Stress is a critical inducer in the onset and progression of many chronic diseases. Prolonged or intense stress can disrupt the overall balance between the nervous, immune, and endocrine systems. The resulting biological signals may act on corresponding receptors in the cervical spine region, leading to adverse pathological changes. The vertebral artery and the surrounding muscular and connective tissues are influenced by biomechanical abnormalities and inflammatory cascades associated with cervical spondylosis of vertebral artery type (CSA), which promotes the release of various hormones. These hormones, through the neuroendocrine-immune system, affect the central nervous system, inducing or exacerbating negative emotional feedback and thereby establishing a "central-local-central" vicious cycle. This article explores the mechanisms underlying the impact of stress on the key CSA symptoms through the neuroendocrine-immune network (NEI) theory, providing a more comprehensive framework for targeted therapeutic interventions in CSA.
Humans ; Neurosecretory Systems/immunology* ; Spondylosis/etiology* ; Vertebral Artery/immunology* ; Stress, Psychological/complications* ; Chronic Disease

Objective To compare the effect of sodium hualuronate(SH)and platelet rich plasma(PRP)injections in the treatment of glenohumeral joint osteoarthritis(GJO).Methods Sixty-three patients with GJO were randomly assigned to receive either PRP(PRP group,n=29)or SH(SH group,n=34)injec-tions.The injections were administered into the glenohumeral joint under ultrasound guidance.The patients were assessed by the Visual Analogue Scale(VAS),American Shoulder and Elbow Surgeons(ASES)score and modified University of California(UCLA)shoulder joint score before injection and at 1,6,12 months of injection.Results There were no statistically significant differences in the general data between the two groups(P>0.05).Compared with before injection,the VAS scores at 1,6,and 12 months after injection in the two groups were significantly decreased(P<0.05).The VAS score at 12 months after injection in the SH group was significantly increased(P<0.05).The VAS score at 12 months after injection in the PRP group was lower than that in the SH group(P<0.05).The ASES scores showed a significant increase at 1 month after injection compared to before treatment(P<0.05),moreover the ASES scores at 6 months after injection in the PRP group were higher than those in the SH group(P<0.05).Compared with before injection,the modified UCLA shoulder joint scores at 1,6 months after injection in the two groups were significantly in-creased(P<0.05),moreover the scores of the modified UCLA shouder joint scores at 6 months after injec-tion in the PRP group were higher than those in the SH group(P<0.05).Conclusion Pain relief in intraar-ticular injection of PRP in GJO patients is more significant than intraarticular injection of SH,moreover PRP is significantly superior to SH in improving the shoulder joint function of the patients.

Objective::To evaluate the feasibility, safety, and effectiveness of a novel edge-to-edge mitral valve repair system (the NovoClasp system) in patients with severe mitral regurgitation.Methods::In this prospective, single-arm, first-in-human study conducted at Beijing Anzhen Hospital, data were collected from patients undergoing transcatheter edge-to-edge repair using the NovoClasp system. The study candidates were patients exhibiting a mitral regurgitation severity of 3+ or more and were at high-risk or contraindicated for surgical intervention. Technical success and device success according to the Mitral Valve Academic Research Consortium definitions were used as primary outcomes. Other safety and efficacy outcomes were prospectively assessed at device implantation, discharge, and 30 d, 6 months, and 12 months post-procedure.Results::Between October 1, 2021, and January 31, 2022, 11 patients were treated for moderate-to-severe (grade 3+) or severe (grade 4+) mitral regurgitation using the NovoClasp system. All patients had a baseline New York Heart Association functional class of III-IV, with 7/11 exhibiting complex mitral valve disease. All patients achieved the primary endpoints of technical and device success, with a post-operative 30-d mitral regurgitation grade reduction to 2+ or lower, which was maintained at 12 months. One patient had minor bleeding and hematoma at the access site before discharge, and 2 patients were readmitted due to fast atrial fibrillation within 12 months post-discharge. No additional cases of death, adverse cerebral or cardiovascular events, or device-related complications was observed during the follow-up.Conclusion::This study suggested the potential feasibility and safety of the NovoClasp system, showing a promising technical and device success rate, along with a decrease in mitral regurgitation severity. A further pivotal study is needed to assess the procedural and long-term outcomes.

