ObjectiveTo investigate the effects of Xixintang （XXT）-medicated serum on the amyloid β-protein （Aβ）_25-35-induced polarization of BV-2 microglial cells by a cell experiment and uncover the potential mechanisms of this formula in the prevention and treatment of Alzheimer's disease （AD）， thus providing scientific evidence for the clinical application of XXT. MethodsBV-2 microglial cells were subcultured. The optimal concentrations of XXT-medicated serum and Aβ_25-35 were determined via the cell-counting kit-8 （CCK-8） assay. The cell experiment was carried out with the following groups： blank control， model （Aβ_25-35 at 40 μmol·L^-1）， XXT-medicated serum （Aβ_25-35 at 40 μmol·L^-1 + 10% XXT-medicated serum）， and blank serum （Aβ_25-35 at 40 μmol·L^-1 + 10% blank serum）. After 24 hours of cell incubation， immunofluorescence was used to detect the expression of ionized calcium-binding adaptor molecule 1 （IBA1）， CD16/32， and CD206. Real-time PCR was performed to measure the mRNA levels of CD206， CD163， inducible nitric oxide synthase （iNOS）， and arginase 1 （Arg-1）. Enzyme-linked immunosorbent assay （ELISA） was employed to quantify the levels of nerve growth factor （NGF）， iNOS， and Arg-1. The nitric oxide （NO） concentration was determined via the nitrate reductase method. ResultsCompared with the blank control group， the model group showed increased expression of IBA1 and CD16/32 （P<0.01）， decreased expression of CD206 （P<0.05）， upregulation in the mRNA level （P<0.01） and content （P<0.05） of iNOS， downregulation in the mRNA levels of CD206， CD163， and Arg-1 （P<0.05， P<0.01）， lowered levels of Arg-1 and NGF （P<0.05）， and an elevation in the NO level （P<0.05）. Compared with the model group， the XXT-medicated serum group exhibited reduced expression of IBA1 and CD16/32 （P<0.05， P<0.01） and increased expression of CD206 （P<0.01）. Both the content and mRNA level of iNOS were downregulated （P<0.05， P<0.01）， while the mRNA levels of CD206， CD163， and Arg-1 were upregulated （P<0.01） in the XXT-medicated serum group. In addition， the XXT-medicated serum group showed elevated levels of Arg-1 and NGF （P<0.05） and a lowered level of NO （P<0.05）. The blank serum group showed no statistically significant differences in the measured parameters compared with the model group. ConclusionThe XXT-medicated serum can inhibit the polarization toward the M1 phenotype and promote the polarization toward the M2 phenotype， exerting anti-inflammatory and neurotrophic effects.

ObjectiveTo explore the potential mechanism of Xixin Decoction （洗心汤， XD） in treating Alzheimer's disease （AD）. MethodsXD-containing serum was prepared， and the BV-2 microglial cell viability was assessed using the CCK8 assay to determine the optimal intervention concentrations of XD-containing serum and amyloid-beta _25-35 （Aβ_25-35） for subsequent experiments. BV-2 cells were divided into four groups， control group， model group （Aβ_25-35）， XD-containing serum group （Aβ_25-35+ XD-containing serum）， and blank serum group （Aβ_25-35 + blank serum）. After 24 hours of culture， the levels of interleukin-1β（IL-1β）， cyclooxygenase-2 （COX-2）， and arginase-2 （Arg-2） in the supernatent were detected by ELISA. Immunofluorescence staining was performed to detect the protein levels of ionized calcium-binding adaptor molecule 1 （IBA1）， CD86， and CD206. RT-PCR was used to analyze the mRNA expression of IL-1β， interleukin-6 （IL-6）， and interleukin-10 （IL-10）. ResultsThe concentrations of 10% XD-containing serum and 40 μmol·L^-¹ Aβ_25-35 were selected for subsequent experiments. Compared to the control group， the model group showed significantly increased levels of IL-1β and COX-2 in the supernatant， as well as elevated protein expression of IBA1 and CD86 and increased mRNA expression of IL-1β and IL-6， while exhibiting significantly reduced levels of Arg-2 in the supernatant， CD206 protein expression， and IL-10 mRNA expression （P＜0.05 or P＜0.01）. Compared to the model group， the XD-containing serum group showed significant improvement in all these indicators （P＜0.01）， whereas no statistically significant differences were observed in the blank serum group （P＞0.05）. ConclusionXD may regulate microglial activation， inhibit pro-inflammatory factors， and enhance anti-inflammatory factor release， thereby improving neuroimmune inflammation and inhibiting the progression of Alzheimer's disease.

