ObjectiveTo investigate the mechanism of Acanthopanacis Senticosi Radix et Rhizoma seu Caulis extract （ASH） in treating Parkinson's disease （PD） in mice by Data-Independent Acquisition （DIA） proteomics. MethodsThe α-Synuclein （α-Syn） transgenic PD mice were selected as suitable models for PD， and they were randomly assigned into PD， ASH （61.25 mg·kg^-1）， and Madopar （97.5 mg·kg^-1） groups. Male C57BL/6 mice of the same age were selected as the control group， with eight mice in each group. Mice were administrated with corresponding drugs by gavage once a day for 20 days. The pole climbing time and the number of autonomic activities were recorded to evaluate the exercise ability of mice. Hematoxylin-eosin staining was employed to observe neuronal changes in the substantia nigra of PD mice. Immunohistochemistry （IHC） was employed to measure the tyrosine hydroxylase （TH） activity in the substantia nigra and assess the areal density of α-Syn in the striatum. DIA proteomics was used to compare protein expression in the substantia nigra between groups. IHC was utilized to validate key differentially expressed proteins， including Lactotransferrin， Notch2， Ndrg2， and TMEM 166. The cell counting kit-8 （CCK-8） method was used to investigate the effect of ASH on the viability of PD cells with overexpression of α-Syn. Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） and Western blot were employed to determine the protein and mRNA levels of Lactotransferrin， Notch2， Ndrg2， and TMEM 166 in PD cells. ResultsCompared with the control group， the model group showed prolonged pole climbing time， diminished coordination ability， reduced autonomic activities （P<0.01）， and reduced swelling neurons. Compared with the model group， ASH and Madopar reduced the climbing time， increased autonomic activities （P<0.01）， and ameliorated neuronal damage. Compared with the control group， the model group showed a decrease in TH activity in the substantia nigra and an increase in α-Syn accumulation in the striatum （P<0.01）. Compared with the model group， the ASH group showed an increase in TH activity and a reduction in α-Syn accumulation （P<0.05）. DIA proteomics revealed a total of 464 differentially expressed proteins in the model group compared with the control group， with 323 proteins being up-regulated and 141 down-regulated. A total of 262 differentially expressed proteins were screened in the ASH group compared with the model group， including 85 proteins being up-regulated and 177 down-regulated. Kyoto encylopedia of genes and genomes （KEGG） pathway analysis indicated that ASH primarily regulated the Notch signaling pathway. The model group showed up-regulation in protein levels of Notch2， Ndrg2， and TMEM 166 and down-regulation in the protein level of Lactotransferrin compared with the control group （P<0.01）. Compared with the model group， ASH down-regulated the protein levels of Notch2， Ndrg2， and TMEM 166 （P<0.05） while up-regulating the protein level of Lactotransferrin （P<0.01）. The IHC results corroborated the proteomics findings. The cell experiment results showed that compared with the control group， the modeling up-regulated the mRNA and protein levels of Notch2， Ndrg2， and TMEM 166 （P<0.01）， while down-regulating the mRNA and protein levels of Lactotransferrin （P<0.01）. Compared with the model group， ASH reduced the mRNA and protein levels of Notch2， Ndrg2， and TMEM 166 （P<0.01）， while increasing the mRNA and protein levels of Lactotransferrin （P<0.05， P<0.01）. ConclusionASH may Synergistically inhibit the Notch signaling pathway and mitigate neuronal damage by down-regulating the expression of Notch2 and Ndrg2. Additionally， by up-regulating the expression of Lactotransferrin and down-regulating the expression of TMEM166， ASH can address brain iron accumulation， intervene in ferroptosis， inhibit mitophagy， and mitigate reactive oxygen species damage， thereby protecting nerve cells and contributing to the treatment of PD.

