Objective To investigate the mechanism by which suppressor of cytokine signaling 3(SOCS3)regulates microglial inflammation through nuclear factor-kappaB(NF-κB),providing novel mechanistic insights into microglial involvement in Parkinson's disease(PD)pathogenesis.Methods ① Ten male C57BL/6 mice(12 weeks old,weighing 20～25 g)were subjected to intraperitoneal injection of 15 mg/kg MPTP to establish a PD model.Rotarod test was used to assess motor function.Western blotting was employed to detect the protein expression of tyrosine hydroxylase(TH)and ionized calcium-binding adapter molecule 1(IBA-1)in the substantia nigra.RT-qPCR was utilized to measure the mRNA level of SOCS3 in the substantia nigra.Immunohistochemistry was performed to assess NF-κB p65 subunit expression.The expression of SOCS3,NF-κB and p-NF-κB was measured with Western blotting.② Microglial cell line BV2 was stimulated with 1 000 ng/mL lipopolysaccharide(LPS)for 6 h to establish an inflammatory model.Subsequently,SOCS3 was knocked down.NF-κB inhibitor BAY 11-7082 was used to treat the cells.RT-qPCR and Western blotting were used to measure the expression of SOCS3 at mRNA and protein levels.Western blotting was also applied to detect the expression of NF-κB and p-NF-κB,and ELISA was conducted to measure TNF-α and IL-1β levels in the culture supernatant.Immunofluorescence assay was carried out to localize NF-κB(nuclear vs cytoplasmic).③ A co-culture system of BV2 microglia and N2a neuroblastoma cells was established to investigate the regulatory effects of microglia on neuronal cells.MTT assay and TUNEL staining were used respectively to determine cell viability and apoptosis of N2a cells.Results ① Compared to the control mice,the PD mouse model exhibited reduced rotarod fall latency,down-regulation in TH and SOCS3(P<0.01),up-regulation in IBA-1 and increased p-NF-κB/NF-κB ratio(P<0.01).② In BV2 cells,LPS stimulation increased TNF-α,IL-1β,and p-NF-κB/NF-κB ratio(P<0.01),while down-regulated SOCS3 expression(P<0.01).SOCS3 knockdown in LPS-stimulated BV2 cells further increased the p-NF-κB/NF-κB ratio(P<0.01),increased nuclear localization of NF-κB,and elevated TNF-α and IL-1β levels(P<0.01).BAY 11-7082 treatment in these SOCS3-knockdown,LPS-stimulated cells resulted in reduced p-NF-κB/NF-κB ratio,TNF-α,and IL-1β(P<0.01),and decreased NF-κB nuclear distribution.③ LPS-stimulated BV2 cells reduced cell viability and increased cell apoptosis in N2a cells(P<0.01).SOCS3 knockdown in BV2 cells exacerbated the reduction in N2a cell viability(P<0.01)and the increase in cell apoptosis in N2a cells(P<0.01).BAY 11-7082 treatment of these SOCS3-knockdown BV2 microglia attenuated the reduction in N2a cell viability and decreased apoptosis in N2a cells(P<0.01).Conclusion SOCS3 inhibits microglia inflammatory response through down-regulation of NF-kB activity,and in turn attenuates neuronal cell death and ameliorates PD nerve injury.

