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.

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.

This article summarizes the experience of providing remote nursing care for a pediatric patient with severe burns using augmented reality(AR)technology.Key nursing points include:to establish a remote management team to enhance multidisciplinary collaboration;to conduct remote nursing ward rounds to provide real-time guidance for clinical nursing practice;to remotely guide PICC(Peripherally Inserted Central Catheter)insertions and conduct precise fluid management;to remotely assess ward environments and provide guidance on disinfection and isolation measures;to alleviate pediatric pain through comprehensive management measures.After meticulous care and treatment,the patient's condition stabilized after 23 days,and the patient was transferred to a specialized hospital for continued treatment requiring skin grafting.

Objective This review aims to investigate the application of eye tracking(ET)in patients with speech impairment in the ICU.The review summarizes the current status and prospects of ET technology applications.Methods Following the scoping reviews framework,a systematic search was conducted across Web of Science,PubMed,Cochrane Library,Embase,CINAHL,CNKI,Wanfang Data,Chinese Medical Database,and Chinese biomedical database.The search covered publications from the inception of each database to October 29th,2024.The included studies were comprehensively analyzed.Results A total of 12 pieces of the literature were included,including 4 prospective cohort studies,4 experimental studies,3 prospective observational studies,and 1 randomized controlled trial.The application population of ET in the ICU mainly includes patients on mechanical ventilation,those at high risk of delirium,patients with spinal cord injury,etc.The types of integrated ET system equipment are mainly head-mounted and fixed;the types of ET involve gaze,blinking,etc.;the functions include standardized scale assessment,free interaction,and eye-movement model recognition.The main outcome indicators of the research are feasibility,physical symptoms and social-psychological status.Conclusion ET is applicable to a specific group of ICU patients with aphasia,and has shown good feasibility and effectiveness in the expression of patients'basic needs,self-assessment of symptoms and improvement of psychosocial status.

Objective To investigate the predictive value of serum lipoprotein-associated phospholipase A2(Lp-PLA2)and homocysteine(Hcy)combined with white matter hyperintensities(WMH)for cognitive impairment in patients with cerebral small vessel disease(CSVD).Methods A total of 240 patients with CSVD were selected.According to the Montreal Cognitive Assessment(MoCA)scale,all subjects were divided into the non-cognitive impairment group(MoCA≥26 points,120 cases)and the cognitive impairment group(MoCA＜26 points,120 cases).Paraventricular white matter high signal(PWMHs)and deep white matter high signal(DWMHs)were scored by Fazekas scale.The sum of the two parts was the total score,and the severity of DWMHs was graded by the score.The basic information,serum Lp-PLA2,Hcy level and severity of WMH were compared between the two groups.Logistic regression was applied to analyze influencing factors of cognitive impairment in CSVD patients.The predictive value of serum level of Lp-PLA2 and Hcy and WMH for cognitive impairment in CSVD patients was analyzed by receiver operating characteristic(ROC)curve.Results Compared with the non-cognitive impairment group,patients of the cognitive impairment group were older,had higher serum levels of Lp-PLA2 and Hcy,and had more severe of WMH(P＜0.05).Results of Logistic regression analysis showed that serum Lp-PLA2,Hcy levels and severity of WMH were influencing factors for cognitive impairment of patients with CSVD(P＜0.05).The results of ROC curve analysis showed that the area under the curve of serum Lp-PLA2,Hcy level combined with severity of WMH predicting cognitive impairment in patents with CSVD was 0.812,the sensitivity was 81.7%and the specificity was 71.7%(P＜0.05).Conclusion Patients with cognitive impairment caused by CSVD have higher serum levels of Lp-PLA2 and Hcy,and more severe WMH.The combination of the three has a relatively high predictive value for cognitive impairment in patents with CSVD.

Objective:To explore any effect of electrical stimulation of the right median nerve (RMNS) in modulating arousal patterns in the prefrontal cortex of a healthy adult.Methods:Twenty-three right-handed healthy participants received block-designed patterns of RMNS arousal. Functional near-infrared spectroscopy (fNIRS) was used to record any hemodynamic response in their prefrontal cortex. Changes in oxyhemoglobin (HbO), deoxyhemoglobin (HbR), and total hemoglobin (HbT) were analyzed by comparing the levels in stimulation blocks with resting-state periods.Results:fNIRS revealed significant activation of HbO signals in the left frontopolar area (channel 15) and the right frontopolar area (channels 37, 43 and 48) following RMNS arousal. There were significant differences in the HbR signals from the right frontopolar area (channel 41). There were, however, no significant differences in the HbT signals across all the measured channels.Conclusion:RMNS arousal enhances neurometabolic activity within the frontopolar sub-region of the prefrontal cortex in healthy adults.

