Objective To investigate the therapeutic effects and mechanisms of Jianyang Tablets(mainly with the functions of tonifying the kidneys,replenishing essence,invigorating yang,and alleviating erectile dysfunction)on erectile dysfunction(ED)in rats with liver depression and kidney deficiency syndrome.Methods The 60 male SD rats were randomly divided into a normal group,a model group,a Tadalafil group,and low-,medium-,and high-dose Jianyang Tablets groups.Except for the normal group,all other groups underwent a 14-day composite modeling protocol combining intramuscular hydrocortisone injections and limb immobilization to induce ED with liver depression and kidney deficiency syndrome.Treatments were administered for 28 consecutive days after successful modeling.The body mass differences were recorded and compared before and after the experiment.Behavioral assessments included open-field test and mounting test were conducted.Enzyme-linked immunosorbent assay(ELISA)was used to measure nitric oxide synthase(NOS),cyclic adenosine monophosphate(cAMP),and cyclic guanosine monophosphate(cGMP)levels in penile cavernous tissues.Nitric oxide(NO)level was quantified using the Griess reagent colorimetric method.Results Compared with the normal group,the model group exhibited reduced horizontal activity grid counts in the open-field test,prolonged mounting latency,decreased mounting frequency,decreased body mass,and reduced levels of NOS,NO,cGMP,and cAMP in penile cavernous tissues,with statistical significance(P＜0.05 or P＜0.01).Compared with the model group,the Tadalafil group and medium-and high-dose Jianyang Tablets groups showed increased horizontal activity grid counts and vertical activity counts in the open-field test,shortened mounting latency,elevated mounting frequency,increased body mass,and upregulated levels of NOS,NO,cGMP,and cAMP in penile cavernous tissues,with statistical significance(P＜0.05 or P＜0.01).No significant differences were observed among the intervention groups for the aforementioned indices(P＞0.05).Conclusion Jianyang Tablets effectively improves erectile function in rats with liver depression and kidney deficiency syndrome,potentially mediated by modulation of the NO-cGMP signaling pathway.

Objective:To construct a dispatching system based on ultra wide band(UWB)positioning technique,so as to enhance dynamic management capabilities for equipment and clinical response efficiency.Methods:The dispatching system based on UWB positioning technique for emergency equipment included internet of things(IoTs)perception layer of network,network layer,data service layer,and business application layer of intelligently medical equipment,which integrated the positioning technique with UWB centimeter level and the deep Q-network(DQN)algorithm,and it can realize real-time localization and intelligent dispatching decisions for equipment.The used thirty-five emergency equipment in the intensive care unit(ICU)ward of Eastern Branch of Ningbo Medical Center Li Huili Hospital from January 2023 to December 2024 were selected.Based on different management modes,25 equipment using conventional manual dispatching during January and June 2023 were divided into control group,while 25 equipment using the UWB dispatching technique-based dispatching system during July and December 2023(included 15 equipment of the original control group and 10 new equipment at later stage)were used as observation group.The dispatching efficiency,utilization rate,positioning precision,and maintenance efficiency of equipment between two groups were compared.Results:The dispatching time for equipment in the observation group was(7.2±0.8)min,which significantly shorter than(12.2±1.5)min in the control group,and the difference was significant(t=18.34,P<0.05).The distance of movement,and response time for fault in the observation group were significantly lower than those in the control group,and the utilization rate of equipment was significantly higher than that in the control group,and the differences were significant(t=15.67,14.28,6.92,P<0.05).The repair rate for fault in the observation group was significantly higher than that in the control group,and the difference was significant(x2=7.80,P<0.05).The positioning error of the system is(35±10)cm.Conclusion:The UWB-based dispatching system can significantly optimize the dispatching process for resource of emergency equipment,which can improve utilization and management efficiency for equipment.It can provide reliably technical support for rapid response in clinical emergency.

