Novel Pt(IV) complexes containing salvigenin ligand reverse cisplatin-induced resistance by inhibiting Rap1b-mediated cancer cell stemness in esophageal squamous cell carcinoma treatments.

Esophageal squamous cell carcinoma (ESCC) is a malignant tumor that is highly susceptible to metastasis, recurrence and resistance, and few therapeutic targets have been identified and proven effective. Herein, we demonstrated for the first time that Rap1b can positively regulate ESCC cell stemness, as well as designed and synthesized a novel class of Pt(IV) complexes that can effectively inhibit Raplb. In vitro biological studies showed that complex-1 exhibited stronger cytotoxicity than cisplatin and oxaliplatin against a variety of ESCC cells, and effectively reversed cisplatin-induced resistance of TE6 cells by increasing cellular accumulation of platinum and inhibiting cancer cell stemness. Significantly, complex-1 also exhibited strong ability to reversal cisplatin-induced cancer cell resistance and inhibit tumor growth in TE6/cDDP xenograft mice models, with a tumor growth inhibition rate of 73.3 % at 13 mg/kg and did not show significant systemic toxicity. Overall, Rap1b is a promising target to be developed as an effective treatment for ESCC. Complex-1, as the first Pt(IV) complex that can strongly inhibit Rap1b, is also worthy of further in-depth study.

Predicting the prognosis of esophageal cancer based on extensive analysis of new inflammatory response-related signature.

The prognosis of esophageal cancer (ESCA) is very poor, with a 5-year survival rate of less than 20%. On the other hand, inflammation is the characteristic hallmark of ESCA; however, the prognostic relationship between inflammatory response-related genes and ESCA has not been clarified yet. Therefore, in the present manuscript, we intend to investigate the correlation and specific signature of inflammation for the prediction of the prognosis of ESCA. A total of 173 samples were obtained from The Cancer Genome Atlas (TCGA) database, including 162 tumors and 11 normal specimens. The prognostic signature was established by least absolute shrinkage and selection operator Cox regression analysis. The transcription factor regulatory network with genes of the prognostic signature was analyzed from the transcriptional regulatory relationships unravelled by sentence-based text-mining database. Chemotherapy sensitivity and immunotherapy analysis were also performed. Multivariate Cox analysis showed that the signature was an independent prognostic risk factor. The low-risk group had poorer outcomes than the high-risk group. In the high-risk group, the infiltration of most immune cells was high and strongly correlated with the riskScore. In chemotherapeutic drug sensitivity analysis, OSM, AHR, and BTG2 were significantly correlated with the current chemotherapeutic drugs of ESCA. We have demonstrated a valid prognostic signature of inflammatory response-related genes and found strong associations with immune cells, targeted genes, and chemotherapeutic agents.

Influence factors of channel geometry for separation of circulating tumor cells by four-ring inertial focusing microchannel.

Inertial microfluidics is a high-throughput and high-efficiency cell separation approach to which attention has been progressively paid in recent years. However, research on the influencing factors that compromise the efficiency of cell separation is still lacking. Therefore, the aim of this study was to evaluate the cell separation efficiency by changing the influencing factors. A four-ring inertial focusing spiral microchannel was designed to separate two kinds of circulating tumor cells (CTCs) from blood. Human breast cancer (MCF-7) cells and human epithelial cervical cancer (HeLa) cells enter the four-ring inertial focusing spiral microchannel together with blood cells, and cancer cells and blood cells were separated from each other at the outlet of the channel by inertial force. The cell separation efficiency at the inlet flow rate in the Reynolds number range of 40-52 was studied by changing the influencing factors such as the cross-sectional shape of the microchannel, the average thickness of the cross-section, and the trapezoidal inclination angle. The results showed that the reduction of the channel thickness and the increase of a certain trapezoidal inclination enhanced the cell separation efficiency to a certain extent, the study showed that when the channel inclination was 6 ° and the average channel thickness was 160 µm. The two kinds of CTC cells could be completely separated from the blood and the efficiency could reached 100%.

CircTUBGCP3 facilitates the tumorigenesis of lung adenocarcinoma by sponging miR-885-3p.

