Objective: To fabricate a hydrogel loaded with inositol hexaphosphate-zinc and preliminarily evaluate its performance in self-mineralization and osteoinduction, thereby providing a theoretical basis for the development of bone regeneration materials. Methods: The hydrogel framework (designated DF0) was formed by copolymerizing methacryloyloxyethyltrimethylammonium chloride and four-armed poly(ethylene glycol) acrylate, followed by sequentially loading inositol hexaphosphate anions via electrostatic interaction and zinc ions via chelation. The hydrogel loaded only with inositol hexaphosphate anions was named DF1, while the co-loaded hydrogel was named DF2. The self-mineralization efficacy of the DF0 , DF1 and DF2 hydrogels was characterized using scanning electron microscopy, transmission electron microscopy (TEM), energy dispersive spectroscopy (EDS), and selected area electron diffraction (SAED). The biocompatibility was assessed via live/dead cell staining and a CCK-8 assay. The osteoinductive capacity of the DF0 , DF1 and DF2 hydrogels on MC3T3-E1 cells was assessed via alkaline phosphatase (ALP) and Alizarin Red S (ARS) staining. In the aforementioned cell experiments, cells cultured in standard medium served as the control group Results: The DF0, DF1, and DF2 hydrogels were successfully synthesized. Notably, DF1 and DF2 exhibited distinct self-mineralization within 6 days. Results from TEM, EDS, and SAED confirmed that the mineralization products were amorphous calcium phosphate in group DF1, and amorphous calciumzinc phosphate in group DF2. Biocompatibility tests revealed that none of the hydrogels (DF0, DF1, and DF2) adversely affected cell viability or proliferation. In osteogenic induction experiments, both ALP and ARS staining were intensified in the DF1 and DF2 groups, with the most profound staining observed in the DF2 group. Conclusion The developed inositol hexaphosphate-zinc hydrogel (DF2) demonstrates the dual capacity to generate calcium-phosphate compounds through self-mineralization while exhibiting excellent osteoinductive properties. This biocompatible, dual-promoting osteogenic hydrogel presents a novel strategy for bone regeneration.

OBJECTIVE To conduct a clinical rapid evaluation of the marketed proprotein convertase subtilisin/kexin type 9 （PCSK9） inhibitors in China， including evolocumab， tafolecimab， recaticimab， ebronucimab， ongericimab and inclisiran. METHODS Based on the Rapid Guide for Drug Evaluation and Selection in Chinese Medical Institutions （second edition）， drug instructions， clinical diagnosis and treatment guidelines， and literature for six drugs were retrieved from CNKI， Wanfang Data， VIP， PubMed， Embase， Cochrane Library and related official websites. The clinical rapid evaluation was conducted from five aspects： pharmaceutical characteristics， effectiveness， safety， economy， and other attributes. RESULTS The pharmaceutical characteristics， effectiveness， safety， economy， other attributes， and total score of evolocumab scored 24， 27， 15.7， 10， 5.3， and 82 points， respectively. Tafolecimab scored 23.5， 23， 11.5， 9.97， 4.6， and 72.57 points， respectively. Recaticimab scored 20.5， 22， 15.5， 6.37， 3.5， and 67.87 points. Ebronucimab scored 20， 23， 11， 6.48， 3.5， and 63.98 points. Ongericimab scored 20.5， 23， 8.5， 4.83， 3.5， and 60.33 points. Inclisiran scored 25.5， 24， 13， 6.48， 5， and 73.98 points. CONCLUSIONS Evolocumab is the optimal choice for treating hypercholesterolemia and is recommended as the first-line option. Tafolecimab is the second-line option， and recaticimab is suitable for patients who are sensitive to drug adverse reactions. Inclisiran is suitable for patients with poor compliance. Ebronucimab and ongericimab are weakly recommended due to their later market introduction. Clinicians should make individualized drug selections based on factors such as patient risk level and compliance requirements.

Objectives: . The prognostic value of the pretreatment albumin-to-alkaline phosphatase ratio (AAPR) in head and neck cancer (HNC) remains uncertain. This meta-analysis aimed to evaluate the predictive role of AAPR for survival outcomes in patients with HNC. Methods: . A comprehensive search of the Cochrane Library, PubMed, and Embase databases was conducted to identify relevant studies published up to July 30, 2024. We included studies on AAPR and survival outcomes in HNC patients. Results: . Eight studies comprising 1,737 HNC patients were analyzed using random-effects models. Lower AAPR values were significantly correlated with worse overall survival (hazard ratio [HR], 2.08), progression-free survival (HR, 2.00), and disease-free survival (HR, 2.18). Sensitivity analyses confirmed the robustness of these results, with no significant publication bias detected. Conclusion . Our findings suggest that pretreatment AAPR could serve as a valuable and cost-effective prognostic indicator in HNC, potentially aiding clinicians in risk stratification and treatment decision-making. However, additional validation studies are warranted to confirm its clinical applicability.