OBJECTIVE To predict and validate the potential mechanisms of Kaixinsan （KXS） in ameliorating neuroinflammation in Alzheimer’s disease （AD）. METHODS Network pharmacology was employed to identify core anti- inflammatory components and key inflammatory targets of KXS for AD. Gene ontology （GO） functional annotation， Kyoto Encyclopedia of Genes and Genomes （KEGG） pathway enrichment， and molecular docking were performed. Based on these findings， male SD rats were used to establish an AD model via chronic D-galactose induction. The effects of KXS on AD rats were evaluated， including quantitative behavioral score， learning and memory parameters （escape latency， platform crossings， platform quadrant distance and time）， organ indexes （heart， liver， spleen， thymus）， histopathological alterations in the hippocampus， and expressions of inflammation-related pathway proteins and their upstream/downstream regulators. RESULTS Core anti-inflammatory components of KXS for AD included gomisin B， panaxytriol， gomisin A， enhydrin， vulgarin and panaxydol， while key inflammatory targets involved nuclear factor-kappa B subunit 1（ NFKB1）， nuclear factor-κB p65（ NF-κB p65）， interleukin-1β（ IL- 1β）， IL-6， Toll-like receptor 4 （TLR4）， tumor necrosis factor， nucleotide-binding domain leucine-rich repeat and pyrin domain- containing receptor 3 （NLRP3） and caspase-1 （CASP1）. GO and KEGG pathway enrichment involved inflammatory response， phosphorylation and the NF-κB signaling pathway. Molecular docking confirmed strong binding affinities between core components and key targets. Animal experiments demonstrated that， compared to the model group， KXS significantly alleviated histopathological damage （e.g.， neuronal shrinkage， reduced Nissl bodies in hippocampal CA1， CA3， and DG regions）， increased organ indexes （except for liver index） and Nissl-stained positive cells， improved learning and memory performance， and reduced behavioral scores （at the 8 and 12 weeks of the experiment） and protein expression of NF- κB p65， phosphorylated NF- κB p65， TLR4， NLRP3， CASP1 and IL-1β. CONCLUSIONS KXS effectively mitigates neuroinflammation， reduces hippocampal neuronal injury， and enhances learning and memory ability in AD rats， potentially through suppressing the NF-κB signaling pathway and its upstream/ downstream regulators.

