ObjectiveTo evaluate pharmacological effects of Shengmai injection（SMI）on cerebral ischemia and study its neuroprotective mechanism. MethodsMale specific pathogen-free （SPF） Sprague-Dawley （SD） rats were randomly divided into a sham group， a model group， a low-dose SMI group（3 mL·kg^-1）， a middle-dose SMI group（6 mL·kg^-1）， a high-dose SMI group（12 mL·kg^-1）， and a Ginaton group（4 mL·kg^-1）according to the random number table method， with 12 rats in each group. The rat model of cerebral ischemia-reperfusion（MCAO/R）was prepared via the suture method. The administration groups were intraperitoneally injected with corresponding concentrations of SMI or Ginaton injection after reperfusion， which was conducted for 3 consecutive days. The sham group and model group were administered the equivalent volume of physiological saline. The pharmacological effects of SMI on brain injury in MCAO/R rats were evaluated by neurological function scores， cerebral infarction area， hematoxylin-eosin （HE） staining， Nissl staining， terminal deoxynucleotidyl transferase dUTP nick-end labeling （TUNEL） staining， and Western blot. The dominant link and key protein of SMI treating cerebral injury were explored using proteomic analysis. The related mechanisms of SMI were further validated using enzyme-linked immunosorbent assay （ELISA）， Western blot， and chloride ion fluorescence probe with oxygen-glucose deprivation/reoxygenation（OGD/R）-treated PC12 cells and MCAO/R rats. ResultsCompared with the sham group， the model group showed significantly increased neurological function scores， cerebral infarction area， neuronal apoptosis rate， and expression levels of apoptosis related proteins （P<0.05， P<0.01）and significantly decreased density of Nissl bodies and neurons（P<0.01）. Compared with the model group， the SMI groups exhibited significantly decreased neurological function scores， cerebral infarction area， neuronal apoptosis rate， and expression levels of apoptosis related proteins （P<0.05， P<0.01）and significantly increased density of Nissl bodies and neurons （P<0.05）. The proteomic analysis results showed that oxidative stress and inflammatory response were important processes of SMI intervening in MCAO/R injury， and the chloride intracellular channel protein 1 （CLIC1） was one of key proteins in its action network. The levels of representative indicators of oxidative stress and inflammatory response in the MCAO/R rats of the SMI groups were significantly reduced， compared with those in the model group（P<0.05， P<0.01）， and the expression levels of CLIC1 and downstream NOD-like receptor protein 3 （NLRP3） decreased （P<0.01）. In addition， the experimental results based on the OGD/R PC12 cells showed that SMI significantly increased the cell survival rate（P<0.01） and significantly decreased the intracellular chloride ion concentration（P<0.05）. ConclusionSMI has neuroprotective effects. Oxidative stress and inflammatory response are key processes of SMI intervening in MCAO/R injury. The potential mechanism is closely related to the regulation of CLIC1.

Objective To investigate the characteristics of tremor in Parkinson disease （PD）， essential tremor （ET）， and neuronal intranuclear inclusion disease （NIID）. Methods The surface electromyography （sEMG） data of both upper limbs were collected from 73 patients with tremor （30 patients in PD group， 23 in ET group， and 20 in NIID group）， and the a power spectral analysis was used to investigate frequency characteristics. A one-way analysis of variance and the chi-square test were used for comparison of electrophysiological parameters on sEMG between the three groups. Results The ET group had a higher tremor frequency than the PD group （F=41.86， P<0.01）， while the PD group had a higher tremor frequency than the NIID group in resting state （F=41.86， P=0.002） and in postural state （F=41.86， P=0.011）. The PD group had a higher proportion of patients with alternating contractions than the NIID group in resting state （χ2=5.70， P=0.017） and in postural state （χ2=7.24， P=0.007）， as well as a higher proportion of such patients than the ET group （χ2=9.67， P=0.002）. The PD group also had a higher proportion of patients with harmonic resonances than the NIID group in resting state （χ2=4.64， P=0.031） and in postural state （χ2=7.73， P=0.005）， as well as a higher proportion of such patients than the ET group （χ2=6.52， P=0.011）. Conclusion The highest tremor frequency is observed in ET， while the lowest tremor frequency is observed in NIID； patients with PD have a higher proportion of individuals with alternating contractions or harmonic resonances than patients with NIID and ET.
Parkinson Disease ; Tremor

