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.

ObjectiveTo analyze the changing trend of the disease burden of acute viral hepatitis （AVH） globally and in China from 1990 to 2021， and to provide a basis for optimizing prevention and control strategies. MethodsRelated data were extracted from the Global Burden of Disease 2021 database， including incidence rate， mortality rate， and disability-adjusted life years （DALY） for AVH globally and in China from 1990 to 2021， and the patients were divided into groups according to region， age， sex， and type of hepatitis. The Joinpoint regression model was used to calculate average annual percentage change （AAPC） and its 95% confidence interval （CI）. ResultsFrom 1990 to 2021， there was a tendency of reduction in the age-standardized incidence rate， mortality rate， and DALY rate of AVH globally， with an average annual reduction of 1.02% （95%CI： -1.10% to -0.94%， P<0.001）， 3.97% （95%CI： -4.12% to -3.82%， P<0.001）， and 3.64% （95%CI： -3.84% to -3.44%， P<0.001）， respectively； in China， there was also a tendency of reduction in these indicators， with an average annual reduction of 1.63% （95%CI： -1.70% to -1.57%， P<0.001）， 9.24% （95%CI： -9.51% to -8.97%， P<0.001）， and 7.93% （95%CI： -8.15% to -7.71%， P<0.001）， respectively. In addition， China’s share of the global disease burden of AVH continued to decrease； the proportion of new cases decreased from 24% in 1990 to 15% in 2021， the proportion of deaths decreased from 19% to 4%， and the proportion of DALY decreased from 16% to 4%. From 1990 to 2021 globally， the peaks in the incidence rate， mortality， and DALY of AVH were observed in children under 5 years of age； in China， although the peak incidence rate of the disease was still observed in children under 5 years of age， there was a tendency of increase in the incidence rate of AVH among young adults aged 25 — 29 years in recent years， with the most significant increase in the cases of acute hepatitis B （accounting for 59% of the cases in this age group）， while the disease burden of mortality and DALY mainly affected the middle-aged and elderly populations. The disease burden of AVH in the male population was higher than that in the female population. As for the distribution of disease types， acute hepatitis A was the predominant type of AVH， accounting for 64% globally and 48% in China， whereas acute hepatitis B was the leading cause of mortality and DALY， accounting for 50% of deaths globally， 80% of deaths in China， 47% of DALY globally， and 69% of DALY in China. ConclusionThere is a tendency of reduction in the disease burden of AVH globally and in China from 1990 to 2021， but there is a tendency of increase in the incidence rate of AVH among young adults in China， especially acute hepatitis B. It is necessary to implement targeted prevention and control strategies.

Intervertebral disc degeneration (IDD) is largely attributed to impaired endogenous repair. Nucleus pulposus-derived stem cells (NPSCs) senescence leads to endogenous repair failure. Small extracellular vesicles/exosomes derived from mesenchymal stem cells (mExo) have shown great therapeutic potential in IDD, while whether mExo could alleviate NPSCs senescence and its mechanisms remained unknown. We established a compression-induced NPSCs senescence model and rat IDD models to evaluate the therapeutic efficiency of mExo and investigate the mechanisms. We found that mExo significantly alleviated NPSCs senescence and promoted disc regeneration while knocking down thioredoxin (TXN) impaired the protective effects of mExo. TXN was bound to various endosomal sorting complex required for transport (ESCRT) proteins. Autocrine motility factor receptor (AMFR) mediated TXN K63 ubiquitination to promote the binding of TXN on ESCRT proteins and sorting of TXN into mExo. Knocking down exosomal TXN inhibited the transcriptional activity of nuclear factor erythroid 2-related factor 2 (NRF2) and activator protein 1 (AP-1). NRF2 and AP-1 inhibition reduced endogenous TXN production that was promoted by exosomal TXN. Inhibition of NRF2 in vivo diminished the anti-senescence and regenerative effects of mExo. Conclusively, AMFR-mediated TXN ubiquitination promoted the sorting of TXN into mExo, allowing exosomal TXN to promote endogenous TXN production in NPSCs via TXN/NRF2/AP-1 feed-forward circuit to alleviate NPSCs senescence and disc degeneration.