BACKGROUND: Circular RNAs (circRNAs) act pivotal roles in the progression of multiple malignancies. However, the underlying mechanisms by which hsa_circ_0007031 (circTUBGCP3) contributes to lung adenocarcinoma (LAC) remain largely unknown. METHODS: The association of circTUBGCP3 expression with clinicopathological characteristics and prognosis in patients with LAC was determined by RT-qPCR and fluorescence in situ hybridization. The in vitro functional experiments as well as a subcutaneous tumorigenesis model were executed to estimate the role of circTUBGCP3 in LAC cells. The interaction between circTUBGCP3 and miR-885-3p was confirmed by RNA immunoprecipitation, luciferase gene report and RT-qPCR assays. The effects of circTUBGCP3 on miR-885-3p-mediated Wnt10b/ß-catenin signaling were evaluated by Western blot. RESULTS: The upregulation of circTUBGCP3 or downregulation of miR-885-3p was associated with the pathological stage and poor survival in patients with LAC. Restored expression of circTUBGCP3 facilitated the growth and invasion of LAC cells, but knockdown of circTUBGCP3 harbored the opposite effects. In mechanism, circTUBGCP3 could act as a sponge of miR-885-3p, which suppressed the cell proliferation and colony formation and attenuated the tumor-promoting effects of circTUBGCP3. Wnt10b as a target of miR-885-3p could be upregulated be circTUBGCP3 and indicate poor survival in patient with LAC. CONCLUSIONS: Our findings demonstrated that circTUBGCP3 promoted LAC progression by sponging miR-885-3p, and might represent a prognostic factor for LAC.

PAR1 and PAR4 exert opposite effects on tumor growth and metastasis of esophageal squamous cell carcinoma via STAT3 and NF-κB signaling pathways.

BACKGROUND: Esophageal carcinogenesis is a multifactorial process in which genetic and environmental factors interact to activate intracellular signals, leading to the uncontrolled survival and growth of esophageal squamous cell carcinoma (ESCC) cells. The intracellular pathways of ESCC cells could be regulated by proteinase activated-receptors (PARs), which are comprised of four receptors (i.e., PAR-1, PAR-2, PAR-3, and PAR-4). Therefore, the function and possible mechanism of PAR1 and PAR4 in the progression of ECSS were explored in our study. METHODS: First, we detected the expression levels of PAR1 and PAR4 in 27 cases of ESCC specimens and cell lines by RT-qPCR, IHC and western blot. Meanwhile, the correlation between PAR1/PAR4 expression levels, clinicopathological characteristics, and disease free survival was analyzed. Then, we constructed PAR1/PAR4 knockdown cell models and investigated the role of PAR1/PAR4 knockdown on the proliferation, apoptosis, changes of calcium flow, and metastasis of ESCC cells via MTT, flow cytometry, transwell and wound healing assays in vitro. Further, an experimental metastasis model in vivo was established to explore the role of stable PAR1/PAR4 knockdown on the growth and metastasis of ESCC cells. Finally, the role of nSMase2 in the activation of NF-κB induced by PAR4 and the role of NF-κB and STAT3 signaling pathways in the PAR1/PAR4-mediated tumor promoting or suppressive functions were measured by immunoprecipitation, western blot and immunofluorescence assays. RESULTS: First, the integrated results demonstrated the expression levels of PAR1 and PAR4 are inversely proportional in ESCC. PAR1 potently enhanced tumor growth and metastasis, while PAR4 had an inhibitory effect. Further, the co-activation of STAT3 and NF-κB was involved in the PAR1 activation-induced tumor promoting effect, while only NF-κB participated in the PAR4 activation-induced tumor inhibitory effect in ESCC. To be specific, FAK/PI3K/AKT/STAT3/NF-κB signaling mediated PAR1 activation-induced tumor promoting effect and nSMase2/MAPK/NF-κB signaling mediated PAR4 activation-induced tumor inhibitory effect. CONCLUSIONS: Overall, the study has provided new insights into the potential implication of PAR1 and PAR4 in the pathogenesis of ESCC. Besides, FAK/PI3K/AKT/STAT3/NF-κB and nSMase2/MAPK/NF-κB pathways may be novel targets for regulating tumor growth and metastasis in ESCC patients.

microRNA-10b confers cisplatin resistance by activating AKT/mTOR/P70S6K signaling via targeting PPARγ in esophageal cancer.

