Study of the influence of peer support service on social function of patients with chronic schizophrenia / 四川精神卫生

BackgroundThe improvement of social function in patients with schizophrenia is an important part of their rehabilitation， and peer support services， as a rehabilitation method， may be of great significance to improve the social function of patients with schizophrenia. ObjectiveTo explore the influence of peer support service on the daily living ability and social function of patients with chronic schizophrenia， and to provide references for promoting the rehabilitation of patients with chronic schizophrenia. MethodsA total of 100 patients with chronic schizophrenia who were hospitalized in The Third People's Hospital of Tianshui from January 1 to December 31， 2020 and met the diagnostic criteria of the International Classification of Diseases， 10th edition （ICD-10） were selected as the study objects， and they were divided into the control group and the study group with 50 cases each by random number table method. Patients in both groups received routine treatment and nursing care， on this basis， the study group received peer support service once or twice a week for 12 weeks， and the control group received the same peer support service at the end of the study. Before and at the 1st， 2nd， 4th， 8th and 12th week of the treatment， Activity of Daily Living Scale （ADL） and Social Disability Screening Schedule （SDSS） were used to evaluate the activities of daily living and social function of the two groups. ResultsThe ADL scores of the study group were lower than those of the control group at the 8th week and 12th week of the treatment （ t=-2.420， -2.814， P<0.05 or 0.01） . The SDSS scores of the study group were lower than those of the control group at the 8th week an 12th week of the treatment （t=-2.057， -2.322， P<0.05） . ConclusionPeer support services may help improve the ability of daily life and social function of patients with chronic schizophrenia. ［Funded by Tianshui City Livelihood Science and Technology Plan Project （number， 2020-SHFZKJK-9344）］

A study on using comprehensive geriatric assessment to improve the teaching level of doctor-patient communication from the perspective of Johari Window / 中华医学教育探索杂志

Based on the theory of "Johari Window", this study introduced how to stimulate information content obtained in doctor-patient communication and how to apply the comprehensive geriatric assessment creatively from the four modules of open area, blind area, hidden area and unknown area in the model. It helped students to gain the trust and cooperation of patients, rapidly narrow down the blind area, hidden area and unknown area, guide patients to actively extend the open area, improve the teaching quality of doctor-patient communication in a scientific way.

Renin-angiotensin system inhibitor is associated with the reduced risk of all-cause mortality in COVID-19 among patients with/without hypertension / 医学前沿

Consecutively hospitalized patients with confirmed coronavirus disease 2019 (COVID-19) in Wuhan, China were retrospectively enrolled from January 2020 to March 2020 to investigate the association between the use of renin-angiotensin system inhibitor (RAS-I) and the outcome of this disease. Associations between the use of RAS-I (angiotensin-converting enzyme inhibitor (ACEI) or angiotensin receptor blocker (ARB)), ACEI, and ARB and in-hospital mortality were analyzed using multivariate Cox proportional hazards regression models in overall and subgroup of hypertension status. A total of 2771 patients with COVID-19 were included, with moderate and severe cases accounting for 45.0% and 36.5%, respectively. A total of 195 (7.0%) patients died. RAS-I (hazard ratio (HR)= 0.499, 95% confidence interval (CI) 0.325-0.767) and ARB (HR = 0.410, 95% CI 0.240-0.700) use was associated with a reduced risk of all-cause mortality among patients with COVID-19. For patients with hypertension, RAS-I and ARB applications were also associated with a reduced risk of mortality with HR of 0.352 (95% CI 0.162-0.764) and 0.279 (95% CI 0.115-0.677), respectively. RAS-I exhibited protective effects on the survival outcome of COVID-19. ARB use was associated with a reduced risk of all-cause mortality among patients with COVID-19.

