ObjectiveTo investigate the improvement effect of Qibai Pingfei capsules on pulmonary vascular remodeling in rats at different stages of chronic obstructive pulmonary disease （COPD） and to analyze its possible mechanism of action. MethodsMale Sprague-Dawley （SD） rats were randomly divided into a normal group， an early COPD model group， an advanced COPD model group， an early-intervention high-dose group， a late-intervention high-dose group， an early-intervention low-dose group， a late-intervention low-dose group， an early-intervention pyrrolidine dithiocarbamate （PDTC） group， and a late-intervention PDTC group， with 15 rats in each group. A rat model of early COPD was constructed by using cigarette smoke combined with airway infusion using lipopolysaccharide（LPS）， and a rat model of advanced COPD was constructed by using airway infusion with LPS， cigarette smoke， and hypoxia. All groups except the normal group were given LPS airway drops on days 1 and 14 of the experiment， smoked for 1 h per day， and administered the drug once a day for 40 weeks from day 15 onward. In the high- and low-dose groups， rats were given 1 g·kg^-1 and 250 mg·kg^-1 Qibai Pingfei capsules， respectively by gavage， and in PDTC groups， rats were given 100 mg·kg^-1 of PDTC by intraperitoneal injection. The advanced COPD model group underwent 6 h of hypoxia per day in weeks 5-6. Lung function and mean pulmonary artery pressure were tested in rats. Morphologic changes in lung tissues were detected by hematoxylin-eosin（HE）staining. Collagen deposition in lung tissues was examined by Masson staining， and the levels of inflammatory factors including interleukin-1β（IL-1β）， interleukin-6（IL-6）， and tumor necrosis factor-α（TNF-α）in lung tissues were detected by enzyme-linked immunosorbent assay （ELISA）. The number of inflammatory cells in the alveolar lavage fluid of rats in each group was detected by Giemsa staining， and the protein expression of Toll-like receptor 4（TLR4）， myeloid differentiation factor 88（MyD88）， nuclear factor-κB（NF-κB）， TNF-α， vascular endothelial-cadherin（VE-cadherin）， α-smooth muscle actin（α-SMA）， and platelet endothelial cell adhesion molecule-1（CD31） was detected by Western blot in the lung tissues of rats. ResultsCompared with the normal group， the model group showed significantly decreased forced expiratory volume in 0.3 s （FEV_0.3）， forced vital capacity （FVC）， and FEV_0.3/FVC ratio related to lung function （P<0.05）， thickening of pulmonary vasculature， increased collagen deposition in the lungs， and enhanced mean pulmonary arterial pressure and expression levels of IL-6， IL-1β， and TNF-α （P<0.05）. Additionally， the model group also exhibited increased numbers of macrophages， lymphocytes， and neutrophils （P<0.05）， significantly higher protein expression of TLR4， MyD88， NF-κB， TNF-α， and α-SMA （P<0.05）， and significantly lower protein expression of VE-cadherin and CD31 （P<0.05）. Lung function was significantly improved in the Qibai Pingfei capsules groups compared with the model group （P<0.05）， with mean pulmonary arterial pressure reduced and pulmonary vascular thickening and collagen deposition in the lungs ameliorated. The Qibai Pingfei capsules groups also showed reduced expression levels of IL-6， IL-1β， and TNF-α （P<0.05） and decreased numbers of macrophages， lymphocytes， and neutrophils （P<0.05）， as well as reduced protein expression of TLR4， MyD88， NF-κB， TNF-α， and α-SMA （P<0.05） and elevated protein expression of VE-cadherin and CD31 （P<0.05） in rat lung tissues. ConclusionQibai Pingfei capsules inhibits inflammatory response and endothelial-to-mesenchymal transition probably by regulating the TLR4/NF-κB signaling pathway， thus improving pulmonary vascular remodeling in COPD model rats and showing therapeutic effects in the early stage of COPD.

