[Clinical Analysis of Children with Thalassemia in Chongqing].

OBJECTIVE: To analyze the genotype distribution and hematological characteristics of children with thalassemia in Chongqing. METHODS: A total of 207 children with thalassemia admitted to Chongqing University Three Gorges Hospital from January 2021 to October 2022 were selected as the research objects. The genotype distribution and hematological characteristics were retrospectively analyzed. RESULTS: 207 cases of thalassemia were confirmed from 482 samples by gene detection, the detection rate was 42.95%, α-thalassemia accounted for 17.63%(85/482), ß-thalassemia accounted for 24.27%(117/482), and compound αß thalassemia accounted for 1.04%(5/482). A total of 5 gene mutation types of α-thalassaemia were detected in this study, which constituted 6 genotypes, αα/-SEA was the most common one, followed by αα/-α3.7. A total of 8 gene mutation types of ß-thalassemia were detected, which constituted 9 genotypes, the top three were CD17/N, CD654/N and CD41-42/N. The highest detection rate was found in the patients aged 0-3 years (57%), and the degree of anemia was mainly mild (88.41%). 97.58% of the patients were MCV< 80 fl, 98.55% were MCH< 28 pg, 60.87% were MCHC< 320 g/L, and 71.50% were RDW-SD < 37%. The MCV and MCH of ß-thalassemia group were lower than that of α-thalassemia group, and the MCHC was higher than that of α-thalassemia group (P <0.05), but RDW-SD was not significantly different between the two groups (P >0.05). There were no significant differences in MCV, MCH, MCHC and RDW-SD between ß+/ßN and ß0/ßN groups ( P >0.05). The MCV and RDW-SD of --/αα thalassemia group were lower than that in -α/αα thalassemia group, the differences were statistically significant (P < 0.05), but MCH and MCHC were not significantly different between the two groups (P >0.05). CONCLUSION: The genotypes of children with thalassemia in Chongqing are diverse and heterogeneous, and the majority of them are mild anemia. There are differences in haematological indexes among different genotypes of thalassemia.

Alternation of the gut microbiota in irritable bowel syndrome: an integrated analysis based on multicenter amplicon sequencing data.

BACKGROUND: Gut dysbacteriosis has been reported as one of the etiologies for irritable bowel syndrome (IBS). However, the association between gut microbiota and IBS is still inconclusive. METHOD: A paired-sample study was designed by retrieving original multicenter 16 s-rRNA data of IBS patients and healthy controls from the GMrepo database. The propensity score matching (PSM) algorithm was applied to reduce confounding bias. The differential analysis of microbiota composition was performed at different taxonomic levels. The co-occurrence network was established. Subgroup analysis was performed to identify specific microbial compositions in different IBS subtypes. RESULTS: A total of 1522 amplicon samples were initially enrolled. After PSM, 708 individuals (354 IBS and 354 healthy controls) were eligible for further analysis. A total of 1,160 genera were identified. We identified significantly changed taxa in IBS groups (IBS-enriched: the families Enterobacteriaceae, Moraxellaceae and Sphingobacteriaceae; the genera Streptococcus, Bacillus, Enterocloster, Sphingobacterium, Holdemania and Acinetobacter. IBS-depleted: the phyla Firmicutes, Euryarchaeota, Cyanobacteria, Acidobacteria and Lentisphaerae; the families Bifidobacteriaceae, Ruminococcaceae, Methanobacteriaceae and the other 25 families; the genera Faecalibacterium, Bifidobacterium and other 68 genera). The co-occurrence network identified three hub genera and six hub species (including Faecalibacterium prausnitzii) that may be involved in IBS pathophysiology. Strong positive interactions were identified among the Bifidobacterium longum, Bifidobacterium breve and Bifidobacterium adolescentis in the Bifidobacterium community. CONCLUSION: This study provides quantitative analysis and visualization of the interaction between the gut microbiota and IBS. The identification of key species should be further validated to evaluate their causal relationships with the pathogenesis of IBS.

Epidemiological and Clinical Characteristics of Influenza Outbreaks Among Children in Chongqing, China.

