OBJECTIVE To evaluate the immunoprotection effect of a novel inactivated whole cell vaccine against Acinetobacter baumannii based on ultrasonic microbubble physical damage technique(IWC)and explore its poten-tial of clinical transformation.METHODS Totally 48 C57BL/6 mice were randomly assigned to divide into three groups and receive the nasal inoculation of corresponding preparations,the IWC group and the paraformalde-hyde inactivated vaccine group were inoculated with 20 μl of 1× 107 CFU vaccine,the control group was treated with 20 μl phosphate buffered salt solution.The infection models were established 7 days after intraperitoneal in-jection of a lethal dose of A.baumannii.The 7-day mortality rates of the mice were statistically analyzed after tox-in attack.The counts of colonized bacterial colonies on lung and spleen tissues were determined by plate count method after toxin attack for 24 hours.The levels of inflammatory factors interleukin(IL)-6,tumor necro-sis factor α(TNF-α)and IL-1β in the lung tissues were detected by enzyme-linked immunosorbent assay(ELISA),and the pathological damage was observed.RESULTS The survival rate of the IWC group was higher than that of the control group,and the counts of colonized bacterial colonies on lung and spleen tissues were less in the IWC group than those in the control group(P＜0.05).As compared the paraformaldehyde inactivated vaccine group,the survival rate of the IWC group increased by 10.00％,and the counts of colonized bacterial colonies on the lung tissues were slightly less in the IWC group than those in the paraformaldehyde inactivated vaccine group(P＜0.05),and the counts of colonized bacterial colonies on spleens were basically the same.The levels of lung tis-sue inflammatory factors of the IWC group were lower than those of the other two groups(P＜0.05).The patho-logical damage was alleviated,and the IWC group was superior to the control group in the integrity of alveolar structure.CONCLUSIONS IWC can maintain the immunogenicity of pathogens through physical damage technique,effectively activate the immune response of the hose,and reduce the bacterial load and inflammatory injury,show-ing better immunoprotection effect than the traditional chemical inactivation method.The study has provided ex-perimental bases for development of novel,specific,safe and highly efficient vaccine as well as new ideas and strategies for clinical prevention and treatment of A.baumannii infection.

Objective To rexplore the content structure characteristics and psychometric properties of assessment scales for funda-mental movement skills(FMS)in school-aged children,based on International Classification of Functioning,Dis-ability and Health-Children and Youth Version(ICF-CY)framework.Methods Literatures on assessment scales for FMS in school-aged children were retrieved from PubMed,Science Di-rect,Web of Science,EMBase,PsycINFO,CNKI and Wanfang data from inception to July,2025.The contents of the included scales were analyzed using the ICF-CY linking rule.The COSMIN RoB tool was used to assess the psychometric properties of the scales,and the GRADE system was applied to evaluate the overall quality of evi-dence.Results A total of 29 studies were included,involving six assessment scales:Bruininks-Oseretsky Test of Motor Profi-ciency-2(BOT-2),Canadian Assessment of Movement Skill and Agility(CAMSA),K?rperkoordinationstest für Kinder(KTK),Movement Assessment Battery for Children-2(MABC-2),Motorische Basiskompetenzen test Battery(MOBAK),and Test of Gross Motor Development-3(TGMD-3).In the ICF-CY linking analysis,all six tools addressed joint mobility functions(b710)and joint stability functions(b715),while five of them also in-volved hand and arm use(d445).The number of linked items ranged from 5 to 11.BOT-2 and TGMD-3 linked to 11 items,showing broad coverage;BOT-2 focused more on the body function dimension,whereas TGMD-3 em-phasized activity and participation dimensions,especially the performance of hand function in daily activities.In bias risk assessment,TGMD-3 showed the lowest risk(50%rated A and 50%rated B),while MABC-2 had the highest proportion of C ratings(55.6%),followed by BOT-2(33.3%).In evidence grading,TGMD-3 was rated high quality,KTK moderate,BOT-2 and CAMSA low,and MABC-2 and MOBAK very low.Conclusion TGMD-3 is recommended as the primary tool for assessing FMS in school-aged children for broad coverage of ICF-CY items,strong psychometric properties and high evidence quality.KTK,with moderate evidence quali-ty,may serve as a secondary option,but should be used cautiously in China.Although CAMSA is easy to admin-ister,its validity and reliability are low,so it is only suitable for rapid classroom screening.BOT-2,despite cover-ing more ICF-CY items,has a higher bias risk and low evidence quality.MOBAK and MABC-2 have very low evidence quality and are not recommended for current use.

