BackgroundInvasive vagus nerve stimulation therapy has been approved for the adjunctive treatment of treatment-resistant depression， which may contribute to the anti-inflammatory properties of vagus nerve stimulation （VNS）， whereas the efficacy of non-invasive transcutaneous cervical vagus nerve stimulation （tcVNS） in treating major depressive disorder （MDD） and its impact on plasma inflammatory factors remain unclear. ObjectiveTo observe the effect of escitaloprom combined with tcVNS on the status of depression， anxiety and sleep quality as well as the plasma levels of interleukin-6 （IL-6） and interleukin-10 （IL-10） in MDD patients， in order to provide references for the recovery and treatment of MDD patients. MethodsFrom August 21， 2019 to April 17， 2024， 45 patients who met the diagnostic criteria for MDD in the Diagnostic and Statistical Manual of Mental Disorders， fifth edition （DSM-5） were recruited from the psychosomatic outpatient clinic of the First Affiliated Hospital of Air Force Military Medical University. Subjects were divided into study group （n=23） and control group （n=22） using random number table method. All patients were treated with escitalopram. On this basis， study group added a 30-minute tcVNS therapy once a day for 4 weeks. While control group was given corresponding sham stimulation， and the duration of each stimulation lasted 30 seconds. Before and after 4 weeks of treatment， Hamilton Depression Scale-17 item （HAMD-17） was used to assess depressive symptoms， and HAMD-17 anxiety/somatization subfactor and insomnia subfactor were used to assess patients' anxiety/somatization symptoms and sleep quality. Levels of plasma IL-6 and IL-10 were measured by enzyme-linked immunosorbent assay （ELISA）. ResultsThe generalized estimating equation model yielded a significant time effect for HAMD-17 total score， anxiety/somatization subfactor score and insomnia subfactor score in both groups （Wald χ²=315.226， 495.481， 82.420， P<0.01）. After 4 weeks of treatment， HAMD-17 total score and anxiety/somatization subfactor score of study group were lower than those of control group， with statistically significant differences （Wald χ²=4.967， 32.543， P<0.05 or 0.01）， while no statistically significant difference was found in the insomnia subfactor score between two groups （Wald χ²=0.819， P=0.366）. Significant time effects were reported on plasma IL-6 and IL-10 levels in both groups （Wald χ²=21.792， 5.242， P<0.05 or 0.01）. Compared with baseline data， a reduction in plasma IL-6 levels was detected in both groups （Wald χ²=22.015， 6.803， P<0.01）， and an increase in plasma IL-10 levels was reported in study group （Wald χ²=5.118， P=0.024） after 4 weeks of treatment. ConclusionEscitalopram combined with tcVNS therapy is effective in improving depressive symptoms， anxiety/somatization symptoms and sleep quality in patients with MDD. Additionally， it helps reduce plasma IL-6 levels and increase IL-10 levels. ［Funded by Shaanxi Provincial Key Research and Development Program-General Project （number， 2023-YBSF-185）， www.clinicaltrials.gov number， NCT04037111］

BACKGROUND:Eucommia ulmoides has a certain osteogenic effect,which can promote the proliferation and differentiation of osteoblasts.However,it is unclear whether Eucommia ulmoides has effects on alveolar bone formation and Wnt/β-Catenin signaling pathway. OBJECTIVE:To investigate the mechanism by which Eucommia ulmoides promotes alveolar bone formation in ovariectomized rats based on the Wnt/β-Catenin signaling pathway. METHODS:Sixty female Sprague-Dawley rats were selected and randomly divided into five groups:blank control group,sham-operation group,model group,low-dose group Eucommia ulmoides group,and high-dose Eucommia ulmoides group,with twelve rats in each group.Osteoporosis animal models were constructed by bilateral oophorectomy in the model group and the low-dose and high-dose Eucommia ulmoides groups.The sham-operation group underwent the same method to remove adipose tissue of equal mass around the bilateral ovaries.Three months after surgery,the low-and high-dose Eucommia ulmoides groups were given 2.1 g/kg/d and 4.2 g/kg/d Eucommia ulmoides by gavage,respectively.The sham-operation group and model group were given the same amount of physiological saline by gavage.After 12 weeks of drug intervention,the changes in alveolar bone mass of rats in each group were observed through Micro-CT;hematoxylin-eosin staining was used to observe the pathological