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Background: Health technology assessment has been increasingly used in China, having been legally mandated in 2019, to inform reimbursement decisions and price negotiations between the National Healthcare Security Administration and pharmaceutical companies around the price of new pharmaceuticals. The criteria currently used to judge cost effectiveness and inform pricing negotiations, 3 × GDP per capita, is based on the rule of thumb previously recommended by the World Health Organization rather than an estimate based on an empirical assessment of health opportunity costs. Objective: The objective of this study was to inform a cost-effectiveness threshold for health technology assessment in China that accounts for health opportunity cost. Methods: The elasticity of health outcomes with respect to health expenditure was estimated using variations across 30 provincial-level administrative divisions in 2017 controlling for a range of other factors and using an instrumental variable approach to account for endogeneity to assess robustness of results. The estimated elasticity was then used to calculate the cost per disability-adjusted life-year (DALY) averted by variations in Chinese health expenditure at the margin. Results: The range estimated from this study, 27,923–52,247 (2017 RMB) (central estimate 37,446) per DALY averted or 47–88% of GDP per capita (central estimate 63%), shows that a cost per DALY averted cost-effectiveness threshold that reflects health opportunity costs is below 1 × GDP per capita. Conclusion: Our results suggest that the current cost-effectiveness threshold used in China is too high; continuing to use it risks decisions that reduce overall population health. [ABSTRACT FROM AUTHOR]

Stereotactic body radiotherapy (SBRT) is a novel noninvasive treatment for hepatocellular carcinoma. SBRT can achieve effective local control, but it requires a relatively high input of resources; this systematic review was performed to assess the cost effectiveness of SBRT in the treatment of hepatocellular carcinoma to provide a basis for government pricing and medical insurance decision-making. The PubMed, EMBASE, Cochrane Library, CNKI, Wanfang and SinoMed databases were searched to collect economic evaluations of SBRT for the treatment of hepatocellular carcinoma from the date of database inception through December 31, 2018. Two reviewers independently screened the studies, extracted the data and performed a descriptive analysis of the basic characteristics, methods of economic evaluation and main results, as well as the quality and heterogeneity of the reports. A total of 5 studies were included. Among them, the level of heterogeneity was relatively acceptable, with a median score of 90%. Four studies were cost-utility analyses (CUAs), and 1 was a cost-effectiveness analysis (CEA). The incremental cost effectiveness ratio (ICER) for sorafenib compared to SBRT was US $114,795 per quality-adjusted life year gained (cost/QALY) in patients with advanced hepatocellular carcinoma. The ICER for proton beam therapy compared to SBRT was US $6465 in patients with inoperable advanced hepatocellular carcinoma. The ICER for SBRT compared to RFA was US $164,660 for patients with unresectable colorectal cancer (CRC) with liver metastases and US $56,301 for patients with early-stage hepatocellular carcinoma. For patients with inoperable localized hepatocellular carcinoma, compared with RFA–SBRT therapy, the ICERs for SBRT–SBRT and SBRT–RFA were US $558,679 and US $2197,000, respectively; RFA–RFA was dominated. In conclusion, there is limited evidence suggesting that SBRT could be cost-effective for highly specific subpopulations of HCC patients, and further economic evaluations based on randomized controlled trials (RCTs) or cohort studies are needed. [ABSTRACT FROM AUTHOR]

Two new strontium tin hydroxy polyselenides [Sr2Sn(OH)6(H2O)6]Se4 ( 1) and [Sr2Sn(OH)6(H2O)5]Se3 ·H2O ( 2) were synthesized from hydrothermal reactions. Their structures were determined from single-crystal X-ray data measured at 218 K. Compound 1 crystallized in the space group P $\bar{1}$ with a = 5.935(1), b = 8.440(1), c = 9.464(2) Å, α = 97.292(2)°, β = 104.957(2)°, γ = 110.328(2)°. Compound 2 crystallized also in the space group P $\bar{1}$ with a = 10.658(2), b = 11.082(2), c = 15.797(2) Å, α = 73.303(4)°, β = 74.942(4)°, γ = 64.627(3)°. Both compounds have structures containing infinite cationic layers of hydrated metal hydroxides built from Sn(OH)6 octahedra and Sr(OH, H2O) n polyhedra. Molecular Se42- and Se32- anions are located in the interlayer spaces of 1 and 2, respectively. The Se42- anions of 1 adopt a flat zigzag conformation with a torsion angle of 0°. [ABSTRACT FROM AUTHOR]

Presents an analysis combining the orthogonal expansion method and Galerkin method for the higher order Eigenmodes in a circular-rectangular waveguide. Cross section of the coaxial waveguide; Propagation coefficient; Imaginary boundary.