Objective To evaluate the cost-effectiveness of roxadustat and darbepoetin alfa on treating renal anemia in dialysis-dependent chronic kidney disease(DD-CKD)patients,thus providing health economics reference for treatment of renal anemia.Methods A Markov model simulating the development and treatment of anemia in DD-CKD patients in a lifetime horizon(20 years)was constructed.Total costs of roxadustat and darbepoetin alfa injection were estimated from the perspective of Chinese healthcare system,with health outcomes converted into quality-adjusted life year(QALY).The incremental cost-effectiveness ratio(ICER)was used to describe the results.The willingness-to-pay(WTP)threshold was set at 257 094 yuan,which was three times China's gross domestic product(GDP)per capita in 2023.Sensitivity analyses were performed to test the uncertainties of the results.Results The total treatment costs of roxadustat and darbepoetin alfa injection were 111 902.41 yuan and 52 927.92 yuan respectively,corresponding to QALY values of 4.76 and 4.74 life-years.The incremental cost-effectiveness(ICER)was 2 654 912.45 yuan/QALY,which exceeded 3 times GDP per capita.Therefore,compared with darbepoetin alfa injection,roxadustat has no cost-effectiveness for patients with DD-CKD.Conclusion In the context of current economic development in China,darbepoetin alfa injection is more cost-effective than roxadustatin for treating anemia in DD-CKD patients.

Objective:To analyze assessment value of the hemodynamics of posterior cerebral artery(PCA)detected by transcranial color-coded Doppler(TCCD)ultrasound for occurring cerebral infarction in patients with fetal-type posterior cerebral artery(FTP).Methods:A total of 300 patients with suspected cerebrovascular disease admitted to the Department of Neurology of The Second Hospital of Harbin City from January,2020 to December 31,2023 were retrospectively selected.In these patients,7 cases with cerebral hemorrhage(without complication of cerebral infarction)did not be included.According to the clinical manifestations and the results of imaging examination,293 patients were divided into transient ischemic attack(TIA)group(176 cases)and acute ischemic stroke(AIS)group(117 cases).The differences in FTP detection between TCCD examination and magnetic resonance angiography(MRA)were compared.The differences in PCA hemodynamics among TIA,anterior circulation infarction,posterior circulation infarction and lacunar infarction were compared.The proportions of patients with TIA,anterior circulation infarction,posterior circulation infarction and lacunar infarction combined with FTP were also compared,and the PCA hemodynamics of patients with posterior circulation infarction of bilateral cFTP,unilateral cFTP,bilateral pFTP,unilateral pFTP and nFTP were compared.The proportions of patients with transient ischemic attack(TIA)who occurring AIS at bilateral cFTP,unilateral cFTP,bilateral pFTP,unilateral pFTP and nFTP in short term were compared.The receiver operating characteristic(ROC)curve and area under curve(AUC)were used to assess the predictive value of abnormal PCA hemodynamics of TIA patients,who combined with and/or without FTP,occurred AIS in short term.Results:MRA revealed that a total of 89 patients combined with FTP in 293 patients,of which 14 cases were bilateral cFTP(accounting for 15.73%),and 25 cases were unilateral cFTP(accounting for 28.09%),and 8 cases were bilateral pFTP(accounting for 8.99%),and 42 cases were unilateral pFTP(accounting for 4 7.19%).According to TCCD testing,it was found that a total of 89 cases combined with FTP in 293 patients,of which 16 cases were bilateral cFTP(accounting for 17.98%),and 23 cases were unilateral cFTP(accounting for 25.84%),and 8 cases were bilateral pFTP(accounting for 8.99%),and 42 cases were unilateral pFTP(accounting for 47.19%).There was favorable consistency between TCCD and MRA(Kappa=0.899).Under TCCD,the blood flow velocity(Vp)and resistance index(RI)of systolic stage of PCA in patients with posterior circulation infarction were significantly higher than those in patients with TIA,anterior circulation infarction,and lacunar cerebral infarction(F=15.392,9.032,P<0.05),respectively.Patients with posterior circulation infarction were more likely to occur bilateral cFTP.The Vp,Vm and Vd of patients with bilateral cFTP were significantly higher than those of patients with bilateral pFTP,unilateral pFTP and non-FTP(F=14.932,8.884,6.054,P<0.05),respectively.The proportion of occurring AIS in TIA patients with bilateral cFTP was significantly higher than that in TIA patients with unilateral cFTP,bilateral pFTP,unilateral pFTP and nFTP(Z=6.883,7.568,6.253,6.772,P<0.05),and the proportions of occurring AIS in TIA patients with unilateral cFTP,bilateral pFTP and unilateral pFTP were significantly higher than that in TIA patients with nFTP(Z=5.986,6.877,6.856,P<0.05),respectively.A total of 45 cases(accounting for 25.57%)of 176 TIA patients occurred AAIS within 3 months after they discharged.The AUC value of predictive value of Vp for occurring AIS in 45 TIA patients with FTP was 0.818,which was significantly higher than that(AUC=0.589)for occurring AIS in 131 TIA patients with non-FTP.Conclusion:Patients with posterior circulation cerebral infarction are prone to occur PCA hemodynamic abnormalities.In patients with posterior circulation infarction,the PCA blood flow velocity in patients with bilateral cFTP significantly accelerates.PCA hemodynamic ultrasound examination has a certain of predictive value for occurring AIS in short term in TIA patients who combine with FTP.

