OBJECTIVE To determine the contents of 15 components in Aurantii Fructus Immaturus from different origins （Citrus aurantium， C. junos， C. aurantium Linn.， C. sinensis Osb.， C. sinensis）， screen differential components， and provide references for the quality evaluation of Aurantii Fructus Immaturus. METHODS HPLC method was adopted to determine the contents of synephrine， N-methyltyramine， 5，7-dihydroxychromone-7-neohesperidoside， neoponcirin， narirutin， naringin， hesperidin， neohesperidin， naringenin， hesperetin， sinensetin， nobiletin， tangeretin， 5-demethylnobiletin， and auraptene in 46 batches of Aurantii Fructus Immaturus from different origins. The determination was performed on Waters Symmetry C18 column with mobile phase consisted of acetonitrile-0.1% formic acid （gradient elution） at the flow rate of 1.0 mL/min； column temperature was set at 40 ℃ ， detection wavelength was 284 nm， and sample injection volume was 5 μL. The differences between different origins of Aurantii Fructus Immaturus were analyzed by cluster analysis， principal component analysis （PCA） and orthogonal partial least squares-discriminant analysis （OPLS-DA）， and differential components were screened. RESULTS The linear relationships of the aforementioned 15 components were all good within the tested mass concentration ranges （all r＞0.999 0）. The RSDs for precision， stability （24 h）， and repeatability tests were all less than 2.00%. The average recovery rate ranged from 91.1% to 103.9% （all RSDs＜3.10%）. Cluster analysis， PCA， and OPLS-DA revealed that C. sinensis Osb. and C. sinensis were clustered into one category， while C. aurantium，C. junos and C. aurantium Linn. were clustered into another category. The variable importance projection values for neohesperidin， auraptene， naringin， neoponcirin， tangeretin， hesperidin， sinensetin， and 5，7-dihydroxychromone-7-neohesperidoside were all greater than 1. CONCLUSIONS In this study， the contents of 15 components in Aurantii Fructus Immaturus from different origins are determined， and 8 differential components， including neohesperidin， auraptene， naringin， and neoponcirin， are screened out.

ObjectiveTo investigate the possible mechanism of Shufeng Jiedu capsules （SFJD） in alleviating influenza A （H1N1） virus pneumonia and focus on its effect on Toll-like receptor （TLR） signaling pathway in respiratory epithelial cells. MethodsA mouse model of viral pneumonia was established via the A/PR/8/34 （PR8） strain of influenza A virus. Mice were randomly divided into a normal group， a PR8 infection （PR8） group， and an SFJD group （8.4 g·kg^-1）， with 10 mice in each group. The day of infection was designated as day 1. The SFJD group was administered intragastrically at a volume of 20 mL·kg^-1 daily， while the normal and PR8 groups were given an equal volume of deionized water. Micro-computed tomography （Micro-CT） was performed on day 5， and the mice were dissected to collect their lungs， after which the lung index was calculated to verify the therapeutic effect of SFJD. Single-cell sequencing was used to analyze the differentially expressed genes in respiratory epithelial cells. Multiplex fluorescence immunohistochemistry was employed to detect the expression of TLR， tumor necrosis factor receptor-associated factor 6 （TRAF6）， and myeloid differentiation factor 88 （MyD88） proteins in epithelial cell adhesion molecule （EpCAM）-positive cells， and the proportion of respiratory epithelial cells expressing TLR pathway proteins was calculated. Respiratory epithelial cells were then sorted by flow cytometry， and Western blot was used to detect the expression of TLR， MyD88， TRAF6， Toll-interleukin receptor domain-containing adaptor inducing interferon-β （TRIF）， inhibitor of κB kinase α （IKKα）， and nuclear factor-κB （NF-κB） in the sorted epithelial cells. Enzyme-linked immunosorbent assay （ELISA） was used to measure the levels of interleukin-1β （IL-1β） and tumor necrosis factor-α （TNF-α） in lung tissue. ResultsAt the transcriptional level， SFJD reversed the expression of TLR signaling pathway genes in respiratory epithelial cells， downregulating multiple TLR signaling pathway-related genes （P<0.01）. At the protein level， SFJD significantly reduced the proportion of respiratory epithelial cells expressing TLR3 （P<0.05）， the expression levels of TLR2， TLR3， TLR4， TRIF， TRAF6， IKKα， and NF-κB in epithelial cells（P<0.05， P<0.01）， as well as the levels of pro-inflammatory cytokines IL-1β and TNF-α in lung tissue （P<0.01）. ConclusionSFJD may alleviate viral pneumonia by suppressing the expression of TLR in respiratory epithelial cells and their subsequent signaling cascades.

