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Objective: To analyze the direct economic burden caused by measles cases in Shanghai from 2017 to 2019 and its influencing factors. Methods: A total of 161 laboratory-confirmed measles cases reported from January 1, 2017, to December 31, 2019, in Shanghai were included in the study through the "Measles Surveillance Information Reporting and Management System" of the "China Disease Surveillance Information Reporting and Management System". Through telephone follow-up and consulting hospital data, the basic information of population, medical treatment situation, medical treatment costs and other information were collected, and the direct economic burden of cases was calculated, including registration fees, examination fees, hospitalization fees, medical fees and other disease treatment expenses, as well as transportation and other expenses of cases. The multiple linear regression model was used to analyze the main influencing factors of the direct economic burden. Results: The age of 161 measles cases M (Q1, Q3) was 28.21 (13.33, 37.00) years. Male cases (56.52%) were more than female cases (43.48%). The largest number of cases was≥18 years old (70.81%). The total direct economic burden of 161 measles cases was 540 851.14 yuan, and the per capita direct economic burden was 3 359.32 yuan. The direct economic burden M (Q1, Q3) was 873.00 (245.01, 4 014.79) yuan per person. The results of multiple linear regression model analysis showed that compared with other and unknown occupations, central areas and non-hospitalized cases, the direct economic burden of measles cases was higher in scattered children, childcare children, students, and cadre staff in the occupational distribution, suburban areas and hospitalized, with the coefficient of β (95%CI) values of 0.388 (0.150-0.627), 0.297 (0.025-0.569), 0.327 (0.148-0.506) and 1.031 (0.853-1.209), respectively (all P values<0.05). Conclusion: The direct economic burden of some measles cases in Shanghai is relatively high. Occupation, area of residence and hospitalization are the main factors influencing the direct economic burden of measles cases.
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Child , Humans , Male , Female , Adolescent , Financial Stress , Cost of Illness , China/epidemiology , Health Care Costs , Measles/epidemiologyABSTRACT
During the global efforts to prevent and control the COVID-19 pandemic, extensive research and development of SARS-CoV-2 vaccines using various technical approaches have taken place. Among these, vaccines based on adenovirus vector have gained substantial knowledge and experience in effectively combating potential emerging infectious diseases, while also providing novel ideas and methodologies for vaccine research and development (R&D). This comprehensive review focuses on the adenovirus vector technology platform in vaccine R&D, emphasizing the importance of mucosal immunity induced by adenoviral vector-based vaccine for COVID-19 prevention. Furthermore, it analyzes the key technical challenges and obstacles encountered in the development of vaccines based on the adenovirus vector technology platform, with the aim of providing valuable insights and references for researchers and professionals in related fields.
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Humans , COVID-19 Vaccines , Pandemics/prevention & control , COVID-19/prevention & control , SARS-CoV-2/genetics , Viral Vaccines/genetics , Adenoviridae/genetics , TechnologyABSTRACT
Background In mainland China, patients with neovascular age-related macular degeneration (nAMD) have approximately an 40% prevalence of polypoidal choroidal vasculopathy (PCV). This disease leads to recurrent retinal pigment epithelium detachment (PED), extensive subretinal or vitreous hemorrhages, and severe vision loss. China has introduced various treatment modalities in the past years and gained comprehensive experience in treating PCV.Methods A total of 14 retinal specialists nationwide with expertise in PCV were empaneled to prioritize six questions and address their corresponding outcomes, regarding opinions on inactive PCV, choices of anti-vascular endothelial growth factor (anti-VEGF) monotherapy, photodynamic therapy (PDT) monotherapy or combined therapy, patients with persistent subretinal fluid (SRF) or intraretinal fluid (IRF) after loading dose anti-VEGF, and patients with massive subretinal hemorrhage. An evidence synthesis team