Search

Taking into account the forthcoming concept, it is proposed to develop Tegermen group of fields with construction of onshore systems for collection, treatment and transportation of natural gas in order to supply the extracted products to the gas treatment point (Samantepe gas treatment unit-2) in a single-phase state. Natural hydrocarbon systems consist of a large number of components, and these are not only hydrocarbons of the paraffin series, but also hydrocarbons belonging to other groups. The phase state of a hydrocarbon mixture depends on its composition, as well as on the properties of individual components. Construction in a wide range of temperature and pressure values of phase diagrams of reservoir fluids with low condensate factor allows to determine with high accuracy the parameters of the beginning of condensate precipitation (dew point) in the system of gas gathering and transportation to supply the produced products of Tegermen group of fields.

Diabetes mellitus (DM) has detrimental effects on the function of microvascular beds, resulting in blood–brain barrier (BBB) dysfunction. The objective of the study was to investigate whether DM affects the brain physiology through composition of cerebrospinal fluid (CSF) and compare gas tension and electrolyte levels in CSF between the diabetic and nondiabetic populations.

Objective: To study the factors affecting extracellular glycerol (Gly) in patients with severe traumatic brain injury (STBI).Methods: Perilesional extracellular Gly and cerebral blood flow (CBF) in 53 patients with STBI were consecutively monitored. Simultaneously, the intracranial pressure (ICP) and cerebral perfusion pressure (CCP) were monitored. The hourly minimum of CCP and CBF and the hourly maximum of ICP levels were matched with the hourly Gly. Gly values were divided into several groups according to regional ICP (less than 15 mm Hg or larger than 15 mm Hg), CCP (less than 70 mm Hg or larger than 70 mm Hg), CBF (less than 50 AU or 50-150 AU) and the outcomes (death or persistent vegetative state group, severe or moderate disability group, and good recovery group).Results: In comparison with the severe or moderate disability group, the Gly concentration of the death or persistent vegetative state group increased significantly, but CBF and CCP decreased significantly. In comparison with the good recovery group, the Gly concentration of the severe or moderate disability group increased significantly, but CBF and CCP decreased significantly. The Gly concentrations in patients with ICP larger than 15 mm Hg, CCP less than 70 mm Hg and CBF less than 50 AU were respectively higher than those of patients with ICP less than 15 mm Hg, CCP larger than 70 mm Hg and 50 AU less than CBF less than 150 AU. In patients with diffuse axial injury, the mean Gly concentration was (201.17+/-55.00) micromol/L, which was significantly higher than that of the patients with epidural hematoma (n equal to 7, 73.26+/-8.37, P less than 0.05) or subdural hematoma (n equal to 9, 114.67+/-62.88, P less than 0.05), but it did not increase significantly when compared with those in patients with contusion(n equal to 24, 167.48+/-52.63).Conclusion: Gly can be taken as a marker for degradation of membrane phospholipids and ischemia, which reflects the severity of primary or secondary insult. [ABSTRACT FROM AUTHOR]

Abstract For rapidly time-varying channels, the performance of (orthogonal frequency division multiplexing) OFDM systems with the conventional one tap equalizer will be significantly degraded. Because the orthogonality between subcarriers is destroyed, the conventional way to combat the inter-carrier interference (ICI) is employing the banded minimum mean square error (MMSE) equalizer, which can save computational efforts introduced by a large number of subcarriers. However, the width of the banded channel matrix is mainly determined by the normalized Doppler frequency in the sense that with the high Doppler frequency the complexity of equalization for one OFDM block will significantly increase with the band width D. In order to reduce the equalization complexity, the authors proposed multi-segmental OFDM signal equalization method with piecewise linear model (PLM) to approximate the time variations and mitigate the corresponding ICI. Its complexity is significantly reduced with the small segments. Furthermore, an alternative MMSE method with the iterative rank-1 matrix updates is proposed to further reduce the complexity. We also derive the theoretical pre-equalized and equalized signal to interference ratio (SIR) for different normalized Doppler frequencies and segment numbers, which implies that the larger segment number can achieve the better performance. Simulation results demonstrate that the proposed method outperforms the conventional banded MMSE equalizer and the partial fast Fourier transform (FFT) method in terms of bit error rate (BER) with almost the same complexity.

To identify changes in skeletal muscle microRNA expression after endurance exercise and associate the identified microRNAs with mRNA and protein expression to disease-specific pathways in polymyositis (PM) and dermatomyositis (DM) patients.Following a parallel clinical trial design, patients with probable PM or DM, exercising less than once a week, and on stable medication for at least one month were randomized into two groups at Karolinska University Hospital: a 12-week endurance exercise group (n = 12) or a non-exercised control group (n = 11). Using an Affymetrix microarray, microRNA expression was determined in paired muscle biopsies taken before and after the exercise intervention from 3 patients in each group. Ingenuity pathway analysis with a microRNA target filter was used to identify microRNA transcript targets. These targets were investigated at the mRNA (microarray) and protein (mass spectrometry) levels in patients.Endurance exercise altered 39 microRNAs. The microRNAs with increased expression were predicted to target transcripts involved in inflammatory processes, metabolism, and muscle atrophy. Further, these target transcripts had an associated decrease in mRNA expression in exercised patients. In particular, a decrease in the NF-κB regulator IKBKB was associated with an increase in its target microRNA (miR-196b). At the protein level, there was an increase in mitochondrial proteins (AK3, HIBADH), which were associated with a decrease in microRNAs that were predicted to regulate their expression.Improvement in disease phenotype after exercise is associated with increasing microRNAs that target and downregulate immune processes at the transcript level, as well as decreasing microRNAs that target and upregulate mitochondrial content at the protein level. Therefore, microRNAs may improve disease by decreasing immune responses and increasing mitochondrial biogenesis.ClinicalTrials.gov NCT01184625.