With the widespread use of antibiotics, drug-resistant bacterial infections have become a significant threat to human health. Finding new antibacterial strategies that can effectively control drug-resistant bacterial infections has become an urgent task. Unlike small molecule drugs that target bacterial proteins, antisense oligonucleotide (ASO) can target genes related to bacterial resistance, pathogenesis, growth, reproduction and biofilm formation. By regulating the expression of these genes, ASO can inhibit or kill bacteria, providing a novel approach for the development of antibacterial drugs. To overcome the challenge of delivering antisense oligonucleotide into bacterial cells, various drug delivery systems have been applied in this field, including cell-penetrating peptides, lipid nanoparticles and inorganic nanoparticles, which have injected new momentum into the development of antisense oligonucleotide in the antibacterial realm. This review summarizes the current development of small nucleic acid drugs, the antibacterial mechanisms, targets, sequences and delivery vectors of antisense oligonucleotide, providing a reference for the research and development of antisense oligonucleotide in the treatment of bacterial infections.

AIM:To evaluate the effectiveness of EYESI binocular indirect ophthalmoscope simulation system as a training platform for fundus examination skills of general practitioner.METHODS:Prospective randomized study. A total of 40 general practitioners who received clinical ophthalmology training at Shenzhen Eye Hospital from January 2021 to December 2024 were selected and randomly divided into two groups by random number table method, with 20 cases in the study group and 20 cases in the control group. The study group was trained by EYESI binocular indirect ophthalmoscope simulation system and the control group was trained by conventional teaching. Training effects of the two groups were analyzed.RESULTS: The general information of the two groups was comparable. Through training with the EYESI binocular indirect ophthalmoscope simulator, the study group showed significant improvements in total examination and drawing scores compared to pre-training results(all P<0.001). Additionally, examination duration, retinal light exposure time, and drawing time were all significantly shorter than those before training(all P<0.001).The study group achieved significantly higher total examination and drawing scores than the control group during the EYESI binocular indirect ophthalmoscope simulator assessment(all P<0.001). Furthermore, examination duration, retinal light exposure time, and drawing time were all significantly shorter in the study group compared to the control group(all P<0.001). Moreover, ratings for the novelty of the training method and overall satisfaction with the training were significantly higher in the study group than in the control group(all P<0.001); while the perceived psychological stress during training was significantly lower in the study group(P<0.001).CONCLUSION:The EYESI binocular indirect ophthalmoscope simulaton system effectively enhances both the proficiency in fundus examination skills and overall training satisfaction among general practitioners.

The incidence of myopia among Chinese adolescents is progressively rising, indicating a distinct trend toward younger age onset.This paper aims to comprehensively review the impact of various visual performance on myopia and its progression, with a specific emphasis on accommodative function, convergence function, and ocular position. A meticulous exploration of accommodation function, encompassing accommodative amplitude, accommodative facility, accommodative response, positive relative accommodation, and negative relative accommodation, has been undertaken to elucidate its contributory role in myopia progression. Concurrently, an exhaustive analysis of convergence function has been conducted including esotropia and exotropia, convergence insufficiency and convergence excess, fusional function vergence, divergence insufficiency, and excess, providing a nuanced understanding of convergence's implications for myopia advancement. Furthermore, the influence of ocular position on myopia progression, along with other factors affecting perceptual ocular position and intermittent exotropia, is discussed. The primary objective of this article is to unveil the multifaceted visual performance influencing myopia and its progression, elucidating the paramount significance of accommodative function, convergence function, and ocular position in this context.

Platycodonis Radix is the dry root of Platycodon grandiflorum of Campanulaceae, which has a variety of pharmacological effects and is a commonly used bulk Chinese medicine. In this study, the chloroplast genome sequences of six P. grandiflorum from different producing areas has been sequenced with Illumina HiSeq X Ten platform. The specific DNA barcodes were screened, and the germplasm resources and genetic diversity were analyzed according to the specific barcodes. The total length of the chloroplast genome of 6 P. grandiflorum samples was 172 260-172 275 bp, and all chloroplast genomes showed a typical circular tetrad structure and encoded 141 genes. The comparative genomics analysis and results of amplification efficiency demonstrated that trnG-UCC and ndhG_ndhF were the potential specific DNA barcodes for identification the germplasm resources of P. grandiflorum. A total of 305 P. grandiflorum samples were collected from 15 production areas in 9 provinces, for which the fragments of trnG-UCC and ndhG_ndhF were amplificated and the sequences were analyzed. The results showed that trnG-UCC and ndhG_ndhF have 5 and 11 mutation sites, respectively, and 5 and 7 haplotypes were identified, respectively. The combined analysis of the two sequences formed 13 haplotypes (named Hap1-Hap13), and Hap4 is the main genotype, followed by Hap1. The unique haplotypes possessed by the three producing areas can be used as DNA molecular tags in this area to distinguish from the germplasm resources of P. grandiflorum from other areas. The haplotype diversity, nucleotide diversity and genetic distance were 0.94, 4.79×10^-3 and 0.000 0-0.020 3, respectively, suggesting that the genetic diversity was abundant and intraspecific kinship was relatively close. This study laid a foundation for the identification of P. grandiflorum, the protection and utilization of germplasm resources, and molecular breeding.

