AIM:To investigate the protective effects of soy isoflavones on retinal ganglion cells(RGCs)damage in diabetic rats and related mechanisms.METHODS: Totally 80 male SD rats(80 eyes), aged 4-6 weeks, were randomly divided into four groups(n=20 per group): a control group, a diabetic model group, a low-dose soy isoflavone treatment group, and a high-dose soy isoflavone treatment group. Among them, the control group was fed normal chow, while the diabetic group, soy isoflavone low-dose-treated group, and soy isoflavone high-dose-treated group were fed high-fat chow. After a feeding period of 4 wk, rats in the diabetic group, as well as those in the soy isoflavone low-dose and high-dose treatment groups, were injected intraperitoneally with streptozotocin(STZ)at a dose of 50 mg/kg to establish a diabetic model. Rats in the control group received an equivalent volume of sodium citrate buffer acid. The soy isoflavone low-dose-treated group was administered 360 mg/kg of soy isoflavones daily via gavage, while the soy isoflavone high-dose-treated group received 540 mg/kg of soy isoflavones daily via gavage. Both the control group and the diabetic group were given an equal amount of purified water daily via gavage. Body weight and blood glucose levels were measured at 4 and 8 wk post-gavage treatment. The eyes were extracted and the retinas were dissected at 8 wk following the gavage treatment. The number of RGCs in each group was determined using immunochemical tissue staining and protein blotting techniques, while the superoxide dismutase(SOD)activity and malondialdehyde(MDA)content of the rat retinal tissue were measured through histochemical methods.RESULTS: Compared with diabetic rats, treatment with high-dose soy isoflavones for 8 wk resulted in a reduction of blood glucose to 8.9±1.23 mmol/L, an increase in intraretinal SOD activity to 849.93±63.71 U/mgprot, a decrease in MDA content to 45.77±0.59 nmol/mgprot, and an increase in the number of RGCs to 76±1 cells/mm2, which is comparable to the control group's data(all P<0.05).CONCLUSION: Soy isoflavones can reduce retinal oxidative stress in diabetic rats and protect RGCs.

[摘 要] 目的：探讨环状RNA hsa_circ_0046701在胶质瘤组织中的表达及其对胶质瘤U251细胞增殖、迁移与侵袭的影响。方法：收集2022年6月至2023年3月期间在同济大学附属普陀人民医院接受手术治疗的52例胶质瘤患者的瘤组织标本及临床资料，另收集30例正常脑组织标本作为对照。通过qPCR法检测胶质瘤组织中hsa_circ_0046701表达水平，分析其与患者临床特征间的关系，通过Kaplan-Meier法分析hsa_circ_0046701水平与生存预后的关系。利用RNA干扰技术，分别将circ_0046701过表达及空载体（vector）、siRNA-circ_0046701及阴性对照（si-NC）质粒转染到胶质瘤U251细胞中，实验分为si-circ_0046701组、si-NC组、circ_0046701 OE组、Vector组。应用CCK-8法、Transwell小室实验检测各组细胞的增殖、迁移及侵袭能力，WB法检测各组细胞中vimentin、Snail、E-cadherin和cyclin D1蛋白的表达。结果：胶质瘤组织中hsa_circ_0046701表达显著高于正常脑组织（P < 0.01）。hsa_circ_0046701高表达组患者WHO脑胶质瘤分级（Ⅲ~Ⅳ级）占比显著高于低表达组（P < 0.01），其高表达组患者术后生存期显著短于低表达组。与si-NC组相比，si-circ_0046701组U251细胞的增殖能力显著降低（P < 0.05或P < 0.01）、迁移及侵袭细胞数均显著减少（均P < 0.01），细胞中vimentin、Snail、cyclin D1蛋白表达均明显降低（均P < 0.01）、E-cadherin蛋白表达明显增高（P < 0.01）；与Vector组相比，circ_0046701 OE组U251细胞的增殖能力显著升高（P < 0.01）、迁移及侵袭细胞数均显著增多（均P < 0.01），细胞中vimentin、Snail、cyclin D1蛋白表达均显著增高（均P < 0.01）、E-cadherin蛋白表达明显降低（P < 0.01）。结论：环状RNA hsa_circ_0046701在胶质瘤组织中呈高表达，并与患者的不良预后密切相关；敲低hsa_circ_0046701表达能够抑制脑胶质瘤U251细胞的增殖、迁移及侵袭能力。

