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Objective:To explore the potential mechanisms of anterior cingulate cortex (ACC) in modulating pain behavior and anxiety-like behavior of rats with chronic non-specific low back pain induced by nerve growth factor (NGF).Methods:Ninety-six male SPF grade SD rats aged 8 weeks were randomly divided into four groups according the random number table method: control group, model group, control+ D-2-amino-5-phosphonopentanoate (D-AP5) group (control+ D-AP5 group) and model+ D-AP5 group, with 24 rats in each group.Low back pain model of rat was established by injection of NGF into multifidus muscle (left side) of the low backs of rats(two times with a five-day interval). Five days after modeling, rats in model+ D-AP5 group and control+ D-AP5 group were injected with the N-methyl-D-aspartate (NMDA) receptor antagonist D-AP5(2 μg, 0.3 μL) at the right side of the ACC once a day for consecutive 3 days, and rats in control group and model group were injected with the same amount of 0.9% sodium chloride solution. Seven days after modeling, the pain threshold of rats was evaluated by mechanical stimulation test and hot and cold plate test.The anxiety-like behavior was tested by open field test.The density of glial fibrillary acidic protein (GFAP) positive cells and c-Fos(a kind of immediate early gene) positive cells of the spinal cord were observed by immunofluorescence. The expression of GFAP, c-Fos, phosphorylated-c-Jun N-terminal kinases (p-JNK), monocyte chemoattractant protein-1 (MCP-1), and chemokine (C-X-C motif) ligand 1 (CXCL-1) proteins in the L2 segment of the spinal cord were detected by Western blot. SPSS 23.0 software was used for statistical analysis. One-way ANOVA was used to analyze normal distribution measurement data for comparison among multiple groups, and Tukey test was used for further pairwise comparisons. The Kruakal-Wallis H test was used for non-normal distribution measurement data, and Mann-Whitney U test was used for further pairwise comparisons with Bonferroni-corrected P-values. Results:In the experiments measuring pressure pain threshold (PPT) and paw withdrawal threshold (PWT), there were statistically significant differences in the PPT and PWT of rats among the four groups ( F=53.498, 41.939, both P<0.001). Seven days after modeling, PPT ((418.5±46.9) g) and PWT ( (55.6±7.1) g) in the ipsilateral side of the rats in model+ D-AP5 group were higher than those in model group ((290.0±32.0) g, (30.5±7.5) g) (both P<0.001). In the open field test, there were statistically significant differences in percentage of the inner zone distance ( H=11.922, P<0.01) and the percentage of inner zone time ( H=21.614, P<0.001) of rats among the four groups. The percentage of inner zone time in model+ D-AP5 group was higher than that in model group (5.6(4.3, 7.9) %, 3.1(2.1, 3.8) %) ( P<0.01). The results of immunofluorescence showed that there were statistically significant differences in the density of GFAP positive cells and c-Fos positive cells at the ipsilateral side of the superficial laminae of rats among the four groups ( H=49.085, F=18.120, both P<0.001). The density of GFAP positive cells (34.3(21.1, 47.5) cells/mm 2) and c-Fos positive cells ((52.7±39.4) cells/mm 2) at the ipsilateral side of the superficial laminae in model+ D-AP5 group were less than those in model group (76.5(68.6, 94.9) cells/mm 2, (112.4±63.7) cells/mm 2) (both P<0.001). The Western blot results showed that there were statistically significant differences in the protein expression of GFAP, c-Fos, p-JNK, MCP-1 and CXCL-1 in the L2 segment of rats among the four groups ( F=49.413, 38.437, 41.867, 36.735, 130.951, all P<0.001). The protein expression of GFAP (1.7±0.5), c-Fos (1.1±0.1), p-JNK (1.7±0.3), MCP-1 (1.0±0.4) and CXCL-1 (0.8±0.1) in the L2 segment in model+ D-AP5 group were lower than those in model group ((4.3±0.7), (2.6±0.5), (2.8±0.4), (2.9±0.4), (3.5±0.4)) (all P<0.01). Conclusion:ACC modulates mechanical hyperalgesia and anxiety-like behavior in chronic non-specific low back pain rats, which might be associated with the involvement of spinal astrocytes, p-JNK signal pathway and chemokines such as MCP-1 and CXCL-1.
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Objective:To study the clinical characteristics of neonatal gastric perforation (NGP) and risk factors of mortality.Methods:From January 2015 to May 2022, infants with NGP admitted to NICU of our hospital were retrospectively studied. They were assigned into the survival group and the death group. Clinical manifestations, laboratory and imaging results, surgical treatments and prognosis were compared and risk factors of mortality were determined.Results:A total of 27 infants with NGP were enrolled, including 17 males and 10 females. 24 were premature infants and 3 were term infants. 26 infants had low birth weight. 3 infants had neonatal resuscitation due to asphyxia, 10 received positive pressure ventilation before the onset of perforation symptoms, 2 showed gastrointestinal malformations and 3 with septic shock before surgery. The median age of onset was 2.0 d. The main presenting symptom was abdominal distension, with most perforations occurring at the greater curvature of the stomach. 20 cases had congenital gastric muscular layer defects. 21 cases survived and 6 cases died. Age of onset was later in the death group than the survival group [2.5 (2.0, 7.8) days vs. 1.9 (1.4, 3.0) days]. The survival group had higher preoperative platelet count than the death group [(218±80) ×10 9/L vs. (126±73)×10 9/L]. The incidences of thrombocytopenia, septic shock and multi-organ dysfunction syndrome before surgery in the survival group were significantly lower than the death group ( P<0.05). Logistic regression analysis showed that preoperative thrombocytopenia was a risk factor for NGP mortality ( OR=19.000, 95% CI 2.029-177.932, P=0.010). Conclusions:NGP is more common in male infants, premature infants and low birth weight infants. The most common etiology is congenital gastric muscular layer defects. The mortality rate is high and preoperative thrombocytopenia is a risk factor for mortality.
