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Human alveolar echinococcosis is a hard-to-treat and largely untreated parasitic disease with high associated health care costs. The current antiparasitic treatment for alveolar echinococcosis relies exclusively on albendazole, which does not act parasiticidally and can induce severe adverse effects. Alternative, and most importantly, improved treatment options are urgently required. A drug repurposing strategy identified the approved antimalarial pyronaridine as a promising candidate against Echinococcus multilocularis infections. Following a 30-day oral regimen (80 mg kg−1 day−1), pyronaridine achieved an excellent therapeutic outcome in a clinically relevant hepatic alveolar echinococcosis murine model, showing a significant reduction in both metacestode size (72.0%) and counts (85.2%) compared to unmedicated infected mice, which revealed significantly more potent anti-echinococcal potency than albendazole treatment at an equal dose (metacestode size: 42.3%; counts: 4.1%). The strong parasiticidal activity of pyronaridine was further confirmed by the destructive damage to metacestode tissues observed morphologically. In addition, a screening campaign combined with computational similarity searching against an approved drug library led to the identification of pirenzepine, a gastric acid-inhibiting drug, exhibiting potent parasiticidal activity against protoscoleces and in vitro cultured small cysts, which warranted further in vivo investigation as a promising anti-echinococcal lead compound. Pyronaridine has a known drug profile and a long track record of safety, and its repurposing could translate rapidly to clinical use for human patients with alveolar echinococcosis as an alternative or salvage treatment.
Head-up tilt test (HUTT) is an important tool in the diagnosis of pediatric vasovagal syncope. This research will explore the relationship between syncopal symptoms and HUTT modes in pediatric vasovagal syncope.
Methods:
A retrospective analysis was performed on the clinical data of 2513 children aged 3–18 years, who were diagnosed with vasovagal syncope, from Jan. 2001 to Dec. 2021 due to unexplained syncope or pre-syncope. The average age was 11.76 ± 2.83 years, including 1124 males and 1389 females. The patients were divided into the basic head-up tilt test (BHUT) group (596 patients) and the sublingual nitroglycerine head-up tilt test (SNHUT) group (1917 patients) according to the mode of positive HUTT at the time of confirmed pediatric vasovagal syncope.
Results:
(1) Baseline characteristics: Age, height, weight, heart rate (HR), systolic blood pressure (SBP), diastolic blood pressure (DBP), and composition ratio of syncope at baseline status were higher in the BHUT group than in the SNHUT group (all P < 0.05). (2) Univariate analysis: Age, height, weight, HR, SBP, DBP, and syncope were potential risk factors for BHUT positive (all P < 0.05). (3) Multivariate analysis: syncope was an independent risk factor for BHUT positive, with a probability increase of 121% compared to pre-syncope (P<0.001).
Conclusion:
The probability of BHUT positivity was significantly higher than SNHUT in pediatric vasovagal syncope with previous syncopal episodes.
From 2020 to December 2022, China implemented strict measures to contain the spread of severe acute respiratory syndrome coronavirus 2. However, despite these efforts, sustained outbreaks of the Omicron variants occurred in 2022. We extracted COVID-19 case numbers from May 2021 to October 2022 to identify outbreaks of the Delta and Omicron variants in all provinces of mainland China. We found that omicron outbreaks were more frequent (4.3 vs. 1.6 outbreaks per month) and longer-lasting (mean duration: 13 vs. 4 weeks per outbreak) than Delta outbreaks, resulting in a total of 865,100 cases, of which 85% were asymptomatic. Despite the average Government Response Index being 12% higher (95% confidence interval (CI): 9%, 15%) in Omicron outbreaks, the average daily effective reproduction number (Rt) was 0.45 higher (95% CI: 0.38, 0.52, p < 0.001) than in Delta outbreaks. Omicron outbreaks were suppressed in 32 days on average (95% CI: 26, 39), which was substantially longer than Delta outbreaks (14 days; 95% CI: 11, 19; p = 0.004). We concluded that control measures effective against Delta could not contain Omicron outbreaks in China. This highlights the need for continuous evaluation of new variants’ epidemiology to inform COVID-19 response decisions.