conducted systematic reviews, which informed the recommendations that address these questions. This guideline used the GRADE (Grading of Recommendations, Assessment, Development, and Evaluation) approach to assess the certainty of evidence and grade the strengths of recommendations. Results The panel proposed the following six conditional recommendations regarding treatment choices. (1) For patients with inactive PCV, we suggest observation over treatment. (2) For treatment-na?ve PCV patients, we suggest either anti-VEGF monotherapy or combined anti-VEGF and PDT rather than PDT monotherapy. (3) For patients with PCV who plan to initiate combined anti-VEGF and PDT treatment, we suggest later/rescue PDT over initiate PDT. (4) For PCV patients who plan to initiate anti-VEGF monotherapy, we suggest the treat and extend (T&E) regimen rather than the pro re nata (PRN) regimen following three monthly loading doses. (5) For patients with persistent SRF or IRF on optical coherence tomography (OCT) after three monthly anti-VEGF treatments, we suggest proceeding with anti-VEGF treatment rather than observation. (6) For PCV patients with massive subretinal hemorrhage (equal to or more than four optic disc areas) involving the central macula, we suggest surgery (vitrectomy in combination with tissue-plasminogen activator (tPA) intraocular injection and gas tamponade) rather than anti-VEGF monotherapy. Conclusions Six evidence-based recommendations support optimal care for PCV patients' management.
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Objective: To develop a rapid risk assessment tool for imported COVID-19 cases and provide reference evidences for prevention and control of COVID-19 at ports. Methods: The information about COVID-19 pandemic and control strategies of 12 concerned countries was collected during July to August 2021, and 12 indexes were selected to assess the importation risk of COVID-19 by risk matrix. Results: The risk for imported COVID-19 cases from 12 countries to China was high or extremely high, and the risk from Russia and the USA was highest. Conclusions: The developed rapid risk assessment tool based on the risk matrix method can be used to determine the risk level of countries for imported COVID-19 cases to China at ports, and the risk of imported COVID-19 was high at Beijing port in August 2021.
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Humans , Beijing , COVID-19/epidemiology , China/epidemiology , Pandemics , Risk AssessmentABSTRACT
Proportion and rate have multiple and overlapping meanings, which blur their concepts. Based on the existence of the states and the occurrence of the events and their measuring process, we first put forward the concept of "cumulative number of states in point time". Considering the general meaning of "rate" in mathematics and the units of the elements in indexes, this paper puts forward the concept of "the change of cumulative number of states in point time", which is equal to the commonly acknowledged concept "number of incident event within observation period" or "absolute rate", and further constructs relative rate and proportion. Proportions can be classified into three types: time-point (or rate-type) constitutional proportion, time-period incidence proportion and their synthesis, time-period constitutional proportion. The essential difference between relative rate and time-period proportions is whether the observation period is regarded as a one-unit-length fixed period which would be further moved to the description of the indexes. Furthermore, the sources populations of relative rate and proportions are exclusively those at the beginning of the observation period. Thus, we established a unified identification route about ratios, proportions, and rates, the basic indicators of categorical data in populations. These are applicable to both fixed and dynamic populations. The paper aims to clarify the connotation of the indexes and the feasible understanding route and provide some reference for the population researchers.
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Humans , IncidenceABSTRACT
A case report of pneumonia vaccination followed by death due to Guillain-Barré syndrome was fully presented and discussed. The association between the vaccination and Guillain-Barré syndrome could not be completely ruled out; however, the diagnosis of coincidental event was preferred, which may provide a reference for future similar case investigation.
