OBJECTIVE To explore the effect and mechanism of Zhiqiao gancao decoction （ZQGCD） on pathological angiogenesis of degenerative intervertebral disc. METHODS The rats were randomly divided into sham operation group （normal saline）， model group （normal saline）， hypoxia inducible factor-1α （HIF-1α） inhibitor （YC-1） group [2 mg/（kg·d）， tail vein injection]， and ZQGCD low-dose， medium-dose and high-dose groups [3.06， 6.12， 12.24 g/（kg·d）]， with 8 rats in each group. Except for sham operation group， lumbar disc degeneration model of rat was constructed in all other groups. After modeling， they were given relevant medicine once a day， for consecutive 3 weeks. After the last medication， pathological changes and angiogenesis of the intervertebral disc tissue in rats were observed； the levels of inflammatory factors [interleukin-1β （IL-1β）， IL-6， tumor necrosis factor-α （TNF-α）] and the expressions of angiogenesis-related proteins [HIF-1α， vascular endothelial growth factor （VEGF）， VEGF receptor 2 （VEGFR2）， angiotensin 1（Ang 1）， Ang 2] in the com intervertebral disc tissue in rats were all determined. In cell experiment， the primary nucleus pulposus cells were isolated and cultured from rats， and cellular degeneration was induced using 50 ng/mL TNF-α. The cells were divided into blank control group （10% blank control serum）， TNF-α group （10% blank control serum）， YC-1 group （10% blank control serum+0.2 mmol/L YC-1）， and 5%， 10%， 15% drug-containing serum group （5%， 10%， 15% drug-containing serum）. After 24 hours of intervention， the nucleus pulposus cells were co-cultured with HUVEC. The expressions of Collagen Ⅱ， matrix metalloproteinase-3 （MMP-3） in nucleus pulposus cells were detected. HUVEC proliferation， migration and tube forming ability were detected， and the expression levels of the HIF-1α/VEGF/Ang signal axis and angiogenesis- related proteins （add MMP-2， MMP-9） in HUVEC were detected. RESULTS Animal experiments had shown that compared with model group， the positive expression of CD31 in the intervertebral disc tissues of rats in each drug group was down-regulated （P＜ 0.05）， the levels of inflammatory factors and angiogenesis-related proteins were decreased significantly （P＜0.05）， and the pathological changes in the intervertebral disc were alleviated. Cell experiments had shown that compared with TNF-α group， the expression of Collagen Ⅱ in nucleus pulposus cells of all drug groups was significantly up-regulated （P＜0.05）， and the expression of MMP-3 was significantly down-regulated （P＜0.05）； the proliferation， migration and tubulogenesis of HUVEC were significantly weakened （P＜0.05）. The mRNA and protein expressions of HIF-1α， VEGF， Ang 2 as well as the expression of angiogenesis-related proteins （except for the expression of Ang 2 mRNA and HIF-1α， VEGFR2， Ang 2 protein in 5% drug- containing serum group） were significantly down-regulated （P＜0.05）. CONCLUSIONS ZQGCD may inhibit the HIF-1α/VEGF/ Ang signal axis to weaken the angiogenic ability of vascular endothelial cells， improve pathological angiogenesis in the intervertebral disc， and delay the degeneration of the intervertebral disc.