Influenza is a global serious public health threat. Seasonal influenza among children in Chongqing has been a heavy health burden. To date, few studies have examined the spatial and temporal characteristics of influenza. This research sheds new light on correlating them with influenza outbreaks with data of over 5 years (2014-2018). All cluster outbreaks among preschool and school-age children reported in Chongqing were collected through the Public Health Emergency Management Information System. The demographical, epidemiological, and clinical data of the cases were analyzed. From 2014 to 2018, a total of 111 preschool- and school-based influenza-like illness outbreaks involving 3,549 cases were identified. Several clinical symptoms that were analyzed in this study showed significant contrast between influenza A and B. Spatial autocorrelation analysis over the 5-year data detected Xiushan district being the most likely cluster. The exploration of the spatial distribution and clinical characteristics of influenza cluster of children in Chongqing could help the effective implementation of health policies. Future studies should be conducted to monitor the outbreaks of influenza among children.

Forecasting the incidence of mumps in Chongqing based on a SARIMA model.

BACKGROUND: Mumps is classified as a class C infection disease in China, and the Chongqing area has one of the highest incidence rates in the country. We aimed to establish a prediction model for mumps in Chongqing and analyze its seasonality, which is important for risk analysis and allocation of resources in the health sector. METHODS: Data on incidence of mumps from January 2004 to December 2018 were obtained from Chongqing Municipal Bureau of Disease Control and Prevention. The incidence of mumps from 2004 to 2017 was fitted using a seasonal autoregressive comprehensive moving average (SARIMA) model. The root mean square error (RMSE) and mean absolute percentage error (MAPE) were used to compare the goodness of fit of the models. The 2018 incidence data were used for validation. RESULTS: From 2004 to 2018, a total of 159,181 cases (93,655 males and 65,526 females) of mumps were reported in Chongqing, with significantly more men than women. The age group of 0-19 years old accounted for 92.41% of all reported cases, and students made up the largest proportion (62.83%), followed by scattered children and children in kindergarten. The SARIMA(2, 1, 1) × (0, 1, 1)12 was the best fit model, RMSE and MAPE were 0.9950 and 39.8396%, respectively. CONCLUSION: Based on the study findings, the incidence of mumps in Chongqing has an obvious seasonal trend, and SARIMA(2, 1, 1) × (0, 1, 1)12 model can also predict the incidence of mumps well. The SARIMA model of time series analysis is a feasible and simple method for predicting mumps in Chongqing.

Overcoming resistance to STING agonist therapy to incite durable protective antitumor immunity.

BACKGROUND: Activating the Stimulator of Interferon Genes (STING) adaptor incites antitumor immunity against immunogenic tumors in mice, prompting clinical trials to test STING activators. However, STING signaling in the tumor microenvironment (TME) during development of Lewis lung carcinoma (LLC) suppresses antitumor immunity to promote tumor growth. We hypothesized that local immune balance favoring suppression of antitumor immunity also attenuates antitumor responses following STING activation. The purpose of this study was to evaluate how STING activation impacts antitumor responses in mice bearing LLC tumors. METHODS: Mice bearing established LLC tumors were treated with synthetic cyclic diadenyl monophosphate (CDA) to activate STING. Mice were monitored to assess LLC tumor growth, survival and protective antitumor immunity. Transcriptional and metabolic analyses were used to identify pathways responsive to CDA, and mice were co-treated with CDA and drugs that disrupt these pathways. RESULTS: CDA slowed LLC tumor growth but most CDA-treated mice (77%) succumbed to tumor growth. No evidence of tumor relapse was found in surviving CDA-treated mice at experimental end points but mice were not immune to LLC challenge. CDA induced rapid increase in immune regulatory pathways involving programmed death-1 (PD-1), indoleamine 2,3 dioxygenase (IDO) and cyclooxygenase-2 (COX2) in the TME. PD-1 blockade enhanced antitumor responses to CDA and increased mouse survival but mice did not eliminate primary tumor burdens. Two IDO inhibitor drugs had little or no beneficial effects on antitumor responses to CDA. A third IDO inhibitor drug synergized with CDA to enhance tumor control and survival but mice did not eliminate primary tumor burdens. In contrast, co-treatments with CDA and the COX2-selective inhibitor celecoxib controlled tumor growth, leading to uniform survival without relapse, and mice acquired resistance to LLC re-challenge and growth of distal tumors not exposed directly to CDA. Thus, mice co-treated with CDA and celecoxib acquired stable and systemic antitumor immunity. CONCLUSIONS: STING activation incites potent antitumor responses and boosts local immune regulation to attenuate antitumor responses. Blocking STING-responsive regulatory pathways synergizes with CDA to enhance antitumor responses, particularly COX2 inhibition. Thus, therapy-induced resistance to STING may necessitate co-treatments to disrupt regulatory pathways responsive to STING in patients with cancer.