We have developed two whole genome-scanning techniques to aid in the discovery of polymorphisms as well as horizontally acquired genes in prokaryotic organisms. First, two-dimensional bacterial genomic display (2DBGD) was developed using restriction enzyme fragmentation to separate genomic DNA based on size, and then employing denaturing gradient gel electrophoresis (DGGE) in the second dimension to exploit differences in sequence composition. This technique was used to generate high-resolution displays that enable the direct comparison of > 800 genomic fragments simultaneously and can be adapted for the high-throughput comparison of bacterial genomes. 2DBGDs are capable of detecting acquired and altered DNA, however, only in very closely related strains. If used to compare more distantly related strains (e.g. different species within a genus) numerous small changes (i.e. small deletions and point mutations) unrelated to the interesting phenotype, would encumber the comparison of 2DBGDs. For this reason a second method, bacterial comparative genomic hybridization (BCGH), was developed to directly compare bacterial genomes to identify gain or loss of genomic DNA. BCGH relies on performing 2DBGD on a pooled sample of genomic DNA from 2 strains to be compared and subsequently hybridizing the resulting 2DBGD blot separately with DNA from each individual strain. Unique spots (hybridization signals) represent foreign DNA. The identification of novel DNA is easily achieved by excising the DNA from a dried gel followed by subsequent cloning and sequencing. 2DBGD and BCGH thus represent novel high resolution genome scanning techniques for directly identifying altered and/or acquired DNA.

Abstract Background Rare genetic variation in the human population is a major source of pathophysiological variability and has been implicated in a host of complex phenotypes and diseases. Finding disease-related genes harboring disparate functional rare variants requires sequencing of many individuals across many genomic regions and comparing against unaffected cohorts. However, despite persistent declines in sequencing costs, population-based rare variant detection across large genomic target regions remains cost prohibitive for most investigators. In addition, DNA samples are often precious and hybridization methods typically require large amounts of input DNA. Pooled sample DNA sequencing is a cost and time-efficient strategy for surveying populations of individuals for rare variants. We set out to 1) create a scalable, multiplexing method for custom capture with or without individual DNA indexing that was amenable to low amounts of input DNA and 2) expand the functionality of the SPLINTER algorithm for calling substitutions, insertions and deletions across either candidate genes or the entire exome by integrating the variant calling algorithm with the dynamic programming aligner, Novoalign. Results We report methodology for pooled hybridization capture with pre-enrichment, indexed multiplexing of up to 48 individuals or non-indexed pooled sequencing of up to 92 individuals with as little as 70 ng of DNA per person. Modified solid phase reversible immobilization bead purification strategies enable no sample transfers from sonication in 96-well plates through adapter ligation, resulting in 50% less library preparation reagent consumption. Custom Y-shaped adapters containing novel 7 base pair index sequences with a Hamming distance of ≥2 were directly ligated onto fragmented source DNA eliminating the need for PCR to incorporate indexes, and was followed by a custom blocking strategy using a single oligonucleotide regardless of index sequence. These results were obtained aligning raw reads against the entire genome using Novoalign followed by variant calling of non-indexed pools using SPLINTER or SAMtools for indexed samples. With these pipelines, we find sensitivity and specificity of 99.4% and 99.7% for pooled exome sequencing. Sensitivity, and to a lesser degree specificity, proved to be a function of coverage. For rare variants (≤2% minor allele frequency), we achieved sensitivity and specificity of ≥94.9% and ≥99.99% for custom capture of 2.5 Mb in multiplexed libraries of 22–48 individuals with only ≥5-fold coverage/chromosome, but these parameters improved to ≥98.7 and 100% with 20-fold coverage/chromosome. Conclusions This highly scalable methodology enables accurate rare variant detection, with or without individual DNA sample indexing, while reducing the amount of required source DNA and total costs through less hybridization reagent consumption, multi-sample sonication in a standard PCR plate, multiplexed pre-enrichment pooling with a single hybridization and lesser sequencing coverage required to obtain high sensitivity.

