ObjectiveTo establish a mouse model of hypoxic pulmonary hypertension (HPH) through intermittent hypoxia induction, and to develop a comprehensive and reliable evaluation system for the HPH model, thereby providing experimental evidence for mechanistic studies and translational applications related to this disease. MethodsTwenty-four male specific pathogen-free (SPF) BALB/c mice were randomly divided into a control group and a model group, with 12 mice per group. Mice in the model group were placed in a hypobaric oxygen chamber control system to establish the HPH model, whereas mice in the control group received no intervention. After 28 days of modeling, a comprehensive evaluation of the pathophysiological characteristics of both groups was performed using a general condition scoring scale, echocardiography, hemodynamic measurements, blood gas analysis, hematological tests, organ coefficient determination, histopathological examination, and enzyme-linked immunosorbent assay (ELISA). In addition, correlation analyses were conducted among echocardiographic parameters, the contents of endothelin‑1 (ET‑1) and N‑terminal pro‑B‑type natriuretic peptide (NT‑proBNP) in lung tissue, and other measured indices. ResultsWith prolonged modeling duration time, body weight, water intake, and activity level of mice in the model group were significantly decreased compared with the control group (P<0.05). Echocardiography showed that, compared with the control group, the model group exhibited increased right ventricular dimensions (P<0.01), right ventricular anterior wall thickening (P<0.01), and widened main pulmonary artery diameter (P<0.01), whereas the peak systolic velocity across the pulmonary valve, tricuspid annular plane systolic excursion, and peak systolic velocity of the tricuspid annulus were significantly decreased (P<0.001); tricuspid regurgitation was observed in some model animals. Hemodynamic results revealed that right ventricular systolic pressure was elevated in the model group compared with the control group (P<0.001). Blood gas analysis showed that pH, partial pressure of oxygen, oxygen saturation, actual bicarbonate, and total carbon dioxide were all decreased in the model group compared with the control group (P<0.01). Hematological indices demonstrated that lymphocyte counts (P<0.05) and reticulocyte counts (P<0.001) were decreased in the model group compared with the control group. Compared with the control group, the organ coefficients of heart and lung in the model group were significantly increased (P<0.05 and P<0.001). Pathological examination revealed that the right ventricular hypertrophy index was significantly increased in the model group (P<0.001), with varying degrees of damage to the right ventricle, pulmonary artery, and pulmonary vessels; both the pulmonary artery wall thickness percentage and the pulmonary wall area percentage were significantly elevated (P<0.001). ELISA results showed that the levels of ET‑1 and NT‑proBNP in lung tissues were significantly increased in the model group compared with the control group (P<0.05 and P<0.001, respectively). Correlation analysis indicated that some echocardiographic parameters were highly correlated with multiple indices in the development of HPH (P<0.05). ConclusionEchocardiography can accurately assess a series of hemodynamic changes in HPH, including right ventricular structural, functional impairment, and pulmonary hypertension. Laboratory tests not only help verify whether the model has been successfully established, but also provide deeper insights into the pathogenesis of HPH, evaluate the effects of interventions, and offer scientific evidence for clinical outcomes. Pathological examination can further confirm the alterations in pulmonary vascular remodeling and increased right heart load. This multimodal analysis provides a reliable animal model and evaluation paradigm for both basic and translational research on HPH, and is of great significance for exploring disease mechanisms and developing precision therapeutic strategies.

[This corrects the article DOI: 10.1016/j.apsb.2021.10.012.].

Objective To observe the efficacy of a nomogram based on conventional ultrasonic manifestations for predicting malignant risk of breast non-mass lesions(NML).Methods A total of 120 NML diagnosed with ultrasound in 113 female patients were retrospectively included and divided into malignant group(n=44)and benign group(n=76)based on pathological results.Patients' age,ultrasonic manifestations of NML and ipsilateral axillary lymph node were compared between groups.Then a nomogram was constructed using a multivariable logistic regression model,and its diagnostic performance and accuracy were validated.Results The ratios of patients' aged≥45 years,with abnormal ipsilateral axillary lymph nodes,NML with maximum diameter≥2 cm,posterior echo attenuation,rich blood flow signals,architectural distortion and microcalcification were significantly different between groups(all P＜0.05).Patient's age≥45 years,with abnormal ipsilateral axillary lymph nodes,and NML with rich blood flow signals,architectural distortion and microcalcification were all independent predictive factors for high malignant risk of breast NML(all P＜0.05).The constructed nomogram achieved an area under the receiver operating characteristic curve of 0.901 for predicting malignant risk of breast NML,and its predicting probabilities demonstrated good agreement with the actual probabilities(Hosmer-Lemeshow test P＞0.05).Conclusion The nomogram incorporating patient's age,ultrasonic manifestations of NML and ipsilateral axillary lymph node could effectively quantify malignancy risk of breast NML.