Objective To rexplore the content structure characteristics and psychometric properties of assessment scales for funda-mental movement skills(FMS)in school-aged children,based on International Classification of Functioning,Dis-ability and Health-Children and Youth Version(ICF-CY)framework.Methods Literatures on assessment scales for FMS in school-aged children were retrieved from PubMed,Science Di-rect,Web of Science,EMBase,PsycINFO,CNKI and Wanfang data from inception to July,2025.The contents of the included scales were analyzed using the ICF-CY linking rule.The COSMIN RoB tool was used to assess the psychometric properties of the scales,and the GRADE system was applied to evaluate the overall quality of evi-dence.Results A total of 29 studies were included,involving six assessment scales:Bruininks-Oseretsky Test of Motor Profi-ciency-2(BOT-2),Canadian Assessment of Movement Skill and Agility(CAMSA),K?rperkoordinationstest für Kinder(KTK),Movement Assessment Battery for Children-2(MABC-2),Motorische Basiskompetenzen test Battery(MOBAK),and Test of Gross Motor Development-3(TGMD-3).In the ICF-CY linking analysis,all six tools addressed joint mobility functions(b710)and joint stability functions(b715),while five of them also in-volved hand and arm use(d445).The number of linked items ranged from 5 to 11.BOT-2 and TGMD-3 linked to 11 items,showing broad coverage;BOT-2 focused more on the body function dimension,whereas TGMD-3 em-phasized activity and participation dimensions,especially the performance of hand function in daily activities.In bias risk assessment,TGMD-3 showed the lowest risk(50%rated A and 50%rated B),while MABC-2 had the highest proportion of C ratings(55.6%),followed by BOT-2(33.3%).In evidence grading,TGMD-3 was rated high quality,KTK moderate,BOT-2 and CAMSA low,and MABC-2 and MOBAK very low.Conclusion TGMD-3 is recommended as the primary tool for assessing FMS in school-aged children for broad coverage of ICF-CY items,strong psychometric properties and high evidence quality.KTK,with moderate evidence quali-ty,may serve as a secondary option,but should be used cautiously in China.Although CAMSA is easy to admin-ister,its validity and reliability are low,so it is only suitable for rapid classroom screening.BOT-2,despite cover-ing more ICF-CY items,has a higher bias risk and low evidence quality.MOBAK and MABC-2 have very low evidence quality and are not recommended for current use.

OBJECTIVE To evaluate the immunoprotection effect of a novel inactivated whole cell vaccine against Acinetobacter baumannii based on ultrasonic microbubble physical damage technique(IWC)and explore its poten-tial of clinical transformation.METHODS Totally 48 C57BL/6 mice were randomly assigned to divide into three groups and receive the nasal inoculation of corresponding preparations,the IWC group and the paraformalde-hyde inactivated vaccine group were inoculated with 20 μl of 1× 107 CFU vaccine,the control group was treated with 20 μl phosphate buffered salt solution.The infection models were established 7 days after intraperitoneal in-jection of a lethal dose of A.baumannii.The 7-day mortality rates of the mice were statistically analyzed after tox-in attack.The counts of colonized bacterial colonies on lung and spleen tissues were determined by plate count method after toxin attack for 24 hours.The levels of inflammatory factors interleukin(IL)-6,tumor necro-sis factor α(TNF-α)and IL-1β in the lung tissues were detected by enzyme-linked immunosorbent assay(ELISA),and the pathological damage was observed.RESULTS The survival rate of the IWC group was higher than that of the control group,and the counts of colonized bacterial colonies on lung and spleen tissues were less in the IWC group than those in the control group(P＜0.05).As compared the paraformaldehyde inactivated vaccine group,the survival rate of the IWC group increased by 10.00％,and the counts of colonized bacterial colonies on the lung tissues were slightly less in the IWC group than those in the paraformaldehyde inactivated vaccine group(P＜0.05),and the counts of colonized bacterial colonies on spleens were basically the same.The levels of lung tis-sue inflammatory factors of the IWC group were lower than those of the other two groups(P＜0.05).The patho-logical damage was alleviated,and the IWC group was superior to the control group in the integrity of alveolar structure.CONCLUSIONS IWC can maintain the immunogenicity of pathogens through physical damage technique,effectively activate the immune response of the hose,and reduce the bacterial load and inflammatory injury,show-ing better immunoprotection effect than the traditional chemical inactivation method.The study has provided ex-perimental bases for development of novel,specific,safe and highly efficient vaccine as well as new ideas and strategies for clinical prevention and treatment of A.baumannii infection.

