1.Development of a High-throughput Sequencing Platform for Detection of Viral Encephalitis Pathogens Based on Amplicon Sequencing
Li Ya ZHANG ; Zhe Wen SU ; Chen Rui WANG ; Yan LI ; Feng Jun ZHANG ; Hui Sheng LIU ; He Dan HU ; Xiao Chong XU ; Yu Jia YIN ; Kai Qi YIN ; Ying HE ; Fan LI ; Hong Shi FU ; Kai NIE ; Dong Guo LIANG ; Yong TAO ; Tao Song XU ; Feng Chao MA ; Yu Huan WANG
Biomedical and Environmental Sciences 2024;37(3):294-302
		                        		
		                        			
		                        			Objective Viral encephalitis is an infectious disease severely affecting human health.It is caused by a wide variety of viral pathogens,including herpes viruses,flaviviruses,enteroviruses,and other viruses.The laboratory diagnosis of viral encephalitis is a worldwide challenge.Recently,high-throughput sequencing technology has provided new tools for diagnosing central nervous system infections.Thus,In this study,we established a multipathogen detection platform for viral encephalitis based on amplicon sequencing. Methods We designed nine pairs of specific polymerase chain reaction(PCR)primers for the 12 viruses by reviewing the relevant literature.The detection ability of the primers was verified by software simulation and the detection of known positive samples.Amplicon sequencing was used to validate the samples,and consistency was compared with Sanger sequencing. Results The results showed that the target sequences of various pathogens were obtained at a coverage depth level greater than 20×,and the sequence lengths were consistent with the sizes of the predicted amplicons.The sequences were verified using the National Center for Biotechnology Information BLAST,and all results were consistent with the results of Sanger sequencing. Conclusion Amplicon-based high-throughput sequencing technology is feasible as a supplementary method for the pathogenic detection of viral encephalitis.It is also a useful tool for the high-volume screening of clinical samples.
		                        		
		                        		
		                        		
		                        	
2.Pathogenic investigation of human respiratory syncytial virus infection in kindergarten children in Tongzhou District, Beijing City in 2023
Lin ZOU ; Chong ZHANG ; Ling TONG ; Xiao LIU ; Jing MA ; Jianguo WANG ; Fang WANG ; Xiang GAO ; Lu XI ; Jianming ZHANG
Chinese Journal of Preventive Medicine 2024;58(8):1150-1153
		                        		
		                        			
		                        			The study focused on individuals with influenza-like symptoms (fever, cough, sore throat, runny nose, and other respiratory symptoms) in three kindergartens in Tongzhou District, Beijing City, in April 2023. Nasopharyngeal swab specimens were collected, and real-time fluorescent quantitative PCR was used to detect common respiratory pathogens in the collected specimens. Positive specimens were subjected to sequencing analysis of the highly variable region of human respiratory syncytial virus (HRSV) G protein, homology analysis and phylogenetic tree analysis. A total of 25 fever cases were collected from 3 kindergartens, aged 3-8 years old, with an age M ( Q1, Q3) of 4 (3.5, 5) years old. Ten confirmed cases of HRSV positive were screened and detected using the fluorescent quantitative PCR method, with a total detection rate of 40% (10/25). Typing identification and sequencing analysis confirmed that the main epidemic type was HRSV subtype B, which was highly homologous and closely related to previous epidemic strains in the region. Through pathogen investigation and analysis, it was preliminarily determined that this epidemic was dominated by HRSV subtype B.
		                        		
		                        		
		                        		
		                        	
3.Pathogenic investigation of human respiratory syncytial virus infection in kindergarten children in Tongzhou District, Beijing City in 2023
Lin ZOU ; Chong ZHANG ; Ling TONG ; Xiao LIU ; Jing MA ; Jianguo WANG ; Fang WANG ; Xiang GAO ; Lu XI ; Jianming ZHANG
Chinese Journal of Preventive Medicine 2024;58(8):1150-1153
		                        		
		                        			
		                        			The study focused on individuals with influenza-like symptoms (fever, cough, sore throat, runny nose, and other respiratory symptoms) in three kindergartens in Tongzhou District, Beijing City, in April 2023. Nasopharyngeal swab specimens were collected, and real-time fluorescent quantitative PCR was used to detect common respiratory pathogens in the collected specimens. Positive specimens were subjected to sequencing analysis of the highly variable region of human respiratory syncytial virus (HRSV) G protein, homology analysis and phylogenetic tree analysis. A total of 25 fever cases were collected from 3 kindergartens, aged 3-8 years old, with an age M ( Q1, Q3) of 4 (3.5, 5) years old. Ten confirmed cases of HRSV positive were screened and detected using the fluorescent quantitative PCR method, with a total detection rate of 40% (10/25). Typing identification and sequencing analysis confirmed that the main epidemic type was HRSV subtype B, which was highly homologous and closely related to previous epidemic strains in the region. Through pathogen investigation and analysis, it was preliminarily determined that this epidemic was dominated by HRSV subtype B.
		                        		
