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.

Objective:To analyze the time to reach full enteral feedings (TFEF) among preterm infants with gestational age (GA)<32 weeks admitted to the neonatal intensive care unit (NICU) of Chinese Neonatal Network (CHNN).Methods:This was a retrospective analysis based on the database from the CHNN 89 participating centers between January 1 st, 2019 and December 31 st, 2022. All 16 155 preterm infants with a GA <32 weeks and a birth weight <1 500 g, admitted to the NICU within 24 h after birth, hospitalization for at least 7 d and achieved full enteral feedings before discharge were included. According to the birth weight, these infants were divided into extremely low birth weight (ELBW) group and very low birth weight (VLBW) group. The practice characteristics of TFEF across different GA, the severity of neonatal admission, the NICU interventions before reaching full enteral feeding, and relevant neonatal diseases were described. Mann-Whitney U tests or Kruskal-Wallis H tests was used for comparison between groups. Results:Among the 16 155 preterm infants with a GA <32 weeks, 8 505 case (52.6%) were male. The TFEF in 3 374 cases of ELBW groups was 32 (22, 46) d, 351 cases (10.4%) with TFEF ≤2 weeks, 1 050 cases (31.1%) with TFEF >2-4 weeks, 964 cases (28.6%) with TFEF >4-6 weeks, and 1 009 cases (29.9%) with TFEF >6 weeks. The TFEF in 12 781 cases of VLBW group was 22 (15, 32) d, 439 cases (3.4%) with TFEF ≤1 week, 2 565 cases (20.1%) with TFEF >1-2 weeks, 5 526 cases (43.2%) with TFEF >2-4 weeks, and 4 251 cases (33.3%) with TFEF >4 weeks. The TFEF was 36(23, 52) d of 625 preterm infants at a GA ≤25 weeks and 20 (13, 28) d of 2 606 preterm infants at a GA 31 weeks. Inborn infants had a shorter TFEF than those outborn infants and the infants with breast-fed achieved shorter than formula and mixed feeding both in ELBW and VLBW groups (all P<0.001). The earlier enteral feeding started, the shorter TFEF will be both in ELBW and VLBW groups (both P<0.001). The TFEF of preterm infants who were treated before full enteral feeding like peripherally inserted central catheters, and blood transfusions and blood product providers were all longer than those who were not treated (all P<0.001). The TFEF of preterm infants with complications like hemodynamically significant patent ductus arteriosus, necrotizing enterocolitis, late onset sepsis, severe retinopathy of prematurity and bronchopulmonary dysplasia were all longer than those without (all P<0.001). Conclusions:The distribution of TFEF in VLBW and ELBW has a large difference. The TFEF of preterm infants varies with different GA, treatment measures and complications. Further quality improvement is required to shorten TFEF.

Objective:To investigate the expression levels of serum receptor activator of nuclear factor-κB (RANK), RANK ligand (RANKL), and osteoprotegerin (OPG) in children with dental fluorosis.Methods:In April 2018, a case-control study was conducted to select 8 - 12 year old children diagnosed with dental fluorosis residing within 1.5 km of an aluminum smelting facility in Guangxi Zhuang Autonomous Region as the dental fluorosis group ( n = 49) according to the criteria of "Diagnosis of Dental Fluorosis" (WS/T 208-2011). The control group ( n = 98) comprised healthy children aged 8 - 12 years old without dental fluorosis lived more than 5.0 km from the aluminum smelting facility. Fasting venous blood samples were collected from all participants. Blood fluoride level were measured using an ion-selective electrode method. Serum RANK, RANKL, and OPG levels were determined using double-antibody sandwich enzyme-linked immunosorbent assay. Results:The levels of serum fluoride [ M ( Q1, Q3): 0.033 (0.032, 0.036) vs 0.026 (0.025, 0.028) mg/L], RANK [1.21 (0.87, 1.64) vs 0.73 (0.50, 1.13) μg/L], RANKL [81.3 (50.6, 118.6) vs 134.3 (98.1, 199.2) ng/L], OPG [433.3 (321.6, 574.3) vs 509.1 (406.8, 709.3) μg/L], and OPG/RANKL ratio [5.6 (3.1, 7.8) vs 3.6 (2.9, 5.0)] were compared between the fluorosis group and the control group, and the differences were statistically significant ( Z = 8.35, 3.83, 3.99, 2.35, 2.47, P < 0.05). Correlation analysis revealed that dental fluorosis severity was positively correlated with serum fluoride level( r s = 0.68, P < 0.001). Serum fluoride level was negatively correlated with both serum RANKL and OPG levels ( r s = - 0.49, - 0.17, P < 0.05). Conclusion:The level of serum RANK in children with dental fluorosis is higher than that in healthy children, while the levels of RANKL and OPG are lower than those in healthy children.

Objective:To explore the effect of acceptance and commitment therapy matrix(ACT Matrix)for somatic symptoms associated with pre-exam anxiety in a high school student.Methods:An 8-session intervention was conducted,conceptualized by the ACT Matrix.The comprehensive assessment of Acceptance and Commitment Therapy processes(CompACT)and the evaluation of inverted U-shaped pressure curve were used for pre-and post-assessment.Results:The client's CompACT score increased from 56 to 71,and his stress level score decreased from 9 to 6.The client's somatic symptoms were significantly alleviated,the sleep improved,the relationship with his par-ents enhanced.Furthermore,The client exceeded expectation in the final semester exam.Conclusion:ACT Matrix effectively alleviated pre-exam anxiety-related somatic symptoms in a high school student,which is a useful tool to guide and facilitate the counseling.