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Objective:To analyze the safety of measles-containing vaccines （MCV） in Shanghai city. Methods:Adverse event following immunization cases related to measles attenuated live vaccine （MV）， measles and rubella combined attenuated live vaccine （MR） and measles， mumps and rubella combined attenuated live vaccine （MMR） vaccination in Shanghai during 2011—2018 were collected from the National AEFI Surveillance System for epidemiological analysis. Results:A total of 15 055 MVC-related AEFI cases were reported， for an incidence of 139.74 per 100 000 doses. Among all MVC-related AEFI cases， the male to female ratio was 1.17∶1， and 12 068 （111.70 per 100 000 doses） were common reactions， with 1 050 from MV（64.66 per 100 000）， 5 484 from MR（134.36 per 100 000）and 5 534 from MMR（108.60 per 100 000. Most of common reactions were fever （96.01 per 100 000）， but 2 939 （27.20 per 100 000） were rare reactions， with 408 from MV （25.12 per 100 000）， 1 983 from MR （48.59 per 100 000） and 548 from MMR （10.75 per 100 000）. Most of rare reactions were allergic rash （25.00 per 100 000）. Conclusion:MCV has a good safety profile but we should continue to strengthen MCV-related AEFI surveillance.
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ObjectiveThe occurrence of atrial septal defect in Cornelia DE Lange syndrome are rarely reported in previous studies. The objective of this study is to investigate the relationship between the formation of atrial septal defect and Foxa2 gene expression in NIPBL+/- mouse model through the analysis of the expression of Foxa2 gene in heart tissue. MethodsThe NIPBL+/- mice were used as the experimental group, and wild-type NIPBL+/+ mice were used as the normal group. There were six mice in each group. The weights of the mice at 1, 2, 3, and 4 weeks were measured and recorded. Mouse heart tissues were collected at 4 weeks, and the expression of Foxa2 gene and protein were determined by real-time fluorescence quantitative PCR (Qrt-PCR) and Western blot. Pathological sections and HE staining were carried out to observe the effect of NIPBL gene defect on the development and changes of the mouse heart, as well as the anatomical structure of the atrial septum of the heart. ResultsThe weight of mice in the experimental group was significantly lower than that of the normal group (P<0.05) at all four time points. Foxa2 gene expression and protein expression in heart tissues of the experimental group were statistically lower than those of the normal group (P<0.05). Abnormal defect was observed in the atrial septum of the heart pathological sections of the NIPBL deficient mice. ConclusionThe decreased expression of Foxa2 gene in the heart tissue of NIPBL+/- deficient mice may be a factor inducing growth retardation and weight loss in mice. The abnormal defect in the atrial septum of nipbl-deficient mice might be associated with the down-regulation of Foxa2 gene expression in cardiomyocytes.
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Objective To investigate the status of non-immunization program vaccination among children in Shanghai. Methods Three districts were randomly selected for investigation in Shanghai.In the survey area, probability proportional to size sampling method was used to investigate the vaccination situation of non-immunization program and willingness to accept vaccination service in children aged 0-6 years old. Results A total of 416 children aged 0-6 years and their parents were investigated, 93.27%(388) of children received 1 dose or more of non-immunization program vaccines and 36.54% of children received 5 or more non-immunization program vaccines.The coverage of haemophilus influenzae type b conjugate vaccine, 13-valent pneumococcal conjugate vaccine, enterovirus 71 inactivated vaccine, oral rotavirus vaccine and influenza vaccine were 25.00%, 20.91%, 57.45%, 53.37% and 14.42%, respectively.64.95% of parents decided to vaccinate their children with non-immunization program vaccines because of the recommendation of vaccination staff.And 85.58% of parents requested vaccination staff to inform them or make appointments with non-immunization program vaccination.84.62% of parents could accept the charge for vaccination service. Conclusion In Shanghai, the proportion of children receiving multiple non-immunization program vaccination is relatively low and their parents′ demand for vaccination notification services is high.Vaccination staff should be encouraged to actively provide non-immunization program vaccination services, meeting the diverse needs of the public.
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In order to ensure the safety of the vaccine cold chain to the greatest extent, the newly regulations still require daily manual recording of temperature data and operation conditions based on the configuration of the automatic temperature measurement and alarm system.Therefore, on the basis of Shanghai Vaccine Cold-chain Monitoring System, Shanghai has introduced an electronic signature technology to implement a new model of remotely checking the temperature by mobile-phone and keeping records of the electronic signature as certificates.This technology reduces the on-site workload of cold chain management personnel.It also guarantees the authority, legitimacy, and non-tampering of recorded information through blockchain certificate storage technology.The application of the electronic signature technology is compatible with technical defense and civil defense methods, and is worthy of further promotion and use.
