Intracranial seminoma is a rare malignant tumor originating from the germ cells,usually occurring in the pineal gland or pituitary gland.In June 2020,the Department of Endocrinology at the First Affiliated Hospital of Army Military Medical University admitted a 20-year-old male patient with an intracranial germ cell tumor and spinal metastases.The patient presented with headache,dizziness,and visual impairment.Enhanced magnetic resonance imaging(MRI)of the head indicated thickening of the pituitary stalk.After multidisciplinary consultation,the patient underwent endonasal transsphenoidal resection of the tumor,with the pathological diagnosis confirming germ cell tumor.The patient received regular radiotherapy postoperatively.One year later,the tumor recurred and metastasized,leading to a second surgery for tumor resection in the thoracic spinal canal,followed by continued chemotherapy.The patient's clinical symptoms,such as headache and visual disturbances,improved,but he continued to experience panhypopituitarism and required long-term hormone replacement therapy.Early diagnosis of intracranial germ cell tumors is challenging,and they are prone to metastasis and highly sensitive to radiotherapy and chemotherapy.Early diagnosis and multidisciplinary comprehensive treatment can help improve the quality of life and prognosis for patients.

Purpose To evaluate the added value of time of flight(TOF)and point spread dispersion(PSF)reconstruction in mediastinal lymph node metastasis of lung cancer in 18F-FDG PET/CT imaging.Materials and Methods Sixty-eight lung cancer patients with mediastinal lymph node metastasis who underwent PET/CT examination in the First People's Hospital of Foshan from March 9,2020 to July 23,2021 were analyzed retrospectively.The different methods,including ordered subsets estimation maximization(OSEM),OSEM+TOF,OSEM+PSF,OSEM+TOF+PSF,were used to reconstruct the images.The resolution of different reconstruction algorithms for mediastinal lymph node metastasis of lung cancer,as well as the differences of signal-to-noise ratio(SNR)and standard uptake value(SUV)were compared,respectively.Results The highest values of SUVmean,SUVmax and SNR were obtained via OSEM+TOF+PSF method,which increased by 21.99%,22.86%and 60.14%,compared with conventional OSEM method(t=28.321,19.11,11.059,all P<0.01).The difference percentage in smaller lesions that diameter≤22 mm was significantly higher than that in larger lesions that diameter>22 mm(24.1%vs.21.1%,25.3%vs.19.3%,70.6%vs.63.3%;Z=-3.658,-4.313,-2.154,all P<0.05),and the difference percentage in low contrast lesions that SNR≤15.31 was significantly higher than that in high contrast lesions that SNR>15.31(23.6%vs.21.4%,25.3%vs.21.1%,85.7%vs.46.0%;Z=-3.519,-2.336,-5.106,all P<0.05).Among the evaluation results of lesion detectability of different reconstruction algorithms,OSEM+TOF+PSF image showed the mediastinal lymph node metastasis most clearly(87.4%of the lesions were clearly existing),which was significantly higher than that of OSEM image(73.1%of lesions were clearly existing)(χ2=11.704,P=0.001),however,the proportion of lesions clearly existing in OSEM+PSF image did not significantly increase compared with OSEM image(73.1%vs.75.8%;χ2=0.361,P=0.548).Conclusion The combination of TOF and PSF can significantly improve the detection ability,SNR and SUV of mediastinal lymph node metastasis of lung cancer,especially in small and low contrast lesions.