Objective:To investigate the relationship between intramuscular adipose tissue index (IATI) calculated from computed tomography images at transverse process of the first lumbar and all-cause mortality in maintenance dialysis patients, and to provide a reference for improving the prognosis in these patients.Methods:It was a multicenter retrospective cohort study. The clinical data of patients who received maintenance hemodialysis or peritoneal dialysis treatment from January 1, 2017 to December 31, 2019 in 4 grade Ⅲ hospitals including Zhongda Hospital Affiliated to Southeast University, Taizhou People's Hospital Affiliated to Nanjing Medical University, Affiliated Hospital of Yangzhou University, and the Third Affiliated Hospital of Soochow University were retrospectively collected. IATI was calculated by low attenuation muscle (LAM) density/skeletal muscle density. The receiver-operating characteristic curve was used to determine the optimal cut-off value of IATI, and the patients were divided into high IATI group and low IATI group according to the optimal cut-off value. The differences of baseline clinical data and measurement parameters of the first lumbar level between the two groups were compared. The follow-up ended on December 23, 2022. The endpoint event was defined as all-cause mortality within 3 years. Kaplan-Meier survival curve and log-rank test were used to analyze the survival rates and the differences between the two groups. Multivariate Cox regression analysis models were used to analyze the association between IATI and the risk of all-cause mortality in maintenance dialysis patients. Multivariate logistic regression analysis model was used to analyze the influencing factors of high IATI.Results:A total of 478 patients were eligibly recruited in this study, with age of (53.55±13.19) years old and 319 (66.7%) males, including 365 (76.4%) hemodialysis patients and 113 (23.6%) peritoneal dialysis patients. There were 376 (78.7%) patients in low IATI (<0.42) group and 102 (21.3%) patients in high IATI (≥0.42) group. The proportion of age ≥ 60 years old ( χ2=24.746, P<0.001), proportion of diabetes mellitus ( χ2=5.570, P=0.018), fasting blood glucose ( t=-2.145, P=0.032), LAM density ( t=-3.735, P<0.001), LAM index ( t=-7.072, P<0.001), and LAM area/skeletal muscle area ratio ( Z=-9.630, P<0.001) in high IATI group were all higher than those in low IATI group, while proportion of males ( χ2=11.116, P<0.001), serum albumin ( Z=2.708, P=0.007) and skeletal muscle density ( t=12.380, P<0.001) were lower than those in low IATI group. Kaplan-Meier survival analysis showed that the 3-years overall survival rate of low IATI group was significantly higher than that in high IATI group (Log-rank χ2=19.188, P<0.001). Multivariate Cox regression analysis showed that IATI<0.42 [<0.42/≥0.42, HR(95% CI): 0.50 (0.31-0.83), P=0.007] was an independent protective factor of all-cause mortality, and age ≥60 years old [ HR (95% CI): 2.61 (1.60-4.23), P<0.001], diabetes mellitus [ HR (95% CI): 1.71 (1.06-2.78), P=0.029] and high blood neutrophil/lymphocyte ratio [ HR (95% CI): 1.04 (1.00-1.07), P=0.049] were the independent risk factors of all-cause mortality in maintenance dialysis patients. Stepwise Cox regression analysis showed that IATI<0.42 was still an independent protective factor of all-cause mortality in maintenance dialysis patients [<0.42/≥0.42, HR (95% CI): 0.45 (0.27-0.76), P=0.003]. Multivariate logistic regression analysis showed that low skeletal muscle density [ OR (95% CI): 0.84 (0.81-0.88), P<0.001] and high serum triglyceride [ OR (95% CI): 1.39 (1.07-1.82), P=0.015] were the independent influencing factors of IATI≥0.42. Conclusion:IATI<0.42 of the first lumbar level is an independent protective factor of all-cause mortality in maintenance dialysis patients. Localized myosteatosis within high-quality skeletal muscle may reduce the risk of all-cause mortality in these patients.