OBJECTIVES: The purinergic receptor P2X2 (P2RX2) encodes an ATP-gated ion channel permeable to Na⁺, K⁺, and especially Ca²⁺. Loss-of-function mutations in P2RX2 are known to cause autosomal dominant nonsyndromic deafness 41 (DFNA41), which manifests as high-frequency hearing loss, accelerated presbycusis, and increased susceptibility to noise-induced damage. Zebrafish, owing to their small size, rapid development, high fecundity, transparent embryos, and high gene conservation with humans, provide an ideal model for studying human diseases and developmental mechanisms. This study aims to generate a p2rx2 knockout zebrafish model using CRISPR/Cas9 gene editing system to investigate the effect of p2rx2 deficiency on the auditory system, providing a basis for understanding P2RX2-related hearing loss and developing gene therapy strategies. METHODS: Two CRISPR targets (sgRNA1 and sgRNA2) spaced 47 bp apart were designed within the zebrafish p2rx2 gene. Synthesized sgRNAs and Cas9 protein were microinjected into single-cell stage Tübingen (TU)-strain zebrafish embryos. PCR and gel electrophoresis verified editing efficiency at 36 hours post-fertilization (hpf). Surviving embryos were raised to adulthood (F0), tail-clipped, genotyped, and screened for positive mosaics. F1 heterozygotes were generated by outcrossing, and F2 homozygous mutants were obtained by intercrossing. Polymerase chain reaction (PCR) combined with sequencing verified mutation type and heritability. At 5 days post-fertilization (dpf), YO-PRO-1 staining was used to examine hair cell morphology and count in lateral line neuromasts and the otolith region. Auditory evoked potential (AEP) thresholds at 600, 800, 1 000, and 2 000 Hz were measured in nine 4-month-old wild type and mutant zebrafish per group. RESULTS: A stable p2rx2 knockout zebrafish line was successfully established. Sequencing revealed a 66 bp insertion at the first target site introducing a premature stop codon (TAA), leading to early termination of protein translation and loss of function. Embryos developed normally with no gross malformations. At 5 dpf, mutants exhibited significantly reduced hair cell density in the otolith region compared with wild type, although lateral line neuromasts were unaffected. AEP testing showed significantly elevated auditory thresholds at all 4 frequencies in homozygous mutants compared with wild type (all P<0.001), indicating reduced hearing sensitivity. CONCLUSIONS We successfully generated a p2rx2 loss-of-function zebrafish model using CRISPR/Cas9 technology. p2rx2 deficiency caused hair cell defects in the otolith region and increased auditory thresholds across frequencies, indicating its key role in maintaining zebrafish auditory hair cell function and hearing perception. The phenotype's restriction to the otolith region suggests tissue-specific roles of p2rx2 in sensory organs. This model provides a valuable tool for elucidating the molecular mechanisms of P2RX2-related hearing loss and for screening otoprotective drugs and developing gene therapies.
Animals ; Zebrafish/genetics* ; Receptors, Purinergic P2X2/deficiency* ; CRISPR-Cas Systems/genetics* ; Gene Knockout Techniques ; Phenotype ; Zebrafish Proteins/genetics* ; Disease Models, Animal

Objective To investigate the clinical features,treatment and prognosis of primary testicular lymphoma(PTL),so as to provide reference for the standardized diagnosis and treatment of this disease.Methods Clinical data of 13 PTL cases treated in Xijing Hospital during Jan.2014 and Dec.2024 were retrospectively collected.The patients' diagnosis,treatment methods and prognosis were summarized.Results All 13 patients underwent orchiectomy of the affected side.According to the postoperative pathological results,11 cases were diagnosed as diffuse large B-cell lymphoma and 2 as NK/T-cell lymphoma.Among the 11 cases with diffuse large B-cell lymphoma,10 received immunotherapy and chemotherapy according to the international standardized treatment plan,and 5 received preventive myeloablative injection therapy.Recurrence in the contralateral testis occurred in 3 cases,1 complicated with central nervous system infiltration died,and another 1 refusing chemotherapy had contralateral testicular metastasis.Of the 2 cases with NK/T-cell lymphoma,1 received systemic chemotherapy and died after central nervous system recurrence,and another 1 died 1 month after surgery whithout undergoing chemotherapy.Conclusion Primary testicular lymphoma is highly invasive with poor prognosis.Patients with NK/T-cell lymphoma have extremely poor prognosis,while those with diffuse large B-cell lymphoma have relatively better prognosis.However,even after comprehensive treatment,it is still prone to recurrence in the testis and the central nervous system.