Genomic epidemiology of SARS-CoV-2 in the United Arab Emirates reveals novel virus mutation, patterns of co-infection and tissue specific host responses

To unravel the source of SARS-CoV-2 introduction and the pattern of its spreading and evolution in the United Arab Emirates, we conducted meta-transcriptome sequencing of 1,067 nasopharyngeal swab samples collected between May 9th and Jun 29th, 2020 during the first peak of the local COVID-19 epidemic. We identified global clade distribution and eleven novel genetic variants that were almost absent in the rest of the world defined five subclades specific to the UAE viral population. Cross-settlement human-to-human transmission was related to the local business activity. Perhaps surprisingly, at least 5% of the population were co-infected by SARS-CoV-2 of multiple clades within the same host. We also discovered an enrichment of cytosine-to-uracil mutation among the viral population collected from the nasopharynx, that is different from the adenosine-to-inosine change previously reported in the bronchoalveolar lavage fluid samples and a previously unidentified upregulation of APOBEC4 expression in nasopharynx among infected patients, indicating the innate immune host response mediated by ADAR and APOBEC gene families could be tissue-specific. The genomic epidemiological and molecular biological knowledge reported here provides new insights for the SARS-CoV-2 evolution and transmission and points out future direction on host-pathogen interaction investigation.

Expression of programmed death ligand 1 in rectal cancer and its significance / 肿瘤研究与临床

Objective:To investigate the expression of programmed death ligand 1 (PD-L1) in rectal cancer tissues and the correlation of PD-L1 expression with clinicopathological characteristics and overall survival of patients.Methods:The clinical data of 200 newly treated rectal cancer patients in Shanxi Provincial Cancer Hospital from January 2014 to December 2015 were retrospectively analyzed. The expression of PD-L1 in rectal cancer tissues was detected by immunohistochemistry. The correlations of PD-L1 expression with gender, age, tumor T stage, lymph node metastasis, tumor differentiation, histological type, tumor TNM stage, neutrophil-to-lymphocyte ratio (NLR) and overall survival of patients were analyzed.Results:The positive expression rate of PD-L1 was 24% (48/200). The positive expression rate of PD-L1 was high in patients with lymph node metastasis and high NLR (≥ 3.5) (both P < 0.05). The 5-year overall survival rate in PD-L1-positive group was 42%, and the PD-L1-negative group was 59%, and the difference between the two groups was statistically significant ( P < 0.05). The results of multivariate analysis showed that lymph node metastasis ( HR = 3.456, 95% CI 2.148-5.556, P < 0.01), NLR ≥ 3.5 ( HR = 1.871, 95% CI 1.169-2.996, P = 0.009), and PD-L1-positive expression ( HR = 2.187, 95% CI 1.373-3.484, P = 0.001) were independent adverse influencing factors for the overall survival of rectal cancer patients. Conclusion:PD-L1 is highly expressed in rectal cancer tissues, and the positive expression of PD-L1 is associated with poor overall survival of patients.

A preliminary study on the teaching mode of constructivism in physical diagnostics teaching / 中华医学教育探索杂志

The efficacy of constructivism teaching mode in physical diagnostics teaching was evaluated in this study. We built up the constructivism teaching mode in diagnostics teaching taking the clinical symptoms as the theme, and through such aspects as courseware design, teaching plan preparation, SP playing and inquiry, SimMan simulated physical examination, condition analysis, etc. Then questionnaires were conducted to analyze the role of the constructivism teaching mode in diagnostics teaching. The diagnostics constructivism teaching mode can provide students with a platform for self-construction of diagnostics and integrated application of knowledge. Meanwhile, students' sense of participation can be improved and multiple learning skills are enhanced during the course.

Safety and immunogenicity of a recombinant tandem-repeat dimeric RBD protein vaccine against COVID-19 in adults: pooled analysis of two randomized, double-blind, placebo-controlled, phase 1 and 2 trials