		                        		
		                        		
		                        	
4.Action mechanisms of Qianlie Jindan Tablets on chronic nonbcterial prostatitis in rats:An exploration based on non-targeted urine metabolomics
Teng-Fei CHEN ; Zhi-Chao JIA ; Zhuo-Zhuo SHI ; Jun-Guo MA ; Xiao-Lin LI ; Chong-Fu ZHONG
National Journal of Andrology 2024;30(6):531-539
		                        		
		                        			
		                        			Objective:To explore the mechanisms of Qianlie Jindan Tablets(QLJD)acting on chronic nonbacterial prostatitis(CNP)in rats based on non-targeted urine metabolomics.Methods:According to the body mass index,we equally randomized 30 eight-week-old male SD rats into a blank control,a CNP model control and a QLJD medication group.We established the CNP model in the latter groups and,from the 4th day of modeling,treated the rats in the blank and model control groups intragastrically with nor-mal saline and those in the QLJD medication group with QLJD suspension,qd,for 30 successive days.Then we detected the changes in the metabolites of the rats by ultra-high-performance liquid chromatography-tandem mass spectrometry,and identified the differential metabolites in different groups by multivariate statistical analysis,followed by functional annotation of the differential metabolites.Results:Eight common metabolites were identified by metabolomics analysis,of which 5 were decreased in the CNP model controls and increased in the QLJD medication group,while the other 3 increased in the former and decreased in the latter group.Creatinine and genistein were important differential metabolites,and the arginine and proline metabolic pathways and isoflavone biosynthesis pathways were the main ones for QLJD acting on CNP.Compared with the blank controls,the model controls showed up-regulated arginine and proline metabolic pathways,increased production of creatinine,down-regulated isoflavone biosynthetic pathway and decreased produc-tion of genistein.The above changes in the model controls were all reversed in the QLJD medication group.Conclusion:QLJD acts effectively on CNP in male rats by regulating L-arginine and proline metabolic pathways,as well as the isoflavone biosynthesis pathway and naringenin metabolism.
		                        		
		                        		
		                        		
		                        	
5.Rhodojaponin VI indirectly targets Cav2.2 channels via N-ethylmaleimide-sensitive fusion protein to alleviate neuropathic pain.
Keliang CHEN ; Tao WANG ; Yong LI ; Jun WU ; Cheng-Xiao ZHAO ; Sheng LIU ; Fengrun SUN ; Yehong FANG ; Jiahuan HU ; Jinping HU ; Chong-Jing ZHANG ; Haibo YU ; Chao MA ; Shi-Shan YU
Acta Pharmaceutica Sinica B 2023;13(3):1326-1336
		                        		
		                        			
		                        			Neuropathic pain is a chronic disease that severely afflicts the life and emotional status of patients, but currently available treatments are often ineffective. Novel therapeutic targets for the alleviation of neuropathic pain are urgently needed. Rhodojaponin VI, a grayanotoxin from Rhododendron molle, showed remarkable antinociceptive efficacy in models of neuropathic pain, but its biotargets and mechanisms are unknown. Given the reversible action of rhodojaponin VI and the narrow range over which its structure can be modified, we perforwmed thermal proteome profiling of the rat dorsal root ganglion to determine the protein target of rhodojaponin VI. N-Ethylmaleimide-sensitive fusion (NSF) was confirmed as the key target of rhodojaponin VI through biological and biophysical experiments. Functional validation showed for the first time that NSF facilitated trafficking of the Cav2.2 channel to induce an increase in Ca2+ current intensity, whereas rhodojaponin VI reversed the effects of NSF. In conclusion, rhodojaponin VI represents a unique class of analgesic natural products targeting Cav2.2 channels via NSF.
		                        		
		                        		
		                        		
		                        	
6.Automated Classification of Inherited Retinal Diseases in Optical Coherence Tomography Images Using Few-shot Learning.
Qi ZHAO ; Si Wei MAI ; Qian LI ; Guan Chong HUANG ; Ming Chen GAO ; Wen Li YANG ; Ge WANG ; Ya MA ; Lei LI ; Xiao Yan PENG
Biomedical and Environmental Sciences 2023;36(5):431-440
		                        		
		                        			OBJECTIVE:
		                        			To develop a few-shot learning (FSL) approach for classifying optical coherence tomography (OCT) images in patients with inherited retinal disorders (IRDs).
		                        		
