The varying clinical effectiveness of single, three and five intraarticular injections of platelet-rich plasma in knee osteoarthritis.

OBJECTIVE: To investigate the variations in clinical effectiveness among patients diagnosed with knee osteoarthritis who underwent intra-articular administration of platelet-rich plasma using single, triple, or quintuple injections. METHODS: One hundred twenty patients with grade I-III knee osteoarthritis were randomly assigned to three groups: PRP1 group, who received a single injection of platelet-rich plasma; PRP3 group, who received three PRP injections one week apart; PRP5 group, who received five PRP injections one week apart. The patients' conditions were evaluated using the Visual Analogue Scale (VAS) and the Western Ontario and McMaster Universities Arthritis Index-VA3.1 version (WOMAC-VA3.1) at baseline and 6, 12, 24, and 52 weeks 52 weeks follow up. RESULTS: Out of the total participants, 106 patients (30 males and 76 females) completed the study. The primary outcome measure, WOMAC pain score, registered significant improvements across all groups when compared to pre-treatment levels. However, the application of 3 and 5 injections of platelet-rich plasma was substantially more effective than that of a single injection in reducing knee pain and stiffness, as well as enhancing physical function in patients with knee osteoarthritis. No statistically discernable difference was observed between PRP3 and PRP5 at all follow-up intervals, and there was no discernable difference between 3 and 5 PRP injections either. Mild side effects occurred in all three groups. CONCLUSIONS: The administration of three or five injections of platelet-rich plasma is safe, substantially more effective than single injections, and leads to remarkable clinical improvement by significantly reducing knee pain, improving joint stiffness, and enhancing physical function in patients with grade I-III knee osteoarthritis. Furthermore, no significant difference was observed in the efficacy of three or five injections. Therefore, we recommend using three injections of PRP in the treatment of patients with knee osteoarthritis of grade I-III.

Characterization of Potting Epoxy Resins Performance Parameters Based on a Viscoelastic Constitutive Model.

To describe the evolution of residual stresses in epoxy resin during the curing process, a more detailed characterization of its viscoelastic properties is necessary. In this study, we have devised a simplified apparatus for assessing the viscoelastic properties of epoxy resin. This apparatus employs a confining cylinder to restrict the circumferential and radial deformations of the material. Following the application of load by the testing machine, the epoxy resin sample gradually reduces the gap between its surface and the inner wall of the confining cylinder, ultimately achieving full contact and establishing a continuous interface. By recording the circumferential stress-strain on the outer surface of the confining cylinder, we can deduce the variations in material bulk and shear moduli with time. This characterization spans eight temperature points surrounding the glass transition temperature, revealing the bulk and shear relaxation moduli of the epoxy resin. Throughout the experiments, the epoxy resin's viscoelastic response demonstrated a pronounced time-temperature dependency. Below the glass transition temperature, the stress relaxation response progressively accelerated with increasing temperature, while beyond the glass transition temperature, the stress relaxation time underwent a substantial reduction. By applying the time-temperature superposition principle, it is possible to construct the relaxation master curves for the bulk and shear moduli of the epoxy resin. By fitting the data, we can obtain expressions for the constitutive model describing the viscoelastic behavior of the epoxy resin. In order to validate the reliability of the test results, a uniaxial tensile relaxation test was conducted on the epoxy resin casting body. The results show good agreement between the obtained uniaxial relaxation modulus curves and those derived from the bulk and shear relaxation modulus equations, confirming the validity of both the device design and the testing methodology.

Impact of autologous platelet-rich plasma therapy vs. hyaluronic acid on synovial fluid biomarkers in knee osteoarthritis: a randomized controlled clinical trial.

Objective: Observe the effects of platelet-rich plasma (PRP) therapy on inflammatory cytokines in the synovial fluid of the knee joint of patients with KOA, and explore the effects of PRP intra-articular injection on the inflammation of the knee joint environment and the possible mechanism of action. Methods: Seventy patients were randomized to undergo three blinded weekly intra-articular injections of PRP or hyaluronic acid (HA). The concentrations of inflammatory cytokines, including interleukin (IL)-6, IL-1ß, tumor necrosis factor (TNF)-α, IL-8, IL-17A, IL-17F, IL-4, IL-5, and IL-10, in the synovial fluid were evaluated before the intervention and 1 month after the third injection. The Western Ontario and McMaster University (WOMAC) and visual analog scale (VAS) scores were used to assess pain and functional status of the knee joints in both groups before the intervention, immediately post-intervention, and 1, 3, 6, and 12 months after the intervention. Results: Baseline characteristics were similar in both groups with no statistical difference. The IL-6, IL-1ß, TNF-α, IL-17A, and IL-10 levels in the synovial fluid of the observation group decreased significantly after, vs. before, the intervention (p < 0.05), whereas the IL-8, IL-17F, and IL-4 levels decreased (p > 0.05) and IL-5 levels increased (p > 0.05). There was no statistically significant difference between inflammatory cytokine levels in the synovial fluid of the samples from the control group before and after the intervention (p > 0.05). There were no statistically significant differences between the two groups immediately after intervention (p > 0.05). At 1, 3, 6, and 12 months after intervention, the WOMAC and VAS scores were significantly better in the observation group than in the control group (p < 0.05). Conclusion: Platelet plasma therapy can reduce the concentrations of inflammatory cytokines IL-6, IL-1ß, TNF-α, IL-17A, and IL-10 in the synovial fluid of KOA patients, reduce the expression levels of IL-8, IL-17F, and IL-4, clear the pro-inflammatory factors, improve the inflammatory environment of the affected knee joint, and alleviate pain caused by inflammation. Thus, alleviating pain and improving knee function in patients with KOA.

