Objective:At present,the doctor-patient relationship is tense.The prevalence of negative emotions,such as depression and anxiety,among healthcare workers is increasing every year.Negative attitudes of medical workers toward mental problems may aggravate the doctor-patient conflict and psychological problems of medical workers.This study aims to explore the complex network relationships between outpatient medical workers'attitudes toward mental problems,doctor-patient relationships,and their depression/anxiety levels. Methods:A total of 578 outpatient medical staff from the Second Xiangya Hospital of Central South University(167 males,411 females)completed questionnaires on their attitudes toward mental problems,doctor-patient relationships,and depression/anxiety symptoms.Network analysis was conducted separately to construct the"attitude towards mental problems-doctor-patient relationship network"and"depression-anxiety related network". Results:The edge between"M15(insulting words)"and"D8(waste time)"showed the strongest strength in the"attitude towards mental problems-doctor-patient relationship network",and"M15(insulting words)"had the highest bridge strength in the network.For the analysis of emotional variables,"P1(anhedonia)"showed the most obvious association with"D10(communication difficulties)"in the doctor-patient relationship and"M2(poor quality of life)"in the psychiatric attitudes,and"P1(anhedonia)"was the key bridge symptom in the network. Conclusion:The"insulting words"may be an intervention target for medical workers'attitudes toward mental problems.The"anhedonia"in depression is the potential symptom that needs to be treated.Intervention targeting these variables may be beneficial to improve the mental health level of medical workers and the doctor-patient relationship.

Metastatic triple-negative breast cancer (TNBC) is the most aggressive type of breast cancer. Combination of systemic chemotherapy and immune checkpoint blockade is effective but of limited benefit due to insufficient intratumoral infiltration of cytotoxic T lymphocytes (CTLs) and the accumulation of immunosuppressive cells. Herein, we designed a lenvatinib- and vadimezan-loaded synthetic high-density lipoprotein (LV-sHDL) for combinational immunochemotherapy of metastatic TNBC. The LV-sHDL targeted scavenger receptor class B type 1-overexpressing 4T1 cells in the tumor after intravenous injection. The multitargeted tyrosine kinase inhibitor (TKI) lenvatinib induced immunogenic cell death of the cancer cells, and the stimulator of interferon genes (STING) agonist vadimezan triggered local inflammation to facilitate dendritic cell maturation and antitumor macrophage differentiation, which synergistically improved the intratumoral infiltration of total and active CTLs by 33- and 13-fold, respectively. LV-sHDL inhibited the growth of orthotopic 4T1 tumors, reduced pulmonary metastasis, and prolonged the survival of animals. The efficacy could be further improved when LV-sHDL was used in combination with antibody against programmed cell death ligand 1. This study highlights the combination use of multitargeted TKI and STING agonist a promising treatment for metastatic TNBC.

Objective:To investigate the epidemic trend and epidemiological characteristics of human brucellosis in Chengyang District of Qingdao City, and to provide a theoretical reference for formulating scientific prevention and control measures.Methods:The data of confirmed and clinically diagnosed brucellosis cases with current address in Chengyang District of Qingdao City reported by China Disease Control and Prevention Information System from January 2016 to December 2020 were collected, and the epidemic trend, three-dimensional distribution, clinical characteristics, case consultation and disease outcome and epidemiological history of human brucellosis were descriptively analyzed.Results:From 2016 to 2020, 23 cases of human brucellosis were reported in Chengyang District of Qingdao City, with an annual incidence of 0.52/100 000, and the incidence was decreasing year by year (χ 2trend = 7.83, P = 0.005). The onset time was mainly distributed in spring and summer, of which spring (1, 5 and 5 cases respectively from March to May) accounted for 47.83% (11/23), and summer (1, 4 and 1 cases respectively from June to August) accounted for 26.09% (6/23). There were 13 cases of males and 10 cases of females, the ratio of male to female was 1.30 ∶ 1.00; the age of onset was (52.52 ± 14.67) years old, mainly from 40 to 65 years old, accounted for 65.22% (15/23); farmers accounted for 69.57% (16/23). The largest number of reported cases was in Chengyang Street (6 cases), followed by Xiazhuang Street (4 cases) and Liuting Street (4 cases), accounted for 60.87% (14/23). The main clinical manifestations were fever (21 cases, 91.30%), followed by muscle and joint soreness (18 cases, 78.26%), fatigue (18 cases, 78.26%), and hyperhidrosis (15 cases, 65.22%). The median time interval from onset to diagnosis was 27 days, and 82.61% (19/23) of the cases were diagnosed as brucellosis at the acute stage. After follow-up, 21 cases (91.30%) reached the recovery standard, and 2 cases (8.70%) improved. Verified by the epidemiological investigation, 23 cases of human brucellosis had multiple routes of infection. The main mode of infection was direct contact, including feeding suspected sick animals (8 cases, 34.78%), contacting urine, feces and other excrement of suspected sick animals (8 cases, 34.78%), delivering suspected sick animals/disposing the apoblema (5 cases, 21.74%), and slaughtering/contacting raw lamb (4 cases, 17.39%). Conclusions:From 2016 to 2020, the incidence of human brucellosis in Chengyang District of Qingdao City has decreased year by year. It occurs frequently in spring and summer, mainly in middle-aged and elderly male farmers. The main clinical manifestation is fever and there are multiple ways of infection. It is recommended to take multiple measures to strengthen health education, behavioral intervention and regular monitoring.