Abstract Background Inflammation or nerve injury-induced upregulation and release of chemokine CC chemokine ligand 2 (CCL2) within the dorsal root ganglion (DRG) is believed to enhance the activity of DRG nociceptive neurons and cause hyperalgesia. Transient receptor potential vanilloid receptor 1 (TRPV1) and tetrodotoxin (TTX)-resistant Nav1.8 sodium channels play an essential role in regulating the excitability and pain transmission of DRG nociceptive neurons. We therefore tested the hypothesis that CCL2 causes peripheral sensitization of nociceptive DRG neurons by upregulating the function and expression of TRPV1 and Nav1.8 channels. Methods DRG neuronal culture was prepared from 3-week-old Sprague–Dawley rats and incubated with various concentrations of CCL2 for 24 to 36 hours. Whole-cell voltage-clamp recordings were performed to record TRPV1 agonist capsaicin-evoked inward currents or TTX-insensitive Na+ currents from control or CCL2-treated small DRG sensory neurons. The CCL2 effect on the mRNA expression of TRPV1 or Nav1.8 was measured by real-time quantitative RT-PCR assay. Results Pretreatment of CCL2 for 24 to 36 hours dose-dependently (EC50 value = 0.6 ± 0.05 nM) increased the density of capsaicin-induced currents in small putative DRG nociceptive neurons. TRPV1 mRNA expression was greatly upregulated in DRG neurons preincubated with 5 nM CCL2. Pretreating small DRG sensory neurons with CCL2 also increased the density of TTX-resistant Na+ currents with a concentration-dependent manner (EC50 value = 0.7 ± 0.06 nM). The Nav1.8 mRNA level was significantly increased in DRG neurons pretreated with CCL2. In contrast, CCL2 preincubation failed to affect the mRNA level of TTX-resistant Nav1.9. In the presence of the specific phosphatidylinositol-3 kinase (PI3K) inhibitor LY294002 or Akt inhibitor IV, CCL2 pretreatment failed to increase the current density of capsaicin-evoked inward currents or TTX-insensitive Na+ currents and the mRNA level of TRPV1 or Nav1.8. Conclusions Our results showed that CCL2 increased the function and mRNA level of TRPV1 channels and Nav1.8 sodium channels in small DRG sensory neurons via activating the PI3K/Akt signaling pathway. These findings suggest that following tissue inflammation or peripheral nerve injury, upregulation and release of CCL2 within the DRG could facilitate pain transmission mediated by nociceptive DRG neurons and could induce hyperalgesia by upregulating the expression and function of TRPV1 and Nav1.8 channels in DRG nociceptive neurons.

Abstract Background Clinical prediction rules (CPRs) represent well-validated but underutilized evidence-based medicine tools at the point-of-care. To date, an inability to integrate these rules into an electronic health record (EHR) has been a major limitation and we are not aware of a study demonstrating the use of CPR's in an ambulatory EHR setting. The integrated clinical prediction rule (iCPR) trial integrates two CPR's in an EHR and assesses both the usability and the effect on evidence-based practice in the primary care setting. Methods A multi-disciplinary design team was assembled to develop a prototype iCPR for validated streptococcal pharyngitis and bacterial pneumonia CPRs. The iCPR tool was built as an active Clinical Decision Support (CDS) tool that can be triggered by user action during typical workflow. Using the EHR CDS toolkit, the iCPR risk score calculator was linked to tailored ordered sets, documentation, and patient instructions. The team subsequently conducted two levels of 'real world' usability testing with eight providers per group. Usability data were used to refine and create a production tool. Participating primary care providers (n = 149) were randomized and intervention providers were trained in the use of the new iCPR tool. Rates of iCPR tool triggering in the intervention and control (simulated) groups are monitored and subsequent use of the various components of the iCPR tool among intervention encounters is also tracked. The primary outcome is the difference in antibiotic prescribing rates (strep and pneumonia iCPR's encounters) and chest x-rays (pneumonia iCPR only) between intervention and control providers. Discussion Using iterative usability testing and development paired with provider training, the iCPR CDS tool leverages user-centered design principles to overcome pervasive underutilization of EBM and support evidence-based practice at the point-of-care. The ongoing trial will determine if this collaborative process will lead to higher rates of utilization and EBM guided use of antibiotics and chest x-ray's in primary care. Trial Registration ClinicalTrials.gov Identifier NCT01386047

Abstract Background Childhood and adolescence are critical periods of habit formation with substantial tracking of lifestyle and cardiovascular risk into adulthood. There are various guidelines on recommended levels of physical activity in youth of school-age. Despite the epidemic of obesity and diabetes in China, there is a paucity of data in this regard in Chinese youth. We examined the association of self-reported level of physical activity and cardiovascular risk in Hong Kong Chinese youth of school-age. Methods This was a cross-sectional study conducted in 2007-8 in a school setting with 2119 Hong Kong Chinese youth aged 6-20 years. Physical activity level was assessed using a validated questionnaire, CUHK-PARCY (The Chinese University of Hong Kong: Physical Activity Rating for Children and Youth). A summary risk score comprising of waist circumference, blood pressure, fasting plasma glucose and lipids was constructed to quantify cardiovascular risk. Results In this cohort, 21.5% reported high level of physical activity with boys being more active than girls (32.1% versus 14.1%, p < 0.001). Regression analysis showed physical activity level, sex and pubertal stage were independently associated with cardiovascular risk score. Conclusion Self-reported level of physical activity is associated with cardiovascular risk factors in Chinese youth after adjusting for sex and pubertal stage.

Abstract We report a case of aortoesophageal fistula (AEF) caused by a fish bone that had a successful outcome. Aortoesophageal fistula is a rare complication of foreign body ingestion from which few patients survive. Over one hundred cases of AEF secondary to foreign body ingestion have been documented but only seven, including our case, have survived over 12 months. Treatment involved stabilising the patient with a Sengstaken-Blakemore tube and insertion of a thoracic aortic endovascular stent-graft. Unfortunately the stent became infected and definitive open surgical repair involved removing the stent, replacing the aorta with a homograft and coverage with a left trapezius flap while under deep hypothermic arrest.

Abstract Background Central body fat is a better predictor than overall body fat for cardiovascular (CV) risk factors in both adults and children. Waist circumference (WC) has been used as a proxy measure of central body fat. Children at high CV risk may be identified by WC measurements. Waist-to-height ratio (WHTR) has been proposed as an alternative, conveniently age-independent measure of CV risk although WHTR percentiles have not been reported. We aim to provide age- and sex-specific reference values for WC and WHTR in Hong Kong Chinese children. Methods Cross sectional study in a large representative sample of 14,842 children aged 6 to 18 years in 2005/6. Sex-specific descriptive statistics for whole-year age groups and smoothed percentile curves of WC and WHTR were derived and presented. Results WC increased with age, although less after age 14 years in girls. WHTR decreased with age (particularly up to age 14). WHTR correlated less closely than WC with BMI (r = 0.65, 0.59 cf. 0.93, 0.91, for boys and girls respectively). Conclusion Reference values and percentile curves for WC and WHRT of Chinese children and adolescents are provided. Both WC and WHTR are age dependent. Since the use of WHRT does not obviate the need for age-related reference standards, simple WC measurement is a more convenient method for central fat estimation than WHRT.