AIM To investigate the promotional effects of esculin combined with bone marrow mesenchymal stem cells(BM-MSCs)transplantation on the repair of spinal cord injury(SCI)in rats.METHODS The rats were randomly divided into the sham operation group,the model group,the esculin group for gavage of 20 mg/kg esculin,the BM-MSCs group for tail vein injection of 1 mL of 1×106/mL BM-MSCs,and the combinaiton treatment group.The SCI rat model was established using Allen's method,followed by the 14 days consecutive corresponding drug administration starting from the 2nd day after modeling.On days 3,7 and 14 of drug administration,the rats had their hind limbs motor function evaluated by the BBB scoring;and their footprint experiment conducted on the 14th day after modeling.After 14 days of administration,the rats had their morphological changes of spinal cord tissue observed with HE staining and Nissl staining;their activities of SOD and GSH,and level of MDA in spinal cord tissue detected by kits;their expressions of MAP2,GAP43 and GFAP in spinal cord tissue detected by immunofluorescence;and their expressions of NQO-1,Nrf-2,Bcl-2 and Bax proteins in spinal cord tissue detected by Western blot.RESULTS Compared with the model group,the groups interved with esculin,or BM-MSCs,or the combination treatment showed improvements in hind limb function and spinal cord tissue morphology(P＜0.05);decreased MDA levels(P＜0.05);increased SOD and GSH activities(P＜0.05);increased MAP2 and GAP43 fluorescence intensity(P＜0.05);decreased GFAP fluorescence intensity(P＜0.05);increased NQO-1,Nrf-2 and Bcl-2 protein expressions(P＜0.05);and decreased Bax protein expression(P＜0.05).And the combination treatment group was observed with an even better effects(P＜0.05).CONCLUSION The combination of esculin and BM-MSCs transplantation can effectively improve the spinal cord tissue damage and hind limb function in SCI rats.This effect may be achieved by activating the Nrf-2/NQO-1 signaling pathway to inhibit oxidative stress response,thereby reducing neuronal apoptosis,blocking glial scar formation,and promoting stem cell differentiation to rebuild neurons.

AIM:This study aimed to investigate the protective effects of Carthamus tinctorius L.-derived nanovesicles(CDNVs)and their regulatory mechanisms in endothelial cell injury induced by oxidized low-density lipopro-tein(ox-LDL).METHODS:Human umbilical vein endothelial cells(HUVECs)were cultured in vitro and subjected to ox-LDL treatment to establish an endothelial cell injury model.The experimental groups included the normal control(NC)group,ox-LDL group(HUVECs treated with 100 mg/L ox-LDL for 24 h),and CDNVs+ox-LDL group(pre-treated with 40 mg/L CDNVs for 1 hour followed by co-culture with 100 mg/L ox-LDL for 24 hours).Cell proliferation and apoptosis were assessed by the EdU incorporation assay and flow cytometry,respectively.Changes in signal-induced proliferation-associ-ated 1-like protein 2(SIPA1L2)mRNA expression were measured by RT-qPCR,and the expression levels of autophagy-related proteins and SIPA1L2 were evaluated by Western blot.SIPA1L2 ubiquitination was evaluated by immunoprecipita-tion assay.RESULTS:(1)CDNVs were successfully isolated and purified,characterized as nanoscale vesicles with a circular shape and a double-layered membrane structure.(2)CDNVs promoted the proliferation and inhibited apoptosis of ox-LDL-treated HUVECs(P＜0.05).(3)CDNVs suppressed the prorein expression of SIPA1L2 and promoted autophagy in ox-LDL-treated HUVECs(P＜0.05).(4)CDNVs facilitated the ubiquitination of SIPA1L2 protein,and reduced its protein level through the ubiquitin-proteasome pathway(P＜0.05).CONCLUSION:CDNVs exert a protective effect against ox-LDL-induced endothelial cell injury by mediating SIPA1L2 ubiquitination and promoting endothelial cell au-tophagy.