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Objective To assess the accuracy of immunization program vaccination rates through the immunization program information system by comparing immunization program vaccination rates among children between field investigation and information system sample survey in Shanghai. Methods From three districts in Shanghai， samples were stratified and randomly selected.The PPS sampling method (probability proportional to size) was used for 634 children aged 0-6 years for field investigation and 630 children aged 0-6 years were randomly selected for information system sample survey.The immunization program vaccination rates of children surveyed were investigated， statistically analyzed and compared. Results Statistically significant differences (P < 0.05) were found in the age composition and household registration composition of children sampled by the field investigation and information system sample survey.The national immunization program vaccination rate was 99.91% and timely vaccination rate was 94.29% by the field investigation.The national immunization program vaccination rate was 97.49% and timely vaccination rate was 87.90% by the information system sample survey.All 26 doses of immunization program vaccine surveyed had lower rates of coverage and timely vaccination in the information system sample survey than in the field investigation.Eighteen doses of vaccination rates by information system sample survey data were statistically significantly (P < 0.05) lower than those by field investigation and 20 doses of timely vaccination rates by information system sample survey data were statistically significantly (P < 0.05) lower than those by field investigation. Conclusion There are advantages and disadvantages to both field investigation and information system sample survey of immunization program vaccination rates.Field investigation and information system sample survey should be used in combination to evaluate the vaccination rate in future.
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ObjectiveGut microbiota plays an important role in Parkinson′s disease, but the mechanisms behind this remain unknown. This study aims to investigate the characteristics of intestinal microbiota in patients with Parkinson′s disease, and to study the changes of intestinal Prevotella_copri and their role in this disease.Methods The study was carried out in 46 patients with Parkinson′s disease and their spouses. The spouse has been living with the patient for a long time, not suffering from any disease. Fecal samples from all subjects were collected using sterile containers. The bacterial DNA was extracted on ice following the Kit protocol. We used the BGISEQ-500 high-throughput sequencing platform to conduct metagenomic shotgun sequencing, to explore the changes of patients′ intestinal microbiota through bioinformatics, and to analyze the function and role of differential microorganisms in disease.ResultsCompared to healthy spouse, the gut microbiota of patients with Parkinson′s disease was significantly changed, which was characterized by decreased Prevotellaceae and Prevotella_copri, but by significantly elevated Bacteroides_stercoris and Escherichia_coli. Prevotella_copri was decreased with age increasing. The correlation analysis showed a significantly negative correlation between the abundance of Prevotella_copri and age, H-Ystage, UPDR total score, and UPDRS Ⅲ score. Results of the random forest model indicated five items including Prevotella_copri had good predictive value for the disease. The functional analysis stated pathways associated with super-pathway of thiamin diphosphate biosynthesis, 4-aminobutanoate degradation. The glucose-1-phosphate degradation and methyl phosphonate degradation significantly increased in patients, while pathways associated with aromatic amino acid biosynthesis, chorismate biosynthesis, thiamin formation, and pyrimidine deoxyribonucleosides salvage significantly decreased. Pathways of Prevotella_copri were mainly concentrated in UMP biosynthesis, S-adenosyl-L-methionine cycle, and guanosine ribonucleotides de novo biosynthesis.ConclusionStructural composition and metabolic functions of gut microbiota were significantly changed in patients with Parkinson′s disease. Prevotella_copri plays an important role in the occurrence and progression of the disease and can be used as a potential biomarker for Parkinson′s disease.
