Objective To simulate modern social stress using a pre-pregnancy chronic mild stress(CMS)model and to explore the mechanisms of emotional,behavioral,and neurodevelopmental changes in male offspring of pre-pregnancy liver qi stagnation female mice through corticosterone(CORT)-brain-derived neurotrophic factor(BDNF)extracellular signal-regulated kinase(ERK)1/2 signaling cascade-mediated hippocampal injury.This study aimed to elucidate the impact of negative life events on offspring and the interventional mechanism of Shuyu Capsules.Methods CMS stress was used to induce pre-pregnancy depression in female rats(liver qi stagnation state),followed by intervention with Shuyu and fluoxetine capsules.After screening,male rats were mated and 12 male offspring from each group were selected for behavioral testing and detection of serum CORT levels by enzyme-linked immunosorbent assay.BDNF,ERK1/2,phospho(p)-ERK1/2,cAMP-response element binding protein(CREB),and p-CREB protein levels in the hippocampus were detected by Western Blot,and BDNF,ERK1,ERK2,and CREB mRNA levels in the hippocampus were detected by reverse transcription-polymerase chain reaction(RT-PCR),to verify the effects of pre-pregnancy CMS on the BDNF-ERK1/2-CREB signaling pathway and to investigate the key micro-mechanisms of Shuyu Capsules on emotional and learning memory-related behaviors of male offspring of females with pre-pregnancy liver qi stagnation syndrome.Results The distance,number of entries,and duration of stay in the central area in open-field experiments were significantly reduced in offspring in the model group(all P＜0.05).The escape latency during the exploration period of the water-maze experiment was significantly prolonged(P＜0.05)and the swimming distance,duration of the target quadrant,and number of platform crossings were significantly reduced(P＜0.05,P＜0.05,P＜0.01),the suspension time and frequency in the forced-swimming experiment were increased(P＜0.05,P＜0.01),and the incubation period was shortened(P＜0.05)in offspring in the model group.Prophylactic treatment with Shuyu Capsules and fluoxetine improved the depression-like behavior and cognitive impairment in the offspring in the model group.Biochemical tests showed that CORT levels were increased in the CMS model group(P＜0.05),BDNF,p-ERK1/2,and p-CREB protein levels in the hippocampus were decreased(all P＜0.05),and BDNF,ERK1,ERK2,and CREB mRNA levels were significantly reduced(P＜0.01,P＜0.05,P＜0.01,P＜0.05).Treatment with Shuyu Capsules and fluoxetine increased the CORT content and BDNF,ERK1/2,and CREB protein and mRNA levels in male offspring to varying degrees.Conclusions High levels of CORT in offspring act selectively on the hippocampus,exerting adverse effects on the emotional and learning memory functions of rats by downregulating the BDNF-ERK1/2 signaling cascade.The Chinese medicine Shuyu Capsules can reduce the impact of an adverse intrauterine environment on offspring development by correcting abnormal levels and pathways of glucocorticoids.

