BACKGROUND:Osteoporotic fracture is the most serious complication of osteoporosis.Previous studies have demonstrated that gut microbiota has a regulatory effect on skeletal tissue and that gut microbiota has an important relationship with osteoporotic fracture,but the causal relationship between the two is unclear. OBJECTIVE:To explore the causal relationship between gut microbiota and osteoporotic fractures using Mendelian randomization method. METHODS:The genome-wide association study(GWAS)datasets of gut microbiota and osteoporotic fracture were obtained from the IEU Open GWAS database and the Finnish database R9,respectively.Using gut microbiota as the exposure factor and osteoporotic fracture as the outcome variable,Mendelian randomization analyses with random-effects inverse variance weighted,MR-Egger regression,weighted median,simple model,and weighted model methods were performed to assess whether there is a causal relationship between gut microbiota and osteoporotic fracture.Sensitivity analyses were performed to test the reliability and robustness of the results.Reverse Mendelian randomization analyses were performed to further validate the causal relationship identified in the forward Mendelian randomization analyses. RESULTS AND CONCLUSION:The results of this Mendelian randomization analysis indicated a causal relationship between gut microbiota and osteoporotic fracture.Elevated abundance of Actinomycetales[odds ratio(OR)=1.562,95%confidence interval(CI):1.027-2.375,P=0.037),Actinomycetaceae(OR=1.561,95%CI:1.027-2.374,P=0.037),Actinomyces(OR=1.544,95%CI:1.130-2.110,P=0.006),Butyricicoccus(OR=1.781,95%CI:1.194-2.657,P=0.005),Coprococcus 2(OR=1.550,95%CI:1.068-2.251,P=0.021),Family ⅩⅢ UCG-001(OR=1.473,95%CI:1.001-2.168,P=0.049),Methanobrevibacter(OR=1.274,95%CI:1.001-1.621,P=0.049),and Roseburia(OR=1.429,95%CI:1.015-2.013,P=0.041)would increase the risk of osteoporotic fractures in patients.Elevated abundance of Bacteroidia(OR=0.660,95%CI:0.455-0.959,P=0.029),Bacteroidales(OR=0.660,95%CI:0.455-0.959,P=0.029),Christensenellacea(OR=0.725,95%CI:0.529-0.995,P=0.047),Ruminococcaceae(OR=0.643,95%CI:0.443-0.933,P=0.020),Enterorhabdus(OR=0.558,95%CI:0.395-0.788,P=0.001),Eubacterium rectale group(OR=0.631,95%CI:0.435-0.916,P=0.016),Lachnospiraceae UCG008(OR=0.738,95%CI:0.546-0.998,P=0.048),and Ruminiclostridium 9(OR=0.492,95%CI:0.324-0.746,P=0.001)would reduce the risk of osteoporotic fractures in patients.We identified 16 gut microbiota associated with osteoporotic fracture by the Mendelian randomization method.That is,using gut microbiota as the exposure factor and osteoporotic fracture as the outcome variable,eight gut microbiota showed positive causal associations with osteoporotic fracture and another eight gut microbiota showed negative causal associations with osteoporotic fracture.The results of this study not only identify new biomarkers for the early prediction of osteoporotic fracture and potential therapeutic targets in clinical practice,but also provide an experimental basis and theoretical basis for the study of improving the occurrence and prognosis of osteoporotic fracture through gut microbiota in bone tissue engineering.