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Objective: Headspace-solid phase microextraction-gas chromatography-mass spectrometry (HS-SPME-GC-MS) was used to analyze the characteristic volatile compounds from 18 heat-clearing herbs. Method: HS-SPME was used to extract the volatile components from different heat-clearing herbs,and the chemical compositions were analyzed by GC-MS. The GC was performed at the injector temperature of 250℃,the high-purity helium was used as the carrier gas at a constant column flow of 1.0 mL·min-1 with no split sampling. The solvent delay time was 3 min. Mass spectrum conditions included electron bombardment ion source,electron bombardment energy of 70 eV,ion source temperature of 230℃,quadrupoles temperature of 150℃,and scanning range of m/z 29-370.The volatile components were confirmed according to NIST2013 database,and the relative content percentage of each component was calculated by peak area normalization method. PCA was used to detect clustering and discuss the characteristics of volatile compounds of 18 heat-clearing herbs. Result: A total of 328 volatile compounds were detected in 18 heat-clearing herbs,including alkanes,unsaturated hydrocarbon,alcohols,aldehyde,ketones,esters,furan and other unknown compounds. The number and relative content of volatile components in different heat-clearing herbs varied dramatically. Several important characteristic volatile compounds,such as l-camphor,torreyol,caryophyllene oxide,globulol and 2,4-cycloheptadien-1-one,2,6,6-trimethyl,were detected in the 18 heat-clearing herbs by principal component analysis. Conclusion: Heat-clearing herbs contains rich volatile components,which are the main contributors to the formation of unique aroma of herbs,as well as the main active substances.
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Objective To understand the laboratory technicians’ abilities in blood slide making and reading in 10 prefectures of Yunnan Province which have passed the provincial malaria elimination evaluation, so as to provide the evidence for improving the malaria elimination surveillance and parasite examination. Methods Thirty negative blood slides were randomly sampled to evaluate coating, dyeing and clean quality and reading results, and 4 laboratory technicians were sampled to evaluate their reading abilities from each prefecture level and its 2 subordinate counties (districts) respectively, and then the results were analyzed. Results A total of 869 negative blood samples were evaluated. The coincidence rate was 100%. The proportions of good coating, dyeing and clean quality were 96.09%, 91.71% and 96.89%, respectively. Totally 576 blood slides were used to evaluate the reading ability. The number of correct reading was 505, and the correct rate was 87.67%. Among them, the Plasmodium vivax correct reading rate was 87.76%, the P. falciparum correct reading rate was 87.50%, and the correct reading rate of mixed infections was 47.62%. The laboratory technicians’ ability to the mixed infections was significantly lower than the ability to the others (χ2 = 37.169, P < 0.05), however, in the laboratory technicians’ abilities, there was no significant difference among the center (s) for disease control and prevention, general hospitals and township hospitals (χ2 = 2.782, P > 0.05), and the prefecture, county and township levels (χ2 = 0.358, P > 0.05) . Conclusion The 10 prefectures have passed the provincial evaluation in blood slide making and microscopic examination skill indicators requested, but the medical and public health institutions at all levels still should further improve their laboratory technicians’ abilities in blood slide making and microscopic examination skills.
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Objective To understand the laboratory technicians’ abilities in blood slide making and reading in 10 prefectures of Yunnan Province which have passed the provincial malaria elimination evaluation, so as to provide the evidence for improving the malaria elimination surveillance and parasite examination. Methods Thirty negative blood slides were randomly sampled to evaluate coating, dyeing and clean quality and reading results, and 4 laboratory technicians were sampled to evaluate their reading abilities from each prefecture level and its 2 subordinate counties (districts) respectively, and then the results were analyzed. Results A total of 869 negative blood samples were evaluated. The coincidence rate was 100%. The proportions of good coating, dyeing and clean quality were 96.09%, 91.71% and 96.89%, respectively. Totally 576 blood slides were used to evaluate the reading ability. The number of correct reading was 505, and the correct rate was 87.67%. Among them, the Plasmodium vivax correct reading rate was 87.76%, the P. falciparum correct reading rate was 87.50%, and the correct reading rate of mixed infections was 47.62%. The laboratory technicians’ ability to the mixed infections was significantly lower than the ability to the others (χ2 = 37.169, P < 0.05), however, in the laboratory technicians’ abilities, there was no significant difference among the center (s) for disease control and prevention, general hospitals and township hospitals (χ2 = 2.782, P > 0.05), and the prefecture, county and township levels (χ2 = 0.358, P > 0.05) . Conclusion The 10 prefectures have passed the provincial evaluation in blood slide making and microscopic examination skill indicators requested, but the medical and public health institutions at all levels still should further improve their laboratory technicians’ abilities in blood slide making and microscopic examination skills.