We conducted a retrospective, analytical cross-sectional and single-centre study that included 190 hospitalised COVID-19 patients in the Fujian Provincial Hospital South Branch between December 2022 and January 2023 to analyse the correlation of viral loads of throat swabs with clinical progression and outcomes. To normalise the Ct value as quantification of viral loads, we used RNase P gene as internal control gene and subtracted the Ct value of SARS-CoV-2 N gene from the Ct value of RNase P gene, termed △Ct. Most patients were discharged (84.2%), and only 10 (5.6%) individuals who had a lower △Ct value died. The initial △Ct value of participants was also significantly correlated with some abnormal laboratory characteristics, and the duration time of SARS-CoV-2 was longer in patients with severe symptoms and a lower △Ct value at admission. Our study suggested that the △Ct value may be used as a predictor of disease progression and outcomes in hospitalised COVID-19 patients.
This study aims to understand the epidemiological characteristics of SARS-CoV-2 infection in the paediatric population during the outbreak of the Omicron variant in Shanghai. We retrospectively analysed the population-based epidemiological characteristics and clinical outcome of SARS-CoV-2 Omicron variant infection in children in Minhang District, Shanghai, based on the citywide surveillance system during the outbreak period in 2022 (March to May). During this time, a total of 63,969 cases of SARS-CoV-2 infection were notified in Minhang District, out of which 4,652 (7.3%) were children and adolescents <18 years. The incidence rate of SARS-CoV-2 infections in children was 153 per 10,000. Of all paediatric cases, 50% reported to be clinically symptomatic within 1–3 days after PCR confirmation by parents or themselves, with 36.3% and 18.9% of paediatric cases reporting fever and cough. Also, 58.4% of paediatric cases had received at least one dose of the COVID-19 vaccine and 52.1% had received two doses of the COVID-19 vaccination. Our findings are informative for the implementation of appropriate measures to protect children from the threat of SARS-CoV-2 infection.
Maternal gestational weight gain (GWG) is an important determinant of infant birth weight, and having adequate total GWG has been widely recommended. However, the association of timing of GWG with birth weight remains controversial. We aimed to evaluate this association, especially among women with adequate total GWG. In a prospective cohort study, pregnant women’s weight was routinely measured during pregnancy, and their GWG was calculated for the ten intervals: the first 13, 14–18, 19–23, 24–28, 29–30, 31–32, 33–34, 35–36, 37–38 and 39–40 weeks. Birth weight was measured, and small-for-gestational-age (SGA) and large-for-gestational-age were assessed. Generalized linear and Poisson models were used to evaluate the associations of GWG with birth weight and its outcomes after multivariate adjustment, respectively. Of the 5049 women, increased GWG in the first 30 weeks was associated with increased birth weight for male infants, and increased GWG in the first 28 weeks was associated with increased birth weight for females. Among 1713 women with adequate total GWG, increased GWG percent between 14 and 23 weeks was associated with increased birth weight. Moreover, inadequate GWG between 14 and 23 weeks, compared with the adequate GWG, was associated with an increased risk of SGA (43 (13·7 %) v. 42 (7·2 %); relative risk 1·83, 95 % CI 1·21, 2·76). Timing of GWG may influence infant birth weight differentially, and women with inadequate GWG between 14 and 23 weeks may be at higher risk of delivering SGA infants, despite having adequate total GWG.