Co-treatments to Boost IDO Activity and Inhibit Production of Downstream Catabolites Induce Durable Suppression of Experimental Autoimmune Encephalomyelitis.

Reinforcing defective tolerogenic processes slows progression of autoimmune (AI) diseases and has potential to promote drug-free disease remission. Previously, we reported that DNA nanoparticles (DNPs) and cyclic dinucleotides (CDNs) slow progression of experimental autoimmune encephalomyelitis (EAE), a mouse model of multiple sclerosis, by activating the Stimulator of Interferon Genes (STING) signaling adaptor to stimulate interferon type 1 (IFN-I) production, which induced dendritic cells to express indoleamine 2,3 dioxygenase (IDO) and acquire immune regulatory phenotypes. Here, we show that therapeutic responses to DNPs depend on DNA sensing via cyclic GAMP synthase (cGAS) and interactions between Programmed Death-1 (PD-1) and PD-1 ligands. To investigate how increased tryptophan (Trp) metabolism by IDO promotes therapeutic responses mice were co-treated at EAE onset with DNPs and drugs that inhibit kynurenine aminotransferase-II (KatII) or 3-hydroxyanthranilic acid dioxygenase (HAAO) activity downstream of IDO in the kynurenine (Kyn) pathway. DNP and KatII or HAAO inhibitor co-treatments suppressed EAE progression more effectively than DNPs, while KatII inhibition had no significant therapeutic benefit and HAAO inhibition attenuated but did not prevent EAE progression. Moreover, therapeutic responses to co-treatments were durable as EAE progression did not resume after co-treatment. Thus, using STING agonists to boost IDO activity and manipulating the Kyn pathway downstream of IDO is an effective strategy to enhance tolerogenic responses that overcome autoimmunity to suppress EAE progression.

Epidemiological Characteristics and Spatiotemporal Analysis of Acute Hemorrhagic Conjunctivitis from 2004 to 2018 in Chongqing, China.

Chongqing is one of the five provinces in China that has the highest incidence of acute hemorrhagic conjunctivitis (AHC). Data of AHC cases from 2004 to 2018 were obtained from National Notifiable Diseases Reporting Information System (NNDRIS). Descriptive statistical methods were used to analyze the epidemiological characteristics; incidence maps were used to reflect incidence trends in each district; spatial autocorrelation was used to identify hotspot regions and spatiotemporal patterns of AHC outbreaks; spatiotemporal scan were conducted to identify AHC clusters. A total of 30,686 cases were reported with an annual incidence of 7.04 per 100,000. The incidence rates were high in 2007 and 2014, and large epidemics were observed in 2010 with the seasonal peak in September. Individuals aged 10-19 years, males, students and farmers were the prime high-risk groups. Except for 2012 and 2013, the spatial distribution of AHC did not exhibit significant global spatial autocorrelation. Local indicators of spatial association showed that the high-risk regions are Chengkou and Wuxi. The spatiotemporal scan indicated that all clusters occurred in September 2010, and the high-incidence clusters were mainly distributed in the northeast of Chongqing. The results could assist public health agencies to consider effective preventive measures based on epidemiological factors and spatiotemporal clusters in different regions.

Epidemiological and clinical characteristics of severe hand-foot-and-mouth disease (HFMD) among children: a 6-year population-based study.

BACKGROUND: Hand-foot-and-mouth disease (HFMD) is considered to be self-limited, however, severe HFMD is a deadly threat for children worldwide, therefore, it is essential to define the clinical and epidemiologic characteristics of children with severe HFMD and identify the risk factors of death. METHODS: Between 2013 and 2018, children who diagnosed with severe HFMD from Chongqing, China were enrolled in this population-based study. A total of 459 severe HFMD children cases were identified during the study period, including 415 survivors and 44 fatal cases. Demographic, geographical, epidemiological and clinical data of the cases were acquired and analyzed. RESULTS: Risk factors of the death because of severe HFMD children included female, aged 1 ~ 3 years, enterovirus 71 infection, falling ill in winter, more than one children in home, being taken care of by grandparents, the caregivers' education not more than 9 years, having fever more than 3 days, consciousness disorders, general weakness, vomiting, general weakness, abnormal pupillary light reflex, repeated cough, tachypnea, moist rales, white frothy sputum, pink frothy sputum, and cyanosis on lips or the whole body, tachycardia, arrhythmia, cold limbs, pale complexion, weakened pulse. (all p < 0.05). Spatial-temporal analysis detected high-value clusters, the most likely cluster located at rural countries in the northern parts of Chongqing, from January, 2015 to July, 2017. (p < 0.01). Besides, some urban districts were also found high incidence of severe HFMD cases according to the incidence maps. CONCLUSIONS: The detection of clinical risk factors and the temporal, spatial and socio-demographic distribution epidemiological characteristics of severe HFMD contribute to the timely diagnosis and intervention, the results of this study can be the reference of further clinical and public health practice.