Abstract Background Large population growth surveys of children and adolescents aged 6 to 18 y were undertaken in Hong Kong in 1963 and 1993. The global epidemic of obesity is a major public health concern. To monitor the impact of this epidemic in Hong Kong children and to identify secular changes in growth, a further growth survey was undertaken in 2005/6. Methods Cross-sectional height and weight measurements of 14,842 children and adolescents aged 6 to 18 y from Hong Kong's 18 districts were obtained during the 2005/6 school year. Percentile curves were constructed using LMS method and sex-specific percentile values of weight-for-age, height-for-age, and BMI-for-age were compared with those data from 1963 and 1993. Results Secular changes in height, weight and BMI were noted between 1963 and 1993 and between 1993 and 2005/6. In the latter period, greater changes were observed at younger ages, and particularly in boys. On an annual basis, the 1993–2005/6 changes were less than those during 1963–1993. Using the International Obesity Task Force cut-offs, 16.7% of children were overweight or obese in 2005/6, which was a 5.1% increase since 1993. Conclusion These data provide policy-makers with further evidence of the secular changes in child growth and the increasing obesity epidemic among Hong Kong children.

Abstract Background Restrictive impairment is the commonest reported pulmonary deficit in AIS, which improves following surgical operation. However, exact mechanism of how improvement is brought about is unknown. Dynamic fast breath-hold (BH)-MR imaging is a recent advance which provides direct quantitative visual assessment of pulmonary function. By using above technique, change in lung volume, chest wall and diaphragmatic motion in AIS patients before and six months after posterior spinal fusion surgery were measured. Methods 16 patients with severe right-sided predominant thoracic scoliosis (standing Cobb's angle 50° -82°, mean 60°) received posterior spinal fusion without thoracoplasty were recruited into this study. BH-MR sequences were used to obtain coronal images of the whole chest during full inspiration and expiration. The following measurements were assessed: (1) inspiratory, expiratory and change in lung volume; (2) change in anteroposterior (AP) and transverse (TS) diameter of the chest wall at two levels: carina and apex (3) change in diaphragmatic heights. The changes in parameters before and after operation were compared using Wilcoxon signed ranks test. Patients were also asked to score their breathing effort before and after operation using a scale of 1–9 with ascending order of effort. The degree of spinal surgical correction at three planes was also assessed by reformatted MR images and correction rate of Cobb's angle was calculated. Results The individual or total inspiratory and expiratory volume showed slight but insignificant increase after operation. There was significantly increase in bilateral TS chest wall movement at carina level and increase in bilateral diaphragmatic movements between inspiration and expiration. The AP chest wall movements, however, did not significantly change. The median breathing effort after operation was lower than that before operation (p < 0.05). There was significant reduction in coronal Cobb's angle after operation but the change in sagittal and axial angle at scoliosis apex was not significant. Conclusion There is improvement of lateral chest wall and diaphragmatic motions in AIS patients six months after posterior spinal fusion, associated with subjective symptomatic improvement. Lung volumes however, do not significantly change after operation. BH-MR is novel non-invasive method for long term post operative assessment of pulmonary function in AIS patients.

Abstract Background The choice of operation for tumours at or around the gastro-oesophageal junction remains controversial with little evidence to support one technique over another. This study examines the prevalence of margin involvement and nodal disease and their impact on outcome following three surgical approaches (Ivor Lewis, transhiatal and left thoraco-laparotomy) for these tumours. Methods A retrospective analysis was conducted of patients undergoing surgery for distal oesophageal and gastro-oesophageal junction tumours by a single surgeon over ten years. Comparisons were undertaken in terms of tumour clearance, nodal yield, postoperative morbidity, mortality, and median survival. All patients were followed up until death or the end of the data collection (mean follow up 33.2 months). Results A total of 104 patients were operated on of which 102 underwent resection (98%). Median age was 64.1 yrs (range 32.1–79.4) with 77 males and 25 females. Procedures included 29 Ivor Lewis, 31 transhiatal and 42 left-thoraco-laparotomies. Postoperative mortality was 2.9% and median survival 23 months. Margin involvement was 24.1% (two distal, one proximal and 17 circumferential margins). Operative approach had no significant effect on nodal clearance, margin involvement, postoperative mortality or morbidity and survival. Lymph node positive disease had a significantly worse median survival of 15.8 months compared to 39.7 months for node negative (p = 0.007), irrespective of approach. Conclusion Surgical approach had no effect on postoperative mortality, circumferential tumour, nodal clearance or survival. This suggests that the choice of operative approach for tumours at the gastro-oesophageal junction may be based on the individual patient and tumour location rather than surgical dogma.

