Objective:To investigate the effects of PD-1 monoclonal antibody therapy on the peripheral and local immune microenvironment of patients with microsatellite instability-high(MSI-H)rectal cancer.Methods:Samples of peripheral blood and tumor biopsy were collected from a patient with MSI-H rectal cancer before and after PD-1 monoclonal antibody treatment.The samples were dissociated into single-cell suspensions using a combination of enzymatic and mechanical methods.Immune-related marker expression on peripheral and tumor-infiltrating im-mune cells was analyzed using single-cell mass cytometry(CyTOF).Results:According to the results of CyTOF analysis,CD45+immune cells in the peripheral blood and tumor tissues were categorized into 39 and 34 cell subsets,respectively,before and after PD-1 monoclonal antibody treatment(the correlation is unclear and ambiguous).After PD-1 monoclonal antibody treatment,differences were observed in the relative abundance of immune cell subsets:B cells significantly decreased in the peripheral blood,while B cells and γδT cells significantly increased in the tumor tissue;neutrophils significantly decreased,and the proportion of CD4+TEM cells in T cell subsets significantly increased,whereas CD4+Treg cells significantly decreased.Additionally,there were differences in the expression of immune-related markers in multiple immune cell subsets in both peripheral blood and tumor tissues,with CCR6 showing a significant increase in expression across all subsets,while ICOS and PD-1 expressions in T cell subsets were significantly reduced(the specific tissues for these cells or factors are unclear).Conclusion:After PD-1 monoclonal antibody treatment in MSI-H rectal cancer,changes occurred in the composition of immune cells and the expression of immune-related markers in both peripheral blood and tumor tissues.This study reveals the dynamic adjustment of the immune microenvironment and provides important evidence for understanding the therapeutic mechanism of PD-1 monoclonal antibodies.

Objective:To introduce a surgical method involving the indwelling of double-J tubes(DJT)in the seminal vesicles after transurethral seminal vesiculoscopy(TSV)in order to reduce the recurrence of refractory ejaculatory duct obstruction(EDO).Methods:This randomized controlled trial included 67 EDO patients undergoing TSV in our hospitals,27 with(the trial group)and 29 without postoperative indwelling of DJTs in the seminal vesicles(the control group).We collected the general information on the pa-tients and TSV-related parameters,including age,body mass index(BMI),preoperative use of antibiotics,history of urinary tract dis-ease,operation time,hospital stay and intra-and postoperative complications,and performed comparative analyses particularly on the surgical effect,complications,recurrence rate and time to recurrence in the two groups of patients.Results:The patients in the trial and control groups were followed up for(40.5±10.6)and(32.5±14.8)months,respectively.There were no statistically signifi-cant differences in the baseline data,intra-and postoperative complications,and postoperative hospital days between the two groups(P＞0.05).Compared with the controls,the patients in the trial group showed a significantly shorter operation time([62.8±6.1]vs[49.5±7.7]min,P＜0.05)and a lower recurrence rate than the controls(18.5％vs 44.8％,P＜0.05),but with no statisti-cally significant difference in the median time to recurrence(21.0 mo vs 22.0 mo,P＞0.05).Conclusion:The novel technique of indwelling double-J tubes in the seminal vesicles after TSV can significantly reduce the recurrence rate of refractory EDO.