Facilitators and Barriers Associated with Uptake of HIV Self-Testing among Men Who Have Sex with Men in Chongqing, China: A Cross-Sectional Survey.

While studies on human immunodeficiency virus self-testing (HIVST) continue to accumulate after the World Health Organization's recommendation of HIVST as an additional approach to HIV testing services in 2016, few studies have focused on men who have sex with men (MSM) in Chinese cities. A cross-sectional study was conducted to describe the HIVST status of MSM in Chongqing, China. MSM participants were recruited by random sampling, and qualified interviewers collected data, using confidential self-administered questionnaires. Blood specimens were collected for HIV antibody detection. The survey evaluated the uptake and accuracy of HIVST kits and identified factors that may be associated with HIVST. The proportion of HIVST uptake was 15.6%. The sensitivity and specificity of HIVST were 74.2% (95% confidence interval [CI] 66.6%-80.7%) and 99.0% (95% CI 96.9%-99.7%), respectively. The consistency between the HIVST kit and antibody detection results was 90.5% (95% CI 87.5%-93.0%), and the Kappa value was 0.777 (p < 0.001). The positive predictive value of self-testing kits is 80.9% and the negative predictive value is 17.7%. Having been tested ≥2 times in the last year, higher educational levels, and higher scores of basic HIV/AIDS knowledge facilitated higher uptake of HIVST. Self-reported existing barriers for HIVST uptake included older age, marital status, and having resided in Chongqing for more than two years.

Changing Trends of HIV, Syphilis, and Hepatitis C among Male Migrant Workers in Chongqing, China: Nine Consecutive Cross-Sectional Surveys, 2010-2018.