Although immune checkpoint inhibitors (ICIs) have produced remarkable responses in non-small cell lung cancer (NSCLC) patients, receivers still have a relatively low response rate. Initial response assessment by conventional imaging and evaluation criteria is often unable to identify whether patients can achieve durable clinical benefit from ICIs. Overall, there are sparse effective biomarkers identified to screen NSCLC patients responding to this therapy. A lot of studies have reported that patients with specific gene mutations may benefit from or resist to immunotherapy. However, the single gene mutation may be not effective enough to predict the benefit from immunotherapy for patients. With the advancement in sequencing technology, further studies indicate that many mutations often co-occur and suggest a drastic transformation of tumour microenvironment phenotype. Moreover, co-mutation events have been reported to synergise to activate or suppress signalling pathways of anti-tumour immune response, which also indicates a potential target for combining intervention. Thus, the different mutation profile (especially co-mutation) of patients may be an important concern for predicting or promoting the efficacy of ICIs. However, there is a lack of comprehensive knowledge of this field until now. Therefore, in this study, we reviewed and elaborated the value of cancer mutation profile in predicting the efficacy of immunotherapy and analysed the underlying mechanisms, to provide an alternative way for screening dominant groups, and thereby, optimising individualised therapy for NSCLC patients.
This study deploys RTK-GNSS in 2012, TLS in 2015 and UAV in 2018 to monitor the changes of Urumqi Glacier No. 1 (UG1), eastern Tien Shan, and analyzes the feasibility of three technologies in monitoring the mountain glaciers. DEM differencing shows that UG1 has experienced a pronounced thinning and mass loss for the period of 2012–18. The glacier surface elevation change of −0.83 ± 0.57 m w.e. a−1 has been recorded for 2012–15, whereas the changes of glacier tongue surface elevation in 2015–18 and 2012–18 were −2.03 ± 0.95 and −1.34 ± 0.88 m w.e. a−1, respectively. The glacier area shrunk by 0.07 ± 0.07 × 10−3 km2 and the terminus retreat rate was 6.28 ± 0.83 m a−1 during 2012–18. The good agreement between the glaciological and geodetic specific mass-balances is promising, showing the combination of the three technologies is suitable to monitor glacier mass change. We recommend application of the three technologies to assess each other in different locations of the glacier, e.g. RTK-GNSS base stations, ground control points, glacier tongue and terminus, in order to avoid the inherent limitations of each technology and to provide reliable data for the future studies of mountain glacier changes in western China.
The study aimed to investigate behavioural intentions to receive free and self-paid COVID-19 vaccinations (BICV-F and BICV-SP) among Chinese university students if the vaccine was 80% effective with rare mild side effects, to examine their associations with social media exposures and peer discussions regarding COVID-19 vaccination, and to explore the mediational role of perceived information sufficiency about COVID-19 vaccination. An online anonymous survey (N = 6922) was conducted in November 2020 in five Chinese provinces. Logistic regression and path analysis were adopted. The prevalence of BICV-F and BICV-SP were 78.1% and 57.7%. BICV-F was positively associated with the frequencies of passive social media exposure (adjusted odds ratio (AOR) = 1.32, P < 0.001), active social media interaction (AOR = 1.13, P < 0.001) and peer discussions (AOR = 1.17, P < 0.001). Indirect effects of the three factors on BICV-F via perceived information sufficiency were all significant (P < 0.001). The direct effect of active social media interaction on BICV-F was significantly negative (P < 0.001). Similar associations/mediations were observed for BICV-SP. The COVID-19 vaccination intention of Chinese university students needs improvement. Boosting social media exposures and peer discussions may raise students' perceived information sufficiency and subsequently increase their vaccination intention. Considering the potential negative effect of active social media interaction, caution is needed when using social media to promote COVID-19 vaccination.