It is well known that the acquisition of chemoresistance is a major obstacle for the effective treatment of human cancers. It is reported that microRNAs (miRNAs) are implicated in chemotherapy resistance of various malignancies. miR-10b was previously proved as an oncogene in multiple malignancies, including esophageal cancer. However, its biological significance in regulating cisplatin (DDP) resistance in esophageal cancer is still elusive. Here, we observed that miR-10b expression was upregulated and peroxisome proliferator-activated receptor-γ (PPARγ) expression was downregulated in esophageal cancer tumor tissues and cells. PPARγ was proved as a functional target of miR-10b. Moreover, suppression of miR-10b enhanced the chemosensitivity of esophageal cancer cells to DDP in vitro and in vivo. In addition, PPARγ-mediated DDP sensitivity was weakened by miR-10b overexpression. Furthermore, miR-10b-activated AKT/mTOR/p70S6K signaling pathway through targeting PPARγ. Inactivation of AKT/mTOR/p70S6K by AKT inhibitor (GSK690693) attenuated miR-10b-induced DDP resistance in esophageal cancer cells. Taken together these observation, miRNA-10b-mediated PPARγ inhibition enhanced DDP resistance by activating the AKT/mTOR/P70S6K signaling in esophageal cancer, suggesting a potential target to improve therapeutic response of patients with esophageal cancer to DDP.

Long noncoding RNA ADAMTS9-AS2 suppresses the progression of esophageal cancer by mediating CDH3 promoter methylation.

Long noncoding RNAs (lncRNAs) have been implicated in the biology of esophageal cancer via mRNA degradation or translational inhibition. CDH3 is also aberrantly expressed in numerous cancers. This study was conducted with the hypothesis that ADAMTS9-AS2 or CDH3 methylation plays a role in esophageal cancer cell activity and in vivo development. Firstly, mRNA levels of ADAMTS9-AS2 and CDH3 in esophageal cancer tissues and cells were detected by reverse-transcription quantitative polymerase chain reaction. Afterward, esophageal cancer OE21 cells were treated with overexpression of ADAMTS9-AS2, siRNA against ADAMTS9-AS2, overexpression of CDH3 and demethylating agent 5-aza-dc. The biological functions of esophageal cancer OE21 cells were assayed to define the regulatory mechanisms of ADAMTS9-AS2 in esophageal cancer. The interactions among ADAMTS9-AS2, DNMT1/DNMT3 (A/B) and CDH3 were detected by MSP, RNA pull-down, RIP, and ChIP assays. The in vitro findings were reproduced in nude mice to explore the role of ADAMTS9-AS2 in the development of esophageal cancer in vivo. Esophageal cancers expressed low levels of ADAMTS9-AS2 and high levels of CDH3. Methylation of CDH3 promoter was induced by ADAMTS9-AS2 via DNMT1/DNMT3 (A/B). Furthermore, proliferation, invasion, and migration of esophageal cancer cells were inhibited by ADAMTS9-AS2 via downregulation of CDH3. Suppressed esophageal cancer development in vivo was also detected after ADAMTS9-AS2 overexpression. Overexpressed ADAMTS9-AS2 aids in the suppression of esophageal cancer development, which is achieved via inducing CDH3 promoter methylation.

Upregulation of long noncoding RNA SPRY4-IT1 promotes metastasis of esophageal squamous cell carcinoma via induction of epithelial-mesenchymal transition.

Esophageal squamous cell carcinoma (ESCC) is one of the prevalent and deadly cancers worldwide, especially in Eastern Asia. Recent studies show that long noncoding RNAs (lncRNAs) have critical roles in diverse biological processes, including tumorigenesis. In the present study, we find that the expression of lncRNA SPRY4-IT1 is significantly upregulated in ESCC cell lines as compared with human esophageal epithelial cell line HEEC. Overexpression of SPRY4-IT1 can increase in vitro motility of ESCC cells via induction of epithelial-mesenchymal transition (EMT), which is characterized by increasing the expression of vimentin (Vim) and fibronectin (FN) with a concomitant decrease of E-cadherin (E-Cad) and ZO-1, while silencing of SPRY4-IT1 significantly inhibits the in vitro motility of ESCC cells. Further, the knockdown of SPRY4-IT1 also significantly attenuates TFG-ß-induced EMT of ESCC cells. Further, lncRNA SPRY4-IT1 can directly increase the transcription, expression, and nuclear localization of Snail, one key transcription factor during the EMT processes of cancer cells, while siRNA-mediated specific knockdown of Snail can significantly attenuate SPRY4-IT1-induced EMT of ESCC cells. Our results suggest that lncRNA SPRY4-IT1 might be considered as a novel oncogene involved in ESCC progression.