Objective: To explore the clinical features, treatment and prognosis of emphysematous pyelonephritis (EPN), so as to enhance the clinical awareness of this disease. Methods: A retrospective analysis was conducted on the clinical data of one EPN patient at The Second Affiliated Hospital, Guangzhou University of Chinese Medicine, and a literature review was performed on articles published in the China National Knowledge Infrastructure and PubMed databases from Jan.1, 2015 to Dec.31, 2024. Results: The patient, a 62-year-old male with a 5 years' history of type 2 diabetes, was admitted due to left flank pain for 4 days, with a temperature of 39.4 ℃.Laboratory tests indicated significantly elevated inflammatory markers, decreased platelet count, and abnormal coagulation function.Preoperative blood and urine cultures showed positivity for Escherichia coli.Computed tomography (CT) revealed complete erosion of the left kidney, with gas in the left ureter and surrounding effusion, as well as multiple free gas in the abdominal cavity, bilateral ureteral stones, right renal lower calyx stones.After a multidisciplinary consultation, he underwent emergency phase Ⅰ left pyeloplasty and perirenal drainage with ureteral stenting.After discharge, the patient received maintenance hemodialysis once every two days in the outpatient clinic.One week after-discharge, the patient was readmitted due to polypnea.Following symptomatic management, vital signs stabilized.Approximately 2 months after the first-stage surgery, ureteroscopic stone extraction was successfully performed.One month after the stone extraction procedure, a follow-up CT showed normalization of the left kidney, renal pelvis and calyces, leading to phase Ⅱ laparoscopic left nephrectomy via the abdominal approach, with postoperative pathology indicating renal necrosis.Among 89 EPN patients reported in 35 articles, the median age was 58(24-92) years old；there were 59（66.3%） females and 30（33.7%） males；fever was the most common clinical symptom (60.7%)；73(82.0%) had diabetes, 12 (13.5%) had urinary tract obstruction；55 (61.8%) were infected with Escherichia coli, and 7 (7.9%) were infected with Klebsiella pneumoniae; 13 died due to ineffective treatmen. Conclusion: EPN presents acutely and progresses rapidly, often leading to misdiagnosis due to the lack of specific early symptoms.Abdominal CT is the preferred imaging modality for rapid diagnosis, and proactive interdisciplinary intervention can improve survival rates, reduce the need for nephrectomy, and enhance prognosis.

Dental stem cells (DSCs), a distinct subset of mesenchymal stem cells (MSCs), are isolated from dental tissues, such as dental pulp, exfoliated deciduous teeth, periodontal ligament, and apical papilla. They have emerged as a promising source of stem cell therapy for tissue regeneration and autoimmune disorders. The main types of DSCs include dental pulp stem cells (DPSCs), stem cells from human exfoliated deciduous teeth (SHED), periodontal ligament stem cells (PDLSCs), and stem cells from apical papilla (SCAP). Each type exhibits distinct advantages: easy access via minimally invasive procedures, multi-lineage differentiation potential, and excellent ethical acceptability. DSCs have demonstrated outstanding clinical efficacy in oral and maxillofacial regeneration, and their long-term safety has been verified. In oral tissue regeneration, DSCs are highly effective in oral tissue regeneration for critical applications such as the restoration of dental pulp vitality and periodontal tissue repair. A defining advantage of DSCs lies in their ability to integrate with host tissues and promote physiological regeneration, which render them a better option for oral tissue regenerative therapies. Beyond oral applications, DSCs also exhibit promising potential in the treatment of systemic diseases, including type Ⅱ diabetes and autoimmune diseases due to their immunomodulatory effects. Moreover, extracellular vesicles (EVs) derived from DSCs act as critical mediators for DSCs' paracrine functions. Possessing regulatory properties similar to their parental cells, EVs are extensively utilized in research targeting tissue repair, immunomodulation, and regenerative therapy-offering a "cell-free" strategy to mitigate the limitations associated with cell-based therapies. Despite these advancements, standardizing large-scale manufacturing, maintaining strict quality control, and clarifying the molecular mechanisms underlying the interaction of DSCs and their EVs with recipient tissues remain major obstacles to the clinical translation of these treatments into broad clinical use. Addressing these barriers will be critical to enhancing their clinical applicability and therapeutic efficacy. In conclusion, DSCs and their EVs represent a transformative approach in regenerative medicine, and increasing clinical evidence supports their application in oral and systemic diseases. Continuous innovation remains essential to unlocking the widespread clinical potential of DSCs.
Humans ; Dental Pulp/cytology* ; Translational Research, Biomedical ; Mesenchymal Stem Cells/cytology* ; Periodontal Ligament/cytology* ; Stem Cells/cytology* ; Regeneration ; Tooth, Deciduous/cytology* ; Cell Differentiation ; Tissue Engineering/methods* ; Regenerative Medicine

