Temporal interference (TI) is a form of stimulation that epitomizes an innovative and non-invasive approach for profound neuromodulation of the brain, a technique that has been validated in mice. Yet, the thin cranial bone structure of mice has a marginal influence on the effect of the TI technique and may not effectively showcase its effectiveness in larger animals. Based on this, we carried out TI stimulation experiments on rats. Following the TI intervention, analysis of electrophysiological data and immunofluorescence staining indicated the generation of a stimulation focus within the nucleus accumbens (depth, 8.5 mm) in rats. Our findings affirm the viability of the TI methodology in the presence of thick cranial bones, furnishing efficacious parameters for profound stimulation with TI administered under such conditions. This experiment not only sheds light on the intervention effects of TI deep in the brain but also furnishes robust evidence in support of its prospective clinical utility.
Animals ; Deep Brain Stimulation/methods* ; Nucleus Accumbens/physiology* ; Male ; Rats ; Rats, Sprague-Dawley ; Time Factors

Objective:To understand the distribution characteristics of pulse oxygen saturation (SpO 2) in the high altitude areas. Methods:From September 2016 to December 2017, all healthy and full-term live births in the First Hospital of Lanzhou University and Dunhuang, Jiuquan, Jingning and Lintao branches were selected as the research objects.Critical congenital heart disease or pulmonary diseases were excluded in advance.SpO 2 in different parts of newborns within 12 hours of birth was measured.Statistical comparisons of SpO 2 in different parts of male and female neonates in the same area and SpO 2 in different parts of different regions were made.The number of SpO 2 and the distribution of percentile difference between the lower limbs and the right upper limb of newborns at different altitude areas were obtained. Results:There were no significant difference between male and female infants in SpO 2 value at any lo-wer extremity and right upper extremity and the difference value in the same area (all P>0.05). There were significant differences in the median ( M) values of SpO 2 and the M value of the difference between the two values of any lower limb and right upper limb at different altitudes (all P<0.05). The results showed that the M value of SpO 2 of the right upper limb ( M=96%) in Lanzhou (1 520 m above sea level) was lower than that in Dunhuang (1 138 m above sea level, M=97%) and Jiuquan (1 481 m above sea level, M=97%), and the M value of the difference between the two values ( M=2%) was higher than that in Dunhuang and Jiuquan ( M=1%) ( P<0.05). The M of SpO 2 of any lower limb ( M=96%) and right upper limb ( M=96%) in Jingning areas (1 668 m above sea level) were lower than that in Dunhuang and Jiuquan area (all P<0.05). The median value of SpO 2 of any lower limb ( M=96%) and right upper limb ( M=96%) in Lintao area (1 883 m above sea level) was lower than that in Dunhuang and Jiuquan areas, and the M value of the difference between the two values ( M=2%) was higher than that in Dunhuang and Jiuquan (all P< 0.05). When the altitude was lower than 1 500 m, the M value of SpO 2 was 97%, P3- P97 was 93%-100%; the M value of the difference between any lower limb and right upper limb was 1, and P3- P97 was 0-4.When the altitude was higher than 1 500 m, the M value of SpO 2 was 95%-96%, P3- P97 was 89%-100%; the M value of SpO 2 of an lower limb and right upper limb was 1%-2%, and P3- P97 was 0-9%. Conclusions:The SpO 2 number and percentage distribution of the difference between any lower limb and right upper limb of newborns at different altitudes are different.

Objective: To investigate the knowledge regarding clinical research among children at 8-18 years of age. The survey results will form the basis for developing public education program for this population. Methods: The survey was conducted among children at 8-18 years of age using WeChat and spot investigation between January 2016 and January 2017. According to different developmental stages, the survey population was divided into four groups: age 8-10, 11-13, 14-15 and 16-18 years. The level of knowledge regarding clinical research was analyzed. Results: Totally 1 329 questionnaires were issued and 1 233 effective questionnaires were returned with a recovery rate of 92.8%. The overall awareness rate regarding clinical research was 32.8% (405/1 233) . It revealed that 282 (22.9%) individuals thought that clinical research was to treat people like experimental rats. When asked "who have the final decision on research participation", the percentages of those who chose oneself, parents or guardian and doctor were 44.6% (550/1 233), 74.2% (915/1 233) and 36.8% (454/1 233) respectively. When asked "If you want to participate a study, but your parents or guardian do not agree, what would you do?", 33.9% (418/1 233) of individuals will "give up". As to "If you do not want to participate a study, but your parents or guardian think you should, what would you do?", 51.3% (632/1 233) chose "listen to parents" and 28.8% (355/1 233) chose "refuse the suggestions of parents or guardian". As to "what are your greatest concerns of participating an investigation?" , 68.1% (840/1 233) chose "worry about added pain or discomfort". but 58.0% (715/1 233) thought if "doctors and nurses take good care of me" their "concerns will reduce" or "feel better to participate in the research?". 55.6% (686/1 233) and 49.3% (608/1 233) individuals responded that they will "participate in an research?" when they "know that other people also participate the research" and when they "know the details regarding what will happen after the enrollment". Conclusions The knowledge level of clinical research among children aged 8-18 years were not high. It is very necessary to promote the public education of clinical research for this population and also very necessary to address their concern regarding the research.