ObjectiveTo decipher the mechanism of Wenxiao powder in alleviating corticosterone-induced depression-like behaviors in mice. MethodMale ICR mice were randomized into normal， model， paroxetine （20 mg·kg^-1）， and low- and high-dose （3.27， 6.54 g·kg^-1， respectively） Wenxiao powder groups. The mice in normal and model groups received equal volume of saline. Other groups except the normal group were injected with corticosterone subcutaneously 0.5 h after gavage to induce depression. Mice were tested for depression-like behaviors after drug administration. Enzyme-linked immunosorbent assay （ELISA） was performed to measure the corticosterone content in the serum. Nissl staining was performed to observe the damage of hippocampal neurons. Immunofluorescence staining was employed to observe the expression of double cortin （DCX） in the dentate gyrus （DG） of the hippocampus. Western blot was employed to determine the expression of proteins in the brain-derived neurotrophic factor （BDNF）/tyrosine kinase receptor B （TrkB）/extracellular signal-regulated kinase （ERK）/cAMP-response element-binding protein （CREB） pathway in the hippocampus. ResultCompared with the normal group， the model group showed decreased sucrose preference rate， increased immobility time in the tail suspension test （P<0.01）， and reduced residence time in the central area of the open field and the total movement distance （P<0.05， P<0.01）. In addition， the modeling elevated the corticosterone level in the serum （P<0.01）， decreased the volume and intensified the nuclear staining of hippocampal neurons in the DG area， reduced the expression of DCX in the DG area， and down-regulated the protein levels of BDNF， phosphorylated （p）-TrkB， p-ERK， and p-CREB in the hippocampus （P<0.05， P<0.01）. Compared with the model group， low-dose Wenxiao powder improved the mouse behavivors in the sucrose preference， open field， and tail suspension tests （P<0.05， P<0.01）， and high-dose Wenxiao powder improved the behaviors in the sucrose preference and open field tests （P<0.05， P<0.01）. In addition， Wenxiao powder lowered the serum corticosterone level （P<0.01） and recovered the structure and morphology of neurons with obvious nuclei and presence of Nissl bodies in the DG area of the hippocampus. Moreover， Wenxiao powder at both doses promoted the expression of DCX in the DG area， and high-dose Wenxiao powder up-regulated the protein levels of BDNF， p-TrkB， p-ERK， and p-CREB in the hippocampus （P<0.05， P<0.01）. ConclusionWenxiao powder can alleviate corticosterone-induced depression-like behaviors and promote neurogenesis in mice possibly by activating the BDNF/TrkB/ERK/CREB signaling pathway.