OBJECTIVE To evaluate the impact of the specialized centralized procurement policy for insulin on daily cost and affordability of insulin,and provide data support for the enhancement of relevant policies.METHODS In this research,the insulin purchasing data were obtained from provincial centralized procurement platforms in provinces before and after the specialized centralized procurement of insulin(October-December 2021 and October-December 2022),and the cost variations of insulin before and after the centralized procurement were analyzed by the defined daily dose cost(DDDc)of various types of insulins.The changes in the affordability of various types of insulins before and after the specialized centralized procurement were evaluated,using the percentage of annual expenditure on various types of insulins relative to annual per capita disposable income(i.e.the proportion of annual expenditure)as an indicator.RESULTS After the specialized centralized procurement,DDDc of various types of insulins decreased by 20.7%-71.8%,with an average reduction of 45.7%.Moreover,the reduction in DDDc for third-generation insulin exceeded that for second-generation insulin.The reduction in the proportion of annual expenditure on insulin ranged from 24.3%to 73.4%,with an average decrease of 48.5%.Premixed insulin analogs experienced the greatest reduction(73.4%).Following the specialized centralized procurement,DDDc of insulin decreased in all provinces.Except for Guangxi(10.2%),the average proportion of annual expenditure on insulin in the remaining provinces dropped to below 10%.CONCLUSIONS The specialized centralized procurement policy for insulin has significantly reduced insulin costs and improved affordability,thereby alleviating the economic pressure on patients with diabetes.There are notable cost disparities among provinces and among insulin categories,which require attention.

Ovarian cancer poses a significant threat to women's health, necessitating effective therapeutic strategies. Emd-D, an emodin derivative, demonstrates enhanced pharmaceutical properties and bioavailability. In this study, Cell Counting Kit 8 (CCK8) assays and Ki-67 staining revealed dose-dependent inhibition of cell proliferation by Emd-D. Migration and invasion experiments confirmed its inhibitory effects on OVHM cells, while flow cytometry analysis demonstrated Emd-D-induced apoptosis. Mechanistic investigations elucidated that Emd-D functions as an inhibitor by directly binding to the glycolysis-related enzyme PFKFB4. This was corroborated by alterations in intracellular lactate and pyruvate levels, as well as glucose transporter 1 (GLUT1) and hexokinase 2 (HK2) expression. PFKFB4 overexpression experiments further supported the dependence of Emd-D on PFKFB4-mediated glycolysis and SRC3/mTORC1 pathway-associated apoptosis. In vivo experiments exhibited reduced xenograft tumor sizes upon Emd-D treatment, accompanied by suppressed glycolysis and increased expression of Bax/Bcl-2 apoptotic proteins within the tumors. In conclusion, our findings demonstrate Emd-D's potential as an anti-ovarian cancer agent through inhibition of the PFKFB4-dependent glycolysis pathway and induction of apoptosis. These results provide a foundation for further exploration of Emd-D as a promising drug candidate for ovarian cancer treatment.
Female ; Humans ; Ovarian Neoplasms/physiopathology* ; Phosphofructokinase-2/genetics* ; Apoptosis/drug effects* ; Glycolysis/drug effects* ; Animals ; Cell Line, Tumor ; Mice ; Cell Proliferation/drug effects* ; Emodin/administration & dosage* ; Mice, Nude ; Mice, Inbred BALB C ; Hexokinase/metabolism* ; Xenograft Model Antitumor Assays

Obesity is a significant risk factor for cancer and is associated with breast cancer metastasis. Nevertheless, the mechanism by which alterations in systemic metabolism affect tumor microenvironment (TME) and consequently influence tumor metastasis remains inadequately understood. Herein, we found that perturbations in circulating metabolites induced by obesity promote metastasis-like phenotypes in breast cancer. Oleoylcarnitine (OLCarn) concentrations were elevated in the serum of obese mice and humans. Administration of exogenous OLCarn induces metastasis-like characteristics in breast cancer cells. Mechanistically, OLCarn directly interacts with the Arg176 site of adenylate cyclase 10 (ADCY10), leading to the activation of ADCY10 and enhancement of cAMP production. Mutations at Arg176 prevent OLCarn from binding to ADCY10, disrupting the ADCY10-mediated activation of cyclic adenosine monophosphate (cAMP) signaling pathway. This activation promotes transcription factor 4 (TCF4)-dependent kinesin family member C1 (KIFC1) transcription, thereby driving breast cancer metastasis. Conversely, the neutralization of both ADCY10 and KIFC1 through knockdown or pharmacological inhibition abrogates the oncogenic effects mediated by OLCarn. Hence, obesity-induced systemic environmental changes lead to the aberrant accumulation of OLCarn within the TME, making it a potential therapeutic target and biomarker for breast cancer.

To explore the impact of an airway stepwise management strategy in the treatment of hospital acquired pneumonia (HAP) in the ultra elderly critically ill patients.

