Objective To explore the differences of total bile acid in carotid atherosclerosis(CAS)patients with different traditional Chinese medicine(TCM)constitution.Methods CAS patients who were treated in Tai'an Municipal Hospital from December 2022 to May 2023 were selected,clinical data of patients were collected and TCM constitution was identified,and differences in serum total bile acid among patients with different TCM constitutions were analyzed.Results A total of 212 CAS patients were included,including 151 patients with biased constitution.The top 3 biased constitution included yang-deficiency constitution(49 cases,23.1％),qi-depression constitution(25 cases,11.8％),blood-stasis constitution(19 cases,9.0％).The body mass index of patients with yin-deficiency constitution was significantly lower than that of other patients(P＜0.05).The total bile acid level of patients with yang-deficiency constitution was significantly higher than that of patients with normal constitution,qi-depression constitution,blood-stasis constitution,phlegm-dampness constitution,humid heat constitution(P＜0.05).Conclusion There are differences of total bile acid in CAS patients with different TCM constitution,and yang-deficiency constitution is closely related to total bile acid metabolism.

The anterior disc displacement (ADD) leads to temporomandibular joint osteoarthritis (TMJOA) and mandibular growth retardation in adolescents. To investigate the potential functional role of fibrocartilage stem cells (FCSCs) during the process, a surgical ADD-TMJOA mouse model was established. From 1 week after model generation, ADD mice exhibited aggravated mandibular growth retardation with osteoarthritis (OA)-like joint cartilage degeneration, manifesting with impaired chondrogenic differentiation and loss of subchondral bone homeostasis. Lineage tracing using Gli1-CreER⁺; Tm^fl/-mice and Sox9-CreER⁺;Tm^fl/-mice showed that ADD interfered with the chondrogenic capacity of Gli1⁺ FCSCs as well as osteogenic differentiation of Sox9⁺ lineage, mainly in the middle zone of TMJ cartilage. Then, a surgically induced disc reposition (DR) mouse model was generated. The inhibited FCSCs capacity was significantly alleviated by DR treatment in ADD mice. And both the ADD mice and adolescent ADD patients had significantly relieved OA phenotype and improved condylar growth after DR treatment. In conclusion, ADD-TMJOA leads to impaired chondrogenic progenitor capacity and osteogenesis differentiation of FCSCs lineage, resulting in cartilage degeneration and loss of subchondral bone homeostasis, finally causing TMJ growth retardation. DR at an early stage could significantly alleviate cartilage degeneration and restore TMJ cartilage growth potential.
Animals ; Mice ; Osteogenesis ; Zinc Finger Protein GLI1 ; Fibrocartilage ; Temporomandibular Joint ; Disease Models, Animal ; Osteoarthritis ; Stem Cells ; Growth Disorders

Objective:To explore the relationship between intestinal flora disorder and intestinal barrier dysfunction in patients with sepsis.Methods:A prospective observational study was conducted to include 10 patients with sepsis (sepsis group) admitted to the ICU of General Hospital of Ningxia Medical University from February 2017 to June 2017, 10 normal postoperative patients (non-sepsis group) admitted to the ICU of General Hospital of Ningxia Medical University in the same period, and 10 healthy persons (control group) were served as controls. General information was recorded. Fecal samples of the three groups of experimental subjects were detected and analyzed by using 16S rRNA gene sequencing technology. The venous blood of the sepsis and non-sepsis groups were collected and the levels of D-lactic acid and bacterial endotoxin in were measured by enzymatic method at the corresponding time points. The correlation between the levels of D-lactic acid and bacterial endotoxin and intestinal flora of patients with sepsis was analyzed.Results:The change consistency of pathogenic bacteria between clinical infection and intestinal pathogenic bacteria in patients with sepsis was observed and analyzed. Sputum culture of patients with sepsis was Acinetobacter baumannii (corresponding patient number: S5, S6, S8), Stenotrophomonas maltophilia (corresponding patient number: S6, S7), and Enterococcus (corresponding patient number: S7). In the intestinal flora of corresponding patients, the OUT abundance were increased. Patients with sepsis (corresponding patient number S7) showed E. coli in blood culture, and in his intestinal flora the OUT abundance was increased. Correlation analysis showed that the serum D-lactic acid level was negatively correlated with the proportion of Firmicutes in intestinal flora in the non-sepsis and sepsis groups, while was positively correlated with the proportion of Firmicutes (r value: -0.532, 0.468, respectively, P<0.05). Conclusions:The gut microbiota dysbiosis is correlated with intestinal barrier function in sepsis patients with sepsis. The spread of pathogenic bacteria between clinical infection and intestinal bacteria in sepsis patients has potential consistency.