Objective:To explore the improvement of the quality standard of Ginkgo Leaf Extract and Dipyridamole Injection and conduct safety tests including abnormal toxicity test,allergic reaction test,hemolysis and coagulation test.Methods:Ginkgo Leaf Extract and Dipyridamole Injection from 3 different manufactures(A,B and C)were tested respectively through abnormal toxicity test and acute toxicity test in mice,active systemic anaphylaxis test in guinea pigs and hemolysis test in vitro.Five mice were used in each batch for abnormal toxicity test according to the abnormal toxicity test method in general notice of the Chinese Pharmacopoeia 2020 Volume Ⅳ(1141),and 50 mice were selected in each batch for acute toxicity test to determine the median lethal dose(LD50)or maximum tol-erable dose(MTD)of Ginkgo Leaf Extract and Dipyridamole Injection,which were used to establish the method of abnormal toxicity experiment.The anaphylaxis of Ginkgo Leaf Extract and Dipyridamole Injection was evaluated by active systemic anaphylaxis test in guinea pigs,which was used to establish the method of allergic test.The hemoly-sis test of Ginkgo Leaf Extract and Dipyridamole Injection was studied by conventional tube method in vitro(macro-scopic observation)and improved hemolysis method in vitro(spectrophotometric method),which were used to establish the method of hemolysis and coagulation test.Results:① In manufacture A,the results of abnormal toxicity test were showed that LD50 was20.8 mL·kg-1and MTD was 16.5 mL·kg-1.No death or abnormal reac-tions were observed in mice tested for abnormal toxicity of 2 manufactures(B and C),and MTD was 50 and 40 mL·kg-1,respectively.②The no-observed-adverse-effect dose of Ginkgo Leaf Extract and Dipyridamole Injec-tion from 3 manufactures to guinea pig intravenous was 0.83 mL·kg-1,and no allergic reaction symptoms were observed when Ginkgo Leaf Extract and Dipyridamole Injection was diluted 4 times to challenge the sensitized guinea pigs(equivalent to human clinical dosage).③Differences were observed in the hemolytic effects of Ginkgo Leaf Extract and Dipyridamole Injection from 3 manufactures,but no obvious hemolytic reaction occurred when it was diluted 1.2 times(equivalent to 5%of the maximum clinical concentration).Conclusion:It is recommended to add abnormal toxicity test,allergic reaction test,hemolysis and coagulation test in the quality standard of Ginkgo Leaf Extract and Dipyridamole Injection as safety test items to control the risk.The proposed method is diluting Ginkgo Leaf Extract and Dipyridamole Injection by 5 times,4 times and 1.2 times to perform abnormal toxicity test,allergic reaction test,hemolysis test and coagulation test respectively.

Objective:To explore the improvement of the quality standard of Ginkgo Leaf Extract and Dipyridamole Injection and conduct safety tests including abnormal toxicity test,allergic reaction test,hemolysis and coagulation test.Methods:Ginkgo Leaf Extract and Dipyridamole Injection from 3 different manufactures(A,B and C)were tested respectively through abnormal toxicity test and acute toxicity test in mice,active systemic anaphylaxis test in guinea pigs and hemolysis test in vitro.Five mice were used in each batch for abnormal toxicity test according to the abnormal toxicity test method in general notice of the Chinese Pharmacopoeia 2020 Volume Ⅳ(1141),and 50 mice were selected in each batch for acute toxicity test to determine the median lethal dose(LD50)or maximum tol-erable dose(MTD)of Ginkgo Leaf Extract and Dipyridamole Injection,which were used to establish the method of abnormal toxicity experiment.The anaphylaxis of Ginkgo Leaf Extract and Dipyridamole Injection was evaluated by active systemic anaphylaxis test in guinea pigs,which was used to establish the method of allergic test.The hemoly-sis test of Ginkgo Leaf Extract and Dipyridamole Injection was studied by conventional tube method in vitro(macro-scopic observation)and improved hemolysis method in vitro(spectrophotometric method),which were used to establish the method of hemolysis and coagulation test.Results:① In manufacture A,the results of abnormal toxicity test were showed that LD50 was20.8 mL·kg-1and MTD was 16.5 mL·kg-1.No death or abnormal reac-tions were observed in mice tested for abnormal toxicity of 2 manufactures(B and C),and MTD was 50 and 40 mL·kg-1,respectively.②The no-observed-adverse-effect dose of Ginkgo Leaf Extract and Dipyridamole Injec-tion from 3 manufactures to guinea pig intravenous was 0.83 mL·kg-1,and no allergic reaction symptoms were observed when Ginkgo Leaf Extract and Dipyridamole Injection was diluted 4 times to challenge the sensitized guinea pigs(equivalent to human clinical dosage).③Differences were observed in the hemolytic effects of Ginkgo Leaf Extract and Dipyridamole Injection from 3 manufactures,but no obvious hemolytic reaction occurred when it was diluted 1.2 times(equivalent to 5%of the maximum clinical concentration).Conclusion:It is recommended to add abnormal toxicity test,allergic reaction test,hemolysis and coagulation test in the quality standard of Ginkgo Leaf Extract and Dipyridamole Injection as safety test items to control the risk.The proposed method is diluting Ginkgo Leaf Extract and Dipyridamole Injection by 5 times,4 times and 1.2 times to perform abnormal toxicity test,allergic reaction test,hemolysis test and coagulation test respectively.