ObjectiveTo investigate the prevalence of gynecological and breast diseases among retired or economically disadvantaged women in part of Pudong New Area of Shanghai under the policy support of screening gynecological diseases and breast diseases for retired and women with economic difficulties in life in Shanghai, to analyze the characteristics of these diseases, so as to provide a scientific basis for the improvement of relevant prevention and treatment strategies. MethodsBased on the gynecological census data of 13 031 cases in five towns, including Xinchang Town, Xuanqiao Town, Laogang Town, Wanxiang Town and Shuyuan Town, conducted by Shanghai Pudong Hospital in 2023, descriptive analysis methods were used to explore the prevalence and age characteristics of common gynecological and breast diseases. ResultsThe total detection rate of gynecological and breast diseases among women in the screening area in this study was 68.29%, with uterine fibroid (22.35%), sarcoidosis of the breast (17.06%), cervicitis (15.37%), vaginitis (8.39%) and ovarian cyst (2.61%) ranking the top 5 in the detection rate among the screening population. The differences of the detection rates in the four major diseases [uterine fibroid (χ²=233.217, P<0.001), breast nodules(χ²=169.896, P<0.001), cervicitis (χ²=388.683, P<0.001), and ovarian cysts (χ²=72.298, P<0.001)] by different age groups were statistically significant (P<0.05) . Moreover, the results of pairwise comparison of different age groups showed that the detection rates in the age group under 45 years old and 45‒55 years old were higher than that in the age group of 55‒65 years old and over 65 years old. ConclusionThe detection rate of gynecological and breast diseases in the younger age group was higher, indicating a certain trend of younger onset of diseases. Uterine fibroid, sarcoidosis of the breast , and reproductive tract diseases such as cervicitis, vaginitis, and ovarian cyst are the main diseases affecting the research subjects. Therefore, medical institutions can combine routine work in screening diseases and carry out corresponding health education and health promotion activities for these key diseases to improve women’s health.

ObjectiveTo investigate the possible mechanism by which Zhiqiao Gancao Decoction （枳壳甘草汤， ZGD） delays intervertebral disc degeneration （IDD） based on the Hippo-yes-associated protein （YAP）/transcriptional co-activator with PDZ-binding motif （TAZ） signaling pathway. MethodsA total of 50 SD rats were randomly divided into sham surgery group， model group， low-dose ZGD group， high-dose ZGD group， and high-dose ZGD + inhibitor group， with 10 rats in each group. In the sham surgery group， the rats were pierced in the skin and muscle at the Co6/7/8 segments of the tail with a 21G needle （depth approximately 2 mm） without damaging the intervertebral disc. In the other groups， rats were injected with a 21G needle at the Co6/7/8 segments of the tail to establish an IDD model by piercing the tail intervertebral disc 5 mm. One week after modeling， rats in the low-dose and high-dose ZGD groups were given 6.24 and 12.24 g/（kg·d） of the decoction via gastric gavage， respectively. The high-dose ZGD + inhibitor group was given 12.24 g/（kg·d） of the decoction and an intraperitoneal injection of YAP/TAZ inhibitor Verteporfin 10 mg/kg. The sham surgery and model groups were given 5 ml/（kg·d） of normal saline via gavage. The gavage was given once a day， and the intraperitoneal injection was given every other day. After 4 weeks of continuous intervention， the pathological changes of the tail intervertebral discs were observed using HE staining， Oil Red O-Green staining， and Toluidine Blue staining. Immunohistochemistry was used to detect the expression of aggrecan and MMP3 in the nucleus pulposus. TUNEL fluorescence staining was performed to detect apoptosis in the nucleus pulposus， and the apoptosis rate was calculated. Western blot was used to detect the Hippo-YAP/TAZ signaling pathway， including YAP， phosphorylated YAP （p-YAP）， phosphorylated MST1/2 （p-MST1/2）， phosphorylated TAZ （p-TAZ） and apoptosis-related proteins， such as Cleaved Caspase 3， P53， Bcl-2 and Bax. ResultsCompared with sham surgery group， the rats in the model group showed significant degenerative changes in the intervertebral disc. The levels of aggrecan， Bcl-2， and YAP proteins in the nucleus pulposus decreased， while the levels of p-MST1/2， p-YAP， p-TAZ， P53， Bax， Cleaved Caspase 3， MMP3 proteins， and the apoptosis rate increased （P < 0.01）. Compared with the model group， the drug intervention groups showed partial recovery in intervertebral disc degeneration. The levels of aggrecan， Bcl-2， and YAP proteins increased， while the levels of p-MST1/2， p-YAP， p-TAZ， P53， Bax， Cleaved Caspase 3， MMP3 proteins， and the apoptosis rate decreased （P＜0.05 or P＜0.01）. The high-dose ZGD group showed more significant recovery in intervertebral disc degeneration compared to the low-dose ZGD group， with a decrease in the levels of p-MST1/2， p-YAP， p-TAZ， P53， Bax， Cleaved Caspase 3， MMP3 proteins， and apoptosis rate， and an increase in the levels of aggrecan， Bcl-2， and YAP proteins （P＜0.05 or P＜0.01）. Compared with the high-dose ZGD group， the high-dose ZGD + inhibitor group showed a reduced recovery in intervertebral disc degeneration， with an increase in the levels of p-MST1/2， p-YAP， p-TAZ， P53， Bax， Cleaved Caspase 3， MMP3 proteins， and apoptosis rate， and a decrease in the levels of aggrecan， Bcl-2， and YAP proteins （P＜0.05 or P＜0.01）. ConclusionZGD may delay intervertebral disc degeneration by inhibiting the phosphorylation of YAP in the nucleus pulposus， maintaining the function of the Hippo-YAP/TAZ signaling pathway， and reducing apoptosis of nucleus pulposus cells.

