[Epidemiological characteristics of typhoid fever in Fujian Province, 2011-2022].

Objective: To analyze the incidence trend and epidemiological characteristics of typhoid fever in Fujian Province from 2011 to 2022, and understand the high-incidence population and hotspot areas, and provide evidences to develop more targeted prevention and control measures. Methods: The surveillance data of typhoid fever during 2011-2022 in Fujian Province were obtained from the National Disease Reporting Information System and analyzed with SAS 9.4. The spatial autocorrelation analysis of typhoid fever incidence at county/district levels was performed with ArcGlS 10.8. Results: A total of 5 126 cases of typhoid fever were reported in Fujian Province from 2011 to 2022, with an average annual incidence rate of 1.10/100 000. The average annual incidence rate was 0.96/100 000 from 2011 to 2015, 1.49/100 000 from 2016 to 2019, and 0.81/100 000 from 2020 to 2022. The disease occurred all the year round, with high epidemic season from May to September. A total of 23.59% (1 209/5 126) of the cases occurred at the age of 0-4, and 9.62% (493/5 126) at the age of 5-9. The male to female ratio of the cases was 0.97∶1 (2 524∶2 602) for the whole population, 1.19∶1 (925∶777) for people under 10 years old, 0.75∶1 (1 060∶1 404) for people between 10 and 54 years old, and 1.28∶1 (539∶421) for people over 55 years old. Cases in Ningde City accounted for 30.65% (1 571/5 126) of the total cases. Most hotspots were occurred in Ningde City. Recurrent and clustered cases were found in family members. Conclusions: Typhoid fever was prevalent at a low level in Fujian Province during 2011-2022, indicating that strengthening the prevention and control measures should target key areas and populations. The incidence of typhoid fever in Fujian Province showed spatial aggregation phenomenon, and most cases gathered in Ningde City. Intensive study for the influencing factors of spatial clustering should be conducted.

[Analysis on repetitive reporting of hepatitis B in Fujian province, 2016-2020].

Objective: To analyze the repetitive reporting of hepatitis B in Fujian province during 2016-2020, and provide evidence for the improvement of hepatitis B surveillance. Methods: The reporting cards from the China Information System for Disease Control and Prevention were collected and divided into repetitive reporting cards and non-repetitive reporting cards from the report cards collected according to the valid ID number on the cards, and the proportion of repetitive report cards and related factors were analyzed by using software SAS 9.4. Results: A total of 314 551 hepatitis B reporting cards were submitted in Fujian from 2016 to 2020, in which 90.93% (286 020/314 551) were included in the analysis. The repetitive reporting cards accounted for 10.48% (29 982/286 020). The annual proportion of the repetitive reporting cards from 2016 to 2020 was between 2.98% and 3.71%, showing an overall increasing trend year by year (Z=2.26, P=0.024). The proportions of the repetitive reporting cards in 1-5 years were 3.17%, 5.40%, 7.74%, 9.27% and 10.48%, respectively, showing an increase trend with year (Z=128.16, P<0.001). The proportions of the repetitive reporting cards in 10 areas of Fujian ranged from 5.44% to 13.48% with significant difference (χ2=2 050.41, P<0.001) and increased with the increase of reported incidence of hepatitis B (Z=26.92, P<0.001). There were significant differences in relationships between repetitive reporting proportion and sex, age and type of the cases between the areas with high incidence and low incidence of hepatitis B. Conclusions: The reported incidence of hepatitis B was seriously affected by the repetitive reporting in Fujian from 2016 to 2020. A cross-year and cross-area surveillance mechanism for hepatitis B should be established and targeted measures should be taken to strengthen the control of the repetitive reporting and improve the surveillance for hepatitis B.

lncRNA CASC2 suppresses the growth of hemangioma cells by regulating miR-18a-5p/FBXL3 axis.