Objective To observe the efficacy of a nomogram based on conventional ultrasonic manifestations for predicting malignant risk of breast non-mass lesions(NML).Methods A total of 120 NML diagnosed with ultrasound in 113 female patients were retrospectively included and divided into malignant group(n=44)and benign group(n=76)based on pathological results.Patients' age,ultrasonic manifestations of NML and ipsilateral axillary lymph node were compared between groups.Then a nomogram was constructed using a multivariable logistic regression model,and its diagnostic performance and accuracy were validated.Results The ratios of patients' aged≥45 years,with abnormal ipsilateral axillary lymph nodes,NML with maximum diameter≥2 cm,posterior echo attenuation,rich blood flow signals,architectural distortion and microcalcification were significantly different between groups(all P＜0.05).Patient's age≥45 years,with abnormal ipsilateral axillary lymph nodes,and NML with rich blood flow signals,architectural distortion and microcalcification were all independent predictive factors for high malignant risk of breast NML(all P＜0.05).The constructed nomogram achieved an area under the receiver operating characteristic curve of 0.901 for predicting malignant risk of breast NML,and its predicting probabilities demonstrated good agreement with the actual probabilities(Hosmer-Lemeshow test P＞0.05).Conclusion The nomogram incorporating patient's age,ultrasonic manifestations of NML and ipsilateral axillary lymph node could effectively quantify malignancy risk of breast NML.

Objective To investigate the role and mechanism of sine oculis homeobox 1(Six1),a nephrogenic transcription factor,in regulating injury repair after acute kidney injury(AKI).Methods C57BL/6J mice were inflicted with renal ischemia reperfusion(IR)injury to establish AKI model,and then the serum samples and kidney tissues were collected at days 1,2,and 3 after modeling.Serum creatinine(Cr)and blood urea nitrogen(BUN)levels were measured and renal morphology was observed with HE staining.The expression and distribution of nephrogenic molecules(Six1 and Pax2,etc.)and cell proliferation/migration genes(Cyclin A1,MMP9,etc.)were detected with RT-PCR,Western blotting,and immunofluorescence assay and immunohistochemical assay.The expression of apoptosis pathway(Bc12,Caspase3,etc.)and cell proliferation related molecules were evaluated in Six1 overexpression/knockout human epithelial cells(HK2)with CoCl2-induced injury.Additionally,after the adeno-associated viruses carrying Six1 overexpression vector were used to overexpress the molecule in the mice,the expression of Six1 and other related molecules were detected after IR injury modeling.Results After renal IR injury,Six1 was significantly activated in epithelial cells,the expression of nephrogenic and cell proliferation/migration molecules(Pax2,Cyclin A1,MMP9,etc.)was obviously up-regulated(P＜0.05),which was positively correlated with Six1 expression,while the proliferation/migration molecules(Ki67,MMP9)were also localized within the tubular epithelial cells.In cellular models of Six1 overexpression,the expression levels of nephrogenic and cell proliferation/migration molecules(Pax2,Cyclin A1,MMP9,etc.)were also notably up-regulated(P＜0.05).In the mice with renal overexpression of Six1,the nephrogenic molecules as well as anti-apoptotic ones(Six2,Pax2,Bc12,etc.)were up-regulated,while the expression of kidney injury-related molecule(Kim1)in kidneys was reduced in the renal tissues.While,in 2 d after IR injury,the anti-apoptotic gene(Bc12,Stat3)was significantly up-regulated(P＜0.05),and the apoptotic and injury molecules(Kim1,Caspase3)showed remarkable down-regulation(P＜0.05)in the mice with renal Six1 overexpression.Furthermore,CoCl2-inducion significantly decreased the cell proliferation rate in the Six1 knockoutgroup(TCMK1-Six1-/-)(P＜0.05)but increased the rate in the Six1 overexpression group(TCMK1-Six1)when compared to the control cells(P＜0.05).And,the expression of nephrogenic,anti-apoptotic pathways and cell proliferation/migration molecules(Pax2,Bc12,Cyclin A1,MMP9,etc.)were reduced in TCMK1-Six1-/-group,and apoptosis and kidney injury molecules(Caspase3,Kim1)were significantly down-regulated in TCMK1-Six1 group(P＜0.05).Conclusion Activation of Six1 after AKI can promote the proliferation/migration of renal tubular epithelial cells by up-regulating nephrogenic molecules and inducing anti-apoptotic pathway molecules,and then,participate in IR-induced renal injury repair.

