This study investigated the potential pathogenicity and genetic characteristics of ST314 Salmonella Kentucky(S.Ken-tucky)isolates from a broiler slaughterhouse.Antimicrobial susceptibility testing and whole-genome sequencing(WGS)were used to determine antimicrobial resistance,virulence factors,and the presence of antimicrobial resistance genes(ARGs)and mobile genetic elements(MGEs)among the isolates.The three multidrug resistant(MDR)isolates exhibited high resistance to multiple antimicrobial agents.The F4-2S strain exhibited resistance to 14 drugs across seven categories,whereas the F4T strain showed resistance to 13 drugs in the same number of categories.In contrast,the Y23 strain was resistant to nine drugs in six categories.Notably,F4-2S dem-onstrated high homology with F4T:both possessed 13 ARGs distributed across nine categories,in addition to a wide range of virulence factors,including secretion systems and effector proteins.The presence of IncR and IncX1 plasmids significantly enhanced both the antimicrobial resistance and pathogenicity of the isolates.The genome map of Y23 revealed a chromosome alongside two plasmids.The chromosome containedonly one resistance gene but several virulence factors,including the type III secretion system(T3SS),which is crucial for bacterial invasion.The plasmid pY23-1 contained eight types of 19 ARGs.Comparative analysis indicated that pY23-1 ex-hibited high homology with pZ1323SSL0055 and pSAL-045,all of which contained multiple ARGs,thus suggesting critical roles of these genes in the evolution of bacterial resistance.In conclusion,ST314 S.Kentucky demonstrated a complex mechanism of resis-tance coupled with significant pathogenic potential.The ARGs and MGEs in the plasmid contributed to the emergence and dissemina-tion of antimicrobial resistance.The multiple virulence factors present in the chromosome may be key factors driving the increasing virulence of ST314 S.Kentucky.

To investigate the anti-atherosclerotic effects of dietary hesperidin and naringin on ather-osclerosis in rabbits.Twenty-four adult healthy male New Zealand Large White rabbits were ran-domly assigned to four groups based on one factor:control(Con),model(Mod),hesperidin(HP),and naringenin(NG),each containing six rabbits and housed in solitary cages.During the experi-mental period,the control group received normal feed;the model group was fed high-fat for 30 d to establish the atherosclerosis,(AS)model and continued to be fed high-fat feed;the hesperidin and naringenin groups were fed high-fat for 30 d and then underwent AS modeling,and at a later stage,150 mg of hesperidin(or naringenin)was added to the diets at a rate of 1.5 mg per kg of di-et,respectively,for 30 d.Relative body quality,blood lipids,oxidation,and inflammatory factor lev-els were all assessed.At the end of the test period,the test rabbits were sacrificed to obtain the common carotid artery for histopathological section HE staining,Oil red O staining,and Sirius red staining in order to observe vascular tissue structure,lipid and inflammatory cell infiltration,and e-lastic plate and elastic fiber damage.The results indicated that the relative body quality of the mod-el,HP and NG groups increased rapidly,and the difference with the control group within the same period was highly significant(P＜0.01);The HP and NG interventions significantly decreased to-tal cholesterol(TC)and low-density lipoprotein cholesterol(LDL-C)levels(P＜0.01),while also leading to a significant increase in high-density lipoprotein cholesterol(HDL-C)levels(P＜0.01);MDA levels exhibited a significant decrease(P＜0.01),while SOD levels showed a notable in-crease(P＜0.01)following the HP and NG interventions;After HP and NG interventions,TNF-α and IL-1 were regressed(P＜0.01)and IL-10 was significantly elevated(P＜0.01);Compared with the control group,the model group showed approximately 41.8 and 2.5 fold thickening of the maximal endo-medial membrane,respectively,and the HP and NG interventions showed approxi-mately 13 and 15 fold thickening of the maximal endo-medial membrane,and both of the maximal medial membranes thickened by approximately 1.4 fold;Staining of pathological sections showed that HP and NG intervened to significantly reduce inflammatory cell infiltration,deposition of lipid components,slight thickening of the endothelium,and intact fibroblastic components.The results showed that the addition of HP and NG to diets could regulate blood lipids and exert anti-inflam-matory and antioxidant effects by inhibiting the expression of inflammatory factors and oxidizing factors,showing significant anti-AS effects,and the two effects were comparable.