Background: The maintenance treatment of ESRD puts a great burden on individual patients, society, and the country of China as a whole. Hemoperfusion plus hemodialysis (HP + HD) in ESRD patients can yield modified outcomes such as prolonged life expectancy and improved dialysis quality and quality of life. This study aimed to systematically analyze the effect of HP + HD on the overall survival (OS) rates of ESRD patients and to provide support for clinical decision-making. Methods: A computerized search was performed in the PubMed, Embase, Cochrane Library, CNKI, WanFang Data and SinoMed databases for relevant original research articles. Studies were included or excluded based on their compliance with predefined selection criteria. Results: Twelve studies were included in the qualitative synthesis and quantitative synthesis (meta-analysis). The meta-analysis showed that the 1-year OS rate (odds ratio [OR]: 3.35, 95% CI: 1.89, 5.91, p < 0.05), 2-year OS rate (OR: 2.88, 95% CI: 1.84, 4.53, p < 0.05), and 5-year OS rate (χ2 = 4.3092, p < 0.05) of patients with ESRD treated with HP + HD were better than those treated with HD, but there was no significant difference in 3-year OS rate (OR: 1.97, 95% CI: 0.76, 5.06, p > 0.05). Subgroup analysis showed the same outcomes in different study designs (1-year OS rate: randomized controlled trials [RCTs]: OR: 4.38, 95% CI: 1.61, 11.88, p < 0.05; cohort studies: OR: 2.90, 95% CI: 1.44, 5.85, p < 0.05; 2-year OS rate: RCTs: OR: 2.99, 95% CI: 1.84, 4.84, p < 0.05) and different age-groups (1-year OS rate: 45–50 years: OR: 3.19, 95% CI: 1.55, 6.57, p < 0.05; 55–60 years: OR: 3.37, 95% CI: 1.07, 10.61, p < 0.05; 2-year OS rate: 50–55 years: OR: 2.86, 95% CI: 1.59, 5.16, p < 0.05: 60–65 years: OR: 4.41, 95% CI: 1.19, 16.30, p < 0.05). Conclusions: This meta-analysis suggests that the OS rates of ESRD patients treated with HP + HD were better than those of patients treated with HD. A speculative hypothesis for why this is the case may be that HP + HD can achieve the complementary elimination of metabolites, effectively preventing and treating complications caused by long-term dialysis and prolonging life expectancy. Therefore, HP + HD should be widely used in ESRD patients. [ABSTRACT FROM AUTHOR]

Background: In October 2015, China's one-child policy was universally replaced by a so-called two-child policy. This study investigated the association between the enactment of the new policy and changes in the number of births, and health-related birth outcomes.Methods: We used difference-in-difference model to analyse the birth record data in Pudong New Area, Shanghai.The design is descriptive before-and-after comparative study.Results: The data covered three policy periods: the one-child policy period (January 2008 to November 2014); the partial two-child policy period (December 2014 to June 2016); the universal two-child policy period (July 2016 to December 2017). There was an estimate of 7656 additional births during the 18 months of the implementation of the universal two-child policy. The trend of monthly percentage of births to mothers aged ≥35 increased by 0.24 percentage points (95% confidence interval 0.19 to 0.28, p < 0.001) during the same period. Being a baby boy, preterm birth, low birth weight, parents with lower educational attainment, and assisted delivery were associated with a higher risk of birth defects.Conclusions: The universal two-child policy was associated with an increase in the number of births and maternal age. Preterm birth, low birth weight, and assisted delivery were associated with a higher risk of birth defects, which suggested that these infants needed additional attention in the future. [ABSTRACT FROM AUTHOR]

