BACKGROUND:Transcranial magneto-acoustic-electrical stimulation is a novel non-invasive neural regulation technique that utilizes the induced electric field generated by the coupling effect of ultrasound and static magnetic field to regulate the discharge activity of the nervous system.However,the mechanism by which it affects synaptic plasticity in the brain is still not enough. OBJECTIVE:To explore the effect of transcranial magneto-acoustic-electrical stimulation intensity on synaptic plasticity of the prefrontal cortex neural network in mice. METHODS:(1)Animal experiment:Twenty-four C57 mice were equally and randomly divided into four groups:the control group receiving pseudo-stimulation,the 6.35 W/cm2 stimulation group receiving coupled stimulation of 0.3 T,6.35 W/cm2,the 17.36 W/cm2 stimulation group receiving coupled stimulation of 0.3 T,17.36 W/cm2,and the 56.25 W/cm2 stimulation group receiving coupled stimulation of 0.3 T,56.25 W/cm2.The local field potential signals and behavioral correctness were recorded during the execution of T-maze in mice.(2)Modeling and simulation experiments:A neural network model of the prefrontal cortex in mice stimulated by transcranial magneto-acoustic-electrical stimulation was constructed to compare the structural connectivity characteristics of the neural network under different stimulation intensities. RESULTS AND CONCLUSION:Transcranial magneto-acoustic-electrical stimulation could effectively shorten the behavior learning time,improve the working memory ability of mice(P＜0.05),and continue to stimulate the frontal lobe of mice after learning behavior.There was no significant difference in the accuracy of the T-maze behavioral experiment among the experimental groups(P＞0.1).Analysis of local field potential signals in the frontal lobe of mice revealed that transcranial magneto-acoustic-electrical stimulation promoted energy enhancement of β and γ rhythms.As the stimulation intensity increased,there was an asynchronous decrease in β and γ rhythms.Through β-γ phase amplitude coupling,it was found that stimuli could enhance the neural network's ability to adapt to new information and task requirements.Modeling and simulation experiments found that stimulation could enhance the discharge level of the neural network,increase the long-term synaptic weight level,and decrease the short-term synaptic weight level only when the stimulation intensity was high.To conclude,there is a complex nonlinear relationship between different stimulus intensities and the functional structure of neural networks.This neural regulation technique may provide new possibilities for the treatment of related neurological diseases such as synaptic dysfunction and neural network abnormalities.

Angiokinases, such as vascular endothelial-, fibroblast- and platelet-derived growth factor receptors (VEGFRs, FGFRs and PDGFRs) play crucial roles in tumor angiogenesis. Anti-angiogenesis therapy using multi-angiokinase inhibitor has achieved great success in recent years. In this study, we presented the design, synthesis, target identification, molecular mechanism, pharmacodynamics (PD) and pharmacokinetics (PK) research of a novel triple-angiokinase inhibitor WXFL-152. WXFL-152, identified from a series of 4-oxyquinoline derivatives based on a structure-activity relationship study, inhibited the proliferation of vascular endothelial cells (ECs) and pericytes by blocking the angiokinase signals VEGF/VEGFR2, FGF/FGFRs and PDGF/PDGFR simultaneously . Significant anticancer effects of WXFL-152 were confirmed in multiple preclinical tumor xenograft models, including a patient-derived tumor xenograft (PDX) model. Pharmacokinetic studies of WXFL-152 demonstrated high favourable bioavailability with single-dose and continuous multi-dose by oral administration in rats and beagles. In conclusion, WXFL-152, which is currently in phase Ib clinical trials, is a novel and effective triple-angiokinase inhibitor with clear PD and PK in tumor therapy.

