Etiological diagnosis value of metagenomic next generation sequencing in the patients with spinal infection / 中华传染病杂志

Objective:To investigate the efficacy of metagenomic next generation sequencing (mNGS) in the etiological diagnosis of patients with spinal infection, so as to provide reference for timely diagnosis and treatment.Methods:A total of 40 patients with suspected spinal infection admitted to the Department of Infectious Diseases in Henan Provincial People′s Hospital from January 2020 to July 2022 were included. The results of tissue culture, histopathological examination and tissue mNGS detection were analyzed retrospectively. According to the clinical diagnose, the patients were divided into the spinal infection group (28 cases) and the non-spinal infection group (12 cases). The positive rate, sensitivity and specificity of mNGS and tissue culture in the pathogen detection of patients with spinal infection were compared. McNemar test was used for statistical analysis.Results:There were 23 males and 17 females in 40 patients. The positive rate of mNGS was higher than that of tissue culture (75.0%(30/40) vs 12.5%(5/40)), and the difference was statistically significant ( χ2=0.08, P<0.001). Based on clinical diagnostic criteria, the sensitivity of mNGS in the diagnosis of spinal infection was higher than that of tissue culture (82.1% vs 17.9%), with a statistically significant difference ( χ2=0.02, P<0.001), while the specificity compared to the tissue culture (33.3% vs 100.0%), the difference was not statistically significant ( P>0.05). Conclusions:mNGS has a high pathogen detection rate and sensitivity in the etiological diagnosis of patients with spinal infection, which could provide clinical guidance for the diagnosis and treatment of patients with spinal infection.

Study of the urban-impact on microbial communities and their virulence factors and antibiotic resistance genomes in the Nandu River, Haikou / 中华流行病学杂志

Objective: To explore the changes in bacterial community structure, antibiotic resistance genome, and pathogen virulence genome in river water before and after the river flowing through Haikou City and their transmission and dispersal patterns and to reveal anthropogenic disturbance's effects on microorganisms and resistance genes in the aquatic environment. Methods: The Nandu River was divided into three study areas: the front, middle and rear sections from the upstream before it flowed through Haikou City to the estuary. Three sampling sites were selected in each area, and six copies of the sample were collected in parallel at each site and mixed for 3 L per sample. Microbial community structure, antibiotic resistance, virulence factors, and mobile genetic elements were analyzed through bioinformatic data obtained by metagenomic sequencing and full-length sequencing of 16S rRNA genes. Variations in the distribution of bacterial communities between samples and correlation of transmission patterns were analyzed by principal co-ordinates analysis, procrustes analysis, and Mantel test. Results: As the river flowed through Haikou City, microbes' alpha diversity gradually decreased. Among them, Proteobacteria dominates in the bacterial community in the front, middle, and rear sections, and the relative abundance of Proteobacteria in the middle and rear sections was higher than that in the front segment. The diversity and abundance of antibiotic resistance genes, virulence factors, and mobile genetic elements were all at low levels in the front section and all increased significantly after flow through Haikou City. At the same time, horizontal transmission mediated by mobile genetic elements played a more significant role in the spread of antibiotic-resistance genes and virulence factors. Conclusions: Urbanization significantly impacts river bacteria and the resistance genes, virulence factors, and mobile genetic elements they carry. The Nandu River in Haikou flows through the city, receiving antibiotic-resistant and pathogen-associated bacteria excreted by the population. In contrast, antibiotic-resistant genes and virulence factors are enriched in bacteria, which indicates a threat to environmental health and public health. Comparison of river microbiomes and antibiotic resistance genomes before and after flow through cities is a valuable early warning indicator for monitoring the spread of antibiotic resistance.

Drug resistance and genomic characteristics of a strain of O139 Vibrio cholerae isolated from human bloodstream infection / 中华预防医学杂志

Objective: To analyze the drug resistance and genomic characteristics of a strain of serogroup O139 Vibrio cholerae producing cholera toxin isolated from the bloodstream of a person with bacteremia. Methods: The broth dilution method and automatic drug sensitivity analyzer were used to determine the antibiotic sensitivity of the strain. The complete genome sequence of the strain was obtained by using second-generation gene sequencing and nanopore sequencing. BLAST software was used for comparison and analysis with CARD, Resfinder, ISfinder, VFDB, and other databases. The drug-resistant genes, insertion sequences and virulence genes carried by the strain were identified. MEGA 5.1 software was used to construct a genetic phylogenetic tree based on the core genomic single nucleotide polymorphisms. Results: V. cholerae SH400, as the toxigenic strain, carried multiple virulence-related genes and four virulence islands. The strain was resistant to streptomycin, tetracycline and cotrimoxazole, carrying corresponding drug-resistant genes. The strain also carried IncA/C plasmid with the size of 172914 bp and contained 10 drug-resistant genes. Combined with the genomic evolutionary relationship, this study found that the drug-resistant genes and drug-resistant plasmids carried among strains showed certain aggregation. The traditional ST type of strain SH400 was ST69, and the cgMLST type was a new type highly similar to cgST-252. Conclusion: This strain of serogroup O139 V. cholerae carries the ctxAB gene, multiple drug-resistant genes and IncA/C plasmid, and there are multiple drug-resistant islands.