Dust source tracing and their transport mechanisms before monsoon season from three glaciers at the Tibetan Plateau: revelations from REE analysis and an indirect tracing approach.

Understanding the origins of Tibetan Plateau (TP) glacier dust is vital for glacier dynamics and regional climate understanding. In May 2016, snow pit samples were collected from glaciers on the TP: Qiyi (QY) in the north, Yuzhufeng (YZF) in the center, and Xiaodongkemadi (XDK) in the south. Rare earth element (REE) concentrations were analyzed using inductively coupled plasma mass spectrometry (ICP-MS), and near-surface PM10 concentrations were extracted from a dataset of Chinese near-surface PM10. Two tracing approaches were used: direct REE tracing and an indirect approach combining potential source contribution function (PSCF) and concentration-weighted trajectory (CWT). Both methods yielded consistent results. Pre-monsoon, TP surface soils, Taklimakan Desert, and Qaidam Basin contributed to glacier dust. Notably, central and southern glaciers showed Thar Desert influence, unlike the northern ones. Taklimakan and Thar Deserts were major contributors due to their substantial contribution and high dust concentration. Taklimakan dust, influenced by terrain and westerly winds, affected central and southern glaciers more than northern ones. Westerlies carried Thar Desert dust to the TP after it was uplifted by updrafts in northwest India, significantly affecting southern glaciers. Furthermore, comparing the two tracer methods, the indirect approach combining PSCF and CWT proved more effective for short-term dust source tracing.

Pollution revealed by stable lead isotopes in recent snow from the northern and central Tibetan Plateau.

Lead (Pb) isotopes are less fractionated than those from different sources, and thus were used to trace the sources of Pb in the environment. To investigate the sources of Pb in the atmosphere of the Tibetan Plateau, stable Pb isotopes (206Pb, 207Pb and 208Pb) in acidified snow pit samples collected from five glaciers (i.e., Qiyi-QY, Meikuang-MK, Yuzhufeng-YZF, Hariqin-HRQ and Xiaodongkemadi-XDKMD) in May 2016 of the northern and central Tibetan Plateau were measured. The results showed narrow ranges of 1.158-1.187 for 206Pb/207Pb and 2.450-2.489 for 208Pb/207Pb respectively. The 206Pb/207Pb ratios in all samples were obviously lower than the environmental background value of 1.196, indicating the primary contributions of anthropogenic sources. At least 60% of Pb was contributed by various human activities, which was supported by the Pb isotopes in the snow pit samples from the QY, MK, YZF, HRQ and XDKMD glaciers. By comparing Pb isotope data, we found that the primary anthropogenic sources are coal combustion, mining and smelting activities in northwestern China and mixed emissions from cities located in western China and close to the glaciers. These sources contributed to the Pb in the northern glaciers (QY and MK) in particular. Coal combustion in India probably contributes to the central glaciers (HRQ and XDKMD). Another potential source could be parts of central Asia (e.g., Kyrgyzstan and Uzbekistan) through long range transport. The above potential source areas of contaminants were traced further by the air mass back-trajectory tracing method.

Application of vagus nerve stimulation on the rehabilitation of upper limb dysfunction after stroke: a systematic review and meta-analysis.