ObjectiveTo evaluate the clinical efficacy of Huayu Tongluo Formula （化瘀通络方， HTF） in patients with mid-stage diabetic kidney disease of blood stasis syndrome and explore its potential mechanisms. MethodsA multi-center， randomized， double-blind， placebo-controlled clinical trial was conducted. Ninety patients of mid-stage diabetic kidney disease of blood stasis syndrome were divided into a control group of 46 cases and a treatment group of 44 cases. Both groups received conventional western medicine treatment， the treatment group additionally taking HTF， while the control group taking a placebo of the formula. The treatment was administered once daily for 24 weeks. The primary outcomes included 24-hour urine total protein （24 h-UTP）， serum albumin （Alb）， glycated hemoglobin （HbA1c）， and serum creatinine （Scr）.The secondary outcomes included changes in levels of endothelin-1 （ET-1）， nitric oxide （NO）， vascular endothelial growth factor （VEGF）， and traditional Chinese medicine （TCM） syndrome scores before and after treatment. Clinical efficacy was evaluated based on TCM syndrome scores and overall disease outcomes. Adverse reactions and endpoint events were recorded. ResultsIn the treatment group after treatment， 24 h-UTP， ET-1， and VEGF levels significantly decreased （P＜0.05）， Alb and NO levels significantly increased （P＜0.05）； while the TCM syndrome scores for edema， lumbar pain， numbness of limbs， dark purple lips， dark purple tongue or purpura， and thin， rough pulse all significantly decreased （P＜0.05）. In the control group， no significant changes were observed in any of the indicators after treatment （P＞0.05）.Compared with the control group， the treatment group showed significant reductions in 24 h-UTP， ET-1， and VEGF levels， and increases in Alb and NO levels （P＜0.05）. The TCM syndrome scores for edema， lumbar pain， dark purple tongue or purpura， and thin， rough pulse were all lower in the treatment group than in the control group （P＜0.05）. The total effective rate of TCM syndrome in the treatment group was 59.09% （26/44）， and the overall clinical effective rate was 45.45% （20/44）. In the control group， these rates were 15.22% （7/46） and 8.7% （4/46）， respectively， with the treatment group showing significantly better outcomes （P＜0.05）. A total of 7 adverse events occurred across both groups， with no significant difference （P＞0.05）. No endpoint events occurred during the study. ConclusionOn the basis of conventional treatment of Western medicine， HTF can further reduce urinary protein levels and improve clinical symptoms in patients with mid-stage diabetic kidney disease of blood stasis syndrome. The mechanism may be related to its effects on endothelial function.