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Objective To investigate the effect of fluid shear stress (FSS) on the expression of B lymphoma Mo-MLV insertion region 1 (Bmi-1) in bone mesenchymal stem cells (BMSCs) and possible signal transduction mechanism. Methods BMSCs were isolated from SD rats and FSS at different magnitude (0.5, 1.5, 3.0 Pa) and under different time phase (1, 2, 6, 24 h) were loaded by parallel-plate flow chamber system. The expression of Bmi-1 was measured by real-time RT-PCR at mRNA level and the levels of phosphorylated Akt (p-Akt) and extracellular signalregulated kinase 1/2 (p-ERK1/2) were detected by Western blotting. The signaling inhibitors, wortmannin (PI3K specific inhabitor) and PD98059 (ERK1/2 specific inhabitor), were used to investigate possible mechanical signal transduction pathway. Results Bmi-1mRNA expression increased when BMSCs were exposed to 1.5 Pa FSS for 1 h and reached the peak at 24 h. All FSS with different magnitude could increase Bmi-1 expression, especial at high FSS (3.0 Pa). Meanwhile, FSS resulted in a significant activation of p-Akt and p-ERK1/2 in BMSCs. After treated with wortmannin, the expression of Bmi-1 was inhibited prominently, however, PD98059, the expression of Bmi-1 did not change. Conclusions FSS can activate the expression of Bmi-1, the amount of Bmi-1 expression was closely related to the stimulating time and the magnitude of FSS, and Akt signal molecule plays an important role during the process. These findings provide significant references for studying the mechanical biological mechanisms of stem cell differentiation.
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Objective To investigate the effect of fluid shear stress (FSS) on the expression of B lymphoma MoMLV insertion region 1 (Bmi-1) in bone mesenchymal stem cells (BMSCs) and possible signal transduction mechanism.Methods BMSCs were isolated from SD rats and FSS at different magnitude (0.5,1.5,3.0 Pa)and under different time phase (1,2,6,24 h) were loaded by parallel-plate flow chamber system.The expression of Bmi-1 was measured by real-time RT-PCR at mRNA level and the levels of phosphorylated Akt (p-Akt)and extracellular signalregulated kinase 1/2 (p-ERK1/2) were detected by Western blotting.The signaling inhibitors,wortmannin (PI3K specific inhabitor) and PD98059 (ERK1/2 specific inhabitor),were used to investigate possible mechanical signal transduction pathway.Results Bmi-1mRNA expression increased when BMSCs were exposed to 1.5 Pa FSS for 1 h and reached the peak at 24 h.All FSS with different magnitude could increase Bmi-1 expression,especial at high FSS (3.0 Pa).Meanwhile,FSS resulted in a significant activation of p-Akt and p-ERK1/2 in BMSCs.After treated with wortmannin,the expression of Bmi-1 was inhibited prominently,however,PD98059,the expression of Bmi-1 did not change.Conclusions FSS can activate the expression of Bmi-1,the amount of Bmi-1 expression was closely related to the stimulating time and the magnitude of FSS,and Akt signal molecule plays an important role during the process.These findings provide significant references for studying the mechanical biological mechanisms of stem cell differentiation.
