Parallel evolution and control method for predicting the effectiveness of non-pharmaceutical interventions in pandemics.

Aim: Nonpharmaceutical interventions (NPIs) are important strategies to utilize in reducing the negative systemic impact pandemic disasters have on human health. However, early on in the pandemic, the lack of prior knowledge and the rapidly changing nature of pandemics make it challenging to construct effective epidemiological models that can be used for anti-contagion decision-making. Subject and methods: Based on the parallel control and management theory (PCM) and epidemiological models, we developed a Parallel Evolution and Control Framework for Epidemics (PECFE), which can optimize epidemiological models according to the dynamic information during the evolution of pandemics. Results: The cross-application between PCM and epidemiological models enabled us to successfully construct an anti-contagion decision-making model for the early stages of COVID-19 in Wuhan, China. Using the model, we estimated the effects of gathering bans, intra-city traffic blockades, emergency hospitals, and disinfection, forecasted pandemic trends under different NPIs strategies, and analyzed specific strategies to prevent pandemic rebounds. Conclusion: The successful simulation and forecasting of the pandemic showed that the PECFE could be effective in constructing decision models during pandemic outbreaks, which is crucial for emergency management where every second counts. Supplementary Information: The online version contains supplementary material available at 10.1007/s10389-023-01843-2.

Parallel evolution and response decision method for public sentiment based on system dynamics.

Governments face difficulties in policy making in many areas such as health, food safety, and large-scale projects where public perceptions can be misplaced. For example, the adoption of the MMR vaccine has been opposed due to the publicity indicating an erroneous link between the vaccine and autism. This research proposes the "Parallel Evolution and Response Decision Framework for Public Sentiments" as a real-time decision-making method to simulate and control the public sentiment evolution mechanisms. This framework is based on the theories of Parallel Control and Management (PCM) and System Dynamics (SD) and includes four iterative steps: namely, SD modelling, simulating, optimizing, and controlling. A concrete case of an anti-nuclear mass incident that sparked public sentiment in China is introduced as a study sample to test the effectiveness of the proposed method. In addition, the results indicate the effects by adjusting the key control variables of response strategies. These variables include response time, response capacity, and transparency of the government regarding public sentiment. Furthermore, the advantages and disadvantages of the proposed method will be analyzed to determine how it can be used by policy makers in predicting public opinion and offering effective response strategies.

Tick-borne agents in rodents, China, 2004-2006.

A total of 705 rodents from 6 provinces and autonomous regions of mainland People's Republic of China were tested by PCRs for tick-borne agents (Anaplasma phagocytophilum, Borrelia burgdorferi sensu lato, spotted fever group rickettsiae, and Francisella tularensis). Infection rates were 5.5%, 6.7%, 9.1% and 5.0%, respectively. Eighteen (2.6%) rodents of 10 species were positive for 2 or 3 agents. Sequence analysis of PCR products confirmed the presence and genotypes of detected agents. These findings demonstrate that these tick-borne agents cocirculate and that a variety of rodent species may be involved in their enzootic maintenance.

[Preliminary study on the use of DNA suspension array for the identification of corneal pathogenic fungi].

OBJECTIVE: To develop a multiplex, microsphere-based DNA suspension array for the identification of important pathogenic fungi of cornea and to study the feasibility of its application in the clinical diagnosis of fungal keratitis. METHODS: Fusarium solani, Fusarium moniliforme, Fusarium oxysporum, Aspergillus fumigatus and Aspergillus flavus, which covered about 80% of pathogenic fungi of fungal keratitis, were chosen as target species of this study. Five species-specific capture probes were designed in the internal transcribed spacer (ITS) regions of ribosomal DNA and synthesized with 5' amino modifier C12 to covalently bind to different sets of fluorescent beads. Biotinylated amplicons of 5 reference strains and 42 clinical strains were generated with a pair of universal primers to yield fragments for detection. Comparison between single species detection and multiplex detection were designed, as well as detection between array and agarose gel electrophoresis (AGE). Spearman rank correlation analysis and t test were applied to evaluate the specificity, sensibility and reproducibility of suspension array. RESULTS: Five reference strains and 40 of 42 (95.2%) clinical strains were correctly identified within 3 h post-PCR amplification while 2 other clinical strains were not identified because of their high background fluorescence intensity. Positive S/B ranged from 5.6 to 13.3. There was no significant difference between respective detection and mixed detection of 5 species (t = 0.2524, P = 0.8132). The sensitivity limit for this assay was determined to be 0.94 ng PCR products. The MFI presented positive correlation with amount of PCR products (r(s) = 1.0000, P < 0.01). Coefficient variation of four repeated detections was 1.8% - 13.7%. CONCLUSION: The suspension array is a rapid, sensitive and specific method for the identification of the most important species of corneal pathogenic fungi and might be used in the clinical laboratories.

MDR1 single nucleotide polymorphism G2677T/A and haplotype are correlated with response to docetaxel-cisplatin chemotherapy in patients with non-small-cell lung cancer.