Objective To assess the risk of human Spirometra mansoni infections and investigate the knowledge, attitude and practice (KAP) towards sparganosis mansoni among residents in Henan Province, so as to provide insights into formulation of the sparganosis mansoni control measures. Methods Qinling Village in Fugou County of Zhoukou City, Bali Village in Yancheng District of Luohe City, Duzhai Village in Puyang County of Puyang City and Doushan Village in Luoshan County of Xinyang City were sampled as survey sites in Henan Province from July to August 2023, and more than 40 frogs were sampled from ponds or streams in each survey site for detection of Sparganum mansoni infections. At least 150 residents were sampled using a cluster sampling method from each survey site, and the sero-prevalence of anti-S. mansoni IgG antibody was estimated. In addition, a questionnaire survey was conducted on the KAP towards sparganosis mansoni among participants, and the proportion of eligible KAP, rate of correct KAP and KAP scores were calculated. Results A total 229 frogs were collected from 4 survey sites in 2023, and the overall prevalence of S. mansoni infection was 4.37% (10/229) in frogs, with 7.75% (10/129) prevalence in wild frogs and 0 in farm-bred frogs. A questionnaire survey was performed among 649 residents sampled from 4 survey sites, and 649 serum samples were collected. The seroprevalence of anti-S.mansoni IgG antibody was 0.15% (1/649) and the overall proportion of eligible KAP was 23.73% (154/649) among participants. There were age- (χ² = 30.905, P = 0.000), educational level- (χ² = 41.011, P = 0.000), and occupation-specific proportions of eligible KAP among participants (χ² = 10.721, P = 0.005), and the proportion of eligible KAP decreased with age (χ² _trend = 22.717, P = 0.000) and increased with education levels (χ² _trend = 40.025, P = 0.000). The rates of correct KAP towards sparganosis mansoni were 40.81% (2 119/5 192), 96.66% (1 882/1 947) and 63.81% (3 727/5 841) (χ² = 1 913.731, P = 0.000) among residents, respectively. The rates of correct KAP towards sparganosis mansoni varied significantly among survey sites (χ² = 136.872, 42.347 and 255.157; all P values= 0.000, with the highest rate of correct knowledge (51.94%, 748/1 440) and practices (75.86%, 1 229/1 620) in Yancheng District of Luohe City and the highest rate of correct attitudes in Puyang County of Puyang City (99.11%, 446/450) (all P values< 0.05). Conclusions There is still a high transmission risk of sparganosis mansoni in Henan Province, and the KAP towards sparganosis mansoni is required to be improved among residents.

ObjectiveBased on ultra performance liquid chromatography-quadrupole-electrostatic field orbital trap high-resolution mass spectrometry（UPLC-Q-Orbitrap-MS）， to identify the in vivo and in vitro chemical components of total phenolic acids in Gei Herba（TPAGH）， and to clarify the pharmacological effects and potential mechanisms of the effective part in promoting acute wound healing and inhibiting scar formation. MethodsUPLC-Q-Orbitrap-MS was used to identify the chemical components of TPAGH and ingredients absorbed in vivo after topical administration. A total of 120 ICR mice were randomly divided into the model group， recombinant human epidermal growth factor（rhEGF） group（4 mg·kg^-1）， and low， medium， and high dose groups of TPAGH（3.5， 7， 14 mg·kg^-1）， with 24 mice in each group. A full-thickness skin excision model was constructed， and each administration group was coated with the drug at the wound site， and the model group was treated with an equal volume of normal saline， the treatment was continued for 30 days， during which 8 mice from each group were sacrificed on days 6， 12， and 30. The healing of the wounds in the mice was observed， and histopathological changes in the skin tissues were dynamically observed by hematoxylin-eosin（HE）， Masson， and Sirius red staining， and enzyme-linked immunosorbent assay（ELISA） was used to dynamically measure the contents of interleukin-6（IL-6）， tumor necrosis factor-α（TNF-α）， vascular endothelial growth factor A（VEGFA）， matrix metalloproteinase（MMP）-3 and MMP-9 in skin tissues. Network pharmacology was used to predict the targets related to the promotion of acute wound healing and the inhibition of scar formation by TPAGH， and molecular docking of key components and targets was performed. Gene Ontology（GO） biological process analysis and Kyoto Encyclopedia of Genes and Genomes（KEGG） pathway enrichment analysis were carried out for the related targets， so as to construct a network diagram of herbal material-compound-target-pathway-pharmacological effect-disease for further exploring its potential mechanisms. ResultsA total of 146 compounds were identified in TPAGH， including 28 phenylpropanoids， 31 tannins， 23 triterpenes， 49 flavonoids， and 15 others， and 16 prototype components were found in the serum of mice. Pharmacodynamic results showed that， compared with the model group， the TPAGH groups