velopment of a multi-target combination therapy approach could greatly enhance the treatment outcomes for SNOFH.Through a thorough investigation of miRNA interactions in the regulation of osteogenesis and angiogenesis,the progression of the disease can be elucidated,offering a fundamental basis for early diagnosis,precise treatment,and prognosis evalua-tion of SNOFH.This paper aims to uncover the pivotal nodes and regulatory connections in SNOFH by summarizing the in-volvement of miRNAs in the coupling of osteogenesis and angiogenesis.By identifying potential therapeutic targets and un-derstanding the coordinated function of miRNAs in osteogenesis and angiogenesis coupling,valuable insights can be gained for the personalized treatment of SNOFH.

Objective To explore the effect of step frequency-controlled walking exercise on vascular endothelial injury in postmenopausal patients with essential hypertension.Methods According to the screening criteria,postmenopausal women aged 55～60 years with essential hypertension and age-matched healthy women with normal blood pressure were recruited.The hypertensive patients were fur-ther divided into an exercise training group(ET)(n=23)that received step frequency-based walking intervention,and a positive control group(PC)(n=23)without exercise intervention.The normotensive healthy subjects were assigned to a negative control group(NC)(n=23).The exercise training lasted 45 to 60 minutes every other day,at least three times a week,for 12 weeks.Before and after the in-tervention,the following parameters were measured:morphological indices[body fat percentage and waist-to-hip ratio(WHR)],blood pressure indicators[systolic blood pressure(SBP)and diastolic blood pressure(SDP)],lipid metabolism markers consisting of the total cholesterol(TC),triglycerides(TG),low-density lipoprotein cholesterol(LDL-c),and high-density lipoprotein cholesterol,and vascular en-dothelial injury parameters such as endothelial microparticles(EMPs),high-sensitivity C-reactive pro-tein(hs-CRP),and superoxide dismutase(SOD).Results After the intervention,the ET group exhibit-ed significant improvements compared to baseline(P<0.05).Specifically,reductions were observed in body fat percentage,WHR,SBP,TC,TG,LDL-c,EMPs,and hs-CRP(P<0.05).Meanwhile,HDL-c and SOD levels increased significantly(P<0.05).Most of the above indicators demonstrated sig-nificant improvements in the ET group compared to the PC group after the intervention(P<0.05).Con-clusion A 12-week step frequency-controlled walking exercise at moderate intensity improves body com-position,SBP,lipid metabolism,and vascular endothelial function in postmenopausal patients with hy-pertension,suggesting its potentialto reduce cardiovascular risk in this population.

Steroid-induced osteonecrosis of the femoral head(SNOFH)is a prevalent challenging condition in orthopedics,characterized by a high disability rate and intricate pathophysiological mechanisms including diminished an-giogenesis and impaired osteogenic function.The concept of osteogenesis-angiogenesis coupling involves the interplay be-tween osteoblasts and angiogenesis.Restoring the blood supply to bone tissue,boosting bone cell activity,and facilitating bone regeneration are crucial for the recovery of SNOFH patients.Research has demonstrated the significant role of mi-croRNAs(miRNAs)in the coordination of osteogenesis and angiogenesis.MiRNAs have the ability to concurrently regu-late multiple target genes and signaling pathways associated with osteogenesis and angiogenesis,effectively stimulating the regeneration of bones and blood vessels.By considering the interaction of multiple miRNAs and their target genes,the de-velopment of a multi-target combination therapy approach could greatly enhance the treatment outcomes for SNOFH.Through a thorough investigation of miRNA interactions in the regulation of osteogenesis and angiogenesis,the progression of the disease can be elucidated,offering a fundamental basis for early diagnosis,precise treatment,and prognosis evalua-tion of SNOFH.This paper aims to uncover the pivotal nodes and regulatory connections in SNOFH by summarizing the in-volvement of miRNAs in the coupling of osteogenesis and angiogenesis.By identifying potential therapeutic targets and un-derstanding the coordinated function of miRNAs in osteogenesis and angiogenesis coupling,valuable insights can be gained for the personalized treatment of SNOFH.

Objective To develop a refined printer management system based on the PDCA cycle,aiming to improve both operational cost efficiency and medical service quality through full-process management.Methods A total of 400 printers in use at the Third Affiliated Hospital of Sun Yat-sen University(Zhaoqing Hospital)were included from June 2024 to May 2025.The period from June to November 2024 was designated as the pre-refinement phase(under conventional management),while December 2024 to May 2025 served as the post-refinement phase(under PDCA-based refined management).A fishbone diagram was used to identify root causes of previous management inefficiencies,and targeted measures were developed and implemented.Outcomes were compared between the two phases.Results After implementing the PDCA cycle,the average equipment utiliza-tion rate increased by 5.41％,indicating optimized resource allocation.The average page yield per drum increased by 3.51％,reflecting improved consumable efficiency and reduced operational costs.The incidence of driver failures decreased by 34.71％,and operational issues dropped by 7.25％,demonstrating enhanced device reliability and system stability.Consultation-related work orders increased by 78.68％,and routine maintenance tasks rose by 30.62％,signaling a shift from reactive repairs to pro-active preventive maintenance.Conclusion The PDCA-based refined management model effectively enhances printer operational efficiency,reduces resource waste,and improves device reliability.This approach reinforces a patient-centered service philosophy by increasing the accuracy and efficiency of medical documentation output,thereby supporting safer and more efficient healthcare delivery.