IKBKG is the essential modulator for nuclear factor-κB(NF-κB) signaling pathway, and mutations within this gene can lead to anhidrotic ectodermal dysplasia and immunodeficiency (EDA-ID). Here we report a male patient, who presented with mild frontal bossing, sparse hair, skin pigmentation, conical teeth, and recurrent infections involving bacteria, fungi, and viruses after one month of age, together with hypogammaglobulinemia. These symptoms were consistent with the phenotype of EDA-ID. Genetic analysis revealed a hemizygous mutation c.1249T > G (p.Cys417Gly) in exon 10 of the IKBKG gene in the patient. The mother of the patient was identified as heterozygous carriers of the same mutation. Immunological assessment revealed a significant reduction in memory B cells. The patient showed no skewed TCR diversity. PHA-induced T-cell proliferation was impaired. IFN-γ secretion by Th cells was significantly reduced after PHA stimulation. IκBα degradation rate retained the same in the patient. We summarized the clinical features of the patient and conducted immunological analysis, in order to increase pediatricians′awareness of this rare disease. For boys with early-onset recurrent infections together with ectodermal dysplasia, IKBKG mutation should be considered. In addition, genetic analysis is needed to exclude pseudogene interference and functional evaluations are required.

Objective: To investigate the incidence and influencing factors of falls among the elderly in Ningbo City, Zhejiang Province, so as to provide the basis for developing effective prevention strategies. Methods: The residents aged 60 years and above in Haishu District and Yuyao City of Ningbo City were selected by the multi-stage cluster random sampling method from June to October 2022. Demographic information, fall incidence in the past year, history of disease and self-rated health were collected through questionnaire surveys. Incidence of falls was descriptively analyzed, and factors affecting falls were identified using a multivariable logistic regression model stratified by gender and age. Results: A total of 1 275 elderly people were surveyed, including 635 men and 640 women. The median age was 72.00 (interquartile range, 13.00) years. In the past year, 158 residents fell, accounting for 12.39%. Additionally, 14 individuals experienced two or more falls, accounting for 8.86%. The incidence of falls was 14.69% in women, which was higher than the 10.08% in men (P<0.05). The incidence of falls was 14.86% in the elderly over 70 years, which was higher than the 9.39% in those aged 60 to 70 years (P<0.05). Multivariable logistic regression showed that the educational level (primary school and above, OR=0.501, 95%CI: 0.301-0.836), heart disease (present, OR=1.996, 95%CI: 1.076-3.703), and self-rated health status (good, OR=0.529, 95%CI: 0.319-0.875) were factors affecting falls in women; educational level (primary school and above, OR=0.514, 95%CI: 0.285-0.928) and self-rated health status (good, OR=0.456, 95%CI: 0.253-0.824) were factors affecting falls in residents aged 60 to 70 years. Conclusion Fall risk among the elderly is associated with gender, age, heart disease, educational level and self-rated health status, and the influencing factors for falls vary in different genders and ages.

