Objective To explore the expression profile of adenosine A1 receptor in the paraventricular thalamic nucleus(PVT)in wakefulness/sleep state and its role in regulating sleep.Methods Male C57BL/6J mice(6～12 weeks old,weighing 22～28 g)were randomly divided into ZT0,ZT6,ZT10,ZT12,and sleep deprivation and recover0y sleep groups(n=16 or n=4).RT-qPCR and fluorescence in situ hybridization were used to observe the changes of adenosine A1 receptor in PVT.Whole-cell patch-clamp recording was conducted to determine the effects of adenosine on the membrane potential and discharge frequency of PVT neurons.The experimental animals were divided into adenosine A1 receptor interference group(n=8)and interference control group(n=7).After RNA interference,electroencephalography(EEG)and electromyography(EMG)were applied simultaneously to observe the changes in wake and sleep time between the 2 groups during sleep deprivation for 6 h and sleep recovery for 4 h.Results RT-qPCR and fluorescence in situ hybridization confirmed that the expression of adenosine A1 receptor in PVT was affected by wakefulness/sleep state,with the level in the ZT0 group(active stage)significantly higher than that in the ZT12 group(non-active stage,P<0.05).Whole-cell patch clamp recording indicated that adenosine exerted inhibitory effects on PVT neurons through 2 distinct response types(P<0.05),and the inhibition was in a diminishing trend with a decrease in the expression level of adenosine A1 receptor.After sleep deprivation,the expression level of adenosine A1 receptor showed significant intergroup differences:the level was significantly higher in the sleep deprivation group than the recovery sleep group(P<0.05),while that of the recovery sleep group was higher than that of the ZT6 group and that of the ZT10 group(P<0.05).After knocking down adenosine A1 receptor(shRNA-A1R)in the PVT,the wakefulness timing of the shRNA-A1R group was significantly increased,while the sleep timing was significantly decreased within 1 h after sleep recovery when compared with the interference control group(P<0.05).Conclusion The expression of adenosine A1 receptor in the PVT is dynamically regulated by sleep pressure,which was increasing as sleep pressure rises.

Colon cancer is a complex disease characterized by the impairment of body,qi and spirit,as well as the establishment of a tumor immune microenvironment(TIME)induced by chronic stress.Chronic stress is classified as a micro-level mental disorder,while TIME serves as the biological foundation for qi disorders.The observable manifestation of colon cancer is the tangible representation of physical disease.The interconnected mechanism of"chronic stress-TIME-colon cancer"aligns with the traditional Chinese medicine's understanding of disease as involving the interplay between the body,qi and spirit.In treatment,we should cooperate to improve the"regulating mind"of chronic stress and reshape the"invigorating qi"of TIME,and finally achieve the purpose of shape treatment to delay the progression of colon cancer.The paper is to provide new insights into the treatment of colon cancer with traditional Chinese medicine.

Colon cancer is a complex disease characterized by the impairment of body,qi and spirit,as well as the establishment of a tumor immune microenvironment(TIME)induced by chronic stress.Chronic stress is classified as a micro-level mental disorder,while TIME serves as the biological foundation for qi disorders.The observable manifestation of colon cancer is the tangible representation of physical disease.The interconnected mechanism of"chronic stress-TIME-colon cancer"aligns with the traditional Chinese medicine's understanding of disease as involving the interplay between the body,qi and spirit.In treatment,we should cooperate to improve the"regulating mind"of chronic stress and reshape the"invigorating qi"of TIME,and finally achieve the purpose of shape treatment to delay the progression of colon cancer.The paper is to provide new insights into the treatment of colon cancer with traditional Chinese medicine.

Objective To explore the changes in Th1 cell,B cell and related gene expression during the healing of diabetic foot ulcers(DFU).Methods Lesional skin tissues from DFU patients surgically treated in our hospital from January 2022 to January 2023 were selected.DFU associated gene expression data were collected from GSE80178 and GSE143735 datasets.The expressions of genes(DEGs)between ulcer and no-ulcer patients were identified.Bioinformatics methods were used to identify abnormal immune cells and key genes.Finally,the key results were detected by RT-qPCR and flow cytometry.Results A total of 548 common DEGs were identified in two datasets.In 14 co-expression modules,darkgrey and darkgreen were most related to ulcer,which were mainly associated with the regulation of enzyme activity,immune function and endocrine regulation.Flow cytometry showed that Th1 and B cells were highly infiltrated in ulcer tissue and decreased in healing tissue.MMP13,S100A9 and STAT4 were involved in immune signaling pathways.MMP13 and STAT4 were lowly expressed in healed ulcers,whereas S100A9 was highly expressed.Conclusion Reduced levels of Th1 and B cell infiltration may promote DFU healing.