structural changes of alveolar bone in rats;enzyme linked immunosorbent assay was used to detect the expression levels of alkaline phosphatase and osteocalcin in the serum of rats;western blot was used to detect the expression levels of β-Catenin and Frizzled9 receptor proteins in the alveolar bone of rats;and real-time fluorescence quantitative PCR was used to detect the expression of osteocalcin,Runt-related transcription factor 2(Runx2),alkaline phosphatase,β-catenin,and frizzled9 mRNAs in alveolar bone tissues of rats. RESULTS AND CONCLUSION:Compared with the blank control group,bone volume fraction,trabecular number,trabecular thickness,and bone mineral density were reduced in the model group(P＜0.05),and trabecular separation was elevated(P＜0.05).Pathological observation showed that the arrangement of trabeculae was disordered and irregular,the trabeculae were thinned or broken,and the marrow cavity was enlarged in the model group,with a significant reduction in bone volume;the level of alkaline phosphatase in the serum was increased(P＜0.05),and the level of osteocalcin was decreased(P＜0.05);mRNA expression of alkaline phosphatase,osteocalcin,Runx2,β-catenin,and frizzled9 were decreased(P＜0.05);protein expression of β-Catenin and Frizzled9 was decreased(P＜0.05).Compared with the model group,the low-and high-dose Eucommia ulmoides groups showed an increase in bone volume fraction,trabecular number,trabecular thickness,and bone mineral density(P＜0.05)and a decrease in trabecular separation(P＜0.05).In the low-and high-dose Eucommia ulmoides groups,bone trabeculae were slightly aligned and thickened,with a significant increase in bone mass.Compared with the model group,the serum level of alkaline phosphatase was reduced(P＜0.05)and the serum level of osteocalcin was elevated(P＜0.05)in the low-and high-dose Eucommia ulmoides groups.Compared with the model group,the mRNA expression of alkaline phosphatase,osteocalcin,Runx2,β-catenin,and frizzled9 were increased in the low-and high-dose Eucommia ulmoides groups(P＜0.05).Compared with the model group,the protein expression of Frizzled9 was increased in the low-dose Eucommia ulmoides group(P＜0.05),while the protein expression of β-Catenin and Frizzled9 was increased in the high-dose Eucommia ulmoides group(P＜0.05).Compared with the low-dose Eucommia ulmoides group,the high-dose Eucommia ulmoides group had a more significant improvement in the above indexes.To conclude,Eucommia ulmoides can effectively promote the alveolar bone formation,and its mechanism of action might be related to the activation of the Wnt/β-catenin signaling pathway.

Background Injury poses a serious threat to human health. As global warming continues to intensify, there is an urgent need to explore the impact of temperature changes on injury deaths. However limited research has focused on this issue. Objective To investigate the relationship between daily mean temperature change (Tm) and injury death, as well as to estimate the associated future death burden in Hunan Province. Methods We employed an individual-level, time-stratified case-crossing design to establish a conditional logistic regression model to analyze the exposure-response relationship between daily mean temperature change and injury death in Hunan Province from 2013 to 2018. Consequently, we conducted subgroup analysis of gender, age group, and injury type. Finally, we estimated the excess burden of injury death attributable to temperature changes under a sustainable development path [low emission scenario (SSP1-2.6)], regional competition path [high emission scenario (SSP3-7.0)], or fossil fuel development path [very high emission scenario (SSP5-8.5)]. Results The study collected 155577 injury deaths in Hunan Province. The results indicated that for each 1 ℃ increment in daily mean temperature, the cumulative excess risk (CER) of injury mortality among Hunan residents increased by 0.71% (95%CI: 0.53%, 0.90%). Notably, the CER for intentional injuries (1.06%, 95%CI: 0.51%, 1.61%) was higher than that for unintentional injuries (0.66%, 95%CI: 0.46%, 0.87%). Warmer temperatures were positively associated with CER of mortality due to drowning, falls, transport injuries, assaults, and suicides, while they were negatively associated with mortality due to poisoning. Compared with 2010–2019, for 2090–2099, the excess mortality rate (EMR) due to ambient temperature increase in Hunan Province under the SSP5-8.5 scenario (14.62/100000, 