Objective To demonstrate that neferine(Nef)alleviates Parkinson's disease(PD)by inhibiting microglial pyroptosis mediated through the reactive oxygen species(ROS)/NOD-like receptor protein 3(NLRP3)/Caspase-1 pathway.Methods BV2 microglial cells were divided into:control group,lipopolysaccharides(LPS)-adenosine triphosphate(ATP)group,and LPS-ATP+Nef group.Pyroptosis was induced by 1 μg/mL LPS+5 mmol/L ATP,with 2 mmol/L Nef pretreatment.Eighteen 10-12-week-old male C57BL/6 mice(22～25 g)were randomly assigned to:control(n=6),1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine(MPTP)(n=6),and MPTP+Nef(n=6)groups.Detection methods included:flow cytometry for pyroptosis,Cell Counting Kit-8(CCK-8)for viability,2',7'-dichlorodihydrofluorescein diacetate(DCFH-DA)for ROS,commercial kits for malondialdehyde(MDA),superoxide dismutase(SOD),glutathione(GSH),ELISA/Western blot for interleukin-1β(IL-1β)/IL-18,immunofluorescence/immunohistochemistry for NLRP3/Caspase-1,tyrosine hydroxylase(TH)immunohistochemistry,hematoxylin-eosin staining for neuropathology,and modified neurological severity score(mNSS).Results Versus control,LPS-ATP group showed decreased viability(P=0.002),increased pyroptosis(P<0.001),elevated ROS(P<0.001)/MDA(P<0.001)/IL-1β(P<0.001)/IL-18(P<0.001),upregulated NLRP3(P<0.001)/Caspase-1(P<0.001),and reduced GSH(P<0.001)/SOD(P<0.001).Nef treatment reversed these effects(all P<0.05).According to the results of murine studies,compared with the control group,the MPTP group had increased mNSS(P<0.001)/tissue ROS(P<0.001),downregulated TH(P<0.001),upregulated NLRP3(P<0.001)/Caspase-1(P<0.001).Nef treatment significantly attenuated the MPTP-induced deleterious effects(P<0.05).Histopathological analysis revealed that control group exhibited uniformly distributed hippocampal neurons with distinct nuclear morphology;MPTP group showed neuronal swelling,interstitial edema,and nuclear atrophy;MPTP+Nef group demonstrated ameliorated neuronal damage.Conclusion Nef inhibits microglial pyroptosis via ROS/NLRP3/Caspase-1 axis,ameliorating PD neuroinflammation and pathology.

Objective To investigate the effectiveness and safety of drug-eluting beads bronchial arterial chemoembolization(DEB-BACE)versus BACE for the treatment of stage Ⅲ-Ⅳ lung squamous cell carcinoma.Methods A total of 104 patients with stage Ⅲ-Ⅳ lung squamous cell carcinoma,who were admitted to the Lishui Municipal Central Hospital of China between January 2013 and August 2021,were enrolled in this study.According to the therapeutic scheme,the patients were divided into DEB-BACE group(n=41)and BACE group(n=63).For patients of DEB-BACE group,Cisplatin at 75 mg/m2 dose and gemcitabine at 1 000 mg/m2 dose(400 mg was used as loaded-drug dose)were injected through a microcatheter,which was followed by embolization with CalliSpheres microspheres loaded with 400 mg of gemcitabine.For patients of BACE group,Cisplatin at 75 mg/m2 and gemcitabatin at 1 000 mg/m2 were injected through a microcatheter,which was followed by arterial embolization with blank microspheres.Three weeks after DEB-BACE or BACE,the patients of both groups were started on intravenous chemotherapy.The primary study endpoint was overall survival(OS).The secondary study endpoints included progression-free survival(PFS),objective response rate(ORR),disease control rate(DCR),adverse reactions,and the remission rate of dyspnea.Results Of the 104 patients,63 received BACE sequential intravenous chemotherapy and 41 received DEB-BACE sequential intravenous chemotherapy.The median OS in DEB-BACE group was 23.0 moths,which was obviously longer than 12.0 months in BACE group(P=0.009).Multivariate Cox regression analysis showed that DEB-BACE treatment was an independent risk factor for OS(HR=0.59,95％ CI:0.38-0.91,Log-rank test P=0.018).Meanwhile,the remission rate of dyspnea in DEB-BACE group was significantly higher than that in BACE group(57.1％ vs 30.6％,P＜0.043).Conclusion Compared with BACE sequential intravenous chemotherapy,DEB-BACE sequential intravenous chemotherapy can significantly prolong the survival time of patients with stage Ⅲ-Ⅳ lung squamous cell carcinoma and significantly improve the symptoms of dyspnea,which has important applications in the treatment of patients with advanced lung squamous cell carcinoma.