Objective To simulate modern social stress using a pre-pregnancy chronic mild stress(CMS)model and to explore the mechanisms of emotional,behavioral,and neurodevelopmental changes in male offspring of pre-pregnancy liver qi stagnation female mice through corticosterone(CORT)-brain-derived neurotrophic factor(BDNF)extracellular signal-regulated kinase(ERK)1/2 signaling cascade-mediated hippocampal injury.This study aimed to elucidate the impact of negative life events on offspring and the interventional mechanism of Shuyu Capsules.Methods CMS stress was used to induce pre-pregnancy depression in female rats(liver qi stagnation state),followed by intervention with Shuyu and fluoxetine capsules.After screening,male rats were mated and 12 male offspring from each group were selected for behavioral testing and detection of serum CORT levels by enzyme-linked immunosorbent assay.BDNF,ERK1/2,phospho(p)-ERK1/2,cAMP-response element binding protein(CREB),and p-CREB protein levels in the hippocampus were detected by Western Blot,and BDNF,ERK1,ERK2,and CREB mRNA levels in the hippocampus were detected by reverse transcription-polymerase chain reaction(RT-PCR),to verify the effects of pre-pregnancy CMS on the BDNF-ERK1/2-CREB signaling pathway and to investigate the key micro-mechanisms of Shuyu Capsules on emotional and learning memory-related behaviors of male offspring of females with pre-pregnancy liver qi stagnation syndrome.Results The distance,number of entries,and duration of stay in the central area in open-field experiments were significantly reduced in offspring in the model group(all P＜0.05).The escape latency during the exploration period of the water-maze experiment was significantly prolonged(P＜0.05)and the swimming distance,duration of the target quadrant,and number of platform crossings were significantly reduced(P＜0.05,P＜0.05,P＜0.01),the suspension time and frequency in the forced-swimming experiment were increased(P＜0.05,P＜0.01),and the incubation period was shortened(P＜0.05)in offspring in the model group.Prophylactic treatment with Shuyu Capsules and fluoxetine improved the depression-like behavior and cognitive impairment in the offspring in the model group.Biochemical tests showed that CORT levels were increased in the CMS model group(P＜0.05),BDNF,p-ERK1/2,and p-CREB protein levels in the hippocampus were decreased(all P＜0.05),and BDNF,ERK1,ERK2,and CREB mRNA levels were significantly reduced(P＜0.01,P＜0.05,P＜0.01,P＜0.05).Treatment with Shuyu Capsules and fluoxetine increased the CORT content and BDNF,ERK1/2,and CREB protein and mRNA levels in male offspring to varying degrees.Conclusions High levels of CORT in offspring act selectively on the hippocampus,exerting adverse effects on the emotional and learning memory functions of rats by downregulating the BDNF-ERK1/2 signaling cascade.The Chinese medicine Shuyu Capsules can reduce the impact of an adverse intrauterine environment on offspring development by correcting abnormal levels and pathways of glucocorticoids.

Objective:To investigate the effect of BOPPPS teaching model combined with virtual simulation technologyin the teaching of Prevention and treatment of Major Infectious Diseases,in order to explore innovative teaching model and provide evidence for improving students'comprehensive ability to deal with major infectious disease events.Methods:Undergraduates from three classes of preventive medicine major in a medical university were selected as the research objects.One class was given the new teaching model,and the other two classes were given the traditional teaching model.The total scores,the theoretical score and the skill score were compared between the two groups.Results:A total of 141 students participated in the survey,49 students in the new teaching model group,and 92 students in the traditional teaching model group.The results showed that compared with the traditional model group,the total score,the theoretical score,the skill score of the new model group was significantly higher(P＜0.01).However,there was no significant difference between male and female students in each group(P＞0.05).Conclusions:Compared with the traditional teaching model,the students in the new teaching model has a good teaching effect,which can improve the students'theoretical knowledge level,cultivate the students'emergency response ability,and improve the students'comprehensive ability of discovery,analysis and solution.Boys and girls have the same acceptance of the two teaching models,and gender does not affect the teaching effect.

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.

