Cold tumors have a poor response to tumor immunotherapy due to low immune cell infiltration and the ability to evade immune attacks. Converting cold tumors into hot tumors can enhance the clinical effectiveness of anti-tumor immunotherapy. High-intensity focused ultrasound (HIFU) as a non-invasive treatment can damage tumors through mechanical effects, but there is a lack of research on its cytotoxic mechanisms at the cellular level and its role in inducing anti-immune responses. In this study, the role of HIFU in triggering tumor ferroptosis by disrupting the GSH/GSSG balance through mechanochemical action and the associated anti-tumor immune priming effect were investigated. The use of a nano-enhancer loaded with PFOB combined with HIFU could enhance ferroptosis in triple-negative breast cancer at a specific stage of tumor growth (UTGR = 0) while promoting the conversion of a cold tumor into a hot tumor, thereby improving the immune response. Overall, this provides valuable guidance for the clinical application of HIFU in tumor immunotherapy.

Objective:To explore the mechanism of Eucommiae Cortex- Epimedii Folium herbal pair in the treatment of osteoporosis through network pharmacology, molecular docking, and molecular dynamics methods. Methods:Search the traditional Chinese medicine systems pharmacology database and analysis platform (TCMSP) and relevant literature to screen the active compounds of Eucommiae Cortex- Epimedii Folium herbal pair. Using TargetNet, SwissTargetPrediction, and STITCH databases to predict the target of active compounds. GeneCards, OMIM, TTD and DisGeNET databases were used to screen the related targets of osteoporosis, and the intersection targets were obtained by Venny 2.1.0 online tool. Using STRING database for protein-protein interaction (PPI) network analysis. Construct a network diagram using Cytoscape 3.8.2 software and perform network feature analysis to determine key targets and core compounds. Using R 3.6.3 software for gene ontology (GO) functional annotation and Kyoto Encyclopedia of genes and genomes (KEGG) signaling pathway analysis. Apply SYBYL-X 2.1.1 software to perform molecular docking between core compounds and key targets, and use GROMACS 2021.6 software for molecular dynamics simulation. Results:Totally 47 active compounds, 329 targets related to compounds, 4 604 targets related to osteoporosis, and 210 intersecting targets of Eucommiae Cortex- Epimedii Folium herbal pair were selected. Network feature analysis showed that luteolin, quercetin, kaempferol, caffeic acid, chryseriol, and pinoresinol were core compounds, while protein kinase B1(Akt1), interleukin-6 (IL-6), steroid receptor coactivator (Src), cysteinyl aspartate specific proteinase-3 (CASP3), epidermal growth factor receptor (EGFR), estrogen receptor 1 (ESR1), prostaglandin-endoperoxide synthase 2 (PTGS2), mitogen-activated protein kinase 8 (MAPK8), and JUN were key targets. GO analysis showed that biological process (BP) mainly involve cellular hormone metabolism, intracellular receptor signaling pathways, oxidative stress responses, hormone metabolism processes, etc. Cell component (CC) mainly involved membrane rafts, membrane microregions, membrane regions, transcription factor complexes, etc. Molecular function (MF) mainly involved nuclear receptor activity, transcription factor activity, steroid hormone receptors, hormone binding, etc. KEGG analysis showed that the signaling pathways of Eucommiae Cortex- Epimedii Folium herbal pair in the treatment of osteoporosis mainly included osteoclast differentiation, PI3K-Akt signaling pathway, and MAPK signaling pathway. Molecular docking showed that the core compounds could accurately bind to the active sites of key target proteins, and molecular dynamics analysis further verified the binding stability between the core compounds and key target proteins. Conclusions:The combination of Eucommiae Cortex- Epimedii Folium herbal pair has the characteristics of multiple components, targets, and pathways in the treatment of osteoporosis, laying a theoretical foundation for its clinical use.