Objective:To investigate the expression levels of serum receptor activator of nuclear factor-κB (RANK), RANK ligand (RANKL), and osteoprotegerin (OPG) in children with dental fluorosis.Methods:In April 2018, a case-control study was conducted to select 8 - 12 year old children diagnosed with dental fluorosis residing within 1.5 km of an aluminum smelting facility in Guangxi Zhuang Autonomous Region as the dental fluorosis group ( n = 49) according to the criteria of "Diagnosis of Dental Fluorosis" (WS/T 208-2011). The control group ( n = 98) comprised healthy children aged 8 - 12 years old without dental fluorosis lived more than 5.0 km from the aluminum smelting facility. Fasting venous blood samples were collected from all participants. Blood fluoride level were measured using an ion-selective electrode method. Serum RANK, RANKL, and OPG levels were determined using double-antibody sandwich enzyme-linked immunosorbent assay. Results:The levels of serum fluoride [ M ( Q1, Q3): 0.033 (0.032, 0.036) vs 0.026 (0.025, 0.028) mg/L], RANK [1.21 (0.87, 1.64) vs 0.73 (0.50, 1.13) μg/L], RANKL [81.3 (50.6, 118.6) vs 134.3 (98.1, 199.2) ng/L], OPG [433.3 (321.6, 574.3) vs 509.1 (406.8, 709.3) μg/L], and OPG/RANKL ratio [5.6 (3.1, 7.8) vs 3.6 (2.9, 5.0)] were compared between the fluorosis group and the control group, and the differences were statistically significant ( Z = 8.35, 3.83, 3.99, 2.35, 2.47, P < 0.05). Correlation analysis revealed that dental fluorosis severity was positively correlated with serum fluoride level( r s = 0.68, P < 0.001). Serum fluoride level was negatively correlated with both serum RANKL and OPG levels ( r s = - 0.49, - 0.17, P < 0.05). Conclusion:The level of serum RANK in children with dental fluorosis is higher than that in healthy children, while the levels of RANKL and OPG are lower than those in healthy children.

Objective:To explore the effect of acceptance and commitment therapy matrix(ACT Matrix)for somatic symptoms associated with pre-exam anxiety in a high school student.Methods:An 8-session intervention was conducted,conceptualized by the ACT Matrix.The comprehensive assessment of Acceptance and Commitment Therapy processes(CompACT)and the evaluation of inverted U-shaped pressure curve were used for pre-and post-assessment.Results:The client's CompACT score increased from 56 to 71,and his stress level score decreased from 9 to 6.The client's somatic symptoms were significantly alleviated,the sleep improved,the relationship with his par-ents enhanced.Furthermore,The client exceeded expectation in the final semester exam.Conclusion:ACT Matrix effectively alleviated pre-exam anxiety-related somatic symptoms in a high school student,which is a useful tool to guide and facilitate the counseling.

Objective:To analyze the time to reach full enteral feedings (TFEF) among preterm infants with gestational age (GA)<32 weeks admitted to the neonatal intensive care unit (NICU) of Chinese Neonatal Network (CHNN).Methods:This was a retrospective analysis based on the database from the CHNN 89 participating centers between January 1 st, 2019 and December 31 st, 2022. All 16 155 preterm infants with a GA <32 weeks and a birth weight <1 500 g, admitted to the NICU within 24 h after birth, hospitalization for at least 7 d and achieved full enteral feedings before discharge were included. According to the birth weight, these infants were divided into extremely low birth weight (ELBW) group and very low birth weight (VLBW) group. The practice characteristics of TFEF across different GA, the severity of neonatal admission, the NICU interventions before reaching full enteral feeding, and relevant neonatal diseases were described. Mann-Whitney U tests or Kruskal-Wallis H tests was used for comparison between groups. Results:Among the 16 155 preterm infants with a GA <32 weeks, 8 505 case (52.6%) were male. The TFEF in 3 374 cases of ELBW groups was 32 (22, 46) d, 351 cases (10.4%) with TFEF ≤2 weeks, 1 050 cases (31.1%) with TFEF >2-4 weeks, 964 cases (28.6%) with TFEF >4-6 weeks, and 1 009 cases (29.9%) with TFEF >6 weeks. The TFEF in 12 781 cases of VLBW group was 22 (15, 32) d, 439 cases (3.4%) with TFEF ≤1 week, 2 565 cases (20.1%) with TFEF >1-2 weeks, 5 526 cases (43.2%) with TFEF >2-4 weeks, and 4 251 cases (33.3%) with TFEF >4 weeks. The TFEF was 36(23, 52) d of 625 preterm infants at a GA ≤25 weeks and 20 (13, 28) d of 2 606 preterm infants at a GA 31 weeks. Inborn infants had a shorter TFEF than those outborn infants and the infants with breast-fed achieved shorter than formula and mixed feeding both in ELBW and VLBW groups (all P<0.001). The earlier enteral feeding started, the shorter TFEF will be both in ELBW and VLBW groups (both P<0.001). The TFEF of preterm infants who were treated before full enteral feeding like peripherally inserted central catheters, and blood transfusions and blood product providers were all longer than those who were not treated (all P<0.001). The TFEF of preterm infants with complications like hemodynamically significant patent ductus arteriosus, necrotizing enterocolitis, late onset sepsis, severe retinopathy of prematurity and bronchopulmonary dysplasia were all longer than those without (all P<0.001). Conclusions:The distribution of TFEF in VLBW and ELBW has a large difference. The TFEF of preterm infants varies with different GA, treatment measures and complications. Further quality improvement is required to shorten TFEF.

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.