RHD Gene Analysis of A Blood Donor with Del Phenotype / 中国实验血液学杂志

OBJECTIVE@#To analyze the RHD genotype of a blood donor with Del phenotype in Yunnan.@*METHODS@#Rh serological phenotype was identified. RHD gene was detected by PCR-SSP typing, and its 10 exons were sequenced. Exon 9 was amplified for sequencing and analysis. RHD zygosity was detected.@*RESULTS@#The Rh phenotype of this specimen was CcDelee. Genomic DNA exhibited a 1 003 bp deletion spanning from intron 8, across exon 9 into intron 9. The deletion breakpoints occurred between two 7-bp short tandem repeat sequences. There was no variation in the sequences of the remaining exons. The Rh hybridization box test showed that there was one RHD negative allele.@*CONCLUSION@#This specimen is Del type caused by deletion of RHD exon 9.

Liver pathological characteristics and the value of serum non-invasive diagnostic model in chronic hepatitis B patients with normal alanine aminotransferase and negative hepatitis B e antigen / 中华传染病杂志

Objective:To analyze the liver pathological characteristics of chronic hepatitis B (CHB) patients with normal alanine aminotransferase (ALT) and negative hepatitis B e antigen (HBeAg), and to evaluate the diagnostic value of different serological models for liver fibrosis.Methods:Retrospective analysis was conducted on the patients with HBeAg-negative CHB who had normal ALT and underwent liver biopsy from August 2016 to December 2019 in the Department of Infectious Diseases, Henan Provincial People′s Hospital. The clinical data, serum indicators of hepatitis B virus (HBV) and HBV DNA were collected. The liver fibrosis stages (S) was assessed by pathological examination. The diagnostic efficacies of gamma-glutamyl transpeptidase to platelet ratio (GPR), fibrosis 4 score (FIB-4), S index, aspartate aminotransferase to platelet ratio index (APRI) and gamma-glutamyl transpeptidase to albumin ratio (γ-GT/ALB) for liver pathological fibrosis were analyzed by the receiver operating characteristic curves. Two variable correlation test was used to explore the relationship between the different models and pathological fibrosis of liver tissue. Chi-square test was used for statistical comparison.Results:The age of 448 patients was (37.98±9.82) years, and the male to female ratio was 1.286 ∶1. The proportions of S≥2 in patients with age>30 years, hepatitis B surface antigen (HBsAg)<2 000 IU/mL and HBV DNA≥2 000 IU/mL were higher than those in patients with age ≤30 years, HBsAg ≥2 000 IU/mL and HBV DNA<2 000 IU/mL, respectively, and the differences were all statistically significant ( χ2=7.68, P=0.006; χ2=11.44, P=0.001; χ2=9.12, P=0.003, respectively). There were 250 cases with pathological fibrosis stage S<2, 162 cases with S=2 and 36 cases with S≥3. FIB-4 (correlation coefficient 0.250), APRI (correlation coefficient 0.218), GPR (correlation coefficient 0.186), S index (correlation coefficient 0.184) and γ-GT/ALB (correlation coefficient 0.127) were positively correlated with the severity of liver fibrosis (all P<0.050). S index had the highest sensitivity (64.1%) in the diagnosis of significant liver fibrosis (S≥2), while γ-GT/ALB had the highest specificity (80.8%). In the diagnosis of severe liver fibrosis (S≥3), γ-GT/ALB had the highest sensitivity (77.8%), while APRI had the highest specificity (78.6%). Conclusions:The incidence of liver fibrosis in CHB patients with normal ALT and negative HBeAg is relatively high. The current serological diagnostic models are not suitable for the evaluation of liver fibrosis in these patients, and timely liver puncture is still necessary.

Advances on the toxicology and molecular mechanisms of different components of ambient fine particulate matter / 中华预防医学杂志

Ambient fine particulate matters (PM2.5) refer to particulate matters with an aerodynamic diameter less than or equal to 2.5 μm. PM2.5 enter the body through the target organ-lung, and can induce a variety of adverse health effects (such as cardiovascular diseases, diabetes, respiratory diseases, neurodegenerative diseases and adverse birth outcomes). PM2.5 are known to have complex compositions (including water-soluble/-insoluble components and biological components), diverse sources and capacity of secondary transformation. Numerous epidemiological and toxicological studies indicated that different components of PM2.5 may induce adverse health effects through different biological mechanisms. In adddition, co-exposure of different components and their interaction should also be considered. Thus here we have systematically reviewed studies in recent years about the toxicological effects and underlying mechanisms of different components of ambient fine particulate matters, including inflammatory response, oxidative stress, endoplasmic reticulum stress, activation of the NF-κB signaling pathway and so on. The information may give some insights into the prevention and treatment of adverse health effects caused by exposure to different components of PM2.5.