Objective:To explore the possible pathogenic mechanism of the central nervous system by studying the neurodegenerative diseases caused by tick-borne encephalitis virus (TBEV) infection in mice.Methods:The mice were intracranially inoculated with TBEV, 8 days later the mice were sacrificed, the brain tissues of all mice were collected and observed after HE staining to verify if the model was successfully established; the expressions of neuronal nuclei (NeuN), glial fibrillary acidic protein (GFAP), proliferating cell nuclear antigen (PCNA) and reduced upon activation, normal T cell expressed and secreted (RANTES) in mouse brain tissue were detected by immunohistochemical method, the number of positive cells was counted and the gray value was analyzed to calculate the score.Immunofluorescence combined with laser scanning confocal microscopy were used to observe the distribution of NeuN and GFAP positive cells and the expression of RANTES and PCNA.Results:The number of NeuN-positive cells in the brain tissue of mice infected with TBEV decreased, while the GFAP-positive cells increased. Furthermore, astrocytes proliferated faster than neurons, and RANTES was mainly produced by astrocytes.Conclusions:TBEV infection could cause neurotoxic reactions in brain tissue, leading to nerve cells death and activating astrocytes which produces many RANTES.

Objective:To explore the effect of five-step literature reading mode based on action research method on scientific research ability and innovative efficiency of young nurses.Methods:A total of 50 young clinical nurses from Henan Cancer Hospital were selected as the research objects, and the five-step literature reading salon scientific research training of 20 phases was carried out from May 2020 to June 2021 using the action research method. Through qualitative interviews, Scientific Research Ability Self-assessment Scale for Nursing Staff, Creative Self-efficacy Scale and scientific research output, the training program improvement and effect evaluation were carried out before training, after the first stage of training, and after the second stage of training.Results:After two stages of training, 50 young nurses wrote 43 papers and published 22 papers. The number of nurses who wrote and published papers was 36 (72%, 36/50) and 17 (34%, 17/50) , respectively. A total of 8 patents were approved. After training, the total score of scientific research ability of young nurses and the scores of each dimension, the total score of creative self-efficacy and the scores of each dimension were higher than before training, and the differences between before and after training were statistically significant ( P<0.05) . Conclusions:The five-step literature reading based on the action research method can improve the overall scientific research level and innovative efficiency of young clinical nurses and increase the scientific research output.

Objective:Based on the analysis of the Nobel Prize in Physiology or Medicine from 1946 to present, summarize key factors of biomedical research management at universities, to provide suggestions for the improvement of biomedical research management in China.Methods:Using the official website of Nobel Foundation as database, combined with documents and literature review, data of the Nobel Prize in Physiology or Medicine, which including the nationality of the winners, the age at which the Nobel Prize were made, the employer as well as the discipline were analyzed.Results:An evaluation system based on peer review plays important roles in scientific and technological innovation.The breakthrough works are usually achieved by the scientists in their youth, however, the time for the recognition of their work is gradually increasing.The interdisciplinary research is more and more important.Conclusions:By analyzing the Nobel Prize in Physiology or Medicine, China needs to establish a comprehensive talent evaluation system that focus on training young scholars and strengthen cross-disciplinary integration to improve the biomedical research management.

BRAF is a serine/threonine kinase that harbors activating mutations in ∼7% of human malignancies and ∼60% of melanomas. Despite initial clinical responses to BRAF inhibitors, patients frequently develop drug resistance. To identify candidate therapeutic targets for BRAF inhibitor resistant melanoma, we conduct CRISPR screens in melanoma cells harboring an activating BRAF mutation that had also acquired resistance to BRAF inhibitors. To investigate the mechanisms and pathways enabling resistance to BRAF inhibitors in melanomas, we integrate expression, ATAC-seq, and CRISPR screen data. We identify the JUN family transcription factors and the ETS family transcription factor ETV5 as key regulators of CDK6, which together enable resistance to BRAF inhibitors in melanoma cells. Our findings reveal genes contributing to resistance to a selective BRAF inhibitor PLX4720, providing new insights into gene regulation in BRAF inhibitor resistant melanoma cells.

Objective To explore the clinical features,diagnoses,differential diagnoses and treatments of superior cerebellar artery aneurysms.Methods The clinical data of 16 patients with superior cerebellar artery aneurysms,admitted to our hospital from January 2013 to March 2018,were retrospectively collected.Their clinical manifestations,imaging features,surgical effects and related problems in the process of diagnoses and treatments were analyzed.Results Among the 16 patients,11 were caused by aneurysm rupture;8 had subarachnoid hemorrhage alone,and three had subarachnoid hemorrhage accompanied by ventricular hemorrhage;CT and CTA confirmed that 8 were superior cerebellar artery aneurysms,two were posterior cerebral artery aneurysms,and one was with unclear diagnosis.In the other 5 patients,three had eyelid ptosis and two had abducent nerve palsy;CT,CTA or MR imaging showed that two were considered as ventral brainstem occupying lesions,and three did not have clear diagnosis.Finally,all patients were diagnosed as having superior cerebellar artery aneurysms by three-dimensional DSA.Five patients were treated with interventional embolization first,and one was treated with surgical clipping because of vertebral artery stenosis and difficulty of catheter access;two patients were transferred to our department for surgical clipping due to aneurysm rupture after embolization treatment in other hospitals;and 9 patients were treated by surgical clipping directly.After treatments,one patient was in bed for a long time due to cerebellar infarction and systemic complications,and the other 15 patients recovered well;two of them underwent ventricular peritoneal shunt due to hydrocephalus.Conclusions Superior cerebellar artery aneurysm has onset of subarachnoid hemorrhage mostly,and oculomotor and abductor nerve paralysis,and space occupying manifestation around the brainstem sometimes.For patients with suspicious posterior circulation aneurysms whose diagnosis or location are unclear,three-dimensional DSA examination should be performed early to confirm the diagnosis.Treatment should be taken as soon as possible once the superior cerebellar artery aneurysm is defined.Interventional embolization may be the first choice,but it is necessary to master the methods of surgical clipping in order to treat the disease timely.

