1.Clinical Observation on Rongjin Tongbi Decoction in Treating Sciatica Caused by Lumbar Intervertebral Disc Herniation with Liver and Kidney Deficiency Type
Yemei GAO ; Zhiqi LIANG ; Yang JIANG ; Xin LI ; Fang SHI ; Fangming HE ; Yang LIU
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(8):134-140
		                        		
		                        			
		                        			ObjectiveTo evaluate the efficacy and safety of Rongjin Tongbi decoction on sciatica caused by lumbar intervertebral disc herniation with liver and kidney deficiency type based on a randomized controlled study. MethodFrom January 2019 to July 2022, 90 patients in the department of Traditional Chinese medicine(TCM) of Beijing Jishuitan Hospital who met the inclusion criteria were selected and divided into two groups according to the random number table, with 45 patients in each group. During the study, 19 cases dropped out, with 41 cases included in the final observation group and 30 cases in the control group. The observation group was given Rongjin Tongbi decoction orally, and the control group was given Loxoprofen Sodium Tablets orally for 28 days. The differences in the visual analog scale (VAS) scores, the Japanese Orthopaedic Association (JOA) scores, activities of daily living (ADL) assessments, TCM clinical symptoms, subjective symptoms, and clinical signs scores between two groups before and after treatment were observed. Liver and kidney functions and gastrointestinal adverse reactions were detected for safety evaluation. ResultBefore treatment, there was no statistically significant difference in scores between the observation group and the control group. After treatment, the absolute values of the differences in VAS and ADL scores in the observation group were higher than those in the control group (P<0.05). There was no statistically significant difference in the absolute value of the difference in JOA scores between two groups. The absolute value of the difference in TCM clinical symptom scores in the observation group was higher than that in the control group (P<0.01). There was no statistically significant difference in the absolute values of the differences in subjective symptom and clinical sign scores between two groups. The levels of liver and kidney function indicators in both groups before and after the experiment were normal, and there was no significant difference in gastrointestinal reactions. ConclusionRongjin Tongbi decoction can significantly improve the symptoms of sciatica patients caused by lumbar intervertebral disc herniation with liver and kidney deficiency type. After treatment, the patients exhibited significant improvements in pain, activity and other aspects, and it is proven to be safe and reliable, which is conducive to the recovery of physical function. 
		                        		
		                        		
		                        		
		                        	
2.Evaluation of chemiluminescence immunoassay kit for detection of hepatitis D virus IgG antibody
Rongchen YUAN ; Fangming CHENG ; Kuanhui XIANG ; Yongcong LI ; Tianxun HUANG ; Zhenchao TIAN ; Xiongwei LIU ; Xiaozhong WANG ; Zhuanguo WANG ; Yahong MA ; Jing ZHOU ; Erhei DAI ; Chungen QIAN ; Tong LI ; Tao SHEN ; Bangning CHENG
Chinese Journal of Laboratory Medicine 2024;47(3):234-238
		                        		
		                        			
		                        			Objective:This study evaluates the performance of chemiluminescence assay, which is designed to detect Hepatitis D Virus (HDV) Immunoglobulin G (IgG) antibodies.Methods:A comparative analysis was conducted among chemiluminescence anti-HDV IgG reagent, the magnetic particle-based domestic reagent A and domestic reagent B, and the Robo Gene HDV RNA kit, using 1909 HBsAg-positive plasma samples. This comparison aimed to delineate clinical specificity and detection accuracy. The anti-HDV IgG reagent precision was assessed at three different concentration levels following the Clinical Laboratory Standards Institute EP5-A2 guidelines. The specificity of the assay was validated using 200 HAV IgM positive, 545 HBsAg-positive but anti-HDV IgG-negative, 350 anti HCV positive plasma samples and 200 healthy human blood samples. Additionally, a concordance study was conducted with 545 HBsAg-positive and 37 anti-HDV IgG-positive plasma samples, comparing the anti-HDV IgG reagent against reagent A.Results:1 909 HBsAg-positive plasma samples were tested using 3 anti HDV IgG reagent and 1 HDV RNA reagent, 19 samples were identified as anti-HDV IgG-positive. The anti-HDV IgG demonstrated superior accuracy and specificity. The assay exhibited excellent precision, with intra-assay coefficient of variation (CV) values ranging from 1.57% to 4.30%, and inter-assay CV values between 1.71% and 4.67% for detecting samples at high, medium, and low concentration levels. Concordance with Reagent A showed consistent results in both positive and negative detections.Conclusion:In this study, the anti-HDV IgG reagent (chemiluminescence method) displayed outstanding specificity in detecting clinical samples and exhibited a high conformity rate with commercialized reagents, making it potentially suitable for screening anti-HDV IgG in HBsAg-positive samples.
		                        		