BACKGROUND: Male migrant workers (MMWs) have been reported to be vulnerable to human immunodeficiency virus (HIV) and other sexually transmitted infections (STIs). Chongqing, China is one of the major migration destinations and hotspots of HIV. This study aims to explore the prevalence of HIV, syphilis, and hepatitis C virus (HCV), as well as HIV-related knowledge and behaviors, among MMWs in Chongqing. METHODS: Questionnaire surveys were conducted, and blood samples were collected and examined among MMWs selected by two-stage stratified sampling in Chongqing from 2010 to 2018. The Cochran-Armitage trend test was conducted to observe the trends in the prevalence of HIV, syphilis, and HCV, as well as HIV-related knowledge and behaviors. The Chi-square test and Binary Logistic Regression were conducted to observe the distinctions between different groups. RESULTS: The overall HIV prevalence was 0.6% with an increasing trend (0.2% to 0.9%, P < 0.001), whereas the overall HCV prevalence was 0.5% with a decreasing trend (0.5% to 0.4%, P < 0.001). The overall syphilis prevalence was 1.3% in the ≥50 age group, 1.0% in the 30-49 age group, and higher than 0.3% in the 16-29 group (X2 = 19.527, P < 0.001). An uptrend (80.2%-80.6%, P < 0.001) was observed in correct HIV-related knowledge. The 16-29 ((Odds Ratio) OR: 1.575; 95%CI (Confidence Interval): 1.380-1.798; P < 0.001) and 30-49 (OR: 1.697; 95%CI: 1.495-1.926; P < 0.001) age groups had 1.575 and 1.697 times correct HIV-related knowledge more than the ≥50 age group. The proportion of subjects engaged in commercial sex in the past year (7.7%-13.3%, P < 0.001), consistent condom use during this activity (20.5%-54.0%, P < 0.001), and condom use in the last commercial sex (48.6%-72.1%, P = 0.020) were increasing. The risk of engaging in commercial sex in the past year in the 16-29 age group was 0.768 times (OR: 0.768; 95%CI: 0.643-0.917; P = 0.003) less than that in the ≥50 age group. The risk of engaging in non-regular sex in the past year in the 16-29 (OR: 2.819; 95%CI: 2.317-3.431; P < 0.001) and 30-49 (OR: 1.432; 95%CI: 1.184-1.733); P < 0.001) age groups were 2.819 and 1.432 times more than that in the ≥50 age group. The risk of engaging in anal sex in the past year in the 16-29 age group was 6.333 times (OR: 6.333; 95%CI: 1.468-27.327); P < 0.013] more than that in the ≥50 age group. The proportion of consistent condom use during non-regular sex in the past year (10.9%-47.3%, P < 0.001) and condom use in the last non-regular sex (40.8%-71.1%, P < 0.001) increased remarkably. The possibilities of consistent condom use during commercial sex in the past year in the 16-29 (OR: 2.606; 95%CI: 1.847-3.677); P < 0.001) and 30-49 (OR: 1.632; 95%CI: 1.214-2.195; P = 0.001) age groups were 2.606 and 1.632 times more than that in the ≥50 age group. The possibilities of condom use in the last commercial sex in the 16-29 (OR: 1.805; 95%CI: 1.258-2.589; P = 0.001) and 30-49 (OR: 1.360; 95%CI: 1.016-1.821; P = 0.039) age groups were 1.805 and 1.360 times more than that in the ≥50 age group. The possibilities of consistent condom use during non-regular sex in the past year (OR: 1.628; 95%CI: 1.066-2.484; P = 0.024) and condom use in the last non-regular sex (OR: 1.671; 95%CI: 1.148-2.433; P = 0.007) in the 16-29 age group were 1.628 and 1.671 times more than those in the ≥50 age group, respectively. CONCLUSION: An upward trend of HIV and a downward trend of HCV were observed among MMWs in Chongqing from 2010 to 2018. We also found an increase in commercial sex and inadequate condom use during high-risk behaviors among this population. The overall syphilis prevalence in the middle-aged and elderly groups was higher than in the young group, and elderly MMWs were more likely to engage in unprotected high-risk behaviors. Thus, targeted STI prevention for MMWs in Chongqing, especially those aged 50 years and above, is urgently needed.

Spatiotemporal Epidemiology of Varicella in Chongqing, China, 2014-2018.

Although immunization against varicella using vaccines has been proven to be significant and effective in the past decades, varicella remains a major public health concern for many developing countries. Varicella vaccination has not been introduced into routine immunization programs in China, and varicella outbreaks have continued to occur. Taking the city of Chongqing, which has a high prevalence of varicella, as an example, this study explored the spatiotemporal epidemiology of varicella. Based on the reported data of varicella cases from 1 January 2014 to 31 December 2018 in Chongqing, hot spots and space-time clusters of varicella were identified using spatial autocorrelation analysis and scan statistics. Within this period, a total of 112,273 varicella cases were reported in Chongqing (average annual incidence: 73.44 per 100,000), including one death. The incidence of varicella showed an increasing trend with significant seasonal peaks, which occurred during April to July and October to January of the following year. The total ratio of male to female patients affected was 1.10:1. Children under the age of 15 and students accounted for the majority of the patient population. The hotspots detected through local spatial autocorrelation analysis, and the most likely clusters identified by scan analysis, were primarily in the main urban districts of Chongqing. The secondary clusters were mostly detected in northeast and southwest Chongqing. There were obvious spatial dependence and spatiotemporal clustering characteristics of varicella in Chongqing from 2014 to 2018. High-risk districts, populations, and peak periods were found in this study, which could be helpful in implementing varicella prevention and control programs, and in adjusting vaccination strategies for the varicella vaccine based on actual conditions.

Double- versus single-balloon catheters for labour induction and cervical ripening: a meta-analysis.