The high overall plant-based diet index (PDI) is considered to protect against type 2 diabetes in the general population. However, whether the PDI affects gestational diabetes mellitus (GDM) risk among pregnant women is still unclear. We evaluated the association between PDI and GDM risk based on a Chinese large prospective cohort – the Tongji Maternal and Child Health Cohort. Dietary data were collected at 13–28 weeks of pregnancy by a validated semi-quantitative FFQ. The PDI was obtained by assigning plant food groups positive scores while assigning animal food groups reverse scores. GDM was diagnosed by a 75 g 2-h oral glucose tolerance test at 24–28 weeks of gestation. Logistic regression models were fitted to estimate OR of GDM, with associated 95 % CI, comparing women in different PDI quartiles. Among the total 2099 participants, 169 (8·1 %) were diagnosed with GDM. The PDI ranged from 21·0 to 52·0 with a median of 36·0 (interquartile range (IQR) 33·0–39·0). After adjusting for social-demographic characteristics and lifestyle factors etc., the participants with the highest quartile of PDI were associated with 57 % reduced odds of GDM compared with women in the lowest quartile of PDI (adjusted OR 0·43; 95 % CI 0·24, 0·77; Pfor trend = 0·005). An IQR increment in PDI was associated with 29 % decreased odds of GDM (adjusted OR 0·71; 95 % CI 0·56, 0·90). Findings suggest that adopting a plant-based diet during pregnancy could reduce GDM risk among Chinese women, which may be valuable for dietary counselling during pregnancy.
We consider the fractional elliptic problem:
where B1 is the unit ball in ℝN, N ⩾ 3, s ∈ (0, 1) and p > (N + 2s)/(N − 2s). We prove that this problem has infinitely many solutions with slow decay O(|x|−2s/(p−1)) at infinity. In addition, for each s ∈ (0, 1) there exists Ps > (N + 2s)/(N − 2s), for any (N + 2s)/(N − 2s) < p < Ps, the above problem has a solution with fast decay O(|x|2s−N). This result is the extension of the work by Dávila, del Pino, Musso and Wei (2008, Calc. Var. Partial Differ. Equ. 32, no. 4, 453–480) to the fractional case.
The aim of this study was to investigate the association between daily Se intake and postpartum weight retention (PPWR) among Chinese lactating women, and the impact of their Se nutritional status on infants’ physical development. Se contents in breast milk and plasma collected from 264 lactating Chinese women at the 42nd day postpartum were analysed with inductively coupled plasma MS. Daily Se intake was calculated based on plasma Se concentration. The dietary data of 24-h records on three consecutive days were collected. Infant growth status was evaluated with WHO standards by Z-scores. Linear regression analyses and multinomial logistic regression were conducted to examine the impact of Se disequilibrium (including other factors) on PPWR and growth of infants, respectively. The results indicated that: (1) the daily Se intake of the subjects was negatively associated with their PPWR (B = −0·002, 95 % CI − 0·003, 0·000, P = 0·039); (2) both insufficient Se daily intake (B = −0·001, OR 0·999, 95 % CI 0·998, 1·000, P = 0·014) and low level of Se in milk (B = −0·025, OR 0·975, 95 % CI 0·951, 0·999, P = 0·021) had potential associations with their infants’ wasting, and low level of Se in milk (B = −0·159, OR 0·853, 95 % CI 0·743, 0·980, P = 0·024) had a significant association with their infants’ overweight. In conclusion, the insufficient Se nutritional status of lactating Chinese women was first found as one possible influencing factor of their PPWR as well as low physical development of their offspring.
The epidemic of coronavirus disease 2019 (COVID-19) began in China and had spread rapidly to many other countries. This study aimed to identify risk factors associated with delayed negative conversion of SARS-CoV-2 in COVID-19 patients. In this retrospective single-centre study, we included 169 consecutive patients with confirmed COVID-19 in Zhongnan Hospital of Wuhan University from 15th January to 2nd March. The cases were divided into two groups according to the median time of SARS-CoV-2 negative conversion. The differences between groups were compared. In total, 169 patients had a median virus negative conversion time of 18 days (interquartile range: 11–25) from symptom onset. Compared with the patients with short-term negative conversion, those with long-term conversion had an older age, higher incidence of comorbidities, chief complaints of cough and chest distress/breath shortness and severer illness on admission, higher level of leucocytes, neutrophils, aspartate aminotransferase, creatine kinase and erythrocyte sedimentation rate (ESR), lower level of CD3+CD4+ lymphocytes and albumin and more likely to receive mechanical ventilation. In multivariate analysis, cough, leucocytes, neutrophils and ESR were positively correlated with delayed virus negative conversion, and CD3+CD4+ lymphocytes were negatively correlated. The integrated indicator of leucocytes, neutrophils and CD3+CD4+ lymphocytes showed a good performance in predicting the negative conversion within 2 weeks (area under ROC curve (AUC) = 0.815), 3 weeks (AUC = 0.804), 4 weeks (AUC = 0.812) and 5 weeks (AUC = 0.786). In conclusion, longer quarantine periods might be more justified for COVID-19 patients with cough, higher levels of leucocytes, neutrophils and ESR and lower levels of CD3+CD4+ lymphocytes.
