ObjectiveTo investigate the mechanism through which miR‑21 improves chronic renal fibrosis in mice via targeted modulation of the phosphatase and tensin homolog （PTEN）/protein kinase B （AKT）/mammalian target of rapamycin （mTOR） pathway. MethodsThirty‑two chronic kidney disease model mice were randomly divided into four groups （n=8 each group）： model group， miR‑21 overexpression group， miR‑21 inhibition group， and miR‑21 inhibition + MK‑2206 group. Eight healthy mice were included as the control group. The miR‑21 overexpression， miR‑21 inhibition， and miR‑21 inhibition + MK‑2206 groups received tail‑vein injections of lentivirus （50 μL， 1×10⁸ TU per mouse） once weekly for three weeks. The control and model groups were injected with an equal volume of empty vector （LV‑NC）. The miR‑21 inhibition + MK‑2206 group additionally received gavage of the AKT/mTOR pathway inhibitor MK‑2206 （480 mg/kg） once weekly for three weeks. The expressions of miR‑21， 24 h urinary protein， serum creatinine （Scr）， blood urea nitrogen （BUN）， and renal tissue levels of collagen Ⅰ， collagen Ⅲ， α‑smooth muscle actin （α‑SMA）， and PTEN protein， as well as p‑AKT/AKT and p‑mTOR/mTOR ratios， were compared among groups. HE staining was used to observe pathological changes in renal tissue， and Masson staining was used to observe the degree of renal fibrosis. A dual‑luciferase assay was performed to verify the targeting relationship between miR‑21 and PTEN. ResultsCompared with the model group， miR‑21 expression in renal tissue increased in the miR‑21 overexpression group （P<0.05） and decreased in the miR‑21 inhibition group （P<0.05）. Compared with the model group， the miR‑21 overexpression group showed increased 24 h urinary protein， Scr， BUN， and renal tissue expression of collagen Ⅰ， collagen Ⅲ， and α‑SMA （all P<0.05）， while these indicators decreased in the miR‑21 inhibition group （P<0.05）. Compared with the miR‑21 inhibition group， the miR‑21 inhibition + MK‑2206 group exhibited lower 24‑h urinary protein， Scr， BUN， and renal tissue expression of Collagen Ⅰ， Collagen Ⅲ， and α‑SMA （all P<0.05）. Compared with the model group， the miR‑21 overexpression group showed decreased PTEN protein expression （P<0.05） and increased p‑AKT/AKT and p‑mTOR/mTOR ratios （P<0.05）， while the miR‑21 inhibition group showed increased PTEN expression （P<0.05） and decreased p‑AKT/AKT and p‑mTOR/mTOR ratios （P<0.05）. Compared with the miR‑21 inhibition group， the miR‑21 inhibition + MK‑2206 group had lower p‑AKT/AKT and p‑mTOR/mTOR ratios （P<0.05）， with no significant difference in PTEN protein expression. HE and Masson staining showed normal kidney structure and almost no fibrosis in the control group. The model group exhibited glomerular enlargement， capillary loop adhesion， and focal fibrosis. The miR-21 overexpression group showed severe destruction of glomerular structure， accompanied by extensive fibrosis and renal tubular atrophy. The pathological changes and degree of fibrosis were alleviated in the miR-21 inhibition group. The miR-21 inhibition + MK-2206 group showed only mild pathological changes and mild fibrosis， with the interstitium being largely normal. Compared with PTEN-WT + NC mimics 1， the relative luciferase activity in the PTEN-WT + miR-21 mimics group decreased （P<0.001）. There was no statistically significant difference in relative luciferase activity between PTEN-WT + NC mimics group and PTEN-MUT + miR-21 mimics group. ConclusionmiR‑21 may improve renal function indicators and alleviate renal fibrosis in chronic kidney disease mice via targeted modulation of PTEN and subsequently inhibiting the AKT/mTOR pathway.