To investigate the knowledge regarding clinical research among children at 8-18 years of age. The survey results will form the basis for developing public education program for this population. Methods The survey was conducted among children at 8-18 years of age using WeChat and spot investigation between January 2016 and January 2017. According to different developmental stages, the survey population was divided into four groups: age 8-10, 11-13, 14-15 and 16-18 years. The level of knowledge regarding clinical research was analyzed. Results Totally 1 329 questionnaires were issued and 1 233 effective questionnaires were returned with a recovery rate of 92.8%. The overall awareness rate regarding clinical research was 32.8% (405/1 233). It revealed that 282 (22.9%) individuals thought that clinical research was to treat people like experimental rats. When asked"who have the final decision on research participation", the percentages of those who chose oneself, parents or guardian and doctor were 44.6% (550/1 233), 74.2% (915/1 233) and 36.8% (454/1 233) respectively. When asked "If you want to participate a study, but your parents or guardian do not agree, what would you do?", 33.9% (418/1 233) of individuals will "give up". As to "If you do not want to participate a study, but your parents or guardian think you should, what would you do? ", 51.3% (632/1 233) chose"listen to parents" and 28.8% (355/1 233) chose"refuse the suggestions of parents or guardian". As to "what are your greatest concerns of participating an investigation?", 68.1% (840/1 233) chose"worry about added pain or discomfort". But 58.0%(715/1 233) thought if"doctors and nurses take good care of me"their "concerns will reduce" or "feel better to participate in the research? ". 55.6% (686/1 233) and 49.3% (608/1 233) individuals responded that they will"participate in an research? "when they"know that other people also participate the research" and when they"know the details regarding what will happen after the enrollment". Conclusions The knowledge level of clinical research among children aged 8-18 years were not high. It is very necessary to promote the public education of clinical research for this population and also very necessary to address their concern regarding the research.

AIM: To investigate the role of chloride channels in the apoptosis of human poorly differentiated nasopharyngeal carcinoma CNE-2Z cells induced by arsenic trioxide (As2O3).METHODS: The apoptotic rates of CNE-2Z cells induced by As2O3 for 24 h or 48 h were monitored by flow cytometry.The technique of whole-cell patch clamp was used to record the currents activated by As2O3 in the CNE-2Z cells.The inhibition of As2O3-induced apoptosis by chloride channel blocker DIDS in the CNE-2Z cells was analyzed by flow cytometry.RESULTS: As2O3 at 5 μmol/L induced apoptosis of CNE-2Z cells in time-dependent manner.The currents with outward rectification were activated when the cells were exposed to 5 μmol/L As2O3.No obvious time-and voltage-dependent inactivation of the currents was observed.The reverse potential of the currents was close to the equilibrium potential for chloride.The activated currents were inhibited by the chloride channel blockers NPPB and DIDS.The 47% hypertonic solution inhibited the activated currents completely.Chloride channel blocker DIDS inhibited the apoptosis of CNE-2Z cells induced by As2O3.CONCLUSION: As2O3 activates volume-sensitive chloride channels, and chloride channels may play an important role in the apoptosis of CNE-2Z cells induced by As2O3.