Objective To analyze the medication law and academic thoughts of Professor Wang Junhong in the treatment of tic disorders(TD)in children.Methods The cases of children with TD diagnosed and treated by Professor Wang Junhong from January 2015 to November 2022 were selected.Excel 2016 was used to analyze the clinical information of children with TD.The frequency ranking,property,taste and meridian tropism,and changes of prescription drugs were analyzed in multiple dimensions.SPSS Modeler 18.0 was used to analyze the drug association rules of prescriptions in 2021 and 2022.Cytoscape 3.9.0 was used to analyze the complex network of drug-drug strong,medium and weak links obtained by SPSS Modeler 18.0.The drug groups were obtained in SPSS,and Excel 2016 was used to analyze the annual changes of high-frequency drugs.Results Totally 5586 prescriptions were included,involving 198 kinds of Chinese materia medica,with a total frequency of 108356 times.The top five kinds of high-frequency Chinese materia medica were Chrysanthemi Flos,Acori Tatarinowii Rhizoma,Coptidis Rhizoma,Crataegi Fructus,Polygalae Radix.The medicinal properties were mostly cold,warm and mild.The medicinal tastes were mainly bitter,sweet and pungent.The main meridians of drugs were liver,heart and lung meridians.The association rule analysis showed that the common couplet medicines were Chrysanthemi Flos-Acori Tatarinowii Rhizoma and Acori Tatarinowii Rhizoma-Scorpio.Commonly used triple combination was Chrysanthemi Flos-Scorpio-Acori Tatarinowii Rhizoma.Clustering analysis showed 4 drug groups,reflecting the characteristics of Professor Wang Junhong's treatment of calming liver and tranquilizing mind.According to the time-flow analysis,since 2020,the proportion of drugs such as Bupleuri Radix,Scutellariae Radix,Haliotidos Concha,Gastrodiae Rhizoma and Margaritifera Concha have gradually increased,indicating that more attention should be paid to treating the liver,resolving phlegm and calming the mind.Conclusion In the treatment of TD in children,Professor Wang Junhong takes heart,liver and lung as the center.The prescription medication is to relieve wind and phlegm,soothe the liver and tranquilize the mind.In recent years,it has attached importance to the role of regulating emotions and resolving phlegm in the treatment of children with TD.

ObjectiveTo investigate the regulatory effect of Mankuining Formula （MKNF） on the gut microbiota and the NOD-like receptor （NLR）P3/Caspase-1/gasdermin D （GSDMD） pyroptosis pathway-mediated inflammation in dextran sulfate sodium （DSS）-induced ulcerative colitis （UC） mice. MethodSixty SPF C57BL/6 mice were randomly divided into a blank group， a model group， a MKNF group （20 g·kg^-1）， and a mesalazine group （0.266 g·kg^-1）， with 15 mice in each group. The UC model was induced in mice by freely drinking a 3% DSS solution for 7 days. After 12 hours of modeling， the treatment groups received daily oral administration， while the other groups received an equal volume of normal saline by gavage. Daily body weight and disease activity index （DAI） were recorded. On the 8th day， mice were euthanized after anesthesia， and the colon and feces were collected. The colon length was measured， and histopathological changes were observed after hematoxylin-eosin （HE） staining. Tumor necrosis factor-α （TNF-α）， interleukin-1β （IL-1β）， and interleukin-18 （IL-18） levels in the colon were detected by enzyme-linked immunosorbent assay （ELISA）. The differences in gut microbiota among the groups were analyzed using 16S rRNA sequencing technology. The protein content of NLRP3/Caspase-1/GSDMD in colon tissues was detected by Western blot. ResultCompared with the blank group， mice in the model group showed increased DAI （P<0.01）， shortened colon length （P<0.01）， severe colon mucosal damage， elevated levels of TNF-α， IL-1β， and IL-18 （P<0.01）， increased protein content of NLRP3/Caspase-1/GSDMD in colon tissues （P<0.01）， altered gut microbiota structure with decreased abundance of Actinobacteria， Bacteroidetes， and Proteobacteria， and increased abundance of Firmicutes at the phylum level. At the genus level， there was a decrease in Lactobacillus， Alloprevotella， and Yersinia， and an increase in Bacteroides， Bacillus， and Lachnospiraceae_NK4A136. Compared with the model group， the MKNF group and the mesalazine group showed a significant reduction in DAI after the 3^rd day （P<0.01）， a significant increase in colon length （P<0.01）， alleviated colon inflammation and mucosal structural damage， and decreased TNF-α， IL-1β， and IL-18 levels in the colon （P<0.01）， reduced protein content of NLRP3/caspase-1/GSDMD in colon tissue （P<0.05， P<0.01），an increase in the abundance of Proteobacteria and Bacteroidetes， and a decrease in Firmicutes at the phylum level. ConclusionMKNF can alleviate UC-induced colonic inflammation， reduce colon damage， and improve dysbiosis of the gut microbiota by inhibiting the classical pyroptosis pathway.