ObjectiveThe malaria parasites remodel the host erythrocyte structure by exporting parasite proteins that interact with the membrane skeleton proteins of red blood cells (RBCs), facilitating their intracellular survival and pathogenicity. Skeleton-binding protein 1 (SBP1) is a conserved exported protein across Plasmodium species. In Plasmodium falciparum, SBP1 has been reported to interact with erythrocyte membrane skeleton proteins 4.1R and spectrin, while its contribution to erythrocyte remodeling and parasite virulence in Plasmodium berghei (Pb) remains unclear. This study aims to determine whether PbSBP1 associates with the host cytoskeletal protein 4.1R and to investigate its role in the remodeling of host RBCs and the pathogenicity of Plasmodium berghei. MethodsIn Plasmodium berghei, the relationship between PbSBP1 and the erythrocyte cytoskeletal protein 4.1R was examined using co-immunoprecipitation. A Pbsbp1 gene knockout mutant of Plasmodium berghei (Pbsbp1∆) was generated based on the principle of double crossover homologous recombination. The deformability of erythrocytes infected with Pbsbp1∆ parasites was assessed using microfluidic methods. Microchannels with an array of cylindrical pillars were used to detect modifications in infected RBC deformability. The infected RBCs were squashed between the rows and recovered between the columns and the transit velocity (μm/s) of infected RBCs travelling through the microchannel was recorded. The component of the erythrocyte membrane skeleton junctional complex, tropomodulin (TMOD), was fluorescently labeled, and the cytoskeletal network of infected erythrocytes was imaged using super-resolution stochastic optical reconstruction microscopy (STORM) to analyze ultrastructural changes in the cytoskeleton of wild-type (WT) and Pbsbp1∆-infected erythrocytes. Actin-based junctional complexes were displayed as individual clusters by the labeled TMOD in the STORM images, and the cluster densities and distances between adjacent clusters of infected RBCs were calculated. Additionally, rodent malaria models (BALB/c mice) and experimental cerebral malaria models (C57BL/6 mice) were employed to monitor the growth of Pbsbp1∆ and WT parasites during the intraerythrocytic stage and their capacity to induce cerebral malaria in mice. ResultsPbSBP1 may participate in the remodeling of infected erythrocytes through direct or indirect interaction with the erythrocyte cytoskeletal protein 4.1R. Microfluidic assays revealed that the deformability of erythrocytes infected with Pbsbp1∆ parasites was significantly enhanced compared to those infected with WT parasites. STORM imaging further demonstrated that the ultrastructure of the erythrocyte cytoskeleton in Pbsbp1∆-infected cells was altered relative to that in WT-infected erythrocytes. The distances between nearest neighbors of clusters had a tendency to increase while the cluster densities were decreased in Pbsbp1∆-infected RBCs compared to WT-infected RBCs. Subsequent phenotypic analysis indicated that the growth rate of Pbsbp1∆ parasites during the intraerythrocytic stage was significantly slower than that of WT parasites, and their ability to induce cerebral malaria in mice was also attenuated. These findings suggest that PbSBP1 is involved in the remodeling of the erythrocyte membrane skeleton, likely through its direct or indirect interaction with protein 4.1R, thereby regulating the deformability of infected erythrocytes and influencing the pathogenicity of the blood-stage parasites. ConclusionThis study establishes a role for PbSBP1 in host erythrocyte remodeling and parasite virulence, providing new research strategies for the prevention and treatment of malaria.

Hepatic alveolar echinococcosis is a highly invasive zoonotic parasitic disease with poor prognosis. Surgical intervention serves as the pivotal approach to achieve radical cure and improve the prognosis of hepatic alveolar echinococcosis patients. In recent years, with the popularization of the concept of precision surgery and the development of the multidisciplinary diagnosis and treatment model, the surgical treatment strategies for hepatic alveolar echinococcosis have been continuously enriched, and the selection of surgical procedures has become increasingly diversified. Although key surgical techniques such as radical hepatectomy, autologous liver transplantation and allogeneic liver transplantation have achieved remarkable progress in clinical application, many insurmountable challenges still remain. Therefore, by sorting out the latest evidence-based advances in the field of surgical treatment for hepatic alveolar echinococcosis, this article focuses on discussing the application status and bottlenecks of radical hepatectomy, autologous liver transplantation and allogeneic liver transplantation in hepatic alveolar echinococcosis, aiming to provide a reference for the clinical treatment of hepatic alveolar echinococcosis.