Objective To investigate the epidemiological characteristics and changing trend of malignant tumor death in Danjiangkou City, the water source area along the middle route of South-to-North Water Diversion Project. Methods The surveillance data of cancer death cases in Danjiangkou City from 2015 to 2022 were collected, and the mortality rate, gender mortality rate, age-specific mortality rate and the rank of cancer cause of death were calculated. Joinpoint regression model was used to analyze the trend of malignant tumor mortality and standardized mortality. Annual percentage change (APC) and average annual percentage change (AAPC) were calculated to analyze the trend changes. Results From 2015 to 2022, a total of 6 254 deaths from malignant tumors were reported in Danjiangkou City, with a crude mortality rate of 178.57/100 000 and a standardized mortality rate of 152.77/100 000. There were 4 366 male deaths, and the crude mortality and standardized mortality were 244.70/100 000 and 212.87/100 000 , respectively. There were 1 888 female deaths, and the crude mortality rate and the standardized mortality rate were 109.89/100 000 and 92.69/100 000, respectively. The crude death rate of malignant tumors in the whole population in Danjiangkou City showed an increasing trend from 2015 to 2022, and the difference was statistically significant (AAPC=5.18%, t=4.07, P<0.05). The crude mortality rates of malignant tumors in both men and women showed an upward trend, and the differences were statistically significant (AAPC =5.56% and 4.35%, both P<0.05). The standardized mortality rates of malignant tumors in the whole population, women and men remained stable, and the differences were not statistically significant (AAPC=0.68, 1.59 and -0.74, all P>0.05). The trend analysis of age-specific mortality of malignant tumors showed that the age-specific mortality of malignant tumors in the whole population, men and women showed an increasing trend with age, and the differences were statistically significant (AAPC =9.22%, 9.40% and 8.53%, P<0.05). The mortality rate of malignant tumors in 0-, 1-, 10-, 45- and 70- age groups decreased year by year (AAPC =-79.62%, -7.19%, -65.99%, -8.88%, and -5.83%, all P<0.05). The mortality rate in the age group of over 75 years old showed an increasing trend (AAPC =12.24%, P<0.05), and the differences were statistically significant. The top 10 malignant tumor deaths in the whole population were lung cancer, gastric cancer, liver cancer, esophageal cancer, colorectal cancer , leukemia , pancreatic cancer , breast cancer , brain malignant tumor and cervical cancer, accounting for 88.49% of all malignant tumor deaths. Mortality rates in lung cancer (AAPC =6.75%), esophageal cancer (AAPC=11.24%), colorectal cancer (AAPC =12.95%), leukemia (AAPC=8.10%), pancreatic cancer (AAPC=15.11%), breast cancer (AAPC=13.11%) and brain malignancies (AAPC=11.16%) showed an increasing trend, and the differences were statistical significant (P<0.05). Conclusion Malignant tumor is the main cause of death in Danjiangkou City. The death rate increases year by year and increases with age. Lung cancer, stomach cancer and liver cancer are the main causes of death. Men and the elderly are high-risk groups of malignant tumors. Early detection and treatment of malignant tumors should be strengthened to reduce the incidence and death.