Objective To construct a predictive model for patients with verte-brobasilar dolichoectasia(VBD)complicated by posterior circulation acute cerebral infarction(ACI)based on the characteristics of verte-brobasilar artery magnetic resonance vascular wall imaging(MR-VWI),thereby providing a reference for clinical prevention.Methods A total of 102 patients with VBD complicated by posterior circulation ACI who were admitted to our hospital between March 2016 and January 2023 were selected as the concurrent group.An addi-tional 102 patients with VBD without concurrent posterior circulation ACI were selected as the non-concurrent group at a 1∶1 ratio.The MR-VWI characteristics(basilar artery[BA]diameter,BA length,vertebral artery[VA]intracranial segment length,BA deviation grade,and BA bifurcation height grade)and clinical data of the two groups were compared,and the factors influencing posterior circulation ACI in patients with VBD were analyzed.Based on the MR-VWI features and related influencing factors,a nomogram prediction model of pos-terior circulation ACI in patients with VBD was constructed,and the clinical significance of the nomogram prediction model was evaluated using receiver operating characteristic(ROC)and calibration curves.Results A significant difference were observed in the D-dimer levels between the two groups(P＜0.05).BA diameter,BA length,and VA intracranial length were greater in the concurrent group than in the non-concurrent group.The proportion of BA bifurcation height grade ≥ 2 and BA deviation grade≥2 in the concurrent group was higher than that in the non-concurrent group(P＜0.05).BA diameter,BA length,BA bifurcation height classification,BA deviation classi-fication,and D-dimer level were all independent risk factors for posterior circulation ACI in patients with VBD(P＜0.05).The area under the curve of the posterior circulation ACI predicted using the nomogram model was 0.900(95％CI:0.858-0.943),and good calibration was noted.Conclusion BA diameter,BA length,BA bifurcation height classification,BA offset classification,and D-dimer level were inde-pendent influencing factors of posterior circulation ACI in patients with VBD.Based on these factors,a nomogram prediction model was constructed with high prediction efficiency and good calibration.

Objective:To analyze the drug resistance status and related risk factors in elderly patients with pulmonary tuberculosis,and to construct and validate a drug resistance risk prediction model for elderly pulmonary tuberculosis patients,providing evidence for early clinical identification of high-risk populations.Methods:A retrospective study was conducted,consecutively enrolling 315 pulmonary tuberculosis patients aged ≥60 years from January 2019 to December 2021.Based on drug susceptibility test results,patients were divided into drug-resistant group(85 cases)and drug-sensitive group(230 cases).Data on demographic characteristics,clinical manifestations,comorbidities,imaging features,and previous treatment history were collected.Univariate and multivariate logistic regression analyses were performed to identify drug resistance-related factors,and a prediction model was constructed accordingly.The model was internally validated using the concordance index(C-index)and Bootstrap method.Results:Among 315 elderly pulmonary tuberculosis patients,the drug resistance rate was 26.98％,predominantly mono-resistance(48.24％)and multidrug-resistance(28.24％).Multivariate logistic regression analysis showed that previous anti-tuberculosis treatment history[OR=4.537,95％CI(1.962-10.498),P=0.005],diabetes mellitus[OR=3.286,95％CI(1.547-6.979),P=0.002],pulmonary cavitation[OR=4.158,95％CI(1.926-8.973),P＜0.001],pleural effusion[OR=2.563,95％CI(1.218-5.390),P=0.013],and tracheobronchial tuberculosis[OR=2.819,95％CI(1.352-5.876),P=0.006]were independent risk factors for drug resistance in elderly pulmonary tuberculosis.The prediction model constructed based on these factors had a C-index of 0.815(95％CI:0.762-0.868).Conclusion:The drug resistance rate is high among elderly pulmonary tuberculosis patients.Previous anti-tuberculosis treatment history,diabetes mellitus,pulmonary cavitation,pleural effusion,and tracheobronchial tuberculosis are independent risk factors for drug resistance in elderly pulmonary tuberculosis.The prediction model constructed based on these factors has good predictive value for identifying high-risk populations,which is helpful for early clinical intervention and individualized treatment strategy formulation.