Objective:To analyze the correlation between serum leptin (LEP), adiponectin (ADP) levels and bone metabolism indexes in pregnant GDM women complicated with osteoporosis.Methods:A total of 120 GDM patients admitted to our hospital from Dec. 2020 to Dec. 2023 were included as the observation group, and 30 healthy pregnant women were chosen as the control group. The levels of serum LEP, ADP, bone metabolism indexes [parathyroid hormone (PTH), alkaline phosphatase (ALP), 25-hydroxyvitamin D, amino terminal and middle osteocalcin (N-MID) ] were compared. The relationship between serum LEP, ADP and PTH, ALP, 25-hydroxyvitamin D and N-MID was analyzed by Pearson correlation, and receiver operating characteristic curve (ROC) was drawn to evaluate the diagnostic value of serum LEP and ADP levels in gestational diabetes mellitus complicated with osteoporosis.Results:The observation group had higher LEP level, but lower ADP, PTH, 25-hydroxyvitamin D and N-MID level ( t=10.08, 7.19, 12.70, 15.05, 20.54, P<0.05), and there was no significant difference in ALP between the two groups ( t=0.78, P>0.05) ; 25 had osteoporosis and 95 did not. LEP levels in the osteoporosis subgroup were significantly higher than those in the non-osteoporosis subgroup, and ADP, PTH, 25-hydroxyvitamin D and N-MID levels were significantly lower ( t=4.44, 3.06, 3.51, 3.18, 3.00, P<0.05). There was no significant difference in ALP level between the two groups ( t=0.38, P>0.05). Pearson correlation analysis showed that serum LEP and ADP were significantly correlated with PTH, 25-hydroxyvitamin D and N-MID in pregnant GDM women ( P<0.05). The area under the curve (AUC) of serum LEP, ADP and combined test in pregnant GDM women complicated with osteoporosis were 0.723, 0.650 and 0.755, respectively. Conclusion:Serum LEP level increases and ADP level decreases significantly in pregnant GDM women complicated with osteoporosis, which is closely related to bone metabolism indexes, and can assist in early diagnosis of gestational diabetes mellitus complicated with osteoporosis.

To explore screening tools for children with autism spectrum disorder (ASD), which are convenient for primary hospitals, it can provide basic data for formulating ASD prevention policies. This was a cross-sectional study by cluster sampling. Huyi District and Xincheng District were extracted for investigation in Xi′an City. From July 2021 to September 2022, all children aged from 3 months to 36 months who live in the two districts were subjected to primary screening. The child care physician used the routine screening tool "warning signs checklist for screening psychological, behavioral and developmental problems of children" and cartoon pictures of "early high-risk warning signs of autism", the children who were positive in the initial screening were referred to the district level maternal and child health hospital for re-screening, and those who were positive in the re-screening were referred to Xi ′an Children′s Hospital for diagnosis. The results showed that a total of 17 905 children aged from 3 months to 36 months were initially screened in the two districts, including 10 588 children aged from 18 months to 36 months, 50 children who were positive in the initial screening and 50 children who were re-screened. 23 children (18 boys and 5 girls) were diagnosed with ASD. The prevalence rate of ASD in children was 2.17‰ (95% confidence interval:1.29‰-3.06‰). 42 children were positive for "warning signs checklist" at the preliminary screening, and 19 were confirmed as ASD. 27 children were positive for "cartoon pictures" in the preliminary screening, and 23 were confirmed with ASD. The "cartoon pictures" in the preliminary screening and diagnosis of consistent rate was higher than the "warning signs checklist", two kinds of screening methods comparison were statistically significant difference in the odds of consistent (χ 2=11.01, P=0.001). In conclusion, relying on the three-level network of maternal and child health care, it is conducive to the whole process management of screening and diagnosis of children with ASD, and to guide the formulation of prevention policies. The cartoon pictures of "early high-risk warning signs of autism" can assist the identification of children with ASD based on the "warning signs checklist", which is simple, effective and suitable for promotion in the community health care.

Objective To identify and verify the interacting protein of α-11 giardin, so as provide the experimental evidence for studies on the α-11 giardin function. Methods The yeast two-hybrid cDNA library of the Giardia lambia C2 strain and the bait plasmid of α-11 giardin were constructed. All proteins interacting with α-11 giardin were screened using the yeast two-hybrid system. α-11 giardin and all screened potential interacting protein genes were constructed into pBiFc-Vc-155 and pBiFc-Vn-173 plasmids, and co-transfected into the breast cancer cell line MDA-MB-231. The interactions between α-11 giardin and interacting proteins were verified using bimolecular fluorescence complementation (BiFC). Results The yeast two-hybrid G. lambia cDNA library which was quantified at 2.715 × 10⁷ colony-forming units (CFU) and the bait plasmid containing α-11 giardin gene without an autoactivation activity were constructed. Following two-round positive screening with the yeast two-hybrid system, two potential proteins interacting with α-11 giardin were screened, including eukaryotic translation initiation factor 5A (EIF5A), calmodulin-dependent protein kinase (CAMKL) and nicotinamide adenine dinucleotide phosphate-specific glutamate dehydrogenase (NADP-GDH), hypothetical protein 1 (GL50803_95880), hypothetical protein 2 (GL50803_87261) and a protein from Giardia canis virus. The α-11 giardin and EIF5A genes were transfected into the pBiFc-Vc-155 and pBiFc-Vn-173 plasmids using BiFC, and the recombinant plasmids pBiFc-Vc-155-α-11 and pBiFc-Vn-173-EIF5A were co-tranfected into MDA-MB-231 cells, which displayed green fluorescence under a microscope, indicating the interaction between α-11 giardin and EIF5A protein in cells. Conclusion The yeast two-hybrid cDNA library of the G. lambia C2 strain has been successfully constructed, and six potential protein interacting with α-11 giardin have been identified, including EIF5A that interacts with α-11 giardin in cells.