Objective:To explore the diagnostic value of chest CT imaging in differential diagnosis between common-type COVID-19 and mycoplasma pneumonia (MP).Methods:From the January to February 2020, the clinical and imaging data of COVID-19 patients (diagnosed in the Affiliated Hospital of Jining Medical University, the Fourth People's Hospital of Jining and the Second People's Hospital of Jining) and MP patients (diagnosed in the Affiliated Hospital of Jining Medical University) were retrospectively collected and analyzed. Forty-three patients with common-type COVID-19 (28 males, 15 females, 43±14 years old) and 50 patients with MP (19 males, 31 females, 37±14 years old) were enrolled as COVID-19 group and MP group, respectively. The clinical manifestations, laboratory results and chest CT findings of these two groups were analyzed and compared.Results:(1) Clinical manifestations: there were more patients with muscle ache and asthenia in COVID-19 group than in MP group (χ 2=5.110, 4.834, P<0.05). No significant difference was found in fever and cough between two groups (χ 2=0.378, 0.097, P>0.05). (2) Laboratory examination: the procalcitonin level of cases in COVID-19 group was significantly lower than that in MP group (χ 2=12.263, P=0.001). No significant difference was found in leukocyte count, lymphocyte count, C-reactive protein level and erythrocyte sedimentation rate ( Z=-1.117, χ 2=2.410, 0.787, 0.800, all P>0.05) between two groups. (3) Chest CT findings bilateral lung involvement was found more in COVID-19 group than in MP group (χ 2=30.012, P<0.001); while the one lobe of ipilateral lung involvement was less in COVID-19 group than in MP group (χ 2=19.927, P<0.001); there was no significant difference in multiple lobes of ipilateral lung involvment between the two groups (χ 2=1.366, P>0.05). Ground glass, paving stone sign and air bronchus sign were found significantly more in COVID-19 group than in MP group (χ 2=30.171, 19.119, 9.790, all P<0.05); while the pulmonary consolidation, central lobular nodule and centripetal thickening of bronchus wall were found significantly less in COVID-19 group than in MP group (χ 2=25.450, 33.532, 48.553, all P<0.001). Conclusions:The clinical manifestations and laboratory examination have limited value in the differential diagnosis of common-type COVID-19 and MP, while chest CT imaging might be more valuable in the early differential diagnosis of these two diseases.

Breast cancer is the most common cancer for Chinese women. Early screening is the best way to improve the rates of early diagnosis and early treatment of breast cancer. The peak ages of breast cancer in Chinese women are obviously different from those in the European and American countries. It is imperative to develop a guideline for breast cancer screening that is suitable for Chinese women. Based on the analysis and summary of breast cancer screening data in China, and the latest guidelines and consensus on breast cancer screening in Europe, the United States and East Asia, China Anti-Cancer Association and National Clinical Research Center for Cancer (Tianjin Medical University Cancer Institute and Hospital) has developed a population-based guideline for breast cancer screening in Chinese women. This guideline has provided detailed recommendations on the screening starting age, screening modalities, and screening interval in Chinese women with average risk and high risk of breast cancer, respectively. This article aims to interpret the above guideline, providing references for professionals in breast cancer screening.

Triple negative breast cancer (TNBC) is a highly aggressive subtype of breast cancer that is characterized by the lack of estro-gen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER-2), thereby making it difficult to treat. Owing to the aggressive clinical behavior of TNBC and the lack of recognized molecular targets for therapy, patients with TNBC have shown poorer outcomes than those with other subtypes of breast cancer. Chemotherapy is the primary established systemic treatment for TNBC. However, various novel therapeutic targets have come into focus with the advances in molecular characterization of TNBC. In recent years, several targeted drugs have undergone clinical trials and have shown certain curative effects with relatively mild adverse reactions. The Food and Drug Administration has approved some of these drugs. In the current review, we have summa-rized the advances in the targeted therapy of TNBC.