Compared with traditional drug therapy, nanomedicines exhibit intriguing biological features to increase therapeutic efficiency, reduce toxicity and achieve targeting delivery. This review provides a snapshot of nanomedicines that have been currently launched or in the clinical trials, which manifests a diversified trend in carrier types, applied indications and mechanisms of action. From the perspective of indications, this article presents an overview of the applications of nanomedicines involving the prevention, diagnosis and treatment of various diseases, which include cancer, infections, blood disorders, cardiovascular diseases, immuno-associated diseases and nervous system diseases, etc. Moreover, the review provides some considerations and perspectives in the research and development of nanomedicines to facilitate their translations in clinic.

Objective:To investigate the MRI and pathological features of intramuscular fibro-adipose vascular anomaly (FAVA).Methods:The clinical and imaging data of 44 patients with intramuscular FAVA confirmed by pathology from December 2012 to March 2021 in Henan Province People′s Hospital were retrospectively analyzed. Twenty-five females and 19 males were included, with the age of (15±6), from 5 to 29 years old. The clinical and MRI features including the type, location, boundary, signal intensity, enhancement mode and degree, and the vascular flow voids in the lesion were summarized and compared with pathological results.Results:The thigh and calf muscles were involved in 1 patient simultaneously, and 1 site was involved in 43 patients, including 20 calf muscles, 15 thigh muscles, 5 forearm muscles, 1 upper arm muscle, 1 gluteal muscle, and 1 shoulder muscle. The gastrocnemius muscle of lower leg was most commonly involved (13/44), followed by soleus muscle (10/44) and quadriceps femoris muscle (9/44). All the lesions were solid on MRI, including 24 cases of focal mass type, 15 cases of diffuse infiltration type and 5 cases of local infiltration type. The long axis of all the lesions were consistent with the long axis of the muscles. All lesions showed inhomogeneously moderate hyperintensity on T 1WI and T 2WI, and significantly hyperintensity on fat suppression T 2WI. All lesions showed tortuous and dilated abnormal vessels, of which 18 cases showed vascular flow voids. Thrombosis was found in 10 cases. On contrast-enhanced imaging, the lesions showed moderate to obvious inhomogeneous enhancement. Pathologically, the diseased skeletal muscle was infiltrated by fibrous tissue, fat components, irregular abnormal veins and vessels, which led to inhomogeneous MRI signals. Among the 7 patients who underwent human PIK3CA gene mutation detection, and 6 were mutant. Conclusions:Intramuscular FAVA has certain characteristics in clinic, MRI imaging and histopathology, and its MRI signal characteristics can reflect its complex pathological components.

Leukemia inhibitory factor (LIF) contributes to the neuroprotection by neural stem cells (NSCs) after ischemic stroke. Our aim was to explore whether LIF-transfected NSCs (LIF-NSCs) can ameliorate brain injury and promote neuroprotection in a rat model of cerebral ischemia. To accomplish this goal, we transfected NSCs with a lentivirus carrying the LIF gene to stably overexpress LIF. The LIF-NSCs reduced caspase 3 activation under conditions of oxygen-glucose deprivation in vitro. Transient cerebral ischemia was induced in rats by 2 h of middle cerebral artery occlusion (MCAo), and LIF-NSCs were intravenously injected at 6 h post-ischemia. LIF-NSC treatment reduced the infarction volume and improved neurological recovery. Moreover, LIF-NSCs improved glial cell regeneration and ameliorated white matter injury in the MCAo rats. The NSCs acted as carriers and increased the expression of LIF in the lesions to protect against cerebral infarction, suggesting that LIF-NSCs could be a potential treatment for cerebral infarction.

Objective To investigate the clonal relatedness of A.baumannii isolates from senile patients by conducting cross-sectional and longitudinal studies on antimicrobial susceptibility profiling and genomic diversity.Methods Cross-sectional study was done among the 170 non-repetitive A.baumannii isolates which were collected from senile patients during two years.Longitudinal study was conducted among 77 A.baumannii collected from 8 senile patients within longtime hospitalization.Results 75.3 ％ of the 170 isolates were non-susceptible to carbapenems,and the phenotype were XDR or MDR which spread evenly all over the senile wards.The isolates belonged to 36 pulsotypes determined by PFGE.Groups Ⅰ (contain119 isolates) were major epidemic strains,which were CRAB with XDR phenotype.In longitudinal study,comparison of pulsotypes was performed for each patient and all isolates were clustered into group Ⅰ except one isolate.All the 77 isolates were XDR.Conclusion Extensive drug-resistance of A.baumannii was a serious problem in the gerontal wards.Clone dissemina tion was the most important style of XDR strains spread.Horizontal infection control measures to interrupt person-to-person transmission should be reinforced to reduce the further spread of XDR A.baumannii.