BACKGROUND:Osteonecrosis of the femoral head is one of the refractory diseases in orthopedic diseases.The natural collapse course of osteonecrosis of the femoral head under different stages and types affects the progression and prognosis of the disease. OBJECTIVE:To explore the progression of natural collapse within 5 years in patients under the different classifications of China-Japan Friendship Hospital(CJFH)with stage Ⅱ osteonecrosis of the International Association for Research Circulation Osseous(ARCO),and to analyze the collapse rate and collapse risk of the femoral head under the different classifications of CJFH. METHODS:A retrospective study was performed to select patients diagnosed with ARCO Ⅱ stage osteonecrosis of the femoral head without collapse in the Honghui Hospital Affiliated to Xi'an Jiaotong University from October 2016 to October 2017.According to whether it collapsed,the number of hips was divided into the collapse group(n=82)and the non-collapsed group(n=70).The collapse risk of patients with osteonecrosis of the femoral head under different CJFH classifications,as well as the collapse time,number of collapses,and collapse rate within 5 years were counted,and then the Kaplan-Meier survival curve of the femoral head under different classification of CJFH was plotted. RESULTS AND CONCLUSION:(1)A total of 97 patients with 152 hips were enrolled,and 82 hips collapsed during the follow-up period,with a total collapse rate of 53.9%,of which the collapse rates of M type,C type,L1 type,L2 type,and L3 type were 0.0%,36.7%,51.4%,72.2%,and 77.8%,respectively,and the comparison between the groups was statistically significant(P<0.05).(2)In terms of collapse risk,the collapse risk of L1 type was 1.704 times that of C-type(P>0.05),while the collapse risks of L2 type and L3 type were 3.866 times and 6.423 times that of C type(P<0.05),respectively.(3)In terms of the Kaplan-Meier survival curve,the median survival time of the femoral head of ARCO Ⅱ stage patients was 3 years,with a 95%confidence interval of 2.885-3.471 years,and the survival rates of the femoral head at the first,third and fifth years were 65.1%(99/152),50.7%(77/152),and 46.1%(70/152),respectively.(4)These findings conclude that different CJFH classifications affect the collapse rate of ARCO Ⅱ stage osteonecrosis of the femoral head patients,among which L3 type patients have the highest collapse rate,followed by L2 type and L1 type patients;C type patients have a lower collapse rate,and M type patients do not collapse,which indicates that the preservation of the lateral column of the femoral head is of great significance for the natural collapse course of osteonecrosis of the femoral head.

Objective To explore the accuracy of the multiplication coefficient method and the moment synthesis method for determining the spatial position of the center of gravity(CoG)of the human body based on machine vision.Methods The mechanical measurement platform was built,and the three-dimensional(3D)human body CoG measurement method under static and dynamic conditions were designed to calculate the space coordinates of the CoG.Through experiments,the calculation accuracy of the multiplication coefficient and moment synthesis method were studied and analyzed.Results In the static experiments,the calculation results of the torque synthesis method were more accurate than those of the multiplication coefficient method for each dimension.The errors in the 3D CoG of the human body in the X,Y,and Z directions calculated using the torque synthesis method were 3.9%,4.1%,and 8.5%,respectively.In the dynamic experiment,the average and relative errors of the torque synthesis method in the X or Y direction were lower than those of the multiplication-coefficient method.When the action decomposition method was used to analyze the height direction of the CoG along the Z axis,the final rendering effect of the torque synthesis method improved.Conclusions The accuracy of the 3D CoG calculated by the moment synthesis method was relatively high,and was closer to the measurement data of the mechanical measurement platform.The 3D CoG calculated using the moment synthesis method can replace the mechanical measurement platform and can be used in subsequent studies.

Anxiety is a major mood disorder, and the high morbidity, co-morbidity and disability of anxiety disorders seriously affect people's quality of life, so the importance and urgency of research on anxiety cannot be overstated. Animal models are the main carriers for studying the mechanism of disease occurrence and development, drug efficacy evaluation and drug development.Unconditioned anxiety model is a common anxiety model.Elevated plus maze test, open field test and light-dark box test are widely accepted paradigms for the detection of unconditioned anxiety.This kind of behavioral paradigm based on environmental exposure takes advantage of the conflict between curiosity and fear of the unfamiliar environment to simulate and detect the anxiety of animals.However, the validity of these behavioral paradigms for evaluating anxiety in animals is questionable.In this paper, we discuss the concept of anxiety, the definition of anxiety behavior in the behavioral test of unconditioned anxiety, and the factors to be considered in the test of unconditioned anxiety behavior.On this basis, new solutions were proposed to the contradictions and blind spots in order to improve the test paradigm of anxiety behavior and provide a more reliable animal model for the evaluation of anxiety.This paper presents a new approach to address the contradictions and blind spots of this paradigm.

Neural recording electrodes enable the acquisition and collection of electrical signals from neu-rons,and these recorded neural electrical signals are an important means of understanding neuronal activity.As a major component of the brain-machine interface,neu-ral recording electrodes serve as a bridge between the nervous system and external devices.The extracted information can be used to understand the state of the brain and acts as a feedback signal to regulate external devices,thus providing important information for the clini-cal treatment of neurological diseases.Moreover,the electrodes can be used as a vehicle for drug injection to directly treat diseases.Since the time that Strumwas-ser used microwires to achieve long-term recordings of neural activity in hibernating squirrels,implantable elec-trode technology has gradually improved over three gen-erations of development,and progress has been made in improving the biocompatibility,mechanical performance(size,shape,density,etc.),and signal-to-noise ratio.Implantable neural recording electrodes can acquire sig-nals from cortical and deep neural clusters,with the advantages of high signal-to-noise ratio,information con-tent,and spatial/temporal resolution.However,there is still a need to improve the structure and performance of these electrodes;for example,their high invasiveness and lack of biocompatibility pose technical difficulties in the process of translation to the clinic.This paper reviews the basic requirements for electrodes,main recording methods and signal types,common types of implant-able neural recording electrodes,and their challenges and future development directions.With the continuous development of electrode materials,equipment,systems,and neurotechnology,it should be possible to apply neu-ral recording electrodes in clinical practice,to promote safe and efficient treatment of human diseases.