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Objective@#To assess the status of current e cigarette perception and its influencing factors among adolescents in Shanghai, so as to provide reference for the refinement of the prevention and control measures of teenagers e cigarette use.@*Methods@#From May to June 2021, a stratified random cluster sampling was used to investigate 7 456 junior high and high school students in Shanghai. Harm and benefit perception of e cigarette as well as its social environment benefits were collected.@*Results@#The rate of adolescents ever and current e cigarette use was 3.19% and 1.09%, respectively. The top four risk factors for low harm perception of e cigarette were adolescent e cigarette use( OR=2.74, 95%CI =2.10-3.59), high school students ( OR=1.47, 95%CI = 1.32 - 1.64 ), family members ( OR=1.45, 95%CI =1.24-1.70) and friends ( OR=1.36, 95%CI =1.20-1.54) using e cigarette. Adolescent ecigarette use ( OR=2.77, 95%CI =1.97-3.89), high school students( OR=2.11, 95%CI =1.89-2.36), friends ( OR= 1.63, 95%CI =1.42-1.87) and family members using e cigarette( OR=1.39, 95%CI =1.18-1.65) were the top four associated factors for high benefit perception of e cigarette. And, adolescent e cigarette use ( OR=1.95, 95%CI =1.47-2.59), high school students ( OR= 1.73, 95%CI =1.55-1.93), friends ( OR=1.60, 95%CI =1.40-1.82) and pocket money≥200 yuan using e cigarette( OR= 1.29 , 95%CI =1.17-1.43) were the top four risk factors for high social environmental benefit perception of e cigarette. Moreover, perception of e cigarette harm, benefit and social environmental benefit were associated with the risk of future use of e cigarette( OR = 0.78,1.44,1.21, P <0.01).@*Conclusion@#Being high school students and using e cigarette by oneself, friends, and family members are the important influencing factors for adolescents e cigarette perception. Both low harm and high benefit perception of e cigarette elevate the risk of future e cigarette use among adolescents, so effective measures should be taken to promote control education about e cigarette and smoke free environment construction.
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Objective:To investigate the current status of hospitalized neonatal death of different gestational ages in Shaanxi Province.Methods:All neonatal deaths in six hospitals in Shaanxi Province from 2016 to 2020 were retrospectively analyzed, and the differences in perinatal complications, the causes of death, and the age at death were compared using Chi-square (or Fisher's exact ) test. Results:(1) Totally, 220 488 neonates were delivered in the obstetric department of the six hospitals during the study period; 71 782 out of them were admitted to the neonatal department. While 424 neonatal death was reported, giving the total hospitalized neonates mortality rate of 5.5‰ (394/71 782), which included 152 deaths of transferred patients ( n=9 103, 16.7‰), 226 premature (53.3%), 196 term (46.2%), and two post-term infants (0.5%). (2) Among mothers of dead neonates, 73.6% were found to have at least one perinatal complication. The most common one was fetal distress (146 cases, 34.4%), followed by gestational diabetes mellitus (113 cases, 26.7%), amniotic fluid abnormalities ( n=73, 17.2%), maternal infectious diseases ( n=71, 16.8%), and hypertensive disorders in pregnancy (HDP) ( n=52, 12.3%). The lower the gestational age, the higher the proportion of multiple pregnancies and assisted reproduction technology applied (Fisher exact test, P<0.05). On the contrary, the higher the gestational age, the higher the cesarean section rate ( χ 2=26.69, P<0.001). HDP was more likely to occur in the gestational age of 28-31 +6 and 32-34 +6 weeks ( χ 2=37.16, P<0.001), and amniotic fluid abnormalities were more likely to occur in those over 37 weeks ( χ 2=27.47, P<0.001). (3) The five leading causes of neonatal death were neonatal respiratory distress syndrome (NRDS, n=100, 23.6%), neonatal asphyxia ( n=88, 20.8%), maternal infectious diseases ( n=80, 18.9%), and birth defects ( n=54, 12.7%), and pulmonary hemorrhage ( n=22, 5.2%). The first three causes of death in term and post-term infants were neonatal asphyxia ( n=65, 32.8%), birth defects ( n=42, 21.2%), and infectious diseases ( n=26, 13.1%). NRDS ( n=83, 36.7%), infectious diseases ( n=54, 23.9%), and neonatal asphyxia ( n=23, 10.2%) were the three leading causes of death of premature babies. (4) Out of the 326 (76.9%) neonatal deaths within seven days after birth, 162 (38.2%) died within 24 h after birth and 164 cases (38.7%) between one to seven days after birth. Conclusions:Most neonatal deaths occurred among preterm ones and within seven days after birth, whose mothers suffered perinatal complications. The causes of neonatal death vary among different gestational age groups.
