BACKGROUND:Nobiletin has been found to improve lipopolysaccharide-induced abnormal activation of microglia,excessive release of inflammatory factors and redox imbalance.However,the specific mechanism is not fully understood. OBJECTIVE:To investigate the molecular mechanism by which nobiletin can inhibit lipopolysaccharide-induced inflammation in BV2 microglia. METHODS:Passage 3 BV2 microglia were divided into three groups:control group was cultured for 24 hours(without any treatment).Lipopolysaccharide group was treated with 10 μg/mL lipopolysaccharide for 24 hours.Lipopolysaccharide+nobiletin group was treated with 20 μmol/L nobiletin for 6 hours and then 10 μg/mL lipopolysaccharide for 24 hours.After the processing,cell proliferation was detected by CCK-8 assay.The level of intracellular reactive oxygen species was detected by fluorescent probe.The mRNA expression levels of nuclear factor κB p65,tumor necrosis factor α,and interleukin-1β were detected by qRT-PCR.The protein expression levels of nuclear factor κB p65,p-nuclear factor κB p65,tumor necrosis factor α,and interleukin-1β were detected by western blot assay. RESULTS AND CONCLUSION:(1)Compared with the control group,the proliferation activity of lipopolysaccharide group was decreased(P<0.001).Compared with the lipopolysaccharide group,the cell proliferation activity of lipopolysaccharide+nobiletin group was increased(P<0.001).(2)Compared with the control group,the level of intracellular reactive oxygen species was increased in the lipopolysaccharide group(P<0.001).Compared with the lipopolysaccharide group,the level of intracellular reactive oxygen species was decreased in the lipopolysaccharide+nobiletin group(P<0.01).(3)Compared with the control group,the mRNA expression levels of tumor necrosis factor α and interleukin-1β were increased in the lipopolysaccharide group(P<0.001,P<0.01).Compared with the lipopolysaccharide group,mRNA expression levels of tumor necrosis factor α and interleukin-1β were decreased in the lipopolysaccharide+nobiletin group(P<0.01,P<0.05).(4)Compared with the control group,the protein expression levels of p-nuclear factor κB p65,tumor necrosis factor α,and interleukin-1β in were increased the lipopolysaccharide group(P<0.001).Compared with the lipopolysaccharide group,the expression of p-nuclear factor κB p65,tumor necrosis factor α,and interleukin-1β was decreased in the lipopolysaccharide+nobiletin group(P<0.001).(5)These findings suggest that nobiletin attenuates lipopolysaccharide-induced inflammatory response in BV2 microglia by suppressing nuclear factor-κB signaling pathway.

BACKGROUND:Traditional Chinese medicine has rich experience and unique advantages in the empirical treatment of phlegm-heat and Fu-organs excess syndrome of ischemic stroke.In order to further explore the therapeutic targets and mechanisms of traditional Chinese medicine for this disease,it is crucial to establish a stable and reliable animal model of phlegm-heat and Fu-organs excess syndrome combined with empirical symptoms of ischemic stroke. OBJECTIVE:To explore the establishment method and evaluation system of the rat model of ischemic stroke with phlegm-heat and Fu-organ excess syndrome. METHODS:Sixty male Sprague-Dawley rats were randomly divided into four groups:blank control group(n=12),ischemic stroke group(n=18),disease+syndrome group(n=18),phlegm-heat and Fu-organ excess syndrome group(n=12),all of which were given high-fat diet for 25 days.On the 26th day,the rats in the blank control group and ischemic stroke group were intragastrically given normal saline and high fat diet,while those in the other two groups were intragastrically given autologous feces suspension and high fat diet for 3 continuous days.After gavage,ischemic stroke models were established using the suture method in the ischemic stroke group and disease+syndrome group.The changes in diet,water intake,body mass,body temperature,fecal traits,nasal secretions,sputum in the throat,and tongue image were recorded.Neurological deficits,tongue image,blood lipid levels,morphological changes of brain tissue and carotid artery,and the serum levels of motilin and somatostatin were detected. RESULTS AND CONCLUSION:Compared with the control group,the rats in the disease+syndrome group had shortness of breath,listlessness,irritability,bradykinesia,a large number of secretions around the nose,audible and heavy sputum in the throat,decreased diet and water intake,increased body mass,body temperature,and slingual vein score,decreased fecal pellet count,Bristol score and fecal moisture content,increased serum total cholesterol,triglyceride,low-density lipoprotein and somatostatin levels,decreased motilin level,increased neurological deficit score,significant pathological changes of the carotid artery,and significant morphological changes of the brain tissue.The ischemic stroke group only showed pathological changes of ischemic brain tissue,without the characteristics of phlegm-heat and Fu-organ excess syndrome.The phlegm-heat and Fu-organ excess syndrome group could present with the typical characteristics of traditional Chinese medicine syndromes,without the pathological changes of brain tissue with ischemic stroke.To conclude,the compound modeling method of high-fat induction combined with suture method and autologous feces gavage can establish an animal model of ischemic stroke with phlegm-heat and Fu-organ excess syndrome.