Objective:To investigate the correlation of the emm genotypes and virulence genes with the isolation sites of Group A Streptococcus (GAS). Methods:It was a retrospective study.The specimens were collected from children with impetigo in Beijing Children′s Hospital, Capital Medical University from 2006 to 2008 for GAS isolation and identification.A total of 24 GAS strains were isolated from 16 children with impetigo, among which 7 pairs of strains were isolated from the throat and skin of 7 children, and 1 pair of strains was isolated from the vulva and skin of one child, and the remaining 8 GAS strains were isolated from the skin pus samples of 8 children.Polymerase chain reaction was applied to detect the emm genotypes and 13 virulence genes ( speA, speB, speC, speF, speG, speH, speI, speJ, speK, speL, speM, smeZ and ssa). The correlation of the emm genotypes and virulence genes with the isolation sites of GAS strains was analyzed. Results:In this study, four emm genotypes were detected, including emm1.0 (15/24), emm12.0 (4/24), emm22.0 (2/24) and emm160.0 (1/24), and one subtype emm12.19 (2/24) was detected as well.The carrying rates of 13 virulence genes speA, speB, speC, speF, speG, speH, speI, speJ, speK, speL, speM, smeZ and ssa were 58.3%, 100%, 91.7%, 100%, 50.0%, 12.5%, 54.2%, 66.7%, 16.7%, 25.0%, 12.5%, 100% and 91.7%, respectively.All strains carried 5 to 11 virulence genes and they all carried speB, speF and smeZ.There were significant differences in the carrying rate of speA and speJ among the strains with different emm genotypes (all P<0.05). There was no significant difference in the distribution of virulence genes between skin isolates and pharyngeal isolates, including the 5 pairs of strains carrying the emm1.0 genotype (all P>0.05). Conclusions:The distribution of virulence gene of GAS in children with impetigo is significantly correlated with the emm genotype, rather than the isolation site.

BACKGROUND:As a dominant breed pig in southwest China,the southern Yunnan small-ear pig has been widely used as an experimental animal in the basic research of other disciplines,but there are still no reports on its application in anterior cruciate ligament reconstruction. OBJECTIVE:To establish a large animal model of the southern Yunnan small-ear pig with anterior cruciate ligament with autologous Achilles tendon was established. METHODS:Twenty adult female Yunnan small-ear pigs were equally randomized into two groups.In the autologous Achilles tendon group,the right knee anterior cruciate ligament was reconstructed with autologous Achilles tendon as a graft,while in the sham-operated group,a similar operation was performed on the right knee without any treatment of the anterior cruciate ligament.General conditions of each pig were observed and recorded before and 12 months after surgery.Ligaments and grafts were taken for gross observation and MAS scoring.Hematoxylin-eosin staining was performed to observe morphological characteristics of ligaments.The staining and arrangement of type I and type Ⅲ collagen were evaluated by immunohistochemistry.Transmission electron microscopy was used to observe the type,size,diameter,ratio,and distribution of collagen fibers in ligaments. RESULTS AND CONCLUSION:All animals had normal diet and activity,good wound healing,no obvious inflammatory reaction,no local purulent infection,and no significant changes in mental and urinary conditions compared with those before surgery.The reconstructed cruciate ligament of the knee was intact,with no stiffness and normal range of motion.Both the anterior drawer and Lachman tests were negative.Gross observation of the graft:12 months after surgery,the grafts was in good position,with good integrity,obvious tension,ligament color close to the original anterior cruciate ligament,and complete surface synovial coverage.Most of the intraarticular ligaments in the autologous Achilles tendon group were defined as MAS I type and a few were defined as MAS Ⅱ type.In the sham-operated group,the intraarticular ligament was defined as MAS I type.Hematoxylin-eosin staining indicated that,12 months after surgery,collagen fibers in the autologous Achilles tendon group began to appear bundled,isotropic,and uniformly arranged,with more obvious isotropic corrugations,and the nuclei were mainly linear or spindle-shaped,which were similar to those in normal anterior cruciate ligament tissue of the sham-operated group.Immunohistochemistry results