Objective: To investigate if high glucose (HG) exacerbates Porphyromonas gingivalis (P.g) lipopolysaccharide (LPS)-induced inflammatory response in human gingival fibroblasts (HGFs) and to explore the underlying mechanisms. To provide a basis for the mechanism of diabetes aggravating periodontitis. Methods: HGFs were divided into four groups: the control group (basal medium), the LPS group (treated with 5 μg/mL P.g-LPS for 24 h), the HG group (treated with 25 mmol/L glucose for 24 h), and the HG+LPS group (treated with 25 mmol/L glucose + 5 μg/mL P.g-LPS for 24 h). After culturing for 24 h in the respective media, the cells were harvested for experiments. Intracellular reactive oxygen species (ROS) and mitochondrial reactive oxygen species (mtROS) were detected using 2 ', 7' - dichlorodihydrofluorescein diacetate (DCFH-DA) and MitoSOX Red staining, respectively. Fluorescence intensity was analyzed by confocal fluorescence microscopy and directly measured in cell suspension. Immunofluorescence was used to detect changes in mitochondrial DNA (mtDNA) content of HGFs. Real-time fluorescence quantitative PCR was used to detect the content of mtDNA in cytoplasm and cell supernatant. Protein expression of the cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) pathway was assessed by western blot, while mRNA expression levels of tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and interleukin-6 (IL-6) were detected by PCR. Results: Compared to the control group, both the LPS group and the HG group exhibited a significant increase in ROS and mtROS, with a more pronounced elevation in the HG+LPS group, demonstrating a synergistic effect (ROS: F = 396.5, P < 0.001; mtROS: F = 29.38, P < 0.001, CI < 1). The cytoplasmic mtDNA content was significantly elevated in the LPS group, with a more marked increase in the HG+LPS group (F = 27.85, P < 0.001). The supernatant mtDNA levels were significantly higher in both the LPS and HG groups, with a more pronounced elevation in the HG+LPS group (F = 15.26, P < 0.001). The phosphorylated proteins p-STING, p-TBK1, and p-P65 in the cGAS-STING pathway showed varying degrees of activation in the LPS and HG groups, reaching the highest levels in the HG+LPS group (p-STING: F = 52.67, P < 0.001; p-TBK1: F = 15.67, P = 0.001; p-P65: F = 9.83, P = 0.005), while p-IRF3 showed no significant differences among the groups (P = 0.072). Pro-inflammatory cytokine TNF-α was significantly higher in the HG+LPS group compared to the control group (F = 15.05, P < 0.001), and IL-1β increased in both the LPS and HG groups, with a more pronounced rise in the HG+LPS group (F = 30.98, P < 0.001). IL-6 showed no significant differences among the groups (P = 0.847). Conclusion High glucose and LPS act synergistically to enhance oxidative stress, accompanied by increased mtDNA release, which activates the cGAS-STING pathway, thereby amplifying the inflammatory response in HGFs.

Objective To develop a virtual reality rehabilitation support system and evaluate its effects on improving discharge readiness in caregivers of laryngectomy patients.Methods The system is equipped with a virtual reality-based home nursing skills guidance module for post-laryngectomy patients and an evidence-based artificial intelligence Q&A module.A convenience sampling method was adopted to select 64 caregivers of patients who underwent laryngectomy for the first time in the otorhinolaryngology head and neck surgery department of a tertiary A hospital in Beijing from July 2024 to January 2025 for a systematic study on application effects.To avoid cross-contamination between an experimental group and a control group,ward-based grouping was applied.A coin toss was used to assign Ward 1 to an experimental group and Ward 2 to a control group,with 32 cases in each group.The experimental group received discharge guidance based on the virtual reality technology,while the control group was provided with conventional verbal and written discharge instructions.The readiness for hospital discharge and the quality of discharge teaching scores of caregivers were compared between the 2 groups after the intervention.Results No sample detachment.After the intervention,the patient caregivers in the experimental group scored significantly higher than those in the control group in terms of discharge readiness and quality of discharge guidance,with a statistically significant difference(P＜0.001).Conclusion This study developed the virtual reality rehabilitation system for laryngeal cancer patients demonstrated good feasibility and effectiveness.The application of this system for discharge education significantly improved discharge readiness of caregivers and quality of discharge guidance for post-laryngectomy patients.It also helped with the optimization of health education models,enhancement of nursing resource utilization efficiency,and improvement of transitional care.

Depressive disorder is one of the common mental diseases, which seriously affects the daily work and life of patients. In recent years, transcranial magnetic stimulation (TMS) treatment has shown satisfactory effects in the clinical application of depression. However, depressive disorder involves complex symptoms, including functional impairment in different dimensions such as emotion, cognition, body and behavior, which leads to significant individual differences in the efficacy of TMS intervention. Therefore, with different symptoms as the starting point, this article systematically reviewed the clinical studies of TMS treatment for different symptom groups of depressive disorder, in order to provide scientific reference for individualized treatment of depressive disorder using TMS treatment.