ObjectiveTo investigate the effect of Fuzheng Huayu prescription on hepatocyte extinction and regeneration in fibrotic liver and its mechanism of action in promoting hepatocyte regeneration. MethodsMice were given intraperitoneal injection of CCl₄ for 6 weeks to establish a model of liver cirrhosis， and there were 10 mice in the model group， 10 in the sorafenib group， 10 in the Fuzheng Huayu prescription group， and 9 in the normal control group. Since week 4 of modeling， the mice in the Fuzheng Huayu prescription group and the sorafenib group were given the corresponding drug by gavage at a dose of 4.8 g/kg and 4 mg/kg， respectively， for three consecutive weeks， and those in the normal group and the model group were given an equal volume of sodium carboxymethyl cellulose. Serum liver function parameters were measured； the METAVIR scoring system was used to evaluate liver inflammation and fibrosis stage； Sirius Red staining and hydroxyproline （Hyp） content in liver tissue were used to evaluate collagen deposition； immunohistochemistry was used to measure the protein expression levels of type IV collagen， CD31， CD32b， Ki67， CyclinD1， glutamine synthetase， Wnt2， and HGF， and Western blot was used to measure the expression levels of Wnt2， LRP6， β-catenin， p-β-catenin， and CyclinD1 in liver tissue. A one-way analysis of variance was used for comparison of continuous data between multiple groups， and the least significant difference t-test was used for further comparison between two groups. ResultsCompared with the model group， the Fuzheng Huayu prescription group and the sorafenib group showed the following changes： significant reductions in the serum levels of alanine aminotransferase and aspartate aminotransferase and the content of Hyp in liver tissue （all P<0.01）； a significant reduction in METAVIR score； significant reductions in the expression levels of type Ⅳ collagen and CD31 （all P<0.05） and a significant increase in the expression level of CD32b （P<0.01）； significant reductions in the number of parenchymal extinction lesions and significant increases in the expression levels of Ki67 and CyclinD1 in liver tissue （all P<0.01）； significant increases in the protein expression levels of Wnt2， LRP6， β-catenin， and CyclinD1 and a significant reduction in the protein expression level of p-β-catenin （all P<0.05）； significant increases in the number of cells stained positive for both CD32b and Wnt2. ConclusionFuzheng Huayu prescription can inhibit hepatic sinusoidal capillarization， improve the Wnt2 exocrine function of liver sinusoidal endothelial cells， activate the Wnt/β-catenin signaling pathway associated with hepatocyte regeneration， and finally reverse liver cirrhosis.

Objective To investigate the effect and mechanism of colchicine on mouse liver cancer via Hippo sig-naling pathway.Methods The 6-week-old male C57BL/6J mice were randomly divided into 3 groups:diethylni-trosamine(DEN)/carbon tetrachloride(CCl4)/ethanol(C2H5OH)induced mouse liver cancer model and col-chicine(0.1 mg/kg)intervention were established in control group,model group and colchicine group.From week 1st to week 2nd,the model group and the colchicine group were intraperitoneally injected with 1.0％DEN once a week.From week 3rd to week 7th,20％CCl4 dissolved in olive oil solution(5 ml/kg)was intragastric ad-ministration twice a week.From week 8th to week 18th,20％CC14 dissolved in olive oil solution(6 ml/kg)was intragastric twice a week.The colchicine group was given continuous intragastric administration for 20 weeks.The control group was given the corresponding solvent.Liver index,alanine aminotransferase(ALT)and aspartate ami-notransferase(AST)serum biochemical indexes were detected.Western blot and immunofluorescence were used to detect the expression levels of MST1,pYAP,YAP,pTAZ and TAZ proteins in liver tissues of mice in each group.Results The liver surface of mice in the control group was smooth and soft,while the liver of mice in the model group was rough and hard with granular nodules.The above lesions were significantly improved in the colchicine group.HE staining showed that the liver lobular structure of mice in the control group was normal,while the liver lobular structure of mice in the model group was disordered,with a small amount of fat droplets,extensive tissue necrosis,inflammatory cell infiltration,and fat vacuoles.The degree of liver lesions of mice after colchicine inter-vention was significantly reduced.The results of immunofluorescence and Western blot showed that compared with the control group,the protein expression levels of pYAP and pTAZ in liver tissue of model group mice were signifi-cantly decreased,while the protein expression levels of MST1,YAP and TAZ increased.After colchicine interven-tion,the protein expression levels of MST1,pYAP and pTAZ were significantly up-regulated,while the protein ex-pression levels of YAP and TAZ were down-regulated.Conclusion The therapeutic effect of colchicine on mouse liver cancer may be related to its activated Hippo signaling pathway.