BACKGROUND: The multidrug resistance gene 1 (MDR1) encodes P-glycoprotein (P-gp), which plays an important role in mediating multidrug resistance to chemotherapeutic agents. MDR1 gene polymorphisms may have an impact on the expression and function of P-gp, thereby influencing the response to chemotherapy. OBJECTIVES: To investigate whether the MDR1 2677 and 3435 genotypes are associated with the sensitivity of non-small-cell lung cancer (NSCLC) to docetaxel. METHODS: In this study we investigated the potential association of MDR1 2677G>T at exon 21, 3435C>T at exon 26 and their haplotypes with chemotherapy response of 54 Han Chinese patients with NSCLC. The patients were treated with docetaxel-cisplatin. RESULTS: The 2677 GG genotype was associated with a significantly better response to chemotherapy compared with the combined 2677 GT and TT genotype (p = 0.035). The 3435 CC genotype was also associated with a better response to chemotherapy compared with the combined 3435 CT and TT genotypes although the difference was not statistically significant (p = 0.123). Moreover, patients harboring the 2677G-3435C haplotype had a statistically significant better response to chemotherapy compared with those with the other haplotypes combined (p = 0.015). CONCLUSION: Our findings suggest that the MDR1 2677G>T/A polymorphism and the 2677G-3435C haplotype are predictors of treatment response to docetaxel-cisplatin chemotherapy in NSCLC patients.

MDR1 single nucleotide polymorphisms predict response to vinorelbine-based chemotherapy in patients with non-small cell lung cancer.

BACKGROUND: The polymorphisms of genes participate in metabolism and transport, and therefore may have an impact on the response to vinorelbine. OBJECTIVES: To investigate whether genotypes of CYP3A5, MDR1 and cyclooxygenase-2 (COX-2) are associated with the response to vinorelbine in non-small cell lung cancers (NSCLC). METHODS: We determined the genotypes of CYP3A5(*3), MDR1 (2677G-->T at exon 21 and 3435C-->T at exon 26 and their haplotypes) and COX-2 (-1195G-->A) polymorphisms by PCR-RFLP and chemotherapy response in 69 Chinese Han patients with NSCLC who received a combination chemotherapy of vinorelbine-cisplatin (VC). The chi(2) test was used to investigate potential associations between genotypes and response to chemotherapy. Odds ratios and 95% confidence intervals were calculated. RESULTS: The 3435 CC genotype was associated with a significantly better chemotherapy response compared with the combined 3435 CT and TT genotypes (p = 0.025). The 2677 GG genotype was also associated with a better chemotherapy response compared with the combined 2677 GT and TT genotype, although it was not statistically significant. Moreover, we analyzed the haplotypes of MDR1 3435-2677: patients harboring the 2677G-3435C haplotype had a statistically significantly better response to chemotherapy compared with those with the other haplotypes combined (p = 0.015). CYP3A5*3 is not likely to correlate with sensitivity to vinorelbine in NSCLC. COX-2 (-1195G) is likely to result in a better response to vinorelbine (nonsignificant). CONCLUSIONS: Our findings suggest that MDR1 2677G-->T/A and 3435C-->T polymorphisms can be used to predict treatment response to VC chemotherapy in NSCLC patients.

[Investigation on Anaplasma phagocytophilum infection in rodents from forest areas in northeastern China].

OBJECTIVE: To investigate the prevalence of Anaplasma phagocytophilum in rodents from forest areas in northeastern China. METHODS: PCR amplification, followed by sequence analysis was carried out. The sequences of 16S rRNA and gltA gene fragment amplified from rodent specimens were compared with corresponding part of the sequences deposited in GenBank. RESULTS: A total number of 276 rodents were tested, including 102 in Jilin province, 61 in Helongjiang province and 113 in Inner Mongolia autonomous region. The positive rates were 8.82%, 1.64% and 0.00%, respectively. The infection rate in rodents infected by ticks was 11.30 times higher than that in rodents without ticks (P = 0.002). The S. A. phagocytophilum 16S rRNA sequences from rodents in Jilin and Heilongjiang were identical and differed in 3-5 bases compared with the corresponding parts of A. phagocytophilum from America, Sweden and Japan. Compared with the sequences registered in GenBank, the nucleotide sequence of gltA varied from 87%-97% and its deduced amino acid sequence changed from 84%-99%. CONCLUSION: A. phagocytophilum infection was presented in rodents from Jilin and Heilongjiang province.

CYP450 polymorphisms predict clinic outcomes to vinorelbine-based chemotherapy in patients with non-small-cell lung cancer.