Dysregulation of lncRNA cancer susceptibility candidate 2 (CASC2) is involved in the pathogenesis of multiple malignancies. However, the underlying mechanisms by which lncRNA CASC2 regulates the proliferation of hemangiomas (HAs) remain undocumented. Herein, the expression levels of lncRNA CASC2 and VEGF in proliferating or involuting phase HAs were assessed by qRT-PCR analysis, and the effects of lncRNA CASC2 on HAs cell growth were evaluated by MTT, colony formation assays and Western blot analysis. lncRNA CASC2 specific binding with miR-18a-5p was confirmed by luciferase report assay. Consequently, we found that the expression of lncRNA CASC2 was reduced in proliferating phase HAs as compared with the involuting phase HAs or normal tissues, and possessed a negative correlation with VEGF expression in proliferating phase HAs. Restored expression of lncRNA CASC2 repressed cell viability and colony formation and downregulated VEGF expression, while silencing lncRNA CASC2 showed the opposite effects. Moreover, lncRNA CASC2 was confirmed to bind with miR-18a-5p, which could reverse lncRNA CASC2-induced anti-proliferative effects by targeting FBXL3 in HAs cells. Altogether, our findings demonstrated that lncRNA CASC2 suppressed the growth of HAs cells by regulating miR-18a-5p/FBXL3 axis.

[Analysis on association between incidence of hand foot and mouth disease and meteorological factors in Xiamen, 2013-2017].

Objective: To study the influence of meteorological factors on the incidence of hand foot and mouth disease (HFMD) in Xiamen, Fujian province, and provide scientific evidence for the early warning, prediction, prevention and control of HFMD. Methods: Correlation analysis and distribution lag nonlinear models (DLNM) analysis of meteorological factors such as daily average pressure, daily average relative humidity, daily average temperature and sunshine hours and the incidence of HFMD in Xiamen during 2013 to 2017 were conducted by using R3.4.3 software. Results: A total of 36 464 cases of HFMD were reported in Xiamen during 2013-2017, and the incidence showed an upward trend (F=40.359, P=0.008). The daily average relative humidity, daily average temperature and sunshine hours were positively correlated with the incidence of HFMD (r>0), and the daily average site pressure was negatively correlated with the incidence of HFMD (r<0). In the case of a lag of 0-5 days, when the daily average pressure of the station was higher than 1 005 hPa, the risk of HFMD gradually increased with the increase of air pressure, and the risk of disease decreased with the increase of lag days. The risk was highest when air pressure was 1 017 hPa and at the lag of 0 day (RR=1.14, 95%CI: 0.67-1.94). When the relative humidity was higher than 95%, the risk of HFMD gradually increased with the increase of relative humidity, and the lag time ranged from 0 day to 10 days, which was most obvious on the 4(th) and 5(th) days. The risk was highest when relative humidity was 100% and at the lag of 5 days (RR=1.32, 95%CI: 1.02-1.71). When the air temperature was >28 ℃ and <8 ℃, the risk of HFMD existed, but the lag time was inconsistent. The relative risk was highest during 15-20 days at low air temperature, and the lag time at high air temperature was mainly during 5-15 days. The risk was highest when air temperature was 28 ℃ and at the lag of 4 days (RR=1.10, 95%CI: 0.94-1.29). The sunshine time was >12 h and lag of 0-3 days was a risk factor for the incidence of HFMD. The risk was highest when sunshine time was 13 h and the lag of 0 day (RR=1.20, 95%CI: 1.05-1.36). Conclusion: Meteorological factors such as daily average pressure, daily average relative humidity, daily average temperature and sunshine hours were associated with the incidence of HFMD with certain lag in Xiamen. So, it is suggested to use these data in the early warning system of HFMD.

[Strategy for prevention and control of imported infectious disease].

The process of globalization increases the risk of global transmission of infectious diseases, resulting in pressure for country's prevention and control of imported infectious disease. Based on the risk assessment of disease importation and local transmission, a strategy that conducting importation prevention and routine prevention and control before the importation of disease and taking emergency control measures after the importation of disease was developed. In addition, it is important to take part in global infectious disease response action, aid the countries with outbreak or epidemic to actively decrease the risk of disease importation.

[Analysis on epidemiology and spatial-temporal clustering of human brucellosis in Fujian province, 2011-2016].