BACKGROUND: The induction of labour is an increasingly common procedure in the obstetrics field. Various methods have been used to induce labour, among which balloon catheters play an important role. Whether the specifically designed double-balloon catheter is better than the single-balloon device in terms of efficacy, efficiency, safety and patient satisfaction remains controversial. Identifying even small differences between these two devices could be useful to guide clinical practices, to further explore their mechanisms, and to promote a better understanding of the optimal methods for inducing labour. METHODS: Using the population, intervention, comparison, outcomes and study designs (PICOS) principle, we searched the PubMed, EMBASE, OVID, SCI, CENTRAL, ClinicalTrial.gov , and CDSR databases to identify relevant randomised controlled trials (RCTs) from inception through February 14, 2018. The primary outcome was the caesarean delivery rate, and the secondary outcomes focused on efficacy, efficiency, safety, and patient satisfaction. The relative risks or mean differences, including their 95% confidence intervals, were calculated using fixed-effects or random-effects models. All statistical analyses were completed with RevMan version 5.3. RESULTS: From a total of 1326 articles, 7 RCTs involving 1159 women were included. There were no significant differences in primary outcomes (RR, 0.88 [0.65, 1.2]; p-value, 0.43) or secondary outcomes identified between single- and double-balloon catheters. However, heterogeneity existed for some aspects. CONCLUSION: Both kinds of balloon catheter have similar levels of efficacy, efficiency, safety and patient satisfaction; however, the single-balloon method is considered to be more cost-effective.

Stimulator of interferon genes agonists attenuate type I diabetes progression in NOD mice.

Reagents that activate the signaling adaptor stimulator of interferon genes (STING) suppress experimentally induced autoimmunity in murine models of multiple sclerosis and arthritis. In this study, we evaluated STING agonists as potential reagents to inhibit spontaneous autoimmune type I diabetes (T1D) onset in non-obese diabetic (NOD) female mice. Treatments with DNA nanoparticles (DNPs), which activate STING when cargo DNA is sensed, delayed T1D onset and reduced T1D incidence when administered before T1D onset. DNP treatment elevated indoleamine 2,3 dioxygenase (IDO) activity, which regulates T-cell immunity, in spleen, pancreatic lymph nodes and pancreas of NOD mice. Therapeutic responses to DNPs were partially reversed by inhibiting IDO and DNP treatment synergized with insulin therapy to further delay T1D onset and reduce T1D incidence. Treating pre-diabetic NOD mice with cyclic guanyl-adenyl dinucleotide (cGAMP) to activate STING directly delayed T1D onset and stimulated interferon-αß (IFN-αß), while treatment with cyclic diguanyl nucleotide (cdiGMP) did not delay T1D onset or induce IFN-αß in NOD mice. DNA sequence analyses revealed that NOD mice possess a STING polymorphism that may explain differential responses to cGAMP and cdiGMP. In summary, STING agonists attenuate T1D progression and DNPs enhance therapeutic responses to insulin therapy.

Epidemiological Characteristics and Spatiotemporal Analysis of Mumps from 2004 to 2018 in Chongqing, China.

Mumps vaccines have been widely used in recent years, but frequent mumps outbreaks and re-emergence around the world have not stopped. Mumps still remains a serious public health problem with a high incidence in China. The status of mumps epidemics in Chongqing, the largest city in China, is still unclear. This study aimed to investigate the epidemiological and spatiotemporal characteristics of mumps and to provide a scientific basis for formulating effective strategies for its prevention and control. Surveillance data of mumps in Chongqing from January 2004 to December 2018 were collected from the National Notifiable Diseases Reporting Information System. A descriptive analysis was conducted to understand the epidemiological characteristics. Hot spots and spatiotemporal patterns were identified by performing a spatial autocorrelation analysis, a purely spatial scan, and a spatiotemporal scan at the county level based on geographic information systems. A total of 895,429 mumps cases were reported in Chongqing, with an annual average incidence of 36.34 per 100,000. The yearly incidence of mumps decreased markedly from 2004 to 2007, increased sharply from 2007 to 2011, and then tapered with a two-year cyclical peak after 2011. The onset of mumps showed an obvious bimodal seasonal distribution, with a higher peak of mumps observed from April to July of each year. Children aged 5-9 years old, males, and students were the prime high-risk groups. The spatial distribution of mumps did not exhibit significant global autocorrelation in most years, but local indicators of spatial autocorrelation and scan statistics detected high-incidence clusters which were mainly located in the midwestern, western, northeastern, and southwestern parts of Chongqing. The aggregation time frame detected by the purely temporal scan was between March 2009 and July 2013. The incidence of mumps in Chongqing from 2004 to 2018 featured significant spatial heterogeneity and spatiotemporal clustering. The findings of this study might assist public health agencies to develop real-time space monitoring, especially in the clustering regions and at peak periods; to improve immunization strategies for long-term prevention; and to deploy health resources reasonably.

Long noncoding RNA SNHG12 promotes the progression of cervical cancer via modulating miR-125b/STAT3 axis.