Objective: This study aimed to elucidate the efficacy, safety, and long-term implications of vagus nerve stimulation (VNS) as a viable therapeutic option for patients with upper limb dysfunction following a stroke. Methods: Data from the following libraries were searched from inception to December 2022: PubMed, Wanfang, Scopus, China Science and Technology Journal Database, Embase, Web of Science, China Biology Medicine Disc, Cochrane Library, and China National Knowledge Infrastructure. Outcomes included indicators of upper limb motor function, indicators of prognosis, and indicators of safety (incidence of adverse events [AEs] and serious AEs [SAEs]). Two of the authors extracted the data independently. A third researcher arbitrated when disputes occurred. The quality of each eligible study was evaluated using the Cochrane Risk of Bias tool. Meta-analysis and bias analysis were performed using Stata (version 16.0) and RevMan (version 5.3). Results: Ten trials (VNS combined with rehabilitation group vs. no or sham VNS combined with rehabilitation group) with 335 patients were included in the meta-analysis. Regarding upper extremity motor function, based on Fugl-Meyer assessment scores, VNS combined with other treatment options had immediate (mean difference [MD] = 2.82, 95% confidence interval [CI] = 1.78-3.91, I2 = 62%, p < 0.00001) and long-term (day-30 MD = 4.20, 95% CI = 2.90-5.50, p < 0.00001; day-90 MD = 3.27, 95% CI = 1.67-4.87, p < 0.00001) beneficial effects compared with that of the control treatment. Subgroup analyses showed that transcutaneous VNS (MD = 2.87, 95% CI = 1.78-3.91, I2 = 62%, p < 0.00001) may be superior to invasive VNS (MD = 3.56, 95% CI = 1.99-5.13, I2 = 77%, p < 0.0001) and that VNS combined with integrated treatment (MD = 2.87, 95% CI = 1.78-3.91, I2 = 62%, p < 0.00001) is superior to VNS combined with upper extremity training alone (MD = 2.24, 95% CI = 0.55-3.93, I2 = 48%, p = 0.009). Moreover, lower frequency VNS (20 Hz) (MD = 3.39, 95% CI = 2.06-4.73, I2 = 65%, p < 0.00001) may be superior to higher frequency VNS (25 Hz or 30 Hz) (MD = 2.29, 95% CI = 0.27-4.32, I2 = 58%, p = 0,03). Regarding prognosis, the VNS group outperformed the control group in the activities of daily living (standardized MD = 1.50, 95% CI = 1.10-1.90, I2 = 0%, p < 0.00001) and depression reduction. In contrast, quality of life did not improve (p = 0.51). Safety was not significantly different between the experimental and control groups (AE p = 0.25; SAE p = 0.26). Conclusion: VNS is an effective and safe treatment for upper extremity motor dysfunction after a stroke. For the functional restoration of the upper extremities, noninvasive integrated therapy and lower-frequency VNS may be more effective. In the future, further high-quality studies with larger study populations, more comprehensive indicators, and thorough data are required to advance the clinical application of VNS. Systematic review registration: https://www.crd.york.ac.uk/prospero/, identifier: CRD42023399820.

Association between short-term exposure to ambient air pollution and number of outpatient Helicobacter pylori infection visits.

Helicobacter pylori infection (HPI) is an important risk factor of gastrointestinal diseases, but factors leading to it are still not fully understood. To investigate the association between short-term exposure to air pollution and HPI during outpatient visits, we collected daily data for HPI outpatient visits and air pollutant concentrations during 2014-2021 in Hefei, Anhui Province, China. A time-stratified case-crossover design was performed to analyze the acute impacts of air pollution on HPI outpatient visits. We also explored potential effect modifiers. A total of 9072 outpatient visits were recorded. We found positive and statistically significant associations of acute exposure to nitrogen dioxide (NO2), sulfur dioxide (SO2), and carbon monoxide (CO) with HPI outpatient visits. Threshold concentrations of the three pollutants with same-day exposure (lag 0 day) for outpatient visits were 37 µg/m3 for NO2, 8 µg/m3 for SO2, and 0.8 mg/m3 for CO. The odds ratios for HPI outpatient visits at the 95th percentile of NO2, SO2, and CO against the thresholds were 1.207 (1.120-1.302), 1.175 (1.052-1.312), and 1.110 (1.019-1.209), respectively. The associations were more evident in patients older than 45 years, females, with health insurance, and in cold seasons. Null associations of exposure to either ozone (O3) or particulate matter (PM) were observed. In summary, short-term exposure to NO2, SO2, and CO above certain concentrations, but not PM or O3, may trigger the increased risk of outpatient visits due to HP infection in Chinese population.

Iron in the NEEM ice core relative to Asian loess records over the last glacial-interglacial cycle.