Objective: To analyze the epidemiological characteristics and spatial distribution of human brucellosis in Fujian province during 2011-2016, and provide evidence for the prevention and control of the disease. Methods: The surveillance data of human brucellosis in Fujian during 2011-2016 was analyzed with software R 3.3.1, ArcGIS 10.3.1, GeoDa 1.8.8 and SaTScan 9.4.3. Results: During 2011-2016, a total of 319 human brucellosis cases were reported, the incidence increased year by year (F=11.838, P=0.026) with the annual incidence of 0.14/100 000. The male to female rate ratio of the incidence was 2.50 ∶ 1. Farmers and herdsmen accounted for 57.37%. The incidence was 0.40/100 000 in Zhangzhou and 0.32/100 000 in Nanping, which were higher than other areas. The number of affected counties (district) increased from 12 in 2011 to 28 in 2016, showing a significant increase (F=13.447, P=0.021). The Moran's I of brucellosis in Fujian between January 2011 and December 2016 was 0.045, indicating the presence of a high value or low value clustering areas. Local spatial autocorrelation analysis showed that, high-high clustering area (hot spots) were distributed in Zhangpu, Longhai, Longwen, etc, while high-low clustering areas were distributed in Nan'an and Jiaocheng, etc. Temporal scanning showed that there were three clustering areas in areas with high incidence, the most possible clustering, occurring during January 1, 2013- December 31,2015, covered 6 counties, including Yunxiao, Pinghe, Longhai, etc, and Zhangpu was the center, (RR=7.96, LLR=92.62, P<0.001). Conclusions: The epidemic of human brucellosis in Fujian is becoming serious, and has spread to general population and non-epidemic areas. It is necessary to strengthen the prevention and control of human brucellosis in areas at high risk.

Knockdown of HMGB1 inhibits cell proliferation and induces apoptosis in hemangioma via downregulation of AKT pathway.

The high mobility group box 1 (HMGB1) as a conserved non-histone nuclear protein has been involved in a variety of biological processes of cancer, such as cell proliferation, apoptosis, angiogenesis and metastasis. Despite the increased expression of HMGB1 in many malignant tumors, the functions and molecular mechanisms by which HMGB1 contributes to the formation of hemangioma (HA) remain unclear. In the present study, immunohistochemistry was used to detect the expression levels of HMGB1 in different phases of human HAs. Cell function experiments, including MTT, cell colony formation and flow cytometry analysis were performed to evaluate the effects of HMGB1 knockdown on cell proliferation and apoptosis in HA CRL-2586 EOMA cells. As a consequence, we found that HMGB1 expression was significantly increased in proliferating phase HAs compared with the involuting phase HAs and normal skin tissues (P less than 0.01). Moreover, knockdown of HMGB1 gene in vitro suppressed EOMA cell proliferation and colony formation and induced cell apoptosis and cycle arrest at G0/G1 phase by downregulation of PCNA, CyclinD1, p-AKT and upregulation of p53 and cleaved PARP. Taken together, our findings demonstrate that HMGB1 may be implicated in the formation of HA through upregulation of AKT pathway, and represent a potential therapeutic target for treating HA.

Oxymatrine suppresses proliferation and induces apoptosis of hemangioma cells through inhibition of HIF-1a signaling.

Oxymatrine (OMT), a natural quinolizidine alkaloid, has been known to have anti-inflammation, anti-anaphylaxis, and chemopreventive effects on various cancer cells. To clarify the underlying role and molecular mechanisms of OMT in human hemangioma (HA), in the present study, we examined the expression of hypoxia-inducible factor-1a (HIF-1a) and vascular endothelial growth factor (VEGF) in different phases of human HA. After HA derived endothelial cells (HDEC) were pretreated with different concentrations of OMT, cell proliferation, apoptosis, and cycle distribution were evaluated by MTT assay and flow cytometry analysis, respectively. The effects of OMT on expression of HIF-1a signaling were determined by real-time PCR and western blot assays. Our results showed that, the expression of HIF-1a and VEGF was significantly increased in proliferating phase HA, but decreased in involuting phase HA. Moreover, OMT in vitro inhibited proliferative activities and induced cell apoptosis and cycle arrest in G0/G1 phase in HA cells with decreased expression of HIF-1a, VEGF, Bcl-2, and CyclinD1, and increased expression of p53. Taken together, our findings suggest that, the expression of HIF-1a and VEGF is increased in proliferating phase HA, and OMT suppresses cell proliferation and induces cell apoptosis and cycle arrest in proliferative phase HA through inhibition of the HIF-1a signaling pathway, suggesting OMT may provide a novel therapeutic strategy for the treatment of HA.

Emissions of halocarbons from mobile vehicle air conditioning system in Hong Kong.