Background Fluorine accumulates in the brain tissue after long-term excessive intake and subsequently cause nerve damage and decline of learning and memory ability. Receptor of advanced glycation end-products (RAGE)/p38 mitogen-activated protein kinase (p38MAPK)/nuclear factor kappa-B (NF-κB) signaling pathway is considered to be involved in the associated mechanism. Objective To study the changes of RAGE/ p38MAPK/ NF-κB signaling pathway in rats with subchronic fluorosis, and to explore the protective effects of extract of Ginkgo biloba 761 (EGb761) and RAGE antagonist (FPS-ZM1) on neuromemory ability. Methods Ninety male clean SD rats were divided into 9 groups with 10 rats in each group. The modeling period was 6 months. Control group (C group): free drinking tap water (fluoride content <0.5 mg·L⁻¹), low- and high-dose fluoride groups (LF group, HF group): free drinking tap water with 10 or 50 mg·L⁻¹ fluoride; intervention group of Ginkgo biloba extract (CE, LFE, and HFE groups): on the basis of the C group, LF group, and HF group, 100 mg·kg⁻¹·d⁻¹ EGb761 was given daily via intragastric administration; FPS-ZM1 intervention groups (CF, LFF, and HFF groups): 7 d before the end of modeling, 1 mg·kg⁻¹·d⁻¹ FPS-ZM1 was injected intraperitoneally daily on the basis of the C group, LF group, and HF group. The contents of fluoride in brain and blood of each group were detected. The learning and memory ability was tested by water maze experiment. The histopathologic changes of the hippocampus were detected by Nissl staining. The protein expression levels of RAGE and its ligand high mobility group protein B1 (HMGB1), NF-κB, p38MAPK, phospho-p38MAPK (p-p38MAPK), interleukin-6 (IL-6), and tumour necrosis factor-α (TNF-α) in brain tissue were detected by Western blotting. The mRNA expression levels of RAGE, HMGB1, and p38MAPK were detected by quantitative real-time PCR. Results Compared with the C group, the contents of blood fluoride and brain fluoride in the LF and the HF groups were increased (P<0.05). The results of the water maze experiment showed that, compared with the C group, the escape latency time of the LF group and the HF group was longer and the crossing times were reduced; compared with the HF group, the escape latency time of the HFE group and the HFF group was shortened, and the crossing times were increased (P<0.05). The Nissl staining results showed that the number of Nissl body in the HF group decreased compared with the C group; compared with the HF group, the number of Nissl body in the HFE group and the HFF group increased. The Western blotting results showed that compared with the relative protein expression levels of RAGE, HMGB1, NF-κB, p38MAPK, p-p38MAPK, IL-6, and TNF-α in the C group , the levels of above indicators in the HF group and the levels of RAGE, HMGB1, NF-κB, p-p38MAPK, and IL-6 in the LF group were up-regulated (P<0.05); compared with the HF group, the levels of above indicators in the HFE group and the HFF group were all down-regulated (P<0.05); compared with the relative protein expression levels of RAGE and HMGB1 in the LF group, the levels in the LFE group and the LFF group were all down-regulated (P<0.05). The quantitative real-time PCR results showed that compared with the C group, the mRNA expression levels of RAGE and HMGB1 in the LF group and the HF group were up-regulated; compared with the LF group, the mRNA expression levels of RAGE in the LFE group and the LFF group were down-regulated ; compared with the HF group, the mRNA expression levels of RAGE and HMGB1 in the HFE group and the HFF group were down-regulated (P<0.05). Conclusion The central nervous system injury caused by subchronic fluorosis may be related to the activation of RAGE/p38-MAPK/NF-κB signaling pathway, which can impair the learning and memory ability of rats, while EGb761 and FPS-ZM1 may have certain protective effects on the nerve injury.

