[Epidemiological characteristics of pulmonary tuberculosis in Motuo County, Tibet Autonomous Region from 2012 to 2021].

To analyze the epidemiological characteristics of pulmonary tuberculosis (PTB) in Motuo County from 2012 to 2021 and provide evidence for the prevention and control of PTB. A total of 223 cases of PTB were reported from 2012 to 2021 in Motuo County, with an average annual reported incidence rate of 171.39/100 000. Joinpoint regression model analysis showed that the average decline rate was 9.2% (P<0.001) from 2012 to 2021. Among the various types of PTB patients reported from 2012 to 2021, there were 69 cases of etiologic-positive cases which increased from 28.57% to 52.63%. Results from the circular distribution methods showed that there was no obvious peak time of PTB in Motuo County. There was no statistical difference in the average annual incidence of PTB between different genders (χ2=0.108, P=0.743). Among all age groups, the 20-29 years group had the highest proportion (26.91%, 60/223). The Monpa ethnic group (153 cases, 68.61%) had the largest number of cases, followed by the Lhoba people (44 cases, 19.73%) and the Tibetan (22 cases, 9.87%). Farmers (168 cases, 75.34%) had the highest occupational composition ratio, followed by students (40 cases, 17.94%). The main detection methods of PTB were clinical consultation and transferring consultation. Overall, the incidence rate of PTB decreased from 2012 to 2021. The majority of PTB patients were young adults with high transmission risk. It is necessary to pay more attention to the key populations and strengthen the comprehensive prevention and control for reducing the risk of PTB.

Transcriptomics analysis reveals key lncRNAs and genes related to the infection of porcine lung macrophages by Glaesserella parasuis.

Glaesserella parasuis (G. parasuis) is the pathogen of Glässer's disease in pig herds, which can cause severe inflammatory responses. However, at present, the pathogenic mechanism of G. parasuis is not very clear. LncRNAs can regulate the expression of mRNA in a variety of ways, thereby causing host cells to produce a variety of functional changes in response to bacterial infection. Here, we detected the changes in lncRNAs and mRNAs of 3D4/21 cells after G. parasuis CY1201 strain (serotype 13) infection. A total of 876 lncRNAs and 2166 mRNAs were differentially expression in 3D4/21 cells after G. parasuis infection. GO and KEGG enrichment analysis showed that the differentially up-regulated lncRNA target genes were mainly involved in the response to extracellular stimuli, cell receptor signaling pathways and chemokine signaling pathways. The differentially down-regulated lncRNA target genes were mainly involved in ERK1/ERK2 cascade reaction and adhesion junctions. 44 lncRNAs were screened that might be related in inflammation. CeRNA regulatory network of the top five difference inflammation-related lncRNAs showed that the up-regulated lncRNA group involved 5 lncRNAs, 50 miRNAs and 49 mRNAs. Meanwhile, there were 26 miRNAs and 36 mRNAs in the top five down-regulated lncRNA group. Our results contribute to understand the basic role of lncRNAs in 3D4/21 cells during G. parasuis infection, and lay the foundation for following research.

LncRNA-MEG3 Regulates the Inflammatory Responses and Apoptosis in Porcine Alveolar Macrophages Infected with Haemophilus parasuis Through Modulating the miR-210/TLR4 Axis.

Haemophilus parasuis (H. parasuis, HPS) can elicit serious inflammatory responses and cause enormous economic loss to swine industry worldwide. However, the factors responsible for systemic infection and inflammatory responses of HPS have not yet been fully clarified. In this study, we found that lncRNA-MEG3 was significantly up-regulated in porcine alveolar macrophages (PAMs) infected with HPS. The gain- and loss-of-function analysis confirmed that lncRNA-MEG3 participated in the inflammatory responses and apoptosis in HPS-infected PAMs, which was assessed via several inflammatory cytokine genes (TNF-α, IL-1ß, and IL-6) and apoptotic factors (Bcl-2, Bax, and C-caspase-3). Based on biotin-labeled RNA pull-down assay, we found that lncRNA-MEG3 bound with miR-210 in HPS-infected PAMs. Based on both overexpression and knockdown analysis of lncRNA-MEG3, our results indicated that lncRNA-MEG3 promoted the expression of TLR4 in HPS-infected PAMs. Using dual-luciferase reporter assays, we showed that lncRNA-MEG3 positively regulated the expression of TLR4 gene in HPS-infected PAMs through miR-210 pathway. Taken together, our results indicated that lncRNA-MEG3 participated in the inflammatory responses and apoptosis in HPS-infected PAMs through modulating the miR-210/TLR4 axis. The results from this investigation provided significant information for a novel target to control HPS infection in swine.