		                        			METHODS:
		                        			In this study, an FSL model based on a student-teacher learning framework was designed to classify images. 2,317 images from 189 participants were included. Of these, 1,126 images revealed IRDs, 533 were normal samples, and 658 were control samples.
		                        		
		                        			RESULTS:
		                        			The FSL model achieved a total accuracy of 0.974-0.983, total sensitivity of 0.934-0.957, total specificity of 0.984-0.990, and total F1 score of 0.935-0.957, which were superior to the total accuracy of the baseline model of 0.943-0.954, total sensitivity of 0.866-0.886, total specificity of 0.962-0.971, and total F1 score of 0.859-0.885. The performance of most subclassifications also exhibited advantages. Moreover, the FSL model had a higher area under curves (AUC) of the receiver operating characteristic (ROC) curves in most subclassifications.
		                        		
		                        			CONCLUSION
		                        			This study demonstrates the effective use of the FSL model for the classification of OCT images from patients with IRDs, normal, and control participants with a smaller volume of data. The general principle and similar network architectures can also be applied to other retinal diseases with a low prevalence.
		                        		
		                        		
		                        		
		                        			Humans
		                        			;
		                        		
		                        			Tomography, Optical Coherence
		                        			;
		                        		
		                        			Deep Learning
		                        			;
		                        		
		                        			Retinal Diseases/diagnostic imaging*
		                        			;
		                        		
		                        			Retina/diagnostic imaging*
		                        			;
		                        		
		                        			ROC Curve
		                        			
		                        		
		                        	
7.Placebo Response among Different Types of Sham Acupuncture for Low Back Pain: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.
Zhi-Yi XIONG ; Xiao-Yu LIU ; Pei-Hong MA ; Chong-Yang SUN ; Cheng-Yi SUN ; Ting-Lan LIU ; Bao-Yan LIU ; Cun-Zhi LIU ; Shi-Yan YAN
Chinese journal of integrative medicine 2023;29(10):941-950
		                        		
		                        			BACKGROUND:
		                        			Low back pain (LBP) is a prevalent and debilitating condition that poses a significant burden on healthcare systems. Acupuncture has been proposed as a promising intervention for LBP, but the evidence supporting its specific effect is insufficient, and the use of sham acupuncture as a control in clinical trials presents challenges due to variations in sham acupuncture techniques and the magnitude of the placebo effect.
		                        		
		                        			OBJECTIVE:
		                        			To investigate the magnitude of the placebo response of sham acupuncture in trials of acupuncture for nonspecific LBP, and to assess whether different types of sham acupuncture are associated with different responses.
		                        		
		                        			METHODS:
		                        			Four databases including PubMed, EMBASE, MEDLINE, and the Cochrane Library were searched through April 15, 2023, and randomized controlled trials (RCTs) were included if they randomized patients with LBP to receive acupuncture or sham acupuncture intervention. The main outcomes included the placebo response in pain intensity, back-specific function and quality of life. Placebo response was defined as the change in these outcome measures from baseline to the end of treatment. Random-effects models were used to synthesize the results, standardized mean differences (SMDs, Hedges'g) were applied to estimate the effect size.
		                        		
		                        			RESULTS:
		                        			A total of 18 RCTs with 3,321 patients were included. Sham acupuncture showed a noteworthy pooled placebo response in pain intensity in patients with LBP [SMD -1.43, 95% confidence interval (CI) -1.95 to -0.91, I2=89%]. A significant placebo response was also shown in back-specific functional status (SMD -0.49, 95% CI -0.70 to -0.29, I2=73%), but not in quality of life (SMD 0.34, 95% CI -0.20 to 0.88, I2=84%). Trials in which the sham acupuncture penetrated the skin or performed with regular needles had a significantly higher placebo response in pain intensity reduction, but other factors such as the location of sham acupuncture did not have a significant impact on the placebo response.
		                        		
		                        			CONCLUSIONS
		                        			Sham acupuncture is associated with a large placebo response in pain intensity among patients with LBP. Researchers should also be aware that the types of sham acupuncture applied may potentially impact the evaluation of the efficacy of acupuncture. Nonetheless, considering the nature of placebo response, the effect of other contextual factors cannot be ruled out in this study. (PROSPERO registration No. CRD42022304416).
		                        		