OBJECTIVE To study the chemical composition and analgesia molecular mechanism of Shuanghu Zhongtongning tincture by UPLC-Q-TOF-MS/MS and network pharmacology. METHODS By comparing the chromatogram and blank chromatogram of Shuanghu Zhongtongning tincture, combined with PubChem, HMDB, MassBank database spectrum and the lysis information of reference substance, the chemical composition of Shuanghu Zhongtongning tincture was analyzed and identified. Protein-protein interaction network was constructed by using STRING database, and potential targets of analgesic effect of Shuanghu Zhongtongning tincture were screened. And GO and KEGG enrichment analysis were performed to analyze the core pathways related to analgesia. The network of "chemical composition-disease-target" was constructed by Cytoscape software to analyze the key compounds related to analgesia. RESULTS Seventeen core components of neochlorogenic acid, chlorogenic acid, hesperidin, neohesperidin, ferulic acid, berberine, ursolic acid, deoxyaconitine, mesaconitine, hypaconitine, benzoylmesaconine, benzoylhypacoitine, caffeic acid, quercetin, oleanolic acid, 4-hydroxycinnamic acid and mefenamic acid were identified, 3 core targets of STAT3, MAPK3 and MAPK1 were found, and 4 key signaling pathways of IL-17, TNF, PI3K-Akt and arachidonic metabolism were revealed. CONCLUSION This study preliminarily clarifies the chemical composition of Shuanghu Zhongtongning tincture and potential mechanism of analgesic effect, and provides a scientific theoretical basis for the study on the material basis and mechanism of Shuanghu Zhongtongning tincture.

Toll-like receptor 3 (TLR3), as an important pattern recognition receptor (PRR), dominates the innate and adaptive immunity regulating many acute and chronic inflammatory diseases. Atherosclerosis is proved as an inflammatory disease, and inflammatory events involved in the entire process of initiation and deterioration. However, the contribution of TLR3 to atherosclerosis remains unclear. Herein, we identified the clinical relevance of TLR3 upregulation and disease processes in human atherosclerosis. Besides, activation of TLR3 also directly led to significant expression of atherogenic chemokines and adhesion molecules. Conversely, silencing TLR3 inhibited the uptake of oxLDL by macrophages and significantly reduced foam cell formation. Given the aberrance in TLR3 functions on atherosclerosis progression, we hypothesized that TLR3 could serve as novel target for clinical atherosclerosis therapy. Therefore, we developed the novel ellipticine derivative SMU-CX24, which specifically inhibited TLR3 (IC₅₀ = 18.87 ± 2.21 nmol/L). In vivo, atherosclerotic burden was alleviated in Western diet fed ApoE^-/- mice in response to SMU-CX24 treatment, accompanying notable reductions in TLR3 expression and inflammation infiltration within atherosclerotic lesion. Thus, for the first time, we revealed that pharmacological downregulation of TLR3 with specific inhibitor regenerated inflammatory environment to counteract atherosclerosis progression, thereby proposing a new strategy and probe for atherosclerosis therapy.

Objective:To establish a candidate reference method for the determination of angiotensin Ⅱ in human plasma by isotope dilution liquid chromatography tandem mass spectrometry (ID-LC-MS/MS) and to evaluate its performance.Methods:Using [ 13C 6- 15N]-angiotensin Ⅱ as the internal standard, the plasma was accurately weighed by gravimetric method and mixed with a certain amount of internal standard. At the same time, enzyme inhibitor was added. After zinc sulfate solution protein precipitation and reversed-phase solid-phase extraction plate treatment, it was analyzed by liquid chromatography tandem mass spectrometry. The multi reaction ion monitoring mode(MRM)was selected by mass spectrometry to detect specific ion fragments of angiotensin Ⅱ and internal standard. The linearity, sensitivity, precision, recovery rate and uncertainty of the performance of the established method were evaluated according to ISO15193. Results:Angiotensin Ⅱ had good linearity in the range of 10-1 000 pg/g ( r=0.999 5), the lower limit of quantification was 7.68 pg/g, the analytical recoveries were 97.14% to 102.85%, intra-batch imprecision≤3.21%, inter-batch imprecision≤2.96%, and total imprecision≤3.67%. Conclusion:A method for the determination of plasma angiotensin Ⅱ was established by ID-LC-MS/MS. The method is accurate and reliable, and is expected to be a reference method for the determination of plasma angiotensin Ⅱ.