95%CI: 10.81/100000, 18.40/100000) would be higher than that of the SSP3-7.0 scenario (10.28/100000, 95%CI: 7.58/100000, 12.97/100000) and the SSP1-2.6 scenario (3.35/100000, 95%CI: 2.46/100000, 4.23/100000); the EMR would be around 2.5 times among men (20.64/100000, 95%CI: 14.44/100000, 26.8/100000) than that among women (8.33/100000, 95%CI: 3.98/100000, 12.6/100000). Among unintentional injuries, the leading contributors to EMR would be drowning (4.46/100000), falls (3.96/100000), and transport injuries (2.96/100000). And among intentional injuries, the EMR for suicide (2.08/100000) would be higher than that for assault (0.47/100000). Conclusion Climate warming will increase the total burden of injury-related deaths among residents in Hunan Province, especially in the absence of effective mitigation strategies and measures. It is necessary to strengthen the prevention and control of severe injuries closely related to temperature changes, such as drowning, falls, traffic, and suicides injuries, in order to reduce injury deaths associated with climate change.

ObjectiveThis study aims to observe the clinical effect of Danggui Liuhuang Tang （DGLHT） on patients with type 2 diabetes mellitus （T2DM） complicated by atherosclerotic cardiovascular disease （ASCVD） at high risk， focus on evaluating the influence of DGLHT on cardiovascular risk indicators such as flow-mediated dilation （FMD）， atherogenic index of plasma （AIP）， and triglyceride-glucose index （TyG）， and explore the regulatory effect of DGLHT on the myeloid differentiation factor 88/nuclear factor-kappa B （MyD88/NF-κB） signaling pathway. MethodsThe clinical study was a single-center， double-blind， and randomized controlled trial. A total of 68 patients with T2DM-ASCVD at high risk for cardiovascular events with Yin deficiency and fire excess syndrome were enrolled and randomly assigned to a treatment group and a control group. The treatment group was given atorvastatin calcium tablets and DGLHT， while the control group was given atorvastatin calcium tablets and placebos. The treatment course was 12 weeks， with a final study completion of 30 patients in the treatment group and 29 in the control group. Changes in cardiovascular risk indicators such as FMD， AIP， TyG， and small dense low-density lipoprotein cholesterol （sdLDL-C） index were compared. Human umbilical vein endothelial cells （HUVECs） were used to establish a vascular endothelial injury and inflammation model. The protective effect of DGLHT on endothelial injury was verified by reverse transcription polymerase chain reaction （Real-time PCR） and Western blot . ResultsAfter 12 weeks of treatment， the AIP in the treatment group significantly decreased compared with that before the treatment （P<0.05）. Compared with the control group， the treatment group showed significant improvements in FMD and TyG （P<0.05）. Additionally， the treatment group demonstrated significant reductions in two-hour postprandial glucose （2 hPG）， glycated albumin （GA）， triglycerides （TG）， apolipoprotein E （Apo E）， and sdLDL-C （P<0.05）. Analysis of traditional Chinese medicine （TCM） syndrome efficacy indicated that in the treatment group， Yin deficiency and fire excess syndromes， including dry throat and mouth （P<0.05）， excessive thirst （P<0.01）， tidal fever and night sweats （P<0.05）， and dry stools （P<0.05）， improved. Compared with the control group， the treatment group showed significant improvements in symptoms of dry throat and mouth （P<0.05） and excessive thirst （P<0.01）. TCM syndrome scores significantly decreased （P<0.01）， and the overall efficacy rate was 56.67%， significantly higher than the 10.34% observed in the control group （P<0.01）. At the cellular level， increasing concentrations of DGLHT led to decreased messenger ribonucleic acid （mRNA） levels of pro-inflammatory cytokines interleukin-6 （IL-6）， tumor necrosis factor-alpha （TNF-α）， and interleukin-1-beta （IL-1β） in lipopolysaccharide （LPS）-stimulated HUVECs （P<0.01）， with significant reductions in the high-concentration group （P<0.01）. DGLHT may inhibit the expressions of MyD88 and phosphorylated （p）-NF-κB p65 proteins in a concentration-dependent manner. ConclusionDGLHT shows significant effects in reducing cardiovascular risks and may exert an anti-inflammatory effect by inhibiting the MyD88/NF-κB signaling pathway. This finding provides a new perspective for the prevention and treatment of cardiovascular diseases in high-risk individuals with T2DM-ASCVD.