indicated that,12 months after surgery,there was a higher expression of type I collagen and significantly less expression of type Ⅲ collagen in the reconstructed anterior cruciate ligament in the autologous Achilles tendon group.The degree of type I and type Ⅲ staining was similar in the two groups.Under the transmission electron microscope,the diameter,arrangement and density of collagen fibers in the reconstructed anterior cruciate ligament of the autologous Achilles tendon group were similar to those of the original anterior cruciate ligament at 12 months after surgery,indicating that the ligament remodeling process had been basically completed in the autologous Achilles tendon group at 12 months after surgery.Through a comprehensive evaluation of animal general conditions,ligament general view,MAS score,hematoxylin-eosin staining,immunohistochemistry,and transmission electron microscopy observation,we successfully established a large animal model of anterior cruciate ligament reconstruction using autogenous Achilles tendon in southern Yunnan small-ear pigs,with good morphological,histological and ultrastructural results.

Objective:To investigate the prognosis of patients with initially resectable gastric cancer liver metastasis (GCLM) who were treated by different modalities, and analyze the influencing factors for prognosis of patients.Methods:The retrospective cohort study was conducted. The clinicopathological data of 327 patients with initially resectable GCLM who were included in the database of a nationwide multicenter retrospective cohort study on GCLM based on real-world data from January 2010 to December 2019 were collected. There were 267 males and 60 females, aged 61(54,68)years. According to the specific situations of patients, treatment modalities included radical surgery combined with systemic treatment, palliative surgery combined with systemic treatment, and systemic treatment alone. Observation indicators: (1) clinical characteristics of patients who were treated by different modalities; (2) prognostic outcomes of patients who were treated by different modalities; (3) analysis of influencing factors for prognosis of patients with initially resectable GCLM; (4) screening of potential beneficiaries in patients who were treated by radical surgery plus systemic treatment and patients who were treated by palliative surgery plus systemic treatment. Measurement data with normal distribution were represented as Mean± SD, and comparison between groups was conducted using the independent sample t test. Measurement data with skewed distribution were represented as M( Q1, Q3), and comparison between groups was conducted using the rank sum test. Count data were described as absolute numbers or percentages, and comparison between groups was conducted using the chi-square test. The Kaplan-Meier method was used to calculate survival rate and draw survival curve, and Log-Rank test was used for survival analysis. Univariate and multivariate analyses were conducted using the COX proportional hazard regression model. The propensity score matching was employed by the 1:1 nearest neighbor matching method with a caliper value of 0.1. The forest plots were utilized to evaluate potential benefits of diverse surgical combined with systemic treatments within the population. Results:(1) Clinical characteristics of patients who were treated by different modalities. Of 327 patients, there were 118 cases undergoing radical surgery plus systemic treatment, 164 cases undergoing palliative surgery plus systemic treatment, and 45 cases undergoing systemic treatment alone. There were significant differences in smoking, drinking, site of primary gastric tumor, diameter of primary gastric tumor, site of liver metastasis, and metastatic interval among the three groups of patients ( P<0.05). (2) Prognostic outcomes of patients who were treated by different modalities. The median overall survival time of the 327 pati-ents was 19.9 months (95% confidence interval as 14.9-24.9 months), with 1-, 3-year overall survival rate of 61.3%, 32.7%, respectively. The 1-year overall survival rates of patients undergoing radical surgery plus systemic treatment, palliative surgery plus systemic treatment and systemic treatment alone were 68.3%, 63.1%, 30.6%, and the 3-year overall survival rates were 41.1%, 29.9%, 11.9%, showing a significant difference in overall survival rate among the three groups of patients ( χ2=19.46, P<0.05). Results