Objective To explore the pharmacodynamic substances of Simiao Wan for the treatment of hyperuricemia and gout.Methods The pharmacological model of hyperuricemia was established.The chemical components in vivo and in vitro of Simiao Wan were analyzed by UPLC-Q-Exactive-MS.Based on the components absorbed in blood,the"active ingredient-target-pathway"network of Simiao Wan for regulating hyperuricemia and gout was constructed by network pharmacology method.The key ingredients were used for molecular docking with key targets[uricogenase(XDH),uric acid transporter(ABCG2,GLUT9,OAT1,URAT1)and inflammatory targets(PTGS2,TLR2,TLR4)]of hyperuricemia and gout.Finally,experimental verification was conducted according to the results of molecular docking.Our aim is to identify the key pharmacodynamic substances of Simiao Wan for the treatment of hyperuricemia and gout.Results Eighty-nine components of Simiao Wan were identified by UPLC-Q-Exactive-MS analysis,including 74 components absorbed in blood,which were confirmed as candidate ingredients.Network pharmacology was used to constructed"components absorbed in blood-target-pathway"network,and components absorbed in blood were matched with 116 targets of hyperuricemia and 173 targets of gout.It is involved in the regulation of biological processes,such as glucose and lipid metabolism,oxidative stress,inflammatory response,ERK1 and ERK2 cascade,MAPK cascade,PI3K signal transduction.Moreover,Simiao Wan plays a role in regulating the network of hyperuricemia and gout through regulating blood lipids and atherosclerosis,apoptosis,AGE-RAGE,TNF,PI3K-Akt,MAPK,TLRs,JAK-STAT,NF-κB and other signaling pathways.Molecular docking studies showed that berberine,phellodendrine,magnoflorine,jatrorrhizine,palmatine,obacunone,limonin,atractylodin,taxifolin,atractylenolide Ⅲ and β-ecdysterone had good affinity with uric acid synthase,uric acid transporter and inflammatory targets.Western Blot test showed that taxifolin negatively regulates the expression of URAT1.The above-mentioned compounds were the main pharmacodynamic substances of Simiao Wan for the treatment of hyperuricemia and gout.Conclusion This article describes the main pharmacodynamic substances of Simiao Wan in the regulation of hyperuricemia and gout,which can provides a scientific basis for the clinical application,improvement in quality evaluation and standard of Simiao Wan.

BACKGROUND: Immune checkpoint inhibitors (ICIs) are increasingly used as first-line therapy for patients with advanced non-small cell lung cancer (NSCLC) harboring no actionable mutations; however, data on their efficacy among patients presenting with intracranial lesions are limited. This study aimed to explore the efficacy and safety of ICIs combined with chemotherapy in advanced NSCLC patients with measurable brain metastasis at initial diagnosis. METHODS: Our study retrospectively analyzed clinical data of a total of 211 patients diagnosed with driver gene mutation-negative advanced NSCLC with measurable, asymptomatic brain metastasis at baseline from Hunan Cancer Hospital between January 1, 2019 and September 30, 2021. The patients were stratified into two groups according to the first-line treatment regimen received: ICI combined with chemotherapy ( n = 102) or chemotherapy ( n = 109). Systemic and intracranial objective response rates (ORRs) and progression-free survival (PFS) were analyzed. Adverse events were also compared between the groups. RESULTS: Compared with the chemotherapy-based regimen, the ICI-containing regimen was associated with a significantly higher intracranial (44.1% [45/102] vs . 28.4% [31/109], χ2 = 5.620, P = 0.013) and systemic (49.0% [50/102] vs . 33.9% [37/109], χ2 = 4.942, P = 0.019) ORRs and longer intracranial (11.0 months vs . 7.0 months, P <0.001) and systemic (9.0 months vs . 5.0 months, P <0.001) PFS. Multivariable analysis consistently revealed an independent association between receiving ICI plus platinum-based chemotherapy as a first-line regimen and prolonged intracranial PFS (hazard ratio [HR] = 0.52, 95% confidence interval [CI]: 0.37-0.73, P <0.001) and systemic PFS (HR = 0.48, 95% CI: 0.35-0.66, P <0.001). No unexpected serious adverse effects were observed. CONCLUSION: Our study provides real-world clinical evidence that ICI combined with chemotherapy is a promising first-line treatment option for driver gene mutation-negative advanced NSCLC patients who present with brain metastasis at initial diagnosis. CLINICAL TRIAL REGISTRATION https://www.clinicaltrials.gov/ , OMESIA, NCT05129202.
Humans ; Carcinoma, Non-Small-Cell Lung/genetics* ; Lung Neoplasms/genetics* ; Immune Checkpoint Inhibitors/therapeutic use* ; Retrospective Studies ; Brain Neoplasms/genetics*