		                        		
		                        		
		                        	
3.Assessment and preliminary clinical application of a domestic nucleic acid detection reagent for hepatitis D virus
Yongcong LI ; Rongchen YUAN ; Kuanhui XIANG ; Guomin OU ; Tianxun HUANG ; Fangming CHENG ; Zhenchao TIAN ; Xiongwei LIU ; Xiaozhong WANG ; Feng GUO ; Yahong MA ; Jing ZHOU ; Erhei DAI ; Bangning CHENG ; Tong LI ; Tao SHEN ; Chungen QIAN
Chinese Journal of Laboratory Medicine 2024;47(3):239-244
		                        		
		                        			
		                        			Objective:This study aims to evaluate the quality and explore the preliminary clinical applications of a domestically developed hepatitis D virus nucleic acid quantification reagent (abbreviated as"domestic HDV RNA reagent").Methods:The sensitivity and accuracy of the reagent were evaluated in accordance with the WHO HDV RNA international standard, employing the Bio-Rad CFX Opus 96 real-time fluorescence quantitative PCR analysis system. Serial dilutions of pseudo-viruses or cell culture-derived virus were used to determine the linear range of the domestic HDV RNA reagent. Specificity was assessed using positive samples of HAV, HBV, HCV infection, and HEV national reference materials. Precision was evaluated with samples at both high and low concentrations. In a comparative analysis, 30 HDV IgG positive samples were tested using both the domestic HDV RNA reagent and the RoboGene HDV RNA kit based on the ABI 7500 FAST DX system. The Pearson correlation coefficient (r) was used to examine the correlation between the two reagents.Results:The domestic HDV RNA reagent demonstrated a high sensitivity of up to 6 IU/ml, consistent with that of the comparator reagent. The calibration curve for WHO HDV RNA standards had a slope of -3.286, with an amplification efficiency of 101.6%. The linear detection range spanned from 10 to 10 8 IU/ml for eight HDV genotypes. The domestic HDV RNA reagent exhibited exceptional specificity, without cross-reactivity observed with HAV, HBV, HCV, or HEV. Accuracy assessments at five concentration levels met the required standards, with intra-assay precision coefficient of variation ( CV) ranging from 1.20% to 4.20%, and inter-assay precision CV from 1.20% to 7.90%. The detection results for HDV IgG positive samples were highly correlated with the comparator reagent ( r=0.984, P<0.001), achieving a diagnostic accuracy of 100% compared to sequencing results. Conclusion:In this study, the domestic HDV RNA reagent possesses excellent specificity, accuracy, precision, and a broad linear range, attaining a sensitivity level on par with international reagents of the same type.
		                        		
		                        		
		                        		
		                        	
4.Oncogenic β-catenin-driven liver cancer is susceptible to methotrexate-mediated disruption of nucleotide synthesis
Fangming LIU ; Yuting WU ; Baohui ZHANG ; Shuhui YANG ; Kezhuo SHANG ; Jie LI ; Pengju ZHANG ; Weiwei DENG ; Linlin CHEN ; Liang ZHENG ; Xiaochen GAI ; Hongbing ZHANG
Chinese Medical Journal 2024;137(2):181-189
		                        		
		                        			
		                        			Background::Liver cancer is largely resistant to chemotherapy. This study aimed to identify the effective chemotherapeutics for β-catenin-activated liver cancer which is caused by gain-of-function mutation of catenin beta 1 ( CTNNB1), the most frequently altered proto-oncogene in hepatic neoplasms. Methods::Constitutive β-catenin-activated mouse embryonic fibroblasts (MEFs) were established by deleting exon 3 ( β-cateninΔ(ex3)/+ ), the most common mutation site in CTNNB1 gene. A screening of 12 widely used chemotherapy drugs was conducted for the ones that selectively inhibited β-cateninΔ(ex3)/+ but not for wild-type MEFs. Untargeted metabolomics was carried out to examine the alterations of metabolites in nucleotide synthesis. The efficacy and selectivity of methotrexate (MTX) on β-catenin-activated human liver cancer cells were determined in vitro. Immuno-deficient nude mice subcutaneously inoculated with β-catenin wild-type or mutant liver cancer cells and hepatitis B virus ( HBV); β-cateninlox(ex3)/+ mice were used, respectively, to evaluate the efficacy of MTX in the treatment of β-catenin mutant liver cancer. Results::MTX was identified and validated as a preferential agent against the proliferation and tumor formation of β-catenin-activated cells. Boosted nucleotide synthesis was the major metabolic aberration in β-catenin-active cells, and this alteration was also the target of MTX. Moreover, MTX abrogated hepatocarcinogenesis of HBV; β-cateninlox(ex3)/+ mice, which stimulated concurrent Ctnnb1-activated mutation and HBV infection in liver cancer. Conclusion::MTX is a promising chemotherapeutic agent for β-catenin hyperactive liver cancer. Since repurposing MTX has the advantages of lower risk, shorter timelines, and less investment in drug discovery and development, a clinical trial is warranted to test its efficacy in the treatment of β-catenin mutant liver cancer.
		                        		