showed a significant increase in relative wound healing rate and relative scar inhibition rate（P<0.05）， and the number of new capillaries， number of fibroblasts， number of new skin appendages， epidermal regeneration rate， collagen deposition ratio， and Ⅲ/Ⅰ collagen ratio in the tissue were significantly improved（P<0.05， 0.01）， the levels of IL-6， TNF-α， MMP-3 and MMP-9 in the skin tissues were reduced to different degrees， while the level of VEGFA was increased. Network pharmacology analysis screened 10 core targets， including tumor protein 53（TP53）， sarcoma receptor coactivator（SRC）， protein kinase B（Akt）1， signal transducer and activator of transcription 3（STAT3）， epidermal growth factor receptor（EGFR） and so on， participating in 75 signaling pathways such as advanced glycation end-products（AGE）-receptor for AGE（AGE/RAGE） signaling pathway， phosphatidylinositol 3-kinase（PI3K）/Akt signaling pathway， mitogen-activated protein kinase（MAPK） signaling pathway. Molecular docking confirmed that the key components genistein， geraniin， and casuariin had good binding ability to TP53， SRC， Akt1， STAT3 and EGFR. ConclusionThis study comprehensively reflects the chemical composition of TPAGH and the absorbed components after topical administration through UPLC-Q-Orbitrap-MS. TPAGH significantly regulates key indicators of skin healing and tissue reconstruction， thereby clarifying its role in promoting acute wound healing and inhibiting scar formation. By combining in vitro and in vivo component identification with network pharmacology， the study explores how key components may bind to targets such as TP53， Akt1 and EGFR， exerting therapeutic effects through related pathways such as immune inflammation and vascular regeneration.

Objective:To understand the development status of maternal and child health care institutions in China from 2012 to 2022, identify the challenges they face, and provide references for further promoting the high-quality development of these institutions.Methods:Data from the China Health Statistics Yearbook (2013—2015), China Health and Family Planning Statistics Yearbook (2016—2017), and China Health and Wellness Statistics Yearbook (2018—2023) were used. Descriptive analysis was conducted on the data related to resource allocation and utilization efficiency, service provision, income and expenditure structure, and operational status of maternal and child health care institutions in China from 2012 to 2022, using methods such as fixed-base growth rate, year-on-year growth rate, and average annual growth rate. Results:From 2012 to 2022, the number of maternal and child health care institutions in China decreased from 3 044 to 3 031. In terms of resource allocation, the average annual growth rates of bed numbers and business-use floor area were 5.404% and 10.923%, respectively, while the average annual growth rate of health professionals was 7.183%. Regarding service provision, the average annual growth rates of outpatient visits and inpatient admissions were 3.954% and 1.572%, respectively. In terms of service efficiency, the bed occupancy rate decreased from 76.9% to 53.9%, and the average number of patients seen per physician per day decreased from 8.85 to 7.30. In terms of income and expenditure and operations, the income-expenditure surplus rate decreased from 9.16% to 5.41%, and the debt-to-asset ratio increased from 27.88% to 33.60%. During the same period, the average annual growth rates of bed numbers and business-use floor area in grassroots maternal and child health care institutions were 4.545% and 10.091%, respectively, lower than the national average. The number of outpatient visits increased from 89.03 million to 126.93 million, with an average annual growth rate of 3.610%, while the number of inpatient admissions decreased from 4.19 million to 3.91 million, with an average annual decline of 0.689%. The income-expenditure surplus rate of grassroots institutions decreased from 7.76% to 4.05%, 1.36 percentage points lower than the national level, and the debt-to-asset ratio increased from 27.53% to 36.37%, higher than the overall level.Conclusions:From 2012 to 2022, maternal and child health care institutions in China achieved certain developments in resource allocation and service scale. However, several challenges remain, including unbalanced resource allocation, decreased utilization efficiency, slowed growth in medical service volume, imbalanced income and expenditure structure, increased asset operation risks, and restricted development of grassroots institutions. It is recommended that relevant management departments and maternal and child health care institutions optimize resource allocation, plan for service transformation and upgrading, expand income sources, strengthen internal financial control, and reinforce the construction of high-quality and efficient maternal and child health care systems to promote the high-quality development of maternal and child health care institutions in China.

