Risk reduction analysis of mix-and-match vaccination strategy in healthcare workers during SARS-CoV-2 Omicron variant predominant period: A multi-center cohort study in Taiwan.

This study investigated the relative effectiveness of a mix-and-match vaccination strategy, primarily comprising ChAdOx1 nCOV-19, mRNA-1273, BNT162b2, and a protein-based vaccine, MVC-COV1901, against COVID-19 in a healthcare worker (HCW) cohort in Taiwan during a period when the Omicron variant was predominant. The analysis included a total of 21,729 HCWs and recorded 3,672 infections with no severe disease nor death. Two main findings were observed from the study. Firstly, for those with ChAdOx1 nCOV-19 as primary series, a booster dose with BNT162b2 was associated with a small decrease in the risk of acquiring infection compared to those with mRNA-1273 as a booster (Adjust hazard ratio [Adj HR] 0.864; 95% confidence interval [CI] 0.761‒0.981, P = .024). Secondly, for HCWs receiving an mRNA-1273 booster, compared to those receiving ChAdOx1 nCOV-19 as the primary series, mixed primary series and homologous mRNA-1273 primary series were associated with a higher (Adj HR 1.144; 95% CI 1.021‒1.282, P = .021) and lower risk (Adj HR 0.735; 95% CI 0.671‒0.805, P < .001) of acquiring infection, respectively. Our study demonstrated that mix-and-match vaccination strategy may be associated with different level of risk reduction in acquiring infection, and sizable, prospective studies are encouraged to further elucidate our observation.

Functional crosstalk between chromatin and hypoxia signalling.

Eukaryotic genomes are organised in a structure called chromatin, comprising of DNA and histone proteins. Chromatin is thus a fundamental regulator of gene expression, as it offers storage and protection but also controls accessibility to DNA. Sensing and responding to reductions in oxygen availability (hypoxia) have recognised importance in both physiological and pathological processes in multicellular organisms. One of the main mechanisms controlling these responses is control of gene expression. Recent findings in the field of hypoxia have highlighted how oxygen and chromatin are intricately linked. This review will focus on mechanisms controlling chromatin in hypoxia, including chromatin regulators such as histone modifications and chromatin remodellers. It will also highlight how these are integrated with hypoxia inducible factors and the knowledge gaps that persist.

10 Year Follow-Up of Randomized Trial of Laparoscopic Nissen Versus Thal Fundoplication in Children.

Introduction: The aim of this study was to compare the long-term outcomes of laparoscopic complete (Nissen) fundoplication (LNF) with laparoscopic partial (Thal) fundoplication (LTF) in children. This is the only prospective, randomized study to follow patients up for more than 10 years. Interim results published in 2011 at median 2.5 year follow-up showed that LNF had a significantly lower failure rate compared with LTF. Materials and Methods: A randomized, controlled trial of LNF versus LTF in children (<16 years) was performed. The primary outcome measure was "absolute" failure of the fundoplication-recurrence of symptoms that merited either reoperation or insertion of transgastric jejunostomy (GJ). Secondary outcomes were "relative" failure (need for postop antireflux medication), complications (e.g., dysphagia), and death. Results: One hundred seventy-five patients were recruited; 89 underwent LNF, and 86 underwent LTF. Eight patients had no follow-up recorded. At long-term follow-up, 59 patients had died (35%); LNF 37/85 (43.5%) and LTF 22/82 (26.8%), P = .02. Median length of follow-up in survivors was 132 months. There was no statistically significant difference in "absolute" failure rate between LNF 8/85(9.4%) and LTF 15/82 (18%), P = .14. There was no difference in "relative" failure between LNF 7/85 (8.2%) and LTF 12/82 (14%), P = .23. Long-term dysphagia affected 5 out of 108 (4.6%) patients; 3/48 (6.2%) of LNF and 2/60 (3.3%) of LTF (P = .65). Conclusions: There was no statistically significant difference in 'absolute' failure between LNF and LTF at long-term follow-up. Neurologically impaired children have a high mortality rate following fundoplication due to comorbidities. This trial commenced in 1998 and was approved by the Oxfordshire Research Ethics Committee (No. 04.OXA.18-1998).