The killing effect of radiation therapy on healthy cells has led to the creation of targeted radionuclide therapy,which effectively reduces the damage to surrounding normal cells.At present,alpha(α)and beta(β)radionuclides are the research hotspots of targeted therapy.Numerous preclinical and clinical studies have shown that radiation therapy not only has local anti-tumor effects,but also exerts systemic anti-tumor effects by triggering the body's immune response.This paper describes in detail the characteristics and clinical applications of commonly used radionuclides,and discusses the mechanism of radiation-triggered body immune response as well as the related research on the combined use of radiation therapy,targeted radionuclide therapy and immunotherapy.

Targeted radiation therapy using radionuclides is a favored approach for treating tumors.This procedure involves the delivery of drugs to the lesion site via carriers or interventional methods,followed by the emission of radiation energy that selectively irradiates the lesion tissue.This approach minimizes damage to normal tissue and achieves the desired therapeutic effect.Factors such as the type of therapeutic radionuclide,radiation energy,physical half-life,method of preparation,and toxicity determine their clinical application.In this paper,the characteristics and clinical application of therapeutic radionuclides were reviewed to providing reference for the clinical application of targeted therapeutic radionuclides.

Objective To investigate the binding and carrying effects of human serum albumin(HSA)from various sources on sphingosine-1-phosphate(S1P).Methods Utilizing human plasma-derived HSA(pHSA)and recombinant HSA(rHSA)samples as the focal points of our investigation,LC-MS/MS technology was employed to meticulously compare and an-alyze the disparities in S1P content among the aforementioned samples.Subsequently,under physiological concentration condi-tions,S1P was directly introduced to HSA samples for loading processing,facilitating a comprehensive comparison of the bind-ing efficacy of HSA from different sources to S1P.Within a serum-free culture setting,HSA samples from various sources were co-cultured with HUVEC cells.The alterations in S1P content within the cell culture supernatant across different treatment groups were meticulously analyzed,allowing for a nuanced comparison of the S1P carry effects exerted by HSA from different sources on cells.The interaction between HSA and S1P molecules from different sources was analyzed and their affinity was cal-culated using surface plasmon resonance(SPR)technology.Furthermore,leveraging AutoDock Vina software and the Mol-prophet platform,the molecular docking analysis of HSA and S1P was conducted,aiming to predict the key binding pocket do-main of S1P within HSA.Results All pHSA samples exhibited detectable levels of S1P(ranging from 3.31±0.03 to 30.35±0.07 μg/L),with significant variations observed among pHSA samples from different manufacturers(P＜0.001).Conversely,S1P was undetectable in all rHSA samples.Upon load treatment,the binding affinity of HSA from diverse sources to S1P dem-onstrated significant discrepancies(P＜0.001),with rHSA exhibiting approximately double the average S1P loading compared to pHSA(ΔCrHSA=801.75±142.45 μg/L vs ΔCpHSA=461.94±85.73 μg/L;P＜0.001,t=5.006).Co-culture treatment out-comes revealed a significant elevation in S1P concentration within the supernatant after 6 hours of co-culture across all HSA sample processing groups with HUVEC cells,while no changes were observed in the supernatant of the blank control group.Notably,significant differences in supernatant S1P concentration were observed among treatment groups at 6 h,12 h,and 24 h(P＜0.001).SPR analysis unveiled a stronger affinity of pHSA for S1P compared to rHSA(KDpHSA-S1P:2.38E-06,KDrHSA-S1P:3.72E-06).Molecular docking analysis and binding pocket prediction suggested that the key binding pocket of HSA and S1P may reside in the IB subdomain of the HSA molecule.Conclusion HSA from various sources exhibits distinct binding and carrying effects on S1P,which appear to be closely associated with the IB subdomain of the HSA molecule.