BackgroundA safe and effective coronavirus disease 2019 (COVID-19) vaccine is urgently needed to control the ongoing pandemic. Although progress has been made recently with several candidates reporting positive efficacy results, COVID-19 vaccines developed so far cannot meet the global vaccine demand. We developed a protein subunit vaccine against COVID-19, using dimeric form of receptor-binding domain (RBD) as the antigen. We aimed to assess the safety and immunogenicity of this vaccine in humans and determine the appropriate dose and schedule for an efficacy study. MethodsWe did two randomized, double-blind, placebo-controlled, phase 1 and 2 trials for an RBD-based protein subunit vaccine, ZF2001. In phase 1 study, 50 healthy adults aged 18-59 years were enrolled and randomly allocated to three groups to receive three doses of vaccine (25 g or 50 g RBD-dimer, with adjuvant) or placebo (adjuvant-only) intramuscularly, 30 days apart. In phase 2 study, 900 healthy adults aged 18-59 years were enrolled and randomly allocated to six groups to receive vaccine (25 g or 50 g RBD-dimer, with adjuvant) or placebo (adjuvant-only) intramuscularly, with the former 3 groups given two doses and the latter 3 groups given three doses, 30 days apart. For phase 1 trial, the primary outcome was safety, as measured by the occurrence of adverse events and serious adverse events. The secondary outcome was immunogenicity as measured by the seroconversion rate and magnitude of antigen-binding antibodies, neutralizing antibodies and T-cell cytokine production. For phase 2 trial, the primary outcome included both safety and immunogenicity. These trials are registered with ClinicaTrials.gov, NCT04445194 and NCT04466085. FindingsBetween June 22 and September 15, 2020, 50 participants were enrolled to the phase 1 study (mean age 32.6 years) and 900 participants were enrolled to phase 2 study (mean age 43.5 years), to receive vaccine or placebo with a two-dose or three-dose schedule. For both trials, local and systemic adverse reactions were absent or mild in most participants. There were no serious adverse events related to vaccine in either trial. After three doses, neutralizing antibodies were detected in all participants receiving either 25 g or 50 g dose of vaccine in phase 1 study, and in 97% (the 25 g group) and 93% (the 50 g group) of participants, respectively, in phase 2 study. The SARS-CoV-2-neutralizing geometric mean titres (GMTs) were 94.5 for the 25 g group and 117.8 for the 50 g group in phase 1, and 102.5 for the 25 g group and 69.1 for the 50 g group in phase 2, exceeding the level of a panel of COVID-19 convalescent samples (GMT, 51). Vaccine induced balanced TH1 and TH2 responses. The 50 g group did not show enhanced immunogenicity compared with the 25 g group. InterpretationThe protein subunit vaccine ZF2001 is well-tolerated and immunogenic. The safety and immunogenicity data from phase 1 and 2 trials for ZF2001 support the use of 25 g vaccine dose with three-dose schedule to an ongoing phase 3 large-scale evaluation for safety and efficacy. FundingNational Program on Key Research Project of China, National Science and Technology Major Projects of Drug Discovery, Strategic Priority Research Program of the Chinese Academy of Sciences, and Anhui Zhifei Longcom Biopharmaceutical.

Developing multiplex ddPCR assays for SARS-CoV-2 detection based on probe mix and amplitude based multiplexing

Multiplexing has been highlighted to save on costs, increase sample throughput, and maximize on the number of targets that can be sensitively detected within a small sample. With the ongoing SARS-CoV-2 pandemic, different articles have been published highlighting the superiority of droplet digital PCR (ddPCR) over the gold reverse transcription PCR (RT-PCR) in SARS-CoV-2 detection. However, few studies have been reported on developing multiplex ddPCR assays for SARS-CoV-2 detection and their performance. In this study, we developed simplex (1 target), duplex (2 targets), triplex probe mix (3 targets), and fourplex (4 targets) assays based on a two color ddPCR system for SARS-CoV-2 detection. Results showed that the fourplex assay had the similar limits of detection and accuracy to the lower multiplex assays. Analyzing 94 clinical isolates demonstrated that the ddPCR triplex probe mix assay had better sensitivity than the RT-qPCR assay. Additionally, the ddPCR multiplex assay showed that remdesivir could inhibit the growth of SARS-CoV-2 in vitro while another testing drug couldnt. Conclusively, our research shows that developing multiplex ddPCR assays is possible by combing probe mix and amplitude based multiplexing, which will help in developing multiplexed ddPCR assays for different SARS-CoV-2 applications.