RETRACTED: Parallel bimodal single-cell sequencing of transcriptome and methylome provides molecular and translational insights on oocyte maturation and maternal aging.

This article has been retracted: please see Elsevier Policy on Article Withdrawal (http://www.elsevier.com/locate/withdrawalpolicy). This article has been retracted at the request of the Editor-in-Chief. It has been brought to our attention that the authors of the article "Parallel bimodal single-cell sequencing of transcriptome and methylome provides molecular and translational insights on oocyte maturation and maternal aging" cannot agree on who should be listed as an author of the article. Further inquiry by the journal revealed that the authorship was also changed at the revision stages of the article without notifying the handling Editor, which is contrary to the journal policy on changes to authorship. The journal considers this unacceptable practice, and the Editor-in-Chief decided to retract the article.

Comparison of Efficacy of 2% Chlorhexidine Gluconate-Alcohol and 10% Povidone-Iodine-Alcohol against Catheter-Related Bloodstream Infections and Bacterial Colonization at Central Venous Catheter Insertion Sites: A Prospective, Single-Center, Open-Label, Crossover Study.

An effective antiseptic agent is an essential component of a central venous catheter (CVC) care bundle, to protect against catheter-related bloodstream infections (CRBSIs). We conducted a trial to compare the incidences of CRBSI and the growth of insertion site flora in patients with CVC using 2% chlorhexidine gluconate−alcohol (CHG) or 10% povidone-iodine−alcohol (PVI) in the CVC care bundle. Patients who were admitted to two medical intensive care units (ICUs) and had CVC placement for >48 h were enrolled. Using a two-way crossover design with two six-month interventions, the ICUs were assigned to use either CHG or PVI in their care bundles. A total of 446 catheters in 390 subjects were enrolled in the study. The detection rate of flora was greater in the PVI group on both day 7 (26.6% versus 6.3%, p < 0.001) and day 14 (43.2% versus 15.8%, p < 0.001). The incidence rate of CRBSI was higher in the PVI group compared to the CHG group (2.15 vs. 0 events per 1000-catheter-days, p = 0.001), although the significance was lost in the multivariate analysis. In conclusion, 2% CHG was superior to 10% PVI in the CVC care bundle in terms of the inhibition of skin flora growth at CVC insertion sites and was potentially associated with lower incidence rates of CRBSI.

A hospital cluster of COVID-19 associated with a SARS-CoV-2 superspreading event.

BACKGROUND/PURPOSE: Superspreading events (SSEs) are pivotal in the spread of SARS-CoV-2. This study aimed to investigate an SSE of COVID-19 in a hospital and explore the transmission dynamics and heterogeneity of SSE. METHODS: We performed contact tracing for all close contacts in a cluster. We did nasopharyngeal or throat swabbing for SARS-CoV-2 by real-time RT-PCR. Environmental survey was performed. The epidemiological and clinical characteristics of the SSE were studied. RESULTS: Patient 1 with congestive heart failure and cellulitis, who had onset of COVID-19 two weeks after hospitalization, was the index case. Patient 1 led to 8 confirmed cases, including four health care workers (HCW). Persons tested positive for SARS-CoV-2 were HCW (n = 4), patient 1's family (n = 2), an accompanying person of an un-infected in-patient (n = 1), and an in-patient admitted before the SSE (n = 1). The attack rate among the HCW was 3.2 % (4/127). Environmental survey confirmed contamination at the bed rails, mattresses, and sink in the room patient 1 stayed, suggesting fomite transmission. The index case's sputum remained positive on illness day 35. Except one asymptomatic patient, at least three patients acquired the infection from the index case at the pre-symptomatic period. The effective reproduction number (Rt) was 0.9 (8/9). CONCLUSION: The host factor (heart failure, longer viral shedding), transmissibility of SARS-CoV-2 (Rt, pre-symptomatic transmission), and possible multiple modes of transmission altogether contributed to the SSE. Rapid response and advance deployment of multi-level protection in hospitals could mitigate COVID-19 transmission to one generation, thereby reducing its impact on the healthcare system.

