Objective:To evaluate the effect of virtual reality arthroscopic simulation system combined with case-based learning (CBL) in orthopedic clinical teaching.Methods:From January 2021 to June 2022, a total of 36 residents who took the standardized residency training at Department of Articular Orthopedics in The Third Affiliated Hospital of Soochow University were enrolled in this study. They were randomized into an experimental group and a control group, with 18 trainees in each group. The experimental group adopted the virtual reality arthroscopic simulation system combined with CBL teaching mode, while the control group adopted simple endoscopic simulation training box with traditional teaching mode. Theoretical and practical tests and questionnaire survey were carried out to evaluate the teaching effects in two groups. SPSS 22.0 was performed to conduct t-test on the measurement data between the two groups. Results:The theoretical and practical test scores of the experimental group [(89.39±3.09) and (82.72±4.28)] were better than those of the control group [(86.22±4.43) and (76.61±5.65)], with statistically significant differences ( t= 2.49, P=0.018; t=3.66, P=0.001). The questionnaire survey showed that the experimental group was better than the control group in creating novel forms of courses [(4.94±0.24) vs. (4.11±0.58), t=5.62, P<0.001], simulating more real scenes [(4.83±0.38) vs. (3.78±0.43), t=7.80, P<0.001], inspiring learning interests [(4.78±0.43) vs. (4.00±0.59), t=4.51, P<0.001], improving practical skills [(4.83±0.38) vs. (3.83±0.51), t=6.61, P<0.001], and building career confidence [(4.50±0.62) vs. (3.06±0.54), t=7.47, P<0.001], with statistically significant differences (all P<0.001). Conclusions:The virtual reality arthroscopic simulation system combined with CBL teaching mode can better simulate the real clinical scenes, help inspire the interest of learning and quickly improve practical skills, thereby improving the effect of orthopedic clinical teaching.

Electroconvulsive therapy (ECT) is an interventional technique capable of highly effective neuromodulation in major depressive disorder (MDD), but its antidepressant mechanism remains unclear. By recording the resting-state electroencephalogram (RS-EEG) of 19 MDD patients before and after ECT, we analyzed the modulation effect of ECT on the resting-state brain functional network of MDD patients from multiple perspectives: estimating spontaneous EEG activity power spectral density (PSD) using Welch algorithm; constructing brain functional network based on imaginary part coherence (iCoh) and calculate functional connectivity; using minimum spanning tree theory to explore the topological characteristics of brain functional network. The results show that PSD, functional connectivity, and topology in multiple frequency bands were significantly changed after ECT in MDD patients. The results of this study reveal that ECT changes the brain activity of MDD patients, which provides an important reference in the clinical treatment and mechanism analysis of MDD.
Humans ; Depressive Disorder, Major/therapy* ; Electroconvulsive Therapy ; Brain ; Algorithms ; Electroencephalography

The well-known insulin-like growth factor 1 (IGF1)/IGF-1 receptor (IGF-1R) signaling pathway is overexpressed in many tumors, and is thus an attractive target for cancer treatment. However, results have often been disappointing due to crosstalk with other signals. Here, we report that IGF-1R signaling stimulates the growth of hepatocellular carcinoma (HCC) cells through the translocation of IGF-1R into the ER to enhance sarco-endoplasmic reticulum calcium ATPase 2 (SERCA2) activity. In response to ligand binding, IGF-1Rβ is translocated into the ER by β-arrestin2 (β-arr2). Mass spectrometry analysis identified SERCA2 as a target of ER IGF-1Rβ. SERCA2 activity is heavily dependent on the increase in ER IGF-1Rβ levels. ER IGF-1Rβ phosphorylates SERCA2 on Tyr⁹⁹⁰ to enhance its activity. Mutation of SERCA2-Tyr⁹⁹⁰ disrupted the interaction of ER IGF-1Rβ with SERCA2, and therefore ER IGF-1Rβ failed to promote SERCA2 activity. The enhancement of SERCA2 activity triggered Ca²⁺_ER perturbation, leading to an increase in autophagy. Thapsigargin blocked the interaction between SERCA2 and ER IGF-1Rβ and therefore SERCA2 activity, resulting in inhibition of HCC growth. In conclusion, the translocation of IGF-1R into the ER triggers Ca²⁺_ER perturbation by enhancing SERCA2 activity through phosphorylating Tyr⁹⁹⁰ in HCC.