Objective To establish a rat model of venous thrombosis in a plateau hypobaric hypoxic environment and to investigate the effect of this environment on venous thrombosis.Methods A total of 144 healthy male SD rats were assigned randomly to four groups(n=36 rats per group):a plains sham operation(A)group,plains operation(B)group,plateau altitude 6000 m+sham operation(C)group,and plateau altitude 6000 m+surgery(D)group.Rats in A and B groups were maintained in a plains normoxic environment,while rats in C and D groups C and D were subjected to a plateau environment.Rats in the surgical groups underwent quantitative constriction to incompletely obstruct the inferior vena cava blood flow.Each group was further divided into subgroups based on time:1,3,5,7,14,and 21 d(n=6 rats per group).Regular vascular ultrasound monitoring was conducted,and blood samples were taken for whole blood viscosity testing and the assessment of inflammatory indicators,including endothelin-1(ET-1),interleukin-6(IL-6)and tissue factor(TF).Coagulation function was evaluated through the activated partial thromboplastin time(APTT),prothrombin time(PT),thrombin time(TT),fibrinogen(FIB)and D-dimer.After the observation period,the experimental animals were sacrificed and the limbs were removed.Thrombus samples were stained with hematoxylin/eosin(HE),and the thrombus wet mass was measured.Results The thrombosis incidence was significantly higher in the plateau D group than in B group,accompanied by a marked increase in blood viscosity and hematocrit(P＜0.01).Additionally,levels of ET-1,IL-6,and TF were significantly elevated(P＜0.05),indicating a coagulation disorder.Conclusions A plateau hypoxic environment model can be successfully simulated by quantitative coarctation of the inferior vena cava,combined with a specialized environmental chamber.The findings of this study suggest that a plateau hypoxic environment promotes venous thrombosis.

Objective To establish a rat model of venous thrombosis in a plateau hypobaric hypoxic environment and to investigate the effect of this environment on venous thrombosis.Methods A total of 144 healthy male SD rats were assigned randomly to four groups(n=36 rats per group):a plains sham operation(A)group,plains operation(B)group,plateau altitude 6000 m+sham operation(C)group,and plateau altitude 6000 m+surgery(D)group.Rats in A and B groups were maintained in a plains normoxic environment,while rats in C and D groups C and D were subjected to a plateau environment.Rats in the surgical groups underwent quantitative constriction to incompletely obstruct the inferior vena cava blood flow.Each group was further divided into subgroups based on time:1,3,5,7,14,and 21 d(n=6 rats per group).Regular vascular ultrasound monitoring was conducted,and blood samples were taken for whole blood viscosity testing and the assessment of inflammatory indicators,including endothelin-1(ET-1),interleukin-6(IL-6)and tissue factor(TF).Coagulation function was evaluated through the activated partial thromboplastin time(APTT),prothrombin time(PT),thrombin time(TT),fibrinogen(FIB)and D-dimer.After the observation period,the experimental animals were sacrificed and the limbs were removed.Thrombus samples were stained with hematoxylin/eosin(HE),and the thrombus wet mass was measured.Results The thrombosis incidence was significantly higher in the plateau D group than in B group,accompanied by a marked increase in blood viscosity and hematocrit(P＜0.01).Additionally,levels of ET-1,IL-6,and TF were significantly elevated(P＜0.05),indicating a coagulation disorder.Conclusions A plateau hypoxic environment model can be successfully simulated by quantitative coarctation of the inferior vena cava,combined with a specialized environmental chamber.The findings of this study suggest that a plateau hypoxic environment promotes venous thrombosis.