Objective:To investigate the safety and efficacy of stent-assisted coil embolization in acute intracranial ruptured wide-necked aneurysms, and explore the safety of different antiplatelet drug regimens during perioperative period and the risk factors for prognoses.Methods:A perspective multicenter study was performed. A total of 417 patients with intracranial ruptured wide-necked aneurysms treated by stent-assisted coil embolization in Neurosurgery Departments of 4 hospitals (First Affiliated Hospital of Wenzhou Medical University [ n=41], Zhujiang Hospital of Southern Medical University [ n=111], Tangdu Hospital of Air Force Military Medical University [ n=100], and Xuanwu Hospital of Capital Medical University [ n=165]) from June 2017 to January 2020 were included. According to the different antiplatelet drugs regimens used in perioperative period, these patients were divided into loaded clopidogrel group ( n=87), loaded clopidogrel combined with aspirin group ( n=212), and tirofiban group ( n=118). Clinical data and perioperative complications of 3 groups were compared. Modified Rankin scale (mRS) was used to evaluate the prognoses of patients at discharge; differences of clinical data between the poor prognosis group and good prognosis group were compared. Independent risk factors for prognoses of patients with intracranial ruptured wide-necked aneurysms were analyzed by multivariate Logistic regression analysis. Receiver operating characteristic (ROC) curve was used to analyze the predictive values of risk factors in poor prognosis. Results:Degrees of aneurysm embolization immediately after surgery: Raymond grading I was noted in 351 patients (84.2%), grading II in 44 patients (10.6%), and grading III in 22 patients (5.2%). Perioperative complications were noted in 44 patients (10.6%), and death was noted in 4 (1%). Intraoperative thrombosis incidence of the loaded clopidogrel group, loaded clopidogrel combined with aspirin group and tirofiban group was 5.7% (5/87), 5.7% (12/212) and 0.8% (1/118); that in tirofiban group was significantly lower than that in the loaded clopidogrel group and loaded clopidogrel combined with aspirin group ( P<0.05). At discharge, 360 patients (86.3%) had good prognosis and 57 patients (13.7%) had poor prognosis. Multivariate Logistic regression analysis showed age≥60 years ( OR=3.407, 95% CI: 1.620-7.166, P=0.001), preoperative Hunt-Hess grading 3 ( OR=11.445, 95% CI: 3.584-36.547, P<0.001), preoperative Hunt-Hess grading 4 ( OR=88.951, 95% CI: 14.519-544.948, P<0.001), preoperative Hunt-Hess grading 5 ( OR=64.949, 95% CI: 12.809-329.325, P<0.001), and multiple stenting ( OR=4.709, 95% CI: 1.215-18.248, P=0.025) were independent risk factors for poor prognosis of these patients. ROC curves showed that area under the curve of combination of age, number of implanted stents, and preoperative Hunt-Hess grading in predicting poor prognosis of these patients was 0.821, with optimal diagnostic threshold of 0.500, sensitivity of 0.667, and specificity of 0.833. Conclusion:Stent-assisted coil embolization is safe and effective in acute intracranial ruptured wide-necked aneurysms; tirofiban is safe as perioperative antiplatelet drug; patients with old age, preoperative Hunt-Hess grading≥3, and multiple stents are prone to have poor prognosis.

