Pulmonary hypertension(PH)is the pulmonary vascular remodeling caused by endothe-lial dysfunction and other factors,which leads to the increase of pulmonary artery pressure and finally right heart failure and patient death.Medications can significantly improve the symptoms of patients with pulmonary hypertension,but drugs can't cure vascular remodeling and right heart failure once for all,so it is urgent to find new treatments.Endothelial cells can obtain mesenchymal phenotypes after hypoxia stimulation,that is,endothelial-to-mesenchymal transition(EndMT).Increasing studies have shown that EndMT plays an important role in pulmonary vascular remodeling of PH.In this review,three signaling pathways related to induction of endothelial-to-mesenchymal transition under hypoxic conditions and research progress in related drugs are elaborated:① Transforming growth factor-β/bone morphogenetic protein(TGF-β/BMP)signaling pathway.The TGF-β/BMP pathway is mediated by Smad,and hypoxia regulates the expressions of EndMT-related genes by inhibiting or inducing the phosphorylation level of Smad in the downstream medium.② Notch signaling pathway.Hypoxia can enhance Jagged/Notch signaling pathway and promote the EndMT process.③Wnt/β-catenin signaling pathway.Hypoxia increases the expression of β-catenin,activates the Wnt signaling pathway,and regulates the expressions of EndMT regulatory genes.The significance of hypoxia-induced EndMT as an impor-tant pathogenic factor in PH is clarified in order to provide new ideas for the improvement of pulmonary vascular remodeling and recommend new effective strategies for the prevention and treatment of PH.

Objective:To study the current status of longitudinal extrauterine growth restriction (EUGR) in extremely preterm infants (EPIs) and to develop a prediction model based on clinical data from multiple NICUs.Methods:From January 2017 to December 2018, EPIs admitted to 32 NICUs in North China were retrospectively studied. Their general conditions, nutritional support, complications during hospitalization and weight changes were reviewed. Weight loss between birth and discharge > 1SD was defined as longitudinal EUGR. The EPIs were assigned into longitudinal EUGR group and non-EUGR group and their nutritional support and weight changes were compared. The EPIs were randomly assigned into the training dataset and the validation dataset with a ratio of 7∶3. Univariate Cox regression analysis and multiple regression analysis were used in the training dataset to select the independent predictive factors. The best-fitting Nomogram model predicting longitudinal EUGR was established based on Akaike Information Criterion. The model was evaluated for discrimination efficacy, calibration and clinical decision curve analysis.Results:A total of 436 EPIs were included in this study, with a mean gestational age of (26.9±0.9) weeks and a birth weight of (989±171) g. The incidence of longitudinal EUGR was 82.3%(359/436). Seven variables (birth weight Z-score, weight loss, weight growth velocity, the proportion of breast milk ≥75% within 3 d before discharge, invasive mechanical ventilation ≥7 d, maternal antenatal corticosteroids use and bronchopulmonary dysplasia) were selected to establish the prediction model. The area under the receiver operating characteristic curve of the training dataset and the validation dataset were 0.870 (95% CI 0.820-0.920) and 0.879 (95% CI 0.815-0.942), suggesting good discrimination efficacy. The calibration curve indicated a good fit of the model ( P>0.05). The decision curve analysis showed positive net benefits at all thresholds. Conclusions:Currently, EPIs have a high incidence of longitudinal EUGR. The prediction model is helpful for early identification and intervention for EPIs with higher risks of longitudinal EUGR. It is necessary to expand the sample size and conduct prospective studies to optimize and validate the prediction model in the future.

