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.

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.

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 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.

Objective To explore the relationship between serum ferritin levels and body fat distribution in patients with type 2 diabetes mellitus(T2DM).Methods A retrospective analysis was conducted on 151 patients with T2DM who were hospitalized in the Department of Endocrinology of the First Hospital of Lanzhou University from June to November 2020,and all the patients were divided into high serum ferritin(n=50)and normal serum ferritin(n=101)groups according to their serum ferritin levels.The visceral fat area(VFA),subcutaneous fat area(SFA),liver fat,height,weight and waist circumference(WC)were measured,as well as blood glucose,lipid indexes,body mass index(BMI)and visceral adiposity index(VAI)were also calculated.t-test or nonparametric test was used to compare the differences between the two groups,and the relationship between serum ferritin levels and body fat distribution was analyzed by Pearson or Spearman correlation analysis,multiple linear regression and logistic regression.Results The VAI and WC were significantly higher in high serum ferritin group[3.13(2.16,4.58)and(96.66±7.78)cm]than in normal serum ferritin group[2.66(1.66,3.81)and(91.96±9.75)cm,P<0.05].The prevalence of central obesity and dyslipidemia was higher in high serum ferritin group(88.0%and 90.0%)than in normal serum ferritin group(68.3%and 75.2%);and the composition ratios of poor glycemic control and insulin resistance(96.0%and 62.0%)were also higher than in normal serum ferritin group(78.2%and 40.6%)(P<0.05),there were no statistically significant differences in BMI,VFA,and SFA levels,as well as antidiabetic drug use and chronic complications of diabetes mellitus between the two groups(P>0.05).Serum ferritin levels in T2DM patients were positively correlated with VAI,WC,triglyceride(TG),fasting blood glucose(FPG),HbA1c,dyslipidemia and serum creatinine(r=0.171,0.207,0.187,0.243,0.270,0.162,0.162;P<0.05),and negatively correlated with age,sex and diabetes course(r=-0.191,-0.434,-0.352;P<0.05).Multivariate linear regression analysis showed that in male T2DM patients,duration of diabetes and FPG were risk factors for increased levels of serum ferritin.However,WC and VAI did not significantly affect serum ferritin levels.In female patients with T2DM,the course of diabetes,TG and VAI were the factors influencing serum ferritin(P<0.05).Conclusion Dyslipidemia and visceral fat accumulation are risk factors for elevated serum ferritin levels in female T 2DM patients.

Objective:To investigate the association of urinary cadmium level with body mass index (BMI) and body circumferences among the older adults over 65 years old in 9 longevity areas of China.Methods:Subjects were older adults over 65 years old from the Healthy Aging and Biomarkers Cohort Study (HABCS) between 2017 and 2018 conducted in 9 longevity areas in China. A total of 1 968 older adults were included in this study. Information including socio-demographic characteristics, lifestyles, diet intake, and health status was collected by using questionnaires and physical examinations. Urine samples were collected to detect urinary cadmium and creatinine levels. Body circumferences included waist circumference, hip circumference and calf circumference. Subjects were divided into three groups (low:<0.77 μg/g·creatinine, middle:0.77-1.69 μg/g·creatinine, high:≥1.69 μg/g·creatinine) by tertiles of creatinine-adjusted urinary cadmium concentration. Multiple linear regression models were used to analyze the association of creatinine-adjusted urinary cadmium level with BMI and body circumferences. The dose-response relationship of creatinine-adjusted urinary cadmium concentration with BMI and body circumferences was analyzed by using restrictive cubic splines fitting multiple linear regression model.Results:The mean age of subjects was (83.34±11.14) years old. The median (Q1, Q3) concentration of creatinine-adjusted urinary cadmium was 1.13 (0.63, 2.09) μg/g·creatinine, and the BMI was (22.70±3.82) kg/m 2. The mean values of waist circumference, hip circumference, and calf circumference were (85.42±10.68) cm, (92.67±8.90) cm, and (31.08±4.76) cm, respectively. After controlling confounding factors, the results of the multiple linear regression model showed that for each increment of 1 μg/g·creatinine in creatinine-adjusted urinary cadmium, the change of BMI, waist circumference, hip circumference, and calf circumference in the high-level group was -0.28 (-0.37, -0.19) kg/m 2, -0.74 (-0.96, -0.52) cm, -0.78 (-0.96, -0.61) cm, and -0.20 (-0.30, -0.11) cm, respectively. The restrictive cubic splines curve showed a negative nonlinear association of creatinine-adjusted urinary cadmium with BMI ( Pnonlinear<0.001) and negative linear associations of creatinine-adjusted urinary cadmium with waist circumference ( Plinear<0.001), hip circumference ( Plinear<0.001), and calf circumference ( Plinear<0.001). Conclusion:Urinary cadmium level is significantly associated with decreased BMI, waist circumference, hip circumference and calf circumference among older adults over 65 years old in 9 longevity areas of China.

Objective:To explore the surgical intervention strategy for metastatic cervical lymph nodes surrounding the carotid artery in head and neck squamous cell carcinoma.Methods:A total of 62 patients with advanced head and neck tumors and carotid wrap by disease treated in Department of Otorhinolaryngology and Head and Neck Surgery, the Affiliated BenQ Hospital of Nanjing Medical University between June 2019 and December 2023 were reviewed, of whom 9 patients presented with metastatic squamous cell carcinoma in cervical lymph nodes of unknown primary or with no recurrence of primary lesion and all the 9 patients were males, aged from 48 to 79 years old, with≤level 2 of Eastern Cooperative Oncology Group-Performance Status (ECOG-PS). Radiographically common carotid artery (CCA) and/or internal carotid artery (ICA) were surrounded by≥270° with tumor. All the 9 patients received implantation of covered stent in carotid artery and radical resection of metastatic cervical lymph nodes. The success rate, complications, surgery-related complications, local recurrence rate, quality of life (QOL) and overall survival (OS) were analyzed. The QOL of patients was compared by paired rank sum test, and P<0.05 indicated statistically significant difference. The OS was analyzed by Kaplan-Meier. Results:The success rate of stent implantation was 100%, with no implantation-related complications. R0 resection was performed in 8 cases and R1 resection in 1 case. The QOL of patients after surgery was improved, and the improvements in "pain", "mood" and "anxiety" were statistically significant( Z values were -2.236, -2.460 and -2.200, respectively, and all P values were<0.05). Follow-up was 1-18 months, with a median of 7 months, and 1 case was lost to follow-up. Local recurrence occurred in 3 patients with an incidence of 37.5% (3/8). OS was 59.9% at 12 months after surgery. Conclusion:Implantation of covered stent in carotid artery combined with radical resection is an effective method for the treatment of cervical lymph node metastasis.

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.