The pathological mechanisms and related physiological indicators of acute mountain sickness(AMS)were introduced,and the present situation of wearable devices applied in AMS auxiliary detection and diagnosis were reviewed.The challenges and future development directions of wearable devices applied in auxiliary detection and diagnosis were pointed out.[Chinese Medical Equipment Journal,2025,46(9):100-107]

Objective To observe the therapeutic effect and mechanism of electroacupuncture at Yanglingquan(GB34)and Quchi(LI11)points for post-stroke spasticity(PSS)in rats.Methods The rats were randomly divided into sham-operated group,model group,electroacupuncture group and electroacupuncture+CA1[Janus kinase 2(JAK2)agonist]group.The PSS model was prepared by the modified middle cerebral artery occlusion combined with internal capsule injection of N-methyl-D-aspartate(NMDA)receptor method in all groups of rats except the sham-operated group.After the intervention,the neurological deficit scale scoring,Ashworth Spasticity Scale(Ashworth)scoring and electrophysiological determination were carried out;the levels of interleukin 6(IL-6),tumor necrosis factor α(TNF-α)and γ-aminobutyric acid(GABA)in the brain tissues were detected by enzyme-linked immunosorbent assay(ELISA);the content of glutamate(Glu)was observed by colorimetry;the pathological changes in brain tissues were observed by hematoxylin-eosin(HE)staining method;the protein expression levels of JAK2,phosphorylated JAK2(p-JAK2),signal transducer and activator of transcription 3(STAT3),and phosphorylated STAT3(p-STAT3)in brain tissues were detected by Western Blot method.Results The neurological deficit scale scores,Ashworth scores,contents of IL-6,TNF-α and Glu as well as p-JAK2/JAK2 and p-STAT3/STAT3 ratios in brain tissues in the model group were all significantly higher than those in the sham-operated group(P<0.05),and the muscular tension signal value and GABA content in brain tissues in the model group were significantly lower than those in the sham-operated group(P<0.05);compared with the model group,the neurological deficit scale scores,Ashworth scores,contents of IL-6,TNF-α and Glu as well as p-JAK2/JAK2 and p-STAT3/STAT3 ratios in brain tissues were significantly lower in the electroacupuncture group(P<0.05),and the muscular tension signal value and GABA content in brain tissues were significantly higher in the electroacupuncture group(P<0.05);compared with the electroacupuncture group,the neurological deficit scale scores,Ashworth scores,contents of IL-6,TNF-α and Glu as well as p-JAK2/JAK2 and p-STAT3/STAT3 ratios in brain tissues in the electroacupuncture+CA1 group were significantly higher(P<0.05),and the muscular tension signal value and GABA content in brain tissues in the electroacupuncture+CA1 group were significantly lower(P<0.05).Conclusion Electroacupuncture may inhibit inflammatory responses and regulate the neuronal excitation/inhibition balance by inhibiting the JAK2/STAT3 pathway,thus relieving PSS in rats.