BackgroundChronic obstructive pulmonary disease （COPD） is a common chronic respiratory disease， and patients with COPD often experience substantially emotional difficulties， such as anxiety and depression， all of which may cause serious detriment to the prognosis of patients. As a non-pharmacological intervention in clinical practice， group mindfulness-based stress reduction therapy （MBSR） is beginning to emerge， while has rarely been studied in COPD patients with concurrent emotional difficulties. ObjectiveTo evaluate the effects of group MBSR on depression， state of mindfulness and pulmonary function in stable COPD patients， so as to provide references for the application of group MBSR in patients with COPD. MethodsA total of 97 patients with stable COPD who were followed up in the Department of Respiratory and Critical Care Medicine of Mianyang Third People's Hospital from January to October 2019 were selected as the study objects， and they were assigned into study group （n=50） and control group （n=47） by random number table method. All individuals received routine medication therapy and an 8-week health education， based on this， participants in study group partook an 8-week intervention comprising group MBSR. At the baseline， 4 weeks and 8 weeks of intervention， participants were assessed with Self-rating Depression Scale （SDS）， Five Facet Mindfulness Questionnaire （FFMQ） and COPD Assessment Test （CAT）， as well as the pulmonary function testing. ResultsThere were 41 patients in study group and 42 cases in control group completed the study. The group * time interaction was interpreted as significant between two groups for SDS， FFMQ and CAT scores （F=54.858， 86.161， 69.862， P<0.01）. Baseline SDS， FFMQ and CAT scores of the two groups yielded no statistical difference between two groups （F=0.240， 0.052， 0.019， P>0.05）， while study group scored lower on SDS and CAT （F=12.900， 38.511， 7.797， 28.824， P<0.01） and higher on FFMQ （F=27.324， 82.412， P<0.01） than those of the control group after 4 and 8 weeks of intervention. With the prolongation of intervention time in study group， participants demonstrated an overall reduction in SDS and CAT scores （F=109.753， 124.144， P<0.01）， and an increase in FFMQ scores （F=228.194， P<0.01）. There were no between-group differences in forced expiratory volume in one second as percentage of predicted volume （FEV1%pred） after 4 and 8 weeks of intervention （F=0.104， P=0.748） ， and the within-group changes in FEV1%pred value over the intervention period in study group was not statistical （F=0.561， P=0.458）. ConclusionGroup MBSR may help relieve depressive symptoms， enhance mindfulness level， and alleviate clinical symptoms in stable COPD patients， but has no effect on pulmonary function. ［Funded by Mianyang Health and Health Commission Scientific Research Project （number， 201916）］

Objective:To analyze the clinical characteristics of patients infected with 2019-nCoV Omicron variants BA.1 and BA.2 in Zhuhai city.Methods:A retrospective study was conducted to compare clinical characteristics of patients infected with 2019-nCoV Omicron variants BA.1 and BA.2, who were admitted in the Fifth Affiliated Hospital of Sun Yat-sen University during January 13 to March 8 2022. The Mann-Whitney U-test or Kruskal-Wallis H test was used for quantitative data, and the χ2 test or Fisher’s exact test was used for qualitative data. Results:Among 122 patients infected with the Omicron variant, there was 79 adults (BA.1 23 cases, BA.2 56 cases) and 43 children (BA.1 19 cases, BA.2 24 cases). In adults, patients infected with BA.2 sub-variant had a higher baseline viral loads at admission than BA.1 infected patients [7.64(6.92, 8.55) lg copies/mL vs. 6.64(6.04, 7.34) lg copies/mL; Z=-3.022, P=0.003]; compared to BA.1 patients, BA.2 patients had a higher proportion of mild and asymptomatic cases and a lower proportion of common infection cases ( χ2=8.052, P=0.012); the proportion of patients with pneumonia imaging changes in BA.1 patients was higher than that in BA.2 infected patients [(6/23, 26.1%) vs. (2/56, 3.6%); χ2=6.776, P=0.009). In children, the rate of fever in BA.2 group was higher than that in BA.1 group [(16/24, 66.7%) vs. ( 5/19, 26.3%); χ2=6.910, P=0.009); the proportion of patients with reduced lymphocyte counts in BA.2 group was higher than that in BA.1 group [(17/24, 70.8%) vs.(1/19, 5.3%); χ2=18.734, P<0.001). Compared with adult cases, children with BA.2 sub-variant infection had higher fever rate [(16/24, 66.7%) vs. (19/56, 33.9%); χ2=7.317, P=0.007). The viral loads of daily nasal swabs in BA.2 infected patients increased first and then decreased in both adults and children, with a greater decrease than BA.1 during the first two weeks. Conclusions:Compare with 2019-nCoV Omicron variant BA.1, BA.2 has a higher baseline viral loads in adults, which means much more contagious in the early stages. But the viral load drops faster in BA.2 infected patients. In children, BA.2 patients are more likely to have fever and reduced lymphocyte counts, which indicates that the prevention and control of 2019-nCoV Omicron sub-variant BA.2 is more difficult.