Objective To investigate the clinical efficacy of platelet-rich plasma (PRP) therapy for interstitial cystitis/bladder pain syndrome (IC/BPS). Methods This single-center prospective study involved 97 IC/BPS patients treated in our hospital during Sep.2023 and Apr.2025, who underwent transurethral bladder injection of PRP. The injections were administered once a month for four sessions. The global response assessment (GRA) score,24-hour urinary frequency, maximum single voiding volume, visual analogue scale (VAS) score, O'Leary score, pelvic pain, urgency and frequency (PUF) score, and Zung self-rating anxiety scale (SAS) score were analyzed. Results All 97 patients completed four injections. The GRA score,24-hour urinary frequency, VAS score, O'Leary score and PUF score were improved significantly after treatment (P<0.007). Intraoperative bladder capacity with significant improvement were observed after the first injection (P<0.01), and the maximum urine output were observed after the fourth injection (P<0.007). The SAS score was not significantly improved. Conclusion Repeated PRP injections can effectively alleviate bladder pain, improve frequent and urgent urination symptoms, and increase the bladder capacity.

Objective:To comprehensively understand the disease burden of liver cirrhosis and other chronic liver diseases caused by alcohol use in China from 1990 to 2019, as well as to predict the trends in disease burden from 2020 to 2030.Methods:The analysis utilized data from the Global Burden of Disease study in 2019 (GBD2019). Key indicators such as incidence rate, mortality rate, disability-adjusted life years (DALY), years of life lost due to premature mortality, and years lived with disability were selected to describe the disease burden of alcohol-related liver cirrhosis and other chronic liver diseases in China from 1990 to 2019. The estimated annual percentage change (EAPC) was used to depict the temporal trends in disease burden. Furthermore, a Bayesian age-period-cohort (BAPC) model was constructed using R software to predict the age-standardized incidence rate (ASIR) and age-standardized mortality rate (ASMR) of alcohol-related liver cirrhosis and other chronic liver diseases in China from 2020 to 2030.Results:From 1990 to 2019, the incidence of alcohol-related liver cirrhosis and other chronic liver diseases in China showed an upward trend, with an EAPC of 0.31% (95% CI: 0.10%-0.52%). However, the DALY declined, with an EAPC of -2.81% (95% CI: -2.92% - -2.70%). The ASMR showed a downward trend, with an EAPC of -2.55% (95% CI: -2.66% - -2.45%). The highest incidence of cirrhosis of liver caused by alcohol and other chronic liver diseases was reported in the age group of 35-49 years, while the ASMR increased gradually with age, with a significant rise after the age of 30. The age-standardized DALY rate peaked between the ages of 55 and 64. The disease burden indicators for males were consistently higher than those for females during the same period. According to the predictions of the BAPC model, from 2020 to 2030, the ASIR for cirrhosis of liver caused by alcohol and other chronic liver diseases in the entire population of China was projected to increase from 3.45/100 000 in 2020 to 3.78/100 000 in 2030, a growth of 9.57%. Conversely, the ASMR was expected to decrease from 1.45/100 000 in 2020 to 1.24/100 000 in 2030, a reduction of 14.48%. Conclusions:The disease burden of cirrhosis of liver caused by alcohol and other chronic liver diseases remained serious in China, especially in men and the middle-aged to elderly population. There is a pressing need to prioritize attention and resources towards these groups. Despite the projected decrease in ASMR, the ASIR continued to rise and is expected to persist in its upward trend until 2030.