A real-world study on the effectiveness of elbasvir/grazoprevir in the treatment of genotype 1 chronic hepatitis C / 中华传染病杂志

Objective:To evaluate the efficacy and safety of elbasvir/grazoprevir (EBR/GZR) in patients with genotype 1 chronic hepatitis C in the real-world.Methods:This was an open-label, single-center, retrospective real-world study. A total of 103 genotype 1 chronic hepatitis C patients who were treated with EBR/GZR in Henan Provincial People′s Hospital from May 2018 to October 2019 were enrolled.And the clinical baseline characteristics of patients and the effectiveness and safety of antiviral therapy were respectively evaluated.Results:A total of 103 patients were enrolled in the study with an age of (47.6±13.9) years. Fifty-five (53.4%) patients were male and 48(46.6%) were female. One point nine percent (2/103) patients were genotype 1a hepatitis C and 98.1%(101/103) were genotype 1b hepatitis C. Seventeen genotype 1b hepatitis C patients were previously treated with interferon, and three patients co-infected with hepatitis B virus (HBV). Among the 103 cases, 35 had underlying diseases and 26 had combined medication. Ninty-eight cases completed 12-week treatment and 89 cases completed 12-week follow-up after treatment.Overall, 89 cases achieved sustained virological response. The overall incidence of adverse reactions was 20.4%(21/103), and the main adverse reactions were fatigue, insomnia and anxiety. No serious adverse event occurred. The three patients with HBV co-infection had no hepatitis B activation after treatment.Conclusion:EBR/GZR is effective and safe in the patients with genotype 1 chronic hepatitis C in China.

Tocilizumab in patients with moderate or severe COVID-19: a randomized, controlled, open-label, multicenter trial / 医学前沿

Tocilizumab has been reported to attenuate the "cytokine storm" in COVID-19 patients. We attempted to verify the effectiveness and safety of tocilizumab therapy in COVID-19 and identify patients most likely to benefit from this treatment. We conducted a randomized, controlled, open-label multicenter trial among COVID-19 patients. The patients were randomly assigned in a 1:1 ratio to receive either tocilizumab in addition to standard care or standard care alone. The cure rate, changes of oxygen saturation and interference, and inflammation biomarkers were observed. Thirty-three patients were randomized to the tocilizumab group, and 32 patients to the control group. The cure rate in the tocilizumab group was higher than that in the control group, but the difference was not statistically significant (94.12% vs. 87.10%, rate difference 95% CI-7.19%-21.23%, P = 0.4133). The improvement in hypoxia for the tocilizumab group was higher from day 4 onward and statistically significant from day 12 (P = 0.0359). In moderate disease patients with bilateral pulmonary lesions, the hypoxia ameliorated earlier after tocilizumab treatment, and less patients (1/12, 8.33%) needed an increase of inhaled oxygen concentration compared with the controls (4/6, 66.67%; rate difference 95% CI-99.17% to-17.50%, P = 0.0217). No severe adverse events occurred. More mild temporary adverse events were recorded in tocilizumab recipients (20/34, 58.82%) than the controls (4/31, 12.90%). Tocilizumab can improve hypoxia without unacceptable side effect profile and significant influences on the time virus load becomes negative. For patients with bilateral pulmonary lesions and elevated IL-6 levels, tocilizumab could be recommended to improve outcome.

Influencing factors for abnormal renal function markers in chronic hepatitis B patients receiving long-term oral administration of entecavir/tenofovir disoproxil fumarate / 临床肝胆病杂志

ObjectiveTo investigate the status of abnormal renal function markers and related influencing factors in chronic hepatitis B (CHB) patients receiving oral antiviral drugs for a long time. MethodsA retrospective analysis was performed for the clinical data of 681 CHB patients who attended Henan Provincial People’s Hospital from January to December 2019 and received long-term oral administration of entecavir (ETV)/tenofovir disoproxil fumarate (TDF). All patients received the measurement of blood renal function markers (urea, creatinine, retinol-binding protein ［RBP］, cystatin C ［Cys-C］, and β2-microglobulin ［β2-MG］), urinary renal function markers (α1-microglobulin ［α1-MG］, Cys-C, and N-acetyl-β-D-glucosaminidase ［NAG］), and urine routine parameters. The incidence rate of abnormal renal function markers were analyzed. The McNemar’s test was used for comparison of categorical data between groups, and the multivariate logistic regression analysis was used to investigate independent influencing factors for abnormal renal markers in urine. ResultsThe 681 patients had a mean age of 39.8±11.0 years and received medication for 1.88 (0.80-3.16) years. There were 417 male patients and 264 female patients, and the incidence rate of liver cirrhosis was 27.02% (184/681). Of all 681 patients, 442 received ETV and 239 received TDF. The measurement of blood renal function markers showed that urea, creatinine, retinol-binding protein, Cys-C, and β2-MG had an abnormal rate of 6.9% (47/681), 0.15% (1/681), 0(0/681), 2.21% (15/681), and 5.03% (30/681), respectively, and the abnormal rate of urinary protein was 7.29% (49/672). The measurement of urinary renal function markers showed that α1-MG, NAG, and Cys-C had an abnormal rate of 38.62% (263/681), 37.74% (257/681), and 19.38% (132/681), respectively. The abnormal rate of urine test was higher than that of blood test (P＜0.001). The multivariate logistic regression analysis with urinary α1-MG as the dependent variable showed that sex (odds ratio ［OR］=0.293, 95% confidence interval ［CI］: 0.204-0.419, P＜0.05), age (OR=1298, 95%CI: 1.108-1.521, P＜0.05), and type of nucleoside drug (OR=2.100, 95%CI: 1.431-3.083, P＜0.05) were influencing factors. The multivariate logistic regression analysis with urinary NAG as the dependent variable showed that age (OR=1.177, 95%CI: 1.008-1.375, P=0.040) was an influencing factor. ConclusionCompared with blood renal function markers, urinary renal function markers can identify renal injury earlier in CHB patients, and the elderly patients and the patients receiving TDF are more likely to develop abnormal renal function. However, it is not observed whether the duration of medication and liver cirrhosis can increase the risk of renal injury in CHB patients.