Characterization of Microbial Co-infections in the Respiratory Tract of hospitalized COVID-19 patients

BackgroundSevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused a global pandemic of Coronavirus disease 2019 (COVID-19). However, microbial composition of the respiratory tract and other infected tissues, as well as their possible pathogenic contributions to varying degrees of disease severity in COVID-19 patients remain unclear. MethodBetween January 27 and February 26, 2020, serial clinical specimens (sputum, nasal and throat swab, anal swab and feces) were collected from a cohort of hospitalized COVID-19 patients, including 8 mildly and 15 severely ill patients (requiring ICU admission and mechanical ventilation), in the Guangdong province, China. Total RNA was extracted and ultra-deep metatranscriptomic sequencing was performed in combination with laboratory diagnostic assays. Co-infection rates, the prevalence and abundance of microbial communities in these COVID-19 patients were determined. FindingsNotably, respiratory microbial co-infections were exclusively found in 84.6% of severely ill patients (11/13), among which viral and bacterial co-infections were detected by sequencing in 30.8% (4/13) and 69.2% (9/13) of the patients, respectively. In addition, for 23.1% (3/13) of the patients, bacterial co-infections with Burkholderia cepacia complex (BCC) and Staphylococcus epidermidis were also confirmed by bacterial culture. Further, a time-dependent, secondary infection of B. cenocepacia with expressions of multiple virulence genes in one severely ill patient was demonstrated, which might be the primary cause of his disease deterioration and death one month after ICU admission. InterpretationOur findings identified distinct patterns of co-infections with SARS-CoV-2 and various respiratory pathogenic microbes in hospitalized COVID-19 patients in relation to disease severity. Detection and tracking of BCC-associated nosocomial infections are recommended to improve the pre-emptive treatment regimen and reduce fatal outcomes of hospitalized patients infected with SARS-CoV-2. FundingNational Science and Technology Major Project of China, National Major Project for Control and Prevention of Infectious Disease in China, the emergency grants for prevention and control of SARS-CoV-2 of Ministry of Science and Technology and Guangdong province, Guangdong Provincial Key Laboratory of Genome Read and Write, Guangdong Provincial Academician Workstation of BGI Synthetic Genomics, and Shenzhen Engineering Laboratory for Innovative Molecular Diagnostics.

Population Bottlenecks and Intra-host Evolution during Human-to-Human Transmission of SARS-CoV-2Population Bottlenecks and Intra-host Evolution during Human-to-Human Transmission of SARS-CoV-2

The emergence of the novel human coronavirus, SARS-CoV-2, causes a global COVID-19 (coronavirus disease 2019) pandemic. Here, we have characterized and compared viral populations of SARS-CoV-2 among COVID-19 patients within and across households. Our work showed an active viral replication activity in the human respiratory tract and the co-existence of genetically distinct viruses within the same host. The inter-host comparison among viral populations further revealed a narrow transmission bottleneck between patients from the same households, suggesting a dominated role of stochastic dynamics in both inter-host and intra-host evolutions. Author summaryIn this study, we compared SARS-CoV-2 populations of 13 Chinese COVID-19 patients. Those viral populations contained a considerable proportion of viral sub-genomic messenger RNAs (sgmRNA), reflecting an active viral replication activity in the respiratory tract tissues. The comparison of 66 identified intra-host variants further showed a low viral genetic distance between intra-household patients and a narrow transmission bottleneck size. Despite the co-existence of genetically distinct viruses within the same host, most intra-host minor variants were not shared between transmission pairs, suggesting a dominated role of stochastic dynamics in both inter-host and intra-host evolutions. Furthermore, the narrow bottleneck and active viral activity in the respiratory tract show that the passage of a small number of virions can cause infection. Our data have therefore delivered a key genomic resource for the SARS-CoV-2 transmission research and enhanced our understanding of the evolutionary dynamics of SARS-CoV-2.

A path towards SARS-CoV-2 attenuation: metabolic pressure on CTP synthesis rules the virus evolution

Fighting the COVID-19 epidemic summons deep understanding of the way SARS-CoV-2 taps into its host cell metabolic resources. We describe here the singular metabolic background that creates a bottleneck constraining coronaviruses to evolve towards likely attenuation in the long term. Cytidine triphosphate (CTP) is at the crossroad of the biosynthetic processes that allow the virus to multiply. This is because CTP is in demand for three essential steps. It is a building block of the virus genome, it is required for synthesis of the cytosine-based liponucleotide precursors of the viral envelope and, finally, it is a critical building block of the host transfer RNAs synthesis. The CCA 3-end of all the transfer RNAs required to translate the RNA genome and further transcripts into the proteins used to build active virus copies is not coded in the human genome. It must be synthesized de novo from CTP and ATP. Furthermore, intermediary metabolism is built on compulsory steps of synthesis and salvage of cytosine-based metabolites via uridine triphosphate (UTP) that keep limiting CTP availability. As a consequence, accidental replication errors tend to replace cytosine by uracil in the genome, unless recombination events allow the sequence to return to its ancestral sequences. We document some of the consequences of this situation in the function of viral proteins. We also highlight and provide a raison detre to viperin, an enzyme of innate antiviral immunity, which synthesizes 3-deoxy-3',4-didehydro-CTP (ddhCTP) as an extremely efficient antiviral nucleotide.