Increasing evidence showed that long noncoding RNAs (lncRNAs) played an important role in the occurrence and development of tumors. To date, lncRNA small nucleolar RNA host gene 12 (SNHG12) has revealed an oncogenic role in various tumors. However, the role of SNHG12 in cervical cancer is still unclear. Therefore, we focused on the biological function and molecular mechanism of SNHG12 in the tumorigenesis of cervical cancer. In this study, the expression of miR-125b was observably downregulated in cervical cancer cells. Meanwhile, the expression of SNHG12 was obviously upregulated in cervical cancer cell lines (HeLa, SiHa, Caski, C4-1, and C33A) compared with the immortalized cervical epithelial cells. The further assay showed that miR-125b was a target of SNHG12 in cervical cancer. Moreover, a negative relationship between miR-125b and SNHG12 was found in cervical cancer. In addition, SNHG12 inhibition restrained the proliferation, migration, and invasion of cervical cancer cells. Meanwhile, miR-125b mimics repressed the expression of signal transducer and activator of transcription 3 (STAT3). The further assay showed that STAT3 was a target of miR-125b in cervical cancer. In addition, sh-STAT3 repressed the migration and invasion of cervical cancer cells. Furthermore, it showed that miR-125b inhibitors reversed STAT3 expression restrained by the reduction of SNHG12 expression. In general, SNHG12 modulated STAT3 by sponging miR-125b in cervical cancer and played an important role in the development of cervical cancer.

Lentiviral-mediated microRNA-26b up-regulation inhibits proliferation and migration of hepatocellular carcinoma cells.

Hepatocellular carcinoma (HCC) is a frequently occurred malignancy worldwide with a high mortality. The treatment for HCC is still controversial. Emerging evidences have demonstrated that microRNAs (miRs) play a role in HCC. This study aims to investigate the effects of lentiviral-mediated miRNA-26b (miR-26b) on the proliferation and metastasis of HCC cells. The normal hepatic cell line HL-7702 and HCC cell lines HepG2 (without metastatic potential), SMMC-7721 (with low metastatic potential) and MHCC97H (with high metastatic potential) were purchased for our experiment. The lentiviral-mediated miR-26b overexpression (miR-26b-LV) and low expression (sh-miR-26b) were constructed to transfect the cells. The miR-26b expression and expressions of Karyopherin α-2 (KPNA2), matrix metalloproteinase 1 (MMP-1), MMP-7 and MMP-14 were determined by RT-qPCR and western blot analysis. The proliferation and metastasis of transfected HCC cells were detected by MTT and Transwell assay respectively. The miR-26b expressions were decreased significantly in MHCC97H cells. With lentiviral-mediated miR-26b overexpression, the proliferation and migration of HepG2, MHCC97H and SMMC-7721 cells were decreased significantly. The RT-qPCR and western blot analysis results revealed that the mRNA and protein expressions of KPNA2, MMP-1, MMP-7 and MMP-14 were decreased by lentiviral-mediated miR-26b overexpression. All the above indexes in the HepG2, MHCC97H and SMMC-7721 cells treated by sh-miR-26b exhibited opposite trends. These results show that overexpressed miR-26b could inhibit the proliferation and metastasis of HCC cells significantly, which provides a novel target and theoretical foundation for the treatment of HCC.

[Effects of Pim-1 inhibitor on mouse model of inflammatory bowel disease induced by TNBS].

OBJECTIVE: To explore the role of Pim-1 in the pathology of inflammatory bowel disease and the potential effect of Pim-1 inhibitor on treating such disease.
 Methods: Forty-five BALB/c mice were randomly divided into 5 groups (n=9): A normal control group, a inflammatory bowel disease group, two different dose of Pim-1 inhibitor treatment groups, and steroidhormone treatment group. The model of inflammatory bowel disease was induced by intracolonic administration of 2, 4, 6-trinitrobenzenestdfonic acid (TNBS) and ethanol mixture. Mice were treated with Pim-1 inhibitor [intraperitoneal inject, 5 or 10 mg/(kg.d)] for 5 days and prednisone (intragastric administration, 0.1 mg/d) for 5 days. The DAI, colon length, gross score and pathological grade were evaluated. The expressions of T cell master transcription factors T-box expressed in T cells (T-bet), GATA binding protein 3 (GATA-3), RA orphan receptorγ (RORγt) and forkhead box P3 (Foxp3) were measured by Real-time PCR and Western blot, respectively.
 Results: Pim-1 inhibitor and prednisone showed therapeutic effect on acute TNBS colitis in vivo. GATA3 and RORγt were significantly up-regulated in acute TNBS colitis (P<0.05). In contrast, the expression of Foxp3 was suppressed in the inflammatory bowel disease group, whereas it did not cause any significant change in T-bet expression (P>0.05). Administration of Pim-1 inhibitor and prednisone resulted in suppression of GATA3, RORγt expression, and the increase of Foxp3 expression (P<0.05). Administration of Pim-1 inhibitor and prednisone resulted in inhibition of T-bet mRNA expression (P<0.05), but only prednisone could inhibit T-bet protein expression (P>0.05).
 Conclusion: Pim-1 inhibitor significantly suppresses Th2- and Th17-type immune responses. Furthermore, Pim-1 inhibitor could induce T-cell differentiation towards a Treg phenotype. Pim-1 inhibitor has therapeutic effect on acute TNBS colitis.