Introduction: Teclistamab, the first approved B-cell maturation antigen-directed bispecific antibody for treatment of triple-class exposed relapsed/refractory multiple myeloma, demonstrated deep, durable responses with a manageable safety profile in the pivotal MajesTEC-1 cohort (NCT03145181/NCT04557098). Efficacy, safety, and pharmacokinetics from the MajesTEC-1 China cohort are reported., Methods: Patients received teclistamab 1.5 mg/kg subcutaneously weekly after step-up dosing; patients could switch to less frequent dosing with continued response., Results: In the China cohort (N = 26; median age, 66 years; median prior lines of therapy, 5) 15-month median follow-up, overall response rates, very good partial response or better, and complete response or better (≥CR) were 76.9%, 76.9%, and 57.7%, respectively. Median time to first response and ≥CR were 1.4 and 6.3 months, respectively; among patients with ≥CR and have available MRD samples, MRD negativity was achieved in 14/15 (93.3%) patients. Median duration of response, progression-free survival, and overall survival were not reached; 12-month duration of response, progression-free survival, and overall survival rates were 78.5%, 68.0%, and 83.5%, respectively. The safety profile was consistent with the pivotal cohort. Although infections occurred in 96.2% of patients, incidence decreased over time with six patients experiencing infections for >12 to 18 months. There were no discontinuations because of adverse events and no dose reductions. Ten patients switched to less frequent dosing. Teclistamab serum concentrations were consistent with the pivotal cohort, with a slightly lower mean pharmacokinetics profile., Conclusions: Teclistamab demonstrated efficacy and safety profiles in the China cohort consistent with the pivotal cohort, supporting teclistamab as a promising treatment option for triple-class exposed relapsed/refractory multiple myeloma in China., (© 2024 The Author(s). Cancer published by Wiley Periodicals LLC on behalf of American Cancer Society.)

Results of retinoid-based therapies in head and neck cancer (HNC) are generally disappointing, indicating a lack of understanding of retinoic acid signaling. The role of retinoic acid receptor gamma (RARγ) and its isoforms in HNC is yet to be established. In this study, we found that RARγ1, 2, 4 are the predominant RARγ isoforms expressed in various types of human cancers, including HNC. The mechanistic study revealed that RARγ1, 2, 4 enhanced the proliferation of HNC cells by accelerating cell cycle progression through interaction with vinexin-β, as well as by ligand-dependent activation of EGFR with downstream Akt, ERK, Src, and YAP signaling pathways. Retinoic acid binding and CDK7-dependent phosphorylation on specific serine residue at the AF-1 domain are mandatory for RARγ-mediated growth promotion of HNC. Knockdown of RARγ abolished proliferation of cultured HNC cells, and completely prevented tumor growth in xenografted nude mice. Similar effects were observed in various human cancer types other than HNC. Our results indicate that RARγ-targeting approach could be a promising therapeutic and chemopreventive strategy for human cancers., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

Diagnosing neurosyphilis in clinical settings poses significant challenges due to the absence of highly efficient diagnostic criteria. Our objective was to enhance the existing diagnostic criteria and assess their sensitivity and specificity for identifying neurosyphilis in HIV-negative patients. We conducted a retrospective review of patient records from a cross-sectional study carried out between December 2019 and May 2023. This study was designed to explore clinical practices in the diagnosis and treatment of neurosyphilis. We proposed and validated a new set of diagnostic criteria across 782 cases, comparing three different NS criteria for diagnostic efficiency. Among the 782 patients analyzed, 410 were diagnosed with neurosyphilis, while 372 were not. The newly developed NS criteria demonstrated a sensitivity of 99.5% and a specificity of 94.6%, with the added benefit of being user-friendly. In subgroups categorized by neurological symptoms and syphilis stages, the new NS criteria also exhibited high sensitivity and specificity. Statistical analyses confirmed that the novel NS criteria performed comparably well to the expanded NS criteria. The novel NS criteria for HIV-negative patients exhibited high sensitivity and specificity, proving to be both effective and convenient for physicians to implement., Competing Interests: Declarations. Competing interests: The authors declare no competing interests. Ethics approval and consent to participate: This study was reviewed and approved by the Medical Ethics Committee of Institute of Dermatology, Chinese Academy of Medical Sciences, and National Center for STD Control, China Centers for Disease Control, in Nanjing, China (approval number: 2019-KY-020). The patients in this manuscript have given written informed consent to publication of their case details., (© 2024. The Author(s).)

Abnormal activation of NLRP3 inflammasome causes the progression of gout, and no small-molecule inhibitor of NLRP3 has been approved yet for clinical use. In this study we established a nigericin-induced inflammasome activation cell model for screening of a natural product library by measuring IL-1β secretion in cell supernatants. Among 432 compounds tested, we found that hypocrellin A (HA), one of the major active components of a traditional ethnic medicinal fungus Hypocrella bambusea in the Northwest Yunnan of China, exhibited the highest inhibition on IL-1β production (IC 50  = 0.103 μM). In PMA-primed THP-1 cells or bone marrow derived macrophages (BMDMs) treated with multiple stimuli (nigericin, ATP or MSU), HA dose-dependently suppressed the activation of NLRP3 inflammasome, reducing the subsequent release of inflammatory cytokines and LDH. Furthermore, the suppression of inflammasome activation by HA was specific to NLRP3, but not to AIM2 or NLRC4. In LPS-primed BMDMs treated with nigericin, HA inhibited ASC oligomerization and speckle formation, and blocked the NLRP3-NEK7 interaction during inflammasome assembly without influencing the priming stage. Moreover, we demonstrated that HA directly bound to the NACHT domain of NLRP3, and that Arg578 and Glu629 were the critical residues for HA binding to NLRP3. In MSU-induced peritonitis and acute gouty arthritis mouse models, administration of HA (10 mg/kg, i.p., once or twice daily) effectively suppressed the inflammatory responses mediated by NLRP3 inflammasome. We conclude that HA is a broad-spectrum and specific NLRP3 inhibitor, and a valuable lead compound to develop novel therapeutic inhibitors against NLRP3-driven diseases. This study also elucidates the anti-inflammation mechanisms and molecular targets of HA, a major active component in medicinal fungus Hypocrella bambusea that has been long used by Chinese ethnic groups., Competing Interests: Competing interests: The authors declare no competing interests., (© 2024. The Author(s), under exclusive licence to Shanghai Institute of Materia Medica, Chinese Academy of Sciences and Chinese Pharmacological Society.)