Objective:To assess the preliminary efficacy and safety of modified Société Internationale d′Oncologie Pédiatrique Epithelial Liver Tumor Study Group (SIOPEL)-4 protocol for pediatric hepatoblastoma (HB) with lung metastases.Methods:This prospective cohort study enrolled 27 newly diagnosed pediatric HB with lung metastases who received the modified SIOPEL-4 protocol at Shanghai Children′s Medical Center, Shanghai Jiao Tong University School of Medicine, and Shanghai Children′s Hospital between January 2020 to December 2023. Clinical characteristics, lung response rates to induction chemotherapy, treatment outcomes, prognostic factors and sever chemotherapy toxicities at different stages were analyzed. Survival analysis was performed by Kaplan-Meier method. Univariate prognostic analysis was conducted by Log-Rank test.Results:Of the 27 patients, there were 17 males and 10 females, with the age of 21 (15, 33) months. During the follow-up of 31 (12, 45) months for 17 continuous complete remission patients, 4 cases disease progression (2 cases death) and 6 cases relapse were observed. The 2-year event free survival (EFS) and overall survival (OS) rate was (58±11)% and (89±7)%, respectively. All the 27 patients had response to block 1-3 induction chemotherapy (cisplatin+doxorubicin), with 14 cases (52%) achieving complete response and 13 cases (48%) achieving partial response of lung metastatic lesions, the 2-year EFS rate was (81±12)% and (34±14)%, respectively ( χ 2=6.76, P=0.009), the 2-year OS rate was 100% and (79±13)%, respectively ( χ2=2.12, P=0.145). Patients with caudate lobe tumors or ≥10 pulmonary metastatic nodules had significantly lower EFS rates ( χ2=5.36, 7.84, P=0.021, 0.005, respectively). The incidence of grade 3/4 neutropenia after block 1-3 induction chemotherapy, CD (carboplatin+doxorubicin), and VI (vincristine+irinotecan) consolidation chemotherapy was 90% (73/81), 75% (58/77), and 31% (11/35), respectively. The incidence of grade 3/4 thrombocytopenia was 77% (62/81), 69% (53/77), and 14% (5/35), respectively. The incidence of grade 3/4 infections was 64% (52/81), 25% (19/77), and 20% (7/35), respectively. The differences between the groups were statistically significant ( χ2=43.51, 42.69, 33.00, all P<0.001). Two patients (10%) of the 20 evaluable patients for ototoxicity occurred grade 3 and higher hearing impairment, with 1 patient requiring a hearing aid. Conclusions:The modified SIOPEL-4 regimen shows good preliminary efficacy and safety in treating pediatric HB with lung metastases. The prognosis for patients with residual lesions in the lungs after induction chemotherapy needs to be improved. Attention should be given to the ototoxicity induced by high-dose cisplatin chemotherapy.

The clinical phenotype heterogeneity of epilepsy patients with ADGRV1 gene mutation is significant, ranging from self limiting febrile seizures to developmental epileptic encephalopathy, even causing sudden epileptic death. A case of infantile epileptic spasms syndrome with a novel heterozygous variant of the ADGRV1 gene c.4100C>A (p.Thr1367Lys) was reported in this article. The site of this variant had not been reported yet, and the clinical manifestations of the child mainly included epileptic spasms (first onset at 4 months old), mild growth and development delay, highly irregular video electroencephalogram, and effective treatment with adrenocorticotropic hormone.

To investigate the anti-atherosclerotic effects of dietary hesperidin and naringin on ather-osclerosis in rabbits.Twenty-four adult healthy male New Zealand Large White rabbits were ran-domly assigned to four groups based on one factor:control(Con),model(Mod),hesperidin(HP),and naringenin(NG),each containing six rabbits and housed in solitary cages.During the experi-mental period,the control group received normal feed;the model group was fed high-fat for 30 d to establish the atherosclerosis,(AS)model and continued to be fed high-fat feed;the hesperidin and naringenin groups were fed high-fat for 30 d and then underwent AS modeling,and at a later stage,150 mg of hesperidin(or naringenin)was added to the diets at a rate of 1.5 mg per kg of di-et,respectively,for 30 d.Relative body quality,blood lipids,oxidation,and inflammatory factor lev-els were all assessed.At the end of the test period,the test rabbits were sacrificed to obtain the common carotid artery for histopathological section HE staining,Oil red O staining,and Sirius red staining in order to observe vascular tissue structure,lipid and inflammatory cell infiltration,and e-lastic plate and elastic fiber damage.The results indicated that the relative body quality of the mod-el,HP and NG groups increased rapidly,and the difference with the control group within the same period was highly significant(P＜0.01);The HP and NG interventions significantly decreased to-tal cholesterol(TC)and low-density lipoprotein cholesterol(LDL-C)levels(P＜0.01),while also leading to a significant increase in high-density lipoprotein cholesterol(HDL-C)levels(P＜0.01);MDA levels exhibited a significant decrease(P＜0.01),while SOD levels showed a notable in-crease(P＜0.01)following the HP and NG interventions;After HP and NG interventions,TNF-α and IL-1 were regressed(P＜0.01)and IL-10 was significantly elevated(P＜0.01);Compared with the control group,the model group showed approximately 41.8 and 2.5 fold thickening of the maximal endo-medial membrane,respectively,and the HP and NG interventions showed approxi-mately 13 and 15 fold thickening of the maximal endo-medial membrane,and both of the maximal medial membranes thickened by approximately 1.4 fold;Staining of pathological sections showed that HP and NG intervened to significantly reduce inflammatory cell infiltration,deposition of lipid components,slight thickening of the endothelium,and intact fibroblastic components.The results showed that the addition of HP and NG to diets could regulate blood lipids and exert anti-inflam-matory and antioxidant effects by inhibiting the expression of inflammatory factors and oxidizing factors,showing significant anti-AS effects,and the two effects were comparable.