Objective:To get comprehensive understanding of the registration characteristics of global clinical trials of coronavirus disease 2019(COVID-19) based on the ClinicalTrials. gov and the Chinese Clinical Trial Registry (ChiCTR).Methods:The clinical trials of COVID-19 in the ClinicalTrials.gov and ChiCTR were retrieved. The search start time was unlimited, with deadlines of 14 December, 2020 and 19 March, 2021, respectively. The registration numbers, registration submitted time, country/region distribution, recruitment status, study types, number of recruits, research phases, and other aspects were analyzed by using bibliometric methods.Results:As of March 19, 2021, there were 775 clinical trials in ChiCTR. As of December 14, 2020, there were 4 137 clinical trials in the ClinicalTrials.gov, and 3 157(76.31%) of the clinical trials recruited subjects who were aged≥18 years old. There were 2 347 intervention trials and 1 759 observational trials. The intervention measures mainly included drugs, biologics and medical devices. The numbers of recruits were 110(48, 308) cases for interventional studies, and 300(100, 1 000) cases for observational trials. The interventional research phases were mainly phaseⅡ (570 items) and phase Ⅲ (358 items). Totally, 50.33%(2 082/4 137) of the clinical trials were under recruitment, 13.10%(542/4 137) had been completed. Among the interventional studies, 729(31.06%) were multi-center studies, with the center numbers of 5(2, 15).Conclusions:At present, there are a large number of clinical trials with various intervention measures in the world. However, the number of recruits is unreasonable, and multi-center study with multi-agency cooperation is insufficient.

Objective To evaluate the clinical value of holographic image navigation in urological laparoscopic and robotic surgery.Methods The data of patients were reviewed retrospectively for whom accepted holographic image navigation laparoscopic and robotic surgery from Jan.2019 to Dec.2019 in Beijing United Family Hospital and other 18 medical centers,including 78 cases of renal tumor,2 cases of bladder cancer,2 cases of adrenal gland tumor,1 cases of renal cyst,1 case of prostate cancer,1 case of sweat gland carcinoma with lymph node metastasis,1 case of pelvic metastasis after radical cystectomy.All the patients underwent operations.In the laparoscopic surgery group,there were 27 cases of partial nephrectomy,1 case of radical prostatectomy,2 cases of radical cystectomy and 2 cases of adrenalectomy.In the da Vinci robotic surgery group of 54 cases,there were 51 cases of partial nephrectomy,1 case of retroperitoneal lymph node dissection,1 case of retroperitoneal bilateral renal cyst deroofing and 1 case of resection of pelvic metastasis.There were 41 partial nephrectomy patients with available clinical data for statistic,with a median age of 53.5 years (range 24-76),including 26 males and 15 females.The median R.E.N.A.L score was 7.8 (range 4-11).Before the operation,the engineers established the holographic image based on the contrast CT images and reports.The surgeon applied the holographic image for preoperative planning.During the operation,the navigation was achieved by real time fusing holographic images with the laparoscopic surgery images in the screen.Results All the procedures had been complete uneventfully.The holographic images helped surgeon in understanding the visual three-dimension structure and relation of vessels supplying tumor or resection tissue,lymph nodes and nerves.By manipulating the holographic images extracorporeally,the fused image guide surgeons about location vessel,lymph node and other important structure and then facilitate the delicate dissection.For the 41 cases with available clinical data including 23 cases of robotic-assisted partial nephrectomy and 18 cases of laparoscopic nephrectomy,the median operation time was 140 (range 50-225) min,the median warm ischemia time was 23 (range 14-60) min,the median blood loss was 80(range 5-1 200) ml.In the robotic surgery group,the median operation time was 140 (range 50-215)min,the median warm i schemia time was 21 (range 17-40)min,the median blood loss was 150(range 30-1 200)ml.In the laparoscopic surgery group,the median operation time was 160(range 80-225)min,the median warm ischemia time was 25 (range 14-60)min,the median blood loss was 50 (range 5-1 200) ml.All the patients had no adjacent organ injury during operation.There were 2 cases with Clavien Ⅱ complications.One required transfusion and the other one suffered hematoma post-operation.However,the tumors were located in the renal hilus for these 2 cases and the R.E.N.A.L scores were both 11.Conclusions Holographic image navigation can help location and recognize important anatomic structures during the surgical procedures..This technique will reduce the tissue injury,decrease the complications and improve the success rate of surgery.