Electromagnetic stimulation is an important neuromodulation technique that modulates the electrical activity of neurons and affects cortical excitability for the purpose of modulating the nervous system. The phenomenon of inverse stochastic resonance is a response mechanism of the biological nervous system to external signals and plays an important role in the signal processing of the nervous system. In this paper, a small-world neural network with electrical synaptic connections was constructed, and the inverse stochastic resonance of the small-world neural network under electromagnetic stimulation was investigated by analyzing the dynamics of the neural network. The results showed that: the Levy channel noise under electromagnetic stimulation could cause the occurrence of inverse stochastic resonance in small-world neural networks; the characteristic index and location parameter of the noise had significant effects on the intensity and duration of the inverse stochastic resonance in neural networks; the larger the probability of randomly adding edges and the number of nearest neighbor nodes in small-world networks, the more favorable the anti-stochastic resonance was; by adjusting the electromagnetic stimulation parameters, a dual regulation of the inverse stochastic resonance of the neural network can be achieved. The results of this study provide some theoretical support for exploring the regulation mechanism of electromagnetic nerve stimulation technology and the signal processing mechanism of nervous system.
Action Potentials/physiology* ; Computer Simulation ; Models, Neurological ; Stochastic Processes ; Neurons/physiology* ; Electromagnetic Phenomena

Objective:To analyze the costs and effectiveness of five common screening modes and genetic screening for thalassemia in China in order to find the optimal way and provide evidence for the implementation of thalassemia prevention and control projects in Hunan Province.Methods:From June 2020 to April 2021, 12 971 couples from 14 cities and autonomous prefectures in Hunan Province were selected as the study population. The diagnosis of thalassemia was based on the results of genetic testing. Results of routine blood test and hemoglobin electrophoresis were collected and analyzed. The efficacy of five screening modes, at the cut-off value of <80 fl or 82 fl for the mean corpuscular volume (MCV), was analyzed by positive predictive value, negative predictive value, Jorden index and cost-effectiveness ratio. Sensitivity analysis was used to assess the feasibility of genetic screening at different costs after fixing the costs of routine blood and hemoglobin electrophoresis. The five thalassemia screening models are as follows: Mode 1: The woman had a blood routine test first. If the result was positive, the spouse required a blood routine test. If both results were positive, a thalassemia gene test should be offered to the couple. Mode 2: Both husband and wife were screened by blood routine and hemoglobin electrophoresis. If one or both of them were positive, both would be tested for thalassemia gene. Mode 3: The couple received blood routine tests initially. If either was positive, both should receive hemoglobin electrophoresis testing. If either was positive, both parties will conduct thalassemia gene testing. Mode 4: The woman was screened by blood routine and hemoglobin electrophoresis. If any one of them was positive, the woman would be tested for thalassemia gene. If the gene test result was positive, the spouse should receive thalassemia gene. Mode 5: Both spouses conducted a blood routine test. If either was positive, both would conduct hemoglobin electrophoresis test. If both were positive, both spouses should receive thalassemia gene testing. Gene testing mode: The woman would be tested for thalassemia, and her spouse would have thalassemia test too if her result was positive.Results:When using MCV<80 fl as the cut-off for diagnosing thalassemia, the Youden indices of the five prenatal screening modes in Hunan Province were 0.551, 0.639, 0.898, 0.555 and 0.356, while when using MCV<82 fl as the cut-off, the Youden indices were 0.549, 0.629, 0.851, 0.548 and 0.356. When the MCV cut-off value was <80 fl, the missed diagnosis rates of the five screening modes were 44.44%, 0.00, 0.00, 18.52% and 62.96%, and the cost-effectiveness ratios were 21 709, 250 939, 76 870, 138 463 and 92 860 yuan (RMB)/couple, respectively. When the price of genetic testing was lower than 55 yuan (RMB), the cost-effectiveness ratio of genetic screening was lower than that of Mode 3.Conclusions:MCV<80 fl can be considered as the positive criteria in blood routine screening for thalassemia in Hunan Province, and the cost-effectiveness ratio of Mode 3 (the couple received blood routine tests initially. If either was positive, both should receive hemoglobin electrophoresis testing. If either was positive, both parties will conduct thalassemia gene testing) is the best. Genetic screening has certain advantages with the decreasing price.