Objective:To study the application effect of the Benner's theory stratified training based on the "Protect the World" platform for nurses specialized in neurological rehabilitation.Methods:A total of 70 nurses who underwent on-the-job training for neurorehabilitation nursing specialists in 2023 were divided into control group ( n=35) and observation group ( n=35) based on random odd and even numbers to receive different training methods. The control group received routine nursing training, while the observation group received Benner's theory stratified training based on the "Protect the World" platform. The theoretical and skill assessment scores, job competency, and satisfaction scores of two groups of nurses were compared before and after training. SPSS 25.0 was used for t-test and chi-square test. Results:Before training, there were no significant differences between the two groups of nurses in terms of theory scores [(88.35±4.41) vs. (89.43±4.07)] and skill assessment scores [(89.22±3.27) vs. (88.43±3.16)]. After training, the theoretical and skill assessment scores were significantly higher in the observation group as compared with the control group [(95.51±5.01) vs. (90.24±4.99) and (95.15±4.24) vs. (91.13±4.33), both P<0.05]. After training, the competency scores and total scores of education guidance, management function, diagnostic function, assistance role, and intervention treatment were significantly higher in the observation group than in the control group ( P<0.05). The satisfaction survey scores were significantly higher in the observation group than in the control group ( P<0.05). Conclusions:The Benner's theory stratified training based on the "Protect the World" platform can improve the theoretical and skill assessment scores of nurses specialized in neurological rehabilitation. This approach significantly boosts their overall professional competence and holds considerable potential for broader adoption.

Replantation of traumatic amputation in children has its own characteristics. This consensus primarily focuses on the issues related to the treatment of traumatically amputated limb injuries in children. Organised along a timeline, the consensus summarises domestic and international clinical experiences in emergency care and injury assessment of traumatic limb amputation limbs, indications and contraindications for replantation surgery, principles and procedures of replantation surgery, postoperative medication and management, as well as rehabilitation in children. The aim of this consensus is to propose standardise the treatment protocols for limb replantation for children therefore to serve as a reference for clinical practitioners in medical practices, and further improve the treatment and care for the traumatic limb amputations in children.

Objective To observe the distribution of atypical memory B cells in peripheral blood of children with frequently relapsing nephrotic syndrome(FRNS).Methods A total of 60 children with primary ne-phrotic syndrome(PNS)admitted to the hospital from October 2020 to March 2023 were selected as the re-search objects.According to the response to glucocorticoid(GC),they were divided into non-frequently relap-sing nephrotic syndrome(NFRNS)group(25 cases)and FRNS group(35 cases).A total of 20 age-and gen-der-matched healthy children were enrolled as the control group.The changes of atypical memory B cells in each group before and after GC treatment were compared,and the correlation between the changes and clinical data was analyzed.Results Before GC treatment,The percentages of total B cells(CD19+CD20+),total memory B cells(CD19+CD20+CD27+),resting memory B cells(CD19+CD20+CD21+CD27+)and atypical memory B cells(CD19+CD20+CD21-CD27-)in FRNS group and NFRNS group were significantly higher than those in control group.And the FRNS group was significantly higher than the NFRNS group(P＜0.05).After GC treatment,the percentages of total B cells,total memory B cells,resting memory B cells,acti-vated memory B cells(CD19+CD20+CD21-CD27+)and atypical memory B cells in FRNS group and NFRNS group were lower than those before GC treatment(P＜0.05).The FRNS group had a significantly higher pro-portion of atypical memory B cells than the NFRNS group and the control group(P＜0.05).Before GC treat-ment,the 24 h urinary protein in FRNS group and NFRNS group were higher than those in control group,and the levels of immunoglobulin G and albumin were lower than those in control group.The 24 h urinary protein in FRNS group was significantly higher than that in NFRNS group(P＜0.05).Before GC treatment,there was a positive correlation between 24 h urinary protein and the proportion of atypical memory B cells in FRNS group(P＜0.05).Conclusion There is abnormal distribution of atypical memory B cells in peripheral blood of FRNS children.The increase of atypical memory B cells can be used as a marker of recurrence of FRNS af-ter GC treatment.