Mineral dust can indirectly affect the climate by supplying bioavailable iron (Fe) to the ocean. Here, we present the records of dissolved Fe (DFe) and total Fe (TDFe) in North Greenland Eemian Ice Drilling (NEEM) ice core over the past 110 kyr BP. The Fe records are significantly negatively correlated with the carbon-dioxide (CO2) concentrations during cold periods. The results suggest that the changes in Fe fluxes over the past 110 kyr BP in the NEEM ice core are consistent with those in Chinese loess records because the mineral-dust distribution is controlled by the East Asian deserts. Furthermore, the variations in the dust input on a global scale are most likely driven by changes in solar radiation during the last glacial-interglacial cycle in response to Earth's orbital cycles. In the last glacial-interglacial cycle, the DFe/TDFe ratios were higher during the warm periods (following the post-Industrial Revolution and during the Holocene and last interglacial period) than during the main cold period (i.e. the last glacial maximum (LGM)), indicating that the aeolian input of iron and the iron fertilization effect on the oceans have a non-linear relationship during different periods. Although the burning of biomass aerosols has released large amounts of DFe since the Industrial Revolution, no significant responses are observed in the DFe and TDFe variations during this period, indicating that severe anthropogenic contamination has no significant effect on the DFe (TDFe) release in the NEEM ice core.

Whole body hypoxic preconditioning-mediated multiorgan protection in db/db mice via nitric oxide-BDNF-GSK-3ß-Nrf2 signaling pathway.

The beneficial effects of hypoxic preconditioning are abolished in the diabetes. The present study was designed to investigate the protective effects and mechanisms of repeated episodes of whole body hypoxic preconditioning (WBHP) in db/db mice. The protective effects of preconditioning were explored on diabetesinduced vascular dysfunction, cognitive impairment and ischemia-reperfusion (IR)-induced increase in myocardial injury. Sixteen-week old db/db (diabetic) and C57BL/6 (non-diabetic) mice were employed. There was a significant impairment in cognitive function (Morris Water Maze test), endothelial function (acetylcholineinduced relaxation in aortic rings) and a significant increase in IR-induced heart injury (Langendorff apparatus) in db/db mice. WBHP stimulus was given by exposing mice to four alternate cycles of low (8%) and normal air O2 for 10 min each. A single episode of WBHP failed to produce protection; however, two and three episodes of WBHP significantly produced beneficial effects on the heart, brain and blood vessels. There was a significant increase in the levels of brain-derived neurotrophic factor (BDNF) and nitric oxide (NO) in response to 3 episodes of WBHP. Moreover, pretreatment with the BDNF receptor, TrkB antagonist (ANA-12) and NO synthase inhibitor (LNAME) attenuated the protective effects imparted by three episodes of WBHP. These pharmacological agents abolished WBHP-induced restoration of p-GSK-3ß/GSK-3ß ratio and Nrf2 levels in IR-subjected hearts. It is concluded that repeated episodes of WHBP attenuate cognitive impairment, vascular dysfunction and enhancement in IRinduced myocardial injury in diabetic mice be due to increase in NO and BDNF levels that may eventually activate GSK-3ß and Nrf2 signaling pathway to confer protection.

Provenance tracing of dust using rare earth elements in recent snow deposited during the pre-monsoon season from mountain glaciers in the central to northern Tibetan Plateau.

To provide insight into dust sources in snow deposited during the non-monsoon period on the Tibetan Plateau, detailed post-Archean Australian shale (PAAS)-normalized rare earth element (REE) distribution patterns and variations in REE tracers, such as La/Yb, La/Er, and Gd/Yb with depth, as well as the distribution of samples in the plots of REE ratio pairs, such as La/Yb vs. Y/ΣREE, La/Er vs. Gd/Er, and Y/La vs. Nd/Er, were compared in seven potential dust source areas in Asia. Snow samples from five glaciers, i.e., Qiumianleike (QMLK), Meikuang (MK), Yuzhufeng (YZF), Xiaodongkemadi (XDKMD), and Gurenhekou (GRHK), were collected from April 26 to May 13 before the onset of monsoon activity. The results show that dust trapped in snow pits from the studied glaciers, i.e., QMLK, MK, XDKMD, and GRHK, has varying degrees of contribution from the Taklimakan Desert, Qaidam Basin, and the surface soil of the Tibetan Plateau. There are signals of the Tengger and Badain Jaran Desert and Chinese Loess in the MK and XDKMD snow pit samples or in the QMLK and GRHK surface samples from the REE tracers; however, from the point of view of the land location, the three dust sources should not be the major contributors. Signals of dust from the Indian Thar Desert were occasionally detected from the MK, YZF, and XDKMD snow pit samples and GRHK surface snow samples, implying the intrusion of early Indian monsoon activities to the sites. The dust signal from the Thar Desert in India from the YZF glacier is significantly greater than that from the XDKMD and MK glaciers. These findings were also supported by the tracer of dust transmitted to the three snow pits through the air mass backward trajectories. The new finding of this study is that dust from the Indian Desert can even reach the Kunlun Mountains in the northern region of the Tibetan Plateau. The conclusions are helpful in interpreting the sources of dust and the pollutants absorbed by dust particles, as well as the extent of the impact of Indian monsoon activities at the end of the non-monsoon season on the plateau.