Objective:To determine the optimal time to perform sentinel lymph node biopsy(SLNB)in patients with clinically node-negative disease and assess clinically node-positive patients who would acquire greater benefits from axillary downstaging surgery af-ter neoadjuvant chemotherapy(NAC).Methods:From October 2010 to November 2017,206 patients with breast cancer who under-went surgery after NAC were included in this retrospective study in Shandong Cancer Hospital Breast Cancer Center.Their clinicopatho-logic data were collected to discuss the correlation between axillary node pathologic complete response(apCR)and different molecu-lar subtypes.Results:Among 206 patients who received NAC,183 patients had clinically node-positive disease.The frequency of apCR after NAC was 33.3%(61/183),which was significantly higher in patients with human epidermal growth factor receptor 2(HER-2)-posi-tive subtype[with targeted therapy,62.1%(18/29);without targeted therapy,34.5%(10/29)]and triple-negative breast cancer(TNBC) (41.0%)(16/39)than in patients with HER-2-negative luminal subtype breast cancer[19.8%(17/86)](P<0.001). Among 23 patients with Cn0 tumors,the rate of positive sentinel lymph nodes after NAC was 26.1%(6/23);this rate was 36.4%(4/11),25.0%(1/4),and 12.5% (1/8)among patients with HER-2-negative luminal subtype breast cancer,TNBC,and HER-2-positive subtype breast cancer,respective-ly.Conclusions:Molecular subtypes could predict the chance of achieving apCR.For patients with clinically node-negative disease,it would be preferable to perform SLNB prior to NAC for patients with HER-2-negative luminal subtype breast cancer.SLNB after NAC for those with TNBC and HER-2-positive subtype breast cancer could decrease the chances of axillary lymph node dissection.For patients with initial clinically node-positive disease converting to clinically node-negative disease after NAC,especially in TNBC and HER-2-posi-tive subtype breast cancer,these patients might benefit more from axillary downstaging surgery after NAC.

Objective To explore the association of nocturnal serum cortisol levels with diabetic microvascular complications in overweight or obese patients with type 2 diabetes mellitus. Methods Serum cortisol levels of 316 overweight or obese type 2 diabetic patients were tested at midnight by the method of chemiluminescence. Diabetic microvascular complications were compared among various groups according to nocturnal serum cortisol levels. All the patients with nocturnal serum cortisol level > 50 nmol/L were asked to undergo overnight low-dose dexamethasone suppression test to rule out the possibility of subclincal Cushing's syndrome. The incidences of diabetic nephropathy ( DN ) , diabetic retinopathy ( DR ) , and diabetic peripheral neuropathy ( DPN ) were examined in all the patients. Results (1)The incidence of DN was gradually increased from 13.3％to 27.7％and 44.2％in patients with low, medium, and high cortisol level groups, showing a statistical difference among 3 groups ( P<0.05) . The incidences of DR in medium and high cortisol level groups were higher than that in low cortisol level group (40.6％and 47.7％vs 22.7％, both P<0.01). The incidence of DPN in high cortisol level group was higher as compared with low cortisol level group (60.5％ vs 38.7％, P<0.01). (2) Nocturnal serum cortisol level in patients with diabetic microvascular complications was higher than that in patients without complications [ (136.87 ± 105.78 vs 97.55 ± 93.48) nmol/L, P<0.01]. Nocturnal serum cortisol level in patients with multiple diabetic microvascular complications was higher than that in patients with single diabetic microvascular complication [ (151.66±114.54vs117.69±90.26)nmol/L,P<0.05].(3)Singlefactorlogisticregressionanalysisshowedthat higher nocturnal serum cortisol level was a risk factor for diabetic microvascular complications in addition to female, age, longer diabetic duration, higher fasting plasma glucose ( FPG ) . Multivariate logistic regression analysis showed that higher nocturnal serum cortisol level was still a risk factor for diabetic microvascular complications after adjusted by diabetic duration, FPG, HbA1C, and the use of insulin (P=0.013). Conclusion Nocturnal serum cortisol level seems to be a risk factor for diabetic microvascular complications in overweight or obese patients with type 2 diabetes mellitus.