This study aims to analyze the differentiating factors between only allergic rhinitis and allergic rhinitis combined with other allergic diseases in pre-school children and to explore the impact of relevant family and maternal factors during pregnancy on pediatric allergic diseases.The study employed an epidemiological cross-sectional survey design, conducted from January to June 2022 at the Helong Street Health Service Center in Baiyun District, Guangzhou City, China. This cross-sectional investigation focused on 15 preschool education centers within the jurisdiction. It encompassed a total of 4 661 pre-school children aged 3-6 years within the district, resulting in the collection of 3 437 valid questionnaires. The study utilized an online survey, covering aspects such as children's birth conditions, early living environment, maternal lifestyle and emotional state during pregnancy, and paternal information. The questionnaire was designed by an expert team and incorporated advanced logic functions to ensure data accuracy. Diagnosis of allergic diseases included evaluation of symptoms such as rhinitis, asthma, eczema and along with collecting family member's allergy information. Factors like maternal emotional stress during pregnancy, premature birth, and breastfeeding were also considered. The analysis of frequency differences between groups was conducted using the Chi-square test. The distribution differences between two groups were examined using the t -test or Mann-Whitney U test. Additionally, binary logistic regression analysis was employed to identify risk factors for the occurrence of allergic diseases. To illustrate the distribution and co-occurrence of different allergic diseases in children, upset plots were created. Furthermore, forest plots were utilized to analyze the risk factors. The study included 455 children with only allergic rhinitis and 759 children with rhinitis combined with other allergic diseases. The results showed no significant demographic differences between the two groups. Logistic model results indicated that children with allergic rhinitis who had suffered from severe eczema within the first 12 months had a OR (95% CI ):19.818 times (2.670-147.095) higher probability of developing combined allergic diseases than those without eczema, while the probability increased 2.345 times (1.825-3.013) for those with mild to moderate eczema. A higher level of maternal education was also identified as a risk factor, increasing the risk by about 1.5 times. Additionally, the risk of developing combined allergic diseases in children with one allergic parent was OR (95% CI ):1.662 times (1.273-2.170) higher than in those with non-allergic parents, and 2.181 times (1.504-3.163) higher if both parents had allergies. Moreover, negative maternal emotional stress during pregnancy was more significant in children with combined allergic diseases. In conclusion, severe eczema in the first 12 months, mild to moderate eczema; allergies in one or both parents; parents' educational level, household disposable income level; firstborn status; and negative maternal emotions during pregnancy are risk factors for children with allergic rhinitis combined with other allergic diseases.

Background: This meta-analysis seeks to assess the efficacy and safety of pembrolizumab in individuals with advanced or recurrent cervical cancer., Methods: Databases from PubMed, Embase, and the Cochrane Library were all thoroughly searched for pertinent research. Outcomes include complete response (CR), partial response (PR), stable disease (SD), disease progression (PD), overall response rate (ORR), disease control rate (DCR), median progression-free survival (mPFS), median overall survival (mOS), and adverse events (AEs) were retrieved for further analysis., Results: Ten trials with 721 patients were included in this meta-analysis. The pooled results for patients with cervical cancer receiving pembrolizumab were as follows: CR (0.06, 95%CI: 0.02-0.10), PR (0.15, 95%CI: 0.08-0.22), SD (0.16, 95%CI: 0.13-0.20), PD (0.50, 95%CI: 0.25-0.75), ORR (0.26, 95%CI: 0.11-0.41) and DCR (0.42, 95%CI: 0.13-0.71), respectively. Regarding survival analysis, the pooled mPFS and mOS were 3.81 and 10.15 months. Subgroup analysis showed that pembrolizumab in combination was more beneficial in CR (0.16 vs. 0.03, p  = 0.012), PR (0.24 vs. 0.08, p  = 0.032), SD (0.11 vs. 0.19, p  = 0.043), ORR (0.42 vs. 0.11, p  = 0.014), and mPFS (5.54 months vs. 2.27 months, p  < 0.001) than as single agent. The three most common AEs were diarrhoea (0.25), anaemia (0.25), and nausea (0.21), and the incidence of grade 3-5 AEs was significantly lower, rarely surpassing 0.10., Conclusions: For patients with advanced or recurrent cervical cancer, this systematic review and meta-analysis demonstrated that pembrolizumab had a favourable efficacy and tolerability. Future research will primarily focus on optimising customised regiments that optimally integrate pembrolizumab into new therapies and combination strategies. Designed to maximise patient benefit and efficiently control adverse effects while maintaining a high standard of living.