Endemic and imported measles virus-associated outbreaks among adults, Beijing, China, 2013.

In 2013, a resurgence of measles occurred in Beijing, China. The outbreaks occurred among adults and were associated with endemic genotype H1 and imported genotype D8 viruses. Migrant workers were disproportionately represented in the outbreaks; thus, vaccinating such workers against measles may be an effective strategy toward the elimination of this disease.

Safety and effectiveness of a 2009 H1N1 vaccine in Beijing.

BACKGROUND: After the first monovalent 2009 pandemic influenza A (H1N1) vaccine became available in September 2009, Chinese officials conducted a mass vaccination program in Beijing. We evaluated the safety and effectiveness of the vaccine. METHODS: During a 5-day period in September 2009, a total of 95,244 children and adults received the PANFLU.1 vaccine (Sinovac Biotech), a monovalent split-virion vaccine of 15 µg of hemagglutinin antigen without adjuvant. We assessed adverse events after immunization through an enhanced passive-surveillance system and through active surveillance, using diary cards and telephone interviews. Active surveillance for neurologic diseases was implemented in hospitals citywide. To assess vaccine effectiveness, we compared the rates of reported laboratory-confirmed cases of 2009 H1N1 virus infection in students who received the vaccine with the rates in those who did not receive the vaccine, starting 2 weeks after the mass vaccination. RESULTS: As of December 31, 2009, adverse events were reported by 193 vaccine recipients. Through hospital-based active surveillance, 362 cases of incident neurologic diseases were identified within 10 weeks after the mass vaccination, including 27 cases of the Guillain-Barré syndrome. None of the neurologic conditions occurred among vaccine recipients. From 245 schools, 25,037 students participated in the mass vaccination and 244,091 did not. During the period from October 9 through November 15, 2009, the incidence of confirmed cases of 2009 H1N1 virus infection per 100,000 students was 35.9 (9 of 25,037) among vaccinated students and 281.4 (687 of 244,091) among unvaccinated students. Thus, the estimated vaccine effectiveness was 87.3% (95% confidence interval, 75.4 to 93.4). CONCLUSIONS: Among 95,244 children and adults in Beijing, the PANFLU.1 vaccine had a safety profile similar to those of seasonal influenza vaccines and appeared to be effective against confirmed H1N1 virus infection in school-age children. (Funded by the Beijing Municipal Health Bureau.).

Rubella epidemic caused by genotype 1E rubella viruses in Beijing, China, in 2007-2011.

BACKGROUND: A series of different rubella vaccination strategies were implemented to control rubella and prevent congenital rubella virus infection in Beijing, China. The rubella vaccine was available in 1995 in Beijing, and was introduced into the Beijing immunization program (vaccine recipients at their own expense vaccination) in 2000, and was introduced into the National Expanded Program on Immunization (vaccine recipients free vaccination) in 2006. Rubella virological surveillance started in Beijing in 2007. RESULTS: The reported rubella incidence rate has decreased dramatically due to the introduction of the vaccine in Beijing since 1995. However, rubella epidemics occurred regardless in 2001 and 2007. The incidence rate among the floating population has gradually increased since 2002, reaching 2 or more times that in the permanent resident population. The peak age of rubella cases gradually changed from <15 years of age to adults after 2005. Phylogenetic analysis was performed and a phylogenetic tree was constructed based on the World Health Organization standard sequence window for rubella virus isolates. All Beijing rubella virus isolates belong to genotype 1E/cluster1 and were clustered interspersed with viruses from other provinces in China. The effective number of infections indicated by a Bayesian skyline plot remained constant from 2007 to 2011. CONCLUSIONS: The proportion of rubella cases among the floating population has increased significantly in Beijing since 2002, and the disease burden gradually shifted to the older age group (15- to 39-year olds), which has become a major group with rubella infection since 2006. Genotype 1E rubella virus continuously caused a rubella epidemic in Beijing in 2007-2011 and was the predominant virus, and all Beijing genotype 1E viruses belong to cluster 1, which is also widely circulated throughout the country.

Autophagy as a novel strategy for treatment of gastric cancer: a hypothesis.