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BackgroundAn outbreak of COVID-19 caused by the SARS-CoV-2 Omicron BA.2 sublineage occurred in Shanghai, China from February to June 2022. The government organized multiple rounds of molecular test screenings for the entire population, providing a unique opportunity to capture the majority of subclinical infections and better characterize disease burden and the full spectrum of Omicron BA.2 clinical severity. MethodsUsing daily reports from the websites of the Shanghai Municipal Health Commission, we estimated the incidence of infections, severe/critical infections, and deaths to assess the disease burden. By adjusting for right censoring and Reverse Transcription-Polymerase Chain Reaction (RT{square}PCR) sensitivity, we provide estimates of clinical severity, including the infection fatality risk, symptomatic case fatality risk, and risk of developing severe/critical disease upon infection. FindingsFrom February 26 to June 30, 2022, the overall infection rate, severe/critical infection rate, and mortality rate were 2.74 (95% CI: 2.73-2.74) per 100 individuals, 6.34 (95% CI: 6.02-6.66) per 100,000 individuals and 2.42 (95% CI: 2.23-2.62) per 100,000 individuals, respectively. The severe/critical infection rate and mortality rate increased with age with the highest rates of 125.29 (95% CI: 117.05-133.44) per 100,000 and 57.17 (95% CI: 51.63-62.71) per 100,000 individuals, respectively, noted in individuals aged 80 years or older. The overall fatality risk and risk of developing severe/critical disease upon infection were 0.09% (95% CI: 0.08-0.10%) and 0.23% (95% CI: 0.20-0.25%), respectively. Having received at least one vaccine dose led to a 10-fold reduction in the risk of death for infected individuals aged 80 years or older. InterpretationUnder the repeated population-based screenings and strict intervention policies implemented in Shanghai, our results found a lower disease burden and mortality of the outbreak compared to other settings and countries, showing the impact of the successful outbreak containment in Shanghai. The estimated low clinical severity of this Omicron BA.2 epidemic in Shanghai highlight the key contribution of vaccination and availability of hospital beds to reduce the risk of death. FundingKey Program of the National Natural Science Foundation of China (82130093). Research in contextO_ST_ABSEvidence before this studyC_ST_ABSWe searched PubMed and Europe PMC for manuscripts published or posted on preprint servers after January 1, 2022 using the following query: ("SARS-CoV-2 Omicron") AND ("burden" OR "severity"). No studies that characterized the whole profile of disease burden and clinical severity during the Shanghai Omicron outbreak were found. One study estimated confirmed case fatality risk between different COVID-19 waves in Hong Kong; other outcomes, such as fatality risk and risk of developing severe/critical illness upon infection, were not estimated. One study based on 21 hospitals across the United States focused on Omicron-specific in-hospital mortality based on a limited sample of inpatients (565). In southern California, United States, a study recruited more than 200 thousand Omicron-infected individuals and estimated the 30-day risk of hospital admission, intensive care unit admission, mechanical ventilation, and death. None of these studies estimated infection and mortality rates or other indictors associated with disease burden. Overall, the disease burden and clinical severity of the Omicron BA.2 variant have not been fully characterized, especially in populations predominantly immunized with inactivated vaccines. Added value of this studyThe large-scale and multiround molecular test screenings conducted on the entire population during the Omicron BA.2 outbreak in Shanghai, leading to a high infection ascertainment ratio, provide a unique opportunity to capture the majority of subclinical infections. As such, our study provides a comprehensive assessment of both the disease burden and clinical severity of the SARS-CoV-2 Omicron BA.2 sublineage, which are especially lacking for populations predominantly immunized with inactivated vaccines. Implications of all the available evidenceWe estimated the disease burden and clinical severity of the Omicron BA.2 outbreak in Shanghai in February-June 2022. These estimates are key to properly interpreting field evidence and assessing the actual spread of Omicron in other settings. Our results also provide support for the importance of strategies to prevent overwhelming the health care system and increasing vaccine coverage to reduce mortality.
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BackgroundIn early March 2022, a major outbreak of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron variant spread rapidly throughout Shanghai, China. Here we aimed to provide a description of the epidemiological characteristics and spatiotemporal transmission dynamics of the Omicron outbreak under the population-based screening and lockdown policies implemented in Shanghai. MethodsWe extracted individual information on SARS-CoV-2 infections reported between January 1 and May 31, 2022, and on the timeline of the adopted non-pharmacological interventions. The epidemic was divided into three phases: i) sporadic infections (January 1-February 28), ii) local transmission (March 1-March 31), and iii) city-wide lockdown (April 1 to May 31). We described the epidemic spread during these three phases and the subdistrict-level spatiotemporal distribution of the infections. To evaluate the impact on the transmission of SARS-CoV-2 of the adopted targeted interventions in Phase 2 and city-wide lockdown in Phase 3, we estimated the dynamics of the net reproduction number (Rt). FindingsA surge in imported infections in Phase 1 triggered cryptic local transmission of the Omicron variant in early March, resulting in the largest coronavirus disease 2019 (COVID-19) outbreak in mainland China since the original wave. A total of 626,000 SARS-CoV-2 infections were reported in 99.5% (215/216) of the subdistricts of Shanghai. The spatial distribution of the infections was highly heterogeneous, with 40% of the subdistricts accounting for 80% of all infections. A clear trend from the city center towards adjacent suburban and rural areas was observed, with a progressive slowdown of the epidemic spread (from 544 to 325 meters/day) prior to the citywide lockdown. During Phase 2, Rt remained well above 1 despite the implementation of multiple targeted interventions. The citywide lockdown imposed on April 1 led to a marked decrease in transmission, bringing Rt below the epidemic threshold in the entire city on April 14 and ultimately leading to containment of the outbreak. InterpretationOur results highlight the risk of widespread outbreaks in mainland China, particularly