Stasis-heat is a pathological factor associated with numerous exogenous and internal injuries, representing a pivotal mechanism in disease progression. Its primary cause is fire-heat toxicity. Based on the theory of qi and the holistic perspective of traditional Chinese medicine, this concept emphasizes that the biochemistry of all natural phenomena relies on the dynamic movement of qi ascending, descending, exiting, and entering. Within six qi, "fire" includes sovereign and ministerial fires. While physiological ministerial fire is the source power of life, pathological ministerial fire manifests as violent, intense energy that readily interacts with blood, leading to the formation of stasis-heat. Therefore, this article examines the formation and treatment of stasis-heat resulting from ministerial fire dysfunction. From the perspectives of ministerial fire gasification, the shape and quality of meridians, and the elevation of ministerial fire, it elucidates why the "pericardium-sanjiao-gallbladder" axis is regarded as pivotal. Furthermore, when the "pericardium-sanjiao-gallbladder" ministerial fire axis is unfavorable, and the stagnation of ministerial fire elevation and blockage is crucial to stasis-heat formation. Additionally, the depletion of essence and blood in the liver and kidneys, preventing the proper storage of ministerial fire, forms the pathological foundation. Drawing upon The Inner Canon of Yellow Emperor, this article explores therapeutic principles based on the rules of odor treatment: "when fires in the interior, the treatment of salty and cold, accompanied by bitter and pungent, acid to astringe, bitter to disperse." These principles are applied to achieve specific therapeutic goals: tempering the excess of ministerial fire to cool the nutritive level and transform stasis; adjusting the imbalance of elevation and depression to vent heat and unblock stasis; and restoring the misplaced fire by nourishing blood to expel stasis. Through these approaches, the article aims to reestablish the proper circulation of ministerial fire, dissipate blood stasis, and ultimately eliminate stasis-heat, thereby offering an integrated perspective on its pathogenesis and treatment.

In recent years,with the continuous innovation of modern war mode,weapons and protective equipment,the mechanism and mode of war trauma have also produced great changes.The widespread use of bulletproof vest and improvised explosive devices has led to increasing incidence of genitourinary trauma.The pattern of genitourinary trauma has also transformed from internal structures(kidney,ureters,bladder)to external structures(scrotum,testes,penis,urethra),suggesting that the research focus of genitourinary system war trauma should be gradually transformed to trauma research of lower urinary tract and external genitalia.This article reviews the incidence,treatment and prognosis of genitourinary trauma in several modern wars,and mainly describes the relevant conditions of lower urinary tract and external genitalia trauma and the relevant progress in the treatment in recent years.