Importance: Innovative nuclear medicine services offer substantial clinical value to patients. However, these advancements often come with high costs. Traditional payment strategies do not incentivize medical institutes to provide new services nor determine the fair price for payers. A shift towards a value-based pricing strategy is imperative to address these challenges. Such a strategy would reconcile the cost of innovation with incentives, foster transparent allocation of healthcare resources, and expedite the accessibility of essential medical services. Objective: This study aims to develop and present a comprehensive, value-based pricing model for new nuclear medicine services, illustrated explicitly through a case study of the radium [223Ra] treatment for bone metastases. In constructing the pricing model, we have considered three primary value determinants: the cost of the new service, associated service risk, and the difficulty of the service provision. Our research can help healthcare leaders design an evidence-based Fee-For-Service (FFS) payment reference pricing with nuclear medicine services and price adjustments. Design, setting and participants: This multi-center study was conducted from March 2021 to February 2022 (including consultation meetings) and employed both qualitative and quantitative methodologies. We organized focus group consultations with physicians from nuclear medicine departments in Beijing, Chongqing, Guangzhou, and Shanghai to standardize the treatment process for radium [223Ra] bone metastases. We used a specially designed 'Radium Nuclide [223Ra] Bone Metastasis Data Collection Form' to gather nationwide resource consumption data to extract information from local databases. Four interviews with groups of experts were conducted to determine the add-up ratio, based on service risk and difficulty. The study organized consultation meeting with key stakeholders, including policymakers, service providers, clinical researchers, and health economists, to finalize the pricing equation and the pricing result of radium [223Ra] bone metastases service. Main outcomes and measures: We developed and detailed a pricing equation tailored for innovative services in the nuclear medicine department, illustrating its application through a step-by-step guide. A standardized service process was established to ensure consistency and accuracy. Adhering to best practice guidelines for health cost data analysis, we emphasized the importance of cross-validation of data, where validated data demonstrated less variation. However, it required a more advanced health information system to manage and analyze the data inputs effectively. Results: The standardized service of radium [223Ra] bone metastases includes: pre-injection assessment, treatment plan, administration, post-administration monitoring, waste disposal and monitoring. The average duration for each stage is 104 min, 39 min, 25 min, 72 min and 56 min. A standardized monetary value for medical consumables is 54.94 yuan ($7.6), and the standardised monetary value (medical consumables cost plus human input) is 763.68 yuan ($109.9). Applying an agreed value add-up ratio of 1.065, the standardized value is 810.19 yuan ($116.9). Feedback from a consultation meeting with policymakers and health economics researchers indicates a consensus that the pricing equation developed was reasonable and well-grounded. Conclusion: This research is the first study in the field of nuclear medicine department pricing methodology. We introduce a comprehensive value-based nuclear medical service pricing method and use radium[223Ra] bone metastases treatment pricing in China as a case study. This study establishes a novel pricing framework and provides practical instructions on its implementation in a real-world healthcare setting. [ABSTRACT FROM AUTHOR]

Background: Stereotactic body radiotherapy (SBRT) is a novel radio-therapeutic technique that has recently emerged as standard-of-care treatment for medically inoperable, early-stage non-small cell lung cancer (NSCLC). In this study, we compared the cost-effectiveness of SBRT with that of conventional fractionated radiotherapy (CFRT) in patients with medically inoperable, early-stage NSCLC from the perspective of the Chinese health system. Methods: A Markov model was developed to describe health states of patients after treatment with SBRT and CFRT. The recurrence risks, treatment toxicities, and utilities inputs were obtained from the literature. The costs were based on listed prices and real-world evidence. A simulation was conducted to determine the post-treatment lifetime years. For each treatment, the total costs, quality-adjusted life-years (QALYs), and incremental cost-effectiveness ratios (ICERs) per QALY were calculated. Deterministic and probabilistic sensitivity analyses were performed to assess the uncertainty of the model parameters. Results: In the base case analysis, SBRT was associated with a mean cost of USD16,933 and 2.05 QALYs, whereas CFRT was associated with a mean cost of USD17,726 and 1.61 QALYs. SBRT is a more cost-effective strategy compared with CFRT for medically inoperable, early-stage NSCLC, with USD 1802 is saved for every incremental QALY. This result was validated by DSA and PSA, in which SBRT remained the most cost-effective option. Conclusions: The findings suggested that, compared to CFRT, SBRT may be considered a more cost-effective strategy for medically inoperable, early-stage NSCLC. [ABSTRACT FROM AUTHOR]