Steroid-induced avascular necrosis of femoral head（SANFH） is a bone and joint disease caused by prolonged and excessive steroid use. Its typical pathological features involve progressive circulatory disorders in the blood supply system of femoral head， leading to osteocyte apoptosis and bone tissue necrosis. As the disease progresses， it ultimately results in structural collapse and necrotic lesions of the femoral head， severely affecting patients' limb function and quality of life. Glucocorticoids mediate pathological damage through dual mechanisms， on the one hand， they disrupt the dynamic equilibrium between bone formation and resorption by suppressing osteoblast differentiation activity and activating osteoclastogenesis， on the other hand， they induce lipid metabolism disorders， inhibit angiogenesis， and impair endothelial cell function， thereby triggering microcirculatory disorders. Epimedii Folium and its active components exhibit multidimensional regulatory effects in SANFH prevention and treatment. Literature review reveals that it is rich in multiple active ingredients， primarily including total flavonoids of Epimedii Folium， icaritin， icariin， kaempferol， icariside Ⅱ， etc. These compounds exert multiple pharmacological effects（regulating bone metabolic homeostasis， modulating angiogenesis， correcting lipid metabolism disorders， and controlling cellular autophagy processes） through multiple signaling pathways， including Wnt/β-catenin， transforming growth factor（TGF）-β/bone morphogenetic protein（BMP）/Smad， mitogen-activated protein kinase（MAPK）， phosphoinositide 3-kinase/protein kinase B（PI3K/Akt）， osteoprotegerin/receptor activator of nuclear transcription factor-κB ligand/receptor activator of nuclear transcription factor-κB（OPG/RANKL/RANK）， etc. Based on existing research findings， this paper systematically elucidates the intervention mechanisms of active components in Epimedii Folium on key pathological processes of SANFH through the above pathways. It also deeply analyzes their regulatory roles in key nodes of different signaling pathways， aiming to provide valuable references for future clinical treatment and experimental research.

AIM: To explore the effect of dihydroquercetin on visual function in mice with form deprivation myopia based on the NOD-like receptor thermoprotein domain-related protein 3(NLRP3)inflammasome pathway.METHODS: The C57BL/6 mice were randomly divided into control group and form deprivation myopia model group, and the form deprivation myopia model group was constructed by covering the right eye with a translucent eye patch. After successful modeling, the mice in the model group of form deprivation myopia were randomly divided into model group, low-, medium- and high-dose dihydroquercetin groups, and high-dose dihydroquercetin + NLRP3 agonist group. The diopter and axial length of mice in each group were detected. The kit was used to detect the levels of superoxide dismutase(SOD)and malondialdehyde(MDA)in retinal tissue. RT-qPCR was used to detect the mRNA expressions of NLRP3, apoptosis-associated spot-like protein(ASC), Caspase-1, IL-1β and IL-18 in retinal tissues. Western blot was used to detect the expression of NLRP3, ASC, cleaved Caspase-1, IL-1β and IL-18 proteins in retinal tissues. TUNEL staining was used to detect apoptosis in retinal tissue.RESULTS: Compared with the control group, the diopter of the mice in the model group decreased, and axial length increased, and the SOD decreased whereas MDA, NLRP3, ASC, Caspase-1, IL-1β, IL-18 increased, and the rate of apoptosis in retinal tissue increased(all P<0.05). Compared with the model group, the diopter of mice in the low-, medium- and high-dose dihydroquercetin groups increased, axial length shortened, the SOD increased, whereas MDA, NLRP3, ASC, Caspase-1, IL-1β, IL-18 decreased, and the rate of apoptosis in retinal tissue decreased(all P<0.05). Compared with the high-dose dihydroquercetin group, the high-dose dihydroquercetin+NLRP3 agonist group had reduced diopter, increased axial length, decreased SOD levels, elevated MDA, NLRP3, ASC, Caspase-1, IL-1β, and IL-18 levels, as well as increased apoptosis rate in retinal tissue(all P<0.05).CONCLUSION: Dihydroquercetin can improve visual function in mice with form deprivation myopia by inhibiting pyroptosis and oxidative stress responses, which may be related to the suppression of NLRP3 inflammasome. NLRP3 agonists can partially mitigate the effects of high-dose dihydroquercetin on form deprivation myopia in mice.