ObjectiveTo compare the development status of health facilities in different regions （non-agricultural and agricultural districts）and different types across four dimensions： organizational management， health environment， health activities， and health outcomes， to explore factors that may affect the current development status and summarize effective experiences， and to provide a foundation for the subsequent comprehensive， standardized， and effective promotion of health facility development and tiered and classified management. MethodsInvestigators conducted a health status survey based on the four dimensions for 50 health facilities in 16 districts of Shanghai， representing three types （including government agencies， enterprises， and communities）. Evaluation forms were filled out through on-site observation and document reviews， which were developed in accordance with the Shanghai Health Settings Evaluation Standards （for trial implementation in 2019）. ResultsThe average total score of health facilities in Shanghai was （88.42±11.93） points， with an overall excellence rate of 86.0%. The excellence rate of each dimension， from highest to lowest， were healthy environment （84.0%）， organizational management （82.0%）， health activities （78.0%）， and health outcomes （44.0%）. Health facilities in agricultural districts scored higher in both total score and average score on the organizational management dimension compared to non-agricultural districts. The excellence rate for the organizational management dimension was also higher in agricultural districts than in non-agricultural districts. There was no statistical significance in the total score， the score of each dimension， the overall excellence rate， and the excellence rate of each dimension among different types of health facilities （P>0.05）. ConclusionThe development of health facilities among government agencies， enterprises， and communities in Shanghai has begun to yield positive results. Health facilities in non-agricultural districts should actively draw on the experience of those in agricultural districts， particularly in organizational management， adjust development ideas and planning based on their own realities， so as to continuously improve the levels of development.

In order to explore the genomic characteristics,its virulence,evolution,the correlation be-tween drug resistance phenotype and resistance genes of S.equi XJ 5012,to laid a theoretical basis for efficient prevention and control of strangles,whole genome sequencing was investigated.In this study,the antimicrobial suceptibility of S.equi XJ 5012 was tested by the paper disk method and its whole genome was sequenced,Then the 16S rRNA evolution,SeM genotyping,antibiotic resist-ance gene and virulence gene were compared and analyzed.Drug susceptibility results showed that S.equi XJ5012 was sensitive to 13 antibiotics,such as amoxicillin,ampicillin,cefuroxime,cefotio-fur,cefoxitin,streptomycin,erythromycin,oxytetracycline,levofloxacin,norfloxacin,ciprofloxacin,rifampicin,clindamycin,sulfadiazine sodium,and resistant to 6 antibiotics,such as penicillin,genta-micin,clarithromycin,doxycycline,tetracycline and sulfonamide isoxazole.The whole genome se-quencing results of showed that the genome size of S.equi XJ 5012 was 2.21 Mb,the GC content was 41.31％and this strain has 2 264 code genes.Antibiotic resistance genes database(ARDB)in-dicated that the S.equi XJ 5012 carried 135 drug resistance gene,among which the resistance genes mainly were macrocyclic lipids,fluoroquinolones,aminoglycosides,peptides,tetracyclines and β-lac-tam antibiotics,correlating well with the results of drug susceptibility test.Virulence Factors Data-base(VFDB)indicated that S.equi XJ 5012 carried 197 virulence genes include adhesion,antiph-agocytosis,extracellular enzyme encoding,secrtion,and iron uptake.The phylogenetic tree based on 16S rRNA gene confirmed that the strain XJ 5012 was closely related to S.equi 4047.The results of SeM genotyping revealed that S.equi XJ 5012 was SeM-217,which was closely related to Xin-jiang isolates SeM-209 and SeM-215 and foreign isolates SeM-195 and SeM-196.In this study,the whole genome sequencing analysis of S.equi XJ 5012 based on the third generation sequencing technology is the first report on the genome of S.equi in China,which provides a reference for a more comprehensive and in-depth understanding the characteristics of the genomic,molecular epi-demic and drug resistance of the strain.It is significant for the further prevention and control of strangles and understanding of pathogenic mechanism of S.equi.