Infection control operations of a large hospital in Taiwan to prevent nosocomial outbreaks during COVID-19 pandemic.

BACKGROUND: Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) that causes coronavirus disease 2019 (COVID-19) is highly contagious, with a potential to cause large nosocomial outbreaks in the hospital setting. We report the advance deployment of comprehensive, multi-level infection control measures in a 3,700-bed large hospital to prevent nosocomial outbreaks of COVID-19 during the pandemic. METHODS: We implemented a series of dynamic infection control policies during the pandemic. A confirmed COVID-19 case was defined by positive real-time reverse transcriptase-polymerase chain reaction (RT-PCR) assay. All healthcare worker (HCW) having symptoms or close contact with the confirmed case received the RT-PCR test. RESULTS: A total of 5,722 patients were tested in our hospital from January to May 2020. Twenty-five patients were confirmed COVID-19, including two inpatients. A cluster of 4 HCWs with COVID-19 associated with the 2nd inpatient was identified in the early stage of epidemic. Our enhanced traffic control bundling, mask wearing, hand hygiene and environmental cleaning were reinforced after the outbreak. All other confirmed cases were identified at our outdoor quarantine station or epidemic clinic afterwards, and the results of testing for 146 symptomatic HCWs were all negative. CONCLUSIONS: Integrated teamwork, advance deployment of infection control measures and efficient diagnostic testing and response protected HCW and facilities from large SARS-CoV-2 outbreaks and preserved the capacity and function of the health care system during the pandemic.

Genome survey analysis and SSR loci mining of Bupleurum falcatum / 中国中药杂志

Buplewrum falcatum is a traditional Chinese medicine,which is mainly used for the treatment of cold and liver protection. B. falcatum is dominantly cultivated in Japan as well as planted in China,Korea and other countries and regions. In order to determine the appropriate sequencing strategy,the genome survey before large-scale genome sequencing is needed. This survey can provide information about the size and complexity of the whole genome of the target species. In the present study,the next generation sequencing technology( Illumina Hiseq 2000) was used to analyze the genome size and complexity of B. falcatum. In addition,SSR loci were analyzed from the sequenced data. Primer 3 was used to design specific primers and 33 pairs of primers were randomly selected for PCR with template DNA of B. falcatum,and the PCR system and optimal annealing temperature were screened. A total of 288. 64 G genome sequence data was obtained,and the estimated genome size of B. falcatum was 2 119. 58 Mb. The measured genome data depth was138×; the rate of heterozygosity was 1. 84%; and the ratio of repeat sequence was 83. 89%. It is speculated that the genome of B. falcatum is complex. The preliminary assembly was performed with K-mer = 41,and the contig N50 was 224 bp,the total length 896. 97 Mb,the scaffold N50 313 bp,and the total length was 922. 67 Mb. A total of 91 377 SSR sequences were detected in the sequenced genome data which were distributed in 70 809 unigenes.The main type is dinucleotide repeats,with 49 680 sequences,accounting for70. 16%. Among the 33 pairs of primers randomly synthesized according to the obtained SSR sequences,21 pairs were successfully amplifying the target sequences. The results will be helpful for later large scale genome sequencing and SSR molecular markers development for germplasm identification and trait mapping.

Application of CRISPR/Cas9 in plant biology

The CRISPR/Cas (clustered regularly interspaced short palindromic repeats/CRISPR-associated proteins) system was first identified in bacteria and archaea and can degrade exogenous substrates. It was developed as a gene editing technology in 2013. Over the subsequent years, it has received extensive attention owing to its easy manipulation, high efficiency, and wide application in gene mutation and transcriptional regulation in mammals and plants. The process of CRISPR/Cas is optimized constantly and its application has also expanded dramatically. Therefore, CRISPR/Cas is considered a revolutionary technology in plant biology. Here, we introduce the mechanism of the type II CRISPR/Cas called CRISPR/Cas9, update its recent advances in various applications in plants, and discuss its future prospects to provide an argument for its use in the study of medicinal plants.