Gastric cancer is the second most frequent cause of cancer-related death in the world and also causes much morbidity. The acquired resistance of cancer cells to drug reagents is becoming a major obstacle for successful cancer therapy. Recently, many studies have revealed that macroautophagy (here referred to as autophagy) may be a prosurvival factor and protect the cancer cell from the development of drug-induced death. Thus, we propose that autophagy may play an important role in the resistance of gastric cancer to therapy. Although the exact role of autophagy in tumor cells is still unclear and further studies are needed to prove the role of autophagy in gastric cancer, recent research findings suggest a new direction in investigating the mechanism underlying resistance of gastric cancer to therapy.

Autophagy facilitates ventilator-induced lung injury partly through activation of NF-kappaB pathway.

Mechanical ventilation is an important supportive therapy in the intensive care unit (ICU) to assist the critically ill patients with respiratory failure. But longer ventilation time has been proven to contribute to the lung injury which has been recognized as ventilator-induced lung injury (VILI). Recently studies have suggested that NF-kappaB signaling pathways may play a critical role in the process of inflammation and autophagy, and autophagy can reduce the damage of VILI partly by activating the NF-kappaB pathways. Thus, we propose that autophagy may facilitate ventilator-induced lung injury partly through activation of NF-kappaB pathway, which might be a new potential therapeutic target for ventilator-induced lung injury. Although the exact mechanism of autophagy and its exact role in the VILI need to be further explored, at least it provides us a potential target in the future prevention of VILI.

A 60-year review on the changing epidemiology of measles in capital Beijing, China, 1951-2011.

BACKGROUND: China pledged to join the global effort to eliminate measles by 2012. To improve measles control strategy, the epidemic trend and population immunity of measles were investigated in 1951-2011 in Beijing. METHODS: The changing trend of measles since 1951 was described based on measles surveillance data from Beijing Centre of Disease Control and Prevention (CDC). The measles vaccination coverage and antibody level were assessed by routinely reported measles vaccination data and twenty-one sero-epidemiological surveys. RESULTS: The incidence of measles has decreased significantly from 593.5/100,000 in 1951 (peaked at 2721.0/100,000 in 1955), to 0.5/100,000 in 2011 due to increasing vaccination coverage of 95%-99%. Incidence rebounded from 6.6/100,000 to 24.5/100,000 since 2005 and decreased after measles vaccine (MV) supplementary immunization activities (SIAs) in 2010. Measles antibody positive rate was 85%-95% in most of years since 1981. High-risk districts were spotted in Chaoyang, Fengtai and Changping districts in recent 15 years. Age-specific incidence and proportion of measles varied over time. The most affected population were younger children of 1-4 years before 1978, older children of 5-14 years in 1978-1996, infant of <1 years and adults of ≥15 years in period of aim to measles elimination. CONCLUSION: Strategies at different stages had a prevailing effect on the epidemic dynamics of measles in recent 60 years in Beijing. It will be essential to validate reported vaccination coverage, improve vaccination coverage in adults and strengthen measles surveillance in the anticipated elimination campaign for measles.

[Immunogenicity and safety of a booster dose of inactivated polio vaccine].