Objective:To investigate the correlations between serum E selectin, intercellular adhesion molecule 1 (ICAM-1), vascular cell adhesion molecule 1 (VCAM-1) and left ventricular geometry and function in patients with obstructive sleep apnea syndrome (OSAS) combined with prehypertension (pre-HT).Methods:A total of 462 patients with pre-HT and OSAS diagnosed by polysomnography (PSG) in the sleep monitoring unit of the Department of Respiratory and Critical Care Medicine at the First Hospital of Shanxi Medical University from July 2019 to July 2022 were restrospectively analysed, and 52 patients with pure pre-HT (pre-HT group) and 73 patients with pure OSAS (OSAS group) in the same period were selected as the control group. OSAS and pre-HT patients were divided into four groups according to left ventricular geometry: normal geometry (NG) group, concentric remodeling (CR) group, eccentric hypertrophy (EH) group and concentric hypertrophy (CH) group. The general clinical data, PSG parameters, blood biochemical parameters and left ventricular structure and function parameters were compared among the six groups. Pearson correlation and multivariate Logistic regression were used to analyze the correlation between E-selection, ICAM-1, VCAM-1, general clinical data, PSG parameters, blood biochemical parameters with left ventricular geometry and function.Results:①Serum E selectin, ICAM-1, and VCAM-1 concentrations increased sequentially from the NG, CR, and EH to CH groups, with the most significant increase in CH group (all P<0.05). In addition, there were statistically significant differences in age, body mass index (BMI), OSAS severity, neck circumference, waist circumference, systolic blood pressure (SBP), diastolic blood pressure (DBP), Glu, lowest oxygen saturation (Lowest-SaO 2), mean oxygen saturation (Mean-SaO 2), percentage of time with oxygen saturation below 90% of total sleep time (T90), left ventricular end-diastolic diameter (LVEDd), interventricular septal thickness (IVST), left ventricular posterior wall thickness (LVPWT), left ventricular mass index (LVMI), relative ventricular wall thickness (RWT), left ventricular ejection fraction (LVEF), peak mitral early diastolic flow velocity/peak mitral late diastolic flow velocity (E/A), E wave deceleration time (DT), A wave duration (AD), and isovolumic relaxation time (IVRT), and overall long-axis longitudinal strain (GLS) and so on(all P<0.05). ②Pearson correlation analysis showed that E selectin was negatively correlated with LVEF, E/A, e′, E/e′, IVRT, and GLS ( r=-0.236, -0.131, -0.224, -0.215, -0.285, -0.336; all P<0.05). ICAM-1 was negatively correlated with LVEF, E, E/A, e′, IVRT, and GLS( r=-0.130, -0.129, -0.104, -0.351, -0.252, -0.259; all P<0.05). VCAM-1 was negatively correlated with E, e′, and IVRT ( r=-0.132, -0.312, -0.387; all P<0.001). ③Multifactorial logistic regression analysis showed that E selectin and VCAM-1 were independently correlated with EH (β=1.139, OR=3.124, P=0.030; β=1.288, OR=3.626, P<0.001) and with CH (β=1.178, OR=3.248, P=0.013; β=1.108, OR=3.028, P<0.001). Conclusions:E selection and VCAM-1 were independently correlated with hypertrophic left ventricular geometry, suggesting that E selectin and VCAM-1 may be involved in the process of abnormal left ventricular structure and function in patients with OSAS combined with pre-HT.