under the heightened pressure of imported infections. The targeted interventions adopted in March 2022 were not capable of halting transmission, and the implementation of a strict, prolonged city-wide lockdown was needed to successfully contain the outbreak, highlighting the challenges for successfully containing Omicron outbreaks. FundingKey Program of the National Natural Science Foundation of China (82130093). Research in contextO_ST_ABSEvidence before this studyC_ST_ABSOn May 24, 2022, we searched PubMed and Europe PMC for papers published or posted on preprint servers after January 1, 2022, using the following query: ("SARS-CoV-2" OR "Omicron" OR "BA.2") AND ("epidemiology" OR "epidemiological" OR "transmission dynamics") AND ("Shanghai"). A total of 26 studies were identified; among them, two aimed to describe or project the spread of the 2022 Omicron outbreak in Shanghai. One preprint described the epidemiological and clinical characteristics of 376 pediatric SARS-CoV-2 infections in March 2022, and the other preprint projected the epidemic progress in Shanghai, without providing an analysis of field data. In sum, none of these studies provided a comprehensive description of the epidemiological characteristics and spatiotemporal transmission dynamics of the outbreak. Added value of this studyWe collected individual information on SARS-CoV-2 infection and the timeline of the public health response. Population-based screenings were repeatedly implemented during the outbreak, which allowed us to investigate the spatiotemporal spread of the Omicron BA.2 variant as well as the impact of the implemented interventions, all without enduring significant amounts of underreporting from surveillance systems, as experienced in other areas. This study provides the first comprehensive assessment of the Omicron outbreak in Shanghai, China. Implications of all the available evidenceThis descriptive study provides a comprehensive understanding of the epidemiological features and transmission dynamics of the Omicron outbreak in Shanghai, China. The empirical evidence from Shanghai, which was ultimately able to curtail the outbreak, provides invaluable information to policymakers on the impact of the containment strategies adopted by the Shanghai public health officials to prepare for potential outbreaks caused by Omicron or novel variants.
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Objective:To investigate the effect of milk on sebum secretion in golden hamsters, and to explore its possible mechanism of action.Methods:Eighteen golden hamsters were randomly and equally divided into 3 groups: blank control group receiving no intervention, whole-milk group gavaged with whole milk, and skimmed-milk group gavaged with skimmed milk. The gavage feeding was performed at a dose of 2.5 ml twice a day for 4 consecutive weeks. The maximum transverse diameter and maximum longitudinal diameter of bilateral sebaceous gland spots were measured on days 0, 7, 14, 21 and 28 after the start of intervention, and the area of sebaceous gland spots was calculated; at 24 hours after the last gavage, bilateral sebaceous gland spot tissues were resected, and subjected to immunohistochemical study to determine the expression of insulin-like growth factor-1 (IGF-1) /sterol regulatory element-binding protein-1 (SREBP-1) /acetyl-coenzyme A carboxylase (ACC-1) signaling pathway in sebaceous gland spots. Statistical analysis was carried out by using repeated measures analysis of variance, one-way analysis of variance for independent groups, Kruskal-Wallis H test, and least significant difference- t test for multiple comparisons. Results:Repeated measures analysis of variance showed that there was no significant difference in the area of sebaceous gland spots of golden hamsters among the 3 groups ( F= 0.96, P= 0.417) . The IGF-1 expression was significantly higher in the skimmed-milk group (0.39 ± 0.03) than in the blank control group (0.35 ± 0.03, t= 2.62, P= 0.021) and whole-milk group (0.33 ± 0.02, t= 3.82, P= 0.002) ; compared with the blank control group (0.36 ± 0.02) , the skimmed-milk group showed significantly increased SREBP-1 expression (0.42 ± 0.04, t= 2.64, P= 0.021) ; the ACC-1 expression was significantly higher in the skimmed-milk group (0.40 ± 0.03) and whole-milk group (0.40 ± 0.05) than in the blank control group (0.34 ± 0.03; t= 2.39, 2.47, P= 0.031, 0.026, respectively) . Conclusion:Milk may promote sebum secretion in golden hamsters through the IGF-1/SREBP-1/ACC-1 signaling pathway.
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Objective:To explore the methods of standardized residency training for internal medicine residents in the post-epidemic era, and to provide theoretical basis for improving and optimizing the standardized residency training.Methods:A total of 228 resident physicians from Batch 2017 to Batch 2019 were recruited, and a questionnaire survey was conducted to investigate their basic information, their attitudes and actions in facing the epidemic and the epidemic impact on the occupational planning and rotation plan. Original data of this study were exported through the questionnaire platform "Questionnaire Network", sorted out by Microsoft Excel, and plotted and analyzed by Origin software.Results:Residents of our hospital, socialized medical residents, other unit sponsor residents and combined professional masters willing to go to Hubei for medical support accounted for 100% (30 people), 86% (6 people), 84% (80 people) and 77% (72 people) respectively. Almost all of the residents were willing to learn the knowledge of COVID-19 and to educate the public (99%-100%). Eighty percent (24 people) of the residents of our hospital participated in anti-epidemic, while the proportion of other unit sponsor residents, socialized medical residents and combined professional masters were 46% (44 people), 14% (1 people) and 12% (11 people), respectively. Additionally, 97% (29 people) of our hospital residents, 89% (85 people) of other unit sponsor residents, 86% (6 people) of the socialized medical residents, and 82% (76 people) of the combined professional masters would still like to engage in the clinical work in the future. What's more, the resident physicians who thought that phylaxiology, epidemiology, general practice medicine, traditional Chinese medicine and critical care medicine should be strengthened to train accounted for 98% (221 people), 98% (221 people), 90% (203 people), 70% (158 people) and 60% (135 people) respectively.Conclusion:Most resident physicians have strong awareness and active actions in fighting against the epidemic. In the future, the standardized residency training of physicians should further strengthen the training of phylaxiology, epidemiology, general practice medicine, traditional Chinese medicine and critical care medicine.