YM155 enhances docetaxel efficacy in ovarian cancer.

YM155 (Sepantronium bromide) is a potent small molecule inhibitor of survivin by suppression of survivin expression and shows the promising anticancer activity in many types of cancers. Docetaxel (Taxotere®) is a member of the taxane drugs used in the treatment of a number of cancers in clinic. Despite the therapeutic efficacy of docetaxel is encouraging, the emergent resistance is an urgent issue. In this study, we investigate the effect of YM155 on docetaxel efficacy in ovarian cancer cells. Our data showed that YM155 actively induced cell growth inhibition, cell cycle arrest and apoptosis with downregualtion of survivin in ovarian cancer cells. Moreover, YM155 increased the intracellular ROS levels, and pretreatment with either NAC or GSH partially reversed the YM155-induced ROS accumulation and apoptosis only in the parental A2780 cells, but not in the resistant A2780/Taxol cells. Furthermore, YM155 enhanced docetaxel efficacy to inhibit the growth and induce apoptosis in ovarian cancer cells. Take together, our results suggested that combination of YM155 and docetaxel may be a feasible strategy for the treatment of ovarian cancer.

Crizotinib synergizes with cisplatin in preclinical models of ovarian cancer.

Crizotinib, a small molecule inhibitor of anaplastic lymphoma kinase (ALK), c-ros oncogene 1 (ROS1) and c-MET (also called MET or hepatocyte growth factor receptor), has been approved by the Food and Drug Administration for the treatment of patients with advanced non-small cell lung cancer whose tumors have rearrangements in the ALK or ROS1 gene. However, the anticancer effect of crizotinib on ovarian cancer is still unclear. In this study, our data show that crizotinib can actively induce cell growth inhibition, cell cycle arrest at G2/M phase and apoptosis with the decreasing phosphorylation of the downstream signaling effectors AKT and ERK in human ovarian cancer cells. Crizotinib also increases the intracellular reactive oxidative species (ROS) levels, and pretreating with ROS scavenger N-acety-L-cysteine partially reverses crizotinib-induced apoptosis. Moreover, crizotinib can synergistically inhibit ovarian cancer cells growth in vitro and in vivo when combines with cisplatin. Altogether, crizotinib potently potentiates the activity of cisplatin in ovarian cancer, suggesting the synergistic effect of crizotinib and cisplatin may be valuable for ovarian cancer patients' treatment.

Corticosteroid in Combination with Leflunomide and Mesenchymal Stem Cells for Treatment of Pediatric Idiopathic Pulmonary Hemosiderosis.

Background: This study evaluated the efficiency of corticosteroid, leflunomide and mesenchymal stem cells (MSCs) in the treatment of pediatric idiopathic pulmonary hemosiderosis (IPH). Methods: Ten patients were included in the study. The diagnosis of IPH was based on clinical symptoms, laboratory examinations and pulmonary hemosiderosis. Induction therapy consisted of methylprednisolone pulse therapy, followed by prednisone plus leflunomide. Maintenance therapy consisted of low-dose prednisone, leflunomide and administration of MSCs. Results: All the patients achieved complete response after treatment with corticosteroid, leflunomide and MSCs. The median follow-up was 23 months (range: 4-34 months). Moreover, administration of MSCs induced an increase in the percentage of CD4+ CD25+ regulatory T cells but a decrease in the percentage of Th17 cells. Conclusion: Treatment with corticosteroid, leflunomide and MSCs for pediatric IPH was safe and effective.