		                        		
		                        		
		                        	
8.Pregnancy Benefit of Acupuncture on in vitro Fertilization: A Systematic Review and Meta-Analysis.
Hao-Ran ZHANG ; Cheng ZHANG ; Pei-Hong MA ; Cheng-Yi SUN ; Chong-Yang SUN ; Xiao-Yu LIU ; Zhen-Qing PU ; Yu-Han LIN ; Bao-Yan LIU ; Cun-Zhi LIU ; Shi-Yan YAN
Chinese journal of integrative medicine 2023;29(11):1021-1032
		                        		
		                        			BACKGROUND:
		                        			Currently, more and more infertility couples are opting for combined acupuncture to improve success rate of in vitro fertilization (IVF). However, evidence from acupuncture for improving IVF pregnancy outcomes remains a matter of debate.
		                        		
		                        			OBJECTIVE:
		                        			To quantitatively summarized the evidence of the efficacy of acupuncture among women undergoing IVF by means of systematic review and meta-analysis.
		                        		
		                        			METHODS:
		                        			Four English (PubMed, Web of Science, EMBASE, and Cochrane Register of Controlled Clinical Trials) and Four Chinese databases (Wanfang Databases, Chinese National Knowledge Infrastructure, Chinese Science and Technology Periodical Database, and SinoMed) were searched from database inception until July 2, 2023. Randomized controlled trials (RCTs) that evaluated the acupuncture's effects for women undergoing IVF were included. The subgroup analysis was conducted with respect to the age of participants, different acupuncture types, type of control, acupuncture timing, geographical origin of the study, whether or not repeated IVF failure, and acupuncture sessions. Sensitivity analyses were predefifined to explore the robustness of results. The primary outcomes were clinical pregnancy rate (CPR) and live birth rate (LBR), and the secondary outcomes were ongoing pregnancy rate and miscarriage rate. Random effects model with I2 statistics were used to quantify heterogeneity. Publication bias was estimated by funnel plots and Egger's tests.
		                        		
		                        			RESULTS:
		                        			A total of 58 eligible RCTs representing 10,968 women undergoing IVF for pregnant success were identifified. Pooled CPR and LBR showed a signifificant difference between acupuncture and control groups [69 comparisons, relative risk (RR) 1.19, 95% confifidence intervals (CI) 1.12 to 1.25, I2=0], extremely low evidence; 23 comparisons, RR 1.11, 95%CI 1.02 to 1.21, I2=14.6, low evidence, respectively). Only transcutaneous electrical acupoint stimulation showed a positive effect on both CPR (16 comparisons, RR 1.17, 95%CI 1.06 to 1.29; I2=0, moderate evidence) and LBR (9 comparisons, RR 1.20, 95%CI 1.04 to 1.37; I2=8.5, extremely low evidence). Heterogeneity across studies was found and no studies were graded as high-quality evidence.
		                        		
		                        			CONCLUSION
		                        			Results showed that the convincing evidence levels on the associations between acupuncture and IVF pregnant outcomes were relatively low, and the varied methodological design and heterogeneity might inflfluence the fifindings. (Registration No. PROSPERO CRD42021232430).
		                        		
		                        		
		                        		
		                        			Pregnancy
		                        			;
		                        		
		                        			Female
		                        			;
		                        		
		                        			Humans
		                        			;
		                        		
		                        			Live Birth
		                        			;
		                        		
		                        			Fertilization in Vitro/methods*
		                        			;
		                        		
		                        			Pregnancy Outcome
		                        			;
		                        		
		                        			Abortion, Spontaneous
		                        			;
		                        		
		                        			Acupuncture Therapy
		                        			
		                        		
		                        	
9.Placebo response of sham acupuncture in patients with primary dysmenorrhea: A meta-analysis.
Chong-Yang SUN ; Zhi-Yi XIONG ; Cheng-Yi SUN ; Pei-Hong MA ; Xiao-Yu LIU ; Chi-Yun SUN ; Ze-Yin XIN ; Bao-Yan LIU ; Cun-Zhi LIU ; Shi-Yan YAN
Journal of Integrative Medicine 2023;21(5):455-463
		                        		
		                        			BACKGROUND:
		                        			The placebo response of sham acupuncture in patients with primary dysmenorrhea is a substantial factor associated with analgesia. However, the magnitude of the placebo response is unclear.
		                        		
		                        			OBJECTIVE:
		                        			This meta-analysis assessed the effects of sham acupuncture in patients with primary dysmenorrhea and the factors contributing to these effects.
		                        		
		                        			SEARCH STRATEGY:
		                        			PubMed, Embase, Web of Science, and Cochrane CENTRAL databases were searched from inception up to August 20, 2022.
		                        		