[Clinical and pathological features of Dubin-Johnson syndrome].

Objective: To explore the clinical and pathological features of Dubin-Johnson syndrome. Methods: The clinical and pathological characteristics of 18 cases of Dubin-Johnson syndrome diagnosed in the Department of Pathology of the Third Affiliated Hospital of Sun Yat-sen University from 2008 to 2018 were analyzed. Related literature was reviewed. Results: There were 15 male and three female patients. The male-to-female ratio was 5∶1. The age of the patients ranged from 17 to 73 years (median 24 years). Common clinical manifestations were jaundice, anorexia, and abnormal liver function tests. The pathological feature was the deposition of dark brown particles in the hepatocytes, especially those around the central veins. Conclusions: Dubin-Johnson syndrome mainly occurs in young people. The characteristic pathological changes are the deposition of dark brown particles in the hepatocytes around the central veins of the liver. The diagnosis of Dubin-Johnson syndrome mainly relies on clinical manifestations, laboratory examinations, histopathological examinations and genetic testing. The understanding of Dubin-Johnson syndrome can help reduce the rates of missed diagnosis and misdiagnosis of the disease.

[An investigation and analysis on a poisoning tetramine accident].

From August 21 to December 13, 2018, a tetramine poisoning incident in Wenzhou, Zhejiang Province was investigated, and the clinical diagnosis and treatment of tetramine poisoning was analyzed. There were 6 cases of poisoning caused by artificial tetramine poisoning. The diagnosis was delayed, coma and convulsions were severe manifestations continuous renal replacement therapy (CRRT) was effective in the treatment of severe cases, and all 6 cases were cured. The possibility of poisoning should be considered for unexplained coma and/or convulsions. Although tetramine is banned, it still needs to be highly vigilant and avoids the recurrence of delayed diagnosis and treatment.

Immunological methods for the diagnosis of oral mucosal diseases.

Immunological methods, which have been widely used in autoimmune blistering diseases (AIBDs) of the oral mucosa, can also be adopted as auxiliary diagnostic tools in oral lichen planus (OLP) and discoid lupus erythematosus (DLE). AIBDs, characterized by autoantibodies against structural proteins of keratinocytes or the basement membrane zone, clinically present as blisters and erosions of the oral mucosa. When atypical lesions occur, OLP or DLE may be confused with AIBDs. The improvement of diagnostic accuracy is necessary due to the significant differences in treatment and prognosis among these diseases. A variety of immunological methods are used for qualitative and quantitative detection of target antigens and autoantibodies. These methods can evaluate efficacy of treatment, monitor diseases and guide treatment decisions. In this review, we discuss the application of immunofluorescence, biochemical tests, and protein microarrays for AIBDs, OLP and DLE, as well as the differential diagnostic methods using immunological tests.

Topical calcineurin inhibitors in the treatment of oral lichen planus: a systematic review and meta-analysis.