During the implementation of Montreal Protocol, emission inventories of halocarbons in different sectors at regional scale are fundamental to the formulation of relevant management strategy and inspection of the implementation efficiency. This study investigated the emission profile of halocarbons used in the mobile vehicle air conditioning system, the leading sector of refrigeration industry in terms of the refrigerant bank, market and emission, in the Hong Kong Special Administrative Region, using a bottom-up approach developed by 2006 IPCC Good Practice Guidance. The results showed that emissions of CFC-12 peaked at 53 tons ODP (Ozone Depletion Potential) in 1992 and then gradually diminished, whereas HFC-134a presented an increasing emission trend since 1990s and the emissions of HFC-134a reached 65,000 tons CO2-equivelant (CO2-eq) by the end of 2011. Uncertainty analysis revealed relatively high levels of uncertainties for special-purpose vehicles and government vehicles. Moreover, greenhouse gas (GHG) abatements under different scenarios indicated that potential emission reduction of HFC-134a ranged from 4.1 to 8.4 × 10(5)tons CO2-eq. The findings in this study advance our knowledge of halocarbon emissions from mobile vehicle air conditioning system in Hong Kong.

Knockdown of IGF2R suppresses proliferation and induces apoptosis in hemangioma cells in vitro and in vivo.

Insulin-like growth factor-II (IGF-II)/IGF2R signaling plays a pivotal role in cell growth, migration and differentiation in many malignancies. An individual with high IGF-II expression levels has a high risk of developing cancer, but IGF2R is often considered to be a tumor suppressor. To date, little has been reported about the role of IGF-II/IGF2R signaling in hemangiomas (HAs). Thus, uncovering the mechanisms of IGF-II/IGF2R signaling is very important to understanding the development of HAs. In the present study, the expression of IGF-II and IGF2R was investigated in 27 cases of HAs of different phases by immunohistochemistry. Through lentivirus-mediated IGF2R siRNA (Lv-siIGF2R) in HA-derived endothelial cells (HDECs), we observed the effects of IGF2R knockdown on the biological behavior of HA cells. We found that the expression of IGF-II and IGF2R was significantly increased in proliferating phase HAs, but decreased in involuting phase HAs. Furthermore, knockdown of IGF2R in vitro significantly diminished the proliferative activity and induced apoptosis and cycle arrest with decreased expression of PCNA, Ki-67, Bcl-2, Cyclin D1 and E and increased the expression of Bax in the proliferative phase HAs (HDEC and CRL-2586 EOMA cells). In addition, the tumor volumes in a subcutaneous HDEC nude mouse model treated with Lv-siIGF2R were significantly smaller than those of the control group. Taken together, our findings indicate that the expression of IGF-II and IGF2R is increased in proliferating phase HAs, and knockdown of IGF2R suppresses proliferation and induces apoptosis in HA cells in vitro and in vivo, suggesting that IGF2R may represent a novel therapeutic target for the treatment of human HAs.

Knockdown of VEGFR2 inhibits proliferation and induces apoptosis in hemangioma-derived endothelial cells.

Angiogenesis is a process of development and growth of new capillary blood vessels from pre-existing vessels. Angiogenic growth factors play important roles in the development and maintenance of some malignancies, of which vascular endothelial growth factor (VEGF)/VEGFR2 interactions are involved in proliferation, migration, and survival of many cancer cells. The aim of this study was to investigate the function of VEGFR2 in human hemangiomas (HAs). Using immunohistochemistry assay, we examined the expression levels of VEGF, VEGFR2, Ki-67, glucose transporter-1 (Glut-1), phosphorylated protein kinase B (p-AKT) and p-ERK in different phases of human HAs. Positive expression of VEGF, VEGFR2, Ki-67, Glut-1, p-AKT and p-ERK was significantly increased in proliferating phase HAs, while decreased in involuting phase HAs (P=0.001; P=0.003). In contrast, cell apoptotic indexes were decreased in proliferating phase HAs, but increased in involuting phase HAs (P<0.01). Furthermore, we used small hairpin RNA (shRNA)-mediated VEGFR2 knockdown in primary HA-derived endothelial cells (HemECs) to understand  the  role  of  VEGF/VEGFR2 signaling. Knockdown of VEGFR2 by Lv-shVEGFR2 inhibited cell viability and induced apoptosis in primary HemECs companied with decreased expression of p-AKT, p-ERK, p-p38MAPK and Ki-67 and increased expression of caspase-3 (CAS-3). Overexpression of VEGFR2 promoted cell viability and blocked apoptosis in Lv-VEGFR2-transfected HemECs. Taken together, our findings demonstrate that, increased expression of VEGFR2 is involved in the development of primary HemECs possibly through regulation of the AKT and ERK pathways, suggesting that VEGFR2 may be a potential therapeutic target for HAs. 