Background: In light of the limited availability of healthcare resources, providing universal access to healthcare is a challenging task. As a result, prioritizing healthcare services has emerged as a crucial issue. This study aims to explore the preferences of the public regarding healthcare prioritization for rare and common diseases. By examining public attitudes, this study seeks to inform government decisions concerning resource allocation and distribution within healthcare.Methods: "Social preference" and "rare disease" were searched as MeSH terms in the electronic databases of Ovid Medline, Web of Science, Embase, and Econlit for articles published since their establishment, and the information on the characteristics of the articles and the results of social preferences for rare diseases were analyzed and summarized.Results: The public held predominantly neutral views on the setting of healthcare priorities for rare and common diseases. The results of the included studies showed that with all else being equal, no social preference for rarity was found, but when the public considered the proportional advantage of rare diseases or when the respondents were young, a social preference for rarity existed. In addition, the public weighed attributes such as the health benefits of treatments, the effectiveness of treatment options, the safety of treatment, equity, unmet needs, and disease severity in the process of setting of treatment priorities for rare diseases. Furthermore, in consideration of equity, the public showed a willingness to pay for rare diseases in spite of the high medical costs.Conclusion: International studies on social preferences provide some evidence for the setting of healthcare priorities for rare diseases, and health policymakers should consider social preferences in an integrated manner in order to set healthcare priorities appropriately. [ABSTRACT FROM AUTHOR]

The new compound [Sr2Sn(OH)6(H2O)6]Se4 (I) is synthesized by hydrothermal reaction of Sn, Se, Sr(OH)2, and LiOH·H2O in water (autoclave, 220 °C, 2 d; 40% yield). [ABSTRACT FROM AUTHOR]

In order to study the similarities and differences of physical-chemical properties of collagens from different parts of the fish body, acid-soluble collagens and pepsin-soluble collagens were isolated from skin, scale, and bone of grass carp (Ctenopharyngodon idellus), with yields ranging from 0.7 to 25.5% on the basis of dry weight. The content of acid-soluble collagen in skin and scale was much higher than that in bone according to the data of extraction yield. Collagens from grass carp have similar amino acid composition, protein patterns, and sequences of primary structure. Thermal transition temperatures of collagens from different parts of grass carp body decreased in the order of bone > skin > scale. The pepsin-soluble collagens showed more resistance to collagenase, compared to acid-soluble collagens extracted from the same part of the grass carp body. All grass carp collagens did not induce a significant cytotoxic effect according to the results ofin vitrocytotoxicity test. [ABSTRACT FROM PUBLISHER]

Objectives: Movement restriction policies (MRPs) are effective in preventing/delaying COVID-19 transmission but are associated with high societal cost. This study aims to estimate the health burden of the first wave of COVID-19 in China and the cost-effectiveness of early versus late implementation of MRPs to inform preparation for future waves.Methods: The SEIR (susceptible, exposed, infectious, and recovered) modeling framework was adapted to simulate the health and cost outcomes of initiating MRPs at different times: rapid implementation (January 23, the real-world scenario), delayed by 1 week, delayed by 2 weeks, and delayed by 4 weeks. The end point was set as the day when newly confirmed cases reached zero. Two costing perspectives were adopted: healthcare and societal. Input data were obtained from official statistics and published literature. The primary outcomes were disability-adjusted life-years, cost, and net monetary benefit. Costs were reported in both Chinese renminbi (RMB) and US dollars (USD) at 2019 values.Results: The first wave of COVID-19 in China resulted in 38 348 disability adjusted life-years lost (95% CI 19 417-64 130) and 2639 billion RMB losses (95% CI 1347-4688). The rapid implementation strategy dominated all other delayed strategies. This conclusion was robust to all scenarios tested. At a willingness-to-pay threshold of 70 892 RMB (the national annual GDP per capita) per disability-adjusted life-year saved, the probability for the rapid implementation to be the optimal strategy was 96%.Conclusions: Early implementation of MRPs in response to COVID-19 reduced both the health burden and societal cost and thus should be used for future waves of COVID-19. [ABSTRACT FROM AUTHOR]