BACKGROUND: TCS (topical corticosteroids) are the first-line drug in the treatment of oral lichen planus (OLP). However, the value of topical calcineurin inhibitors (TCI) including tacrolimus, pimecrolimus and ciclosporin for OLP is still controversial. OBJECTIVES: To compare the efficacy and safety of TCI vs. TCS for OLP. METHODS: The authors searched PubMed, Embase, Cochrane Central Register of Controlled Trials, Web of Science and four Chinese databases from 1950 to May 2018. The randomized controlled trials comparing TCI and TCS for OLP reported at least one of the following outcomes: improvement of clinical signs and/or symptoms, relapse, blood levels of TCI and adverse events. RESULTS: Twenty-one trials involving 965 patients were included in the analysis. For the treatment of OLP (3-8 weeks), TCI including tacrolimus, pimecrolimus and ciclosporin were similar to TCS in efficacy. Tacrolimus-TCS resulted in similar outcomes, with relapse at 3 weeks to 6 months. Blood levels of TCI were usually undetectable. In addition, tacrolimus showed a statistically higher incidence of local adverse events than TCS for short-term treatment. A few systemic adverse events occurred in the tacrolimus and ciclosporin groups, but they were not serious. CONCLUSIONS: The evidence for tacrolimus (n = 12), pimecrolimus (n = 3) and ciclosporin (n = 6) demonstrated that treatment with TCI may be an alternative approach when OLP does not respond to the standard protocols. Tacrolimus 0·1% should be the first drug of choice when selecting TCI for short-term treatment in recalcitrant OLP. Further well-designed trials are warranted to evaluate the long-term efficacy and safety of TCI. What's already known about this topic? The main topical drug for oral lichen planus (OLP) is topical corticosteroids (TCS). Patients with OLP who are not responsive to TCS or are at risk of adverse events from TCS need other alternative drugs. Topical calcineurin inhibitors (TCI), including tacrolimus, pimecrolimus and ciclosporin, have become a hot topic in a variety of mucocutaneous immune-mediated diseases. What does this study add? TCI including tacrolimus, pimecrolimus and ciclosporin were similar to TCS in efficacy for the short-term treatment of OLP. The local adverse events of tacrolimus were higher than with TCS. A few systemic adverse events were reported with TCI, but they were all tolerable and not serious. The limited evidence for pimecrolimus (three trials) and ciclosporin (six trials) requires further studies to evaluate the short-term and long-term efficacy and safety of TCI compared with TCS.

ACY 1215, a histone deacetylase 6 inhibitor, inhibits cancer cell growth in melanoma.

Histone deacetylase 6 (HDAC6) plays critical roles in dozens of malignant cancers, including melanoma. Therefore, inhibition of HDAC6 can be a potential strategy of targeting melanoma. ACY 1215 (ricolinostat), a selective HDAC6 inhibitor, is currently being clinically trialed in multiple cancers but not in melanoma. In this study, we tested the pre-clinical efficacy of ACY 1215 in melanoma cell lines. First, we found higher HDAC6 expression in melanoma cell lines than in an epidermal melanocyte cell line. Then, we observed the dose- and time-dependent reduction of cell proliferation caused by ACY 1215 treatment. Proliferation inhibition by ACY 1215 was associated with accumulation of acetylated tubulin but did not affect histone H3K9 acetylation. In addition, ACY 1215 induced cell apoptosis and G0/G1 cell cycle arrest. Finally, we show that ACY 1215 reduced tumor burden and increased survival in an in vivo mouse cell line xenograft model. All of these pre-clinical data indicate that HDAC6 is a potential target in melanoma, and that targeting HDAC6 in melanoma using ACY 1215 may be translationally relevant.

Association of PELI1 polymorphisms in systemic lupus erythematosus susceptibility in a Chinese population.

OBJECTIVE: Studies in animal models have indicated that Pellino 1 is involved in inflammatory and autoimmune diseases, such as systemic lupus erythematosus (SLE). The current study was designed to determine whether PELI1 confers genetic susceptibility to SLE in humans, as assessed in a Chinese Han population. METHODS: Blood samples were drawn from patients diagnosed with SLE and healthy volunteers. Three single nucleotide polymorphism (SNP) loci with a minor allele frequency of at least 0.05 were chosen to evaluate the correlation between PELI1 genotype and the incidence of SLE. RESULTS: There was a significant difference in the frequency distribution of the rs329497 allele between the SLE patients and the healthy controls (A vs. G; Bonferroni corrected p = 0.036, odds ratio = 0.75, 95% confidence interval = 0.60-0.94). No differences in the genotype and allele frequencies of other SNP loci were observed between the two groups. Furthermore, the alleles and genotypes of the three SNPs were not associated with lupus nephritis. CONCLUSION: In the Chinese Han population, PELI1 SNPs may be associated with SLE susceptibility.

Clozapine prescription and quality of life in Chinese patients with schizophrenia treated in primary care.