Objective:To investigate the mechanism of histone deacetylase (HDAC) inhibitor in down-regulating the expression of HER-2 in breast cancer cells and to provide an innovative therapeutic option to overcome the disadvantages of anti-HER-2 therapy. Meth-ods:HER-2-positive breast cell lines were treated with HDAC inhibitors. The changes in the gene and protein levels of HER-2 were de-tected by qPCR and Western blot. MiRNA microarray was used to identify the HDAC inhibitors, whereas qPCR was used to verify the miRNA expression. Results:In vitro cell experiments confirmed that the HDAC inhibitors TSA and SAHA can down-regulate the expres-sion of HER-2 in breast cancer cell lines. TSA can down-regulate the expression of HER-2 gene in BT474 and decrease the concentra-tions of 100 nmol by 10.7%and 200 nmol by 38.9%(P<0.05). TSA had no effect on the primary cells. The expression of HER-2 gene of BT474 was down-regulated by 93.9%(P<0.05) in the 5μmol/L group but not in the 1μmol/L group. SAHA significantly affected the pri-mary cells at a concentration of 1μmol/L and reduced the cells at 87.1%at a concentration of 5μmol/L. Seven miRNAs were identified from the miRNA microarray. MiR-762 was used as a basis to identify the changes in miRNA. The miRNA sputum identified by miRNA microarray and qPCR may be associated with the down-regulation of HER-2 by HDAC inhibitors. Conclusion: HDAC inhibitors may down-regulate the expression of HER-2 in breast cancer cells by changing some miRNAs.

OBJECTIVETo investigate the association of neuroendocrine differentiation with progression and prognosis of gastric adenocarcinoma.

METHODSClinicopathological data of 240 patients with gastric adenocarcinomas were retrospectively analyzed. The expression of chromogranin A, synaptophysin and secrectagogin in cancer tissue was assessed by immunohistochemistry. The association of neuoroendocrine differentiation parameters with disease progression and survival of patients was analyzed.

RESULTSThe expression of synaptophysin was positively correlated with depth of invasion and secretagogin more often expressed in cases with lymph node metastasis. In Lauren diffuse type of cancer, expression of chromogranin A and secretagogin was unfavorable prognostic predictor. In TNM stage II adenocarcinoma, expression of chromogranin A and synaptophysin related to poor survival, and multivariate Cox proportional hazard model showed that synaptophysin was an independent predictor for poor survival.

CONCLUSIONNeuroendocrine differentiation predicts deeper depth of invasion, more possibility of lymph node metastasis and poor survival in gastric adenocarcinoma.

Adenocarcinoma ; diagnosis ; pathology ; Biomarkers, Tumor ; metabolism ; Chromogranin A ; metabolism ; Disease Progression ; Humans ; Immunohistochemistry ; Lymphatic Metastasis ; Neoplasm Staging ; Neuroendocrine Tumors ; diagnosis ; pathology ; Prognosis ; Proportional Hazards Models ; Retrospective Studies ; Secretagogins ; metabolism ; Stomach Neoplasms ; diagnosis ; pathology ; Synaptophysin ; metabolism

Objective:To explore the feasibility of inguinal subcutaneous immunotherapy for allergic rhinitis ( AR ) in mice. Methods:36 female BALB/c mice were divided randomly into six groups( n=6 per group) including the control A,the model A, the treatment A groups,and the control B,the model B,the treatment B groups(inguinal subcutaneous immunotherapy for group A, cervical back subcutaneous immunotherapy for for group B). AR model was established with ovalbumin. At 25 to 55 days,ovalbumin im-munotherapy were performed in treatment groups,once two days,15 times totally. After intranasal rechallenge was performed at 56 to 62 days the AR symptom scores were documented. The eosinophils(EOS)in the nasal mucosa were measured by chromotropic acid 2R staining. Ovalbumin-specific IgE( OVA-sIgE) in the serum and expression of interferon-γ and interleukin-4 in the nasal lavage were measured by enzyme-linked immunosorbent assay meanwhile the ratio of interferon-γ and interleukin-4 was calc μlated. SPSS17. 0 software was used to analyze the data. Results:Before treatment ,the AR symptom scores of the model and treatment groups were more than 5. After treatment,the treatment A group were less than 5. The EOS count of the control A,model A,treatment A groups and the control B,model B, treatment B groups was 0. 78 ± 0. 31, 21. 60 ± 2. 90, 10. 43 ± 2. 56, 0. 83 ± 0. 46, 22. 44 ± 3. 39, 23. 40 ± 4. 24, respectively. The EOS count of the treatment A group was significantly lower than those in model A group ( P<0. 05 ) . There was no significant difference between treatment B and model B group ( P>0. 05 ) . OVA-sIgE expressed was negative in control groups and positive in other groups. The ratio of interferon-γ and interleukin-4 was 10. 75 ± 3. 38,10. 38 ± 3. 08,3. 02 ± 0. 69,2. 71 ± 0. 89,2. 52 ± 0. 30,5. 45±1. 41,respectively. The ratio in treatment A group was significantly higher than those in model A group(P<0. 05). There was no significant difference between treatment B and model B group ( P>0. 05 ) . Conclusion: Inguinal subcutaneous immunotherapy has a good effect on this disease. It spends short time ,has simple operation and good feasibility,which is a novel treatment method for AR in mice.