This study aims to explore the effects of Buzhong Yiqi Decoction(BYD) on the cyclic guanosine monophosphate-adenosine monophosphate synthase(cGAS)-stimulator of interferon genes(STING) signaling pathway in the mouse model of autoimmune thyroiditis(AIT) and the mechanism of BYD in alleviating the immune injury. Forty-eight NOD.H-2~(h4) mice were assigned into normal, model, low-, medium-, and high-dose BYD, and selenium yeast tablets groups(n=8). Mice of 8 weeks old were treated with 0.05% sodium iodide solution for 8 weeks for the modeling of AIT and then administrated with corresponding drugs by gavage for 8 weeks before sampling. High performance liquid chromatography was employed to measure the astragaloside Ⅳ content in BYD. Hematoxylin-eosin staining was employed to observe the pathological changes in the mouse thyroid tissue. Enzyme-linked immunosorbent assay was employed to measure the serum levels of thyroid peroxidase antibody(TPO-Ab), thyroglobulin antibody(TgAb), and interferon-γ(IFN-γ). Flow cytometry was employed to detect the distribution of T cell subsets in the spleen. The immunohistochemical method was used to detect the expression of cGAS, STING, TANK-binding kinase 1(TBK1), and interferon regulatory factor 3(IRF3). Real-time PCR and Western blot were employed to determine the mRNA and protein levels, respectively, of markers related to the cGAS-STING signaling pathway in the thyroid tissue. The results showed that the content of astragaloside Ⅳ in BYD was(7.06±0.08) mg·mL~(-1). Compared with the normal group, the model group showed disrupted structures of thyroid follicular epithelial cells, massive infiltration of lymphocytes, and elevated levels of TgAb and TPO-Ab. Compared with the model group, the four treatment groups showed intact epithelial cells, reduced lymphocyte infiltration, and lowered levels of TgAb and TPO-Ab. Compared with the normal group, the model group showed increases in the proportions of Th1 and Th17 cells, a decrease in the proportion of Th2 cells, and an increase in the IFN-γ level. Compared with the model group, the four treatment groups presented decreased proportions of Th1 and Th17 cells and lowered levels of IFN-γ, and the medium-dose BYD group showed an increase in the proportion of Th2 cells. Compared with the normal group, the modeling up-regulated the mRNA levels of cGAS, STING, TBK1, and IRF3 and the protein levels of cGAS, p-STING, p-TBK1, and p-IRF3. Compared with the model group, the four treatment groups showed reduced levels of cGAS, STING, TBK1, and IRF3-positive products, down-regulated mRNA levels of cGAS, STING, and TBK1, and down-regulated protein levels of cGAS and p-STING. The high-dose BYD group showed down-regulations in the mRNA level of IRF3 and the protein levels of p-TBK1 and p-IRF3. The above results indicate that BYD can repair the imbalance of T cell subsets, alleviate immune injury, and reduce thyroid lymphocyte infiltration in AIT mice by inhibiting the cGAS-STING signaling pathway.
Animals ; Drugs, Chinese Herbal/administration & dosage* ; Signal Transduction/drug effects* ; Thyroiditis, Autoimmune/metabolism* ; Mice ; Membrane Proteins/metabolism* ; Mice, Inbred NOD ; Humans ; Female ; Nucleotidyltransferases/metabolism* ; Male ; Disease Models, Animal