Objective To explore the safety and efficacy of sequential tirofiban in patients with small artery occlusion(SAO)cerebral infarction after intravenous thrombolysis.Methods A retrospective collection of 90 cases of small artery occlable cerebral infarction who underwent intravenous thrombolytic treatment within the time window at the Department of Neurology,Heji Hospital,Affiliated to Changzhi Medical College from December 2019 to June 2022.It was divided into observation group(receiving tirofiban,conventional antiplatelet aggregation,lipid regulation and stabilization)and control group(conventional antiplatelet aggregation,lipid regulation and plaque stabilization).Baseline feature differences were balanced by propensity score matchingd.The main evaluation index was the long-term prognosis,the ratio of good prognosis(mRS≤2 points)at 3 months.The secondary outcome was early neurological impairment and clinical outcome.Results At 3 months,the long-term functional outcome of the tirofiban group was better than that of the control group(P>0.05).Compared with the control group,the early neurological function NIHSS score of the tirofiban group was significantly reduced(P<0.05).On the 7th day,the total efficiency of tirofiban treatment was higher than that of the control group(P<0.05).On the 14th day,the data was still significantly higher(P<0.05).Conclusion Sequential tirofiban treatment after thrombolysis is safe and effective for SAO,which may be the remedial treatment of AIS patients after thrombolysis and recanalization.

Objective:To assess the value of S-Detect and contrast-enhanced ultrasound (CEUS) in the differential diagnosis of Breast Imaging Reporting and Data System(BI-RADS) 4 breast lesions.Methods:A total of 104 breast lesions in 100 patients diagnosed as BI-RADS category 4 by conventional ultrasound were prospectively enrolled, and all of them were received S-Detect and CEUS examination at the same time. Taking pathology as the gold standard, ROC curve was constructed to compare the diagnostic efficacy of conventional ultrasound, S-Detect, CEUS and their combination.Results:Among the 104 BI-RADS category 4 breast lesions, 63 were benign and 41 were malignant. The sensitivities of conventional ultrasound, S-Detect, CEUS and S-Detect combined with CEUS were 73.17%, 87.80%, 87.80%, 90.24%; the specificities were 57.14%, 60.32%, 68.25%, 77.78%; the positive predictive values were 52.63%, 59.02%, 64.29% and 72.55%; the negative predictive values were 76.60%, 88.37%, 89.59% and 92.45%; the accuracies were 63.46%, 71.15%, 75.96% and 82.69%; and the areas under the ROC curve (AUC) were 0.652, 0.741, 0.780 and 0.840. The sensitivity, specificity, positive predictive value, negative predictive value and accuracy of S-Detect and CEUS diagnosis were improved compared with conventional ultrasound. The AUC of combined diagnosis was higher than that of S-Detect, CEUS alone, and the differences were statistically significant(all P<0.05). The AUC of CEUS was higher than that of conventional ultrasound, and the difference was statistically significant ( P<0.05). There were no significant differences in AUC between any two of other groups (all P>0.05). Conclusions:The combined application of S-Detect and CEUS could achieve complementary advantages, which is of great significance for the differential diagnosis of benign and malignant in BI-RADS 4 breast lesions.