Analysis of the epidemiological characteristics and response to public health emergencies in Putuo District of Shanghai from 2004 to 2019 / 上海预防医学

ObjectiveTo analyze the epidemiological characteristics of public health emergencies in Putuo District and provide scientific evidence to effectively respond to public health emergencies in the future. MethodsDescriptive epidemiological methods were used to analyze the data of public health emergencies reported by the national online system in Putuo District from 2004 to 2019. ResultsA total of 59 public health emergencies were reported from 2004 to 2019， during which 1 252 patients and 6 death cases were involved. From 2004 to 2019， the number of public health emergencies in Putuo District first increased and then decreased， fluctuating at a low level yearly. Most of the emergencies were general events （72.88%， 43/59）. 69.49 percent （41/59） of the events were infectious diseases， and 67.80 percent （40/59） occurred in schools and child care institutes， with primary schools with the highest number of events. The peaks of infectious disease events occurred in June and November， while the majority of occupational poisoning and heat stoke events occurred in July and August， with 4 patients dead from heat stroke. The medians of events detection， verification， reporting and controlling timelines were 10.81， 3.00， 1.70 and 307.40 h； different categories of events varied in their detection and controlling time interval （all P<0.01）. Multiple linear regression analysis showed that events detection and verification timelines were correlated with controlling timelines （b=0.766， 0.758， F=3.84， 5.65， all P<0.01）. ConclusionsThe majority of public health emergencies in Putuo District are caused by infectious diseases， especially chicken pox. The prevention and control measures should be strengthened in schools. For occupational poisoning and heat stoke events， attention should be paid to different occupational groups. The capacity of emergency detection and verification should be enhanced to improve the efficiency of incident control.

Analysis of the epidemiological characteristics and response to public health emergencies in Putuo District of Shanghai from 2004 to 2019 / 上海预防医学

ObjectiveTo analyze the epidemiological characteristics of public health emergencies in Putuo District and provide scientific evidence to effectively respond to public health emergencies in the future. MethodsDescriptive epidemiological methods were used to analyze the data of public health emergencies reported by the national online system in Putuo District from 2004 to 2019. ResultsA total of 59 public health emergencies were reported from 2004 to 2019， during which 1 252 patients and 6 death cases were involved. From 2004 to 2019， the number of public health emergencies in Putuo District first increased and then decreased， fluctuating at a low level yearly. Most of the emergencies were general events （72.88%， 43/59）. 69.49 percent （41/59） of the events were infectious diseases， and 67.80 percent （40/59） occurred in schools and child care institutes， with primary schools with the highest number of events. The peaks of infectious disease events occurred in June and November， while the majority of occupational poisoning and heat stoke events occurred in July and August， with 4 patients dead from heat stroke. The medians of events detection， verification， reporting and controlling timelines were 10.81， 3.00， 1.70 and 307.40 h； different categories of events varied in their detection and controlling time interval （all P<0.01）. Multiple linear regression analysis showed that events detection and verification timelines were correlated with controlling timelines （b=0.766， 0.758， F=3.84， 5.65， all P<0.01）. ConclusionsThe majority of public health emergencies in Putuo District are caused by infectious diseases， especially chicken pox. The prevention and control measures should be strengthened in schools. For occupational poisoning and heat stoke events， attention should be paid to different occupational groups. The capacity of emergency detection and verification should be enhanced to improve the efficiency of incident control.