Objective:To investigate the effects of low-frequency and high frequency repetitive transcranial magnetic stimulation (rTMS) combined with levodopa and benserazide hydrochloride on mild cognitive impairment in patients with Parkinson disease (PD).Methods:Totally 90 PD patients with mild cognitive impairment who visited from January 2020 to June 2022 were included , and they were divided into a simple drug group ( n=30), drug+ low-frequency group ( n=30), and drug+ high-frequency group ( n=30) according to the order of admission.The patients in the simple drug group were treated with oral levodopa and benserazide hydrochloride, while the patients in drug+ low-frequency and drug+ high-frequency groups were treated with low-frequency or high-frequency rTMS on the basis of oral levodopa and benserazide hydrochloride.Montreal cognitive assessment(MoCA), digital span (DS), Chinese auditory learning test (CALT), the judgment of line orientation test (JLOT) and verbal fluency test (VFT) were used to evaluate the cognitive function of patients before and after 4 weeks of treatment.SPSS 26.0 was used for statistical analysis.The paired t-test was used for intra-group comparison before and after treatment, while one-way ANOVA was used for inter-group comparison. Results:There were no significant differences in MoCA, DS anterograde, DS backward, CALT immediate recall, CALT delayed recall, JLOT, and VFT scores among patients in the simple drug group before and after 4 weeks of treatment( t=-1.157, -0.648, -0.215, -0.290, -0.154, -0.782, -0.960, all P>0.05). After 4 weeks of treatment, MoCA, DS anterograde, DS backward, CALT immediate recall, CALT delayed recall, JLOT and VFT scores in drug+ low-frequency group and drug+ high-frequency group were higher than before treatment (drug+ low frequency group: t=-16.357, -11.379, -7.999, -11.805, -16.624, -15.996, -17.241, all P<0.05; drug+ high-frequency group: t=-25.198, -13.971, -13.904, -25.831, -26.382, -20.108, -15.643, all P<0.05). There were no statistically significant differences in the scores of MoCA, DS anterograde, DS backward, CALT immediate recall, CALT delayed recall, JLOT and VFT among the three groups before treatment (all P>0.05). After treatment, there were statistically significant differences in the scores of MoCA, DS anterograde, DS backward, CALT immediate recall, CALT delayed recall, JLOT and VFT among the three groups (simple drug group : (20.37±1.96), (4.37±1.19), (2.80±0.55), (6.93±1.70), (5.17±1.09), (15.50±2.69), (10.73±1.55); drug+ low-frequency group: (23.83±2.32), (5.87±0.94), (3.87±0.73), (9.17±1.74), (8.13±1.50), (20.77±2.19), (13.30±1.73); drug+ high-frequency group: (27.17±1.64), (6.73±1.01), (4.80±0.81), (11.20±2.06), (10.03±1.54), (25.17±3.14), (15.87±2.05)) (all P<0.05). Further analysis showed that both the drug+ low-frequency and drug+ high-frequency groups had higher scores than the simple drug group, and the drug+ high-frequency group had higher scores than the drug+ low-frequency group(all P<0.05). Conclusion:The combination of drug+ low-frequency or drug+ high-frequency rTMS and drug therapy can help improve cognitive function in patients with PD, and the efficacy of drug+ high-frequency rTMS may be more significant, which provides a new therapeutic idea for clinical treatment of patients with PD.

Objective VATER/VACTERL-like association is associated with adverse pregnancy outcomes.Genetic evidence of this disorder is sporadic.In this study,we aimed to provide genetic insights to improve the diagnosis of VACTERL. Methods We have described a Chinese family in which four members were affected by renal defects or agenesis,anal atresia,and anovaginal fistula,which is consistent with the diagnosis of a VACTERL-like association.Pedigree and genetic analyses were conducted using genome and exome sequencing. Results Segregation analysis revealed the presence of a recessive X-linked microdeletion in two living affected individuals,harboring a 196-380 kb microdeletion on Xq27.1,which was identified by familial exome sequencing.Genome sequencing was performed on the affected male,confirming a-196 kb microdeletion in Xq27.1,which included a 28%loss of the CDR-1 gene.Four family members were included in the co-segregation analysis,and only VACTERL-like cases with microdeletions were reported in X27.1. Conclusion These results suggest that the 196-380 kb microdeletion in Xq27.1 could be a possible cause of the VATER/VACTERL-like association.However,further genetic and functional analyses are required to confirm or rule out genetic background as the definitive cause of the VACTERL association.