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Lower limb ankle exoskeletons have been used to improve walking efficiency and assist the elderly and patients with motor dysfunction in daily activities or rehabilitation training, while the assistance patterns may influence the wearer's lower limb muscle activities and coordination patterns. In this paper, we aim to evaluate the effects of different ankle exoskeleton assistance patterns on wearer's lower limb muscle activities and coordination patterns. A tethered ankle exoskeleton with nine assistance patterns that combined with differenet actuation timing values and torque magnitude levels was used to assist human walking. Lower limb muscle surface electromyography signals were collected from 7 participants walking on a treadmill at a speed of 1.25 m/s. Results showed that the soleus muscle activities were significantly reduced during assisted walking. In one assistance pattern with peak time in 49% of stride and peak torque at 0.7 N·m/kg, the soleus muscle activity was decreased by (38.5 ± 10.8)%. Compared with actuation timing, the assistance torque magnitude had a more significant influence on soleus muscle activity. In all assistance patterns, the eight lower limb muscle activities could be decomposed to five basic muscle synergies. The muscle synergies changed little under assistance with appropriate actuation timing and torque magnitude. Besides, co-contraction indexs of soleus and tibialis anterior, rectus femoris and semitendinosus under exoskeleton assistance were higher than normal walking. Our results are expected to help to understand how healthy wearers adjust their neuromuscular control mechanisms to adapt to different exoskeleton assistance patterns, and provide reference to select appropriate assistance to improve walking efficiency.
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Idoso , Humanos , Tornozelo/fisiologia , Articulação do Tornozelo/fisiologia , Fenômenos Biomecânicos/fisiologia , Eletromiografia , Exoesqueleto Energizado , Marcha/fisiologia , Contração Muscular , Músculo Esquelético/fisiologia , Caminhada/fisiologiaRESUMO
BackgroundTo allow a return to a pre-COVID-19 lifestyle, virtually every country has initiated a vaccination program to mitigate severe disease burden and control transmission. However, it remains to be seen whether herd immunity will be within reach of these programs. MethodsWe developed a data-driven model of SARS-CoV-2 transmission for China, a population with low prior immunity from natural infection. The model is calibrated considering COVID-19 natural history and the estimated transmissibility of the Delta variant. Three vaccination programs are tested, including the one currently enacted in China and model-based estimates of the herd immunity level are provided. ResultsWe found that it is unlike to reach herd immunity for the Delta variant given the relatively low efficacy of the vaccines used in China throughout 2021, the exclusion of underage individuals from the targeted population, and the lack of prior natural immunity. We estimate that, assuming a vaccine efficacy of 90% against the infection, vaccine-induced herd immunity would require a coverage of 93% or higher of the Chinese population. However, even when vaccine-induced herd immunity is not reached, we estimated that vaccination programs can reduce SARS-CoV-2 infections by 53-58% in case of an epidemic starts to unfold in the fall of 2021. ConclusionsEfforts should be taken to increase populations confidence and willingness to be vaccinated and to guarantee highly efficacious vaccines for a wider age range.
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BackgroundTransmission of respiratory pathogens such as SARS-CoV-2 depends on patterns of contact and mixing across populations. Understanding this is crucial to predict pathogen spread and the effectiveness of control efforts. Most analyses of contact patterns to date have focussed on high-income settings. MethodsHere, we conduct a systematic review and individual-participant meta-analysis of surveys carried out in low- and middle-income countries and compare patterns of contact in these settings to surveys previously carried out in high-income countries. Using individual-level data from 28,503 participants and 413,069 contacts across 27 surveys we explored how contact characteristics (number, location, duration and whether physical) vary across income settings. ResultsContact rates declined with age in high- and upper-middle-income settings, but not in low-income settings, where adults aged 65+ made similar numbers of contacts as younger individuals and mixed with all age-groups. Across all settings, increasing household size was a key determinant of contact frequency and characteristics, but low-income settings were characterised by the largest, most intergenerational households. A higher proportion of contacts were made at home in low-income settings, and work/school contacts were more frequent in high-income strata. We also observed contrasting effects of gender across income-strata on the frequency, duration and type of contacts individuals made. ConclusionsThese differences in contact patterns between settings have material consequences for both spread of respiratory pathogens, as well as the effectiveness of different non-pharmaceutical interventions. FundingThis work is primarily being funded by joint Centre funding from the UK Medical Research Council and DFID (MR/R015600/1).