Objective:To understand the development status of maternal and child health care institutions in China from 2012 to 2022, identify the challenges they face, and provide references for further promoting the high-quality development of these institutions.Methods:Data from the China Health Statistics Yearbook (2013—2015), China Health and Family Planning Statistics Yearbook (2016—2017), and China Health and Wellness Statistics Yearbook (2018—2023) were used. Descriptive analysis was conducted on the data related to resource allocation and utilization efficiency, service provision, income and expenditure structure, and operational status of maternal and child health care institutions in China from 2012 to 2022, using methods such as fixed-base growth rate, year-on-year growth rate, and average annual growth rate. Results:From 2012 to 2022, the number of maternal and child health care institutions in China decreased from 3 044 to 3 031. In terms of resource allocation, the average annual growth rates of bed numbers and business-use floor area were 5.404% and 10.923%, respectively, while the average annual growth rate of health professionals was 7.183%. Regarding service provision, the average annual growth rates of outpatient visits and inpatient admissions were 3.954% and 1.572%, respectively. In terms of service efficiency, the bed occupancy rate decreased from 76.9% to 53.9%, and the average number of patients seen per physician per day decreased from 8.85 to 7.30. In terms of income and expenditure and operations, the income-expenditure surplus rate decreased from 9.16% to 5.41%, and the debt-to-asset ratio increased from 27.88% to 33.60%. During the same period, the average annual growth rates of bed numbers and business-use floor area in grassroots maternal and child health care institutions were 4.545% and 10.091%, respectively, lower than the national average. The number of outpatient visits increased from 89.03 million to 126.93 million, with an average annual growth rate of 3.610%, while the number of inpatient admissions decreased from 4.19 million to 3.91 million, with an average annual decline of 0.689%. The income-expenditure surplus rate of grassroots institutions decreased from 7.76% to 4.05%, 1.36 percentage points lower than the national level, and the debt-to-asset ratio increased from 27.53% to 36.37%, higher than the overall level.Conclusions:From 2012 to 2022, maternal and child health care institutions in China achieved certain developments in resource allocation and service scale. However, several challenges remain, including unbalanced resource allocation, decreased utilization efficiency, slowed growth in medical service volume, imbalanced income and expenditure structure, increased asset operation risks, and restricted development of grassroots institutions. It is recommended that relevant management departments and maternal and child health care institutions optimize resource allocation, plan for service transformation and upgrading, expand income sources, strengthen internal financial control, and reinforce the construction of high-quality and efficient maternal and child health care systems to promote the high-quality development of maternal and child health care institutions in China.

Oleanolic acid (OA), a pentacyclic triterpenoid, exhibits a broad spectrum of biological activities, including antitumor, antiviral, antibacterial, anti-inflammatory, hepatoprotective, hypoglycemic, and hypolipidemic effects. Since its initial isolation and identification, numerous studies have reported on the structural modifications and pharmacological activities of OA and its derivatives. Despite this, there has been a dearth of comprehensive reviews in the past two decades, leading to challenges in subsequent research on OA. Based on the main biological activities of OA, this paper comprehensively summarized the modification strategies and structure-activity relationships (SARs) of OA and its derivatives to provide valuable reference for future investigations into OA.