In this study, fibrillogenesis and thermal dissociation of pepsin-soluble collagen ( PSC ), extracted from snakehead ( Channa argus ) skin, were monitored by fluorescence method based on thioflavin T (Th-T), where the accuracy and sensitivity were evaluated and compared with those of turbidity assay. The fluorescence method revealed the fibrillogenesis dynamics of collagen with better sensitivity, especially at nucleation and plateau stages. The melting temperature ( T m ) of PSC was estimated to be 47 °C by circular dichroism spectroscopy; below this temperature, the triple-helical structure should be intact. After that, the dynamic process of collagen dissociation was explored by the fluorescence method, and verified by morphological analysis of the fibrils and the proportion of retained fibrils. The thermal dissociation critical temperature (TDCT) of PSC fibrils was confirmed to be 39 °C. The fluorescence intensity of fibril-incorporated Th-T gradually decreases in the dissociation process, and the decrease rate can be accelerated by increasing temperature. Finally, the thermal stability of triple-helical structures of free-, assembled- and dissociated- PSC was compared. Thus, we demonstrated the formation and thermal dissociation of collagen fibrils in vitro by a fluorescence method based on Th-T. This approach may advance the understanding of fibril formation and inverse dissociation of fish-sourced collagen in vitro . [ABSTRACT FROM AUTHOR]

Controlling the fibril-formation process of collagen in vitro to fabricate novel biomaterials is a new area in the field of collagen research. This study aimed to determine the effect of ultrasonication on collagen fibril formation and the properties of the resulting collagen gels. Native collagen, extracted from the skin of grass carp, self-assembled under ultrasonic conditions (at different ultrasonic power and duration). The self-assembly kinetics, fibrillar morphology, and physical and cell growth-promoting properties of the collagen gels were analyzed and compared. The results showed that the self-assembly rate of collagen was increased by ultrasonication at the nucleation stage. The resulting fibrils exhibited smaller diameters and D-periodicity lengths than that of the untreated collagen samples ( p < 0.05). The viscoelasticity and textural properties of collagen gels also changed after ultrasonication at the nucleation stage. Texture profile analysis and cell proliferation assays showed that ultrasonication produced softer collagen gel colloids, which were more suitable for cell proliferation than the untreated collagen gels. [ABSTRACT FROM AUTHOR]

Capsule null locus ( cnl ) strains, one type of specific unencapsulated Neisseria spp., only have regions D and E of the capsule gene cluster which encodes the genes for capsule biosynthesis, modification, and transportation. Compared with encapsulated strains, regions A and C of cnl strains have been replaced by 113 or 114 bp conserved non-coding sequences. Cnl strains include multiple clonal complexes (CC). According to previous studies, CC198 is the major clonal lineage in both cnl patients and healthy cnl carriers. We hypothesized that CC198 possesses different genome characteristics compared with other cnl strains. In this study, we obtained the draft genomes of two CC198 strains from healthy carriers. Using 75071 single nucleotide polymorphisms located in 1163 core genes, we constructed the phylogenetic relationships between a batch of representative Neisseria meningitidis genomes. CC198 and CC1136 clustered together, but apart from other N. meningitidis strains including CC53. We also aligned the sequences of genes located in regions D and E of the capsule gene locus from encapsulated and unencapsulated strains. A number of possible recombination events were identified in the galE and tex genes between different serogroups of encapsulated N. meningitidis and CC53 strains, especially in tex . In contrast, there is almost no recombination in N. meningitidis CC198 strains. These results showed that CC198 belongs to a phylogenetically distinct group within the species N. meningitidis , which may be directly derived from the cnl -type ancestor of N. meningitidis . The encapsulated strains may acquire other necessary genes for capsule formation by horizontal transfer. [ABSTRACT FROM AUTHOR]

BACKGROUND The molecular configuration, molecular weight distribution and thermal transition enthalpy (Δ H) of grass carp skin ( GCS) collagens after heat treatment under different conditions were measured using circular dichroism, gel filtration chromatography and differential scanning calorimetry ( DSC). The enzymatic stability of collagen was evaluated using different enzymes, while the ability to form fibrils in vitro was assessed by morphological observation of collagen fibrils and turbidity testing. RESULTS The Δ H values, in-solution molecular aggregation and the stability to enzymatic hydrolysis of GCS collagen decreased irreversibly and progressively with the duration of heat treatment at 33 °C, which was the onset endothermic temperature obtained from the DSC curve. A strong positive linear correlation between the enzymatic sensitivity of collagen and the degree of thermal denaturation was found. A decrease in fibril diameter and D-periodicity length with denaturation could also be observed in the SEM and TEM images. CONCLUSION The onset endothermic temperature ( To) rather than the denaturation temperature ( Td) is the threshold temperature for configurational stability of GCS collagen in acidic solution, and the biological properties would obviously change if the collagen was heat treated at this temperature. © 2014 Society of Chemical Industry [ABSTRACT FROM AUTHOR]