AIM:To explore the influence of exogenous hydrogen sulfide ( H2 S) on coagulation and fibrinoly-sis in ferric chloride ( FeCl3 )-induced mouse carotid artery thrombosis .METHODS: The mice were divided into sham control group, model group, different concentrations (12.5, 25 and 50μmol/kg) of sodium hydrosulfide (NaHS, H2S do-nor) groups and 30 mg/kg clopidogrel ( positive control ) group.Intraperitoneal injection of NaHS at different concentra-tions and oral administration of clopidogrel bisulfate were performed for 3 d prior to FeCl 3-induced carotid artery thrombo-sis.The frozen sections of the carotid artery were collected to perform HE staining , and the thrombus pattern and the chan-ges of vascular pathology were observed .The thrombus was weighed to calculate thrombosis inhibitory rate .Prothrombin time ( PT) , activated partial thromboplastin time ( APTT) , fibrinogen ( FIB) and fibrinogen degradation product ( FDP) in the mice were also measured by a coagulometer .The plasma levels of thromboxane B 2 ( TXB2 ) , 6-keto-prostaglandin F 1α(6-keto-PGF1α) and plasminogen activator inhibitor (PAI) were detected by ELISA.RESULTS: Compared with model group, NaHS dose-dependently inhibited the formation of carotid artery thrombus .NaHS treatment reduced the contents of TXB2 and PAI, and recovered 6-keto-PGF1αcontent in thrombosis model group .In NaHS treatment groups , 6-keto-PGF1α/TXB2 and thrombus weight was negatively correlated .NaHS treatment prolonged PT and APTT , reduced the content of FIB, but increased the level of FDP in thrombosis model group .CONCLUSION:Hydrogen sulfide prevents FeCl 3-induced carotid artery thrombosis by inhibiting coagulation and activating fibrinolysis .

AIM To explore the radioprotective function of Xihuang Capsules (Bovis Calculus artijactus,Moschus,Olibanum,Myrrha) in patients with acute radiation-induced oral mucositis and its mechanisms.METHODS Eighty patients with nasopharyngeal carcinoma undergone radiotherapy were randomized into two groups:treatment group (radiation plus Xihuang Capsules) and control group (radiation alone).The comparison of two groups in the onset and the tolerated dose of mucositis was made according to the acute radiation injury classification standard.The levels of TNF-α and IL-6 in saliva were detected by ELISA.RESULTS After the treatment with Xihuang Capsules,the onset of oral mucositis delayed significantly and the tolerated dose elevated markedly comparing with the control group (t =2.180,12.930,P ＜ 0.05).The morbidity rate of Ⅲ-N-degree of oral mucositis in the treatment group was lower than that of the control group at the dosage of 40 Gy and 70 Gy,respectively (Z =3.661,4.270,P ＜0.01).Furthermore,there was no difference in the levels of TNF-α and IL-6 in the pre-treatment in the two groups (t =1.010,1.469,P ＞ 0.05).With the increase in radiant dose,the levels of TNF-α and IL-6 in the two groups both elevated dramatically,and peaked at the dose of 40 Gy,but both levels in the treatment group were lower than those of the control group (t =8.305,6.069,P ＜ 0.05).When DT =70 Gy,the levels of TNF-α and IL-6 were lower than pre-radiation,and the levels of TNF-α and IL-6 in the treatment group were lower than those in the radiation alone group (t =3.835,2.488,P ＜ 0.05).CONCLUSION Xihuang Capsules can delay and reduce acute radiation-induced oral mucositis and improve radiation tolerated dose,so it may involve the release of TNF-oα and IL-6 in saliva.

[ ABSTRACT] AIM:To investigate the effect of the overexpression of voltage-gated chloride channel family protein 3 ( ClC-3) gene on bones of mice .METHODS: The tail gene detection assay was used to confirm the overexpression of ClC-3.The male FVB mice of three months old were divided into two groups , the wild type ( WT) group and the ClC-3 overexpressed (ClC-3 transgene) group.The body weight, length and weight of the right tibias were measured .The upper and middle parts of the tibias were dissected , decalcified, paraffin-imbed, sectioned and stained with HE staining .The bone morphology metrology was used to analyze the changes of bone structures .The percent trabecular area (%Tb.Ar), trabecular number ( Tb.N) , trabecular width ( Tb.Wi) and trabecular separation ( Tb.Sp) of cancellous bone in the upper part of the tibia were measured.The total tissue area (T.Ar), cortical area (Ct.Ar), percent cortical area (%Ct.Ar), marrow area ( Ma.Ar) and percent marrow area (%Ma.Ar) of the cortical bone in the middle part of the tibia were detec-ted .RESULTS:The wild type mice and the ClC-3-overexpressed mice were verified by the tail gene detection assay . Compared with WT group , the body weight and the length and weight of the tibia were decreased in ClC -3 transgene mice (P<0.05).In the cancellous bones of ClC-3 transgene mice, the%Tb.Ar and Tb.Wi were decreased (P<0.05), the Tb.Sp was increased (P<0.05) and the Tb.N was not significantly changed .In the cortical bones of ClC-3 transgene mice, the T.Ar, Ct.Ar and%Ct.Ar were decreased (P<0.05), the%Ma.Ar was increased (P<0.05), and the Ma. Ar was not significantly changed .CONCLUSION:ClC-3 overexpression may lead to the reduction of the bone mass and the destructure of the cancellous and cortical bones .The results suggest that ClC-3 may be involved in the regulation of bone resorption and/or formation.