Increase of emm1 isolates among group A Streptococcus strains causing scarlet fever in Shanghai, China.

OBJECTIVE: Scarlet fever epidemics caused by group A Streptococcus (GAS) have been ongoing in China since 2011. However, limited data are available on the dynamic molecular characterizations of the epidemic strains. METHOD: Epidemiological data of scarlet fever in Shanghai were obtained from the National Notifiable Infectious Disease Surveillance System. Throat swabs of patients with scarlet fever and asymptomatic school-age children were cultured. Illumina sequencing was performed on 39emm1 isolates. RESULTS: The annual incidence of scarlet fever was 7.5-19.4/100,000 persons in Shanghai during 2011-2015, with an average GAS carriage rate being 7.6% in school-age children. The proportion ofemm1 GAS strains increased from 3.8% in 2011 to 48.6% in 2014; they harbored a superantigen profile similar to emm12 isolates, except for the speA gene. Two predominant clones, SH001-emm12, and SH002-emm1, circulated in 66.9% of scarlet fever cases and 44.8% of carriers. Genomic analysis showed emm1 isolates throughout China constituted distinct clades, enriched by the presence of mobile genetic elements carrying the multidrug-resistant determinants ermB and tetM and virulence genes speA, speC, and spd1. CONCLUSION: A significant increase in the proportion ofemm1 strains occurred in the GAS population, causing scarlet fever in China. Ongoing surveillance is warranted to monitor the dynamic changes of GAS clones.

Atmospheric pollution revealed by trace elements in recent snow from the central to the northern Tibetan Plateau.

In order to determine the current levels, spatial distribution patterns, and potential pollution of trace elements (TEs) in the atmosphere of the Tibetan Plateau (TP), snow pit samples were collected in May 2016 from five TP glaciers: Qiyi (QY), Hariqin (HRQ), Meikuang (MK), Yuzhufeng (YZF), and Xiaodongkemadi (XDKMD). Concentrations of 13 TEs (Al, Ba, Cd, Co, Cr, Cu, Fe, Li, Pb, Sb, Sr, U, and Zn) in the snow were measured. The spatial distribution patterns and depth profiles of TEs from the studies sites revealed that the influence of dust on TEs was more significant on the MK and YZF glaciers than on the QY, HRQ, and XDKMD glaciers. The spatial distributions of TE EFFe values differed from their concentrations, however. The enrichment factor (EF) values and concentrations of some TEs in the YZF, QY, and XDKMD glaciers revealed that the pollution levels of these elements were significantly lower than those found in previous research. Examination based on EFs, principal component analysis, as well as the calculated non-dust contributions of TEs, revealed that dust was the principal source for most TEs in all five glaciers, while biomass burning was another potential natural source for TEs in some glaciers, such as QY. In contrast, Cd, Ba, Sr, Cu, Pb, Zn, and Sb were occasionally affected by anthropogenic sources such as road traffic emissions, fossil fuel combustion, and mining and smelting of nonferrous metals in and beyond the TP. Air mass backward trajectories revealed that potential pollutants were transported not only from local sources but also from Xinjiang Province in northwestern China, as well as South Asia, Central Asia, the Middle East, and Europe.

Salmonella Typhimurium and Salmonella Enteritidis Infections in Sporadic Diarrhea in Children: Source Tracing and Resistance to Third-Generation Cephalosporins and Ciprofloxacin.

OBJECTIVES: This study aimed to trace the transmission source of Salmonella enterica serovar Typhimurium and Salmonella enterica serovar Enteritidis strains associated with enteric infections in Shanghainese children, and understand the molecular mechanism of resistance to third-generation cephalosporins and ciprofloxacin. MATERIALS AND METHODS: The profiles of pulsed-field gel electrophoresis (PFGE) were compared among the isolates from children, animal, and environment. Antimicrobial susceptibility was determined using the minimal inhibitory concentrations and Kirby-Bauer disk diffusion method. Extended-spectrum ß-lactamase (ESBL) producing isolates mediated by resistance genes were identified using polymerase chain reaction and sequencing. RESULTS: Based on PFGE patterns, 49 (33.1%) of 148 human Salmonella Typhimurium isolates located in the dominant PFGE clusters were genetically related to the isolates from poultry source, environment water, aquatic products, and reptiles, whereas 97 (97.0%) of 100 human Salmonella Enteritidis isolates were genetically related to isolates from poultry and water. The rates of resistance to ceftriaxone among clinical Salmonella Typhimurium and Salmonella Enteritidis isolates were 42.0% and 14.2%, respectively. Besides, 35.1% of Salmonella Typhimurium isolates displayed resistance to ciprofloxacin; 64.9% of Salmonella Typhimurium isolates and 97.0% of Salmonella Enteritidis isolates displayed reduced susceptibility to ciprofloxacin. Of 64 ESBL/AmpC-producing strains, CTX-M, TEM, DHA, and CMY were detected at frequencies of 86.0%, 62.5%, 7.8%, 3.1%, and 3.1%, respectively. CONCLUSIONS: The transmission sources of Salmonella Typhimurium and Salmonella Enteritidis infections in Shanghainese children were diverse. The high prevalence of resistance to third-generation cephalosporins and ciprofloxacin mediated by multiple molecular mechanisms needs continuous monitoring and intervention.