Objective: To rapidly identify triazole(fluconazole, voliconazole, iriconazole) drug resistance and sensitiveCandida tropicalusing matrix-assisted laser desorption/ionization-time-of-flight mass spectrometry(MALDI-TOF MS) platform data analysis and machine learning algorithms. Methods: A total of 191Candida tropicalwere collected from various clinical specimens, 71 of which were triazole-resistantCandida tropicaland 120 were triazole-sensitiveCandida tropicalstrains. Data acquisition was performed using the MALDI-TOF MS platform, and the mass and charge ratio features of resistant and susceptible strains were classified and selected based on the Mann-Whitney Rank-sum Test(Mann-WhitneyU-test) and the importance score obtained by the Random Forest(RF) algorithm. The classification model was constructed using the RF algorithm and a nonlinear support vector machine with a radial basis function kernel(RBF-SVM), calculating the accuracy, sensitivity, specificity, F1 value and the area under the subject worker curve(AUC) of the RBF-SVM model under the same experimental data to evaluate the model discrimination performance. Results: All strains obtained 76 unique mass spectrum peaks after analysis on the MALDI-TOF MS platform. Among them, six peaks 3 481,7 549,6 500,3 048,6 892,2 596 m/z were selected as the model feature peaks established by the feature dimensionality reduction treatment. The accuracy of both the RBF-SVM and RF models was 0.84, and the AUC scores were 0.930 5 and 0.927 3, respectively. Conclusion Machine learning algorithms combined with the MALDI-TOF MS platform for data analysis can serve as a possible method to rapidly distinguish triazole-resistantCandida tropicaland triazole-sensitive strains.

Objective: To explore the value of contrast-enhanced ultrasound in the biopsy of patients with breast imaging reporting and data system (BI-RADS) score of 4 lesions. Methods: Total of 136 cases of breast BI-RADS scores of 4 lesions admitted to Dongguan People′s Hospital from June 2017 to May 2018 were enrolled and randomly divided into contrast-enhanced ultrasound group and general ultrasound group, 68 cases in both group. The contrast-enhanced ultrasound group received contrast-enhanced ultrasound-guided breast nodule biopsy, and the general ultrasound group received general ultrasound-guided breast nodule biopsy. The success rate of puncture, the number of puncture needles, the satisfaction rate of the materials, the diagnostic sensitivity, the diagnostic specificity, the diagnostic coincidence rate, and the incidence of adverse puncture reactions were compared between two groups. Results: The puncture success rate of both groups were 100%. The number of puncture needles in contrast-enhanced ultrasound group was (2.89±0.56)times, and the general ultrasound group was (2.93±0.62)times, with no statistically significant difference (P>0.05). The satisfaction rate of materials in the contrast-enhanced ultrasound group was 100%(68/68), and the general ultrasound group was 94.12%(64/68), with no statistically significant difference (P>0.05). The sensitivity in the contrast-enhanced ultrasound group and the general ultrasound group were 88.89%(32/36) and 81.82%(27/33), respectively, with no statistically significant difference (P>0.05). The specificity and coincidence rate in contrast-enhanced ultrasound group were 100%(32/32) and 94.12%(64/68), which were higher than 80.65%(25/31) and 81.25%(52/64) of the general ultrasound group, with statistically significant difference (P<0.05). The incidence of adverse reactions in the general ultrasound group and the contrast-enhanced ultrasound group were 10.94%(7/64) and 2.94%(2/68), respectively, with no statistically significant difference (P>0.05). Conclusions The contrast-enhanced ultrasound-guided breast nodule biopsy can achieve high puncture success rate in patients with breast cancer with BI-RADS scores 4 lesions, and help to confirm lesion activity, necrotic liquefaction area, more accurate localization, improved material satisfaction rate and biopsy, diagnostic efficacy, with significant clinical value.

Objective To investigate the effects of water extracts of Lepidium meyenii walp (LMWE) collected from two different places in Xinjiang on the maturation and function of dendritic cells (DCs) and to evaluate their roles in immunoregulation. Methods Water extracts of LMWE growing in Tashikuergan County (Ta xian) and A La gou of Xinjiang were prepared and named as LMWE-T and LMWE-A,respectively. Bone marrow-derived DCs and splenocytes isolated from C57BL/6 mice were treated with different concentrations of polysaccharide extracts from LMWE-T/A. Effects of LMWE-T/A on the per-centage and apoptosis of DC,expression of co-stimulatory molecules and secretion of cytokines were detected by flow cytometry and ELISA. MTT assay was used to analyze the proliferation of splenocytes. Changes in the functions of DC were evaluated by mixed lymphocyte reaction(MLR). Results LMWE-T/A had no in-fluence on the percentage and viability of DC. Expression of CD40 and CD86,and secretion of TNF-α,IL-12p40 and IFN-γ were significantly increased by LMWE-T/A treatment in a dose-dependent manner. LMWE-T/A treatment enhanced the functions of DCs and also dose-dependently promoted the proliferation of splenocytes. LMWE-A was more effective than LMWE-T in promoting CD86 expression,IFN-γ secretion and splenocyte proliferation. Pretreatment with TAK-242,an inhibitor of Toll-like receptor 4(TLR4),could sig-nificantly inhibit the regulatory effects of LMWE-T/A on CD40 expression and the secretion of TNF-α and IL-12p40. Conclusion This study shows that LMWE could promote the maturation of DC through TLR4 signaling pathway,enhance the functions of DC without side effects on DC survival,and increase the prolif-eration of splenocytes,indicating that LMWE has a potential immunopotentiating effect. LMWE-A has better effects than LMWE-T on immune enhancement.