Objective:To dynamically study the iodine nutritional status of pregnant women in Guangxi Zhuang Autonomous Region (referred to as Guangxi), providing a basis for timely implementation of targeted prevention and control measures and scientific adjustment of intervention strategies.Methods:From 2015 to 2022, a survey was conducted in Guangxi on a county-by-county basis. One township/street was selected from each county based on the east, west, south, north, and center directions, and 20 pregnant women were selected from each township/street. Salt and urine samples were collected from the homes of pregnant women to detect salt and urine iodine levels.Results:A total of 78 034 pregnant women were surveyed from 2015 to 2022, with a median salt iodine concentration of 24.4 mg/kg. The overall coverage rate of iodized salt, qualification rate of iodized salt, consumption rate of qualified iodized salt, and the rate of non-iodized salt were 99.0% (77 250/78 034), 95.9% (74 105/77 250), 95.0% (74 105/78 034), and 1.0% (784/78 034), respectively. The comparison of qualified iodized salt consumption rates in different regions (cities) showed statistically significant difference (χ 2 = 3 801.28, P < 0.001), with Baise City had the highest (98.1%, 8 328/8 488) and Beihai City had the lowest (70.7%, 1 909/2 700); except for Beihai City, the consumption rate of qualified iodized salt in all other cities was over 90%. The median urinary iodine level among pregnant was 148 μg/L. The difference in urinary iodine levels among pregnant women between different years was statistically significant ( H = 2 516.52, P < 0.001), with the highest level in 2020 (169 μg/L) and the lowest level in 2015 (126 μg/L). From 2020 to 2022, the median urinary iodine level for pregnant women was ≥150 μg/L, while from 2015 to 2019, it was < 150 μg/L. There were statistically significant difference in urinary iodine levels among pregnant women in different regions (cities, H = 495.69, P < 0.001), with Liuzhou City and Guilin City had the highest levels (both at 156 μg/L), and Beihai City had the lowest level (132 μg/L). The median urinary iodine levels of pregnant women in the early, middle, and late stages of pregnancy were 154, 147, and 154 μg/L, respectively. There were statistically significant differences in urine iodine levels among pregnant women in different pregnancy stages ( H = 158.64, P < 0.001), with mid pregnancy being lower than early and late pregnancy ( P < 0.017). Conclusions:The overall iodine nutrition level of pregnant women in Guangxi is slightly insufficient, especially in coastal cities such as Beihai City. We should continue to adhere to the strategy of using iodized salt to prevent and control iodine deficiency disorders. At the same time, we should strengthen health education for pregnant women, and adopt targeted and precise iodine supplementation measures for pregnant women in different regions and during pregnancy.

Objective:To investigate the awareness and behavior of iodine deficiency disorders prevention and control knowledge among pregnant women in Guangxi Zhuang Autonomous Region (referred to as Guangxi), and provide a basis for further targeted health education.Methods:From June to August 2023, a cross-sectional study method was used conduct a questionnaire survey about the awareness and behavior of iodine deficiency disorders prevention and control knowledge on 819 pregnant women who underwent prenatal or inpatient examinations at county people's hospitals, maternal and child health centers, and township health centers in 14 counties of 7 cities in Guangxi.Results:A total of 819 valid questionnaires were collected in this survey. The score of iodine deficiency disorders prevention and control knowledge among pregnant women was (6.1 ± 2.8) points, with an awareness rate of 62.4% (511/819). There were statistically significant differences in the awareness rate of iodine deficiency disorders prevention and control knowledge among pregnant women of different ages, residence areas, fertility status, educational level, employmnet status, occupation, and per capita monthly income(χ 2 = 9.17, 37.51, 5.15, 87.12, 54.22, 50.17, 67.623, P < 0.05). There were statistically significant differences in various behaviors related to salt consumption habits, home salt packaging, awareness of which salt to eat, choices made when buying salt, salt preservation habits, whether or not the subject had eaten iodine-rich foods in the week before the survey, how often they had eaten iodine-rich foods in the year before the survey, and whether or not they had actively learned about iodine knowledge during pregnancy or before pregnancy between pregnant women with different levels of knowledge (χ 2 = 21.64, 12.81, 101.79, 123.20, 36.78, 59.76, 109.14, 98.10, P < 0.05). The main ways to obtain knowledge on prevention and control of iodine deficiency disorders were medical workers(71.3%, 381/534), traditional media(54.5%, 291/534), community advocacy(53.4%, 285/534), news client and new media(50.2%, 268/534). Conclusions:The overall awareness rate of iodine deficiency disorders prevention and control knowledge among pregnant women in Guangxi is not high. We should strengthen health education for pregnant women, especially young and multiparous women, those with low education and low income.