Objective:To carry out the policy diffusion analysis of centralized and volume-based drug procurement in China in recent years,and to provide reference for the formulation of centralized and volume-based drug procurement policy.Methods:Through the official websites of the central and provincial governments,the official websites of the Health Commission and the official websites of the Medical Security Bureau,the policy documents related to centralized and volume-based drug procurement from January 1,2009 to December 31,2023 were searched.Based on the policy diffusion theory,the reference network analysis method is used to analyze the intensity,breadth and speed of policy diffusion,and the sequential analysis method of policy keywords is used to analyze the direction of policy diffusion.Results:In the two stages of the development of centralized and volume-based drug procurement policy,the number of policies issued in the medical insurance management stage reached the peak;The top ten policies with the highest diffusion intensity and breadth are all central policies,and most of them are notices and opinions.In addition,the newly promulgated policies have a faster diffusion speed.In the direction of diffusion,top-down and parallel diffusion trends are obvious.Conclusion:The diffusion of centralized and volume-based drug procurement policy in China focuses on the central policy,and the diffusion speed is increasing year by year.It is suggested to strengthen the policy coordination between the central and local governments,establish a unified national information platform for centralized drug procurement,optimize the learning and competition mechanism between governments at all levels,and give play to the advantages of"policy experiment".

Objective:To explore the impact of organizational capacity on organizational performance in community health centers(CHCs),and to provide a scientific basis for improving the organizational performance of CHCs.Methods:Randomly select one administrative district from each of the four functional zones in Beijing,and all the 66 CHCs in the four administrative districts were chosen as sample cases.Fuzzy set qualitative comparative analysis(fsQCA)was used to explore the effect of nine secondary competencies of organizational competence segmentation on high and low organisational performance in CHCs.Results:There are three groupings of high and low performing CHCs,and the strengthening of medical service capacity,public health capacity,decision-making capacity,normative capacity and learning capacity play a universal role in improving the organizational performance of CHCs.Conclusions:The performance of community health service centres is the result of a variety of elements linked to each other,and multiple paths can enable them to achieve high organizational performance,community health service centres can be combined with their own advantages of differentiated development,and lower-performing community health service centres can give priority to the development of medical service capacity and learning capacity to promote the rapid improvement of organizational performance.

Objective To explore the value of serum microRNAs-145(miR-145)and P53 antibody detection in the evaluation of therapeutic effect and prognosis in the treatment of breast cancer with Long Bei Xiaoyao Powder.Methods Ninety cases of breast cancer patients admitted to Beijing Aerospace General Hospital from January 2020 to January 2021 were selected as the study subjects.The patients were randomly divided into an observation group and a control group by random number table method,with 45 cases in each group.All of the patients in the two groups received individualized comprehensive treatment,and additionally the observation group was treated with Long Bei Xiaoyao Powder.The course of treatment covered three months.Real-time fluorescence quantitative polymerase chain reaction(PCR)method was used to detect serum miR-145 expression level,and enzyme-linked immunosorbent assay(ELISA)was used to detect serum P53 antibody expression level.The differences in the pre-and post-treatment expression levels of serum miR-145 and P53 antibodies in the two groups were compared,the relationship between the serum miR-145 and P53 antibody expression level and the poor prognosis of the patients in the observation group was explored by logistic regression analysis,and receiver operating characteristic curve(ROC)was drawn to analyze the value of the serum miR-145 and P53 antibody detection in the prediction of poor prognosis in the observation group.Results(1)After treatment,the detection value of serum miR-145 in the two groups of patients showed an increasing trend(P＜0.05),while that of the P53 antibody showed a decreasing trend(P＜0.05).The intergroup comparison showed that the detection value of serum miR-145 in the observation group was significantly higher than that of the control group,while the detection value of P53 antibody was significantly lower than that of the control group,the differences being all statistically significant(P＜0.05).(2)In the observation group,the detection value of serum miR-145 in the patients with good prognosis was significantly higher than that in the patients with poor prognosis,and the detection value of serum P53 antibody in the patients with good prognosis was significantly lower than that in the patients with poor prognosis,the differences being all statistically significant(P＜0.05).(3)Logistic regression analysis showed that high expression of miR-145 was a protective factor for the patients with poor prognosis in the observation group,and high expression of P53 antibody was a risk factor for the patients with poor prognosis in the observation group(P＜0.05).(4)The area under the ROC curve(AUC)for the prediction of prognosis of the patients in the observation group by the combination of serum miR-145 and P53 antibody was the largest(0.877,95%CI:0.769-0.985),and its sensitivity and specificity were 93.75%and 93.10%,respectively,with statistically significant differences(P＜0.05).Conclusion Low expression of serum miR-145 and high expression of serum P53 antibody are presented in the breast cancer patients with poor prognosis,and Long Bei Xiaoyao Powder exerts satisfactory therapeutic effect in treating breast cancer,which is conducive to enhancing the expression level of serum miR-145 and reducing the expression level of serum P53 antibody.