The extreme environment of space could affect microbial behavior and may increase the risk of infectious disease during spaceflight. However, the molecular genetic changes of methicillin-resistant Staphylococcus aureus (MRSA) in response to the spaceflight environment have not been fully clarified. In the present study, we determined the draft genome sequences for an ancestral S. aureus strain (LCT-SAO) isolated from a clinical sample and three derivative strains, LCT-SAS, LCT-SAM and LCT-SAG, cultured in parallel during the spaceflight Shenzhou-X, under simulated microgravity and on the ground, respectively. To evaluate the impact of short-term spaceflight on the MRSA strains, comparative genomic analysis was implemented. Genome-based mapping of toxin genes and antibiotic resistance genes confirmed that these strains have the conventional pathogenicity and resistance to drugs, as none of the strains showed significant changes in these regions after culturing in the three different environments; this result suggests that spaceflight may not change bacterial virulence or drug resistance. Thirty-nine strain-specific sequence variants (SVs) were identified throughout the genomes, and the three derivatives exhibited almost the same mutation rates. Fifty-nine percent of SVs were located in the intergenic regions of the genomes, indicating that S. aureus may have an extremely robust repair mechanism responsible for recognizing and repairing DNA replication mismatches. It is noteworthy that strain LCT-SAS, cultured in space, presented the most unique SVs ( n = 9) and shared the fewest SVs with LCT-SAM ( n = 5) and LCT-SAG ( n = 4). Furthermore, we identified 10 potential deletion regions and 2 potential insertion regions, with LCT-SAS appearing more fragile than other strains by this measure. These results suggest that the environment of space is inherently complicated, with multiple variables, and cannot be simulated in a simple manner. Our results represent the first analysis of nucleotide structure variation of S. aureus strains in a spaceflight environment and also provide a valuable insight for understanding the mutation strategies of MRSA on earth. [ABSTRACT FROM AUTHOR]

Chromosomal integron (CI) arrays in Vibrio spp. are generally large and display great variation. Here we determined the sequence of CI array in a toxigenic O139 V ibrio cholerae strain and compared it with the arrays from the genome of different O1 biotypes available in GenBank. Then PCR scanning was used to determine the CI array variations in 83 epidemic O139 strains and subsequently these variations were compared with that found in toxigenic O1 El Tor strains in our previous work. Few differences were observed in the cohort of toxigenic O139 strains compared to the toxigenic O1 El Tor strains. On the basis of CI arrays, the toxigenic O1 El Tor and O139 strains isolated concurrently in recent years appear to be more similar to each other than to the O1 strains isolated in previous decades, suggesting a closer evolutionary relationship between them. Comparison of CI arrays in toxigenic O1 El Tor and O139 V. cholerae strains isolated between 1961 and 2009 revealed a purifying trend in the CI arrays in the chronological order during the seventh pandemic. [ABSTRACT FROM AUTHOR]

Abstract: Interpretation of 16S rRNA sequences is a difficult problem faced by clinical microbiologists and technicians. In this study, we evaluated the updated 16SpathDB 2.0 database, using 689 16S rRNA sequences from 689 complete genomes of medically important bacteria. Among these 689 16S rRNA sequences, none was wrongly identified, with 35.8% reported as a single bacterial species having >98% identity with the query sequence (category 1), 63.9% reported as more than 1 bacterial species having >98% identity with the query sequence (category 2), 0.3% reported to the genus level (category 3), and none reported as no match (category 4). For the 16S rRNA sequences of non-duplicated bacterial species reported as category 1 or 2, the percentage of bacterial species reported as category 1 was significantly higher for anaerobic Gram-positive/Gram-negative bacteria than aerobic/facultative anaerobic Gram-positive/Gram-negative bacteria. 16SpathDB 2.0 is a user-friendly and accurate database for 16S rRNA sequence interpretation in clinical laboratories. [Copyright &y& Elsevier]