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.

As a representative chemotherapeutic drug, docetaxel (DTX) has been used for breast cancer treatment for decades. However, the poor solubility of DTX limits its efficacy, and the DTX based therapy increases the metastasis risk due to the upregulation of C-X-C chemokine receptor type 4 (CXCR4) expression during the treatment. Herein, we conjugated CXCR4 antagonist peptide (CTCE) with DTX (termed CTCE-DTX) as an anti-metastasis agent to treat breast cancer. CTCE-DTX could self-assemble to nanoparticles, targeting CXCR4-upregulated metastatic tumor cells and enhancing the DTX efficacy. Thus, the CTCE-DTX NPs achieved promising efficacy on inhibiting both bone-specific metastasis and lung metastasis of triple-negative breast cancer. Our work provided a rational strategy on designing peptide-drug conjugates with synergistic anti-tumor efficacy.

Objective:To investigate potential effective components of traditional Chinese medicine and their molecular mechanisms of action in the anti-angiogenic treatment of Kaposi′s sarcoma based on network pharmacology, and to predict key targets and signal pathways in the anti-angiogenic treatment of Kaposi′s sarcoma with traditional Chinese medicine.Methods:According to the previous network pharmacology-based analysis results, main chemical components and targets of Rhizoma Polygoni Cuspidati, Cortex Mori, Rhizoma Smilacis Glabrae and Fructus Perillae were obtained by using the traditional Chinese medicine systems pharmacology database and analysis platform (TCMSP); potential therapeutic targets for angiogenesis and Kaposi′s sarcoma were obtained by searching the GeneCard, OMIM, DrugBank and TTD databases, and a Venn diagram was constructed to obtain targets for the interaction between Kaposi′s sarcoma and anti-angiogenic drug components; a protein-protein interaction model was constructed using the STRING 11.5 platform; the Cytoscape 3.6.0 software was used to construct the component-target visual network. Meanwhile, the Metascape platform was used to analyze the Gene Ontology (GO) functions and the enrichment of Kyoto Encyclopedia of Genes and Genome (KEGG) -based pathways. The main active ingredients and core targets obtained through the above analyses were then verified by molecular docking. Results:The core components of anti-Kaposi′s sarcoma angiogenesis drugs were resveratrol (degree: 142), quercetin (degree: 141), kaempferol (degree: 56), luteolin (degree: 56), β-sitosterol (degree: 37), arachidonic acid (degree: 36), naringenin (degree: 36), etc., and the core target was prostaglandin-endoperoxide synthase 2 (PTGS2). KEGG analysis revealed that the cancer signaling pathways were the important pathways related to the inhibiton of angiogenesis in Kaposi′s sarcoma; functional enrichment analysis showed that the positive regulation of cell migration was the most significantly enriched GO term in the biological process category. Molecular docking results showed that resveratrol, quercetin, kaempferol and luteolin had good affinity with PTGS2, especially quercetin and luteolin exhibited the strongest binding abilities to PTGS2, with the binding energies being -9.4 and -9.5 kcal/mol, respectively.Conclusion:This study showed that the 4 traditional Chinese medicines recorded in TCMSP (including Rhizoma Polygoni Cuspidati., Cortex Mori, Rhizoma Smilacis Glabrae and Fructus Perillae) may play an anti-angiogenic role by regulating cancer signaling pathways and acting on targets such as PTGS2, and predicted the possible anti-angiogenesis mechanisms of traditional Chinese medicines in Kaposi′s sarcoma.