Intra-host Variation and Evolutionary Dynamics of SARS-CoV-2 Population in COVID-19 Patients

As of middle May 2020, the causative agent of COVID-19, SARS-CoV-2, has infected over 4 million people with more than 300 thousand death as official reports1,2. The key to understanding the biology and virus-host interactions of SARS-CoV-2 requires the knowledge of mutation and evolution of this virus at both inter- and intra-host levels. However, despite quite a few polymorphic sites identified among SARS-CoV-2 populations, intra-host variant spectra and their evolutionary dynamics remain mostly unknown. Here, using deep sequencing data, we achieved and characterized consensus genomes and intra-host genomic variants from 32 serial samples collected from eight patients with COVID-19. The 32 consensus genomes revealed the coexistence of different genotypes within the same patient. We further identified 40 intra-host single nucleotide variants (iSNVs). Most (30/40) iSNVs presented in single patient, while ten iSNVs were found in at least two patients or identical to consensus variants. Comparison of allele frequencies of the iSNVs revealed genetic divergence between intra-host populations of the respiratory tract (RT) and gastrointestinal tract (GIT), mostly driven by bottleneck events among intra-host transmissions. Nonetheless, we observed a maintained viral genetic diversity within GIT, showing an increased population with accumulated mutations developed in the tissue-specific environments. The iSNVs identified here not only show spatial divergence of intra-host viral populations, but also provide new insights into the complex virus-host interactions.

Effect of continuous renal replacement therapy on all-cause mortality in COVID-19 patients undergoing invasive mechanical ventilation: a retrospective cohort study

BackgroundFor the coronavirus disease 2019 (COVID-19), critically ill patients had a high mortality rate. We aimed to assess the association between prolonged intermittent renal replacement therapy (PIRRT) and mortality in patients with COVID-19 undergoing invasive mechanical ventilation. MethodsIn this retrospective cohort study, we included all patients with COVID-19 undergoing invasive mechanical ventilation from February 12nd to March 2nd, 2020. All patients were followed until death or March 28th, and all survivors were followed for at least 30 days. ResultsFor 36 hospitalized COVID-19 patients with invasive mechanical ventilation, the mean age was 69.4 ({+/-} 10.8) years, and 30 patients (83.3%) were men. Twenty-two (61.1%) patients received PIRRT (PIRRT group) and 14 cases (38.9%) were managed with conventional strategy (non-PIRRT group). There were no differences in age, sex, comorbidities, complications, treatments and most of the laboratory findings. During median follow-up period of 9.5 (interquartile range 4.3-33.5) days, 13 of 22 (59.1%) patients in the PIRRT group and 11 of 14 (78.6%) patients in the non-PIRRT group died. Kaplan-Meier analysis demonstrated prolonged survival in patients in the PIRRT group compared with that in the non-PIRRT group (P = 0.042). The association between PIRRT and a reduced risk of mortality remained significant in three different models, with adjusted hazard ratios varying from 0.332 to 0.398. Higher levels of IL-2 receptor, TNF-, procalcitonin, prothrombin time, and NT-proBNP were significantly associated with an increased risk of mortality in patients with PIRRT. ConclusionPIRRT may be beneficial for the treatment of COVID-19 patients with invasive mechanical ventilation. Further prospective multicenter studies with larger sample sizes are required.

Multiple approaches for massively parallel sequencing of HCoV-19 genomes directly from clinical samples

COVID-19 has caused a major epidemic worldwide, however, much is yet to be known about the epidemiology and evolution of the virus. One reason is that the challenges underneath sequencing HCoV-19 directly from clinical samples have not been completely tackled. Here we illustrate the application of amplicon and hybrid capture (capture)-based sequencing, as well as ultra-high-throughput metatranscriptomic (meta) sequencing in retrieving complete genomes, inter-individual and intra-individual variations of HCoV-19 from clinical samples covering a range of sample types and viral load. We also examine and compare the bias, sensitivity, accuracy, and other characteristics of these approaches in a comprehensive manner. This is, to date, the first work systematically implements amplicon and capture approaches in sequencing HCoV-19, as well as the first comparative study across methods. Our work offers practical solutions for genome sequencing and analyses of HCoV-19 and other emerging viruses.