Insulin-like growth factor-1 receptor (IGF-1R) has been made an attractive anticancer target due to its overexpression in cancers. However, targeting it has often produced the disappointing results as the role played by cross talk with numerous downstream signalings. Here, we report a disobliging IGF-1R signaling which promotes growth of cancer through triggering the E3 ubiquitin ligase MEX3A-mediated degradation of RIG-I. The active β-arrestin-2 scaffolds this disobliging signaling to talk with MEX3A. In response to ligands, IGF-1Rβ activated the basal βarr2 into its active state by phosphorylating the interdomain domain on Tyr64 and Tyr250, opening the middle loop (Leu130‒Cys141) to the RING domain of MEX3A through the conformational changes of βarr2. The models of βarr2/IGF-1Rβ and βarr2/MEX3A could interpret the mechanism of the activated-IGF-1R in triggering degradation of RIG-I. The assay of the mutants βarr2^Y64A and βarr2^Y250A further confirmed the role of these two Tyr residues of the interlobe in mediating the talk between IGF-1Rβ and the RING domain of MEX3A. The truncated-βarr2 and the peptide ATQAIRIF, which mimicked the RING domain of MEX3A could prevent the formation of βarr2/IGF-1Rβ and βarr2/MEX3A complexes, thus blocking the IGF-1R-triggered RIG-I degradation. Degradation of RIG-I resulted in the suppression of the IFN-I-associated immune cells in the TME due to the blockade of the RIG-I-MAVS-IFN-I pathway. Poly(I:C) could reverse anti-PD-L1 insensitivity by recovery of RIG-I. In summary, we revealed a disobliging IGF-1R signaling by which IGF-1Rβ promoted cancer growth through triggering the MEX3A-mediated degradation of RIG-I.

Objective:To investigate the effect of visceral obesity on the short-term curative effect of Da Vinci robotic-assisted radical resec-tion for rectal cancers.Methods:Clinical and pathological data of patients with rectal cancer undergoing Da Vinci robotic-assisted surgery,admitted to People's Hospital of Zhengzhou University and Cancer Hospital of Zhengzhou University from November 2019 to June 2022 were retrospectively analyzed.Visceral fat area(VFA)≥100 cm2 was used as the standard to define visceral obesity.Patients were categorized in-to visceral and non-visceral obesity groups.The short-term efficacy of the two groups was evaluated,and the influencing factors of post-operative complications were analyzed using univariate and multivariate Logistic regression.Results:Among a total of 169 patients,93 were included in the visceral obesity group and 76 in the non-visceral obesity group.There was no significant difference in the baseline data between the two groups(P>0.05).There was no conversion to laparotomy in the non-visceral obesity group,and the conversion rate was 1.1%(1/93)in the visceral obesity group.The second operation rate was 2.2%(2/93)in the visceral obesity group and 1.3%(1/76)in the non-visceral obesity group with no statistical difference between the two groups.There were no significant differences in the operation dur-ation,intraoperative blood loss,number of lymph node dissections,and total postoperative complication rate between the two groups(P>0.05).Multivariate Logistic regression analysis revealed that an NRS≥3 independently contributed as a risk factor for postoperative com-plications(OR=3.190,95%CI:1.240-8.210,P=0.016).Conclusions:An NRS≥3 is an independent risk factor for complications post-robotic rad-ical rectal cancer surgery.The robotic surgical platform can overcome obesity-related limitations and is equally safe and effective for pa-tients with visceral obesity presenting with rectal cancer.

Objective:In order to allow the large instruments to play the greatest role in scientific research management and technology coverage.Methods:Texts review of the opening and sharing of large-scale instrument platforms of domestic and foreign universities and scientific research institutions was conducted, combined with the experience of more than 10-year operation of the technology platform of State Key Laboratory of Natural and Biomimetic Drugs of Peking University.Results:There are particular problems in the opening and sharing of large-scale instrument technology service platforms at this stage. Through building the hierarchical management of large instruments and equipment, building an efficient and flexible shared management information system, introducing high-level instrument management and high-level talents, and strengthening the security management of the shared platform, State Key Laboratory of Natural and Biomimetic Drugs of Peking University realized the opening and sharing of large-scale instrument technology service platforms. We consider that the current large-scale instrument technology service platforms of universities and research institutes are necessary and feasible to be shared. It is greatly significant to improve the utilization rate of scientific research instruments and to innovate to the ability of the whole society.Conclusions:At this stage, efficient management, system capabilities, and team building can effectively promote the opening and sharing of large-scale instrument technology service platforms.