Identification of Prototype Components and Their Metabolites in Rat Serum, Urine and Feces After Oral Administration of Phellodendri Amurensis Cortex Aqueous Extract by UPLC-Orbitrap Fusion Lumos Tribrid-MS / 中国实验方剂学杂志

Objective:An ultra-performance liquid chromatography coupled with Orbitrap Fusion Lumos Tribrid mass spectrometry （UPLC-Orbitrap Fusion Lumos Tribrid-MS） was applied to analyze the prototypes and their metabolites of Phellodendri Amurensis Cortex aqueous extract in the serum， urine and feces of normal rats， and to investigate the pharmacodynamic material basis of Phellodendri Amurensis<italic> </italic>Cortex in rats. Method:Chromatographic separation was performed on the ACQUITY UPLC^® CSH^TM C₁₈ column （2.1 mm×100 mm， 1.7 μm） with the mobile phase of 0.1% formic acid aqueous solution （A）-acetonitrile （B） for gradient elution （0-15 min， 2%-25%B； 15-25 min， 25%-50%B； 25-28 min， 50%-98%B）， flow rate was 0.3 mL·min^-1， the injection volume was 10 μL and the column temperature was 40 ℃. Heated electrospray ionization （HESI） was used to collect data in the positive ion modes with the scanning range of <italic>m</italic>/<italic>z</italic> 100-1 000. By comparing chromatogram differences between the blank samples and the samples after administration， prototypes and their metabolites of biological samples after oral administration of Phellodendri Amurensis Cortex aqueous extract were identified. Result:After oral administration of Phellodendri Amurensis Cortex aqueous extract， a total of 70 compounds including 15 prototypes and 55 metabolites in rat serum， urine and feces were detected. Among them， 15 prototypes included 12 alkaloids and 3 limonoids， and 55 metabolites included 52 alkaloids and 3 limonoids. Desaturation， methylation， oxidation， sulfonation and glucuronide conjugation were observed as the primary metabolic pathways for the chemical constituents of Phellodendri Amurensis Cortex aqueous extract. Conclusion:Alkaloids in Phellodendri Amurensis Cortex aqueous extract undergo phase Ⅰ and phase Ⅱ metabolism in rats， and limonoids mainly undergo phase Ⅰ metabolism in rats. This paper can provide experimental basis for further analyzing the process <italic>in vivo</italic> of Phellodendri Amurensis Cortex and elucidating its pharmacodynamic substance basis<italic>.</italic>

Value of lymphocyte subset testing in predicting HBsAg decline in chronic hepatitis B patients receiving antiviral therapy / 临床肝胆病杂志

Objective To investigate whether there are differences in lymphocyte subsets between chronic hepatitis B (CHB) patients receiving different antiviral treatment regimens, and to determine related predictive factors for HBsAg decline. Methods A retrospective analysis was performed for 68 treatment-experienced CHB patients who attended the outpatient service in Department of Infectious Diseases, Henan Provincial People's Hospital, from October to December 2019, and according to the antiviral treatment regimen, they were divided into PEG-IFNα treatment group with 10 patients, PEG-IFNα+nucleos(t)ide analogues (NAs) treatment group with 21 patients, and NAs treatment group with 37 patients. Related data were recorded, including demographic features, blood routine, albumin, HBsAg, and measurement of lymphocyte subsets. A one-way analysis of variance was used for comparison of normally distributed continuous data between groups, and the Kruskal-Wallis H test was used for comparison of non-normally distributed continuous data between groups; the chi-square test was used for comparison of categorical data between groups; the multivariate logistic regression analysis was used to investigate independent influencing factors for HBsAg decline. Results There were significant differences between the three groups in HBsAg decline ( H =8.348, P =0.015), absolute value of lymphocytes ( F =4.643, P =0.013), and T lymphocyte count ( F =7.721, P =0.001). The multivariate logistic regression analysis showed that sex (odds ratio [ OR ]=0.227, 95% confidence interval [ CI ]: 0.059-0.878, P =0.032), age ( OR =0.931, 95% CI : 0.868-0.999, P =0.047), antiviral treatment regimen (PEG-IFN-α treatment group vs NAs treatment group: OR =9.600, 95% CI : 1.982-46.498, P =0.005; PEG-IFN-α+NAs treatment group vs NAs treatment group: OR =4.800, 95% CI : 1.336-17.243, P =0.016), and T lymphocyte count ( OR =0.804, 95% CI : 0.684-0.944, P =0.008) were independent influencing factors for HBsAg decline. Conclusion For CHB patients receiving PEG-IFNα alone or in combination with NAs, monitoring of lymphocyte subsets during the treatment process may help to judge HBsAg decline, and the lower the absolute value of T lymphocytes, the greater the possibility of HBsAg decline.

Panax Notoginseng Saponins Inhibits Ventricular Remodeling after Myocardial Infarction in Rats Through Regulating ATF3/MAP2K3/p38 MAPK and NF κ B Pathway / 中国结合医学杂志