Kidney impairment is associated with in-hospital death of COVID-19 patients

BackgroundInformation on kidney impairment in patients with coronavirus disease 2019 (COVID-19) is limited. This study aims to assess the prevalence and impact of abnormal urine analysis and kidney dysfunction in hospitalized COVID-19 patients in Wuhan. MethodsWe conducted a consecutive cohort study of COVID-19 patients admitted in a tertiary teaching hospital with 3 branches following a major outbreak in Wuhan in 2020. Hematuria, proteinuria, serum creatinine concentration and other clinical parameters were extracted from the electronic hospitalization databases and laboratory databases. Incidence rate for acute kidney injury (AKI) was examined during the study period. Association between kidney impairment and in-hospital death was analyzed. ResultsWe included 710 consecutive COVID-19 patients, 89 (12.3%) of whom died in hospital. The median age of the patients was 63 years (inter quartile range, 51-71), including 374 men and 336 women. On admission, 44% of patients have proteinuria hematuria and 26.9% have hematuria, and the prevalence of elevated serum creatinine and blood urea nitrogen were 15.5% and 14.1% respectively. During the study period, AKI occurred in 3.2% patients. Kaplan-Meier analysis demonstrated that patients with kidney impairment have higher risk for in-hospital death. Cox proportional hazard regression confirmed that elevated serum creatinine, elevated urea nitrogen, AKI, proteinuria and hematuria was an independent risk factor for in-hospital death after adjusting for age, sex, disease severity, leukocyte count and lymphocyte count. ConclusionsThe prevalence of kidney impairment (hematuria, proteinuria and kidney dysfunction) in hospitalized COVID-19 patients was high. After adjustment for confounders, kidney impairment indicators were associated with higher risk of in-hospital death. Clinicians should increase their awareness of kidney impairment in hospitalized COVID-19 patients.

Correlation between psychological control and health risk behaviors of college students’ parents / 中国学校卫生

Objective@#To explore the characteristics of psychological control of parents of college students and their correlation with health risk behaviors, and to provide a reference for further improving parenting styles and improving the physical and mental health of college students.@*Methods@#With the method of multi-stage stratified random sampling, 3 318 college students from 6 universities in Guizhou Province were selected. The parents’ psychological control questionnaire and Chinese adolescent health-related behavior questionnaire were used to conduct anonymous field survey.@*Results@#A total of 660 students’ parents have got low score of mental control in low-score group (<26), 1 844 in the middle group (26-49) and 814 in the high group (>49). Students who had suicide plans scored higher in the dimensions of invasion of privacy, inhibition of speech expression, and sense of disability than those who had not(t=4.08, 3.74, 3.82, P<0.01); The scores of smokers in achievement expectation, invasion of privacy and ability ineffectiveness were higher than those of non-smokers(t=7.12, 3.91, 8.10, P<0.01); the scores of drinkers in all dimensions were higher than those of non drinkers(t=9.35, 4.64, 5.90, 8.78, P<0.01); the scores of Internet addicts in all dimensions were higher than those of non-smokers(t=8.92, 14.27, 3.70, 15.94, P<0.01). Spearman correlation analysis showed that smoking, drinking and Internet addiction were positively correlated with parents’ psychological control(r=0.11, 0.15, 0.19, P<0.01).@*Conclusion@#Parents’ psychological control of college students in achievement expectation, ability ineffectiveness and speech inhibition; parents’ psychological control is positively related to smoking, drinking and Internet addiction behavior. Parents should give more active encouragement and guidance to their children and strengthen communication.