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Objective To investigate the effect of fluid shear stress (FSS) on the expression of B lymphoma MoMLV insertion region 1 (Bmi-1) in bone mesenchymal stem cells (BMSCs) and possible signal transduction mechanism.Methods BMSCs were isolated from SD rats and FSS at different magnitude (0.5,1.5,3.0 Pa)and under different time phase (1,2,6,24 h) were loaded by parallel-plate flow chamber system.The expression of Bmi-1 was measured by real-time RT-PCR at mRNA level and the levels of phosphorylated Akt (p-Akt)and extracellular signalregulated kinase 1/2 (p-ERK1/2) were detected by Western blotting.The signaling inhibitors,wortmannin (PI3K specific inhabitor) and PD98059 (ERK1/2 specific inhabitor),were used to investigate possible mechanical signal transduction pathway.Results Bmi-1mRNA expression increased when BMSCs were exposed to 1.5 Pa FSS for 1 h and reached the peak at 24 h.All FSS with different magnitude could increase Bmi-1 expression,especial at high FSS (3.0 Pa).Meanwhile,FSS resulted in a significant activation of p-Akt and p-ERK1/2 in BMSCs.After treated with wortmannin,the expression of Bmi-1 was inhibited prominently,however,PD98059,the expression of Bmi-1 did not change.Conclusions FSS can activate the expression of Bmi-1,the amount of Bmi-1 expression was closely related to the stimulating time and the magnitude of FSS,and Akt signal molecule plays an important role during the process.These findings provide significant references for studying the mechanical biological mechanisms of stem cell differentiation.
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Acute graft-versus-host disease (GVHD) following liver transplantation is a rare but fatal complication. The correct diagnosis and management of GVHD after liver transplantation are still major challenges. Herein, we reported successful salvage treatment of acute GVHD by withdrawal of immunosuppression in a patient who presented with fever, skin rashes, and decreased blood cell counts after liver transplantation. This case highlights the need for awareness of drug-induced liver injury if liver function tests are elevated during treatment, especially in patients taking multiple potentially hepatotoxic drugs, such as broad-spectrum antibiotics. When occurs, an artificial liver support system is a useful tool to provide temporary support of liver function for the patient in the event of drug-induced liver injury.
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Humans , Anti-Bacterial Agents , Blood Cell Count , Diagnosis , Chemical and Drug Induced Liver Injury , Exanthema , Fever , Graft vs Host Disease , Immunosuppression Therapy , Liver Function Tests , Liver Transplantation , Liver , Liver, ArtificialABSTRACT
<p><b>BACKGROUND</b>Atopic dermatitis (AD) is characterized by defective skin barrier and imbalance in T helper 1/T helper 2 (Th1/Th2) cytokine expression. Filaggrin (FLG) is the key protein to maintaining skin barrier function. Recent studies indicated that Th1/Th2 cytokines influence FLG expression in keratinocytes. However, the role of Th1/Th2 cytokines on FLG processing is not substantially documented. Our aim was to investigate the impact of Th1/Th2 cytokines on FLG processing.</p><p><b>METHODS</b>HaCaT cells and normal human keratinocytes were cultured in low and high calcium media and stimulated by either interleukin (IL)-4, 13 or interferon-γ (IFN-γ). FLG, its major processing proteases and key protease inhibitor lymphoepithelial Kazal-type-related inhibitor (LEKTI) were measured by both real-time quantitative polymerase chain reaction and Western blotting. Their expression was also evaluated in acute and chronic AD lesions by immunohistochemistry.</p><p><b>RESULTS</b>IL-4/13 significantly reduced, while IFN-γ significantly up-regulated FLG expression. IL-4/13 significantly increased, whereas IFN-γ significantly decreased the expression of kallikreins 5 and 7, matriptase and channel-activating serine protease 1. On the contrary, IL-4/13 significantly decreased, while IFN-γ increased the expression of LEKTI and caspase-14. Similar trends were observed in AD lesions.</p><p><b>CONCLUSIONS</b>Our results suggested that Th1/Th2 cytokines differentially regulated the expression of major FLG processing enzymes. The imbalance between Th1 and Th2 polarized immune response seems to extend to FLG homeostasis, through the network of FLG processing enzymes.</p>