AIM: To study the effects of disulfiram/copper complex (DSF/Cu) on ultrastructures and mechan-ical properties of human breast cancer and normal breast epithelial cells by atomic force microscopy (AFM) based on the nanoscale resolution and piconewton force measurement level.METHODS: The change of cell cycle and apoptotic rate of MCF-7 cells and MCF-10A cells induced by DSF/Cu were compared by flow cytometry.The cell surface morphology, ultra-structure, height, width and roughness were detected by AFM.The effects of DSF/Cu on the hardness (Young’s modu-lus) of the 2 kinds of cells were determined by AFM with indentation technique.RESULTS: DSF/Cu significantly in-duced apoptosis of the MCF-7 cells in a dose-dependent manner, whereas had little effect on the MCF-10A cells.The cell cycle analysis showed that DSF/Cu induced G2 /M arrest in the MCF-7 cells, but led to G0 /G1 arrest in the MCF-10A cells.The AFM images showed that the MCF-7 cells shrank and showed smaller and smoother morphology, and the filopo-dia were retracted obviously, even some became into lamellipodia, or disappeared completely after treated with DSF/Cu at concentrations of 400 and 800 nmol/L.The quantitative analysis indicated that the MCF-7 cells showed smaller width and
larger height, and the root mean square roughness and average roughness were decreased significantly in a dose-dependent manner after treated with DSF/Cu at concentrations of 400 and 800 nmol/L.However, little effect in the MCF-10A cells was observed.The biomechanics test at a single cell level demonstrated that the Young’s modulus of the MCF-7 cells and MCF-10A cells were both increased, yet the proportion increased in the MCF-7 cells was much higher than that in the MCF-10A cells after treated with DSF/Cu at concentrations of 400 and 800 nmol/L.CONCLUSION: DSF/Cu has strong antitumor effect on breast cancer with high efficiency and low toxicity by changing the properties of the biomechanics specifically.

Aim To study the mechanism of DSF-Cu induced apoptosis of human nasopharyngeal carcinoma CNE-2 Z cells by affecting the function of mitochondria and cytoskeleton. Methods The cell cycle,the rate of apotosis,the levels of intracellular ROS and MMP in CNE-2 Z cells were tested by flow cytometry after trea-ted with different concentration of DSF-Cu. The chan-ges of the cell surface morphology, ultrastructure, cell height, width and roughness were detected by AFM. The distribution and reorganization of cytoskeleton F-actin were observed by Laser scanning confocal micro-scope. Results Cells were incubated with different concentration of DSF-Cu ( 0 ~200 nmol · L-1 ) for 24 h, the apoptotic ratio increased significantly and the treatment of DSF-Cu resulted in a concentration-de-pendent accumulation of CNE-2Z cells in G2/M phase. Furthermore,the treatment of DSF-Cu was able to in-crease the production of intracellular ROS and decrease the MMP in CNE-2Z cells. In addition,AFM imaging showed that compared to the control group,with the in-crease of DSF-Cu concentration,the CNE-2Z cells be-came smaller, cytoplasm condensed, the height in-creased,and the surface roughness reduced. Moreover, the filopodia became shorter, shrinked and even com-pletely destroyed after treated with different concentra-tion of DSF-Cu. At last,the LSCM image showed that the fluorescence intensity of F-actin networks was de-creased, then the structure was rearranged and de-stroyed obviously by treated with DSF-Cu. Conclusion DSF-Cu can induce apoptosis and arrest cell cycle at G2/M phase in CNE-2Z cell through a mitochondria-dependent pathway. Above findings highlight the appli-cations of AFM at the single cell level for the investiga-tion of antineoplastic drug in nasopharyngeal carcinoma therapy.