Objective: To establish and validate a whole blood (WB) supply model, thereby providing practical experience for the clinical application of WB in domestic trauma emergency care and informing the development of a wartime blood supply system for the military. Methods: A “10×24” WB supply model was established by formulating blood collection protocols, storage standards, and transfusion criteria. Multiple WB samples were tested under specific storage conditions to assess key indicators at different time points, including red blood cell (RBC), white blood cell (WBC), and platelet counts, hemoglobin concentration, coagulation parameters (PT, APTT, TT, FIB), coagulation factor activity, thromboelastography (TEG) parameters, and electrolyte levels. Additionally, clinical data from hemorrhagic patients who met the criteria for WB transfusion and were admitted between March and July 2024 were analyzed to evaluate WB transfusion volume. Results: RBC counts and hemoglobin levels remained stable in WB stored at 4℃ for up to 10 days. However, platelet counts and coagulation function (PT, APTT) significantly declined with prolonged storage, while potassium levels increased. From March to July 2024, the model was successfully applied to 23 patients with acute hemorrhage, with a median WB transfusion volume of 543 mL. A detailed case study of a severe traumatic hemorrhagic shock patient was reported, who was successfully treated with 5.5 units of refrigerated WB combined with component blood. Conclusion: The “10×24” WB supply model demonstrated acceptable changes in critical quality parameters under strict management and a 10-day rotation cycle. This model effectively supports the treatment of acute hemorrhage and holds promise for integration into the future wartime blood supply system of the military.

Objective: Recent studies indicate that 3 morphological types of atlanto-occipital joint (AOJ) exist in the craniovertebral junction and are associated with type II basilar invagination (BI) and atlanto-occipital instability. However, the actual biomechanical effects remain unclear. This study aims to investigate biomechanical differences among AOJ types I, II, and III, and provide further evidence of atlanto-occipital instability in type II BI. Methods: Models of bilateral AOJ containing various AOJ types were created, including I-I, I-II, II-II, II-III, and III-III models, with increasing AOJ dysplasia across models. Then, 1.5 Nm torque simulated cervical motions. The range of motion (ROM), ligament and joint stress, and basion-dental interval (BDI) were analyzed. Results: The C0–1 ROM and accompanying rotational ROM increased progressively from model I-I to model III-III, with the ROM of model III-III showing increases between 27.3% and 123.8% indicating ultra-mobility and instability. In contrast, the C1–2 ROM changes were minimal. Meanwhile, the stress distribution pattern was disrupted; in particular, the C1 superior facet stress was concentrated centrally and decreased substantially across the models. The stress on the C0–1 capsule ligament decreased during cervical flexion and increased during bending and rotating loading. In addition, BDI gradually decreased across the models. Further analysis revealed that the dens showed an increase of 110.1% superiorly and 11.4% posteriorly, indicating an increased risk of spinal cord impingement. Conclusion Progressive AOJ incongruity critically disrupts supportive tissue loading, enabling incremental atlanto-occipital instability. AOJ dysplasia plays a key biomechanical role in the pathogenesis of type II BI.

Chronic intermittent hypoxia (CIH) can lead to vascular dysfunction and increase the risk of cardiovascular diseases, cerebrovascular diseases, and arterial diseases. Nevertheless, mechanisms underlying CIH-induced vascular dysfunction remain unclear. Herein, this study analyzed the role of aortic smooth muscle calciumactivated potassium (BK) channels in CIH-induced vascular dysfunction. CIH models were established in rats and rat aortic smooth muscle cells (RASMCs). Hemodynamic parameters such as mean blood pressure (MBP), diastolic blood pressure (DBP), and systolic blood pressure (SBP) were measured in rats, along with an assessment of vascular tone. NO and ET-1 levels were detected in rat serum, and the levels of ET-1, NO, eNOS, p-eNOS, oxidative stress markers (ROS and MDA), and inflammatory factors (IL-6 and TNF-α) were tested in aortic tissues. The Ca2+ concentration in RASMCs was investigated. The activity of BK channels (BKα and BKβ) was evaluated in aortic tissues and RASMCs. SBP, DBP, and MBP were elevated in CIH-treated rats, along with endothelial dysfunction, cellular edema and partial detachment of endothelial cells. BK channel activity was decreased in CIH-treated rats and RASMCs. BK channel activation increased eNOS, p-eNOS, and NO levels while lowering ET-1, ROS, MDA, IL-6, and TNF-α levels in CIH-treated rats. Ca2+ concentration increased in RASMCs following CIH modeling, which was reversed by BK channel activation. BK channel inhibitor (Iberiotoxin) exacerbated CIH-induced vascular disorders and endothelial dysfunction. BK channel activation promoted vasorelaxation while suppressing vascular endothelial dysfunction, inflammation, and oxidative stress, thereby indirectly improving CIH-induced vascular dysfunction.