BACKGROUND:Relatively or absolutely active bone resorption function of osteoclasts is one of the causative factors of osteoporosis. Therefore,how to inhibit the formation of osteoclasts and reduce the bone resorption activity is a key element in the prevention and treatment of osteoporosis. Liquiritin,which is derived from licorice,plays a role in the clinical treatment of bone diseases,but there are fewer studies addressing the application of liquiritin in osteoporosis and the mechanism is unknown.OBJECTIVE:To confirm,through both in vivo and in vitro experiments,that liquiritin inhibits osteoclast differentiation and alleviates bone loss.METHODS:Cell counting kit-8 was used to detect whether Liquiritin exerts toxic or proliferative effects on mouse bone marrow-derived macrophages,and tartrate-resistant acid phosphatase staining was performed to observe the effect of liquiritin in inhibiting osteoclast differentiation. The affinity of liquiritin binding to proteins related to osteoclast differentiation was verified by network pharmacology. RT-PCR and western blot assays were performed to detect the inhibitory effects of liquiritin on osteoclast-specific protein and gene expression as well as relevant signaling pathways. Finally,the mitigating effect of liquiritin on bone loss was verified in the C57BL/6J mouse osteoporosis model.RESULTS AND CONCLUSION:Liquiritin,at concentrations of 20 μmol/L and below,could inhibit the formation and differentiation of osteoclasts. Concurrently,it exhibited a high affinity with osteoclast-specific proteins such as nuclear factor of activated T-cells 1,Cathepsin K,c-Fos,and matrix metalloproteinase 9,and reduced the relative expression levels of these genes and proteins. Liquiritin could also effectively lower the phosphorylation expression level of JNK in the MAPK signaling pathway at the 15th,30th,45th,and 60th minutes,and it could salvage the degradation of nuclear factor-κB inhibitor α in the nuclear factor-κB signaling pathway at the 60th minute. In vivo experiments demonstrated that liquiritin could mitigate bone loss caused by osteoclasts and improve parameters related to trabecular bone. To conclude,liquiritin possesses the capacity to inhibit osteoclast differentiation and alleviate bone loss,thereby exerting a protective role against osteoporosis.

AIM To investigate the promotional effects of esculin combined with bone marrow mesenchymal stem cells(BM-MSCs)transplantation on the repair of spinal cord injury(SCI)in rats.METHODS The rats were randomly divided into the sham operation group,the model group,the esculin group for gavage of 20 mg/kg esculin,the BM-MSCs group for tail vein injection of 1 mL of 1×106/mL BM-MSCs,and the combinaiton treatment group.The SCI rat model was established using Allen's method,followed by the 14 days consecutive corresponding drug administration starting from the 2nd day after modeling.On days 3,7 and 14 of drug administration,the rats had their hind limbs motor function evaluated by the BBB scoring;and their footprint experiment conducted on the 14th day after modeling.After 14 days of administration,the rats had their morphological changes of spinal cord tissue observed with HE staining and Nissl staining;their activities of SOD and GSH,and level of MDA in spinal cord tissue detected by kits;their expressions of MAP2,GAP43 and GFAP in spinal cord tissue detected by immunofluorescence;and their expressions of NQO-1,Nrf-2,Bcl-2 and Bax proteins in spinal cord tissue detected by Western blot.RESULTS Compared with the model group,the groups interved with esculin,or BM-MSCs,or the combination treatment showed improvements in hind limb function and spinal cord tissue morphology(P＜0.05);decreased MDA levels(P＜0.05);increased SOD and GSH activities(P＜0.05);increased MAP2 and GAP43 fluorescence intensity(P＜0.05);decreased GFAP fluorescence intensity(P＜0.05);increased NQO-1,Nrf-2 and Bcl-2 protein expressions(P＜0.05);and decreased Bax protein expression(P＜0.05).And the combination treatment group was observed with an even better effects(P＜0.05).CONCLUSION The combination of esculin and BM-MSCs transplantation can effectively improve the spinal cord tissue damage and hind limb function in SCI rats.This effect may be achieved by activating the Nrf-2/NQO-1 signaling pathway to inhibit oxidative stress response,thereby reducing neuronal apoptosis,blocking glial scar formation,and promoting stem cell differentiation to rebuild neurons.