Host immune pressure and associated immune evasion of pathogenic bacteria are key features of host-pathogen co-evolution. A previous study showed that human T-cell epitopes of Mycobacterium tuberculosis are evolutionarily hyperconserved and thus it was deduced that M. tuberculosis lacks antigenic variation and immune evasion. Here, we selected 173 clinical M. tuberculosis complex (MTBC) isolates from China, amplified the genes encoding Rv2945c and Rv0309, and compared the sequences. The results showed that genetic diversity existed in these two genes among the MTBC strains and two single nucleotide polymorphisms (SNPs) presented higher polymorphisms. Antigen Rv2945c harbored a higher number of amino acid substitutions of its T-cell epitopes, which may reflect ongoing immune evasion. In addition, the high dN/ dS value of Rv0309 suggested antigen Rv0309 might be involved in diversifying selection to evade host immunity. Finally, a small group of strains were identified based on the genetic diversity of these two genes, which might indicate that they interact differently with human T cells compared with other strains. [ABSTRACT FROM AUTHOR]

Highlights: [•] 64 SNPs were used to type 325 Chinese O157:H7 isolates into 5 SNP genotypes (SGs). [•] SG-1 was further divided into 2 subtypes with SG-1.1 subtype associated with the 1999 Xuzhou outbreak. [•] The most potent stx 2 subtype, stx 2a , is only carried by SG-1 which caused the Xuzhou outbreak. [•] Parallel spread of a limited number of SGs in China. [Copyright &y& Elsevier]

Escherichia coli O157:H7 is an important food-borne pathogen that can cause hemorrhagic colitis and hemolytic-uremic syndrome in humans. pO157_Sal, a novel conjugative plasmid is present in a Chinese O157:H7 outbreak strain Xuzhou21. Here we investigated the phenotypic and transcriptional differences between the wild type strain Xuzhou21 and the pO157_Sal cured mutant strain Xuzhou21m. RNA-Seq analysis found that all 52 ORFs encoded on pO157_Sal were transcribed. One hundred and sixty eight chromosomal and pO157 genes were differentially expressed (≥2 fold difference) between Xuzhou21 and Xuzhou21m. Sixty-seven and 101 genes were up-regulated and down-regulated respectively by pO157_Sal including genes related to stress response, adaption and virulence. The plasmid-cured mutant Xuzhou21m grew slower than wild type Xuzhou21 and pO157_Sal plasmid complemented strain Xuzhou21c in M9 medium under the condition of high NaCl or presence of sodium deoxycholate (NaDC), corroborating with the RNA-Seq data. Seven differentially expressed genes are associated with NaDC resistance, including the adenine-specific DNA-methyltransferase gene (dam), multidrug efflux system subunit gene mdtA, hyperosmotically inducible periplasmic protein gene osmY and oxidation-reduction related genes while two differentially expressed genes (osmY and pspD) are likely to be related to resistance to osmotic pressure. A number of differentially expressed genes were virulence associated including four genes encoding T3SS effectors from the chromosome and ehxD from pO157. Through complementation of Xuzhou21m with a plasmid construct carrying the pO157_Sal hha homolog we further showed that the pO157_Sal hha represses the expression of T3SS effectors. These findings demonstrated that the plasmid pO157_Sal affects the transcription of the chromosomal and pO157 plasmid genes and contributes to the enhanced ability to resist stress. We conclude that pO157_Sal plays an important role in regulating global gene expression and affects the virulence and adaptation of E. coli O157:H7. [ABSTRACT FROM AUTHOR]