of further analysis showed that there was a significant difference in overall survival rate between patients undergoing radical surgery plus systemic treatment and patients undergoing systemic treatment alone ( hazard ratio=0.40, 95% confidence interval as 0.26-0.61, P<0.05), between patients undergoing palliative surgery plus systemic treatment and patients under-going systemic treatment alone ( hazard ratio=0.47, 95% confidence interval as 0.32-0.71, P<0.05). (3) Analysis of influencing factors for prognosis of patients with initially resectable GCLM. Results of multivariate analysis showed that the larger primary gastric tumor, poorly differentiated tumor, larger liver metastasis, multiple hepatic metastases were independent risk factors for prognosis of patients with initially resectable GCLM ( hazard ratio=1.20, 1.70, 1.20, 2.06, 95% confidence interval as 1.14-1.27, 1.25-2.31, 1.04-1.42, 1.45-2.92, P<0.05) and immunotherapy or targeted therapy, the treatment modality of radical or palliative surgery plus systemic therapy were independent protective factors for prognosis of patients with initially resectable GCLM ( hazard ratio=0.60, 0.39, 0.46, 95% confidence interval as 0.42-0.87, 0.25-0.60, 0.30-0.70, P<0.05). (4) Screening of potentinal beneficiaries in patients who were treated by radical surgery plus systemic treatment and patients who were treated by palliative surgery plus systemic treatment. Results of forest plots analysis showed that for patients with high-moderate differentiated GCLM and patients with liver metastasis located in the left liver, the overall survival rate of patients undergoing radical surgery plus systemic treatment was better than patients undergoing palliative surgery plus systemic treatment ( hazard ratio=0.21, 0.42, 95% confidence interval as 0.09-0.48, 0.23-0.78, P<0.05). Conclusions:Compared to systemic therapy alone, both radical and palliative surgery plus systemic therapy can improve the pro-gnosis of patients with initially resectable GCLM. The larger primary gastric tumor, poorly differen-tiated tumor, larger liver metastasis, multiple hepatic metastases are independent risk factors for prognosis of patients with initial resectable GCLM and immunotherapy or targeted therapy, the treatment modality of radical or palliative surgery plus systemic therapy are independent protective factors for prognosis of patients with initially resectable GCLM.

Objective:To evaluate the clinical efficacy, tolerability and safety of adjunctive perampanel in focal epilepsy patients≥12 years old.Methods:One hundred and nineteen focal epilepsy patients≥12 years old accepted adjunctive perampanel in Department of Neurology, First Affiliated Hospital of Guangxi Medical University from July 2020 to December 2022 were chosen. At 1-3 months, 4-6 months, 7-9 months and 10-12 months after adjunctive perampanel, seizure frequency changes every 28 d, medication retention rate and adverse reactions were recorded to evaluate the clinical efficacy (a reduction in seizure frequency≥50% from baseline was defined as overall valid treatment), tolerability and safety of adjunctive perampanel. According to efficacy results after adjunctive perampanel of 4-6 months (short-term) and 10-12 months (long-term), these patients were divided into valid group and invalid group; and the influencing factors for short-term and long-term efficacy were analyzed.Results:At 1-3, 4-6, 7-9, 10-12 months after adjunctive perampanel, reduction in seizure frequency every 28 d was 66.7% (24.3%, 97.2%), 77.5% (48.6%, 100%), 94.6% (50%, 100%), 100% (70.9%, 100%), enjoying overall valid rate of 60.2% (59/98), 75.0% (7/76), 78.9% (45/57), 86.5% (32/37). The retention rate at 3, 6, 9 and 12 months after adjunctive perampanel was 85.2% (98/115), 67.9% (76/112), 54.3% (57/105), 41.1% (37/90). Adverse reactions were reported in 33 patents (27.7%), mainly with dizziness and secondly with mental symptoms. After short-term and long-term adjunctive perampanel, no significant difference was noted in gender, initial age of adjunctive perampanel, course of disease, etiology, EEG results, imaging results, number and type of combined anti-seizure drugs, or maximum dose of pirampanel between the valid group and invalid group ( P>0.05). Conclusion:Perampanel has good efficacy, tolerability and safety in adolescents and adults≥12 years old with focal epilepsy; no clear influencing factors for pirampanel valid treatment is found so far.