Identification and Characterization of Fluoroquinolone Non-susceptible Streptococcus pyogenes Clones Harboring Tetracycline and Macrolide Resistance in Shanghai, China.

Streptococcus pyogenes, also known as group A Streptococcus (GAS), is one of the top 10 infectious causes of death worldwide. Macrolide and tetracycline resistant GAS has emerged as a major health concern in China coinciding with an ongoing scarlet fever epidemic. Furthermore, increasing rates of fluoroquinolone (FQ) non-susceptibility within GAS from geographical regions outside of China has also been reported. Fluoroquinolones are the third most commonly prescribed antibiotic in China and is an therapeutic alternative for multi-drug resistant GAS. The purpose of this study was to investigate the epidemiological and molecular features of GAS fluoroquinolone (FQ) non-susceptibility in Shanghai, China. GAS (n = 2,258) recovered between 2011 and 2016 from children and adults were tested for FQ-non-susceptibility. Efflux phenotype and mutations in parC, parE, gyrA, and gyrB were investigated and genetic relationships were determined by emm typing, pulsed-field gel electrophoresis and phylogenetic analysis. The frequency of GAS FQ-non-susceptibility was 1.3% (30/2,258), with the phenotype more prevalent in GAS isolated from adults (14.3%) than from children (1.2%). Eighty percent (24/30) of FQ-non-susceptible isolates were also resistant to both macrolides (ermB) and tetracycline (tetM) including the GAS sequence types emm12, emm6, emm11, and emm1. Genomic fingerprinting analysis of the 30 isolates revealed that non-susceptibility may arise in various genetic backgrounds even within a single emm type. No efflux phenotype was observed in FQ non-susceptible isolates, and molecular analysis of the quinolone resistance-determining regions (QRDRs) identified several sequence polymorphisms in ParC and ParE, and none in GyrA and GyrB. Expansion of this analysis to 152 publically available GAS whole genome sequences from Hong Kong predicted 7.9% (12/152) of Hong Kong isolates harbored a S79F ParC mutation, of which 66.7% (8/12) were macrolide and tetracycline resistant. Phylogenetic analysis of the parC QRDR sequences suggested the possibility that FQ resistance may be acquired through inter-species lateral gene transfer. This study reports the emergence of macrolide, tetracycline, and fluoroquinolone multidrug-resistant clones across several GAS emm types including emm1 and emm12, warranting continual surveillance given the extensive use of fluoroquinolones in clinical use.

Epidemiological surveillance of hand, foot and mouth disease in Shanghai in 2014-2016, prior to the introduction of the enterovirus 71 vaccine.

Hand, foot, and mouth disease (HFMD) is mainly epidemic in China and Southeast Asian countries. A novel enterovirus 71 vaccine has been available in China for preventing severe HFMD since 2016. Knowledge of the dynamic epidemiology of HFMD in different regions is necessary for appropriate intervention strategies. This study focused on the citywide surveillance data on the epidemiology and etiology of HFMD in Shanghai during 2014-2016. In these 3 years, the total numbers of reported HFMD cases were 65,018, 39,702, and 57,548, respectively; the numbers of severe cases (case-severity ratios) were 248 (0.38%), 35 (0.09%), and 59 (0.10%), respectively. Children <6 years old accounted for 86.65% to 89.34% of HFMD cases and 91.53 to 97.14% of severe cases. EV-A71 caused all three fatal cases. In severe cases, the detection rate of EV-A71 was 77.82% in 2014, 100% in 2015 and 98.31% in 2016. In uncomplicated inpatient cases, the detection rates of EV-A71, CV-A16, CV-A6, and CV-A10 were, respectively, 43.40, 22.10, 30.73, and 1.89% in 2014; 28.52, 6.46, 53.61, and 7.98% in 2015; and 31.79, 14.15, 44.55, and 4.64% in 2016. In mild community cases, the detection rates of EV-A71, CV-A16, CV-A6, and CV-A10 were, respectively, 25.78, 41.64, 22.93, and 1.78% in 2014; 17.41, 21.23, 50.99, and 3.15% in 2015; and 18.92, 27.84, 45.11, and 1.64% in 2016. Among the cluster outbreaks, the most common pathogen was CV-A16 in 2014 (50.69%) and 2015 (38.10%) and CV-A6 in 2016 (36.30%). These findings show that HFMD outbreaks remained at a high level in Shanghai during 2014-2016. CV-A6 was emerging as the most common pathogen causing HFMD.