Objective To investigate the value of optical trocar insertion technique in establishing pneumoperitoneum in patients undergoing laparoscopic surgery after previous abdominal surgery. Methods A total of 29 patients, with a history of abdominal surgery, who planned to undergo laparoscopic liver surgery were enrolled and randomly divided into optical trocar insertion group and open approach group. The independent samples t -test was used for comparison of normally distributed continuous data between groups, and the Mann-Whitney U test was used for comparison of non-normally distributed continuous data between groups; the Fisher's exact test was used for comparison of categorical data between groups; the Mann-Whitney U test was used for comparison of ranked data between groups. Results There were no procedure-related complications in either group. Compared with the open approach group, the optical trocar insertion group had a significantly shorter time required to establish pneumoperitoneum [35.00 (21.00-46.00) seconds vs 180.00 (152.50-252.50) seconds, U =0, P < 0.001] and a significantly smaller incision length [1.10(1.00-1.20) cm vs 2.80(2.45-3.00) cm, U =0, P < 0.001]. Conclusion Both optical trocar insertion and open approach for establishing pneumoperitoneum is relatively safe in patients undergoing laparoscopic liver surgery after previous abdominal surgery, while optical trocar insertion has the advantages of high efficiency and minimal invasiveness in establishing pneumoperitoneum.

Objective:To retrospectively analyze the urodynamics quality in Southwest China, and find out the main issues of urodynamics quality in Southwest China and try to find out the improvement ways.Methods:In this study, a two-stage sampling method was used.In the first stage, 10 medical institutions in Southwest China were selected by cluster sampling from March to June, 2020.In the second stage, according to the development of UDS in Southwest China, the sample size estimation formula was adopted, and the loss of follow-up rate in reports extraction was considered, the initial sample size was 350. As the workload of UDS in the 10 medical institutions involved in the study was equivalent, 35 urodynamics traces from each medical institution were selected. The initial samples should also meet the inclusion criteria: ①patients with clear medical history and complete clinical data; ②UDS traces were clear; ③UDS system was water filled system; ④age>18, and 150 urodynamic traces were included in the final study. We evaluated the quality of enrolled urodynamics traces, and the quality evaluation standard according to the guidelines established by the International Continence Society (ICS). The evaluation conducted by two independent urologist with more than 10 years working experience. Artifacts were divided into non-technical artifacts: abnormal abdominal pressure changes, urine volume <150 ml when did the uroflow test, and technical artifacts: non-standard zero setting, fail to record all urodynamics parameters, baseline drift, catheter displacement, misjudgment of detrusor physiological contraction and detrusor overactive in voiding phase, misjudgment between detrusor overactive and bladder low compliance in filling phase.Results:non-technical artifacts: 32 cases were found abnormal abdominal pressure changes (21.3%), 21 cases (14.0%) were found when did the uroflow test the urine volume <150 ml, and technical artifacts: Non-standard zero setting in 28 cases (18.7%), fail to record all urodynamics parameters in 8 cases, baseline drift in 16 cases, catheter displacement in 9 cases and misjudgment of detrusor physiological contraction and detrusor overactive in voiding phase in 12 cases, misjudgment between detrusor overactive and bladder low compliance in filling phase in 24 cases (16.0%).Conclusions:At present, the urodynamics quality in Southwest China need to be improved. The main issues were that the operator didn’t obey the basic operation and quality control process, and the operator did not have enough basic knowledge of urodynamics. It can be improved by strictly carry out the operation standard of UDS, identifying and correcting artifacts in time, and promoting the standardized urodynamic training courses.

Vav-family proteins are guanosine nucleotide exchange factors(GEFs)and one of RhoGEFs family numbers.Vav proteins can influence cell signaling transduction, cytoskeleton recombination and adherence migration in special cells by RhoA, RhoG and Rac-1 pathway.There are 80 kinds of RhoGEFs in mammalian cell.Vav proteins play an important role in hematological system, nervous system, cardiovascular system and immune system.So the function of vav protein in immune system was reviewed in this paper.