ObjectiveTo investigate the effects of exogenous nitric oxide （NO） on the accumulation and quality formation mechanism of flavonoids in Scutellariae Radix. MethodsFresh roots of Scutellaria baicalensis were treated with sodium nitroprusside （SNP） solutions at concentrations of 0.0， 7.5， and 20 mmol·L^-1， respectively. Kits and supporting reaction systems were used to determine the following indicators of samples in each group， including （1） reactive oxygen species： changes in the content of nitric oxide （NO）， superoxide anion （O2-·）， and hydrogen peroxide （H₂O₂）， （2） lipid oxidation products： changes in the content of malondialdehyde （MDA）， （3） antioxidant enzymes： changes in the activity of superoxide dismutase （SOD）， catalase （CAT）， and peroxidase （POD）， and （4） metabolic key enzymes and metabolic intermediates： Changes in the activity of phenylalanine ammonia-lyase （PAL） and the content of 1，3-diphosphoglycerate （1，3-DPG）. High-performance liquid chromatography （HPLC） was used to determine the changes in the content of secondary metabolites in flavonoids such as baicalin， wogonoside， baicalein， and wogonin in each group. ResultsCompared with that on day 0， during the treatment with 20 mmol·L^-1 SNP solution， the content of NO， O2-·， H₂O₂， and MDA in fresh roots of Scutellaria baicalensis increased significantly （P<0.01）， by 138.7%， 75.7%， 292.9%， and 140.3% respectively. The activity of SOD， CAT， and POD increased by 100.7%， 41.4%， and 70.4% respectively （P<0.01）， and that of PAL increased by 111.1% （P<0.01）. The content of the secondary metabolites baicalin and wogonoside remained basically unchanged， while that of baicalein and wogonin increased by 401.3% and 457.9% respectively （P<0.01）. The content of 1，3-DPG increased by 165.0% （P<0.01）. In the 7.5 mmol·L^-1 SNP solution treatment group， the stress degree was relatively mild. Compared with that on day 0， the content of NO， O2-·， H₂O₂， and MDA increased by 76.2%， 57.7%， 221.4%， and 99.7% respectively （P<0.01）. The activity of antioxidant enzymes SOD， CAT， and POD increased by 79.5%， 55.6%， and 51.9% respectively （P<0.01）， and that of PAL increased by 69.0% （P<0.01）. The content of baicalein and wogonin increased by 204.7% and 272.2% respectively （P<0.01）， and that of 1，3-DPG increased by 128.0% （P<0.01）. The 20 mmol·L^-1 SNP group showed better performance than the 7.5 mmol·L^-1 SNP group. ConclusionSNP can simulate the physiological state of Scutellaria baicalensis under stress conditions， activate the antioxidant protection mechanism， promote the biosynthesis of flavonoids in Scutellariae Radix， and significantly improve the quality of medicinal materials in Scutellariae Radix.