Postcesarean section wound infection caused by Mycobacterium massiliense.

BACKGROUND/PURPOSE: Mycobacterium abscessus subsp. massiliense (a subspecies of the M. abscessus complex) is a rare causative agent of surgical site infection after cesarean section (C section). We tried to seek the common source of infection and unravel the optimal treatment modalities. METHODS: From September 2009 to October 2012, four postpartum women developed C-section wound infections caused by M. massiliense. Speciation of the four isolates was identified using of hsp65, rpoB, and secA1 partial gene sequencing and the Basic Local Alignment Search Tool. The erm(41) and rrl genes were detected for the possibility of inducible macrolide resistance. Pulsed-field gel electrophoresis was used as a tool of molecular epidemiology. All patients underwent intensive intravenous and oral antimycobacterial regimens. Of these patients, three underwent debridement at least once. RESULTS: All four isolates were identified as M. abscessus subsp. massiliense. All of the isolates harbored a truncated erm(41) gene without rrl gene mutations, which explains the susceptibility to clarithromycin and azithromycin. Three isolates were indistinguishable by DNA strain typing, and the fourth strain was clonal with the other three strains. Their infections were not improved in spite of teicoplanin treatment initially. These patients underwent antimycobacterial regimens with/without surgery and were all cured. DISCUSSION: Teicoplanin treatment failure, painful cutaneous nodules, and persistent wound drainage alerted us to the possibility of nontuberculous mycobacterial skin and soft tissue infection. Accurate identification of subspecies, detection of drug resistance genes, susceptibility testing, and optimal antimycobacterial agents with/without surgical debridement are warranted for successful treatment.

Ameliorating effects of traditional Chinese medicine on lipopolysaccharide -induced microcirculatory disturbances and organ injury.

Gram-negative bacteria are one of the major pathogens associated with severe sepsis and septic shock. LPS is a component of the outer membrane of gram-negative bacteria, which causes a systemic, uncontrolled inflammatory response in infected subjects. In microcirculation it manifests multiple insults, including leukocyte and platelet adhesion, ROS and protease overproduction, mast cell degranulation, endothelium hyperpermeabilty, hemorrhage, and microthrombi formation, ultimately results in multiorgan dysfunction, DIC, refractory shock and even death. TCM has been used in China, Korea, Japan and other Asian countries for treatment of a wide range of diseases. In China, the usage of compound traditional preparation to treat inflammation-related diseases dates back to the Han Dynasty and the medical formulary had been developed thousands of years before, which recorded a great number of classical prescriptions for treatment with infectious diseases. This review will summarize the up to date works with respect to the ameliorating effects of compound and single traditional Chinese medicine and active components on LPS-induced inflammation, including clinical trial and experimental studies regarding multiorgan injury and underlying mechanisms.

Studies on Identification of Bupleurum Cultivated Germplasm Using SSR Molecular Markers / 世界科学技术-中医药现代化

This study was aimed to establish the method of identifying bupleurum cultivated germplasm using simple sequence repeat (SSR) molecular markers and to initially establish dataset of characteristic SSR bands to the bred cultivars or strains. From the bupleurum SSR primer pairs which were designed in previous work, 50 primer pairs were selected. Two bred strains and 4 other bupleurum cultivated germplasms were used as test materials. Primers pairs were screened with effective PCR amplification and high polymorphism. Meanwhile, conditions for PCR amplification and electrophoresis were optimized. Then, obtained SSR bands were analyzed and a clustering tree on the basis of genetic distance was constructed. The results showed that 9 SSR primer pairs can be used for identification. The suitable assay conditions were established and characteristic SSR bands were obtained for tested materials. The tested samples can be divided into 4 categories in the genetic similarity coefficient of 0.73. TheB. scorzonerifolium cultivated inHeilongjiang andChuanhongchaiNo. 1 strains were clustered as one category. ChuanbeichaiNo. 1 strain andZhongchai No. 1 cultivar clustered as another category. Cultivated germplasms fromSichuan Fengshunand Rongxian clustered as a unique category. It was concluded that the primer pairs and assay method established in the present study can be used as reference in identification of bupleurum cultivars or cultivated germplasms.