OBJECTIVE: Clozapine is frequently used to treat schizophrenia in China. Maintenance treatment for clinically stable patients with schizophrenia is usually provided by Chinese primary care physicians, but no study has investigated the frequency of its use prescribed by primary care physicians. This study described the frequency, demographic and clinical characteristics of clozapine treatment and its impact on insight and quality of life (QOL) of patients with schizophrenia treated in primary care in China. METHOD: A total of 623 patients with schizophrenia treated in 22 primary care services in Guangzhou, China in 2013 formed the study sample. Patients' socio-demographic and clinical characteristics including psychopathology, medication side effects and QOL were recorded using a standardized protocol and data collection. RESULTS: The frequency of clozapine prescription was 35.6% with a mean daily dose of 127.7±88.2 mg. There were no significant differences between the patients with and without clozapine in either of the QOL domains after controlling the confounding factors. Multiple logistic regression analyses revealed that patients on clozapine had younger age of onset, more hospitalizations, more severe extrapyramidal side effects, but better insight and fewer prescriptions of first generation antipsychotics. CONCLUSIONS: Clozapine use was found to be common and associated with better insight in patients with schizophrenia treated in primary care in China. Further examination of the rationale and appropriateness of clozapine in primary care in China is warranted.

Aspergillus fumigatus diffusates suppress polymorphonuclear neutrophil phagocytic functions and respiratory burst levels in hematopoietic stem cell transplantation patients.

Invasive aspergillosis (IA) is a severe infection that commonly occurs in immunocompromised patients after hematopoietic stem cell transplantation (HSCT). The present study explores the effect of Aspergillus fumigatus diffusates (AfDs) on phagocytic function and superoxide anion (O2(-)) burst levels in polymorphonuclear neutrophils (PMNs) from post-HSCT patients. A. fumigatus conidia with or without AfD were used to stimulate the PMN from healthy donor or HSCT patient for two hours. PMN morphology was visualized by scanning electron microscopy. The levels of respiratory burst O2(-) produced by the PMNs were determined by flow cytometry. PMN phagocytic rates and phagocytic indexes were observed and calculated using periodic acid-Schiff (PAS) staining under a light-field microscope. No difference was found between the PMN phagocytic rates, phagocytic indexes, or O2(-) respiratory burst levels in health donor PMNs following treatments of A. fumigatus conidia with or without AfD. However, significant inhibition of these indices was seen in the PMNs from HSCT patients following treatment of A. fumigatus conidia plus AfD, compared to that with conidium treatment alone (P < 0.05). Therefore, AfD significantly inhibited the phagocytic function of PMNs from HSCT patients, potentially through inhibition of intracellular respiratory burst levels during phagocytosis. This suggests that the reason underlying the greater susceptibility of HSCT patients to aspergillosis might be the existence of AfD in vivo during infection. Further research on the mechanisms by which AfD affects the phagocytic function of PMNs from HSCT patients is therefore of great significance for the prevention of IA.

Effects of different dietary intake on mRNA levels of MSTN, IGF-I, and IGF-II in the skeletal muscle of Dorper and Hu sheep hybrid F1 rams.

MSTN, IGF-І(insulin-like growth factor-І) and IGF-II (insulin-like growth factor-II) regulate skeletal muscle growth. This study investigated the effects of different dietary intake levels on skeletal muscles. Sheep was randomly assigned to 3 feeding groups: 1) the maintenance diet (M), 2) 1.4 x the maintenance diet (1.4M), and 3) 2.15 x the maintenance diet (2.15M). Before slaughtering the animals, blood samples were collected to measure plasma urea, growth hormone, and insulin concentrations. After slaughtering, the longissimus dorsi, semitendinosus, semimembranosus, gastrocnemius, soleus, and chest muscle were removed to record various parameters, including the mRNA expression levels of MSTN and IGFs, in addition to skeletal muscle fiber diameter and cross-sectional area. The result showed that as dietary intake improved, the mRNA expression levels of MSTN and IGF-II decreased, whereas IGF-Іexpression increased. The mRNA expression levels of MSTN and IGFs were significantly different in the same skeletal muscle under different dietary intake. The skeletal muscle fiber diameter and cross-sectional area increased with greater dietary intake, as observed for the mRNA expression of IGF-І; however, it contrasted to that observed for the mRNA expression of MSTN and IGF-II. In conclusion, dietary intake levels have a certain influence on MSTN and IGFs mRNA expression levels, in addition to skeletal muscle fiber diameter and cross-sectional area. This study contributes valuable information for enhancing the molecular-based breeding of sheep.