Effects of high mobility group box-1 protein-nuclear factor-κB signaling pathway on autophagy and chemosensitivity of human hepatocellular carcinoma cells / 肿瘤研究与临床

Objective:To investigate the effect of high mobility group box-1 protein (HMGB1)-nuclear factor-κB (NF-κB) signaling pathway on autophagy and chemosensitivity of human hepatocellular carcinoma cells and its possible mechanism.Methods:Human hepatocellular carcinoma BEL-7402 cells were cultured in vitro and divided into control group (BEL-7402 cells without any treatment), doxorubicin group, recombinant human HMGB1+doxorubicin group, anti-HMGB1 neutralizing antibody+doxorubicin group, pyrrolidine dithiocarbamate+doxorubicin group and 3-methyladenine + doxorubicin group. The methyl thiazolyl tetrazolium (MTT) method was used to detect cell proliferation inhibition rate. Western blot method was used to detect the expressions of HMGB1 and NF-κB subunit p-p65 protein, the autophagy-related proteins Beclin-1, LC3Ⅰ, LC3Ⅱ and apoptosis-related protein bcl-2. Enzyme labeling method was used to detect Caspase-9 and Caspase-3 activity.Results:The cell proliferation inhibition rates in the control group, doxorubicin group, recombinant human HMGB1+doxorubicin group, anti-HMGB1 neutralizing antibody+doxorubicin group, pyrrolidine dithiocarbamate+doxorubicin group and 3-methyladenine+doxorubicin group were (1.31±0.16)%, (47.80±6.30)%, (31.60±5.68)%, (67.20±6.83)%, (66.60±6.27)%, and (68.60±11.19)%, respectively, and the difference was statistically significant ( F = 75.91, P < 0.01), suggesting that doxorubicin had a proliferation inhibitory effect on BEL-7402 cells; the expression levels of HMGB1 were 1.17±0.11, 1.37±0.15, 1.43±0.15, 0.70±0.09, 1.27±0.12, 1.29±0.18, and the difference was statistically significant ( F = 18.70, P < 0.01), suggesting that doxorubicin could increase the expression of HMGB1 in BEL-7402 cells, and the anti-HMGB1 neutralizing antibody could block or attenuate this effect; after pretreatment with recombinant human HMGB1, the proliferation inhibitory effect of doxorubicin on BEL-7402 cells was weakened; after pretreatment with anti-HMGB1 neutralizing antibody, pyrrolidine dithiocarbamate and 3-methyladenine, the proliferation inhibitory effect of doxorubicin on BEL-7402 cells was enhanced. Compared with the control group, the expression of p-p65 protein in the doxorubicin group, recombinant human HMGB1+doxorubicin group and 3-methyladenine+doxorubicin group increased (all P < 0.05). The expression of p-p65 protein in the recombinant human HMGB1+doxorubicin group, anti-HMGB1 neutralizing antibody+doxorubicin group and pyrrolidine dithiocarbamate+doxorubicin group was lower than that in the doxorubicin group (all P < 0.05). Compared with the control group, the expression of bcl-2 protein in doxorubicin group, anti-HMGB1 neutralizing antibody+doxorubicin group, pyrrolidine dithiocarbamate+doxorubicin group and 3-methyladenine+ doxorubicin group decreased (all P < 0.05), and the activity of Caspase-9 and Caspase-3 was enhanced (all P < 0.05); after adding recombinant human HMGB1 pretreatment, the expression of bcl-2 protein in the cells increased compared with doxorubicin alone, and the activity of Caspase-9 and Caspase-3 was weakened (all P < 0.05). The expression levels of autophagy-related protein Beclin-1 in the control group, doxorubicin group, recombinant human HMGB1+doxorubicin group, anti-HMGB1 neutralizing antibody+doxorubicin group, pyrrolidine dithiocarbamate+doxorubicin group, and 3-methyl adenine+doxorubicin group were 0.77±0.12, 0.92±0.07, 1.29±0.10, 0.51±0.03, 0.49±0.06, and 0.42±0.05, and the difference was statistically significant ( F = 97.01, P < 0.01). The expression levels of LC3Ⅱ were 0.24±0.04, 0.39±0.04, 0.49±0.07, 0.23±0.05, 0.20±0.06, and 0.20±0.05, and the difference was statistically significant ( F = 26.98, P < 0.01). Conclusion:The activation of HMGB1-NF-κB signaling pathway can reduce the chemosensitivity of hepatocellular carcinoma cells to doxorubicin, and its mechanism may be related to the regulation of autophagy and down-regulation of doxorubicin inducing apoptosis of hepatocellular carcinoma cells.

