Chemogenetic technology is a receptor-ligand system that regulates cell viability and function by changing receptor specificity and affinity, and it achieves precise neuronal regulation by specifically regulating neurons and neural circuits. At present, this technique is widely used in the study of neural circuits. This article briefly describes the application and progress of chemogenetic technology in the study of depression neural circuits, reviews the application of chemogenetic technology in several brain regions closely related to depression, such as ventral tegmental area, nucleus accumbens, prefrontal cortex, hippocampus and lateral habenula, and discusses the potential and challenges of chemogenetic technology as a technology for precise regulation of neural activity in future research, in order to provide reliable ideas and directions for chemogenetic technology in the study of depression neural circuits.

Objective To establish a method for bacterial endotoxin test of flumazenil bulk drug.Methods According to the bacterial endotoxin test(BET)method in general rule 1143 in the Chinese Pharmacopoeia(2020 Edition,VolumeⅣ),flumazenil was dissolved with dimethyl sulfoxide(DMSO)and diluted with BET water.The gel-clot method and kinetic turbidimetric assay were used to carry out the interference test and endotoxin recovery test.Results Flumazenil was dissolved with DMSO to 10 mg·mL-1,and then diluted 100 times or more by BET water,which has no interference effects on the bacterial endotoxin test.Conclusion The BET method established in this study can be used to control the quality of flumazenil by performing bacterial endotoxin tests.

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.

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 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.

BACKGROUND: Silk fibroin, the main component of silk fibroin biofilm, is a natural protein, but it is still a heterologous protein to the body. Its immunogenicity/toxicity is an important factor in determining the development prospects. OBJECTIVE: To evaluate the toxicity of absorbable silk fibroin biofilm and its degradation products on the rat immune system by muscle implantation experiments in rats. METHODS: Ten Wistar rats from Beijing Weitong Lihua Experimental Animal Technology Co., Ltd. were implanted with a long strip of 1 mm× 10 mm in the right gluteal muscle to observe the implant absorption and determine the implantation cycle. Seventy-two Wistar rats were assigned into control and experimental groups (n=36/group, 18 in either sexes) . A long strip of 1 mm×10 mm was implanted into the rat right gluteal muscle in the experimental group, and the control group received no implantation. Some of the rats were taken for histological examination and calculate the organ/weight ratio, at 26 weeks postoperatively. The spleen lymphocyte proliferation ability, NK cell activity, cell classification of T lymphocytes, and levels of interleukin 2 and tumor necrosis factor α were detected. Another part of the animals was taken for macrophage phagocytosis of erythrocytes cell capacity and antibody producing cell count. RESULTS AND CONCLUSION: (1) Silk fibroin biofilm was completely absorbed after implanted into the rat muscle for 26 weeks. (2) In female or male Wistar rats, the immune organs in the experimental group showed no significant changes in the appearance, weight and histological examination. There were no significant differences in the hematological indexes (hemoglobin, red blood cell count, hematocrit, blood platelet count and white blood cell count and classification) , spleen lymphocyte proliferation, NK cell activity, the ratio of T lymphocytes and their subpopulations, and the levels of interleukin 2 and tumor necrosis factor α had no significant differences between two groups (P> 0.05) . (3) In female or male Wistar rats, the macrophage phagocytosis of chicken erythrocytes cell capacity and antibody producing cell count showed no significant differences between two groups (P> 0.05) . (4) These results indicate that silk fibroin biofilm causes no immunosuppression or immunostimulation on immune organs, immune cells and immune molecules (cytokines) of rats.

Objective:To study the acute toxicity in mice and cytotoxicity of the impuritiy(3-amino-2-piperidinone hydrochloride) in ornithine. Methods:The mice were given the impurity by intravenous injection.The acute toxicity was observed and LD50in mice was calculated by Bliss method. According to the result of LD50,the mice were given the impurity respectively at high,medium and low dose. The changes of general condition and body weight were recorded,and the blood biochemical indices and histomorphology of organs and tissues were observed after 14 days. The cytotoxicity was measured on fibroblasts(L929) cells. Results:The LD50and 95% con-fidence limit of the impurity (intragastric administration) was 758.49-848.08 mg·kg-1.All the detected indices of the three groups (660,330 and 170 mg·kg-1) including general condition,weight change,biochemical indices,organ morphological and histological change were all within the normal ranges. The impurity significantly decreased the viability of L929 cells. The NOAEL value was 660 mg·kg-1in mice. Conclusion:The impurity has certain toxicity to mice and cells. The data can provide experimental basis for the quality standard establishment for ornithine and the safety improvement in clinic use.

Objective: To summarize and critically assess the evidence from randomized controlled trials (RCTs) of acupuncture in treating dry eye syndrome (DES) according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement and the Cochrane Collaboration recommendations. Methods: A search of PubMed, the Cochrane Central Register of Controlled Trials, ClinicalTrials.gov and Embase was made from their inception to August 2016, as well as Chinese, Japanese, and Korean databases. Two reviewers independently selected RCTs and assessed the methodological quality. Meta-analysis and the level of evidence were processed by RevMan 5.3 and the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. Results: After selection, 8 trials were subjected to our systematic review. The methodological quality was low generally. The 3-10 weeks follow-up showed that acupuncture improved the tear film break-up time (BUT) (MD=1.33, 95%CI=1.01-1.66, 619 participants). The mean difference of Schirmer's test was 1.73 mm (95%CI=1.28-2.18, 618 participants) between the acupuncture group and the control group. The subjective variables exhibited no significant differences. Conclusion: The low methodological quality of the trials does not suggest drawing firm conclusions on the value of acupuncture therapy for DES. Acupuncture treatment may have some effects on the tear film BUT and Schirmer's test, but not on the subjective symptoms. Well-planned large-scale high-quality RCTs are needed to make it clear whether acupuncture is effective in treating DES.

Objective:To observe the therapeutic effect of warm needling moxibustion for erectile dysfunction (ED).
Methods:A total of 46 eligible ED patients were randomized into a treatment group (n=24) and a control group (n=22). The treatment group was intervened by warm needling moxibustion while the control group by conventional acupuncture treatment, for a total of 4 courses. The therapeutic effect was evaluated by the international index of erectile function 5 (IIEF-5).
Results:After 4 courses of treatment, the overall effective rate was 91.3% in the treatment group (23 completed), versus 75.0% in the control group (20 completed), with a significant difference (P<0.05). After the treatment, the change of IIEF-5 score in the treatment group was significantly different from that in the control group (P<0.05).
Conclusion:Warm needling moxibustion can produce a more significant efficacy than conventional acupuncture in the treatment of ED.

Objective To develop a method for determination of serumal copper ion in rabbit with implantation of copper intrauterine device.Methods At different time points after implantation,the serumal copper ion concentrations were determined by microwave digestion-inductively coupled plasma mass spectrometry(ICP-MS) using scandium(Sc) and indium(In) as internal standards to compensate sample matrix effects,and the pharmacokinetics parameters were calculated in order to reflect copper ion release and metabolic rule.Results The serumal copper ion concentrations were kept at a low and stable level.The recoveries were in the range of 98.7%-113.3%,with the relative standard deviations of less than 5.0%.Conclusion The analytical method is simple,fast,and can be used for the determination of serumal copper ion in rabbit.