Objective: To investigate the role of midkine(MK)in the pathogenesis of Henoch-Schonlein purpura(HSP) and Henoch-Schonlein purpura nephritis(HSPN). Methods: In the case group, 35 cases were hospitalized in the pediatric kidney rheumatism immunology ward of Shengjing hospital affiliated to China Medical University from December 2016 to January 2018.Among them, 10 cases were HSP, 25 were HSPN.According to quantitative level of 24-hour urine protein, HSPN group was divided into HSPN(nephrotic level of proteinuria)group of 15 cases and HSPN(non-nephrotic level of proteinuria)group of 10 cases.The control group consisted of 12 healthy cases who underwent physical examination at outpatient department in the same period in the developmental pediatric clinic of our hospital.Blood samples were collected to detect MK.The other clinical datas including renal function, 24-hour urine protein quantitative, immunoglobulin, etc were collected.The serum MK and renal function indexes were compared among groups.The correlation between MK and various clinical indicators was analyzed, and the receiver operating characteristic(ROC) curve was used to analyze the diagnostic significance of MK for HSP and HSPN. Results: MK level of case group was higher than that of healthy control group[(289.34±160.70)pg/ml vs.(100.03±56.75)pg/ml, P<0.05]. Moreover, the difference of MK concentration among the HSPN(nephrotic proteinuria)group, the HSPN(non-nephrotic proteinuria)group and the HSP group was still statistically significant[(449.91±141.91)pg/ml vs.(244.04±89.15)pg/ml vs.(175.94±46.30)pg/ml, P<0.05]. MK was positively correlated with urine microalbumin(r=0.54), IgA(r=0.132), IgE(r=0.304), urine β2 microglobulin(r=0.483), 24-hour urine protein /body weight(r=0.503), and urine transferrin level(r=0.509)in the case group(P<0.05). According to the ROC curve, the area under ROC of MK for predicting the diagnosis of HSP was 0.908(95%CI 0.828-0.988). The optimal value in predicting the diagnosis of HSP was 182.762 pg/ml, with sensitivity and specificity of 81.4% and 91.7%.The area under ROC of MK in predicting HSPN was 0.947(95%CI 0.888-1.000), and the optimal value of predicting HSPN was 218.186 pg/ml, with sensitivity and specificity of 84.0% and 95.5%. Conclusion MK may be involved in the pathogenesis of HSP and HSPN.It can provide the basis for clinical diagnosis of HSP and HSPN, and has significance in evaluating the degree of renal damage of HSPN.

Objective To investigate the correction between the levels of vascular endothelial growth factor (VEGF), serum amyloid A (SAA), hypersensitive C-reactive protein (hs-CRP) and acute cerebral infarction (ACI), and to provide the basis for the diagnosis and treatment of ACI.Methods A total of 76patients with ACI in the hospital from August to October 2017were selected as ACI group.In addition, 32healthy subjects underwent physical examination in the same period in this hospital were selected as negative control group (NC group).The levels of SAA and hs-CRP were detected by nephelometry, while the level of VEGF was measured by enzyme-linked immunosorbent assay (ELISA).The differences of detection indexes between two groups were compared, and the diagnostic value of each index and the combined test were evaluated with the Youden index.Results The levels of SAA, hs-CRP and VEGF in ACI group, were significantly higher than those of NC group (P＜0.01).The levels of VEGF was positively correlated with SAA and hs-CRP (r=0.434and0.631, P=0.000and 0.000).The optimal diagnostic critical points of VEGF, SAA and hs-CRP in the diagnosis of ACI were 161.93pg/mL, 3.81mg/L and 4.63mg/L, and the sensitivities were 93.55％, 65.91％and64.44％, the specificities were 60.00％, 93.75％and 90.32％, respectively.Combined detection with hs-CRP and VEGF was superior to single index detection and other joint detection.The sensitivity, specificity and Youden index of combined detection with hs-CRP and VEGF were 96.67％, 95.65％and 0.92respectively.Conclusion The levels of VEGF, SAA and hs-CRP increase in patients with ACI, and they play important roles in the diagnosis of ACI.VEGF are positively related to SAA and hs-CRP, and there may be an synergistic effect exist.VEGF may be involved in the pathological process of cerebral infarction.The combined detection of hs-CRP and VEGF is of high clinical value in the diagnosis of cerebral infarction.