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There are contrasting results concerning the effect of reactive school closure on SARS-CoV-2 transmission. To shed light on this controversy, here we develop a data-driven computational model of SARS-CoV-2 transmission to investigate mechanistically the effect on COVID-19 outbreaks of school closure strategies based on syndromic surveillance and antigen screening of students. We found that by reactively closing classes based on syndromic surveillance, SARS-CoV-2 infections are reduced by no more than 13.1% (95%CI: 8.6%-20.2 %), due to the low probability of timely symptomatic case identification among the young population. We thus investigated an alternative triggering mechanism based on repeated screening of students using antigen tests. Should population-level social distancing measures unrelated to schools enable maintaining the reproduction number (R) at 1.3 or lower, an antigen-based screening strategy is estimated to fully prevent COVID-19 outbreaks in the general population. Depending on the contribution of schools to transmission, this strategy can either prevent COVID-19 outbreaks for R up to 1.9 or to at least greatly reduce outbreak size in very conservative scenarios about school contribution to transmission. Moving forward, the adoption of antigen-based screenings in schools could be instrumental to limit COVID-19 burden while vaccines continue to roll out through 2021, especially in light of possible continued emergence of SARS-CoV-2 variants.
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AbstractCOVID-19 vaccination is being conducted in over 190 countries/regions to control SARS-CoV-2 transmission and return to a pre-pandemic lifestyle. However, understanding when non-pharmaceutical interventions (NPIs) can be lifted as immunity builds up remain a key question for policy makers. To address it, we built a data-driven model of SARS-CoV-2 transmission for China. We estimated that to prevent the escalation of local outbreaks to widespread epidemics, stringent NPIs need to remain in place at least one year after the start of vaccination. Should NPIs alone be capable to keep the reproduction number (Rt) around 1.3, the synergetic effect of NPIs and vaccination could reduce up to 99% of COVID-19 burden and bring Rt below the epidemic threshold in about 9 months. Maintaining strict NPIs throughout 2021 is of paramount importance to reduce COVID-19 burden while vaccines are distributed to the population, especially in large populations with little natural immunity.
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Objective:To investigate the clinical characteristics and influencing factors of pain symptoms in patients with idiopathic Parkinson′s disease.Methods:The King′s Parkinson′s Disease Pain Scale (KPPS) was used to evaluate pain of 106 patients with Parkinson′s disease. The Pittsburgh Sleep Quality Index (PSQI), the Fatigue Scale-14 (FS-14), the Unified Parkinson′s Disease Rating Scale Ⅲ, Hoehn-Yahr scale (H-Y), Mini-Mental State Examination (MMSE), Hamilton Anxiety Scale (HAMA) and Hamilton Depression Scale (HAMD) were used to assess the sleep status of patients, the degree of fatigue, motor function, severity of symptoms, cognitive function, anxiety and depression. Fifty-eight patients were followed up for three to six months.Results:The incidence of pain in Parkinson′s disease patients was 50.0% (53/106), of which skeletal muscle pain was the most common. Parkinson′s disease patients with a longer course of disease were more likely to have pain [course of disease in Parkinson′s disease with pain was 3.0 (1.5, 5.0) years, in Parkinson′s disease without pain was 2.0 (1.5, 2.5) years, Z=-2.0, P=0.046]. Male patients had more severe pain than female patients [KPPS scores in males were 14.5 (8.0, 21.5), in females were 10.0(4.0, 15.3), Z=-2.81, P=0.005]. In the first evaluation, the H-Y grading and the FS-14 scores of Parkinson′s disease patients with pain were significantly higher than those without pain [H-Y grading in Parkinson′s disease patients with pain was 2.0 (1.5, 2.5), in Parkinson′s disease patients without pain was 2.0 (1.5, 2.0), Z=-2.02, P=0.043; FS-14 scores in patients with pain were 10.0 (8.0, 11.0), in patients without pain was 8.0 (5.0, 10.0), Z=-3.32, P=0.001]. The KPPS scores were positively correlated with the scores of HAMA and HAMD ( r=0.39, P=0.005; r=0.38, P=0.007). Binary Logistic regression analysis showed that Parkinson′s disease patients with higher scores of FS-14 had an increased risk of developing pain ( OR=1.27, 95% CI: 1.09-1.48, P=0.002). The changes of KPPS scores were associated with the changes of PSQI and FS-14 scores ( r=0.54, P=0.002; r=0.50, P=0.003). The decrease of KPPS scores was only positively correlated with the decrease of FS-14 scores when the drug and medication status remained unchanged ( r=0.421, P=0.045). Multiple linear regression analysis showed that the decrease of FS-14 scores was associated with the decrease of the KPPS scores ( OR=2.02, P=0.033). Conclusions:Parkinson′s disease patients have a high incidence of pain, and fatigue is a factor for predicting the occurrence and outcome of pain in Parkinson′s disease. The severity and change of pain in Parkinson′s disease patients are related to anxiety, depression, sleep and fatigue, suggesting that there may be a common pathogenesis of pain, emotion, sleep and fatigue in Parkinson′s disease patients.
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Non-pharmaceutical interventions to control COVID-19 spread have been implemented in several countries with different intensity, timing, and impact on transmission. As a result, post-lockdown COVID-19 dynamics are heterogenous and difficult to interpret. Here we describe a set of contact surveys performed in four Chinese cities (Wuhan, Shanghai, Shenzhen, and Changsha) during the pre-pandemic, lockdown, and post-lockdown period to quantify the transmission impact of relaxing interventions via changes in age-specific contact patterns. We estimate that the mean number of contacts increased 5%-17% since the end of the lockdown but are still 3-7 times lower than their pre-pandemic levels. We find that post-lockdown contact patterns in China are still sufficiently low to keep SARS-CoV-2 transmission under control. We also find that the impact of school interventions depends non-linearly on the share of other activities being resumed. When most community activities are halted, school closure leads to a 77% decrease in the reproductive number; in contrast, when social mixing outside of schools is at pre-pandemic level, school closure leads to a 5% reduction in transmission. Moving forward, to control COVID-19 spread without resorting to a lockdown, it will be key to dose relaxation in social mixing in the community and strengthen targeted interventions. One Sentence SummarySocial contacts estimated in the post-lockdown period in four large Chinese cities are not sufficient to sustain local SARS-CoV-2 transmission.