During the detection of industrial hazardous gases, like formaldehyde (HCHO), the selectivity is still a challenging issue. Herein, an alternative HCHO chemosensor that based on the tin oxide nanoparticles is proposed, which was obtained through a facile hydrothermal method. Gas sensing performances showed that the optimal working temperature located at only 180 °C, the response value of 79 via 50 ppm HCHO was much higher than that of 35 at 230 °C. However, the compromised test temperature was selected as 230 °C, taking into account the faster response/recovery speeds than 180 °C, named 20/23versus 53/60 s, respectively. The response (35) of the SnO2 nanoparticles-based sensor to 50 ppm of HCHO is about 400% higher than that of bulk SnO2 sensor (9), especially when the gas concentration is 1 ppm, SnO2 nanoparticles also has a higher sensitivity which may possibly result from more exposed active sites and small size effect for nanoparticles than for bulk ones. The gas sensor based on SnO2 nanoparticles can be utilized as a promising candidate for practical low-temperature detectors of HCHO due to its higher gas response, excellent response–recovery properties, and perfect selectivity.
The purpose of this study was to construct a glycyrrhetinic acid (GA)-mediated, breakable, intracellular, nanoscale drug-delivery carrier via amide and esterification reactions. The structures were identified by Fourier-transformed infrared (FTIR) and 1H-nuclear magnetic resonance (1H-NMR) spectrophotometry. The compatibility and safety of the carrier were evaluated using hemolysis and cytotoxicity tests. The GA-copolymer micelle was prepared using the solvent evaporation method. FTIR and 1H-NMR detection demonstrated the successful construction of the polymer. No hemolysis occurred in any concentration of polymer within 3 h, and the hemolysis rate was less than 5%. 3-(4,5-dimethyl-thiazol-2-yl)-2,5-diphenyl-tetrazolium bromide (MTT) experimental results showed that the novel polymer reduced the cell survival rate and had significant cytotoxic effects. The blank nanoparticles were liquid with light blue opalescence. Transmission electron microscopy revealed that the empty micelles were uniform spheres, with an average size of 62 nm and a zeta potential of −13 mV. The novel GA-mediated polymeric carrier material developed here has the potential to effectively kill human SMMC-7721 cancer cells within 3 days when the dose is above 500 ug/mL.
Only 30% or fewer of individuals at clinical high risk (CHR) convert to full psychosis within 2 years. Efforts are thus underway to refine risk identification strategies to increase their predictive power. Our objective was to develop and validate the predictive accuracy and individualized risk components of a mobile app-based psychosis risk calculator (RC) in a CHR sample from the SHARP (ShangHai At Risk for Psychosis) program.
Method
In total, 400 CHR individuals were identified by the Chinese version of the Structured Interview for Prodromal Syndromes. In the first phase of 300 CHR individuals, 196 subjects (65.3%) who completed neurocognitive assessments and had at least a 2-year follow-up assessment were included in the construction of an RC for psychosis. In the second phase of the SHARP sample of 100 subjects, 93 with data integrity were included to validate the performance of the SHARP-RC.
Results
The SHARP-RC showed good discrimination of subsequent transition to psychosis with an AUC of 0.78 (p < 0.001). The individualized risk generated by the SHARP-RC provided a solid estimation of conversion in the independent validation sample, with an AUC of 0.80 (p = 0.003). A risk estimate of 20% or higher had excellent sensitivity (84%) and moderate specificity (63%) for the prediction of psychosis. The relative contribution of individual risk components can be simultaneously generated. The mobile app-based SHARP-RC was developed as a convenient tool for individualized psychosis risk appraisal.