Background: Drinking water quality for children should be higher than adults due to both behavioral and physiological factors. Thus, to provide enough, safe, and easily accessible drinking water for children at schools, the Shanghai Municipal Government initiated a direct-drinking water project in 2013. However, there has been no study so far to assess the quality of direct-drinking water or to investigate its risk factors in Shanghai elementary and middle schools.Methods: In the present study, we selected direct-drinking water equipment from 183 elementary and middle schools (17% of total) in Shanghai to detect the colony-forming units (CFU), residual chlorine, chemical oxygen demand (COD), and turbidity of water samples, and analyzed the risk factors of its quality using both simple and multiple linear regression analysis.Results: Results showed that the CFU, residual chlorine, COD, and turbidity of direct-drinking water in Shanghai elementary and middle schools ranged from 300 cfu/mL, Conclusions: In order to improve the quality of direct-drinking water, the equipment should be as far away from toilet as possible and direct-drinking water should be kept at room temperature or heated at high temperature (over 60 °C). Furthermore, sanitary standards of direct-drinking water quality and relevant laws and regulations should be established and implemented as soon as possible. Our study demonstrates that it is critical to improve direct-drinking water quality and ensure the safety of drinking water in elementary and middle schools in Shanghai. [ABSTRACT FROM AUTHOR]

Cadmium (Cd) is a widely distributed toxic metal, which is mainly exposed to humans through diet. The impact of dietary guidelines on the Chinese diet structure has indirectly led to changes in dietary Cd exposure. The Chinese Dietary Guidelines were issued in 1997 and revised in 2007. Based on the time between issuance and revision, this study examined the Cd contamination levels in Shanghai foods from 1988 to 2018 and evaluated cancer risk and disease burden of dietary Cd exposure accordingly. Over the time periods of 1988–1997, 1998–2007, and 2008–2018, it was found that Cd dietary exposure of Shanghai residents showed a trend of increasing and then decreasing (39.7, 44.7, and 36.4 μg/day, respectively). In contrast to cereals, the contribution rates of meat and vegetables to Cd exposure have gradually increased over time, and aquatic foods have become the main source of Cd exposure (40.6%). Although the non-cancer risk hazard quotients of dietary Cd exposure and the excess lifetime cancer risks (ELCR) are relatively low (HQ < 1, ELCR < 10−4), 26.6% of Shanghai residents had a potential risk of kidney injury calculated by toxicokinetic model (TK model), and the disability adjusted life years (DALYs) have been rising (from 41.6 to 58.2). Results indicated that in the past three decades, changes of Cd contamination in food due to both limit standards and changes in dietary structure have influenced cancer risk and disease burden from Cd exposure in Shanghai residents. In summary, our study suggested that while regulating the contamination in foods, attention should also be paid to the potential impacts of dietary structure and guidelines on the exposure of pollutants. Unlabelled Image • This study systematically analyzes the dietary Cd exposure of Shanghai residents from 1988 to 2018. • This study explored cancer risk and disease burden caused by changes of diet structure and Cd contamination levels. • In addition to contamination in foods, dietary structure and guidelines also pose effects on the exposure of pollutants. [ABSTRACT FROM AUTHOR]

• Precise exposure assessment were peformed by parameters from "swimming habits" investigation. • The swimmers between 9 and 17 years of age had higher ADD of DBPs than swimmers ≥ 18 years of age. • The LCR of DBPs exceeded NRL (10−6), and inhalation exposure was the most important pathway for the total risk. • Annual disease burden was 19.0 person-years attributed to exposure of DBPs in swimming pool water in Shanghai. Swimming pool disinfection byproducts (DBPs) are becoming increasingly common worldwide. Precise exposure and health risk assessment for DBPs in swimming pool water with optimized parameters for local and specific population is more urgently needed. This study aimed to determine the levels of trihalomethanes (THMs) and haloacetic acids (HAAs) in 16 public indoor swimming pools in Shanghai, China. Swimming habits were also investigated to obtain more accurate exposure assessment parameters. Precise exposure assessment through multiple pathways, resulting cancer risk, and disability-adjusted life years (DALYs) were assessed. Results indicated that the highest total level of THMs and HAAs occurred in autumn. The surveyed swimmers 9–17 years of age had higher average daily dose (ADD) of DBPs than swimmers ≥18 years of age. The total lifetime cancer risk (LCR) attributable to THMs and HAAs exceeded 10−6, which represents a negligible risk level (NRL). The cancer risk from inhalation exposure predominantly by THMs contributed more than 99% of the total risk. Annual disease burden was 19.0 person-years attributed to exposure of DBPs in swimming pool water in Shanghai. This study provides a paradigm and strategic reference of precise exposure assessments, risk assessments, and disease burden estimation of hazards in swimming pool water for other regions. [ABSTRACT FROM AUTHOR]