Objective To compare the outcomes of transplant kidneys and patient survival between simultaneous pancreas-kidney transplantation(SPKT)recipients and deceased donor kidney transplant(DDKT)recipients in patients with type 2 diabetes mellitus(T2DM)complicated with end-stage renal disease(ESRD),and to analyze the risk factors affecting patient survival post-SPKT.Methods Clinical and prognostic data of patients who underwent kidney transplantation from January 27,2003,to January 1,2021,were retrieved from the United Network for Organ Sharing(UNOS)database.A total of 50 230 cases were selected based on inclusion criteria,with 48 669 cases in DDKT group and 1561 cases in SPKT group.Kaplan-Meier analysis was employed to compare transplant kidney and patient survival between the two groups,and propensity score matching(PSM)was utilized to balance confounding factors between the groups.Cox regression model was used to analyze independent risk factors affecting patient survival post-SPKT.Results Compared with DDKT group,recipients in SPKT group had a younger median age(P<0.001),a higher proportion of males(P<0.001),lower BMI(P<0.001),shorter dialysis and transplant waiting times(P<0.001),a higher percentage of private medical insurance(P<0.001),a lower proportion of previous transplants(P<0.001),a younger age at diabetes diagnosis(P<0.001),and a lower incidence of peripheral vascular disease(P=0.033).Compared with DDKT group,the donors in SPKT group had a younger median age(P<0.001),a higher proportion of males(P<0.001),lower BMI(P<0.001),and a lower prevalence of hypertension and diabetes history(P<0.001).In terms of transplant-related factors,the SPKT group had a shorter donor kidney cold ischemia time(P<0.001),a higher degree of HLA mismatch(P<0.001),and a lower Kidney Donor Profile Index(KDPI)(P<0.001)when compared with DDKT group.The SPKT group had lower serum creatinine levels at discharge(P<0.001),lower rates of postoperative delayed graft function(DGF)and acute rejection(AR)(P<0.001),but longer hospital stays(P<0.001)when compared with DDKT group.Kaplan-Meier survival analysis curves,both original and after propensity score matching(PSM),consistently showed significantly higher transplant kidney and patient survival rates in SPKT group compared with DDKT group(P<0.001).Cox regression model analysis indicated that recipient age,recipient race,donor age,and donor kidney cold ischemia time were independent risk factors influencing patient survival post-SPKT.Conclusions For ESRD patients with T2DM,SPKT offers improved long-term graft and patient survival rates compared with DDKT.Recipient age,recipient ethnicity,donor age,and cold ischemia time for the donor's kidney are independent risk factors affecting post-SPKT patient survival.