ObjectiveTo evaluate the effect of Astragali Radix （AR）-Angelicae Sinensis Radix （ASR） drug pair on supplementing Qi and activating blood circulation in rats with Qi deficiency and blood stasis and provide a theoretical basis for clinical rational medication and identification and quality control of compound pharmacodynamic substances from the three aspects of characteristic map， identification of pharmacodynamic substances， and comparison of blood components. MethodHigh-performance liquid chromatography （HPLC） was employed to establish the fingerprint of AR∶ASR （3∶1）， and ultra-high performance liquid chromatography-Q-Exactive Orbitrap-mass spectrometry （UPLC-Q-Exactive Orbitrap-MS） was employed to analyze the ingredients of the decoction. Adult male Wistar rats with SPF grades were selected and randomly divided into a blank group， a model group， a 3∶1 group， and a 5∶1 group. The rat model of Qi deficiency and blood stasis syndrome was prepared by controlling food intake and swimming in cold water every day. In parallel， each group was given medicine （or water） once a day. The dose of drug groups was 10.2 g∙kg^-1， and the model group and blank group were given the same amount of distilled water for 15 d. Animal behavior， body weight， whole blood and plasma viscosity， thymus index， spleen index， the levels of adenosine triphosphate （ATP）， adenosine diphosphate（ADP）， von willebrand factor （vWF）， and ATP/ADP value in serum of rats were recorded. The morphology of vascular endothelium was observed by hematoxylin-eosin （HE） staining and scanning electron microscopy. UPLC-Q-Exactive Orbitrap-MS was used to analyze prototype and metabolic components in serum. ResultThe fingerprint of AR-ASR drug pair （AR-ASR 3∶1） was established. UPLC-Q-Exactive Orbitrap MS identified 49 chemical components in vitro and preliminarily identified 11 prototype components absorbed into blood in vivo. As compared with the blank group， the body mass decreased significantly （P<0.01）， the whole blood （high shear， middle shear， and low shear） viscosity and plasma viscosity were significantly increased （P<0.05， P<0.01）， the thymus index and spleen index decreased significantly （P<0.05， P<0.01）， serum ATP content decreased significantly （P<0.01）， ADP content increased significantly （P<0.01）， ATP/ADP value decreased significantly （P<0.01）， and vWF content increased significantly （P<0.01）. The results of HE staining and scanning electron microscopy showed that the vessels were partially damaged， showing the structural disorder of the intima， the bulge， defect， and roughness of the endothelium， and the obvious cell adhesion and migration in the model group. As compared with the model group， the body mass also increased significantly （P<0.01）. The results of whole blood and plasma viscosity showed that the whole blood low shear viscosity was significantly decreased in the 3∶1 group （P<0.05）. The results of thymus index and spleen index showed that 5∶1 group significantly increased the thymus index of rats （P<0.05）. The results of serum ATP and ADP levels showed that the 5∶1 group had more significant effects on ATP and ADP levels （P<0.05）， and both groups significantly reduced ATP/ADP values （P<0.01）. The results of serum vWF level showed that the vWF content in the 3∶1 group decreased significantly （P<0.05）. The results of HE staining and scanning electronic microscopy showed that the damage of vascular endothelium was improved in the treatment group and the structure of intima was neat. ConclusionAR-ASR drug pair can improve the macro and micro indexes of rats with qi deficiency and blood stasis in the 3∶1 and 5∶1 groups. Overall， the 5∶1 ratio has a better effect on supplementing Qi but 3∶1 ratio has a better effect on promoting blood circulation.

Objective: To observe the efficacy of acupuncture combined with sitting-position knee-adjustment manipulations in treating patellofemoral osteoarthritis. Methods: Ninety-two patients with patellofemoral osteoarthritis were randomized into an observation group and a medication group, with 46 cases in each group. The observation group received acupuncture and sitting-position knee-adjustment manipulations, and the medication group received oral celecoxib capsules. After 8-week treatment, changes in the short-form McGill pain questionnaire (SF-MPQ) and Lysholm knee scoring scale (LKSS) scores were observed, and the clinical efficacy was compared.Results: The total effective rate was 87.0％ in the observation group and 63.0％ in the control group; the between- group difference was statistically significant. Before treatment, there were no significant differences in the SF-MPQ score or LKSS score (P>0.05). After 8-week treatment, the SF-MPQ [including pain rating index (PRI), visual analog scale (VAS), and present pain intensity (PPI)] and LKSS scores showed notable changes in both groups (P<0.05); the SF-MPQ and LKSS scores in the observation group were significantly different from those in the control group (P<0.05).Conclusion: Combining acupuncture and sitting-position knee-adjustment manipulations can reduce pain and ameliorate joint function in patients with patellofemoral osteoarthritis, producing more significant efficacy than oral celecoxib capsules.