Expert consensus on microbiome sequencing and analysis / 生物工程学报

In the past ten years, the research and application of microbiome has continued to increase. The microbiome has gradually become the research focus in the fields of life science, environmental science, and medicine. Meanwhile, many countries and organizations around the world are launching their own microbiome projects and conducting a multi-faceted layout, striving to gain a strategic position in this promising field. In addition, whether it is scientific research or industrial applications, there has been a climax of research and a wave of investment and financing, accordingly, products and services related to the microbiome are constantly emerging. However, due to the rapid development of microbiome sequencing and analysis related technologies and methods, the research and application from various countries have not yet unified on the standards of technology, programs, and data. Domestic industry participants also have insufficient understanding of the microbiome. New methods, technologies, and theories have not yet been fully accepted and used. In addition, some of the existing standards and guidelines are too general with poor practicality. This not only causes obstacles in the integration of scientific research data and waste of resources, but also gives related companies unfair competition opportunity. More importantly, China still lacks national standards related to the microbiome, and the national microbiome project is still in the process of preparation. In this context, the experts and practitioners of the microbiome worked together and developed the consensus of experts. It can not only guide domestic scientific research and industrial institutions to regulate the production, learning and research of the microbiome, the application can also provide reference technical basis for the relevant national functional departments, protect the scale and standardized corporate company's interests, strengthen industry self-discipline, avoid unregulated enterprises from disrupting the market, and ultimately promote the benign development of microbiome-related industries.

Diagnostic significance of non-specific diagnostic indicators for bacterial neonatal late-onset sepsis / 中国基层医药

Objective@#To investigate the diagnostic value of non-specific diagnostic indicators for bacterial neonatal late-onset sepsis.@*Methods@#A total of 55 children with bacterial neonatal late-onset sepsis in Langfang People's Hospital were selected as sepsis group.Another 67 cases of non-infected newborns were selected as control group.White blood cell, platelet and C-reactive protein were retrospectively analyzed for diagnostic value.Meanwhile, percentage of neutrophils and mean platelet volume were analyzed for diagnostic value.@*Results@#When the bacterial neonatal late-onset sepsis occurred, the sensitivity(41.8%), specificity(95.6%) and positive predictive value(92.0%) of C-reactive protein were high.The sensitivity(18.2%, 10.9%), positive predictive value(71.4%, 85.7%) of white blood cell and platelet were low, but specificity(94%, 98.5%) was high.The percentage of neutrophils [(62.01±22.16)] and mean platelet volume[(11.60±0.98)] were higher than those of the control group [(36.58±11.06), (10.88±0.95)], and the differences were statistically significant(all P<0.05).@*Conclusion@#C-reactive protein has greater diagnostic value for bacterial neonatal late-onset sepsis.The percentage of neutrophils and mean platelet volume have some diagnostic value.

Diagnostic significance of non－specific diagnostic indicators for bacterial neonatal late－onset sepsis / 中国基层医药

Objective To investigate the diagnostic value of non －specific diagnostic indicators for bacterial neonatal late－onset sepsis.Methods A total of 55 children with bacterial neonatal late －onset sepsis in Langfang Peopleˊs Hospital were selected as sepsis group.Another 67 cases of non－infected newborns were selected as control group.White blood cell, platelet and C －reactive protein were retrospectively analyzed for diagnostic value. Meanwhile,percentage of neutrophils and mean platelet volume were analyzed for diagnostic value .Results When the bacterial neonatal late －onset sepsis occurred, the sensitivity ( 41.8%), specificity ( 95.6%) and positive predictive value(92.0%) of C －reactive protein were high.The sensitivity (18.2%,10.9%),positive predictive value(71.4%,85.7%) of white blood cell and platelet were low ,but specificity (94%,98.5%) was high.The percentage of neutrophils [(62.01 ±22.16)] and mean platelet volume [(11.60 ±0.98)] were higher than those of the control group [(36.58 ±11.06),(10.88 ±0.95)],and the differences were statistically significant ( all P＜0.05).Conclusion C－reactive protein has greater diagnostic value for bacterial neonatal late －onset sepsis.The percentage of neutrophils and mean platelet volume have some diagnostic value .