Fragile X syndrome (FXS) is the leading inherited cause of intellectual disability, resulting from the lack of functional fragile X mental retardation protein (FMRP), an mRNA binding protein mainly serving as a translational regulator. Loss of FMRP leads to dysregulation of target mRNAs. The Drosophila model of FXS show an abnormal circadian rhythm with disruption of the output pathway downstream of the clock network. Yet the FMRP targets involved in circadian regulation have not been identified. Here, we identified collapsing response mediator protein (CRMP) mRNA as a target of FMRP. Knockdown of pan-neuronal CRMP expression ameliorated the circadian defects and abnormal axonal structures of clock neurons (ventral lateral neurons) in dfmr1 mutant flies. Furthermore, specific reduction of CRMP in the downstream output insulin-producing cells attenuated the aberrant circadian behaviors. Molecular analyses revealed that FMRP binds with CRMP mRNA and negatively regulates its translation. Our results indicate that CRMP is an FMRP target and establish an essential role for CRMP in the circadian output in FXS Drosophila.

Objective:To explore the effect of pathway nursing under multidisciplinary collaboration on self-care ability and rehabilitation effect in patients with acute cerebral infarction.Methods:Using the convenient sampling method, a total of 294 patients with acute cerebral infarction who were admitted to the Department of Neurology in the Fengcheng Hospital, Fengxian District, Shanghai from January 2018 to December 2019 were selected as the research objects. A total of 147 patients with acute cerebral infarction admitted from January to December 2019 were included in the experimental group, while 147 patients with acute cerebral infarction admitted from January to December 2018 were included in the control group. The experimental group adopted pathway nursing under multidisciplinary collaboration, while the control group adopted neurology routine nursing. Scores of Exercise of Self-Care Agency (ESCA) , National Institutes of Health Stroke Scale (NIHSS) , Fugl-Meyer Assessment (FMA) , Barthel Index and nursing satisfaction of patients were compared between the two groups. Finally, 147 patients in the experimental group and 145 patients in the control group completed the experiment.Results:The scores of self-concept, self-responsibility, health knowledge level and self-care skills in ESCA of patients in the experimental group at discharge were respectively (25.36±4.86) , (20.43±3.21) , (53.37±5.89) and (40.02±3.78) and the nursing satisfaction score was (97.26±2.52) , which were higher than (21.48±4.33) , (16.24±3.25) , (46.44±5.47) , (30.08±3.81) and (90.65±3.16) in the control group, and the differences were statistically significant ( P<0.01) . The NIHSS score of the experimental group 60 days after discharge was (3.7±2.2) , lower than (6.9±2.3) of the control group. And FMA and Barthel Index scores were respectively (79.3±9.2) and (78.7±14.5) , higher than (65.6±8.4) and (60.3±16.6) of the control group, and the differences were statistically significant ( P<0.01) . Conclusions:The implementation of pathway nursing under multidisciplinary collaboration for patients with acute cerebral infarction can enhance the consciousness of self-management, contribute to the recovery of neurological function and limb motor function and improve the ability of self-care and nursing satisfaction of patients.

Objective To observe the ultrasonographic findings of patients with basal ganglia hemorrhage by transcranial color-code sonography ( TCCS) and contrast-enhanced transcranial color-code sonography (CE-TCCS) ,and to evaluate the clinical value of TCCS and CE-TCCS in assessing the cerebral perfusion with basal ganglia hemorrhage . Methods Eighty-two patients with basal ganglia hemorrhage were selected ,and hematoma was seen in 58 patients (70 .7％ ) . Forty-six cases of bilateral TCCS with clear display of basal ganglia through temporal window were selected . CE-TCCS was used to observe cerebral perfusion of edema zone ,edema zone edge and peripheral brain parenchyma . Results The bilateral rate displayed by TCCS was 79 .3％ . Among 58 cases ,30 cases had ventricular compression ,14 cases had hematoma rupture into ventricle ,8 cases had midline displacement ,and 10 cases had no complication change . The cerebral perfusion in edema areas around hematoma was reduced by CE-TCCS ,but the degree of reduction was different . There were reduced in a step-like manner in the cerebral perfusion from edema zone and edema zone edge to peripheral brain tissue . Conclusions CE-TCCS is a new method for clinical diagnosis and monitoring the progress of treatments of cerebral hematoma .