Signals of pollution revealed by trace elements in recent snow from mountain glaciers at the Qinghai-Tibetan plateau.

In order to extract pollution signal of trace elements (TEs) in glacier snow at the Qinghai-Tibetan plateau of China by human activities, concentrations of 18 TEs (Al, Ti, Fe, Rb, Sr, Ba, V, Cr, Mn, Li, Cu, Co, Mo, Cs, Sb, Pb, Tl, and U), 14 rare earth elements (La, Ce, Pr, Nd, Sm, Eu, Gd, Tb, Dy, Ho, Er, Tm, Yb, and Lu), Y and Th in digested snow samples from five glaciers in April-May 2013 before monsoon season were measured. Results shown that higher TEs concentrations were found in glaciers at the northern plateau while lower concentrations in glaciers at the central and southern plateau. Discussion revealed that EF values calculated from elements with mass fraction <30% such as Ti and Al, etc in traditional acid leached samples, will overestimate at least 4.6 times the contribution of other sources than dust for TEs such as Sb, Sr, As, Cu and Pb etc. Analysis indicated that most TEs mainly originated from dust sources, whereas Pb, Cu, Mo and Sb showed occasionally significant contributions from polluted sources in three snow pits and the GRHK surface snow samples. The pollution probably originated from mining and smelting, road transport emissions on the plateau and some regions outside of the plateau. Dust provenance tracing results based on REEs indicated that Taklimakan Desert, Qaidam Basin, and Tibetan surface soil were the potential dust sources for the studied glaciers, while the Indian Thar Desert was an occasional dust sources for YZF,XDKMD and GRHK snow samples.

Spatial variations and sources of trace elements in recent snow from glaciers at the Tibetan Plateau.

Trace elements (TEs) could pose a potential threat to the environment and human health and hence they have been paid attention increasingly at present. This study presents the acid-leached concentrations of TEs (e.g., Al, As, Ba, Co, Cr, Cs, Cu, Fe, Li, Mn, Mo, Pb, Rb, Sb, Sr, Ti, Tl, U, V) and dust content sampled from Qiumianleike (QMLK), Meikuang (MK), Yuzhufeng (YZF), Xiaodongkemadi (XDKMD), Gurenhekou (GRHK) glaciers on the Tibetan Plateau (TP) from April to May in 2013. A nonparametric Jonckheere-Terpstra Method was used to test the trend of spatial distribution of TEs. The statistical analysis indicates that TEs were the highest in the QMLK glacier, lowest in the YZF glacier, and comparable in the other three glaciers. Comparison with other glaciers of the plateau, the statistical analysis on As, Cu, Mo, Pb, and Sb shows that their concentrations had, in general, a decreasing distribution characteristic from the north to the south of TP, which indicates that the northern TP is loading more atmospheric-polluted impurity than central and southern TP. Enrichment factor (EF) analysis indicates that Rb, V, U, Cr, Ba, Cs, Li, As, Co, Mn, Tl, Sr, and Cu originated mainly from crustal dust, while anthropogenic inputs such as nonferrous metals melting, coal combustion, and traffic emission made an important contribution to the Mo, Pb, and Sb. Evidences from air mass back trajectories show that TEs in the five studied glaciers might not only come from surrounding areas of glaciers but also might be long-range transported by atmosphere from the Central Asia and South Asia and deposited on these glaciers.

Measles Outbreak in Pediatric Hematology and Oncology Patients in Shanghai, 2015.

BACKGROUND: Despite substantial progress toward measles control are making in China, measles outbreaks in immunocompromised population still pose a challenge to interrupt endemic transmission. This study aimed to investigate the features of measles in pediatric hematology and oncology patients and explore the reasons behind the outbreak. METHODS: We collected demographic, epidemiological, and clinical data of immunocompromised measles children. All suspected measles cases were laboratory-confirmed based on the presence of measles IgM and/or identification of measles RNA. The clinical data were statistically analyzed by t-test for continuous variables and Fisher's exact test for categorical variables. RESULTS: From March 9 to July 25 in 2015, a total of 23 children with malignancies and post hematopoietic stem cell transplantation (post-HSCT) were notified to develop measles in Shanghai. Of these 23 patients with the median age of 5.5 years (range: 11 months-14 years), 20 (87.0%) had received 1-3 doses of measles vaccine previously; all patients had fever with the median fever duration of 8 days; 21 (91.3%) had cough; 18 (78.3%) had rash; 13 (56.5%) had Koplik's spot; 13 (56.5%) had complications including pneumonia and acute liver failure; and five (21.7%) vaccinated patients died from severe pneumonia or acute liver failure. Except the first patient, all patients had hospital visits within 7-21 days before measles onset and 20 patients were likely to be exposed to each other. CONCLUSIONS: The outcome of measles outbreak in previously vaccinated oncology and post-HSCT pediatric patients during chemotherapy and immunosuppressant medication was severe. Complete loss of protective immunity induced by measles vaccine during chemotherapy was the potential reason. Improved infection control practice was critical for the prevention of measles in malignancy patients and transplant recipients.