Ovarian cancer bears the highest mortality in gynecologic cancer, and its 5-year survival rate is about 30%. Although 70% to 80% ovarian cancer is epithelial origin, increasing evidence indicates that reciprocal interactions between tumor cells and various types of stromal cells also play important roles in driving ovarian tumor progression and that these stromal cells represent attractive therapeutic targets. This review discusses the biological signiifcance of the cross-talk between ovarian cancer cells and three major types of stromal cells (endothelial cells, ifbroblasts and macrophages) and the development of new-generation therapies that target the ovarian tumor micro-environment.

Background and purpose: Cancer-associated fibroblasts (CAFs) are known to promote the invasion and metastasis of epithelial cancers. The cytokine IL-6 may mediate the interaction between stromal cells and epithelia in tumor microenvironment to facilitate the invasiveness and metastasis of cancer, however, such mechanism has not been fully covered yet.Methods:We used cervical cancer cell line HeLa as a model for this study. ELISA was used to measure the levels of IL-6 in CAFs and normal ifbroblasts (NFs) isolated from squamous cervical cancer or normal cervical tissues. CAFs conditioned medium or IL-6 was used to treat cervical cancer HeLa cell line. The epithelial-mesenchymal transition (EMT) markers such as N-Cadherin and Vimentin were detected by Western blot in cells before and after treatment. Scratches and transwell chambers were used to test the abilities of cell migration and invasion. Results:The levels of IL-6 were 4-5 folds higher in CAFs than in NFs. Treatment of HeLa cells with CAF conditioned medium or IL-6 upregulated N-Cadherin and Vimentin, but down-regulated E-Cadherin and cytokeratin, compared with control cells, indicating that IL-6 may stimulate HeLa cells to EMT. Further study found that Snail 1, the featured transcription factor for stem cells, was increased along with the enhanced phosphorylation of STAT3. Meanwhile, the migration and invasion of HeLa cells treated with IL-6 or CAF conditioned medium were markedly increased. Conclusion:CAF induces the EMT of cervical epithelial cancer cells through IL-6/STAT3/Snail pathway, which thereby promotes the invasiveness and metastasis cervical epithelial cancer.

Background and purpose:Ovarian cancer-associated ifbroblasts (CAF) are known to promote epithelial malignancy. The chemoattractant cytokine growth-regulated oncogene alpha (Gro-α) secreted from CAF has been reported to mediate the stroma-epithelia interaction in tumor microenvironment, leading to the development of epithelial ovarian cancer, however, the detailed mechanism is unknown.This study was to determine whether Gro-αcould promote ovarian tumorigenesis through activating NF-кB nuclear translocation and VEGF expression in stromal ifbroblasts. Methods:ELISA was used to measure the levels of Gro-αin two cancer-associated ifbroblasts (CAF) and normal ifbroblasts (NF) isolated from high-grade serous ovarian cancer or normal ovarian tissues. CAF conditioned medium (CM) or Gro-αwas used to treat NF, while PS1145, the inhibitor of NF-кB, was used as control. NF-кB subunit p65 and vascular endothelial growth factor (VEGF) were detected by Western blot in cells after treatment. Xenograft tumors from nude mice were generated by injection of CAF, NF, or OVCA429 alone or OVCA429 mixed with CAF or NF, and by injection of OVCA429 mixed with NF cells that were treated with or without CAF-CM or Gro-α, or with NF cells that were treated with CAF-CM or Gro-αplus PS1145. The tumor growth curve was measured and the blood vessel density in xenograft tumor tissues was examined by histopathological analysis. Results:The levels of Gro-αwere 5-6 folds higher in CAF than in NF. Treatment of NF with CAF-CM or Gro-αstimulated the nuclear translocation of NF-кB subunit p65, and the expression of VEGF, but suppressed the expression of thrombospondin 1, the anti-angiogenesis factor, compared with control cells. However, treatment of NF with the NF-кB inhibitor PS1145 reversed these results. The animal assay revealed that CAF stimulated tumor growth stronger than NF, and NF treated with CAF-CM or Gro-α, but not along with PS1145, enhanced xenograft tumor growth through promoting angiogenesis. Conclusion:Ovarian CAF promotes the nuclear translocation of NF-кB and the expression of VEGF through Gro-αautocrine in tumor microenvironment to facilitate angiogenesis and ovarian cancer development.