Objective::To evaluate the feasibility, safety, and effectiveness of a novel edge-to-edge mitral valve repair system (the NovoClasp system) in patients with severe mitral regurgitation.Methods::In this prospective, single-arm, first-in-human study conducted at Beijing Anzhen Hospital, data were collected from patients undergoing transcatheter edge-to-edge repair using the NovoClasp system. The study candidates were patients exhibiting a mitral regurgitation severity of 3+ or more and were at high-risk or contraindicated for surgical intervention. Technical success and device success according to the Mitral Valve Academic Research Consortium definitions were used as primary outcomes. Other safety and efficacy outcomes were prospectively assessed at device implantation, discharge, and 30 d, 6 months, and 12 months post-procedure.Results::Between October 1, 2021, and January 31, 2022, 11 patients were treated for moderate-to-severe (grade 3+) or severe (grade 4+) mitral regurgitation using the NovoClasp system. All patients had a baseline New York Heart Association functional class of III-IV, with 7/11 exhibiting complex mitral valve disease. All patients achieved the primary endpoints of technical and device success, with a post-operative 30-d mitral regurgitation grade reduction to 2+ or lower, which was maintained at 12 months. One patient had minor bleeding and hematoma at the access site before discharge, and 2 patients were readmitted due to fast atrial fibrillation within 12 months post-discharge. No additional cases of death, adverse cerebral or cardiovascular events, or device-related complications was observed during the follow-up.Conclusion::This study suggested the potential feasibility and safety of the NovoClasp system, showing a promising technical and device success rate, along with a decrease in mitral regurgitation severity. A further pivotal study is needed to assess the procedural and long-term outcomes.

ObjectiveTo observe the effects of the South African herb Hoodia gordonii （HG） on glucolipid metabolism in diabetic db/db mice and explore the possible mechanisms of HG on the liver of db/db mice based on the phosphoinositide-3 kinase （PI3K）/protein kinase B （Akt）/factor forkhead protein O1 （FoxO1） signaling pathway. MethodA total of 30 db/db mice were randomly divided into five groups according to fasting blood glucose： model group， metformin group （0.195 g·kg^-1）， and low dose （0.39 g·kg^-1）， medium dose （0.78 g·kg^-1）， and high dose （1.56 g·kg^-1） HG groups， with six m/m mice in each group， and another six m/m mice were set as normal group. The mice in the normal and model groups were given saline of 9 mL·kg^-1 by gavage. Body weight， water intake， and fasting blood glucose of the mice in each group were measured weekly. After six weeks of continuous administration， serum insulin （FINS）， low-density lipoprotein cholesterol （LDL）， total cholesterol （TC）， triglyceride （TG）， alanine aminotransferase （ALT）， aspartate aminotransferase （AST）， urea， and creatinine （CREA） were measured， and liver sections were embedded and stained with hematoxylin-eosin （HE）， periodic acid-Schiff （PAS）， and oil red O. Protein expression of PI3K p85， p-Akt， and p-FoxO1 in liver was detected by immunohistochemistry. The mRNA expression of PI3K， Akt， and FoxO1 in liver tissue was detected by real-time polymerase chain reaction （Real-time PCR）. ResultAfter six weeks of administration intervention， it was found that fasting blood glucose was significantly downregulated in mice in the three HG groups （P<0.05）. The level of islet resistance index was significantly reduced in both the low and medium dose HG groups （P<0.05）. The expression levels of TC， TG， and LDL were reduced in all HG groups （P<0.05， P<0.01）. Pathologically， HG could alleviate hepatocyte steatosis， reduce the volume and content of lipid droplets in liver， and increase the distribution of glycogen granules in liver to some extent in mice. Immunohistochemical assays revealed that PI3K p85 protein expression was significantly increased in the low， medium， and high dose HG groups compared with the model group （P<0.01）. p-Akt protein expression was significantly increased in the medium and high dose HG groups （P<0.05， P<0.01）. p-FoxO1 protein expression was significantly increased in the low， medium， and high dose HG groups （P<0.05， P<0.01）. Compared with the model group， PI3K mRNA was increased in low dose， medium dose， and high dose HG groups （P<0.05）， and Akt mRNA was increased in high dose HG group （P<0.05）. FoxO1 mRNA was decreased in low dose， medium dose， and high dose HG groups （P<0.05）. ConclusionHG can ameliorate the disorder of glucolipid metabolism in db/db mice， which may be related to its activation of the hepatic PI3K/Akt/FoxO1 signaling pathway.