OBJECTIVE@#To explore whether Panax notoginseng saponins (PNS) exhibits heart protective effect in myocardial infarction (MI) rats and to identify the potential signaling pathways involved.@*METHODS@#MI rats induced by ligating the left anterior descending (LAD) coronary artery were assigned to sham coronary artery ligation or coronary artery ligation. Totally 36 Sprague-Dawley rats were randomly divided into sham group (distilled water, n=9), MI group (distilled water, n=9), PNS group (PNS, 40 mg/kg daily, n=9) and fosinopril group (FIP, 1.2 mg/kg daily, n=9) according to a random number table. The left ventricular morphology and function were conducted by echocardiography. Histological alterations were evaluated by the stainings of HE and Masson. The serum levels of C reactive protein (CRP), tumor necrosis factor α (TNF-α), growth differentiation factor-15 (GDF-15) and the ratio of metalloproteinase-9 (MMP-9) and tissue inhibitor of MMP-9 (TIMP-1) were determined by ELISA. The levels of activating transcription factor 3 (ATF3), mitogen-activated protein kinase kinase 3 (MAP2K3), p38 mitogen-activated protein kinase (p38 MAPK), phosphorylation of p38 MAPK (p-p38 MAPK), transforming growth factor-β (TGF-β1), collagen I, nuclear factor kappa B p65 (NFκB p65), phosphorylation of NFκB p65 (p-NFκB p65), and phosphorylation of inhibitory kappa Bα (p-Iκ Bα) in hearts were measured by Western blot and immunohistochemical staining, respectively.@*RESULTS@#PNS improved cardiac function and fibrosis in MI rats (P<0.05). The serum levels of CRP, TNF-α, GDF-15 and the ratio of MMP9/TIMP1 were reversed by PNS in MI rats. The expressions of TGF-β1, collagen I, MAP2K3, p38 MAPK, p-p38 MAPK, NFκB p65, p-NFκB p65, and p-IκBα were down-regulated, while ATF3 increased with the treatment of PNS (P<0.05).@*CONCLUSIONS@#PNS may improve cardiac function and fibrosis in MI rats via regulating ATF3/MAP2K3/p38 MAPK and NFκB signaling pathways. These results suggest the potential of PNS in preventing the development of ventricular remodeling in MI rats.

Distribution of Traditional Chinese Medicine Syndromes and Relevant Factors in 6 Months After Percutaneous Coronary Intervention / 中国实验方剂学杂志

Objective:To investigate the distribution of traditional Chinese medicine (TCM) syndromes in patients with coronary heart disease (CHD) in 6 months after interventional therapy, and to analyze relevant influencing factors. Method:The clinical data of 1 000 patients with coronary heart disease in 6 months after interventional therapy, including the four diagnosis information of TCM, were collected, and the distribution of TCM syndromes and the influencing factors were analyzed. Result:Among 48 kinds of information about the four diagnostic methods of TCM, chest pain was the most frequent (98.10%)， among 9 kinds of common TCM syndrome types, blood stasis was the most frequent (89.90%), and the others were heart-Qi deficiency syndrome, phlegm turbidity syndrome, cold-dampness syndrome, kidney-Qi deficiency syndrome, heart-Yin deficiency syndrome, kidney-Yin deficiency syndrome, Heart-Yang deficiency syndrome and kidney-Yang deficiency syndrome in turn. Among 6 common TCM syndrome types, Qi deficiency and blood stasis syndrome were the most frequent (35.40%), and the others were phlegm turbidity and blood stasis syndrome, cold congealing heart pulse syndrome, Qi-Yin deficiency syndrome, heart-kidney Yin deficiency syndrome and heart-kidney-Yang deficiency syndrome in turn. There was no significant difference in sex ratio among different syndrome types . Patients with heart-kidney Yang deficiency syndrome had no significant difference. Compared with the average age of other syndromes, there were significant differences. Common complications included hypertension, diabetes, cerebrovascular diseases and dyslipidemia, among which hypertension had the highest frequency, with significant differences from other diseases (P<0.05). Phlegm, turbidity and blood stasis were found in patients with hypertension. The risk of syndromes was higher (OR=3.29, 95% CI [2.11, 5.05]), while the risk of cold congealing heart pulse syndrome was lower (OR=0.56, 95% CI [0.32, 0.98]), the risk of Qi and Yin deficiency was higher (OR=2.88, 95% CI [2.01, 4.99]), whereas the risk of heart and kidney Yang deficiency was lower (OR=0.54, 95% CI [0.29, 0.95]) when complicated with cerebrovascular diseases. The risk of Qi deficiency and blood stasis was higher (OR=2.97, 95% CI [2.05, 5.28]), while the risk of heart and kidney Yang deficiency was lower (OR=0.54, 95% CI [0.29, 0.95])， the risk of phlegm turbidity and blood stasis was higher when complicated with dyslipidemia (OR=3.55, 95% CI [2.32, 5.29]), and the risk of heart and kidney Yang deficiency was lower (OR=0.54, 95% CI [0.29, 0.95]). The time distribution of the disease had obvious seasonal characteristics. Conclusion:The main distribution characteristics of TCM syndromes in 6 months after coronary heart disease intervention are basically the same as those in patients without intervention. The main TCM syndromes are Qi deficiency and blood stasis syndrome, phlegm turbidity and blood stasis syndrome, cold congealing heart pulse syndrome, Qi-Yin deficiency syndrome, heart-kidney Yin deficiency syndrome and heart-kidney-Yang deficiency syndrome. The distribution pattern may be related to age, complications and seasons.