Objective To explore the differences in scapular motion and shoulder function between patients suffering from rotator cuff tears(RCT)with and without type Ⅲ scapular dyskinesis(SD).Meth-ods Between September 2021 and March 2023,sixteen patients suffering from rotator cuff tears with SD(SD group)and 17 counterparts without SD(non-SD group)were recruited from the Sports Hospital of the General Administration of Sport of China.Their scapular motion was assessed by measuring three parameters in the X-rays,including scapular spine line(LSS),scapular upward rotation angle(SU-RA),and coracoid upward shift distance(CUSD).Moreover,their shoulder range of motion in flexion,abduction and external rotation were recorded,and further evaluated using the Pain Visual Analog Scale(VAS)and American Shoulder and Elbow Surgeons Score(ASES).Results No significant differenc-es were found between the two groups in the average score of SURA,CUSD and LSS at 0°～30° shoul-der abduction,or in that of CUSD and LSS at 60°～90°shoulder abduction.However,the average SU-RA score of the SD group at 60°～90°shoulder abduction was significantly greater than the other group(P<0.05).The shoulder ranges of motion during active flexion,abduction and external rotation were significantly smaller in the SD group than in the non-SD group(P<0.05).Moreover,the average VAS score in the SD group was significantly higher than the non-SD group(P<0.05),while the average ASES score was significantly lower than the latter group(P<0.05).Conclusions RCT patients type III SD exhibits greater scapular upward rotation during shoulder abduction compared to those without SD.Moreover,the former patients suffer from more severe pain and have worse shoulder range of motion and functional performance than the latter.

Objective To explore the feasibility of CT evaluation of myocardial strain in patients undergoing transcatheter aortic valve replacement(TAVR)with cardiac magnetic resonance(CMR)as the reference standard.Methods A retrospective study was conducted on 43 patients undergoing cardiac CT examination before TAVR in our hospital from June to December 2022.The cardiac CT and CMR data were collected,and myocardial strain parameters were measured.The cardiac function and strain parameters based on cardiac CT were compared with the parame-ters of CMR,including left ventricular ejection fraction(LVEF),left ventricular end-diastolic vol-ume(LVEDV),left ventricular end-systolic volume(LVESV),diastolic myocardial mass(MASS),cardiac output,global peak longitudinal strain(GPLS),global peak circumferential strain(GPCS)and global peak radial strain(GPRS).Results The values of LVEF and cardiac output derived from cardiac CT were close to those from CMR(P＞0.05),while the values of LVEDV,LVESV and MASS from cardiac CT were significantly higher than those from CMR,and those of GPLS,GCPS and GRPS from cardiac CT were obviously lower than those from CMR(P＜0.01).Pearson correlation analysis showed that the LVEF,LVEDV,LVESV,MASS,GCPS and GRPS derived from cardiac CT had strongly positive correlation with those from CMR(r=0.908,r=0.917,r=0.947,r=0.954,r=0.856,r=0.864,P＜0.01),while the cardiac output and GPLS had a moderate positive correlation(r=0.763,r=0.656,P＜0.01).Bland-Altman analysis showed that the LVEF,cardiac output,GPLS,GCPS and GRPS derived from cardiac CT had small biases with those from CMR.Conclusion Cardiac CT quantitative evaluation of cardiac function and strain is feasible in patients undergoing TAVR,and the cardiac function parameters of cardiac CT have good agreement with those from CMR,while the myocardial strain parameters are lower than those from CMR.

The seventh article of Measures for the Ethical Review of Biomedical Research Involving Humans (2016) stipulated that medical and health institutions without an ethics committee shall not carry out biomedical research involving Humans. The Opinions on Strengthening the Governance of Ethics in Science and Technology, issued in March 2022, clearly stated that the institutions that do not meet the conditions for establishing a scientific and technological ethics (review) committee should entrust other institutions to conduct the review. The fourteenth article of Measures for Ethical Review of Life Science and Medical Research Involving Humans (2023) proposes that if an institution, which carries out life science and medical research involving humans, has not established an ethics committee or its ethics committee is not competent for ethics review, it can entrust a competent ethics committee or regional ethics committee in writing to carry out ethical review. Most medical institutions at or above the second level in China have set up ethics committees. While most universities and colleges, scientific research institutions, enterprises and grass-roots medical and health institutions have not set up ethics committees, which lack a working system to protect the safety and interests of the participants, and is difficult to conduct life sciences and medical research involving humans. At present, there is a need for some research institutions that do not have the conditions to establish ethics committees to entrust their projects of life science and medical research involving humans to other institutions for ethical review. The entrusted review is still in the exploratory stage, and there is no relevant specification. The hasty implementation of entrusted review may not achieve the goal of effectively protecting the safety and interests of the participants, and even cause legal disputes. Based on the thematic discussion, with reference to the relevant laws and regulations, departmental rules, ethical standards, and the experience of the ethics committees of some domestic institutions in implementing the entrusted review, the guideline was formulated for the reference of the current entrusted review to ensure the safety and interests of the participants.