		                        		
		                        		
		                        	
5.Study of the effect of mid-ventricular obstruction on left ventricular systolic function in patients with hypertrophic cardiomyopathy by four-dimensional automatic left ventricular quantitation technology
Fangming WANG ; Haiyan LIU ; Lingxiao YANG ; Wenqiang SHI ; Junchang QIN ; Zhengyang HAN ; Shan ZHANG ; Ruifang ZHANG
Chinese Journal of Ultrasonography 2023;32(8):664-671
		                        		
		                        			
		                        			Objective:To investigate the effect of mid-ventricular obstruction (MVO) on left ventricular systolic function in patients with hypertrophic cardiomyopathy(HCM) by four-dimensional automatic left ventricular quantitation technology(4D Auto LVQ).Methods:Fifty-seven hypertrophic obstructive cardiomyopathy patients were selected from December 2020 to October 2022 in the First Affiliated Hospital of Zhengzhou University. According to the presence of MVO, HCM patients were divided into two groups: HCM 1 group, HCM without MVO ( n=34); HCM 2 group, HCM with MVO ( n=23). In addition, 25 healthy subjects in the same period were selected as the control group. Conventional ultrasound parameters were collected, and 4D Auto LVQ technology was used to obtain the mechanical parameters of left ventricular myocardium, including left ventricular longitudinal strain (GLS), circumferential strain (GCS), area strain (GAS), radial strain (GRS), segmental longitudinal strain (SLS) and area strain (SAS). The differences of these parameters among the three groups were compared. Results:①Compared with the control group, the thickness of the maximum basal segment of interventricular septum, the thickness of the middle segment of the maximum interventricular septum, the thickness of the apical segment of the interventricular septum, the thickness of the left ventricular posterior wall and left atrium diameter were significantly increased. Six-minute walk distance and the left ventricular end-diastolic diameter was decreased in the two groups of HCM(all P<0.05). Left ventricular outflow tract gradients in HCM 1 group was higher than HCM 2 group( P<0.05), but there was no significant difference in left ventricular ejection fraction among the three groups( P>0.05). There was significant difference in the incidence of left ventricular apical aneurysm among the three groups( P<0.05). ②Compared with the control group, the GLS in both HCM groups was lower, and it was lower in the HCM 2 group than in the HCM 1 group(all P<0.05) the GRS and GAS in both HCM groups were lower than in the control group ( P<0.05), and there was no significant difference between the two groups of HCM, and there was no significant difference in GCS among the three groups(all P>0.05). ③Compared with the control group, the SLS of basal segment, middle segment, apical cap, posterior septum, inferior wall and lateral wall in HCM group were significantly lower than those in control group. The SLS of apical segment of posterior septum, anterior septum, anterior wall, posterior wall, inferior wall and apical segment of posterior septum, lateral wall and inferior wall in HCM 2 group were significantly lower than HCM 1 group(all P<0.05), but there was no significant difference in SLS of posterior septum, anterior septum, anterior wall, lateral wall and inferior wall between the two groups(all P>0.05). ④Compared with the control group, the SAS of posterior septal basal segment, middle segment, anterior septal middle segment, anterior wall basal segment, middle segment, apical segment, lateral wall basal segment, middle segment, apical segment, posterior wall basal segment, middle segment, inferior wall basal segment, middle segment and apical cap in HCM groups were significantly lower than the control group(all P<0.05), but there was no significant difference in SAS between the two groups of HCM( P>0.05). Conclusions:4D Auto LVQ can quantitatively evaluate the damage of MVO on the left ventricular systolic function in patients with HCM, especially for the evaluation of local myocardial function damage in the medial segment and apical segment.
		                        		