Objective:To analyze the pregnancy outcomes in patients with positive anti-centromere antibodies(ACA)receiving in vitro fertilization(IVF)-embryo transfer(ET)and natural conception.Methods:A case-control study was used to retrospectively analyze the clinical data of 3955 patients who received IVF-ET therapy and had the results of antinuclear antibody(ANA)spectrum at Zhejiang Provincial People's Hospital from June 2016 to June 2023.Patients with positive ACA and negative ACA were matched at a ratio of 1∶3 using propensity score matching.Embryo outcomes of IVF were compared between the two groups,and the impact of different fertilization methods and the use of immunosuppressants on pregnancy outcomes were analyzed using self-matching.The natural conception and disease progress were followed up for ACA-positive patients after IVF failure.Results:The ACA-positive patients accounted for 0.86%of all IVF patients(34/3955)and 2.51%of total ANA-positive IVF patients.Regardless of whether patients received conventional IVF(c-IVF)or intracytoplasmic sperm injection(ICSI),the ACA-positive group exhibited significant differences in oocyte maturity and fertilization compared to the ACA-negative group(both P＜0.01).Moreover,the ACA-positive group had a decreased number of D3 suboptimal embryos and D3 optimal embryos(both P＜0.05).In 5 cases of ACA-positive patients who underwent ICSI cycles,the two pronucleus(2PN)rate did not increase compared to c-IVF cycles(P＞0.05),and there was a decrease in the number of D3 high-quality embryos and D3 suboptimal embryos(both P＜0.05).After 1-2 months of immuno-suppressant treatment,12 ACA-positive patients underwent c-IVF/ICSI again,and there were no changes in egg retrieval and fertilization before and after medication(both P＞0.05),but there was an improvement in the 2PN embryo cleavage rate(P＜0.05).The number of embryos transferred was similar between the ACA-positive and negative groups,but the ACA-positive group had significantly lower embryo implantation rate and clinical pregnancy rate compared to the ACA-negative group(both P＜0.05),with no significant differences in the miscarriage rate between the two groups(P＞0.05).Twenty-seven ACA-positive patients attempted natural conception or artificial insemination after IVF failure,resulting in a total of 7 cases of clinical pregnancy.Conclusions:Serum ACA positivity may disrupt oocyte maturation and normal fertilization processes,with no improvement observed with ICSI and immunosuppressant use.However,ACA-positive patients may still achieve natural pregnancy.

Objective:To investigate the clinical significance of graft-versus host disease (GVHD)accompanied with new T-cell receptor (TCR) genes clonal rearrangement after allogeneic hematopoietic stem cell transplantation (allo-HSCT).Methods:The clinical data of 2 patients admitted to People's Hospital of Henan University from December 2018 to March 2020 who developed GVHD after allo-HSCT accompanied with TCR genes clonal rearrangement were retrospectively analyzed, and the related literatures were reviewed.Results:Patient 1 was diagnosed with peripheral T-cell lymphoma non-specific type (PTCL-NOS), and then developed severe acute GVHD (aGVHD) after identical sibling allo-HSCT, and gradually developed liver chronic GVHD (cGVHD), skin cGVHD and new TCR genes clonal rearrangement. Patient 2 was diagnosed with acute myeloid leukemia (AML)-M 4, and severe aGVHD, hepatic cGVHD, and clonal rearrangement of TCR genes were gradually detected after identical sibling allo-HSCT. Conclusions:The TCR genes clonal rearrangement after allo-HSCT is not necessarily suggestive of tumors, and it may be related to lymphocyte development disorder caused by GVHD, so the comprehensive judgement should be carefully made.