Objective: To investigate the distribution of pupil diameter and its association with myopia in school age children, providing ideas into the mechanisms of the role of pupil diameter in the onset and development of myopia. Methods: Adopting a combination of stratified cluster random sampling and convenience sampling method, 3 839 children from six schools in Shandong Province were included in September 2021. Pupil diameters distribution was analyzed by age, sex, and myopic status. Pearson correlation analysis was used to assess the relationship between pupil diameter and cycloplegic spherical equivalent (SE), as well as axial length (AL) and other variables. Propensity score matching (PSM) was applied to match myopic and non myopic children at a 1∶1 ratio based on age and sex. A generalized linear model (GLM) was constructed with pupil diameter as the dependent variable to identify independent factors influencing pupil size and its association with myopia. Results: The mean pupil diameter of school age children was (5.77±0.80)mm. Pupil diameter exhibited a significant increasing trend with age ( F =49.34， P trend ＜ 0.01). Myopic children had a significantly larger mean pupil diameter [(6.10±0.73)mm] compared to non myopic children [(5.62±0.79)mm] with a statistically significant difference( t=18.10, P <0.01). Multivariable GLM analysis, adjusted for age, amplitude of accommodation, and uncorrected visual acuity, revealed a negative correlation between pupil diameter and cycloplegic SE (before PSM: β =-0.089, after PSM: β =-0.063, both P ＜0.01). Conclusions Myopic school age children exhibite larger pupil diameters than their non myopic counterparts. Pupil diameter may serve as a potential indicator for monitoring myopia development in school age children.

ObjectiveBased on the integrated strategy of "empirical prescriptions in ancient books-medical cases by prestigious doctors-computational analysis"， this study aims to explore and analyze the prescriptions and medical cases for treating tremors in traditional Chinese medicine （TCM）， predict their efficacy， and obtain the core prescriptions for treating tremors in TCM， providing references for clinical application and new drug development. MethodThe Chinese Medicine Prescription Database and the China National Knowledge Infrastructure （CNKI） were searched for relevant prescriptions and medical cases for treating tremors in TCM to establish a database of prescriptions for tremors. The Traditional Chinese Medicine Inheritance Computer System （V3.0） was used to analyze and explore the medication rules including drug frequency， properties， flavor， meridian tropism， and pharmacological effects， as well as core drugs and formula associations. A multi-target drug efficacy prediction platform based on network robustness was used to evaluate the predicted efficacy of the core prescriptions obtained. Based on the integration of ancient prescriptions， prestigious doctors' medical cases， and network analysis results， the priority level of the developed prescriptions was determined through comprehensive evaluation. ResultA total of 81 ancient prescriptions were screened， involving 246 drugs， and 171 prescriptions were screened from prestigious doctors' medical cases， involving 278 drugs. The frequently used TCM drugs were mostly warm in nature and sweet in flavor， mainly acting on the liver， spleen， and kidney meridians. In terms of efficacy， they were mainly effective in tonifying deficiency， soothing liver and extinguishing wind， activating blood and resolving blood stasis， clearing heat， and resolving exterior. Through association rules and K-means clustering， the core prescriptions were composed of high-frequency drugs such as Glycyrrhizae Radix et Rhizoma， Ginseng Radix et Rhizoma， Astragali Radix， Atractylodis Macrocephalae Rhizoma， Angelicae Sinensis Radix， Poria， Gastrodiae Rhizoma， and Uncariae Ramulus Cum Uncis. Drug combinations mainly focused on tonifying Qi and nourishing blood， with the additional functions of calming wind and dredging collaterals. Clustering analysis of core prescriptions from ancient prescriptions and prestigious doctors' medical cases， as well as multi-target drug efficacy prediction， showed that Combination 1 had the highest disturbance score on the disease network. Furthermore， comparative analysis revealed consistent results with both the analysis of ancient prescriptions and prestigious doctors' medical cases， indicating its optimal development potential based on theoretical inheritance and empirical practice. In comparison， Combinations 3， 2， and 4 were less utilized in contemporary clinical practice， with lower rankings in network disturbance scores， suggesting that their development value still warranted further exploration. ConclusionTCM clinical treatment of tremors emphasizes the regulation of the liver， spleen， and kidney. In line of syndrome differentiation， drugs potent in soothing liver， extinguishing wind， activating blood， and resolving blood stasis are added based on deficiency-tonifying drugs. The core prescriptions based on Glycyrrhizae Radix et Rhizoma， Angelicae Sinensis Radix， Paeoniae Radix Alba， Astragali Radix， Poria， and Atractylodis Macrocephalae Rhizoma （combination 1） have the highest potential development value. The integrated strategy "empirical prescriptions in ancient books-medical cases by prestigious doctors-computational analysis" can be used for the screening of candidate prescriptions for new TCM drugs.