Objective To investigate the effects of simultaneous multi-level surgery for moderate to severe obstructive sleep apnea hypopnea syndrome (OSAHS). Methods A retrospective analysis was made on surgical cases of one hundred and thirty seven patients with moderate to severe OSAHS diagnosed by polysomnography (PSG). They were divided into multi-level group (n = 95) and UPPP group (n = 42). The two groups were compared in terms of postoperative complications as well as the related indicators of PSG , calgary sleep apnea quality of life index (SAQLI), epworth sleepiness scale (ESS), snore scales (SS) before operation and after operation. Results Just one patient in the multi-level group had difficulties in respiration and was rescued by timely tracheotomy. The AHI, LSaO2, TS90%, the total score and the scores on the four dimensions of SAQLI, ESS score, SS score in the multi-level group were significantly improved as compared both to the results after operation (P < 0.01) and to the UPPP group (P < 0.05). But only the AHI, LSaO2 and TS90% in the UPPP group were improved (P < 0.05). Conclusions The multi-level surgery is a safe and feasible therapy or moderate to severe OSAHS. The evaluation in subjective and objective ways can be more accurate in comprehensive reflecting the surgical efficacy and effects of OSAHS on patients′ of life quality.

OBJECTIVE: To explore the effects of simultaneous multi-level surgery intervention on the changes of the oxidative stress and the cognitive function in young and middle-aged patients with moderate-severe OSAHS. METHOD: One hundred and sixteen young and middle-aged patients with moderate-severe OSAHS received simultaneous multi-level surgery. PSG,malondialdehyde (MDA), advanced oxidation protein products (AOPP) and 8-isoprostaneF2α (8-iso-PGF2α) were tested, together with the evaluation of the questionnaires of Montreal cognitive assessment (MoCA), mini-mental state examination (MMSE) and Epworth sleepiness scale (ESS) before and 6 months after surgery. RESULT: (1) The AHI, TS90% and LSaO₂ were all improved significantly 6 months after operation. No severe complications were observed in any patient. (2) The preoperative MoCA and MMSE scores were (23.52 ± 2.64) and (26.54 ± 1.07) respectively. The cognitive impairment were detected in OSAHS patients. MoCA was negatively correlated with AHI, TS90%, MDA, AOPP and 8-iso-PGF2a, while positively correlated with LSaO₂ (P < 0.05, r = -0.233, -0.190, -0.256, -0.247, -0.221 and 0.215, respectively). Cognitive impairment was mainly manifested as disorder in the visual space and execu- tive function, memory and delayed recall (mainly short-term memory). (3) MoCA and MMSE scores were both increased (P < 0.05) after the operation. MoCA showed negative correlations with MDA, AOPP, 8-iso-PGF2α, AHI and TS90%, and positive correlation with LSaO₂ (P < 0.05, r = -0.495, -0.463, -0.397, -0.332, -0.292 and 0.336, respectively). CONCLUSION Oxidative stress and cognitive dysfunction are closely related in young and middle-aged patients with Moderate-severe OSAHS. Oxidative stress may play an important role in cognitive function of young and middle-aged patients with Moderate-severe OSAHS. Multi-level surgery can improve oxidative stress so that to improve cognitive impairment.
Adult ; Cognition ; Cognition Disorders ; complications ; Humans ; Middle Aged ; Oxidative Stress ; Sleep Apnea, Obstructive ; surgery