		                        		
		                        		
		                        	
6.The enhanced genomic 6 mA metabolism contributes to the proliferation and migration of TSCC cells.
Lei XI ; Ying YANG ; Ying XU ; Fangming ZHANG ; Jinghui LI ; Xiyang LIU ; Zhenxi ZHANG ; Quan DU
International Journal of Oral Science 2022;14(1):11-11
		                        		
		                        			
		                        			In contrast to the well-established genomic 5-methylcytosine (5mC), the existence of N6-methyladenine (6 mA) in eukaryotic genomes was discovered only recently. Initial studies found that it was actively regulated in cancer cells, suggesting its involvement in the process of carcinogenesis. However, the contribution of 6 mA in tongue squamous cell carcinoma (TSCC) still remains uncharacterized. In this study, a pan-cancer type analysis was first performed, which revealed enhanced 6 mA metabolism in diverse cancer types. The study was then focused on the regulation of 6 mA metabolism, as well as its effects on TSCC cells. To these aspects, genome 6 mA level was found greatly increased in TSCC tissues and cultured cells. By knocking down 6 mA methylases N6AMT1 and METTL4, the level of genomic 6 mA was decreased in TSCC cells. This led to suppressed colony formation and cell migration. By contrast, knockdown of 6 mA demethylase ALKBH1 resulted in an increased 6 mA level, enhanced colony formation, and cell migration. Further study suggested that regulation of the NF-κB pathway might contribute to the enhanced migration of TSCC cells. Therefore, in the case of TSCC, we have shown that genomic 6 mA modification is involved in the proliferation and migration of cancer cells.
		                        		
		                        		
		                        		
		                        			AlkB Homolog 1, Histone H2a Dioxygenase/metabolism*
		                        			;
		                        		
		                        			Carcinoma, Squamous Cell/pathology*
		                        			;
		                        		
		                        			Cell Line, Tumor
		                        			;
		                        		
		                        			Cell Movement/genetics*
		                        			;
		                        		
		                        			Cell Proliferation
		                        			;
		                        		
		                        			Gene Expression Regulation, Neoplastic
		                        			;
		                        		
		                        			Humans
		                        			;
		                        		
		                        			Site-Specific DNA-Methyltransferase (Adenine-Specific)/metabolism*
		                        			;
		                        		
		                        			Tongue Neoplasms/metabolism*
		                        			
		                        		
		                        	
7.Finite Game or Infinite Game: A Philosophical Interpretation of Doctor-patient Conflict
Yi CHEN ; Ruiming LIU ; Fangming ZHAI ; Libin ZENG
Chinese Medical Ethics 2022;35(9):938-948
		                        		
		                        			
		                        			It is a new attempt to interpret the essence of doctor-patient relationship and reveal the mechanism of doctor-patient conflict by using game theory. According to James Cass’s philosophy theory of finite and infinite games, this paper applies the four elements of finite and infinite games: "goal-actor-rule-boundary". Combined with the four elements of game theory, the doctor-patient relationship was systematically interpreted, and the evolution model of finite games and infinite games was constructed. This paper held that the essence of doctor-patient relationship is an infinite game in theory, the nature of doctor-patient relationship is a finite game in reality, and doctor-patient conflict is the result of the evolution of the finite game of doctor-patient relationship. Based on the finite game evolution model, this paper analyzed the causes of doctor-patient conflict in the specific narrative of doctor-patient conflict, and pointed out that the doctor-patient relationship can only be resolved by changing their "game view", so as to achieve the transcendence of the doctor-patient relationship from finite game to infinite game.
		                        		
		                        		
		                        		
		                        	
8.Over 50,000 Metagenomically Assembled Draft Genomes for the Human Oral Microbiome Reveal New Taxa
Zhu JIE ; Tian LIU ; Chen PEISHAN ; Han MO ; Song LIJU ; Tong XIN ; Sun XIAOHUAN ; Yang FANGMING ; Lin ZHIPENG ; Liu XING ; Liu CHUAN ; Wang XIAOHAN ; Lin YUXIANG ; Cai KAIYE ; Hou YONG ; Xu XUN ; Yang HUANMING ; Wang JIAN ; Kristiansen KARSTEN ; Xiao LIANG ; Zhang TAO ; Jia HUIJUE ; Jie ZHUYE
Genomics, Proteomics & Bioinformatics 2022;20(2):246-259
		                        		