Background: Seroprevalence studies across various countries can contribute to achieving the elimination target for measles and rubella. However, in the Mainland of China, the concept of herd immunity remains unclear due to the lack of a nationwide serosurvey., Methods: This systematic review and meta-analysis was conducted by retrieving literature reporting the seroprevalence of measles and rubella published between 2012 and 2023. The pooled positive rates and estimated geometric mean concentrations (GMCs) of measles and rubella immunoglobulin G antibodies were calculated., Results: This study analysed 135 studies on measles and 77 on rubella, including data from 368,023 and 177,422 healthy individuals, respectively. Between 2010 and 2022, the overall pooled positive rates for measles and rubella antibodies were 88.8% and 79.91%, respectively. The age-specific susceptibility analysis showed that infants aged < 1 year had the lowest pooled positive rates. Other age groups had a roughly U-shaped distribution, with relatively higher positive rates and GMC of measles and rubella antibodies in young children and older age groups. However, the positive rates for both measles and rubella antibodies fell below the elimination threshold in almost all age groups other than young children aged 1-4 years, especially in recent years. In addition, antibody positivity rates varied by geographical region and decreased with economic level., Conclusion: Our findings provide preliminary insights into herd immunity for measles and rubella, highlighting the challenges to achieving their elimination in China., Competing Interests: Declarations. Ethical approval: This article does not contain any studies with human participants or animals performed by any of the authors. Conflict of interest: All authors declare that there is no conflict of interest., (© 2024. Children's Hospital, Zhejiang University School of Medicine.)

Short carbon atomic wires, the prototypes of the lacking carbon allotrope carbyne, represent the fundamental 1D system and the first stage in carbon nanostructure growth, which still exhibits many open points regarding their growth and stability. An in situ UV resonance Raman approach is introduced for real-time monitoring of the growth of carbon atomic wires during pulsed laser ablation in liquid without perturbing the synthesis environment. Single-chain species' growth dynamics are tracked, achieving size selectivity by exploiting the peculiar optoelectronic properties of carbon wires and the tunability of synchrotron radiation. Diverse solvents are systematically explored, finding size- and solvent-dependent production rates linked to the solvent's C/H ratio and carbonization tendency. Carbon atomic wires' growth dynamics reveal a complex interplay between formation and degradation, leading to an equilibrium. Water, lacking in carbon atoms and reduced polyynes solubility, yields fewer wires with rapid saturation. Organic solvents exhibit enhanced productivity and near-linear growth, attributed to additional carbon from solvent dissociation and low relative polarity. Exploring the dynamics of the saturation regime provides new insights into advancing carbon atomic wires synthesis via PLAL. Understanding carbon atomic wires' growth dynamics can contribute to optimizing PLAL processes for nanomaterial synthesis., (© 2024 The Author(s). Small published by Wiley‐VCH GmbH.)

Acinar cells have been proposed as a cell-of-origin for pancreatic ductal adenocarcinoma (PDAC) after undergoing acinar-to-ductal metaplasia (ADM). ADM can be triggered by pancreatitis, causing acinar cells to de-differentiate to a ductal-like state. We identify FRA1 (gene name Fosl1) as the most active transcription factor during Kras G12D acute pancreatitis-mediated injury, and we have elucidated a functional role of FRA1 by generating an acinar-specific Fosl1 knockout mouse expressing Kras G12D . Using a gene regulatory network and pseudotime trajectory inferred from single-nuclei ATAC-seq and bulk RNA sequencing (RNA-seq), we hypothesized a regulatory model of the acinar-ADM-pancreatic intraepithelial neoplasia (PanIN) continuum and experimentally validated that Fosl1 knockout mice are delayed in the onset of ADM and neoplastic transformation. Our study also identifies that pro-inflammatory cytokines, such as granulocyte colony stimulating factor (G-CSF), can regulate FRA1 activity to modulate ADM. Our findings identify that FRA1 is a mediator of acinar cell plasticity and is critical for acinar cell de-differentiation and transformation., Competing Interests: Declaration of interests P.A.S. receives patent royalties from Guardant Health. A.M. is listed as an inventor on a patent that has been licensed by Johns Hopkins University to Thrive Earlier Detection. A.M. serves as a consultant for Freenome and Tezcat Biosciences., (Copyright © 2024 Elsevier Inc. All rights reserved.)