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Strict interventions were successful to control the novel coronavirus (COVID-19) outbreak in China. As transmission intensifies in other countries, the interplay between age, contact patterns, social distancing, susceptibility to infection and disease, and COVID-19 dynamics remains unclear. To answer these questions, we analyze contact surveys data for Wuhan and Shanghai before and during the outbreak and contact tracing information from Hunan Province. Daily contacts were reduced 7-9 fold during the COVID-19 social distancing period, with most interactions restricted to the household. Children 0-14 years were 59% (95% CI 7-82%) less susceptible than individuals 65 years and over. A transmission model calibrated against these data indicates that social distancing alone, as implemented in China during the outbreak, is sufficient to control COVID-19. While proactive school closures cannot interrupt transmission on their own, they reduce peak incidence by half and delay the epidemic. These findings can help guide global intervention policies.
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ObjectiveThe outbreak of novel coronavirus disease 2019 (COVID-19) imposed a substantial health burden in mainland China and remains a global epidemic threat. Our objectives are to assess the case fatality risk (CFR) among COVID-19 patients detected in mainland China, stratified by clinical category and age group. MethodsWe collected individual information on laboratory-confirmed COVID-19 cases from publicly available official sources from December 29, 2019 to February 23, 2020. We explored the risk factors associated with mortality. We used methods accounting for right-censoring and survival analyses to estimate the CFR among detected cases. ResultsOf 12,863 cases reported outside Hubei, we obtained individual records for 9,651 cases, including 62 deaths and 1,449 discharged cases. The deceased were significantly older than discharged cases (median age: 77 vs 39 years, p<0.001). 58% (36/62) were male. Older age (OR 1.18 per year; 95%CI: 1.14 to 1.22), being male (OR 2.02; 95%CI: 1.02 to 4.03), and being treated in less developed economic regions (e.g., West and Northeast vs. East, OR 3.93; 95%CI: 1.74 to 8.85) were mortality risk factors. The estimated CFR was 0.89-1.24% among all cases. The fatality risk among critical patients was 2-fold higher than that among severe and critical patients, and 24-fold higher than that among moderate, severe and critical patients. ConclusionsOur estimates of CFR based on laboratory-confirmed cases ascertained outside of Hubei suggest that COVID-19 is not as severe as severe acute respiratory syndrome and Middle East respiratory syndrome, but more similar to the mortality risk of 2009 H1N1 influenza pandemic in hospitalized patients. The fatality risk of COVID-19 is higher in males and increases with age. Our study improves the severity assessment of the ongoing epidemic and can inform the COVID-19 outbreak response in China and beyond.
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BackgroundThe COVID-19 epidemic originated in Wuhan City of Hubei Province in December 2019 and has spread throughout China. Understanding the fast evolving epidemiology and transmission dynamics of the outbreak beyond Hubei would provide timely information to guide intervention policy. MethodsWe collected individual information on 8,579 laboratory-confirmed cases from official publically sources reported outside Hubei in mainland China, as of February 17, 2020. We estimated the temporal variation of the demographic characteristics of cases and key time-to-event intervals. We used a Bayesian approach to estimate the dynamics of the net reproduction number (Rt) at the provincial level. ResultsThe median age of the cases was 44 years, with an increasing of cases in younger age groups and the elderly as the epidemic progressed. The delay from symptom onset to hospital admission decreased from 4.4 days (95%CI: 0.0-14.0) until January 27 to 2.6 days (0.0-9.0) from January 28 to February 17. The mean incubation period was estimated at 5.2 days (1.8-12.4) and the mean serial interval at 5.1 days (1.3-11.6). The epidemic dynamics in provinces outside Hubei was highly variable, but consistently included a mix of case importations and local transmission. We estimate that the epidemic was self-sustained for less than three weeks with Rt reaching peaks between 1.40 (1.04-1.85) in Shenzhen City of Guangdong Province and 2.17 (1.69-2.76) in Shandong Province. In all the analyzed locations (n=10) Rt was estimated to be below the epidemic threshold since the end of January. ConclusionOur findings suggest that the strict containment measures and movement restrictions in place may contribute to the interruption of local COVID-19 transmission outside Hubei Province. The shorter serial interval estimated here implies that transmissibility is not as high as initial estimates suggested.