Objective:To clarify the transitional components in the blood of compound Banlangen Granules; To explore the mechanism of drugs in the treatment of epidemic encephalitis B, hepatitis and parotitis.Methods:The transitional components in blood of compound Banlangen Granules were analyzed by ultra-high performance liquid chromatography-mass spectrometry (UPLC-MS/MS). The regulatory targets and pathways of compound Banlangen Granules in the treatment of epidemic encephalitis B, hepatitis and parotitis were analyzed based on UPLC-MS/MS and network pharmacology.Results:A total of 9 blood components were identified, of which 8 were prototype components, including sucrose, o-aminobenzoic acid, uridine, adenosine, guanosine, indole-3-acetonitrile-2 murine-S-β-D-glucopyranoside and salicylic acid. Through network pharmacological analysis, it was concluded that compound Banlangen Granules may treat epidemic encephalitis B, hepatitis and parotitis by regulating lipid and atherosclerosis, insulin resistance, IL-17 and other signal pathways.Conclusion:The 9 blood components of compound Banlangen Granules may treat epidemic encephalitis B, hepatitis and parotitis by regulating lipid and atherosclerosis, insulin resistance, IL-17 and other signal pathways.

Depressive disorder ranks as a major bur-den of disease worldwide,yet the current antidepressant medications are limited by frequent non-responsiveness and significant side effects.The lateral septum(LS)is thought to control of depression,however,the cellular and circuit substrates are largely unknown.Here,we identified a subpopulation of LS GABAergic adenosine A2A receptors(A2AR)-positive neurons mediating depres-sive symptoms via direct projects to the lateral habenula(LHb)and the dorsomedial hypothalamus(DMH).Activa-tion of A2AR in the LS augmented the spiking frequency of A2AR-positive neurons leading to a decreased activation of surrounding neurons and the bi-directional manipula-tion of LS-A2AR activity demonstrated that LS-A2ARs are necessary and sufficient to trigger depressive pheno-types.Thus,the optogenetic modulation(stimulation or inhibition)of LS-A2AR-positive neuronal activity or LS-A2AR-positive neurons projection terminals to the LHb or DMH,phenocopied depressive behaviors.Moreover,A2AR are upregulated in the LS in two male mouse mod-els of repeated stress-induced depression.This identifica-tion that aberrantly increased A2AR signaling in the LS is a critical upstream regulator of repeated stress-induced depressive-like behaviors provides a neurophysiological and circuit-based justification of the antidepressant poten-tial of A2AR antagonists,prompting their clinical transla-tion.

Objective:To explore the related risk factors for systemic embolism (SE) in patients aged≥75 years with non-valvular atrial fibrillation (NVAF).Methods:A case-control study. NVAF patients aged≥75 years who were hospitalized at the First Affiliated Hospital of Xinjiang Medical University from October 2018 to October 2020 were divided into no SE ( n=1 127) and SE ( n=433) groups according to the occurrence of SE after NVAF. Multivariate logistic regression was used to analyze SE-related factors in patients with NVAF without anticoagulation treatment. Results:In the multivariate model, the following factors were associated with an increased risk of SE in patients with NVAF: history of AF≥5 years [odds ratio ( OR)=2.75, 95% confidence interval ( CI) 1.98-3.82, P<0.01], lipoprotein(a)>300 g/L ( OR=2.07, 95% CI 1.50-2.84, P<0.01), apolipoprotein (Apo)B>1.2 g/L ( OR=1.91, 95% CI 1.25-2.93, P=0.003), left ventricular ejection fraction (LVEF) of 30%-49% ( OR=2.45, 95% CI 1.63-3.69, P<0.01), left atrial diameter>40 mm ( OR=1.54, 95% CI 1.16-2.07, P=0.003), and CHA 2DS 2-VASc score≥3 ( OR=15.14, 95% CI 2.05-112.13, P=0.01). ApoAI>1.6 g/L was negatively correlated with the occurrence of SE ( OR=0.28, 95% CI 0.15-0.51, P<0.01). Conclusions:History of AF≥5 years, lipoprotein(a)>300 g/L, elevated ApoB, left atrial diameter>40 mm, LVEF of 30%-49%, and CHA 2DS 2-VASC score≥3 are independent risk factors for SE whereas ApoAI>1.6 g/L is a protective factor against SE in patients with NVAF.