AIM:To study the protective effect of transient receptor potential vanilic acid subtype 1(TRPV1)agonist capsaicin(CAP)on traumatic blood loss shock rats,and to further explore its possible mechanism by network pharmacology.METHODS:Forty-five SD rats were divided into 5 groups by random number table method:normal group,shock group,lactated Ringer's solution(LR)group,CAP pretreatment(single administration before shock)group,CAP pre-final administration(twice administration before and after shock)group,with 9 rats in each group for survival observation.Then 32 SD rats were divided into 4 groups according to the results of survival experiment:normal group,shock group,LR group,CAP pre-final administration group,with 8 rats in each group for blood pressure,hemodynamics,arterial blood gas,vascular reactivi-ty and hepaticand renal blood flow.At the same time,the potential mechanism of CAP in the treat-ment of traumatic hemorrhagic shock was investi-gated by network pharmacology.Furthermore,ap-ply the dataset to validate and analyse the diagnos-tic value of the hub genes.RESULTS:Rats in shock group died within hours of the completion of the shock model,and the mean survival time was 1.25(0.42,6.21)h.LR resuscitation could improve the survival of rats to some extent.The survival rate and survival time of rats in the CAP pretreatment group were slightly increased as compared with the LR group,while twice administration of CAP be-fore and after shock(CAP pre-final administration)resulted in better outcomes than LR resuscitation alone.Further results indicated that CAP pre-final administration significantly reduced the blood lac-tic acid level,improved the vasoconstrictive and di-astolic reactivity,and increased the liver and kidney blood flow of shock rats as compared with LR group.The improvement of hemodynamics and blood gas indexes in CAP group was slightly higher than LR group,but there was no statistical signifi-cance.A total of 37 genes related to CAP anti-trau-matic hemorrhage shock were obtained by net-work pharmacology.KEGG enrichment analysis showed that the Ca ion signaling pathway and Ras signaling pathway were significantly enriched.Vali-dation of the dataset showed that the expression levels of CXCR4,NF-kB1,GFPA and NTF3 hub gene were significantly different in the normal and shock groups,and that CXCR4 has a high diagnostic value for traumatic haemorrhagic shock.CONCLUSIONS:CAP,the TRPV1 agonist,significantly improved vas-cular function,increased organ blood flow,and cor-rected the lactic acidosis in rats with traumatic hemorrhagic shock,thus markedly improved the survival outcomes.The mechanism may be related to Ca ion signal pathway and Ras signal pathway.CXCR4,NF-kB1,GFPA and NTF3 may be having an important role in it.

A 75-year-old male patient with non-small cell lung cancer in the lower lobe of the left lung underwent left lobectomy, followed by 4 cycles of adjuvant chemotherapy with paclitaxel and platinum, 4 cycles of chemotherapy with docetaxel and cisplatin, and immunotherapy with sintilimab, 13 cycles of immunotherapy with sintilimab monotherapy, and 5 cycles of endostatin and sintilimab, spanning a total of 5 years. Due to disease progression, he received the monotherapy with anlotinib, 42 days later, the patient developed intestinal perforation, and laparoscopic ileal perforation repair surgery was performed. During the operation, a perforation with a diameter of about 1 cm was observed in the ileum, indicating the outflow of digestive fluid and a large amount of purulent fluid accumulation in the pelvic cavity; no signs of gastrointestinal tumor metastasis were observed. After surgery, the patient developed abdominal infection and peritonitis, and was given symptomatic and supportive treatments such as anti-infection for 7 days. However, the patient developed severe complications such as lung infection, heart failure, sepsis, and respiratory failure, and died.

Background::The ratio of high-density lipoprotein cholesterol (HDL-C) to low-density lipoprotein cholesterol (LDL-C) predicts cardiovascular disease (CVD) endpoints, yet its prognostic validity in high-risk populations and for type 2 diabetes mellitus (T2DM)-related adverse events remains unestablished.Methods::This study included 32,609 people aged 35-75 years in Fujian Province, China, who were at high risk for CVD. The primary endpoint was all-cause mortality during follow-up. Cox proportional hazard models and restricted cubic spline (RCS) analysis were used to evaluate the correlation between the HDL-C/LDL-C ratio and the endpoints.Result::On the basis of the restricted RCS curve, the participants were classified as having a low (< 0.3), middle (0.3-0.5), or high (> 0.5) HDL-C/LDL-C ratio. Multivariate Cox regression analyses revealed that the risk of all-cause mortality (HR = 1.48, 95% CI 1.14-1.93, p < 0.01 for low; HR = 1.30, 95% CI 1.06-1.58, p < 0.05 for high) was increased in the low and high groups. Participants without T2DM who were at high risk for CVD had similar prognoses (HR = 1.65, 95% CI 1.19-2.28, p < 0.01 for low; HR = 1.35, 95% CI 1.05-1.74, p < 0.01 for high). However, this association was not found in participants with T2DM who were at high risk for CVD. Conclusion::HDL-C/LDL-C can be used to predict the prognosis of individuals at high risk for CVD, and maintaining HDL-C/LDL-C ratios between 0.3 and 0.5 may be the most helpful range for this population. Furthermore, maintaining this ratio range holds clinical significance for cohorts without T2DM, although further exploration is needed in this T2DM cohort.

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