Objective To analyze the antimicrobial resistance, distribution of resistance genes and staphylococcal cassette chromosome mec ( SCCmec) in 99 strains of mecA gene-positive Staphylococcus epi-dermidis strains isolated from early pregnancy cervical swabs and external environment in Beijing Chaoyang District from 2015 to 2016. Methods Kirby-Bauer disk diffusion method was performed to detect the sus-ceptibility of the 99 Staphylococcus epidermidis strains to cefoxitin. Microbroth dilution method was used to test their susceptibility to vancomycin, daptomycin, penicillin, erythromycin, compound sulfamethoxazole, tetracycline, ciprofloxacin, clindamycin, gentamicin and chloramphenicol. PCR was used to detect drug re-sistance genes of ermA, ermB, ermC, msrA, norA1, norA2, sul1, sul2, sul3, aac(6')/aph(2″), ant(4', 4″), ant(6) and tetM and to analyze the SCCmec types ofⅠ, Ⅱ, Ⅲ, Ⅳa, Ⅳb, Ⅳc, Ⅳd and Ⅴ. The results were compared with those of capillary electrophoresis. SPSS was used for data analysis. Results All of the 99 mecA-positive Staphylococcus epidermidis strains were sensitive to vancomycin and 93. 94％ of them were sensitive to datomycin. The resistance rates to penicillin, erythromycin, cefoxitin, compound sulfame-thoxazole, tetracycline, ciprofloxacin, clindamycin, gentamicin and chloramphenicol were 97. 98％, 85. 86％, 79. 80％, 52. 54％, 27. 27％, 43. 43％, 36. 36％, 23. 23％ and 11. 11％. The strains that car-ried the genes of norA1, norA2, ermA, ermB, ermC, msrA, sul1, sul2, sul3, aac(6')/aph(2″), ant(4', 4″), ant(6) and tetM accounted for 100％, 93. 94％, 0. 00％, 3. 03％, 17. 17％, 57. 58％, 50. 51％, 12. 12％, 4. 04％, 30. 30％, 8. 08％, 4. 04％ and 25. 26％, respectively. Among the 99 strains, 5. 05％, 0％, 43. 43％, 10. 10％, 0. 00％, 3. 03％, 3. 03％ and 19. 19％ belonged to SCCmecⅠ, Ⅱ, Ⅲ, Ⅳa,Ⅳb,Ⅳc,Ⅳd andⅤ, respectively, and 4. 04％ (4/99) were positive to two SCCmec types. The types of 12. 12％ (12/99) of the strains were unidentified. Conclusions All of the 99 strains of mecA-positive Staphylococcus epidermidis were sensitive to vancomycin. Among them, the strains carrying multidrug resist-ance genes accounted for 89. 90％. The main mechanisms of resistance to macrolides, sulfonamides and ami-noglycosides in local strains were related to the resistance genes of msrA, sul1 and aac ( 6')/aph ( 2″) . SCCmec Ⅲ was the prevalent type. There were 88. 37％ of SCCmec Ⅲ type strains and 75％ of unknown type strains carrying multiple resistance genes. Apart from that, the isolated strains of other SCCmecⅢtypes all carried multiple resistance genes.

Objective: To investigate the clinical significance of plasma amino-terminal pro-brain natriuretic peptide(NT-proBNP) in children with bacterial meningitis. Methods: From April 2013 to March 2017, 32 children with bacterial meningitis in PICU of the Second People′s Hospital of Liaocheng Affiliated to Taishan Medical College were selected.The patients were evaluated the severity of the disease by Glasgow coma scale(GCS). Thirty-five cases who admitted to the hospital in the same period were selected as the control group, excluding congenital heart disease, chronic cardiac dysfunction, cardiomyopathy, myocarditis, heart failure, chronic renal insufficiency.The blood samples were collected from the hospital in 24h, and the levels of the plasma NT-proBNP, procalcitonin(PCT), C-reactive protein(CRP) and Na ions were determined. Results: Compared with the control group, the levels of the plasma NT-proBNP was significantly increased[(7 123.97±6 901.60)ng/L vs.(39.29±19.41)ng/L, t=5.839, P<0.01], the level of PCT was significantly increased[(25.14±2.35)ng/dL vs.(0.63±0.15ng/dL, t=10.820, P<0.01], the level of CRP was significantly increased[(97.89±4.63mg/dL vs.(5.23±1.22mg/dL, t=21.130, P<0.01], and the GCS was significantly decreased(t=18.132, P<0.01) in children with bacterial meningitis group.The plasma NT-proBNP level of children with GCS<8points[(13 328.08±7 938.85)ng/L]was significantly higher than that in children with GCS 8~14points[(3 401.50±1 526.75)ng/L](t=5.816, P<0.01) and GCS≥15points[(39.74±18.64)ng/L](t=5.816, P<0.01). There was a significant positive correlation between the level of plasma NT-proBNP and PCT(r=0.969, P<0.01), also a significant positive correlation between the level of plasma NT-proBNP and CRP(r=0.961, P<0.01), while a significant negative correlation between the level of plasma NT-proBNP and sodium ions(r=0.886, P<0.01) in children with bacterial meningitis by Pearson correlation test. Conclusion Detection of the plasma NT-proBNP has significant clinical significance for early diagnosis and assessment of the severity of the illness of children with bacterial meningitis.