Objective:To study the population distribution of Pomacea spp. in Shandong Province and the risk of angiostrongyliasis cantonensis in the local population, and to provide a basis for scientific prevention and control of related diseases. Methods:From July to December 2021, Yanzhou District of Jining City, Ningyang County of Taian City, and Dongying District of Dongying City were selected as surveillance sites to investigate the population and distribution range of Pomacea spp., live snail samples were collected for morphological and genetic identification, and Pomacea spp. infected with the larva of Angiostrongylus cantonensis was detected by lung test. At the same time, sentinel hospital case surveillance was carried out in Yanzhou District, Jining City, and questionnaire was used to study the local residents' awareness of angiostrongyliasis cantonensis and their personal health behaviors. Results:A total of 312 live snail samples were collected. After morphological identification, they were all Pomacea spp.. After gene sequencing, two populations of Pomacea canaliculata and Pomacea maculata were found. No positive snails infected with Angiostrongylus cantonensis were found. A total of 126 patients with headache as the main neurological symptom were admitted to the sentinel hospital, but there were no monitoring cases that met the inclusion criteria. Among the survey population, 48.38% (134/277) of the respondents had heard of angiostrongyliasis cantonensis, 44.77% (124/277) knew that eating Margarya melanioides might cause angiostrongyliasis cantonensis, and 83.39% (231/277) had no related unhealthy eating behavior. Conclusion:Pomacea spp. is found and reported for the first time in Shandong Province, and there is a risk of population infection with angiostrongyliasis cantonensis.

Objective:To predict the Ki-67 expression grading in patients with mass breast cancer based on multimodal ultrasound features to aid clinical diagnosis and treatment.Methods:Ninety-three female patients (93 masses in total) with breast cancers confirmed by pathological examination were retrospectively included in the Second Affiliated Hospital of Harbin Medical University from September 2017 to September 2020. According to the immunohistochemical results, the patients were divided into Ki-67 high expression group (55 cases) and Ki-67 low expression group (38 cases). The qualitative and quantitative features from two-dimensional gray-scale ultrasound, color Doppler flow imaging (CDFI), shear wave elastography (SWE) and contrast-enhanced ultrasound (CEUS) images of all breast masses were retrospectively analyzed, differential features were analyzed based on logistic regression algorithm. ROC curves and Kappa test were used for the evaluation of diagnosis.Results:The univariate analysis revealed statistically significant differences between the two groups for conventional ultrasound features (size, shape, margins), SWE features (stiff rim sign, Eratio), and CEUS features (perfusion defect, IMAX) (all P<0.05). In the multiple logistic regression analysis, the margins, stiff rim sign, and perfusion defect were the independent factors for predicting the Ki-67 expression (all P<0.05). The performance of the predictive model was 0.882 (95%confidence interval of 0.798-0.940, P<0.05) with the sensitivity of 0.818 and specificity of 0.790. Conclusions:A preliminary analysis of the relationship between multi-modal ultrasound features and Ki-67 expression grading in mass breast cancers was performed based on logistic regression algorithm to provide more imaging information for clinical treatment and prognosis assessment.

Objective:To detect the changes of left ventricular myocardial work parameters, and evaluate the left ventricular systolic function in patients with hyperglycemia during pregnancy by left ventricular pressure-strain loop (PSL).Methods:From June 2021 to March 2022, 97 pregnant women who were admitted to the Second Affiliated Hospital of Harbin Medical University and clinically diagnosed as gestational hyperglycemia were prospectively and randomly selected. According to the blood glucose level, the patients were divided into gestational dominant diabetes mellitus (ODM) group(39 cases) and gestational diabetes mellitus (GDM) group(58 cases). Meanwhile, another 62 healthy pregnant women were selected as control group. The basic clinical data of the pregnant women were collected, and the conventional two-dimensional parameters of the heart were collected. The global longitudinal strain (GLS) was analyzed by two-dimensional speckle tracking technique. Then the cuff blood pressure was used as the left ventricular pressure to construct a non-invasive left ventricular pressure-strain loop. The global myocardial work index (GWI), global constructive work (GCW), global wasted work (GWW) and global work efficiency (GWE) of each group were calculated and compared. The correlation between myocardial performance parameters and GLS, glycated hemoglobin(HbA 