The American Association of Hip and Knee Surgeons, the American Academy of Orthopaedic Surgeons, and the American Society of Regional Anesthesia and Pain Medicine collaborated to develop an evidence-based study about the safe and effective use of Ketamine in total joint arthroplasty(TJA). Based on the systematic review and Meta-analysis of several studies, the following conclusions are drawn: Ketamine can effectively relieve the postoperative pain of patients; Ketamine can effectively reduce the occurrence of postoperative nausea and vomiting; Ketamine can reduce the use of postoperative opioids; intraoperative use of Ketamine does not increase the incidence of postoperative adverse reactions. The above conclusions are graded according to the strength of evidence support. This article interprets the guidelines to provide reference for addressing the effectiveness and safety of Ketamine use in TJA.

OBJECTIVE To study the sedative and hypnotic effects of zolpidem and the content of amino acid neurotransmitters in the thalamus and hypothalamus after treatment with zolpidem.METHODS Experiments on the loss of righting reflex(LORR)induced by the upper-threshold dose pentobarbital sodium(50 mg·kg-1,ip)were conducted to establish a hypoxic insomnia model in mice by simulating an altitude of 5500 m.Based on this model,the synergistic effect of zolpidem(0.33,1,3,9 and 27 mg·kg-1,ip)and the subthreshold(20 mg·kg-1,ip)and upper-threshold pentobarbital sodium,as well as the sedative hypnotic effect of zolpidem(10,13,17,20,23,30 and 40 mg·kg-1,ip)were evaluated via the LORR in normoxic and hypoxic environments.One hour after ip given zolpidem,the levels of glutamic acid(Glu)and γ-aminobutyric acid(GABA)in the thalamus and hypothalamus of mice in either environment were determined by the high-performance liquid chromatography(HPLC)with fluorescence detection.RESULTS One-day treatment with hypoxia significantly shortened the duration of LORR induced by the upper-threshold dose pentobarbital sodium.Compared with normoxia vehicle and hypoxia induced insomnia vehicle groups,zolpidem 9 and 27 mg·kg-1 significantly shortened the latency to LORR(P<0.01,P<0.05)and prolonged duration of LORR induced by subthreshold and upper-threshold pentobarbital sodi-um(P<0.01,P<0.05).The median effective dose(ED50)of LORR induced by zolpidem was 16.21 and 20.55 mg·kg-1 in normoxic and hypoxic environments,respectively.The results of neurotransmitter level detection showed that Glu contents in the thalamus and hypothalamus and the ratio of Glu/GABA in the hypothalamus were decreased after treatment with zolpidem 40 mg·kg-1 in a normoxic environment(P<0.01,P<0.05).Compared with the normoxia control group,Glu content and the ratio of Glu/GABA in the hypothalamus were significantly increased after treatment with hypoxia(P<0.01,P<0.05),and zolpidem 40 mg·kg-1 could reverse their elevation.CONCLUSION The sedative-hypnotic effect of zolpidem is weakened in a hypoxic environment,and the effect of zolpidem on the levels of Glu and GABA in the hypothalamus may play an important role in the sedative-hypnotic effect of zolpidem.

Objective:To investigate the correlation between liver stiffness and histopathological changes in a rat model of acute hepatitis using virtual touch tissue imaging quantification (VTIQ) technology.Methods:A total of 100 SPF-grade SD rats were randomly divided into 3 groups: control ( n=30), low-dose ( n=35), and high-dose ( n=35) groups. Acute hepatitis models were induced in the low-dose and high-dose groups using 400 mg/kg and 600 mg/kg of Thioacetamide (TAA), respectively. Liver stiffness parameters of the right median lobe and right lobe were measured using VTIQ technology, Mean-H and Mean-L represent the liver lobes with higher and lower liver stiffness measurments, respectively, while Mean represent the average of the measurements from both liver lobes. Comparative analyses of liver stiffness parameters were performed across three groups and between the two lobes of the liver. The correlations between the Mean values of liver stiffness and semi-quantitative histopathological data were investigated. Ten rats were randomly selected from each of the 3 groups to test the repeatability of VTIQ values before and after euthanasia with intraperitoneal anesthesia. Subsequently, 10 rats after euthanasia from each 3 group were randomly chosen to assess the repeatability of VTIQ measurements for inter-observer and intra-observer variabilities. Results:VTIQ results showed statistically significant differences in Mean, Mean-H, and Mean-L among the 3 groups (all P<0.01). The high-dose group had higher measurements compared to the low-dose and control groups, with significant intergroup differences (all P<0.01). Significant differences in Mean-H and Mean-L were observed between the two liver lobes in both low and high-dose groups (all P<0.01). The Mean value showed significant positive correlations with semi-quantitative histopathological data of hepatocellular edema, periportal inflammatory cell infiltration, macrophage proliferation, and bile duct proliferation ( r=0.391, 0.648, 0.577, 0.542; all P<0.01). Multivariate linear regression analysis indicated that hepatocellular edema, eosinophilic change, and bile duct proliferation significantly and positively predicted the Mean value (β=-0.278, -0.196, -0.333; all P<0.05). There were no significant differences of VTIQ measurements befor and after euthanasia (all P>0.05), with repeatability coefficients of 0.166, 0.182, 0.185 for Mean, Mean-H, and Mean-L, respectively. Post-euthanasia, inter- and intra-observer VTIQ differences remained non-significant (all P>0.05), with Mean, Mean-H, Mean-L coefficients of 0.114, 0.194, 0.165 and 0.206, 0.322, 0.268, respectively. Conclusions:VTIQ technology demonstrates potential clinical value in assessing a rat model of acute hepatitis, offering a new perspective for non-invasive evaluation of acute hepatitis. However, its clinical application requires further validation.