Knockdown of Livin inhibits growth and invasion of gastric cancer cells through blockade of the MAPK pathway in vitro and in vivo.

Livin, a novel member of the human inhibitors of apoptosis protein family, has been shown to be critical for tumor progression and poor prognosis for several types of malignancies. However, limited reports exist regarding the biological functions of Livin in human gastric cancer (GC). The present study investigated the clinical significance of Livin and caspase-3 (CAS-3) in human GC using immunohistochemistry assay, and explore the potential using RNA interference to knockdown Livin expression, including the subsequent effects on tumor growth and invasion in GC cells in vitro and in vivo. Our results showed that the rate of positive expression of Livin was significantly higher in GC tissues compared to that in adjacent non-cancer tissues (ANCT) (64.1 vs. 30.8%, P<0.001), while CAS-3 was lower in GC tissues than in ANCT (33.3 vs. 66.7%, P=0.001). Livin expression was positively correlated with tumor differentiation and lymph node metastases (P=0.009; P=0.007), while CAS-3 was negatively correlated with them (P=0.036; P=0.002) in patients with GC. Furthermore, knockdown of Livin inhibited cell proliferative activities and invasive potential, and induced cell in situ apoptosis in GC cells, accompanied with decreased expression of p38 MAPK, VEGF and MMP-2 and increased expression of CAS-3. In addition, the tumor volumes in the SGC7901 subcutaneous nude mouse model treated with Lv-shLivin was significantly smaller compared to those of the PBS group (P<0.01). Taken together, our findings indicate that the expression of Livin is increased in human GC and correlates with tumor differentiation and lymph node metastases, while knockdown of Livin inhibits cell growth and invasion through blockade of the MAPK pathway in GC cells, suggesting that Livin may be a potential therapeutic target for the treatment of GC.

Combined blockade of AKT/mTOR pathway inhibits growth of human hemangioma via downregulation of proliferating cell nuclear antigen.

Protein kinase B (AKT)/mammalian target of rapamycin (mTOR) signaling pathway plays a crucial role in the tumorigenesis and progression of multiple tumors, and has been shown to be important therapeutic targets for cancer. The present study aimed to explore the role and molecular mechanisms of AKT/mTOR pathway in human hemangioma (HA). Twenty-five cases of human HA tissues were collected. The expression of AKT, mTOR and proliferating cell nuclear antigen (PCNA) proteins was evaluated using semi-quantitative immunohistochemistry in biopsy samples in different phases of HA. AKT/mTOR pathway was blocked by recombinant small hairpin RNA adenovirus vector rAd5-AKT+mTOR (rAd5-Am), used for infecting proliferating phase HA-derived endothelial cells (HDEC). The expression of AKT, mTOR and PCNA was detected by Real-time PCR and Western blot assays. Cell proliferative activities were determined by MTT assay, and cell cycle distribution and apoptosis were analyzed by flow cytometry. As a consequence, the expression of AKT, mTOR and PCNA was significantly increased in proliferative phase HA, while that was decreased in involutive phase. Combined blockade of AKT/mTOR pathway by rAd5-Am diminished cell proliferative activities, and induced cell apoptosis and cycle arrest with the decreased expression of AKT, mTOR and PCNA in proliferative phase HDEC. In conclusion, the activity of AKT/mTOR pathway was increased in proliferative phase HA, while it was decreased in involutive phase. Combined blockade of AKT/mTOR pathway might suppress cell proliferation via down-regulation of PCNA expression, and induce apoptosis and cycle arrest in proliferative phase HDEC, suggesting that AKT/mTOR pathway might represent the important therapeutic targets for human HA.

Protective effects of ligustrazine, kakonein and Panax notoginsenosides on multiple organs in rats with severe acute pancreatitis.

The aim of this study was to compare the protective effects of three traditional Chinese herbal medicines (ligustrazine, kakonein and Panax notoginsenosides) on multiple organs in a rat model of severe acute pancreatitis (SAP) and to explore the underlying mechanisms. The mortality rates in all three treated groups were significantly lower than the control group (P < 0.05). All three herbal medicines significantly alleviated the pathological changes in the pancreas, liver and kidney in SAP rats, induced pancreatic acinar cell apoptosis and effectively prevented the apoptosis of cells in the liver and kidney; however, no obvious lung protection was observed. Panax notoginsenosides showed better pancreatic protection than ligustrazine and kakonein, while kakonein displayed a better role in improving liver and kidney function. The protective effects of ligustrazine were somewhat more comprehensive.