Tumor-associated macrophages(TAMs)are the predominant cell group in the tumor microenvironment(TME)and are the most important regulatory cells of immune system suppression and tumor cell proliferation in TIME.Src homology-2 domain-containing protein tyrosine phosphatase 2(SHP-2)is a non-receptor protein tyrosine phosphatase that plays an important role in the transmission of signals from the cell surface to the nucleus.SHP-2 is a key intracellular regulatory factor mediating cell proliferation and differentiation and is involved in a variety of growth factor and cytokine signaling pathways linking the cell surface to the nucleus.Recent studies have shown that SHP-2 is a key enzyme in determining the function of TAMs,but because of its variable function,it plays different or even opposite roles in different solid TMEs.This paper reviews the function of SHP-2 in TAMs and related solid tumors to provide a comprehensive reference for tumor immunity and targeted therapy research.

Objective To present and discuss beam characteristics of the first Mevion S250i gantry-mounted accelerator pencil beam scanning proton therapy system in China.Methods The output dose was measured using a parallel-plate ionization chamber.The integrated depth dose was measured with a large-radius Bragg peak ionization chamber,covering 19 energy levels ranging from 227 MeV to 28 MeV,to analyze the proton beam characteristics.The spots in the air were measured with Phoenix flat panel detector on the beam central axis,and the precision of the delivery position was verified by measuring the multi-spot beam map.The interleaf leakage and penumbra reduction of adaptive aperture were measured to characterize its performance.Results The proton system was calibrated for a maximum energy of 227 MeV,with a(10×10)cm2uniform field delivering 1 Gy dose at a depth of 5 cm underwater.The system effectively modulated the proton beam range to the patient's surface,maintaining a constant 80%-80%Bragg peak width of 8.6 mm at all energy levels.The spot size of the highest energy beam at the isocenter was about 4 mm in the air,and the spot delivery position error was less than 1 mm.The interleaf leakage rate of the adaptive aperture for the highest energy beam was below 1.5%,and the penumbra was significantly reduced.Conclusion Mevion S250i proton therapy system demonstrates unique design and beam characteristics,which is reflected in the Bragg peak shape,spot size variation with energy,and penumbra sharpening of adaptive aperture;and these differences should be considered in treatment planning system modeling and planning for precision treatment.

Objective:To evaluate the clinical application value of the adaptive aperture by comparing intensity-modulated proton radiotherapy(IMPT) plans using and not using the aperture for brain tumors.Methods:A total of twenty patients treated with postoperative radiotherapy for brain tumors were enrolled in this study. IMPT plans were developed for each patient using and not using the adaptive aperture under the same optimization conditions. The target conformal index (CI) value, target homogeneity index (HI) value, and the dose to normal tissues of the two sets of plans were compared.Results:The IMPT plans designed using the adaptive aperture significantly increased the mean CI value from 0.58 to 0.66, while decreasing the mean 50% prescription dose volume from 797.70 cm 3 to 638.15 cm 3. These plans also reduced the irradiation doses to the cochlea, brainstem, optic chiasm, optic nerve, and lens ( t = 2.06, 3.02, 2.11, 2.58, 2.67, P < 0.05). Additionally, there was no significant difference in the HI value of the target volumes and the machine jumps (MU) between the two sets of plans ( P > 0.05). Conclusions:The adaptive aperture can significantly reduce the irradiation dose to normal tissues outside the target volumes, positively impacting the protection of organs at risk (OARs) around the target values. This demonstrates its great potential for clinical application.