A novel miR-200b-3p/p38IP pair regulates monocyte/macrophage differentiation.

Monocyte/macrophage differentiation represents a major branch of hematopoiesis and is a central event in the immune response, but the molecular mechanisms underlying are not fully delineated. Here we show that p38 mitogen-activated protein kinase (MAPK) interacting protein (p38IP) is downregulated during monocyte/macrophage differentiation in vitro. Overexpression of p38IP halted monocyte/macrophage differentiation, whereas forward knockdown of p38IP by RNA interference induced G1/S arrest and promoted monocyte differentiation into macrophages and the maturation of macrophages as well. Moreover, we found that miR-200b-3p was upregulated during monocyte/macrophage differentiation and mediated the downregulation of p38IP by binding to the 3' untranslated terminal region of p38IP mRNA. Overexpression of a miR-200b-3p mimic resembled the effect of p38IP knockdown, whereas a miR-200b-3p inhibitor blocked monocyte/macrophage differentiation by enhancing p38IP expression. Further western blotting analysis revealed that p38IP downregulation enhanced the activity of p38 MAPK and the subsequent accumulation of cyclin-dependent kinase inhibitor p21, thus promoting G1/S arrest and monocyte/macrophage differentiation. Moreover, the decline of GCN5 acetyltransferase caused by p38IP downregulation was required but was not sufficient for monocyte/macrophage differentiation. This study demonstrated a new role for p38IP and a novel miR-200b-3p/p38IP pair in the regulation of monocyte/macrophage differentiation.

[Epidemiological surveillance of hand, foot and mouth disease in Shanghai, 2010-2014].

OBJECTIVE: To understand the epidemiological profiles of hand, foot and mouth disease (HFMD) and the major enteroviruses causing the epidemics of HFMD in Shanghai from 2010 to 2014. METHOD: The city-wide surveillance data between 2010 and 2014 were used to analyze the epidemiologic characteristics of the HFMD outbreaks in Shanghai. The annual incidence of HFMD was estimated based on the 2010 Shanghai Census data. RESULT: From 2010 to 2014, the reported HFMD cases were 41 080, 37 323, 51 172, 42 198, and 65 018, respectively; the severe cases (case-severity ratio) were 469 (1.14%), 456 (1.22%), 318 (0.62%), 104 (0.25%) and 248 (0.38%), respectively. Based on Shanghai census data by the end of 2010, the attack rates of HFMD in Shanghai were 0.16%-0.28% in the entire population. In terms of the proportion of HFMD cases and severe cases in the specific population, male accounted for 59.62%-61.48% and 62.26%-73.08%, migrant population accounted for 51.86%-62.40% and 72.01%-80.38%; children aged 1.0-1.9 years comprised the highest proportion, up to 22.70%-27.00% and 32.08%-36.40%. HFMD peaked from April to July, in parallel with the peak circulation of enterovirus (EV) 71, and a small peak usually occurred in autumn and winter. All the critically severe and fatal cases were caused by EV71. The detection rates of EV71 and Coxsackievirus A (CA) 16 were 73.08%-88.09% and 1.12%-2.90% in severe HFMD cases, 19.75%-48.74% and 2.02%-23.69% in uncomplicated inpatients, and 16.78%-40.08% and 8.36%-33.39% in mild community cases, respectively. The detection rates of CA6 and CA10 in the mild community cases in 2014 were 18.38% and 1.43%, respectively. In 2013 non-EV71 and non-CA16 enteroviruses comprised 74.86% in the community cases. CONCLUSION: The annual HFMD outbreaks occurred in Shanghai during 2010-2014. Children under 5 years of age, migrant population and male were the major susceptible population. EV71 and CA16 were the predominant pathogens causing the epidemics of HFMD except in 2013, and CA6 was prevalent in the community cases in 2014. The major peak season of HFMD usually overlapped with the peak of EV71 circulation and the majority of severe HFMD cases were associated with EV71 infection.