Conclusions
The SHARP-RC provides a practical tool not only for assessing the probability that an individual at CHR will develop full psychosis, but also personal risk components that might be targeted in early intervention.
To investigate the hypothesis that folic acid supplementation and dietary folate intake before conception and during pregnancy reduce the risk of small for gestational age (SGA) and to examine the joint effect of folic acid supplementation and dietary folate intake on the risk of SGA.
Design:
Participants were interviewed by trained study interviewers using a standardized and structured questionnaire. Information on birth outcomes and maternal complications was abstracted from medical records and dietary information was collected via a semi-quantitative FFQ before conception and during pregnancy.
Setting:
A birth cohort data analysis using the 2010–2012 Gansu Provincial Maternity and Child Care Hospital.
Participants:
Women (n 8758) and their children enrolled in the study.
Results:
Folic acid supplementation was associated with a reduced risk of SGA (OR = 0·72, 95 % CI 0·60, 0·86), with the reduced risk seen mainly for SGA at ≥37 weeks of gestational age (OR = 0·70, 95 % CI 0·58, 0·85) and nulliparous SGA (OR = 0·67, 95 % CI 0·54, 0·84). There was no significant association between dietary folate intake and SGA risk.
Conclusions:
Our study suggested that folic acid supplementation was associated with a reduced risk of SGA and the risk varied by preterm status and parity.
The present study explored the mechanism of Zn-methionine (Zn-Met) influencing eggshell quality of laying hens and investigated whether the mechanism was related to Ca deposition. Hyline grey layers (n 384, 38 weeks old) were divided into four groups: 0 mg Zn/kg, 40, 80 mg Zn/kg as Zn-Met, and 80 mg Zn/kg as zinc sulphate (ZnSO4). Eggshell quality, Zn contents, Zn-containing enzyme activities and expressions of shell matrix proteins in eggshell gland (ESG) were analysed. Zn-Met treatment at 80 mg/kg increased (P < 0·05) egg weight and eggshell strength throughout the experiments. The 80 mg/kg Zn-Met group (P < 0·05) had decreased mammillary knob width and larger relative atomic weight percentage of Ca, stronger signal intensity of Ca in linear distribution and the Ca was more evenly distributed in the transversal surface of eggshell. Zn contents (P < 0·001) in yolk and serum, Ca, albumin (Alb) levels in ESG as well as carbonic anhydrase (CA) activity in serum (P < 0·05) and mRNA levels of CA and Ca-binding protein-d28k (CaBP-D28k) (P < 0·001) in the 80 mg/kg Zn-Met group were the highest among all treatments. In conclusion, shell strength as one of eggshell qualities was mostly related to mammillary cone width in ultrastructure caused by the pattern of Ca deposition in eggshell formation. Also, the increase in Zn-Met-induced Ca deposition may be due to the increased Zn contents in serum and tissues, which were attributable to the increased CA concentrations in serum, Ca, Alb levels and up-regulated CA and CaBP-D28k mRNA levels in ESG.
Spray-painting equipments are important for the automatic spraying of long conical objects such as rocket fairing. This paper proposes a spray-painting equipment that consists of a feed worktable, a gantry frame and two serial–parallel mechanisms and investigates the optimal design of PRR–PRR parallel manipulator in serial–parallel mechanisms. Based on the kinematic model of the parallel manipulator, the conditioning performance, workspace and accuracy performance indices are defined. The dynamic model is derived using virtual work principle and dynamic evaluation index is defined. The conditioning performance, workspace, accuracy performance and dynamic performance are involved in multi-objective optimization design to determine the optimal geometrical parameters of the parallel manipulator. Furthermore, the geometrical parameters of the gantry frame are optimized. An example is given to show how to determine these parameters by taking a long object with conical surface as painted object.