Objective: Blood safety surveillance is a critical measure for the objective assessment of blood quality and enhancing transfusion safety. This study aims to comprehensively understand the current status of blood safety surveillance and management in blood collection and supply institutions in Sichuan Province, systematically analyze existing problems and vulnerabilities, and provide a basis for optimizing management strategies and improving capabilities to ensure blood safety. Methods: The Blood Safety Surveillance questionnaire was designed, covering adverse donor reaction reporting, management of adverse events, and transfusion adverse reaction feedback. An online survey was conducted via Questionnaire Star platform among 21 blood collection and supply institutions in the province, gathering information on management systems, process implementation, and utilization of monitoring data. The collected data were organized and statistically analyzed using Excel. Results: The questionnaire response rate and validity rate were both 100%. Blood collection and supply institutions in Sichuan Province have generally established a blood safety surveillance system and achieved positive outcomes. Regarding adverse events in blood collection and supply, 95.24% (20 institutions) have established reporting procedures, and 66.67% (14) collect information through multiple channels such as internal reports, external reports, and statistical trend feedback. A total of 90.48% (19) institutions regularly summarize and analyze adverse event data, and 85.71% (18) produce reports with improvement recommendations based on this analysis.71.43% (15) institutions implement reward and penalty measures, and 71.43% (15) report underreporting or omission due to accountability or performance concerns. In terms of monitoring adverse blood donation reactions, all blood collection and supply institutions have established full-process management systems.76.19% (16) collect data through multiple approaches, including on-site donation records, voluntary donor reports, and donor follow-ups. Adverse reactions were followed up in 95.24% (20) of institutions with 65% (13) completing follow-ups within 24 hours.80.95% (17) have established investigation procedures, while 66.67% (14) believe underreporting or omission still occurs. All blood collection and supply institutions regularly compile statistics on adverse donation reactions. Of these, 85.71% (18) institutions providing feedback to management departments and 90.48% (19) analyzing the data and making recommendations.76.19% (16) institutions use monitoring data for return donor management and targeted care, and 71.43% (15 stations) incorporate it into management reviews. Regarding adverse transfusion reactions, 95.24% (20) institutions have established and implemented procedures for isolating, recalling, and tracing of problematic blood units. However, only 42.86% (9) have established feedback mechanisms of adverse transfusion reaction with hospitals, and only 19.05% (4) support direct reporting via information systems.47.62% (10) institutions regularly analyze adverse transfusion reaction data, and 19.05% (4) provide feedback and recommendations to relevant hospitals. All blood collection and supply institutions reported challenges in collecting hospital feedback, citing complexities in data collection and reporting processes. Conclusion: Blood safety surveillance systems have been preliminarily established in Sichuan Province. However, further strengthening is still required, including conducting in-depth data analysis and utilization, standardizing the configuration of emergency medications and equipment, and improving feedback mechanisms for adverse transfusion reactions. To improve the overall level of blood safety management, it is recommended to strengthen closed-loop data management, improve feedback mechanisms between blood collection and supply institutions and hospitals, foster a non-punitive reporting culture, and systematically advance the regionalization and standardization of the monitoring system. These efforts will contribute to sustainably improving the overall effectiveness and sustainability of blood safety management.

Ulcerative colitis is a chronic relapsing inflammatory bowel disease. Modern research indicates that immune dysregulation resulting from disruptions in circadian rhythm is closely associated with its pathogenesis. Both Western chronomedicine and traditional Chinese medicine（TCM）" treatment based on temporal factors" emphasize the temporal relationship between natural rhythms and human physiology and pathology. The " midnight-noon and ebb-flow " theory represents the concrete application and deepening of TCM " treatment based on temporal factors" within the realm of chronomedicine. This article correlates the onset time of ulcerative colitis with specific periods in the " midnight-noon and ebb-flow"theory：the Mao period（05：00-07：00），when the yangming large intestine meridian of hand is dominant； the Si period（09：00-11：00），when the taiyin spleen meridian of foot is dominant； and the You period（17：00-19：00），when the shaoyin kidney meridian of foot is dominant. According to this perspective，if the disease manifests during the Mao period，the pathogenesis is attributed to dampnessheat accumulation and disorder of qi and blood. Treatment should focus on clearing heat，resolving dampness，and harmonizing qi and blood，using modified formulas such as Shaoyao Decoction or Baitouweng Decoction. If it occurs during the Si period，the pathogenesis involves spleen deficiency with dampness obstruction and disharmony of qi and blood. Treatment should focus on strengthening the spleen，eliminating dampness，and restoring qi and blood，using modified formulas such as Huangya Decoction or Shenling Baizhu Powder. If it presents during the You period，the pathogenesis is characterized by fire failing to warm earth，and consumption resulting in qi and blood leakage. Treatment should focus on warming the kidney and spleen，and securing qi and blood，using modified formulas such as Sishen Pill or Tianhun Decoction. In addition to oral administration of Chinese herbal medicine，comprehensive therapies including acupuncture，herbal enemas，and acupoint application can provide novel insights for the clinical diagnosis and treatment of ulcerative colitis.