1c) were analyzed, and the independent factors affecting left ventricular systolic function were obtained by Logistic regression analysis. Twenty cases were randomly selected from the study subjects, and the intraclass correlation coefficients(ICC) of within the observers and between observers were calculated for repeatability test. Results:①Conventional ultrasound parameters: There were no significant differences among the three groups (all P>0.05). ②GLS and left ventricular myocardial performance parameters: GWI, GWE, GCW and GLS in GDM and ODM groups were significantly lower than those in control group (all P<0.001), GWW was significantly higher than control group ( P<0.001); GWI, GWE, GCW and GLS in ODM group were lower than those in GDM group (all P<0.001), while GWW was higher than control group ( P<0.001). ③GWE, GWI and GCW were negatively correlated with GLS ( r=-0.525, -0.408, -0.435; all P<0.05), GWW was positively correlated with GLS ( r=0.348, P<0.05). GWE, GWI and GCW were negatively correlated with HbA 1c ( r=-0.325, -0.262, -0.250; all P<0.05), while GWW was positively correlated with HbA 1c ( r=0.175, P<0.05). ④GWE, 1 h oral glucose tolerance test and HbA 1c were the influencing factors of left ventricular systolic function in patients with hyperglycemia during pregnancy. ⑤The predictive values of GWI, GWE, GCW, GWW and GLS for cardiac function in patients with gestational hyperglycemia were high, and the predictive value of GWE was the highest (AUC: 0.87, the best truncation value: 94.5%, specificity: 0.76, sensitivity: 0.82) and better than GLS. ⑥The repeatability of myocardial work parameters was better in both groups. Conclusions:Myocardial work parameters obtained by PSL are early and sensitive parameters for evaluating left ventricular systolic function impairment in patients with hyperglycemia during pregnancy which can provide reliable and objective quantitative indicators for early clinical intervention and improvement of prognosis.

Objective:To investigate whether ultrasound features, mammographic features and immunohistochemical indicators show any association with rates of axillary pathologic complete response(pCR) in cN 1 breast cancer patients receiving neoadjuvant chemotherapy(NAC), and to construct prediction models of axillary pCR to predict axillary lymph nodes (ALN) status, so as to select suitable patients for less invasive axillary surgery after NAC. Methods:This retrospective study evaluated 134 consecutive cN 1 breast cancer patients with ALN metastasis who underwent NAC in the Second Affiliated Hospital and Tumor Hospital of Harbin Medical University from July 2020 to July 2022. According to the pathological results of ALN surgery after NAC, the cases were divided into pCR and non pathologic complete respose(npCR) groups. The ultrasound images, mammographic images and immunohistochemical indicators of the two groups were compared. In terms of logistic regression algorithm, the model A(the ultrasound model), the model B(the ultrasound combined with mammography model), the model C(the ultrasound combined with immunohistochemistry model) and the model D(the ultrasound combined with mammography and immunohistochemistry model) were respectively established for predicting the pathological state of axillary lymph nodes in breast cancer patients, ROC curves were plotted to evaluate the performance of the models, and the diagnostic efficiency of different models was compared by Delong′s test. The model with the best predictive performance was shown in a nomogram. Results:①The P values between two groups of the short diameter of ALN, the ratio of long/short diameter of ALN, fatty hilum and central hilar vascularity, mammographic spiculation, estrogen receptor(ER), progesterone receptor(PR), human epidermal growth factor receptor 2(HER2) were <0.05 by the t test and χ 2 test analysis. ②The ratio of long/short diameter and fatty hilum in the model A were independent factors for predicting the pathological status of ALN after NAC. The independent predictors of model B and Model C were respectively added with mammographic spiculation and immunohistochemical indicators (ER, PR) on the basis of model A. In the model D, the ratio of long/short diameter, short diameter, fatty hilum, mammographic spiculation, and immunohistochemical indicators (ER, PR) remained significant independent predictors associated with axillary pCR. ③The area under ROC curve (AUC) of the model A, B, C, D was 0.78, 0.84, 0.84 and 0.89, respectively. The sensitivity was 0.71, 0.80, 0.78 and 0.86, the specificity was 0.76, 0.74, 0.76 and 0.80, and the accuracy was 0.73, 0.76, 0.77 and 0.83, respectively. ④Delong′s test showed the model D had an improved AUC of 0.89(0.89 vs 0.78, 0.84, 0.84, all P<0.05). Conclusions:The prediction models combining bi-modal imaging and immunohistochemical indicators show good prediction ability and can provide reference for selecting suitable patients for less invasive axillary surgery after NAC.