The sperm DNA fragmentation index (DFI) is a metric used to assess DNA fragmentation within sperm. During in vitro fertilization-embryo transfer (IVF-ET), high sperm DFI can lead to a low fertilization rate, poor embryo development, early miscarriage, etc. A kinase anchoring protein (AKAP) is a scaffold protein that can bind protein kinase A (PKA) to subcellular sites of specific substrates and protects the biophosphorylation reaction. Sperm protein antigen 17 (SPA17) can also bind to AKAP. This study intends to explore the reason for the decreased fertilization rate observed in high sperm DFI (H-DFI) patients during IVF-ET. In addition, the study investigates the expression of AKAP, protein kinase A regulatory subunit (PKARII), and SPA17 between H-DFI and low sperm DFI (L-DFI) patients. SPA17 at the transcriptional level is abnormal, the translational level increases in H-DFI patients, and the expression of AKAP4/PKARII protein decreases. H2O2 has been used to simulate oxidative stress damage to spermatozoa during the formation of sperm DFI. It indicates that H2O2 increases the expression of sperm SPA17 protein and suppresses AKAP4/PKARII protein expression. These processes inhibit sperm capacitation and reduce acrosomal reactions. Embryo culture data and IVF outcomes have been documented. The H-DFI group has a lower fertilization rate. Therefore, the results indicate that the possible causes for the decreased fertilization rate in the H-DFI patients have included loss of sperm AKAP4/PKARII proteins, blocked sperm capacitation, and reduced occurrence of acrosome reaction.

Objective To propose a new multi-joint series venipuncture system, explore the mechanics and kinematics-based related control problems involved in needle insertion and needle picking during the puncture process, and verify feasibility of this system. Methods A puncture manipulator was built, and needle displacement control algorithm was proposed by combing with the puncture mechanics model. The the forward kinematics was calculated by using DH method, so as to obtain the tip coordinates. Then the inverse kinematics was calculated by using the geometric method. The forward and inverse processes were closely connected. The position error of the end coordinates before and after needle picking was compared by using the method of kinematics positive solution-inverse solution-re-positive solution. Finally, experimental verification and simulation were conducted by combining with the physical object. Results Through simulation and experiments, accuracy of the theoretical model was verified. The needle insertion algorithm could be used to achieve success with only one needle insertion, which provided theoretical basis for the control of robot arm. The position error before and after needle picking could be controlled within 1 mm from the end trajectory. The end needle tip of robot arm was almost kept fixed during the needle picking process. Therefore, this needle picking scheme was feasible and could basically verify that the needle picking action of robot arm met the accuracy and safety requirements. Conclusions The venipuncture manipulator truly simulates the needle insertion and needle picking action during the puncture process, and can safely and accurately realize the needle insertion and needle picking action with needle tip as the fixed point, indicating that it has certain clinical value.

Objective: To explore the heterogeneity and correlation of clinical phenotypes and genotypes in children with disorders of sex development (DSD). Methods: A retrospective study of 1 235 patients with clinically proposed DSD in 36 pediatric medical institutions across the country from January 2017 to May 2021. After capturing 277 DSD-related candidate genes, second-generation sequencing was performed to analyzed the heterogeneity and correlation combined with clinical phenotypes. Results: Among 1 235 children with clinically proposed DSD, 980 were males and 255 were females of social gender at the time of initial diagnosis with the age ranged from 1 day of age to 17.92 years. A total of 443 children with pathogenic variants were detected through molecular genetic studies, with a positive detection rate of 35.9%. The most common clinical phenotypes were micropenis (455 cases), hypospadias (321 cases), and cryptorchidism (172 cases) and common mutations detected were in SRD5A2 gene (80 cases), AR gene (53 cases) and CYP21A2 gene (44 cases). Among them, the SRD5A2 mutation is the most common in children with simple micropenis and simple hypospadias, while the AMH mutation is the most common in children with simple cryptorchidism. Conclusions: The SRD5A2 mutation is the most common genetic variant in Chinese children with DSD, and micropenis, cryptorchidism, and hypospadias are the most common clinical phenotypes. Molecular diagnosis can provide clues about the biological basis of DSD, and can also guide clinicians to perform specific clinical examinations. Target sequence capture probes and next-generation sequencing technology can provide effective and economical genetic diagnosis for children with DSD.
3-Oxo-5-alpha-Steroid 4-Dehydrogenase/genetics* ; Child ; China/epidemiology* ; Cryptorchidism/genetics* ; Disorders of Sex Development/genetics* ; Female ; Genital Diseases, Male ; Genotype ; Humans ; Hypospadias/genetics* ; Male ; Membrane Proteins/genetics* ; Penis/abnormalities* ; Phenotype ; Retrospective Studies ; Steroid 21-Hydroxylase/genetics*