AIM:To investigate the effects of high-altitude hypoxic exposure on retinal injury and the associated changes in oxidative stress-related indicators in rats. METHODS: Twenty-four healthy male Sprague-Dawley(SD)rats were randomly divided into a plain group and a high-altitude group, with 12 rats(24 eyes)in each group. Rats in the plain group were housed under normoxic conditions in an SPF-grade animal facility, whereas rats in the high-altitude group were placed in a special environmental chamber simulating an altitude of 6 000 m for 7 d. Optical coherence tomography(OCT)was used to assess retinal layer architecture and quantify retinal thickness. Hematoxylin-eosin(HE)staining was performed to observe retinal histopathological changes. Immunofluorescence(IF)was used to detect the expression of hypoxia-inducible factor-1α(HIF-1α)in retinal tissue. Transmission electron microscopy(TEM)was applied to examine the ultrastructure of retinal ganglion cells(RGCs). Enzyme-linked immunosorbent assay(ELISA)was used to measure the levels of malondialdehyde(MDA), total superoxide dismutase(T-SOD), and reduced glutathione(GSH)in retinal tissue. In addition, intracellular reactive oxygen species(ROS)levels in retinal tissue were assessed using the 2',7'-dichlorodihydrofluorescein diacetate(DCFH-DA)fluorescent probe. RESULTS: OCT examination revealed disorganized retinal architecture in the high-altitude group, with increased inner and middle ring thickness and decreased outer ring thickness compared with the plain group(all P<0.05). HE staining showed varying degrees of retinal layer damage, blurred layer boundaries, loosely arranged RGCs, and partial cellular necrosis in the high-altitude group. IF analysis demonstrated significantly increased HIF-1α expression in the inner nuclear layer of the high-altitude group(P<0.01). TEM revealed mitochondrial swelling, disrupted cristae, and reduced matrix electron density in RGCs of the high-altitude group. ELISA and fluorescence probe assays showed significantly elevated MDA levels and ROS fluorescence intensity, accompanied by decreased T-SOD and GSH levels in the retinal tissue of the high-altitude group(all P<0.05). CONCLUSION: Exposure to a high-altitude hypoxic environment induces marked morphological and ultrastructural damage in the rat retina and significantly enhances oxidative stress, suggesting that oxidative stress may play a critical role in retinal injury induced by high-altitude hypoxia.

ObjectiveIn the context of the digital transformation of education, this study aims to construct a triadic interactive teaching model for surgical animal surgery in clinical medicine using modern information technology. It explores the effectiveness of different teaching methods in improving students' practical skills, aseptic awareness, and teamwork abilities, providing a reference for the reform of clinical practice education. MethodsA quasi-experimental research design was adopted. A total of 80 students from the eight-year clinical medicine program at Nanjing University were selected, including the Class of 2020 (control group, n=40) and the Class of 2021 (experimental group, n=40). The control group received traditional teaching methods, while the experimental group implemented the "Teacher-Student-AI" triadic interactive teaching model. This model utilized a smart teaching platform for personalized pre-class preparation , as well as data-driven post-class review and feedback throughout the entire teaching process. The "assessment indicators and scoring criteria for the surgical animal surgery course" were used to evaluate teaching effectiveness, with independent samples t-tests used for statistical analysis. ResultsPre-course assessments revealed no statistically significant differences in baseline theoretical knowledge or practical skills between the two groups (P>0.05). Upon completion of the course, the experimental group achieved higher scores than the control group across three key dimensions: practical skills (47.98±1.34 vs 46.92±2.51, P=0.022), aseptic awareness (17.84±1.16 vs 16.94±2.29, P=0.029), and teamwork (16.82±1.44 vs 15.95±1.22, P=0.004). However, no statistically significant difference was observed in the scores for humane care awareness between the two groups (8.24±0.70 vs 8.16±0.53, P=0.589). ConclusionThe AI-based triadic interactive teaching model can, to some extent, address the limitations of traditional surgical animal surgery education. It plays a positive role in enhancing medical students' surgical skills, aseptic awareness, and collaborative abilities. This model facilitates the transition from traditional to personalized teaching and offers a practical framework for the digital reform of clinical practice education.