Objective　To establish a dual droplet digital PCR (ddPCR) assay for herpes simplex virus type I (HSV-1) and varicella-zoster virus (VZV). Methods The specific primers and probes were derived based on the conserved regions of HSV-1 and VZV genome. The primer-probe combinations were screened, and the annealing temperatures and primer-probe concentration ratios of the dual-droplet digital PCR reaction were optimized to establish a dual-droplet digital PCR reaction system for HSV-1 and VZV, which was tested for other viruses and validated for clinical samples. The sensitivity, specificity, and reproducibility of the established dual microtiter digital PCR method were analyzed. Results The optimal concentrations of primers and probes for the dual ddPCR detection method of HSV-I and VZV were determined to be 800 nmol/L and 250 nmol/L, respectively, with an optimal annealing temperature of 56 ℃. The correlation coefficient (R2) of the standard curve of the dual ddPCR assay was 0.99, showing a clear linear relationship. The method showed high sensitivity, with the lowest detection limit of herpes simplex virus type I being 2.97 copies/μL, and for VZV being 2.73 copies/μL. The repeatability was high with a small coefficient of variation and stable detection results; the specificity was excellent, and no cross-reaction was found with herpes simplex virus type Ⅱ, Epstein-Barr virus, Adenovirus, Coxsackievirus (CA6/CA10/CA16), Cytomegalovirus, Human Cytomegalovirus, Human enterovirus 71, Japanese Encephalitis virus, West Nile virus, Measles virus, Mumps virus, and human nucleic acids. Conclusions The dual droplet digital PCR assay for herpes simplex virus type I and varicella-zoster virus established in this experiment has strong sensitivity, specificity, and high repeatability, and can provide a solution for rapid quantitative detection of the two viruses in different scenarios.

Chronic intermittent hypoxia (CIH) can lead to vascular dysfunction and increase the risk of cardiovascular diseases, cerebrovascular diseases, and arterial diseases. Nevertheless, mechanisms underlying CIH-induced vascular dysfunction remain unclear. Herein, this study analyzed the role of aortic smooth muscle calciumactivated potassium (BK) channels in CIH-induced vascular dysfunction. CIH models were established in rats and rat aortic smooth muscle cells (RASMCs). Hemodynamic parameters such as mean blood pressure (MBP), diastolic blood pressure (DBP), and systolic blood pressure (SBP) were measured in rats, along with an assessment of vascular tone. NO and ET-1 levels were detected in rat serum, and the levels of ET-1, NO, eNOS, p-eNOS, oxidative stress markers (ROS and MDA), and inflammatory factors (IL-6 and TNF-α) were tested in aortic tissues. The Ca2+ concentration in RASMCs was investigated. The activity of BK channels (BKα and BKβ) was evaluated in aortic tissues and RASMCs. SBP, DBP, and MBP were elevated in CIH-treated rats, along with endothelial dysfunction, cellular edema and partial detachment of endothelial cells. BK channel activity was decreased in CIH-treated rats and RASMCs. BK channel activation increased eNOS, p-eNOS, and NO levels while lowering ET-1, ROS, MDA, IL-6, and TNF-α levels in CIH-treated rats. Ca2+ concentration increased in RASMCs following CIH modeling, which was reversed by BK channel activation. BK channel inhibitor (Iberiotoxin) exacerbated CIH-induced vascular disorders and endothelial dysfunction. BK channel activation promoted vasorelaxation while suppressing vascular endothelial dysfunction, inflammation, and oxidative stress, thereby indirectly improving CIH-induced vascular dysfunction.

Objective: Recent studies indicate that 3 morphological types of atlanto-occipital joint (AOJ) exist in the craniovertebral junction and are associated with type II basilar invagination (BI) and atlanto-occipital instability. However, the actual biomechanical effects remain unclear. This study aims to investigate biomechanical differences among AOJ types I, II, and III, and provide further evidence of atlanto-occipital instability in type II BI. Methods: Models of bilateral AOJ containing various AOJ types were created, including I-I, I-II, II-II, II-III, and III-III models, with increasing AOJ dysplasia across models. Then, 1.5 Nm torque simulated cervical motions. The range of motion (ROM), ligament and joint stress, and basion-dental interval (BDI) were analyzed. Results: The C0–1 ROM and accompanying rotational ROM increased progressively from model I-I to model III-III, with the ROM of model III-III showing increases between 27.3% and 123.8% indicating ultra-mobility and instability. In contrast, the C1–2 ROM changes were minimal. Meanwhile, the stress distribution pattern was disrupted; in particular, the C1 superior facet stress was concentrated centrally and decreased substantially across the models. The stress on the C0–1 capsule ligament decreased during cervical flexion and increased during bending and rotating loading. In addition, BDI gradually decreased across the models. Further analysis revealed that the dens showed an increase of 110.1% superiorly and 11.4% posteriorly, indicating an increased risk of spinal cord impingement. Conclusion Progressive AOJ incongruity critically disrupts supportive tissue loading, enabling incremental atlanto-occipital instability. AOJ dysplasia plays a key biomechanical role in the pathogenesis of type II BI.