OBJECTIVE: To summarize the research progress of suture augmentation (SA) in anterior cruciate ligament (ACL) reconstruction. METHODS: A comprehensive review of recent literature about SA in ACL reconstruction at home and abroad was conducted. The efficacy of SA in ACL reconstruction was evaluated by examining the definition, biomechanics, and histological studies of SA, along with its clinical application status in ACL reconstruction. RESULTS: SA demonstrates significant advantages in enhancing the biomechanical stability of ACL grafts, reducing the risk of re-rupture, and accelerating postoperative recovery. Specifically, SA improves graft stiffness, ultimate failure strength, and cyclic stability, thereby diminishing the risk of early postoperative failure and joint instability. Histologically, it fosters remodeling and tendon-bone integration through early load-sharing mechanisms; however, stress shielding may interfere with natural remodeling processes, warranting further attention. Clinically, SA reduces graft failure rates and the need for revision surgeries, markedly improving knee joint stability and functional recovery in young patients. Nevertheless, its impact on graft maturation and potential complications remains controversial. CONCLUSION Despite the many advantages of SA in ACL reconstruction, future endeavors should focus on optimizing tensioning techniques, developing bioactive materials, and conducting large-scale randomized controlled trials to further elucidate its clinical value and scope of applicability, providing a more reliable solution for ACL reconstruction.
Humans ; Anterior Cruciate Ligament Reconstruction/methods* ; Biomechanical Phenomena ; Anterior Cruciate Ligament/surgery* ; Anterior Cruciate Ligament Injuries/surgery* ; Suture Techniques ; Sutures ; Tendons/transplantation* ; Joint Instability/prevention & control* ; Knee Joint/surgery*

Objective To investigate the effects of electroacupuncture(EA)at"Baihui(GV 20),""Pishu(BL 20),"and"Zusanli(ST 36)"on the learning and memory functions of rats with Alzheimer's disease(AD)induced by Aβ1-42.Additionally,the mechanism of EA in treating AD was explored from the perspective of the inflammatory cascade mediated by the NF-κ B/NLRP3/Caspase-1 signaling pathway.Methods A rat model of Alzheimer's disease was established by bilateral injection of Aβ1-42 solution into the C1 region of the hippocampus.According to the random number table method,32 male SPF-grade rats were divided into four groups(n=8 per group):a sham-operated group,a model group,an electroacupuncture(EA)group,and a Western medicine group(donepezil hydrochloride).The EA group received electroacupuncture at the"Baihui","Pishu",and"Zusanli"acu-points;the Western medicine group received donepezil hydrochloride via gavage.After the treatment period,Morris water maze experiments were conducted to evaluate learning and memory abilities.Hematoxylin and eosin(HE)staining was used to examine morphological changes in hippocampal tissues.Enzyme-linked immunosorbent assay(ELISA)was employed to measure serum levels of TNF-α and IL-1β.Western blotting and immunofluorescence staining were utilized to assess the co-expression levels of NF-κB p65,NLRP3,and Caspase-1 proteins in the hippocampal region.Results Compared with the sham-operated group,rats in the post-modeling group exhibited significantly prolonged escape latency(P<0.05),reduced crossings of the original platform location,and decreased time spent in the target quadrant(P<0.05).Additionally,nuclear morphology was altered,neurons surrounding the hippocampus displayed necrosis,vacuolar degeneration,and chromatin marginalization.Serum levels of TNF-α and IL-1β were elevated(P<0.05),and protein expression levels as well as fluorescent positivity for NF-κB p65,NLRP3,and caspase-1 in the hippocampus were increased(P<0.05).Compared with the model group,rats in both the EA and Western medicine groups showed a trend toward shorter escape latency(P<0.05),increased crossings of the original platform location and time spent in the target quadrant(P<0.05).Cell structures were largely intact,with only a few nuclei showing slight irregularities and some chromatin accumulation at the edges.Serum levels of TNF-α and IL-1β were reduced(P<0.05),and protein expression levels and fluorescence positivity for NF-κB p65,NLRP3,and caspase-1 in the hippocampus were also decreased(P<0.05).Conclusion EA enhances the learning and memory capabilities of AD rats,potentially by downregulating the NF-κ B/NLRP3/Caspase-1+signaling+pathway and decreasing the release of neuroinflammatory factors,thereby alleviating cognitive dysfunction in AD rats.

A 65-year-old male was admitted to Peking Union Medical College Hospital. The patient had intermittent fever for 2 months with a maximum body temperature of 39.3 ℃ and elevated serum creatinine levels for 1 week. He had no other suggestive symptoms or positive signs. Laboratory test results suggested acute kidney injury and a sharp elevation in serum lactic dehydrogenase levels. Abdominal enhanced computed tomography (CT) revealed multiple low-density lesions, and further biopsy pathology demonstrated chronic inflammation. Thereafter, positron emission tomography (PET)/CT showed abnormally elevated uptake value for the bones throughout the entire body, in addition to the liver and brain. Repeated bone marrow biopsy finally confirmed metastatic bone cancer, which possibly originated from the kidney according to immunohistochemical staining. In this rare case of fever of unknown origin, the primary lesion was a renal tumor with bone, liver, and brain metastases. Enhanced CT and PET/CT provided negative results, and the diagnosis was eventually confirmed by repeated bone marrow pathology.