Jiuwei Xifeng Granules have become a Chinese patent medicine in the market. Because the formula contains Os Draconis, a top-level protected fossil of ancient organisms, the formula was to be improved by replacing Os Draconis with Ostreae Concha. To evaluate whether the improved formula has the same effectiveness and safety as the original formula, a randomized, double-blind, parallel-controlled, equivalence clinical trial was conducted. This study enrolled 288 tic disorder(TD) of children and assigned them into two groups in 1∶1. The treatment group and control group took the modified formula and original formula, respectively. The treatment lasted for 6 weeks, and follow-up visits were conducted at weeks 2, 4, and 6. The primary efficacy endpoint was the difference in Yale global tic severity scale(YGTSS)-total tic severity(TTS) score from baseline after 6 weeks of treatment. The results showed that after 6 weeks of treatment, the declines in YGTSS-TSS score showed no statistically significant difference between the two groups. The difference in YGTSS-TSS score(treatment group-control group) and the 95%CI of the full analysis set(FAS) were-0.17[-1.42, 1.08] and those of per-protocol set(PPS) were 0.29[-0.97, 1.56], which were within the equivalence boundary [-3, 3]. The equivalence test was therefore concluded. The two groups showed no significant differences in the secondary efficacy endpoints of effective rate for TD, total score and factor scores of YGTSS, clinical global impressions-severity(CGI-S) score, traditional Chinese medicine(TCM) response rate, or symptom disappearance rate, and thus a complete evidence chain with the primary outcome was formed. A total of 6 adverse reactions were reported, including 4(2.82%) cases in the treatment group and 2(1.41%) cases in the control group, which showed no statistically significant difference between the two groups. No serious suspected unexpected adverse reactions were reported, and no laboratory test results indicated serious clinically significant abnormalities. The results support the replacement of Os Draconis by Ostreae Concha in the original formula, and the efficacy and safety of the modified formula are consistent with those of the original formula.
Adolescent ; Child ; Child, Preschool ; Female ; Humans ; Male ; Double-Blind Method ; Drugs, Chinese Herbal/therapeutic use* ; Tic Disorders/drug therapy* ; Treatment Outcome

This study explored the potential therapeutic targets and mechanisms of Danggui Shaoyao San(DSS) in the prevention and treatment of Alzheimer's disease(AD) through transcriptomics and metabolomics, combined with animal experiments. Fifty male C57BL/6J mice, aged seven weeks, were randomly divided into the following five groups: control, model, positive drug, low-dose DSS, and high-dose DSS groups. After the intervention, the Morris water maze was used to assess learning and memory abilities of mice, and Nissl staining and hematoxylin-eosin(HE) staining were performed to observe pathological changes in the hippocampal tissue. Transcriptomics and metabolomics were employed to sequence brain tissue and identify differential metabolites, analyzing key genes and metabolites related to disease progression. Reverse transcription-quantitative polymerase chain reaction(RT-qPCR) was employed to validate the expression of key genes. The Morris water maze results indicated that DSS significantly improved learning and cognitive function in scopolamine(SCOP)-induced model mice, with the high-dose DSS group showing the best results. Pathological staining showed that DSS effectively reduced hippocampal neuronal damage, increased Nissl body numbers, and reduced nuclear pyknosis and neuronal loss. Transcriptomics identified seven key genes, including neurexin 1(Nrxn1) and sodium voltage-gated channel α subunit 1(Scn1a), and metabolomics revealed 113 differential metabolites, all of which were closely associated with synaptic function, oxidative stress, and metabolic regulation. RT-qPCR experiments confirmed that the expression of these seven key genes was consistent with the transcriptomics results. This study suggests that DSS significantly improves learning and memory in SCOP model mice and alleviates hippocampal neuronal pathological damage. The mechanisms likely involve the modulation of synaptic function, reduction of oxidative stress, and metabolic balance, with these seven key genes serving as important targets for DSS in the treatment of AD.
Animals ; Alzheimer Disease/genetics* ; Male ; Drugs, Chinese Herbal/administration & dosage* ; Mice ; Mice, Inbred C57BL ; Metabolomics ; Transcriptome/drug effects* ; Maze Learning/drug effects* ; Hippocampus/metabolism* ; Humans ; Disease Models, Animal ; Memory/drug effects*