The purple stem mustards (Brassica rapa subsp. chinensis var. purpuraria) (Govaerts R, 2003) are widely cultivated along Yangtze River Valley in China, which is famous for its flavorful and nutritious edible stalks (Wang et al., 2022). In February 2023, a disease of soft rot was observed in multiple purple stem mustards planting fields in Wuhan city, Hubei province, China (30.41°N, 114.22°E). Disease incidence rates were almost 20 to 30% in the planting area (5 ha in size), causing severe economic loss. Infected plants displayed water-soaked symptoms at the base of the petioles, emitting a foul soft rot odor. The severely infected petioles, stems and roots exhibit pus symptoms leading to plant death. To identify the causal agent, small pieces of soft rot symptomatic tissue were cut from the margin of necrotic lesions and surface disinfected with 75% (v/v) ethanol for 30 seconds, followed by three successive rinses with sterile distilled water. The exudates from the clipped tissues were serially diluted and then incubated onto nutrient agar (NA) plates to obtain purified strains at 28°C for 48 hours (Koike et al., 2002). After incubation, 15 strains were obtained and the colonies of all strains were Gram-negative, aerobic, small, round, convex, whitish to dull white, and had smooth slimy edges. Three single bacterial strains CT020801 - CT020803, which were individually isolated from three different diseased samples, were selected as representative strains for further study. Biochemical tests using the BIOLOG GENIII microplate system (Biolog, Hayward, CA, USA) revealed that these strains were positive for methyl red, pectin, dextrin, D-Cellobiose, β-galactosidase, citrate, and maltose, but negative for indole, arginine dihydrolase, urease, ornithine decarboxylase, and gelatinase tests. The 16S ribosomal RNA gene and the three housekeeping genes, atpD, rpoB, and recN were amplified using genomic DNA of Lelliottia amnigena NCTC12124T as the template, with specially designed primers. All amplified fragments were sequenced and deposited in GenBank with accession numbers OQ954706-OQ954707, OQ954713, and OQ953873-OQ953881. BLAST alignments of the 16S rRNA, atpD, rpoB and recN sequences revealed that the sequences of Strain CT020801-03 exhibited the highest identity (100%, ≥97.97%, ≥98.85% and ≥94.52%, respectively) with L. amnigena （Figure S2）. Phylogenetic tree analysis based on multilocus sequence joint 16S rRNA - atpD - rpoB - recN revealed that CT020801 - CT020803 and L. amnigena clustered together in the same clade (Carrie et al., 2013). These results were consistent with those reported for Lelliottia amnigena (Osei et al., 2022). To confirm pathogenicity, healthy base petioles of three-week-old purple stem mustards seedlings were stab inoculated with 20 μL bacterial suspensions (approximately 108 CFU/mL) and then incubated at 28°C and 80% relative humidity in a growth chamber. A sterile liquid NB medium served as the negative control. The test was repeated thrice with each test consisting of five seedlings per treatment. After three days, soft rot symptoms appeared on the stem bases of the inoculated plants, consistent with the initial symptoms observed in the field. Control plants showed no symptoms. The strains were successfully re-isolated from symptomatic plants and identified as L. amnigena, fulfilling Koch's postulates. L. amnigena, a member of the Enterobacter genus (Birlutiu et al., 2023; Brady et al., 2013; Izard et al., 1981), is commonly found in soil and has been identified as an opportunistic pathogen responsible for plant soft rot disease (Reyes-García et al., 2020; Schroeder et al., 2009; Wu et al., 2023). Previous studies have linked L. amnigena to soft rot disease in potato tubers in China. However, this study marks the first documented case of L. amnigena causing soft rot disease in purple stem mustards in China. This discovery expands the known host range of the pathogenic bacteria and will help to provide essential information for making effective measures to manage this disease.

Lettuce (Lactuca sativa) is a leafy vegetable that belongs to the family Asteraceae. This cool-season crop grows well during Spring and Fall in China (Qi et al., 2021). In October 2023, a leaf disease with dark brown to black lesions was observed on lettuce (var. iceberg) in Yongning Town, Yanqing District, Beijing, China (40°53'N, 116°16'E). The disease incidence ranged from 10 to 40% in the surveyed greenhouse and field. Translucent and water-soaked brown spots were observed on the margins of leaf, then coalesced into large necrotic lesions surrounded by a chlorotic halo. Infected sections were soaked with 75% ethyl alcohol for 7 second, rinsed with sterile water for 15 second twice, and cut into pieces in the sterile water. The sample extracts were streaked on Nutrient agar medium. After incubation for 48 hours, 12 colonies were obtained and all the colonies were Gram-negative and aerobic with yellow, round-shape, smooth and glistening appearance. Four isolates SCZX1-SCZX4 with typical characteristics were selected for further identification tests. Pathogenicity test of SCZX1-SCZX4 was performed on the three-week-old lettuce (var. butterhead) by spraying with the bacterial suspension (108 CFU·ml-1). Inoculated lettuce were incubated at 26℃ and 70% relative humidity in the growth chamber. Another set of lettuce plants were mock inoculated with sterile distilled water. Three trials were carried out per isolate, and each treatment included fifteen lettuce plants. Symptoms appeared within 7-10 days after inoculation and are identical to those naturally infected lettuces. Negative control plants had no symptoms. The 16S rRNA region and two housekeeping genes (gyrB and atpD) of each isolate were amplified with universal primers F27/R1492 (Monciardini et al., 2006) and specific primers (Roach et al., 2018), respectively. According to BLAST analysis of each isolate (Genbank accession number PP027925, PP140779, PP140781 to PP140783, PP137422 to PP137428), BLAST searches of the obtained sequences revealed 100.0% of 16S rRNA region(1400/1400 nucleotides), 100.0% of gyrB(774/774 nucleotides), and 100.0% of atpD(768/768 nucleotides) identity and query coverage to Xhv CFBP 498 (Genbank accession number LR828257.1). Phylogenetic analysis revealed that SCZX1-SCZX4 clustered with the neopathotype strain Xhv LMG 938PT, which was isolated from a diseased L. sativa in Zimbabwe (Timilsina, S et al., 2015). Physiological and biochemical tests of SCZX1-SCZX4 were conducted by the BIOLOG GENIII microplate system (Biolog, Hayward, CA, USA), and the test results are consistent with the Xhv LMG 938PT (Morinière, L et al., 2020) and L1-L7 (Pernezny, K et al., 1995). Strains were re-isolated from re-inoculated lettuce, then re-identified as Xhv by the same method, fulfilling Koch's postulates. Bacterial leaf spot (BLS) is a worldwide-spread lettuce disease caused by numerous bacterial pathogens, including Xhv (Dia, N.C et al., 2022), Pseudomonas cichorii (Patel, N et al., 2021) and P. viridiflava (Alippi, A. M et al., 1999) etc. Xhv had been widely reported as the causal pathogen of BLS in Turkey (Sahin, F et al., 2000), United States (Bull, C.T et al., 2007), Saudi Arabia (Al-Saleh, M et al., 2008), and France (Morinière et al., 2020). However, the first report of Xhv causing BLS on lettuce in China is significant to provide pathogen information for growers in making effective measures to manage this disease.