CYP2C19*2(G681A), CYP2C19*3(G636A), CYP2D6*4(C188T), CYP2D6*2(C2938T, G4268C), CYP3AP1*3- G44A and CYP3A5*3(A22893G) are the most common polymorphisms detected among Chinese that may influence the efficacy of vinorelbine-based therapies to treat non-small-cell lung cancer (NSCLC). We detected the genotypes of these polymorphisms by PCR-RFLP in 59 patients with NSCLC and assessed their responses to vinorelbine. CYP2D6*4(C188T), CYP3AP1*3 (G -44 A) and CYP3A5*3 were found to be associated with response to vinorelbine. For the 2D6*4 polymorphism, the 18 of 32 (56.25%) patients with homozygous (C/C) responded to this therapy, while 6 of 27 (22.22%) of those heterozygous (C/T) at this site responded. (chi2=5.68, p < 0.05) For the 3AP1*1/*3 polymorphism, 12 of 42 (28.57%) patients with homozygous (A/A) responded, while 12 of 17 (70.59%) with heterozygous (A/G) and homozygous (G/G) responded (chi2=7.19, p < 0.01). CYP3A5*3 polymorphism has a result corresponding to 3AP1*3 polymorphism. Other polymorphisms were not associated with response to vinorelbine. No significant difference in toxicity and survival was observed according to SNP genotype.

[Study on the coinfection status of Borrelia burgdorferi sensu lato and spotted fever group Rickettsia in ticks from Hunchun, Jilin province].

OBJECTIVE: To understand the coinfection status of Borrelia burgdorferi sensu lato (B.b.s.l) and spotted fever group Rickettsia (SFGR) in Hunchun of Jilin province, China. METHODS: Polymerase chain reaction (PCR) was used to detect the 5S-23S rRNA intergenic spacer of B. b. s. l and ompA of SFGR in ticks was collected in Hunchun,Jilin province. The amplification products of positive ticks were sequenced, and phylogenetic analysis was conducted by PHYLIP software package. RESULTS: The infection rate of B. b. s. l was 36.0% in Ixodes persulcatus ticks and the SFGR was discovered in I. persulcatus ticks,with an infection rate of 2.0%. The coinfection rate of both agents was 2.0%. In 327 Dermacentor siltarum ticks, the positive rates of B. b. s. l and SFGR were 30.9% and 29.1% respectively. 55 ticks (16.8%) were coinfected with the two pathogens. The sequence analysis of B. b. s. l showed that the B. b. s. l in Jilin area, which were highly homologous, all belonged to B. garinii genotypes. The sequence analysis of SFGR positive products showed that the DNA secquence of the newly detected agent (JL-95) was close to the two previously described rickettsiae which were detected in I. ricinus from Slovakia (called IRS3 and IRS4). Phylogenetic relationships inferred from the comparison of these sequences with those of other genus Rickettsiae indicated that JL-95, IRS3 and IRS4 constituted a new rickettsial genotype and formed a separate cluster among the spotted fever group Rickettsiae. CONCLUSION: Coinfection of B. b. s. l and SFGR existed in Hunchun, Jilin province. The sequencing of specific fragment confirmed a new SFGR which was different from other rickettsiae known in China.

Effects of aspirin on metastasis-associated gene expression detected by cDNA microarray.

AIM: To investigate the effect of aspirin on the metastasis-associated gene expression in 3AO ovarian cancer cells. METHODS: 3AO cells were treated with aspirin at the concentration of 1.2 mmol/L for 16 and 48 h, respectively. The total RNA was extracted with Trizol reagents and reverse transcribed with Superscript II and hybridized with cDNA microarray (containing oncogenes, tumor suppressor genes, signal transduction pathway molecules, adhesive molecules, growth factors and ESTs) fabricated in our lab. After normalization, the ratio of gene expression of aspirin treated to untreated 3AO cells being either 2 fold up higher or 0.5 fold down (lower) were defined as differential expression. Semi-quantitative RT-PCR was used to validate the microarray results. RESULTS: Among the 447 metastasis-associated genes, 4 genes were up-regulated and 14 genes were down-regulated in 3AO cells treated with aspirin for 16 h compared with untreated cells. While 24 genes were up-regulated and 10 genes were down-regulated in cells treated with aspirin for 48 h. Several up or down-regulated gene expression changes continued from 16 h to 48 h. CONCLUSION: Aspirin might exert its anti-metastasis effects on ovarian cancer by affecting metastasis-associated gene expression.

[rpsL gene analysis associated with Streptomycin resistance in Mycobacterium tuberculosis].

The mutation of the rpsL gene in Mycobacterium tuberculosis (M.TB) is related to Streptomycin resistance. In this experiment, 77 TB strains obtained in hospital were selected, the routine drug susceptibility test was done by using BACIEC460 system, meanwhile the TB-rspL gene was amplicated by PCR, and analyzed by SSCP, RFLP and sequence analysis. There are 20 strains sensitive to SM and 57 strains resistant to it in routine drug susceptibility test. The SSCP result displayed that 34 strains were rspL gene wild type and 43 strains were mutant type. Compared with routine drug susceptibility test, the specificity was 95% and the positive anticipate value was 98%. RFLP cut by MobII displayed that 81.4% of mutation happened in codon 43 of TB-rspL. Sequence analysis displayed that there was single base mutation in codon 43(AAG-->AGG). In conclusion, Drug resistance of TB to SM is related to rspL gene mutation and the mutation in codon 43 is the most common cause.