		                        			INCLUSION CRITERIA:
		                        			Randomized controlled trials (RCTs) using sham acupuncture as a control for female patients of reproductive age with primary dysmenorrhea were included.
		                        		
		                        			DATA EXTRACTION AND ANALYSIS:
		                        			Pain intensity, retrospective symptom scale, and health-related quality of life were outcome measures used in these trials. Placebo response was defined as the change in the outcome of interest from baseline to endpoint. We used standardized mean difference (SMD) to estimate the effect size of the placebo response.
		                        		
		                        			RESULTS:
		                        			Thirteen RCTs were included. The pooled placebo response size for pain intensity was the largest (SMD = -0.99; 95% confidence interval [CI], -1.31 to -0.68), followed by the retrospective symptom scale (Total frequency rating score: SMD = -0.20; 95% CI, -0.80 to -0.39. Average severity score: SMD = -0.35; 95% CI, -0.90 to -0.20) and physical component of SF-36 (SMD = 0.27; 95% CI, -0.17 to 0.72). Studies using blunt-tip needles, single-center trials, studies with a low risk of bias, studies in which patients had a longer disease course, studies in which clinicians had < 5 years of experience, and trials conducted outside Asia were more likely to have a lower placebo response.
		                        		
		                        			CONCLUSION
		                        			Strong placebo response and some relative factors were found in patients with primary dysmenorrhea. PROSPERO registration number: CRD42022304215. Please cite this article as: Sun CY, Xiong ZY, Sun CY, Ma PH, Liu XY, Sun CY, Xin ZY, Liu BY, Liu CZ, Yan SY. Placebo response of sham acupuncture in patients with primary dysmenorrhea: A meta-analysis. J Integr Med. 2023; 21(5): 455-463.
		                        		
		                        		
		                        		
		                        			Female
		                        			;
		                        		
		                        			Humans
		                        			;
		                        		
		                        			Dysmenorrhea/therapy*
		                        			;
		                        		
		                        			Acupuncture Therapy
		                        			;
		                        		
		                        			Pain Management
		                        			;
		                        		
		                        			Needles
		                        			;
		                        		
		                        			Placebo Effect
		                        			
		                        		
		                        	
10.Correlation between cardiac dysfunction and cognitive impairment in patients with ischemic heart disease
Chong ZHENG ; Yadong CUI ; Shanshan GU ; Bixiao CUI ; Jie MA ; Jin SI ; Keling XIAO ; Jing LI ; Jie LU
Chinese Journal of Geriatric Heart Brain and Vessel Diseases 2023;25(12):1240-1244
		                        		
		                        			
		                        			Objective To investigate the correlation between left ventricular dysfunction and cogni-tive impairment in patients with ischemic heart disease(IHD),and explore the potential patho-genesis of cognitive impairment in IHD patients.Methods Fifty IHD patients who underwent hybrid cardiac PET/MR in our hospital from September 2020 to December 2022 were retrospec-tively enrolled in this study.According to their Montreal cognitive assessment(MoCA)scores,they were categorized into a cognitively normal group(21 cases,MoCA score ≥26)and a cogni-tively declining group(29 cases,MoCA score<26).All patients received 13N-NH3·H2O myocar-dial perfusion imaging and 18F-FDG cardiac PET/MR to evaluate cardiac function and obtain car-diac imaging parameters.Spearman correlation analysis was applied to analyze the correlation between cardiac PET/MR parameters and MoCA scores.General linear model analysis was applied to analyze the correlation between MoCA scores and cardiac PET/MR parameters after adjusting for co variates.Results Compared with the cognitively normal group,the patients in the cognitively declining group had significantly lower stroke volume[56.95(47.51,77.64)ml vs 82.66(73.88,92.92)ml,P=0.001],stroke volume index[34.07(28.93,43.20)ml/m2 vs 44.28(38.06,49.49)ml/m2,P=0.008],cardiac output[3.92(3.18,5.34)L/min vs 5.13(4.58,5.67)L/min,P=0.007],and cardiac index[(2.42±0.68)L/(min·m2)vs(2.78±0.39)L/(min·m2),P=0.021].Spearman correlation analysis revealed that MoCA score was positively correlated with stroke volume(r=0.497,P=0.001),stroke volume index(r=0.365,P=0.009)and cardiac output(r=0.361,P=0.010).After adjusting for sex,age,education level and vascular risk factors,MoCA score re-mained positively correlated with stroke volume(r=0.497,P=0.003).Conclusion Systemic hy-poperfusion in IHD patients may be one of the mechanisms leading to cognitive impairment.
		                        		
		                        		
		                        		
		                        	
            
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