Objective To explore the clinical characteristics and prognostic analysis of acute corpus callosum in-farction.Methods A total of 1 466 patients with acute cerebral infarction admitted to the Neurology Department of Jiangbin Hospital in Guangxi from January 2019 to October 2023 and Neurology Department of Fuwai Hospital,Chinese Academy of Medical Sciences from January 2022 to December 2022.Among them,21 patients with acute corpus callosum infarction confirmed by MRI(observation group)and 25 patients with isolated subcortical infarction at the same period(control group)were selected.By comparing clinical data and follow-up information between two groups,we summarized the clinical characteristics of acute corpus callosum infarction,and analyzed the relevant factors affecting the prognosis of the corpus callosum infarction group.Results Acute corpus callosum infarction accounted for 1.43％(21/1 466)of patients with acute cerebral infarction in the same period.The main clinical manifestations include limb paralysis,cognitive decline,and speech impairment.Compared with the control group,the group with corpus callosum infarction had a longer onset visit time(P<0.05),more cognitive impair-ment(P<0.05),a higher proportion of mild stroke(P<0.05),more worsening symptoms during the course of the disease(P<0.05),a higher proportion of cardioembolic type(P<0.05),a lower proportion of small artery occlu?sion type(P<0.05)and a higher proportion of good prognosis(mRS score≤2 points)(P<0.05).The poor prog?nosis of corpus callosum infarction was found to be related to factors such as large lesions,multiple high?risk factors(≥3),concomitant lobar infarction and worsening of symptoms during the course of the disease.Conclusions Acute corpus callosum infarction often leads to cognitive impairment and mild limb paralysis,which frequently de?lays treatment.The poor prognosis is mainly related to factors such as lobar infarction,major lesions,and worsening of symptoms during the process.

Objective To investigate the effects of exosomal microRNA-1234-3p(miR-1234-3p)of lung cancer cells on the malignant behaviors of lung cancer cells,the polarization of tumor-associat-ed macrophages(TAMs),and the functions of T cells,as well as its potential molecular mecha-nisms.Methods Exosomes were extracted from lung cancer A549 cells,and their morphology was observed using transmission electron microscopy.The expression of exosomal marker proteins[tumor susceptibility gene 101(TSG101),CD63 and CD9]was detected by western blot.The relative ex-pression level of miR-1234-3p was measured using real-time fluorescence quantitative polymerase chain reaction(qRT-PCR).The expression of exosomal miR-1234-3p was inhibited by transfecting,the proliferation,migration,and invasion abilities of A549 cells were detected using the CCK-8 method,wound healing assay,and Transwell invasion assay,respectively.The exosomes were co-cultured with macrophages and T lymphocytes separately.The expression of TAM polarization markers CD206 and CD163 was detected by western blot.The secretion levels of cytokines[interleukin(IL)-6,IL-10,and transforming growth factor-β(TGF-β)]were measured using an enzyme-linked immu-nosorbent assay(ELISA).The proliferation and apoptosis abilities of T lymphocytes,as well as the expression of functional molecules[γ-interferon(IFN-γ)and programmed death receptor 1(PD-1)]were detected through cell experiments.The expression levels of proteins related to the phosphatidylinositol 3-kinase(PI3 K)/protein kinase B(AKT)signaling pathway were detected by western blot.Results The isolated exosomes were round double-layer vesicles with a diameter of 50 to 200 nm and expressed TSG101,CD63 and CD9 proteins.The expression level of miR-1234-3p in A549 cells was higher than that in human normal lung epithelial cells BEAS-2B,and the expression level of miR-1234-3p in A549 cell exosomes was higher than that in parental A549 cells,with statis-tically significant differences(P＜0.001).After inhibiting exosomal miR-1234-3p,the prolifera-tion,migration,and invasion abilities of A549 cells decreased,with statistically significantdifferenc-es(P＜0.001).After inhibiting exosomal miR-1234-3p,the levels of M2-type polarization marker proteins CD206 and CD163 in macrophages decreased,the levels of cytokines IL-10 and TGF-β de-creased,and the level of IL-6 increased,with statistically significant differences(P＜0.001),indi-cating that the polarization of macrophages toward the M2 type was inhibited.In T lymphocytes,af-ter inhibiting exosomal miR-1234-3p,cell viability increased,the apoptosis rate decreased,the ex-pression level of the functional molecule IFN-γ increased,and the expression level of PD-1 de-creased,with statistically significant differences(P＜0.01 orP＜0.001).After inhibiting exosom-al miR-1234-3p,the protein levels of phosphorylated(p)-PI3K and p-AKT in A549 cells de-creased,with statistically significant differences(P＜0.001).Conclusion Exosomal miR-1234-3p of lung cancer cells may promote the malignant behaviors of lung cancer cells,the polarization of TAMs toward the M2 type,and the dysfunction of T lymphocytes by activating the PI3K/AKT signa-ling pathway,thereby regulating the immunosuppressive microenvironment and promoting the pro-gression of lung cancer.