Objective:To explore the effect of digital technology in the surgical treatment of patients with fronto-orbital fibrous dysplasia.Methods:The clinical data of 2 patients with fronto-orbital fibrous dysplasia admitted to the Plastic Surgery Hospital, Chinese Academy of Medical Sciences in February 2016 and February 2018 were retrospectively analyzed. The patients were both male, aged 18 and 16 years, respectively. Preoperative CT scan was performed on the patient to obtain imaging data, imported into Mimics 10.01 for three-dimensional(3D) reconstruction and image analysis of the skull, and the resection range of fibrous dysplasia lesions was designed. Then, the 3D skull defect model was 3D printed, and a personality covering the skull defect was made. Titanium prosthesis was used, and then the bone extraction range of the autologous skull outer plate was designed and simulated to repair the orbital bone defect. Surgery was performed according to the design plan. Postoperatively, the recovery and complications of the patients were observed, skull CT scan was performed, orbital volume, proptosis was measured, visual acuity was checked, and the surgical effect was evaluated.Results:The intraoperative macroscopic lesion boundary in 2 patients was consistent with the preoperative simulation design, and the intraoperative temporal bone was normal bone. One patient recovered well after the operation, and the other had cerebrospinal fluid rhinorrhea 1 day after the operation, without special treatment, and recovered spontaneously after 2 weeks. CT scans after the operation showed that the personalized prosthesis was well integrated with the skull, and the shape of the fronto-orbital area was satisfactory, which was close to the normal anatomical shape. The orbital volume of the affected side of 2 cases was enlarged after operation, which increased by 2.99 ml and 9.99 ml respectively compared with that before operation; the exophthalmos were improved after operation, and decreased by 3.32 mm and 5.11 mm respectively compared with that before operation. Directional movement is good. Patients and their families were satisfied with the morphology.Conclusions:The use of digital technology in the preoperative simulation design of fronto-orbital fibrous dysplasia is helpful for the operator to accurately formulate the surgical plan, improve the utilization efficiency of the grafted bone, and obtain satisfactory postoperative results.

Objective:To explore the effect of digital technology in the surgical treatment of patients with fronto-orbital fibrous dysplasia.Methods:The clinical data of 2 patients with fronto-orbital fibrous dysplasia admitted to the Plastic Surgery Hospital, Chinese Academy of Medical Sciences in February 2016 and February 2018 were retrospectively analyzed. The patients were both male, aged 18 and 16 years, respectively. Preoperative CT scan was performed on the patient to obtain imaging data, imported into Mimics 10.01 for three-dimensional(3D) reconstruction and image analysis of the skull, and the resection range of fibrous dysplasia lesions was designed. Then, the 3D skull defect model was 3D printed, and a personality covering the skull defect was made. Titanium prosthesis was used, and then the bone extraction range of the autologous skull outer plate was designed and simulated to repair the orbital bone defect. Surgery was performed according to the design plan. Postoperatively, the recovery and complications of the patients were observed, skull CT scan was performed, orbital volume, proptosis was measured, visual acuity was checked, and the surgical effect was evaluated.Results:The intraoperative macroscopic lesion boundary in 2 patients was consistent with the preoperative simulation design, and the intraoperative temporal bone was normal bone. One patient recovered well after the operation, and the other had cerebrospinal fluid rhinorrhea 1 day after the operation, without special treatment, and recovered spontaneously after 2 weeks. CT scans after the operation showed that the personalized prosthesis was well integrated with the skull, and the shape of the fronto-orbital area was satisfactory, which was close to the normal anatomical shape. The orbital volume of the affected side of 2 cases was enlarged after operation, which increased by 2.99 ml and 9.99 ml respectively compared with that before operation; the exophthalmos were improved after operation, and decreased by 3.32 mm and 5.11 mm respectively compared with that before operation. Directional movement is good. Patients and their families were satisfied with the morphology.Conclusions:The use of digital technology in the preoperative simulation design of fronto-orbital fibrous dysplasia is helpful for the operator to accurately formulate the surgical plan, improve the utilization efficiency of the grafted bone, and obtain satisfactory postoperative results.