Objective To evaluate the longitudinal imaging features of coronary artery plaques in elderly male patients with CHD and myocardial bridges and explore the longitudinal changing pat-terns.Methods A total of 117 elderly male CHD patients who underwent two examinations of coronary computed tomography angiography in our medical center from January 2018 to Septem-ber 2023 were enrolled in this study.Then 216 small plaques(0.1-50 mm3 in size)were subjec-ted,and classified into the proximal myocardial bridge group(98 plaques)and other heart part group(118 plaques)according to the site of the plaques.Plaque volume,plaque composition vol-ume,FAI,and CT-derived fraction flow reserve(CT-FFR)were calculated and recorded.Results In the 2 groups of plaques,there were no statistically differences in the plaque length,plaque nec-rotic core volume,and FAI derived from the second examination than the baseline one(P＞0.05).The plaque volume,intra-plaque fibers,and dense calcified volume of plaques in the second exami-nation were significantly greater than those at baseline,and CT-FFR was obviously smaller than the baseline level in both groups(P＜0.05,P＜0.01).In the proximal myocardial bridge group,the intra-plaque fibrofat volume in the second examination was significantly larger than that of baseline,while opposite phenomenon was observed in the plaques of the other heart part group(P＜0.05).The annual changing rates of intraplaque fibrofat volume and FAI were significantly higher in the proximal myocardial bridge group than the other heart part group[0.51％(-0.32％,0.51％)vs 0.02％(-0.46％,0.20％),P=0.046;0.55％(-2.44％,1.76％)vs 0.33％(-1.36％,2.63％),P=0.044].Conclusion In elderly male patients,the intraplaque fibrofat vol-ume,FAI and CT-FFR are more likely to change in the proximal plaques of the left anterior de-scending artery myocardial bridge than the plaques of other parts of heart,so the proximal plaques of the left anterior descending artery need more clinical attention and early intervention.

Objective To investigate the role and mechanism of AMP-activated protein kinase(AMPK)in regulating mitochondrial function and cardiomyocyte injury in sepsis.Methods Forty Balb/c mice were randomly divided into four groups:Sham group(n=10),Sham+5-aminoimidazole-4-carboxamide ribonucleotide(AICAR)group(n=10),CLP group(n=10),and CLP+AICAR group(n=10).A sepsis mouse model was established through cecal ligation and puncture(CLP).Echocardiography and histological analysis were used to assess sepsis-induced cardiac injury.Neonatal rat cardiomyocytes(NRCMs)were incubated with lipopolysaccharide(LPS)(10 μg/mL)for 24 h to induce an in vitro sepsis model,and treated with AICAR.Mitochondrial function and dynamics were assessed by using Western blotting,enzyme-linked immunosorbent assay(ELISA),and immunofluorescence assays.Results Compared with the Sham group,AMPK expression in the myocardial tissue of CLP mice was significantly reduced(P<0.05).Compared with the CLP group,AMPK expression in the CLP+AICAR group was significantly increased(P<0.05).Survival analysis showed that CLP led to a high mortality rate(～60％ ),while AICAR treatment significantly improved the survival rate of CLP mice(P<0.05).Compared with the Sham group,cardiac output(CO),stroke volume(SV),and left ventricular end-diastolic volume(LVEDV)were significantly decreased in the CLP group(P<0.05),while left ventricular posterior wall systolic(LVPWs)and left ventricular posterior wall thickness(LVPWd)were significantly increased(P<0.05).AICAR treatment alleviated the cardiac dysfunction induced by CLP.Compared with the CLP group,mitochondrial size and the number of mitochondrial cristae in the myocardial tissue of CLP+AICAR group mice were significantly increased(P<0.05),while DHE fluorescence intensity and the number of TUNEL-positive cells were significantly reduced(P<0.05).Compared with the LPS group,ATP production,mitochondrial respiration rate,and complex Ⅰ,Ⅱ,and Ⅲ activities in NRCMs of the LPS+AICAR group were significantly increased(P<0.05),while mitochondrial and cytoplasmic ROS levels were significantly reduced(P<0.05).Compared with the control group,mitochondrial size in NRCMs of the LPS group was significantly reduced(P<0.05),while Bax and Caspase-3 expression,as well as mitochondrial fission index,were significantly increased(P<0.05),and these changes were mitigated by AICAR(P<0.05).Conclusion AMPK plays a crucial role in maintaining cardiac function and mitigating septic myocardial injury by regulating mitochondrial structure and function,energy metabolism,oxidative stress,and apoptosis.