Expression analyses of BcUGT3 and BcUGT6, and their in vitro expression in Escherichia coli / 中国中药杂志

The tissue-specific and MeJA-induced transcriptional levels of BcUGT3 and BcUGT6 in Bupleurum chinense were analyzed in the present study. The transcriptional levels of BcUGT3 in root, leaf, flower and fruit were similar and they all were higher than those in stem. The transcriptional level of BcUGT6 was the highest in leaf and the lowest in flower among in all tested tissues. With non-treated adventitious roots as control, BcUGT6's transcriptional levels were elevated to nearly 2 folds for 2 h, 8 h, 24 h, 2 d and 4 d in MeJA-treated adventitious roots of B. chinense. It showed that the transcriptional level of BcUGT6 was slightly affected by MeJA. While, BcUGT3's transcriptional levels were gradually elevated, and till 4 d after MeJA treatment, the expression level was about 7 folds than that of non-treated control. Using pET-28a (+), the expressions of two genes was investigated. Induced by IPTG, the target proteins were expressed in E. coli and then purified. All the results obtained in the present study will be helpful for follow-up bio-function analysis of BcUGT3 and BcUGT6.

Outbreak of Serratia marcescens postsurgical bloodstream infection due to contaminated intravenous pain control fluids.

BACKGROUND: Serratia marcescens is an important nosocomial pathogen causing significant outbreaks. Here we report an outbreak of bloodstream infection caused by S. marcescens at a 3500-bed hospital in Taiwan. The effective cooperative efforts of both laboratory personnel and infection control practitioners (ICPs) jointly contributed to the total control of the outbreak. METHODS: A sudden increase in the isolation of S. marcescens from blood cultures was noted in the Clinical Microbiology Laboratory. The information was passed to the ICPs and an investigation was initiated. Pulsed-field gel electrophoresis was used to study the relationships among the isolates. RESULTS: Pulsotype A was identified in 43 (82.7%) of the 52 blood isolates studied. They were isolated from 52 patients distributed across 22 wards that were surveyed by seven ICPs. All patients had undergone surgery before the infection, and fentanyl-containing intravenous fluids were used for pain control in 43 of them. Isolates from 42 belonged to pulsotype A. Three S. marcescens isolates, all from fentanyl-containing fluids and demonstrating pulsotype A, were identified from 251 environmental cultures. All fentanyl-containing fluids that were in use were withdrawn and the outbreak was stopped. CONCLUSIONS: The outbreak of S. marcescens bloodstream infection apparently occurred through the use of fentanyl-containing fluids contaminated by a pulsotype A S. marcescens.

Induction of hairy roots and plantlet regeneration of Bupleurum chinense DC / 药学学报

In this study, the induction of hairy roots of Bupleurum chinense DC. was explored and established after experiments at different conditions: A. rhizogenes A4 was used to infect the leaves bases of B. chinense tube seedlings. The explants were co-cultured on Phytagel-solidified media for 3 days and then, were turned into solid media, similar with the co-culture media except that bacteriostat was added. After 10 days, rootlets began to appear and after 4 to 5 weeks, rootlets can be converted into liquid shaking culture stage. Plants regeneration from hairy root was useful for the research of new germplasm production and the variety improvement breeding. In the present study, the regenerated plants were obtained. One approach was to continuously culture under light conditions the seedlings which parting off spontaneously from the hairy roots during liquid shaking culture. The other approach was to culture the callus-like tissues produced by hairy roots with the optimized regeneration media for the induction of regenerated plants. The results of present study provide a technique to induce hairy roots and plantlet regeneration of B. chinense and this technique is helpful for the researches on metabolism, especially on the Agrobacterium-mediated genetic transformation of B. chinense.