BACKGROUND:Ischemic stroke is a serious threat to human health.After ischemia and hypoxia,astrocyte expresses lipocalin-2 in large amounts to aggravate brain injury,but the specific mechanism is not clear.Hydroxysafflor yellow A has anti-ischemia,anti-oxidation,anti-thrombosis and anti-inflammatory effects.However,whether hydroxysafflor yellow A affects the expression of lipocalin-2 in astrocytes after cerebral ischemia and hypoxia and its mechanism are not clear. OBJECTIVE:To investigate the effect and mechanism of hydroxysafflor yellow A on the expression of lipocalin-2 in astrocytes after cerebral ischemia and reperfusion. METHODS:(1)Thirty adult SD rats were randomly divided into three groups:sham operation group,middle cerebral artery occlusion and reperfusion group,and hydroxysafflor yellow A group.The middle cerebral artery occlusion and reperfusion model was established in the latter two groups,and hydroxysafflor yellow A group was intraperitoneally injected with 12 mg/kg hydroxysafflor yellow A after reperfusion.Longa score was used to evaluate the degree of neurological impairment.Infarct volume was determined by TTC staining.JAK2/STAT3 pathway and lipocalin-2 expression were detected by western blot assay and immunofluorescence.Levels of interleukin 1β,interleukin 6 and tumor necrosis factor α were detected by ELISA.(2)Astrocytes were divided into four groups:Normal group,glucose-oxygen deprivation group,hydroxysafflor yellow A group and AG490 group.In the latter three groups,glucose-oxygen deprivation and glucose-oxygen recovery models were established.Astrocytes were treated with 75 μmol/L hydroxysafflor yellow A and 10 μmol/L tyrosine phosphorylation inhibitor AG490 for 8 hours during glucose-oxygen deprivation,respectively.The mechanism of hydroxysafflor yellow A on lipocalin-2 was further verified. RESULTS AND CONCLUSION:(1)Compared with the sham operation group,cerebral infarction was significantly increased in the middle cerebral artery occlusion and reperfusion group,accompanied by aggravated neurological impairment(P<0.01).Hydroxysafflor yellow A treatment could reduce cerebral infarction volume and improve neurological function(P<0.01).(2)The expressions of p-JAK2,p-STAT3 and lipocalin-2 in the middle cerebral artery occlusion and reperfusion group were higher than those in the sham operation group(P<0.01).Hydroxysafflor yellow A treatment reduced the expressions of JAK2,STAT3 and lipocalin-2(P<0.01).(3)The expression levels of interleukin 1β,interleukin-6 and tumor necrosis factor α in the middle cerebral artery occlusion and reperfusion group were higher than those in the sham operation group(P<0.01).Hydroxysafflor yellow A inhibited the expressions of interleukin 1β,interleukin-6 and tumor necrosis factor α(P<0.01).(4)In vitro,the expressions of p-JAK2,p-STAT3 and lipocalin-2 in the glucose-oxygen deprivation group were significantly higher than those in the normal group(P<0.01).After adding AG490,the phosphorylation of JAK2 and STAT3 decreased,and the expression of lipocalin-2 was inhibited(P<0.01).The results suggest that hydroxysafflor yellow A may inhibit the expression of lipocalin-2 in astrocytes after ischemia and hypoxia by regulating the JAK2/STAT3 signaling pathway,thereby reducing brain injury.

Traumatic fractures and stress fractures are common orthopedic diseases,and there is great potential in researching bone turnover,repair,and promotion of fracture healing.Basic medical experiments often use animal models of long bone fractures in limbs to study the mechanisms of various interventions on fracture healing.Fracture healing is a complex process influenced by multiple factors and involves multiple molecules and pathways.Therefore,to explore the mechanisms more deeply,accelerate the translation of results,and improve the clinical efficacy,it is particularly important to choose the appropriate animal fracture modeling methods in experimental research.Based on this,this paper conducts a literature review of animal species and modeling methods commonly used for long bone fracture models in experimental research.It summarizes five methods:bone defect method,physical impact method,mechanical bending method,open osteotomy method,and drilling method.A side-by-side comparison of their advantages,disadvantages,and scope of application is made,aiming to provide suitable fracture models for studyingthe mechanisms of fracture healing interventions.