Oleanolic Acid ; Structure-Activity Relationship ; Anti-Inflammatory Agents/pharmacology* ; Triterpenes ; Anti-Bacterial Agents/pharmacology*

Objective:To analyze the risk factors of multidrug-resistant organism（MDRO）infection among patients in neurosurgery intensive care unit（NSICU）and to construct a risk prediction nomogram.Methods:A total of 434 patients admitted in the NSICU of the First Affiliated Hospital of Kangda College of Nanjing Medical University from August 2021 to October 2022 were enrolled in the study. Patients were divided into modeling group（ n=217）and validation group（ n=217）. Multivariate Logistic regression was used to analyze the risk factors of MDRO infection in patients，and R software was used to construct a risk prediction nomogram.The prediction power of the nomogram was evaluated with receiver operating characteristic（ROC）curve，the calibration of the model was assessed with Hosmer-Lemeshow（H-L）goodness-of-fit method. Results:Multivariate Logistic regression analysis showed that the underlying disease≥3（ OR=2.580，95% CI 1.322-5.035），the combination of antimicrobial drugs >10 days（ OR=2.336，95% CI 1.182-4.615），hypoproteinemia（ OR=1.962，95% CI 1.031-3.735），invasive operation time（10-20 d： OR=2.358，95% CI 1.048-5.306；>20 d： OR=3.486，95% CI 1.643-7.395）and GCS≤8 points（ OR=2.961，95% CI 1.470-5.963）were independent risk factors of MDRO infection among patients in NSICU. The area under the curve（AUC）of the nomogram in predicting the risk of MDRO infection for patients in modeling group was 0.787（95% CI 0.725-0.849）with a sensitivity of 73.3% and a specificity of 72.5%，the H-L test results were χ2=7.482， P=0.486，the calibration curve was close to the ideal curve，and the mean absolute error was 0.022. The AUC of the nomogram in predicting MDRO infection for patients in verification group was 0.800（95% CI 0.739-0.861）with a sensitivity of 74.7% and a specificity of 73.9%，the H-L test results were χ2=9.824， P=0.278，the calibration curve was close to the ideal curve，and the average absolute error was 0.015. Conclusion:The nomogram constructed based on the risk factors can effectively predict the risk of MDRO infection for patients in neurosurgical ICU，which may be used in clinic pratcice.

Objective To analyze the characteristics of visceral leishmaniasis cases in Henan Province, so as to provide insights into formulation of the visceral leishmaniasis control srtrategy. Methods All epidemiological data of reported visceral leishmaniasis cases in Henan Province from 2021 to 2023 were retrieved from the National Notifiable Disease Report Information Management System of Chinese Center for Disease Control and Prevention, and the epidemiological features and diagnosis of visceral leishmaniasis cases were descriptively analyzed. Results A total of 93 visceral leishmaniasis cases were reported in Henan Province from 2021 to 2023, with a male to female ratio of 2.58∶1, and including 2 imported cases from other provinces and 91 local cases. The number of visceral leishmaniasis cases peaked during the period between March and May, and between July and October. The reported visceral leishmaniasis cases had ages of 7 months to 74 years, with the largest number of cases found at ages of 0 to 9 years (26 cases, 27.96%), followed by at ages of 60 to 70 years (24 cases, 25.81%). Farmer (47 cases, 50.54%) and diaspora children (19 cases, 20.43%) were predominant occupations, and 91 local visceral leishmaniasis cases were found in 6 cities of Zhengzhou, Luoyang, Anyang, Hebi, Sanmenxia and Xuchang. The median duration from onset of visceral leishmaniasis to diagnosis was 20 days, and there were 25.81% (24/93) cases with 10 days and less duration from onset to diagnosis, 38.71% (36/93) cases receiving diagnosis at 11 to 30 days following onset, and 35.48% (33/93) cases receiving diagnosis for more than 30 days following onset. All cases were predominantly diagnosed in province- (60.00%) and city-level (28.89%) medical institutions. Conclusions The number of visceral leishmaniasis is on the rise in Henan Province, with a gradually expanding coverage. Intensified monitoring of visceral leishmaniasis cases, dogs, and vectors, dog management, sandflies control and improved individual protection are recommended to prevent the spread of visceral leishmaniasis.