[Effectiveness of the central government-funded echinococcosis control programme in Tianzhu Tibetan Autonomous County, Gansu Province from 2007 to 2022].

OBJECTIVE: To evaluate the effectiveness of the central government-funded echinococcosis control programme in Tianzhu Tibetan Autonomous County, Gansu Province from 2007 to 2022, so as to provide insights into echinococcosis control. METHODS: Administrative villages were sampled using a multi-stage cluster random sampling method from Tianzhu Tibetan Autonomous County, Gansu Province from 2007 to 2022, and all residents at ages of 12 years and older in the sampled villages were screened for echinococcosis, and schools were sampled using a cluster sampling method, and all children at ages of 12 years and older in the sampled schools were screened for echinococcosis. Domestic dogs were sampled using a systematic random sampling method, and one domestic dog stool sample was collected from each household. Stray dog stool samples were collected outside the villages, and Echinococcus coproantigens were detected using enzyme-linked immunosorbent assay in domestic and stray dogs. In addition, echinococcosis was screened in sheep and cattle in designated slaughterhouses in Tianzhu Tibetan Autonomous County. The trends in the prevalence of echinococcosis in humans and livestock and the positive rate of Echinococcus coproantigens in dogs were examined with the Cochran-Armitage trend test. In addition, individuals screened for echinococcosis were randomly sampled from 2007 to 2022 for survey on the awareness of echinococcosis control knowledge. RESULTS: A total of 290 356 person-times were screened for echinococcosis among residents at ages of 12 years and older in Tianzhu Tibetan Autonomous County, Gansu Province from 2007 to 2022, with 1 094 residents detected with cystic echinococcosis, and the detection of echinococcosis appeared a tendency towards a gradual decline over years (χ2 = 358.602, P < 0.001). A total of 32 931 person-times were screened for echinococcosis among children at ages of 12 years and older in Tianzhu Tibetan Autonomous County, Gansu Province from 2007 to 2022, with 296 children detected with echinococcosis, and the detection of echinococcosis appeared a tendency towards a gradual decline over years (χ2 = 267.673, P < 0.001). A total of 33 230 domestic dog stool samples were tested for Echinococcus coproantigens in Tianzhu Tibetan Autonomous County, Gansu Province from 2007 to 2022, with 1 777 Echinococcus coproantigens-positive samples tested, and the positive rate of Echinococcus coproantigens appeared a tendency towards a decline in domestic dogs over years (χ2 = 2 210.428, P < 0.001), while the positive rate of Echinococcus coproantigens showed a tendency towards a rise in domestic animals from 2016 to 2022 (χ2 = 37.745, P < 0.001). The positive rate of Echinococcus coproantigens remained relatively stable in stray dogs in Tianzhu Tibetan Autonomous County, Gansu Province from 2019 to 2022 (χ2 = 0.315, P = 0.575). A total of 10 973 sheep were screened for echinococcosis in Tianzhu Tibetan Autonomous County from 2007 to 2022, with 334 sheep detected with echinococcosis, and the detection of echinococcosis appeared a tendency towards a decline in sheep over years (χ2 = 53.579, P < 0.001); however, there was no significant change in the detection of echinococcosis during the period from 2015 through 2022 (χ2 = 1.520, P = 0.218). A total of 2 400 cattle were screened for echinococcosis in Tianzhu Tibetan Autonomous County from 2017 to 2022, with 231 cattle detected with echinococcosis, and the detection of echinococcosis showed a tendency towards a decline over years (χ2 = 5.579, P < 0.05). The awareness of echinococcosis control knowledge increased from 44.37% in 2007 to 94.00% in 2022 among residents at ages of 12 years and older and from 52.50% in 2007 to 92.50% in 2022 among children at ages of 12 years and older in Tianzhu Tibetan Autonomous County, respectively. CONCLUSIONS: There has been a reduction in the detection of echinococcosis in humans and domestic animals and the positive rate of Echinococcus coproantigens in dogs and a rise in the awareness of the echinococcosis control knowledge following the implementation of the central government-funded echinococcosis control programme in Tianzhu Tibetan Autonomous County, Gansu Province; however, integrated echinococcosis control measures are still required for further control of the prevalence of echinococcosis.