		                        			
		                        			The oral cavity of each person is home to hundreds of bacterial species.While taxa for oral diseases have been studied using culture-based characterization as well as amplicon sequencing,metagenomic and genomic information remains scarce compared to the fecal microbiome.Here,using metagenomic shotgun data for 3346 oral metagenomic samples together with 808 published samples,we obtain 56,213 metagenome-assembled genomes(MAGs),and more than 64%of the 3589 species-level genome bins(SGBs)contain no publicly available genomes.The resulting genome collection is representative of samples around the world and contains many genomes from candi-date phyla radiation(CPR)that lack monoculture.Also,it enables the discovery of new taxa such as a genus Candidatus Bgiplasma within the family Acholeplasmataceae.Large-scale metagenomic data from massive samples also allow the assembly of strains from important oral taxa such as Por-phyromonas and Neisseria.The oral microbes encode genes that could potentially metabolize drugs.Apart from these findings,a strongly male-enriched Campylobacter species was identified.Oral sam-ples would be more user-friendly collected than fecal samples and have the potential for disease diagnosis.Thus,these data lay down a genomic framework for future inquiries of the human oral microbiome.
		                        		
		                        		
		                        		
		                        	
9.Establishment and validation of prediction model for postoperative sleep disturbance in patients undergoing non-cardiac surgery
Shuting YANG ; Qian ZHANG ; Yifan XU ; Futeng CHEN ; Fangming SHEN ; Qin ZHANG ; He LIU ; Yue-Ying ZHANG
Chinese Journal of Anesthesiology 2021;41(4):421-426
		                        		
		                        			
		                        			Objective:To establish and validate the prediction model for postoperative sleep disturbance (PSD) in patients undergoing non-cardiac surgery.Methods:A total of 454 patients of both sexes, aged≥18 yr, of American Society of Anesthesiologists physical statusⅠ-Ⅲ, underwent non-cardiac surgery under general anesthesia from November 2019 to September 2020 were selected.The perioperative data were collected.The patients were divided into training set and validation set with a ratio of 7∶3 by using a simple random sampling method.The characteristic variables of PSD were selected using LASSO regression analysis and the independent risk factors were identified using multivariate logistic regression analysis in training set.Akaike′s information criterion was used to evaluate the quality of fit of the model.The nomogram of PSD in non-cardiac surgery patients was constructed based on the identified factors.The discrimination of the model was evaluated using receiver operating characteristic (ROC) curve, and the agreement of the model was evaluated using Hosmer-Lemeshow goodness-of-fit test and Brier score.Results:Seven risk factors (gender, preoperative anxiety, satisfaction with the ward environment, anesthesia time, the intraoperative consumption of midazolam and sufentanil and numerical rating scale (NRS) score at 3 days after operation) and two related factors (preoperative NRS score and general anesthesia combined with nerve block) were used to establish and verify the PSD nomogram.The area under the ROC curve was 0.805 (95% confidence interval [CI] 0.721-0.848) in training set.The area under the ROC curve was 0.773 (95% CI 0.684-0.876) in validation set.In training and validation sets, the calibration curves were tested by Hosmer-Lemeshow good of fit test, the P values were 0.590 and 0.950, respectively, and the Brier scores were 0.154 and 0.156, respectively.The nomogram predicated that the sensitivity (95% CI) and specificity (95%CI) were 81.83% (60.32%-95.14%) and 78.15% (71.83%-83.25%), respectively, in training set, and the sensitivity (95% CI) and specificity (95%CI) were 77.86% (39.84%-97.25%) and 78.15% 77.86% (68.74%-85.48%), respectively, in validation set.The optimal cut-off value of nomogram score was 113. Conclusion:In this study, the nomogram prediction model for PSD in patients undergoing non-cardiac surgery has been successfully established, which can visually and individually predict the risk of PSD.
		                        		
		                        		
		                        		
		                        	
10. Clinicopathological features and prognosis of breast cancer patients under 20 years old - report of 3 cases and literature review
Chao LIU ; Fangming LIU ; Yonglin ZHANG ; Xinyi GAO ; Yushuang HE ; Jierong WU ; Zhenhai MA
Chinese Journal of Endocrine Surgery 2019;13(6):522-524
		                        		
		                        			
		                        			 This article reports the clinical data, diagnosis and treatment plan and prognosis of 3 patients with breast cancer under 20 years old. The clinical pathological features, treatment and prognosis were discussed in the literature, and compared with the biological characteristics of young (under 35 years old) breast cancer patients, providing a reference for the clinical individualized treatment of the disease. 
		                        		
		                        		
		                        		
		                        	
            
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