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BackgroundIn response to the COVID-19 outbreak, we aimed to investigate behavioural change on exposure to live animals before and during the outbreak, and public support and confidence for governmental containment measures. MethodsA population-based cross-sectional telephone survey via random dialing was conducted in Wuhan (the epicentre) and Shanghai (an affected city with imported cases) between 1 and 10 February, 2020. 510 residents in Wuhan and 501 residents in Shanghai were randomly sampled. Differences of outcome measures were compared before and during the outbreak, and between two cities. FindingsProportion of respondents visiting wet markets at usual was 23.3% (119/510) in Wuhan and 20.4% (102/501) in Shanghai. During the outbreak, it decreased to 3.1% (16) in Wuhan (p<0{middle dot}001), and 4.4% (22) in Shanghai (p<0{middle dot}001). Proportion of those consuming wild animal products declined from 10.2% (52) to 0.6% (3) in Wuhan (p<0{middle dot}001), and from 5.2% (26) to 0.8% (4) in Shanghai (p<0{middle dot}001). 79.0% (403) of respondents in Wuhan and 66.9% (335) of respondents in Shanghai supported permanent closure of wet markets (P<0.001). 95% and 92% of respondents supported banning wild animal trade and quarantining Wuhan, and 75% were confident towards containment measures. Females and the more educated were more supportive for the above containment measures. InterpretationThe public responded quickly to the outbreak, and reduced exposure to live animals, especially in Wuhan. With high public support in containment measures, better regulation of wet markets and healthy diets should be promoted. FundingNational Science Fund for Distinguished Young Scholars, H2020 MOOD project. Research in contextO_ST_ABSEvidence before this studyC_ST_ABSOn February 19, 2020, we searched PubMed for papers published after January 1, 2020, containing the following terms: "2019 nCoV" or "COVID-19". We identified 179 studies, most of which are research on clinical and epidemiological characteristics of COVID-19. To date there is no primary research to quantify public behavioural response and support in containment measures in response to the outbreak. Only four commentaries mentioned the influence of the outbreak on mental health. One commentary introduced the habit of consuming wild animal products in China. Another commentary briefly introduced isolation, quarantine, social distancing and community containment as public health measures in the outbreak. The Chinese government has introduced a series of strict containment measures, and societal acceptability of these measure is important for effective and sustained response. Evidence is urgently needed to help policy makers understand public response to the outbreak and support for the containment measures, but no evidence available to date. Added value of this studyWe conducted a population-based cross-sectional telephone survey via random digital dialing in Wuhan (the epicentre) and Shanghai (an affected city with imported cases) between 1 and 10 February, 2020. To date, this is the only few analyses on behavioural response to the outbreak and societal acceptability of governmental containment measures, which has been listed as the current priority of China CDC. We provide an assessment of behavioural change on exposure to live animals during the outbreak, by comparison before and during the outbreak, and between two cities with diverse exposure intensities to COVID-19. We also provide evidence on public support in governmental containment measures, including strict regulation on wet markets to reduce animal-to-human transmission and city quarantine to reduce human transmission. Implications of all the available evidenceWe found that wild animal consumption was more prevalent in Wuhan (10.2%) than in Shanghai (5.2%). The public responded quickly to the outbreak, and significantly reduced exposure to live animals and stopped wild animal consumption, especially in Wuhan. They were very supportive of governmental containment measures. With high public support, wet markets should be better regulated, and healthy diets, including changing the traditional habit of eating wild animal products, should be promoted. This can inform policy makers in China and other countries to implement and adjust containment strategies in response to the outbreak in the future.
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Objective:To investigate the expression of macrophage migration inhibitory factor (MIF) in bone marrow fluid and peripheral blood of patients with acute myeloid leukemia (AML) and its effect on the expression of interleukin-8 (IL-8) in bone marrow mesenchymal stem cells (BM-MSC).Methods:Fifty bone marrow fluid samples and 50 peripheral blood samples were collected from 50 patients with AML diagnosed in the First People's Hospital of Yunnan Province from October 2017 to January 2019, of which 17 patients were newly diagnosed, 26 patients were complete remission (CR), and 7 patients were partial remission (PR) or non-remission (NR). Fifty plasma samples from 50 healthy subjects and 50 bone marrow fluid samples from 50 patients with iron deficiency anemia were used as the controls. Enzyme-linked immunosorbent assay (ELISA) was used to detect the level of MIF protein in the samples, and the relationship between MIF expression level and clinicopathological characteristics of AML patients was analyzed. BM-MSC was successfully isolated and cultured from 42 bone marrow fluid samples of AML patients, the suitable samples for experiment were chosen and divided into BM-MSC control group (untreated BM-MSC), recombinant human macrophage migration inhibitory factor (rhMIF) group and rhMIF+ISO-1 group. ELISA and real-time fluorescence quantitative polymerase chain reaction were used to detect the expression level of IL-8 protein and mRNA in each BM-MSC group.Results:The expression levels of MIF protein in bone marrow fluid and plasma in AML group were (24.9±7.7) ng/ml and (60.5±12.1) ng/ml, the difference was statistically significant ( P < 0.01), and those in control group were (5.3±2.6) ng/ml and (2.0±1.1) ng/ml, respectively, and there were statistical differences between the two groups (t values were 136.71, 33.97 and 17.58, all P < 0.01). MIF protein expression levels in bone marrow fluid and plasma of AML patients in newly diagnosed group and PR+NR group were higher than those in CR group, and the differences were statistically significant (all P < 0.01). MIF protein expression levels were higher in bone marrow fluid and plasma of patients with ≥60 years of age, peripheral blood white blood cell count ≥30×10 9/L and bone marrow myeloblast ratio > 0.50 (all P < 0.05), but the differences were not statistically significant between patients with different gender (both P > 0.05). The detection results of each BM-MSC group showed that rhMIF promoted the IL-8 expression in BM-MSC at the gene and protein levels, which could be inhibited by the MIF inhibitor ISO-1 (all P < 0.01). Conclusion:The increased expression levels of MIF in bone marrow fluid and plasma of patients with AML are associated with the disease progression, and rhMIF can promote the expression of IL-8 in BM-MSC.