Distribution Characteristics of Traditional Chinese Medicine Syndromes in Patients with Critical Lesions of Coronary Heart Disease / 中国实验方剂学杂志

Objective::To explore the distribution characteristics of traditional Chinese medicine (TCM) syndromes of critical lesions of coronary heart disease, and determine the classification and diagnostic criteria of syndromes, so as to provide reference for the differentiation and treatment of this disease. Method::Totally 1 000 patients with critical lesions of coronary heart disease treated in the Department of Cardiology, Yunnan Provinceal Hospital of TCM from January 2016 to December 2018 were selected as the subjects by clinical epidemiological research methods. Basic information, diagnosis and treatment of the patients, as well as the information obtained through observation, hearing, inquiry and pulse-taking of TCM were collected. Symptoms, signs, tongue signs, pulse signs and other four diagnostic information, as well as relevant clinical data were collected for mathematical statistics analysis by cluster analysis and factor analysis research methods, and expert group opinions were also included in discussion. Result::First, the results of cluster analysis showed six types of basic TCM syndromes in accordance with the clinically actual critical lesions of coronary heart disease: blood stasis syndrome, phlegm turbidity syndrome, cold congealing heart pulse syndrome, Qi deficiency syndrome, heart-kidney Yin deficiency syndrome, Heart-Yang deficiency syndrome. Second, a factor analysis was carried out on the basis of cluster analysis, and the main syndromes of each basic syndromes were preliminarily determined. Third, because of the duplicate content or the unified combination of different syndromes, the TCM syndromes of the critical lesions of coronary heart disease can be summarized in five categories, namely phlegm turbidity and blood stasis syndrome (368 cases, 36.80%), cold congestion heart pulse syndrome (156 cases, 15.60%), Qi deficiency and blood stasis syndrome (315 cases, 31.50%), Yin deficiency of heart and kidney (91 cases, 9.10%) and Heart-Yang depression (70 cases, 7.00%). The main and secondary syndromes refer to factor analysis results of six basic syndromes. Conclusion::Cluster analysis and factor analysis can be made on TCM syndromes of critical lesions of coronary heart disease to pave the way for the classification of TCM syndromes and the establishment of diagnostic criteria of TCM syndromes of coronary heart disease, with an important clinical significance.

Distribution of Non-ST Segment Elevation Myocardial Infarction Syndromes and Traditional Chinese Medicine Intervention Strategies / 中国实验方剂学杂志

Objective:To analyze the syndrome characteristics and distribution regularity of patients with non-ST segment elevation myocardial infarction (NSTEMI), in order to guide clinical practice and improve the efficacy of traditional Chinese medicine. Method:Inpatients with non-ST segment elevation myocardial infarction in line with the diagnostic criteria were selected, and the frequency statistics method was used to analyze the syndrome elements and their frequency degree and distribution characteristics. Result:According to the analysis of syndrome elements and their frequency degree of 263 patients with NSTEMI, the pathogenesis of NSTEMI was mostly deficiency in origin and excess in superficiality. As for deficiency in origin, Qi deficiency (171 times, 32.39%) was the most common, which was followed by Yin deficiency (42 times, 7.95%), Yang deficiency (16 times, 3.03%), and blood deficiency (1 times, 0.19%). As for excess in superficiality, blood stasis (129 frequency, 24.4%) and phlegm turbidity (125 frequency, 23.7%) were the most common, which were followed by heat accumulation (42 frequency, 7.95%), water drinking (2 frequency, 0.38%). According to the syndrome diagnosis analysis of the combination of syndrome elements, 220 cases (83.65%) had single syndrome differentiation, 42 cases (15.97%) had two syndromes at the same time, and 1 case (0.38%) had three syndromes at the same time. Among all the syndrome types, Qi deficiency and blood stasis syndrome (94 cases, 42.7%) was the most common, which were followed by phlegm and blood stasis syndrome (46 cases, 20.9%), Qi and Yin deficiency syndrome (41 cases, 18.6%) and heart and kidney deficiency syndrome (32 cases, 14.6%). And Yang deficiency and water flooding syndrome (6 cases, 2.73%) and heart fire blazing syndrome (1 case, 0.45%) were relatively rare. According to the distribution regularity of syndrome, traditional Chinese medicine therapies were mainly for tonifying vital qi and protecting kidney Qi, with equal emphasis on removing phlegm, eliminating dampness and diuresis, activating blood circulation and removing blood stasis. Conclusion:The pathogenesis of NSTEMI is deficiency in origin and excess in superficiality. Deficiency in origin is mostly Qi deficiency and Yin deficiency, while excess in superficiality is mostly blood stasis, phlegm and heat accumulation. traditional Chinese medicine therapies are mostly for invigorating Qi and nourishing Yin, promoting blood circulation and removing blood stasis, clearing heat and resolving phlegm.