Objective:To investigate the prevalence and clinical characteristics of Mycoplasma pneumoniae( Mp) genotypes and subtypes in children in Tianjin. Methods:Children with pneumonia admitted to Tianjin Children′s Hospital from December 2017 to December 2019 were selected as the research objects. Bronchoalveolar lavage fluid was collected by fiberoptic bronchoscopy. The positive samples were detected by real-time fluorescent quantitative PCR and Mp culture. PCR-restriction fragment length polymorphism(RFLP) and multiple variable number tandem repeats were used for genotyping. Detailed clinical and laboratory data were collected for all cases. Results:The results of RFLP showed that there were 138 cases (78.9%) of typeⅠand 37 cases (21.1%) of type Ⅱ; 37 cases of type M3-5-6-2, including six subtypes B, G, M, S, V and Y; 138 cases of M4-5-7-2 were detected, including seven subtypes of E, J, P, U, X, Z and a. In M3-5-6-2 type, there were 1 case of P1-Ⅰtype (2.7%), 36 cases of P1-Ⅱtype (97.3%), 137 cases of P1-Ⅰ type (99.2%) and 1 case of P1-Ⅱ type (0.7%) in M4-5-7-2 type. There was no significant difference in genotype distribution among different age groups. There were statistical differences in the distribution of four seasons among the 13 genotypes of B, G, M, S, V, Y and E, J, P, U, X, Z, a. All Mp infected children had symptoms of fever and cough. The hospitalization time, fever duration, high fever (>39℃), cough duration, skin changes, digestive system symptoms and liver function injury rate of P1-Ⅰ/M4-5-7-2 pneumonia children were higher than those of P1-Ⅱ/M3-5-6-2 pneumonia children, but the difference was not statistically significant. The WBC count of P1-Ⅱ/M3-5-6-2 types was higher than that of typeⅠand M4-5-7-2; the LDH of P1-Ⅰ/M4-5-7-2 was higher than that of Ⅱ and M3-5-6-2, with statistical difference. There was no significant difference in the incidence of inflammatory consolidation, atelectasis, pleural thickening and pleural effusion among different genotypes. Conclusions:Mp infection in children with pneumonia in Tianjin is mainly P1-Ⅰ/ M4-5-7-2, and P1-Ⅱ is on the rise. P1-Ⅰ and M4-5-7-2 were associated with fever and severe symptoms.

OBJECTIVE：To provide reference for pharmaceutical enterprises to better fulfill their social responsibilities . METHODS：Taking the pharmaceutical enterprises listed in Shanghai and Shenzhen stock markets as the research objects ，the social responsibility texts and environmental protection texts of the included enterprises from 2017 to 2019 were classified and analyzed according to the three dimensions of time ，ownership and drug production type by using ROST Content Mining 6.0 software. The semantic network and node centrality were analyzed. RESULTS ：From the social responsibility texts of the included enterprises，it could be seen that from the perspective of time dimension ，the included enterprises paid more attention to “employees”，“social responsibility ”and“development”in 2017-2019，and the high-frequency words in the three years were relatively stable. From the perspective of ownership ，state-owned holding enterprises paid more attention to “development”and “targeted poverty reduction ”，while private holding enterprises paid more attention to “employees”，and collective holding enterprises paid more attention to “social responsibility ”. From the perspective of drug production type ，the word frequency of “targeted poverty reduction ”of TCM pharmaceutical enterprises was higher. From the environmental protection texts of the included enterprises，it could be seen that from the time dimension ，the included enterprises paid more and more attention to environmental protection in recent years ，and the description of environmental protection in the texts was more detailed. From the perspective of ownership，private holding enterprises paid more attention to environmental protection than collective holding enterprises and state-owned enterprises. From the perspective of drug production type ，due to the different types of drugs ，chemical drugs ，TCM， biological drugs and active pharmaceutical ingredients enterprises had their own characteristics in pollutants and their treatment processes. The results of semantic network and node centrality analysis showed that ，“development”，“protection” and “targeted poverty reduction ”were three high-frequency words with high centrality in the semantic analysis network of social responsibility text ，the middle centrality was 5.555，1.695，1.521 respectively；“emission”and“testing”were two key words with high centrality in the semantic analysis network of environmental protection texts ，the middle centrality was 3.856， 1.914 respectively，which further reflected that the included enterprises paid more attention to the above issues in terms of social responsibility performance and environmental protection. CONCLUSIONS ：The listed pharmaceutical enterprises have a broad consensus on social responsibility in China ，and have well fulfilled their social responsibility ，which is well combined with the current social hot spots. For environmental protection ，as a high pollution industry ，the pharmaceutical enterprises also performs the responsibility of environmental protection.