OBJECTIVE: To evaluate the immunogenicity and safety of a boost dose of inactivated polio vaccine (IPV) among children aged 18 months who had been administered with primary doses of IPV. METHODS: Form 2011 to 2012, a total of 97 children were enrolled in the present study who were vaccinated with IPV at 2, 3, 4 months of age and boosted with the same vaccine at 18 months of age. Anti-poliovirus neutralizing antibody titers in serum were measured before and after booster vaccination, geometric mean titers (GMT) and seroprotection rate were calculated. Adverse events occurring within 30 days after booster vaccination were observed, including pain, redness/swelling and induration at the injection site, fever, vomit, abnormal crying, drowsiness, loss of appetite, irritability, and all other physical discomfort and related medications were also recorded. A descriptive analysis was performed for the safety assessment. RESULTS: Immunogenicity was assessed in 84 subjects. The pre-booster seropositivity rates of neutralizing antibody against poliovirus type 1, 2, 3 before booster were all 100% (84/84) and the corresponding GMT (95% CI) was 1: 148.5 (116.49-189.29) , 1: 237.68 (178.39-316.67) and 1: 231.87 (181.27-296.58) , respectively. The seropositivity rates of neutralizing antibody against the three types of poliovirus after booster were all 100% (84/84) and the corresponding GMT (95% CI) was 1: 1612.14 (1470.57-1767.34) , 1: 1854.92 (1715.83-2005.29) and 1: 1625.50 (1452.12-1819.58) , respectively. The pre-booster titer of neutralizing antibody against poliovirus type 1, 2, 3 mainly ranged 1: 128-1: 512, which accounted for 65% (55/84) , 55% (46/84) , 74% (62/84) in each type. After the booster immunization, titers of neutralizing antibody against type 1, 2, 3 were increased as subjects with titer ≥ 1: 1024 accounted for 94% (78/84) , 95% (80/84) , 92% (77/84) , respectively.Safety was evaluated in 96 subjects, of which 16 subjects reported adverse events with the rate of 17%. The observed local events were mainly tenderness 3% (3/96) , redness/swelling and induration were not reported. The systemic adverse events included loss of appetite (8%, 8/96) , irritability (8%, 8/96) , fever (7%, 7/96) , abnormal crying (6%, 6/96) , drowsiness (6%, 6/96) and vomit (1%, 1/96) . All reported adverse events were mild or moderate. All of the local events occurred in the day of vaccination and lasted for 1-2 days, while systemic events almost developed within 2 days after vaccination and last less than 3 days. CONCLUSION: IPV booster dose has good immunogenicity and safety profile, which provides effective protection against poliovirus.

[Safety of different sequential immunization schedules of inactivated poliovirus vaccine and oral poliovirus vaccine primary vaccination].

OBJECTIVE: To evaluate safety of different sequential immunization schedules of inactivated poliovirus vaccine (IPV) and oral poliovirus vaccine (OPV) primary vaccination. METHODS: Infants of 2 months old (60-89 days) selected in Beijing, were assigned to four groups, 1 dose IPV plus 2 doses OPV (I-O-O), 2 doses IPV plus 1 dose OPV(I-I-O), 3 doses IPV (I-I-I), and 3 doses OPV (O-O-O), and were vaccinated at the age of 2, 3, 4 months, from 2009 to 2011. The frequencies of systemic as well as local injection site reactions after every dose were recorded and calculated. A total of 553 infants were enrolled in the study and 89 infants were quit, 1492 diseases were observed. RESULTS: The incidence of adverse events in I-O-O, I-I-O, I-I-I, O-O-O were 22.9% (94/410), 18.4% (60/327), 22.0% (78/354) and 17.7% (71/401) with no statistical differences (χ(2) = 4.84, P = 0.184). Dose 1 (22.7% (32/141)-35.3% (54/153) ) was more frequently than dose 2 and dose 3. No serious adverse events (SAE) were reported during the study. The incidence of systemic adverse reactions in I-O-O, I-I-O, I-I-I, O-O-O were 21.5% (88/410), 17.7% (58/327) , 20.1% (71/354) and 17.7% (71/401) with no statistical differences (χ(2) = 2.53, P = 0.472). Abnormal crying were the most frequency reactions (7.2% (29/401)-11.3% (37/327) ) in 4 groups. Rarely severe reactions were observed of abnormal crying, somnolence, irritability and mild or medium reactions occurred in other symptoms. Local adverse reactions such as injection site pain, scleroma and swelling were reported by 2.2% (5/229)-5.6% (22/393) ,0-0.9% (2/229) and 0-1.0% (4/393) in I-O-O,I-I-O and I-I-I, and most reactions were mild. CONCLUSION: Three IPV immunization and IPV/OPV sequential immunization as well as three OPV immunization demonstrated safe.

Impact of 1,25-dihydroxyvitamin D3 PLGA-nanoparticles/chitosan hydrogel on osteoimmunomodulation.