Objective To search the Web of Science for the papers related to case management to understand the present situation and direction of case management. Methods Papers on case management were retrieved in the Web of Science from 1999 to 2017.The Web of Science and excel were used to analyze the publication years, research themes, journals, countries and institutes. Results Totally,970 articles were included,with a sum of cited times,12,075.The number of publications on the case management was going up. Most of the authors were from the USA and China was ranked at 7 in authorship. Most of the papers concerned the research in chronic diseases such as chronic heart failure,mental disease and HIV. Conclusions Case management has been widely researched in the developed countries.China still has a lot of room for improvement in the study.The future research should be focused on the establishment of case manager training,multidisciplinary combination,case management mode suitable for chronic disease and aging population and exploration of the mode's effectiveness.

Objective To observe the effect of Yiqixue Buganshen Recipes(YBR), the compound recipes of Chinese herbal medicine with the actions of replenishing Qi and blood and tonifying liver and kidney, on the endometrial integrin β3 of the mice with embryo implantation dysfunction, and to explore the molecular mechanism of YBR in improving embryo implantation. Methods Ninety mice were divided normal group, model group, and YBR group, 30 mice in each group. YBR group was given Jinghou Zengzhi granules 8mg/kg for promoting post-menstruation proliferation and Cuhuangti granules 8mg/kg for promoting the formation of corpora luteum. At 8∶00 am of pregnant day 4 (Pd4), subcutaneous injection of mifepristone was used for inducing embryo implantation dysfunction in the model group and YBR group. Twenty mice from each group were executed 12 hours after subcutaneous injection of mifepristone, and the uterus was isolated for the detection of mice endometrial integrin β3 mRNA and protein expression with real-time RT-PCR and Western blotting method respectively. Ten mice from each group at Pd4 were executed, and the uterus was isolated and then fixed in 2.5% glutaraldehyde solution for the detection of the formation of pinopode in mice endometrium under scanning electron microscope. Results The detection by real-time PCR and Western blotting method revealed that integrinβ3 mRNA and protein expression levels of the model group were significantly lower than those of the normal group (P<0.05), and YBR group had higher integrin β3 mRNA and protein expression levels than the model group(P<0.05). The formation of pinopodes in the model group was less than the normal group and YBR group, but the number of formed pinopodes in YBR group was similar to that in the normal group. Conclusion YBR can up-regulate the expression of integrin β3 in the endometrium of mice with embryo implantation dysfunction, and have positive regulatory effect on the formation of pinopodes on Pd4.

BACKGROUND:Glial scar and cavity formation fol owing spinal cord injury inhibits axonal entrance, so limited axonal regeneration, less secretion of neurotrophic factor and inhibitors in the microenvironment of axonal growth are considered as major impediments for impacting functional recovery of patients with spinal cord injury.
OBJECTIVE:To analyze literatures home and abroad related to the biological characters of astrocytes and glial scar hyperplasia after spinal cord injury, and to provide a theoretical basis for the mechanism underlying glial scar formation fol owing spinal cord injury.
METHODS:PubMed and Wanfang databases were retrieved using the keywords“astrocytes, reactive astrogliosis, glial scar, spinal cord injury”in English and Chinese, respectively. Final y 62 literatures were selected for overview.
RESULTS AND CONCLUSION:Currently, studies concerning the biological characters of astrocytes, reactive astrogliosis and glial scar formation fol owing spinal cord injury have achieved some progresses. Studies mainly focus on the sole impediment for spinal cord injury, and treatment also aims at inhibiting single factor, but interactions among factors have not been confimed. In addition, the regulatary mechanisms of specific intracel ular and extracel ular signal molecule in the astrocytes, and effective control and interference of glial scar formation fol owing spinal cord injury stil need in-depth study.