The passing of ethical review is a necessary conditions and prerequisite for the development of life science and medical research involving humans. At present, some medical and health institutions have no or insufficient ethical review capabilities. The lack of ethical review ability has become a bottleneck restricting the development of life science and medical research involving humans. According to documents such as Opinions on Deepening the Reform of the Review and Approval System and Encouraging the Innovation of Pharmaceutical and Medical Devices, Opinions on Strengthening the Ethical Governance of Science and Technology, institutions can entrust competent institutional ethics review committees or regional ethics review committees in writing to conduct ethical review. Entrustment ethical review provides a viable solution for institutions that need to carry out life science and medical research involving humans but do not have an ethics (review) committee or the ethics (review) committee is not competent to review. To conduct the entrustment ethical review, the entrustment between the principal and the trustee is required. According to The Measures for Ethical Review of Life Sciences and Medical Research Involving Humans, if medical and health institutions and their ethical review committees do not accept the formal entrustment to provide the ethical review opinions for other institutions, the local health authorities at or above the county level will impose administrative penalties and sanctions on the relevant institutions and personnel in accordance with the law. Signing the entrustment ethical review contract, implementing legal compliance entrusted ethical review to protect the rights and interests of the trustee and the principal, and protect the research participants.

Objective:To evaluate the feasibility of measurement and characteristics of intraocular lens (IOL) tilt using the swept-source optical coherence tomography (SS-OCT) biometer (IOLMaster 700) and to explore its potentially relevant parameters.Methods:A cross-sectional study was conducted.Two hundred and forty-two eyes (119 right eyes, 123 left eyes) of 185 patients after phacoemulsification and IOL implantation were included in Beijing Tongren Hospital from July to September 2018.The IOL position, angle κ, angle α, corneal curvature, anterior chamber depth (ACD), pupil diameter (PD), and axial length (AL) were obtained by IOLMaster 700, and the IOL tilt direction and magnitude were calculated.The within-subject standard deviation and intraclass correlation coefficient were used to evaluate the repeatability of three IOL tilt measurements.Binocular symmetry of IOL tilt and the correlation between IOL tilt and different influencing factors were evaluated by Pearson linear correlation analysis or Spearman rank correlation analysis.Influencing factors for IOL tilt were assessed by multiple linear regression analysis.This study adhered to the Declaration of Helsinki.The study protocol was approved by the Ethics Committee of Beijing Tongren Hospital, Capital Medical University (No.TRECKY2018-049). Patients were informed of the purpose and methods of this study and signed the written informed consent.Results:The repeatability of IOL tilt measurements was excellent with a within-subject standard deviation of 5.16° for IOL tilt direction and 0.13° for IOL tilt magnitude.IOL tilt was mirror symmetric in both eyes.The IOL tilt direction in right eyes ranged from -89.60° to 87.53° with a mean of (18.85±29.65)°, and the tilt magnitude ranged from 1.32° to 7.05° with a mean of (4.16±1.26)°.The IOL tilt direction in left eyes ranged from -84.30° to 89.44° with a mean of (21.17±32.38)°, and the tilt magnitude ranged from 0.58° to 7.40° with a mean of (3.80±1.31)°.There were moderate and weak positive correlations of IOL tilt direction and tilt magnitude between both eyes ( r=0.473, P<0.001; r=0.335, P=0.011). IOL tilt magnitude was weakly positively correlated with angle α and IOL diopter ( rs=0.272, P=0.003; r=0.285, P=0.002), and was weakly negatively correlated with ACD, PD and AL ( r=-0.303, P=0.001; r=-0.233, P=0.011; rs=-0.331, P<0.001). In backward stepwise regression analysis, the regression equation of IOL tilt magnitude, angle α, ACD, PD, AL and IOL diopter in multiple linear regression analysis was as follows: IOL tilt magnitude=10.503+ 1.456×angle α-0.532×ACD-0.196×AL ( R2=0.400; F=8.588, P<0.001). Conclusions:The SS-OCT biometer can be an effective method to assess IOL tilt.IOL tilt is mirror symmetric between the right eyes and left eyes.

AIM: To compare the results calculated by population pharmacokinetic analysis tools Phoenix NLME, Monolix, R nlmixr package and CPhaMAS cloud platform with the gold standard sofeware NONMEM. METHODS: Fifty sparse sampling data sets based on a one-compartment model and fifty dense sampling data sets based on a two-compartment model were simulated, and the above five analysis tools were used to calculate the population typical value, individual variability and individual pharmacokinetic parameters. RESULTS: The population typical value and individual variability calculated by CPhaMAS and Phoenix NLME had the highest matching degree with NONMEM, followed by nlmixr. Monolix had the lowest matching degree, but Monolix and nlmixr might be more robust. The correspondence between clearance and distribution volume was better than the absorption rate constant. Except the absorption rate constant calculated by Monolix and intercompartmental clearance calculated by nlmixr, the correlation coefficients of individual pharmacokinetic parameters calculated by all analytical tools were greater than 0.99. CONCLUSION: The results calculated by the above four population pharmacokinetic analysis tools are highly correlated with that of NONMEM.