Objective Comparing the clinical efficacy of moxifloxacin and azithromycin in the treatment of Mycoplasmal pneumoniae pneumonia(MPP).Methods MPP patients admitted to our hospital from January 2023 to May 2024 were selected and randomly divided into the observation group and the control group.Both groups were given conventional treatment such as salbutamol and budesonide aerosol inhalation.Additionally,the control group was given azithromycin 0.5 g,ivd,qd,and the observation group was given moxifloxacin 0.4 g,ivd,qd.After one week of treatment,the efficacy,symptom disappearance time and adverse drug reactions occurrence of the two groups were compared.The serum inflammatory markers[white blood cell count(WBC),interleukin-6(IL-6),C-reactive protein(CRP),procalcitonin(PCT)],immunoglobulin indicators(IgA,IgG,IgM),T lymphocyte subset indicators(CD3+,CD4+,and CD4+/CD8+)before and after treatment were compared between the two groups.Results A total of 80 patients were included and each group was 40 patients.After treatment,the total effective rate of observation group(95.00％)was higher than that of control group(75.00％)(P＜0.05).The disappearance time of symptoms(cough,fever,and lung rales)in the observation group was significantly lower than that in the control group(P＜0.05).After treatment,the levels of CD3+,CD4+,and CD4+/CD8+in both groups significantly increased,while the levels of serum IL-6,CRP,PCT,WBC,IgA,IgM,and IgG significantly decreased(P＜0.05),with the observation group showing better results(P＜0.05).There was no significantiy difference in the incidence of adverse reactions between the two groups(P＞0.05).Conclusion Moxifloxacin is more effective than azithromycin in the treatment of MPP,which can relieve symptoms,improve immune function,reduce inflammatory response,and has a relatively good safety profile.

Objective Comparing the clinical efficacy of moxifloxacin and azithromycin in the treatment of Mycoplasmal pneumoniae pneumonia(MPP).Methods MPP patients admitted to our hospital from January 2023 to May 2024 were selected and randomly divided into the observation group and the control group.Both groups were given conventional treatment such as salbutamol and budesonide aerosol inhalation.Additionally,the control group was given azithromycin 0.5 g,ivd,qd,and the observation group was given moxifloxacin 0.4 g,ivd,qd.After one week of treatment,the efficacy,symptom disappearance time and adverse drug reactions occurrence of the two groups were compared.The serum inflammatory markers[white blood cell count(WBC),interleukin-6(IL-6),C-reactive protein(CRP),procalcitonin(PCT)],immunoglobulin indicators(IgA,IgG,IgM),T lymphocyte subset indicators(CD3+,CD4+,and CD4+/CD8+)before and after treatment were compared between the two groups.Results A total of 80 patients were included and each group was 40 patients.After treatment,the total effective rate of observation group(95.00％)was higher than that of control group(75.00％)(P＜0.05).The disappearance time of symptoms(cough,fever,and lung rales)in the observation group was significantly lower than that in the control group(P＜0.05).After treatment,the levels of CD3+,CD4+,and CD4+/CD8+in both groups significantly increased,while the levels of serum IL-6,CRP,PCT,WBC,IgA,IgM,and IgG significantly decreased(P＜0.05),with the observation group showing better results(P＜0.05).There was no significantiy difference in the incidence of adverse reactions between the two groups(P＞0.05).Conclusion Moxifloxacin is more effective than azithromycin in the treatment of MPP,which can relieve symptoms,improve immune function,reduce inflammatory response,and has a relatively good safety profile.

To elucidate the genomic characteristics of Salmonella strains derived from sheep,this study employed various methods,including bacterial isolation and identification,biochemical identi-fication,pathogenicity test,whole-genome sequencing,and BLAST comparison,along with the screening of integrative conjugative elements(ICE)using ICEfinder and EasyFig for comparative analysis,as well as plasmid comparisons utilizing PlasmidBrig.The results revealed the isolation of a Gram-negative,non-spore-forming bacillus from nasal swabs of diseased sheep,which formed gray-white,smooth-surfaced,and neatly edged circular colonies on TSA sheep blood agar.On XLT-4 agar medium,it produced smooth-surfaced,white,circular colonies.The bacterium was identified as Salmonella enterica through 16S rRNA sequencing and biochemical identification.This bacteri-um induces hemorrhaging in the intestines of guinea pigs,resulting in their demise within a 48-hour period.The pathogen exhibits high virulence.Whole-genome alignment demonstrated a high degree of homology with Salmonella enterica subsp.diarizonae serotype 61:k:1,5,(7).ICE screen-ing and comparative analysis indicated the presence of a novel ICE in this strain,characterized by a core structural framework that includes an integrative shear module,a mobilizable processing mod-ule,a conjugative pair formation module,and a regulatory module.Notably,ICE from different spe-cies containing the same integrase exhibited identical inverted repeat sequences and insertion sites at tRNAPhe.Plasmid homology comparisons revealed that plasmid sequences from different strains of Salmonella enterica subsp.diarizonae serotype 61:k:1,5,(7)also showed high homology;however,the homology with plasmid sequences from other Salmonella and Escherichia coli strains was only 50％.These findings indicate that the isolated strain is Salmonella enterica subsp.diarizonae serotype 61:k:1,5,(7)and contains a novel ICE as well as a plasmid.This study fur-ther enriches the molecular epidemiology of Salmonella and provides a theoretical basis for the prevention and control of infections caused by this pathogen.