Network Pharmacology-based Mechanism of Xiao Xianxiongtang in Treatment of Coronary Heart Disease / 中国实验方剂学杂志

Objective::To predict Xiao Xianxiongtang's treatment of coronary heart disease (CHD) targets and analyze their function by the network pharmacology method, and build ingredients-targets-channel network pharmacological model, in order to reveal potential pathways and mechanisms of Xiao Xianxiongtang for CHD treatment. Method::Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP) was used to obtain components, and CHD targets over Xiao Xianxiongtang were predicted by using Swiss Target Prediction reverse pharmacophore matching method. CHD targets which Food and Drug Administration (FDA) approved were collected from Therapeutic Target Database (TTD), Drugbank and Disease-gene Net databases (DisGeNET). Wenn diagram was used to obtain the correlation intersection.Target characteristics were analyzed with GEO2R online, Reactome FI was used to analyze the enrichment of target pathways, and Cytoscape software was used to construct the " component-target-pathway" network. Result::Network analysis showed that Xiao Xianxiongtang treated CHD by regulating 24 target proteins through 25 therapeutic components, and acting on 21 specific pathways and 4 biological processes.According to the multiple gene chip analysis of GEO2R online, there were up-down-regulated differences in the targets, including 11 up targets and 13 down targets. Conclusion::Xiao Xianxiongtang treats CHD by involving the biological processes through berberine and flavonoid groups of Coptidis Rhizoma, nucleosides and organic acids of Arum ternatum Thunb, stigmasterols and flavonoids of Trichosanthes kirilowii Maxim, such as gene expression, metabolism and protein metabolism, adjusting the gene expressions of relevant target proteins, regulating gene transcription pathways, such as biological oxidation reaction and lipid and lipoprotein metabolism, insulin-like growth factor binding protein (IGFBPs) of insulin-like growth factor (IGF) transshipment and intake, and the degradation of extracellular matrix signaling pathways.

Research Progress on Processing of Polygalae Radix / 中国实验方剂学杂志

Polygalae Radix， a traditional Chinese medicine， has the functions of improving intelligence， calming nerves， relieving cough and eliminating phlegm. Its processing methods are various， but the purpose of processing is to reduce toxicity and increase efficiency. In this paper， the methods of ancient processing， such as cleansing， cutting， processing with excipient and processing without excipient， were summarized， the processing methods of Polygalae Radix in the different versions of Chinese Pharmacopoeia and the local processing specifications were summarized， in order to compare the differences and research progress of different processing methods. On this basis， taking the modern research of processed products of Polygalae Radix as the breakthrough point， this paper reviewed the modern research on processed products of Polygalae Radix from the aspects of processing technology， chemical composition changes and pharmacodynamics changes before and after processing， and the mechanism of reducing toxicity and increasing efficiency. Based on the research status of processing of Polygalae Radix， some existing problems were analyzed in this paper， including not many ancient processing methods used in modern times， lack of standardized research on processing technology， few studies on the ingredients introduced by excipients， etc. The author thinks that it is necessary to strengthen the research on the ancient processing of Polygalae Radix combined with processing methods with local characteristics. While discussing the processing technology， combining with the composition and efficacy， we should carry out in-depth research on the processing mechanism of different processing products of Polygalae Radix， so as to provide scientific basis for the rationality of processing of Polygalae Radix and ensure the clinical safety of medication.

Therapeutic effect of artificial liver blood purification system on six cases with corona virus disease 2019 / 中华传染病杂志

Objective:To evaluate the efficacy of artificial liver blood purification system in the treatment of severe and critical patients with corona virus disease 2019(COVID-19), and to observe the dynamic changes of lymphocyte subsets and cytokines after treatment.Methods:A total of six patients with COVID-19 admitted to the ward of public health center of Henan Provincial People′s Hospital from January 31 to February 18, 2020 were enrolled, including three severe cases and three critical cases. The protocals of artificial liver treatment were developed according to the patients′ conditions, and the patients′ epidemiological history, clinical characteristics, and laboratory examination data were retrospectively analyzed. At the same time, dynamic changes of lymphocyte subsets and cytokines were detected before and after artificial liver treatment.Results:By February 24, 2020, two severe patients were discharged after cured, and one case was discharged after improved, with an average stay of 19 days. Two critical patients were still hospitalized and one died. Three severe patients were all treated with hemofiltration, while two critical patients were treated with hemofiltration plus plasma exchange, and one was treated with continuous bedside hemofiltration.Among six patients, the ratio of neutrophils to lymphocytes before treatment were 6.42, 2.63, 15.00, 15.09, 12.04 and 30.41, respectively. After treatment, the ratio of neutrophils to lymphocytes became 4.77, 6.05, 4.86, 5.43, 32.77 and 23.46, respectively.The absolute numbers of lymphocytes in six patients before treatment were low, with a median of 382/μL. After treatment of artificial liver, the absolute numbers of lymphocytes increased, with a median of 476/μL. Cytokines were detected in three critical patients, and the interleukin 6 (IL-6) levels in two cases were 26 042.00 ng/L and 282.03 ng/L, respectively before treatment. After treatment, the levels decreased to 226.85 ng/L and 26.15 ng/L, respectively. IL-6 continued increasing from 30.14 ng/L to 709.25 ng/L in one another critical patient, who eventually died.Conclusions:In severe and critical patients with COVID-19, artificial liver treatment can reduce inflammation and increase the absolute numbers of lymphocytes and the subsets. The IL-6 level may be correlated with disease progression and may be a useful prognostic factor for early identification of severe and critical COVID-19.