Objective:To investigate the role and mechanism of human umbilical cord mesenchymal stem cell exosomes (hUCMSC-ex) in wounds with escharectomy and skin grafting in scalded rats.Methods:The study was an experimental study. Twelve male Sprague-Dawley (SD) rats aged 6-8 weeks were divided into combined treatment group, fixed+allogeneic skin group, autologous skin+allogeneic skin group, and allogeneic skin group by random number table method (the same grouping method hereinafter), with 3 rats in each group. The four groups of rats were inflicted with scalded wounds on the back and performed with escharectomy, and then the wounds of rats in combined treatment group were fixed with a metal ring (the same fixing method hereinafter) and transplanted with autologous skin grafts and allogeneic skin grafts, and the other three groups of rats were fixed and/or transplanted with skin grafts corresponding to the group name. At 14, 21, and 28 d after surgery, the wound healing area in the four groups of rats was measured. Another 15 male SD rats aged 6-8 weeks were divided into normal group with no treatment, high exosome group, low exosome group, supernatant group, and phosphate buffer solution (PBS) group, with 3 rats in each group. The last 4 groups of rats were treated as that in the above-mentioned combined treatment group, and then were injected around the wounds with 200 μL of PBS containing 100 μg of hUCMSC-ex, 200 μL of PBS containing 50 μg of hUCMSC-ex, 200 μL of supernatant with no hUCMSC-ex, and 200 μL of PBS at 0 (immediately), 7, 14, and 21 d after surgery, respectively. At 14, 21, and 28 d after surgery, the wound healing area in the four groups of rats was measured. The wound neo-epithelial tissue of rats in high exosome group and PBS group at 28 d after surgery and the normal skin tissue of rats in normal group at the same time point were taken, and the differentially expressed proteins were screened by label-free quantitative proteomics method; the two up-regulated and differentially expressed proteins, the immunoglobulin G1 heavy chain constant region (IGHG1) and cystatin A (CSTA) with the largest and second largest fold changes in comparison between high exosome group and PBS group were selected, and their protein expressions were detected by Western blotting. The number of samples in all experiments was 3.Results:At 14, 21, and 28 d after surgery, the wound healing area in combined treatment group, autologous skin+allogeneic skin group, and allogeneic skin group of rats was significantly larger than that in fixed+allogeneic skin group ( P<0.05), the wound healing area in autologous skin+allogeneic skin group of rats at 21 d after surgery and that in allogeneic skin group of rats at 14 and 21 d after surgery was significantly larger than that in combined treatment group ( P<0.05), and the wound healing area in allogeneic skin group of rats at 14 d after surgery was significantly larger than that in autologous skin+allogeneic skin group ( P<0.05). The wound healing area of rats in high exosome group and low exosome group at 14, 21, and 28 d after surgery and in supernatant group at 14 and 28 d after surgery was significantly larger than that in PBS group ( P<0.05); the wound healing area in high exosome group of rats at 14 and 21 d after surgery was significantly larger than that in supernatant group ( P<0.05), and the wound healing area at 14 d after surgery was significantly larger than that in low exosome group ( P<0.05); the wound healing area in low exosome group of rats at 14 d after surgery was significantly larger than that in supernatant group ( P<0.05). Compared with that in PBS group, 332 proteins were differentially expressed in the neo-epithelial tissue of the wounds in high exosome group of rats at 28 d after surgery ( P<0.05), among which the protein expressions of IGHG1 and CSTA were significantly up-regulated (with fold change of 12.60 and 2.27, respectively, P<0.05). Compared with those of normal skin tissue in normal group, 1 400 and 1 057 proteins were differentially expressed in the neo-epithelial tissue of the wounds in high exosome group and PBS group of rats at 28 d after surgery, respectively. The protein expressions of IGHG1 and CSTA in the wound neo-epithelial tissue in high exosome group of rats at 28 d after surgery were significantly larger than those in normal skin tissue of rats in normal group ( P<0.05) and those in PBS group ( P<0.05). Conclusions:hUCMSC-ex may accelerate the repair process of wounds with escharectomy and skin grafting and improve the quality of wound healing in scalded rats by regulating the protein expressions of IGHG1 and CSTA.