Objective To systematically evaluate the effect of exercise therapy on body structure,function,and activity and partici-pation in patients with chronic nonspecific neck pain(CNSNP)based on the International Classification of Func-tioning,Disability and Health(ICF)framework. Methods A PICO framework was constructed,and randomized controlled trials(RCTs)on the intervention of different types of exercise therapy for patients with CNSNP were retrieved from databases of CBM,Wanfang data,VIP,CNKI,Cochrane Library,Embase,PubMed and Web of Science,from the establishment to March,2024.The quality of the literature was evaluated with Cochrane Risk of Bias Tool and Physiotherapy Evidence Database(PEDro)scale,and the evidence quality of the outcome indicators was evaluated using GRADE.Data were syn-thesized and analyzed using RevMan 5.3,and the risk of bias was evaluated using Stata 18.0. Results A total of eleven RCTs involving 668 subjects were included.The scores of PEDro scale were five to eight.The types of interventions included muscle strength training,stability training,proprioception training,Yoga and Pi-lates.The control groups received placebo,physical factor therapy and health education.Exercise therapy could increase the craniovertebral angle(SMD=0.84,95%CI 0.42 to 1.26,P<0.001),reduce the Visual Analogue Scale score(SMD=-2.05,95%CI-2.58 to-1.52,P<0.001),increase the pressure pain threshold(MD=112.27,95%CI 75.03 to 149.50,P<0.001),increase the range of motion of cervical forward(SMD=1.24,95%CI 0.34 to 2.15,P=0.007)and lateral(SMD=1.52,95%CI 0.40 to 2.65,P=0.008)flexion,and improve the endurance of the deep cervical flexors(SMD=1.02,95%CI 0.10 to 1.94,P=0.03)and position sense of the cervical spine(SMD=-1.00,95%CI-1.47 to-0.53,P<0.001);however,it was not significant in improving the range of motion of backward flexion(SMD=0.85,95%CI-1.04 to 2.75,P=0.38)and rotation(SMD=1.65,95%CI-0.35 to 3.65,P=0.11).Exercise therapy could also reduce the Neck Disability Index score(MD=-11.88,95%CI-16.09 to-7.68,P<0.001),and it was no significant in the Short-Form-36 score(MD=19.04,95%CI-3.00 to 41.08,P=0.09). Conclusion Exercise therapy can improve head posture,pain,motion of forward flexion and lateral flexion,endurance of the cervical flexors and joint position sense,and the overall function in patients with CNSNP.However,fur-ther researches are needed to verify the effects on cervical backward flexion and rotation,and quality of life.

Objective:To construct and validate a nomogram model for predicting the risk of 28-day mortality in sepsis patients.Methods:A retrospective cohort study was conducted. 281 sepsis patients admitted to the department of intensive care unit (ICU) of the 940th Hospital of the Joint Logistics Support Force of PLA from January 2017 to December 2022 were selected as the research subjects. The patients were divided into a training set (197 cases) and a validation set (84 cases) according to a 7∶3 ratio. The general information, clinical treatment measures and laboratory examination results within 24 hours after admission to ICU were collected. Patients were divided into survival group and death group based on 28-day outcomes. The differences in various data were compared between the two groups. The optimal predictive variables were selected using Lasso regression, and univariate and multivariate Logistic regression analyses were performed to identify factors influencing the mortality of sepsis patients and to establish a nomogram model. Receiver operator characteristic curve (ROC curve), calibration curve, decision curve analysis (DCA), and clinical impact curve (CIC) were used to evaluate the nomogram model.Results:Out of 281 cases of sepsis, 82 cases died with a mortality of 29.18%. The number of patients who died in the training and validation sets was 54 and 28, with a mortality of 27.41% and 33.33% respectively. Lasso regression, univariate and multivariate Logistic regression analysis screened for 5 independent predictors associated with 28-day mortality. There were use of vasoactive drugs [odds ratio ( OR) = 5.924, 95% confidence interval (95% CI) was 1.244-44.571, P = 0.043], acute physiology and chronic health evaluation Ⅱ (APACHEⅡ: OR = 1.051, 95% CI was 1.000-1.107, P = 0.050), combined with multiple organ dysfunction syndrome (MODS: OR = 17.298, 95% CI was 5.517-76.985, P < 0.001), neutrophil count (NEU: OR = 0.934, 95% CI was 0.879-0.988, P = 0.022) and oxygenation index (PaO 2/FiO 2: OR = 0.994, 95% CI was 0.988-0.998, P = 0.017). A nomogram model was constructed using the independent predictive factors mentioned above, ROC curve analysis showed that the AUC of the nomogram model was 0.899 (95% CI was 0.856-0.943) and 0.909 (95% CI was 0.845-0.972) for the training and validation sets respectively. The C-index was 0.900 and 0.920 for the training and validation sets respectively, with good discrimination. The Hosmer-Lemeshoe tests both showed P > 0.05, indicating good calibration. Both DCA and CIC plots demonstrate the model's good clinical utility. Conclusions:The use of vasoactive, APACHEⅡ score, comorbid MODS, NEU and PaO 2/FiO 2 are independent risk factors for 28-day mortality in patients with sepsis. The nomogram model based on these 5 indicators has a good predictive ability for the occurrence of mortality in sepsis patients.