Expression analysis of glycosyltransferase BcUGT1 from Bupleurum chinense DC. and its expression in E. coli and the target protein purification / 药学学报

The ORF sequence of glycosyltransferase gene BcUGT1 cloned from Bupleurum chinense DC. was analyzed and its three dimentional structure was predicted. Using qRT-PCR method, the expression characteristics of BcUGT1 after methyl jasmonate (MeJA) induction and in different plant tissues were investigated. The results showed that BcUGT1 may be involved in saikosaponin biosynthesis in B. chinense. Thereafter, the recombinant vectors of BcUGT1 were constructed for its expression in E. coli. The target protein was successfully expressed and purified. In the present study, three vectors, pRSET-A, pET-28a (+) and pET-30a (+), and three isolates of E. coli, BL21 (DE3) plysS, BL21A1 and BL21-CodonPlus (DE3)-RIPL were used under different induction conditions, such as different concentrations and during times of inducers (L-arabinose and IPTG) and different inducing temperatures. The results showed that in the condition of 0.5 or 1 mmol x L(-1) IPTG, 16 degrees C, 20 h, target protein expressed in BL21-CodonPlus (DE3)-RIPL with pET-28a (+) or pET-30a (+) as vector. Using PrepEase His-tagged protein purification kit, the target protein was purified. The present work will be helpful for follow-up bio-function analysis of BcUGT1.

Expression analysis of glycosyltransferase BcUGT1 from Bupleurum chinense DC. and its expression in E. coli and the target protein purification / 药学学报

The ORF sequence of glycosyltransferase gene BcUGT1 cloned from Bupleurum chinense DC. was analyzed and its three dimentional structure was predicted. Using qRT-PCR method, the expression characteristics of BcUGT1 after methyl jasmonate (MeJA) induction and in different plant tissues were investigated. The results showed that BcUGT1 may be involved in saikosaponin biosynthesis in B. chinense. Thereafter, the recombinant vectors of BcUGT1 were constructed for its expression in E. coli. The target protein was successfully expressed and purified. In the present study, three vectors, pRSET-A, pET-28a (+) and pET-30a (+), and three isolates of E. coli, BL21 (DE3) plysS, BL21A1 and BL21-CodonPlus (DE3)-RIPL were used under different induction conditions, such as different concentrations and during times of inducers (L-arabinose and IPTG) and different inducing temperatures. The results showed that in the condition of 0.5 or 1 mmol x L(-1) IPTG, 16 degrees C, 20 h, target protein expressed in BL21-CodonPlus (DE3)-RIPL with pET-28a (+) or pET-30a (+) as vector. Using PrepEase His-tagged protein purification kit, the target protein was purified. The present work will be helpful for follow-up bio-function analysis of BcUGT1.

Induction of hairy roots and plantlet regeneration of Bupleurum chinense DC / 药学学报

In this study, the induction of hairy roots of Bupleurum chinense DC. was explored and established after experiments at different conditions: A. rhizogenes A4 was used to infect the leaves bases of B. chinense tube seedlings. The explants were co-cultured on Phytagel-solidified media for 3 days and then, were turned into solid media, similar with the co-culture media except that bacteriostat was added. After 10 days, rootlets began to appear and after 4 to 5 weeks, rootlets can be converted into liquid shaking culture stage. Plants regeneration from hairy root was useful for the research of new germplasm production and the variety improvement breeding. In the present study, the regenerated plants were obtained. One approach was to continuously culture under light conditions the seedlings which parting off spontaneously from the hairy roots during liquid shaking culture. The other approach was to culture the callus-like tissues produced by hairy roots with the optimized regeneration media for the induction of regenerated plants. The results of present study provide a technique to induce hairy roots and plantlet regeneration of B. chinense and this technique is helpful for the researches on metabolism, especially on the Agrobacterium-mediated genetic transformation of B. chinense.