[Effectiveness of comprehensive echinococcosis control measures with emphasis on management of infectious source in Sichuan Province from 2010 to 2022].

OBJECTIVE: To evaluate the effectiveness of comprehensive echinococcosis control measures with emphasis on management of infectious source in Sichuan Province from 2010 to 2022, so as to provide insights into formulation of future control interventions. METHODS: Data pertaining to comprehensive echinococcosis control measures with emphasis on management of infectious source and echinococcosis surveillance in Sichuan Province from 2010 to 2022 were collected. The effectiveness of comprehensive echinococcosis control measures with emphasis on management of infectious source was evaluated with prevalence of human echinococcosis, detection of newly diagnosed echinococcosis patients, prevalence of Echinococcus infection in domestic dogs, prevalence of cystic echinococcosis in livestock, prevalence of alveolar echinococcosis in small mammals and awareness of echinococcosis control knowledge, and Spearman's rank correlation analysis. RESULTS: The prevalence of human echinococcosis reduced from 1.08% in 2010 to 0.40% in 2022 in Sichuan Province (χ2 = 1 482.97, P < 0.05), with a reduction from 0.30% to 0.02% in the detection of newly diagnosed echinococcosis cases (χ2 = 2 776.41, P < 0.05), a reduction from 15.87% to 0.46% in the prevalence of Echinococcus infection in domestic dogs (χ2 = 20 823.96, P < 0.05), a reduction from 8.05% to 1.07% in the prevalence of cystic echinococcosis in livestock (χ2 = 1 296.02, P < 0.05), and the awareness of echinococcosis control knowledge increased from 50.65% to 95.24% (χ2 = 34 938.63, P < 0.05); in addition, there was a year-specific prevalence rate of alveolar echinococcosis in small mammals (χ2 = 164.07, P < 0.05). Spearman's rank correlation analysis revealed that the detection of newly diagnosed echinococcosis cases correlated positively with the prevalence of Echinococcus infections in domestic dogs (rs = 0.823, P < 0.05) and the prevalence of cystic echinococcosis in livestock (rs = 0.795, P < 0.05), and correlated negatively with the awareness of echinococcosis control knowledge (rs = - 0.918, P < 0.05), and the prevalence of Echinococcus infection in domestic dogs correlated positively with the prevalence of cystic echinococcosis in livestock (rs = 0.753, P < 0.05) and negatively with the awareness of echinococcosis control knowledge (rs = -0.747, P < 0.05); however, there was no correlation between the prevalence of Echinococcus infections in domestic dogs and the prevalence of alveolar echinococcosis in small mammals (rs = -0.750, P > 0.05). CONCLUSIONS: The comprehensive echinococcosis control measures with emphasis on management of infectious source had achieved remarkable effectiveness in Sichuan Province; however, the transmission chain of echinococcosis has not been interrupted. Reinforced comprehensive echinococcosis control measures with emphasis on management of infectious source and sustained tracking evaluation of the effectiveness are recommended in Sichuan Province.

Oct4 and Sox2 overexpression improves the proliferation and differentiation of bone mesenchymal stem cells in Xiaomeishan porcine.

Mesenchymal stem cells derived from bone marrow (BMSCs) are a population of self-renewing multipotent cells that are capable of differentiating into various cellular lineages, and are widely employed in tissue engineering and cell therapy. Recently, clinical research involving BMSCs has become increasingly popular. In order to conduct appropriate research, it is first necessary to amplify large amounts of functional BMSCs in vitro. However, after several passages of expanding in vitro, the proliferation and differentiation potential of BMSCs gradually decline. To determine whether overexpression of Oct4 or Sox2 might prevent this decline, we transfected Oct4 or Sox2, which are essential for the pluripotency and self-renewal of embryonic stem cells, into BMSCs of Xiaomeishan porcine by a lentivirus. The results showed that overexpression of Sox2 or Oct4 BMSCs in culture media containing a basic fibroblast growth factor resulted in higher proliferation and differentiation compared to controls, suggesting that genetic modification of stemness-related genes is an efficient way to maintain the proliferation and differentiation potential of BMSCs.