Objective:To explore the effect and mechanism of different concentrations of metformin on bleomycin (BLM)-induced systemic sclerosis (SSc) mice model.Methods:C57BL/6 mice were divided into the normal group, the model group, the high, the medium and the low metformin (MET) treatment groups randomly. All mice were sacrificed after BLM and metformin treatment for 4 weeks. Local skin was exminedby histopathological staining method to measure the thickness of dermis and collagen, and immunohistochemistry and real-time fluorescence quantitative polymerase chain reaction (RT-qPCR) were used to detect the protein and mRNA levels of Interleukin (IL)-17, forkhead box P3 (Foxp3) and α-smooth muscle actin (α-SMA). Flow cytometry was used to detect the percentage of effector T cell (Teff) and regulatory cells (Treg) in splenic mononuclear cells. The data such as dermal collagen thickness, α-SMA, IL-17, Foxp3, Teff and Treg levels were statistically analyzed by one-way analysis of variance. The data such as dermal collagen thickness, α-SMA, IL-17, Foxp3, Teff and Treg levels were analyzed by one-way analysis of variance, and least significant difference (LSD)- t or Kruskal-Wallis test was used for comparison between groups. Results:Compared with the normal group, remarkable fibrotic lesions appeared in the skin of mice in the model group, and the levels of T-helper cells (Th)1, Th2, Th17, and T follicular helper cells (Tfh) cells were increased, accompanied by a significant decrease in the level of Treg cells. After high-dose metformin treatment, the dermal thickness [(131±25) μm], collagen thickness [(119±18) μm], and α-SMA [(3.0±0.5)/HPH] were significantly reduced( F=14.390, P<0.01; F=40.245, P<0.01; F=44.626, P<0.01). Th1[(27.00±6.68)%], Th17[(0.56±0.20)%], Tfh[(6.4±1.6)%] cells ware significantlyreduced ( F=32.390, P<0.01; F=16.083, P<0.01; F=16.546, P<0.01), and Treg[(11.23±1.52)%] cells were significantly increased ( F=10.171, P<0.01). Conclusion:Metformin can effectively reverse the local skin changesin BLM-induced SSc mouse model, and show immune regulation and anti-fibrosis effects by restoring the Teff/Treg balance.

Objective:To explore the influence of time of flight (TOF) and point spread function (PSF) on PET/CT image quality and standardized uptake value (SUV) based on a phantom study.Methods:PET/CT imaging were performed using Jaszczak phantom and International Electrotechnical Commission (IEC) body phantom respectively, and conventional clinical imaging protocol (3 min/bed) was used for three consecutive imaging. The ordered subsets expectation maximization (OSEM), OSEM+ TOF, OSEM+ PSF and OSEM+ TOF+ PSF were used to reconstruct the raw data respectively. The differences of image resolution, image uniformity, contrast, signal to noise ratio (SNR) and SUV among different reconstruction algorithms were compared by using one-way analysis of variance and the least significant difference (LSD) t test. The correlations between SNR, mean SUV (SUV mean), maximum SUV (SUV max) and the sphere diameter were analyzed by Pearson correlation analysis. Results:The minimum image resolution for the hot column was 6.4 mm by OSEM and OSEM+ PSF reconstruction, while it was 4.8 mm by OSEM+ TOF and OSEM+ TOF+ PSF reconstruction. The contrast was significantly better by OSEM+ TOF ((78.56±1.21)%) and OSEM+ TOF+ PSF ((78.85±1.17)%) reconstruction than that by OSEM reconstruction ((73.44±1.47)%; F=61.068, t values: 9.503, 10.018, both P<0.001). The maximum and minimum nonuniformity percentages were significantly better for images reconstructed with OSEM+ PSF than those reconstructed with OSEM ( F values: 10.286, 27.630, t values: -2.599, 7.698, both P<0.05). In IEC phantom imaging, the SNR and SUV max of hot sphere were higher by OSEM+ PSF and OSEM+ TOF+ PSF reconstruction than those by OSEM reconstruction (SNR: (98.99±34.76)%, (98.29±28.66)%, (73.64±26.05)%; F=5.712, t values: 3.209, 3.412, both P<0.05; SUV max: 8.96±2.72, 9.28±2.17, 8.01±2.21; F=3.931, t values: 2.154, 2.863, both P<0.05), but there was no significant difference between OSEM+ TOF and OSEM reconstruction ( t values: 0.297, 0.272, both P>0.05). Among the four reconstruction methods, the SNR and SUV mean increased with the increase of the sphere diameter ( r values: 0.913-0.963, all P<0.05), but SUV max in images reconstructed with OSEM+ PSF and OSEM+ TOF+ PSF had no significant correlations with the sphere diameter ( r values: 0.496, 0.614, both P>0.05). Conclusions:Under specific acquisition and reconstruction conditions, TOF mainly improves image resolution and contrast, while PSF mainly improves image uniformity and SNR. The combination of the two method can obtain better image quality and significantly improve the SUV of hot lesions.