Objective:To investigate the efficacy and safety of intravenous thrombolysis and antiplatelet therapy in patients with stroke warning syndrome (SWS), as well as influencing factors of the outcome in patients with SWS.Method:Patients with SWS admitted to the 521 st Hospital of Ordnance Group from June 1, 2018 to December 31, 2023 were retrospectively included. Some patients were treated with ateplase intravenous thrombolysis, followed by oral antiplatelet therapy; some patients only received antiplatelet therapy. The main outcome measure was the modified Rankin Scale score at 90 days after onset, with a score of 0-2 defined as good outcome. Results:A total of 35 patients with SWS were included, including 26 males (74.3%) with an age of 58.29±11.06 years. Nineteen patients (54.3%) received intravenous thrombolysis, and 27 (77.1%) had good outcome at 90 days. There was no statistically significant difference in demographic, baseline data, and good outcome between the intravenous thrombolysis group and the antiplatelet therapy group. One patient had new stroke and one had transient ischemic attack in the intravenous thrombolysis group. There were statistically significant differences in ABCD2 score, systolic blood pressure, low-density lipoprotein cholesterol, fasting blood glucose, highest National Institutes of Health Stroke Scale (NIHSS) score at onset, and symptom duration between the good outcome group and the poor outcome group (all P<0.05). Conclusions:The efficacy of intravenous thrombolysis is similar to that of antiplatelet drugs alone in treating SWS. ABCD2 score, systolic blood pressure, low-density lipoprotein cholesterol, fasting blood glucose, highest NIHSS score at onset, and duration of symptoms may be influencing factors for the outcome of patients with SWS.

The United States has established a perfect specialist training system for developmental and behavioral pediatrics (DBP), while the DBP specialist training system in China is still in the early stage of development and has been constantly improved. This article analyzes and compares the current status of DBP specialist training system between the United States and China from the aspects of training pattern, eligibility criteria, training plans and contents, assessment and evaluation, and certification. With reference to the training system in the United States, we can further improve the DBP specialist training system in China by perfecting the training system and related documents, constructing reasonable eligibility criteria, establishing a training pattern guided by post competency, improving the DBP assessment and evaluation system based on competency, and enhancing the certification of DBP physicians.

Objective:To construct an evaluation indicator system for the efficiency of nursing human resources in integrated medical and elderly care institutions using Data Envelopment Analysis (DEA) and subsequently evaluate its effectiveness.Methods:This cross-sectional survey utilized literature review and investigative methods to initially establish a library of evaluation indicators for nursing human resource efficiency. The Delphi method was employed in two rounds of consultations with 17 experts from various fields, including nursing management, elderly care institution management, integrated medical and elderly care institution management, health economics management, and public health. The reliability of the indicator system was assessed based on factors such as expert enthusiasm, authority, concentration of opinions, and coordination. Adjustments, modifications, and improvements were made to the indicators based on expert opinions to establish the final indicator system. From August to December 2022, the DEA model was applied to evaluate the efficiency of 12 integrated medical and elderly care institutions in Haikou city based on this indicator system.Results:The constructed evaluation indicator system comprised 68 items divided into three levels: 9 primary indicators, 19 secondary indicators, and 40 tertiary indicators. The positive coefficients of the two rounds of expert consultations were 100% and 94.1%, with authority coefficients of 0.88 and 0.92, Kendall harmony coefficients of 0.471 and 0.348, and mean coefficients of variation of 0.16 and 0.12 ( P<0.001). DEA evaluation results for the 12 integrated medical and elderly care institutions showed that 5 were DEA effective institutions with comprehensive efficiency (OE), technical efficiency (TE), and scale efficiency (SE) values all equal to 1.000, while 7 were non-DEA effective institutions, including 4 with SE <1.000 but TE=1.000 and 3 with both SE and TE<1.000. Conclusions:The constructed evaluation indicator system demonstrates high enthusiasm, authority coefficients, and coordination in expert consultations, indicating high acceptability and comprehensive content with distinct levels and strong specialty characteristics. The DEA model′s evaluation results objectively and effectively reflect the efficiency of nursing human resources in integrated medical and elderly care institutions, demonstrating practical utility.