Background::Substantial progress in air pollution control has brought considerable health benefits in China, but little is known about the spatio-temporal trends of economic burden from air pollution. This study aimed to explore their spatio-temporal features of disease burden from air pollution in China to provide policy recommendations for efficiently reducing the air pollution and related disease burden in an era of a growing economy.Methods::Using the Global Burden of Disease method and willingness to pay method, we estimated fine particulate matter (PM 2.5) and/or ozone (O 3) related premature mortality and its economic burden across China, and explored their spatio-temporal trends between 2005 and 2017. Results::In 2017, we estimated that the premature mortality and economic burden related to the two pollutants were RMB 0.94 million (68.49 per 100,000) and 1170.31 billion yuan (1.41% of the national gross domestic product [GDP]), respectively. From 2005 to 2017, the total premature mortality was decreasing with the air quality improvement, but the economic burden was increasing along with the economic growth. And the economic growth has contributed more to the growth of economic costs than the economic burden decrease brought by the air quality improvement. The premature mortality and economic burden from O 3 in the total loss from the two pollutants was substantially lower than that of PM 2.5, but it was rapidly growing. The O 3-contribution was highest in the Yangtze River Delta region, the Fen-Wei Plain region, and some western regions. The proportion of economic burden from PM 2.5 and O 3 to GDP significantly declined from 2005 to 2017 and showed a decreasing trend pattern from northeast to southwest. Conclusion::The disease burden from O 3 is lower than that of PM 2.5, the O 3-contribution has a significantly increasing trend with the growth of economy and O 3 concentration.

Objective The objective of this study was to explore the values of hsa-let-7b-5p in the clinical diagnosis and targeted therapy of non-small cell lung cancer(NSCLC).Methods Thirteen pairs of NSCLC tissues and their adjacent tissues with the same pathological type in Harbin Medical University Cancer Hospital from September to October 2020 were collected,and differen-tially expressed miRNAs were obtained by RNA-Seq,and the expression of candidate miRNAs were verified in NSCLC tissues and cells through qRT-PCR.The effects of miRNAs on the proliferation,migration and invasion ability of NSCLC were verified by CCK-8 assay,clone formation assay,scratch assay and Transwell assay.Target genes were predicted using MiRDB,TarBase and ENCORI da-tabases,and gene enrichment analysis was performed using FunRich tool.Results Compared with adjacent tissues and human bron-chial epithelial cells(HBE),hsa-let-7b-5p was downregulated in NSCLC tissues and cell lines(A549 cells,H1299 cells,H358 cells and H460 cells)(P<0.05).The high expression of hsa-let-7b-5p inhibited the proliferation,migration and invasion ability of NSCLC(P<0.01).The results of target genes and enrichment analysis showed that among 378 target genes and related genes of hsa-let-7b-5p,147 genes were negatively correlated with the expression of hsa-let-7b-5p(P<0.05).Conclusion Hsa-let-7b-5phas inhibitory effects on the proliferation,migration and invasion of NSCLC.

As a noval class of nucleic acid drugs,messenger ribonucleic acid(mRNA)has great application potential in vaccines,immunotherapy,regenerative medicine,gene editing and so on.In particular,coronavirus disease 2019(COVID-19)in 2020 has greatly accelerated the mRNA technology development globally.However,mRNA being negatively charged,face challenges in cell entry and is easy to be phagocytized by cells of the innate immune system or degraded by nucleases in vivo.The instability and low delivery efficiency hinder widespread application of mRNA-based therapy.Therefore,safe,effective and stable delivery was needed carriers to protect mRNA from degradation and break through the barrier of cell membrane in order to ensure it express in intracellular.This paper systematically reviews the latest research progress of mRNA delivery carriers and briefly describes lipid carriers,polymer carriers,peptide carriers and viral carriers.The future directions of mRNA delivery carriers research are prospected so as to provide reference for the development of new mRNA drug delivery carriers.