Severe bone defects that extend beyond a critical size do not heal on their own, increasing the risk of complications and leading to poor outcomes for patients. Healing is a highly coordinated and complex process in which immune cells have an important function making the design and preparation of biomaterials with immunomodulatory functions an important new therapeutic strategy. 1,25-dihydroxyvitamin D3 (VD3) is crucial for bone metabolism and immune regulation. For post-defect bone regeneration, we developed a drug delivery system (DDS) based on chitosan (CS) and nanoparticles (NPs) to sustain the release effect of VD3 and desirable biological characteristics. The hydrogel system was physically characterized and confirmed to have good mechanical strength, degradation rate, and drug release rate. In vitro experiments showed that the cells had good biological activity when the hydrogel was co-cultured with MC3T3-E1 and RAW264.7. The high expression of ARG-1 and low expression of iNOS in macrophages confirmed that VD3-NPs/CS-GP hydrogel transformed lipopolysaccharide-induced M1 macrophages into M2 macrophages. Alkaline phosphatase and alizarin red staining showed that VD3-NPs/CS-GP hydrogel promoted osteogenic differentiation under inflammatory conditions. In conclusion, VD3-NPs/CS-GP hydrogel with synergistic anti-inflammatory and pro-osteogenic differentiation effects may serve as a potential immunomodulatory biomaterial for bone repair and regeneration in cases of bone defects.

Vaccination coverage survey of children aged 1-3 years in Beijing, China, 2005-2021.

BACKGROUND: The routine immunization program for children is a primary strategy and a core part of vaccination. Achieving and maintaining high level of vaccination coverage are important to reduce morbidity and mortality caused by vaccine-preventable diseases. In Beijing, annual coverage surveys have been conducted since 2005. It is necessary and possible to assess the level and trend of routine vaccination coverage of children in Beijing as well as the disruption of coronavirus disease 2019 (COVID-19) pandemic and provide the reference for the further improve the vaccination coverage. METHODS: The data of 61,521 children aged 1-3 years in the vaccination coverage surveys during 2005-2021 were analyzed by Beijing Center for Disease Control and Prevention. Descriptive epidemiological method was used to analyze the data and the difference of vaccination coverage within the time period. RESULTS: More than 99 % of participants had immunization cards and electronic immunization records. The concordance rate of both records were also over 99 %. During 2011-2019, the rates of on-time and in-time vaccination of each routine vaccine reached 96 % or more and increased significantly (all P values <0.05), compared with that of 2005-2010. All rates of the investigated vaccine, except for Bacillus Calmette-Guérin vaccine (BCG) and the first dose of hepatitis B vaccine (HepB), decreased in 2020-2021 significantly (all P values <0.05). For the causes of failing to vaccinate on time, delayed vaccination accounted for 47.82 %. The top two vaccines to be missed were the first dose of hepatitis A vaccine and the 4th dose of diphtheria-tetanus-acellular pertussis vaccine, accounting for 21.41 % and 20.79 %, respectively. The main reason for zero-dose/drop-out vaccination was "Guardians regarded the immunization service time as inappropriate", accounting for 72.27 %. CONCLUSION: The coverage level and service quality of routine immunization in Beijing were relatively high. However, as influenced by COVID-19 epidemics, both on-time and in-time vaccination rates decreased significantly, except for BCG and HepB. Under the background of COVID-19 pandemic, the keys to maintain high level of vaccination coverage include flexible immunization service time to ensure the guardians bringing their children for vaccination timely, and more attention from providers to the doses after children's first birthday.

MiR-223-3p affects the proliferation and apoptosis of HCAECs in Kawasaki disease by regulating the expression of FOXP3.

OBJECTIVE: Kawasaki disease (KD) can lead to permanent damage to coronary structures, the pathogenesis of which remains unknown. This experiment was designed to investigate whether miR-223-3p secreted in the serum of KD patients affects the proliferation and apoptosis of HCAECs in KD by regulating FOXP3. METHODS: Blood samples were collected in acute febrile phase of KD, after IVIG treatment, and from healthy controls. Transfected into HCAECs cells by synthetic FOXP3 siRNA/NC. A co-culture system was established between HCAECs cells transfected with FOXP3 siRNA/NC and THP1 cells added with three sera. RESULTS: Compared with the control group, the expressions of miR-223-3p, RORγt, and Th17 in serum of KD patients were significantly upregulated, and the expressions of TGF-ß1, FOXP3 and Treg were significantly downregulated. At the same time, the levels of IL-6, IL-17, and IL-23 were significantly increased, and the levels of IL-10 and FOXP3 were significantly decreased. After IVIG treatment, the patient's above results were reversed. The serum of KD patients increased the expression of miR-223-3p and inhibited the expression of FOXP3 in HCAECs cells. IVIG serum is the opposite. Overexpression of miR-223-3p also promoted the apoptosis of HCAECs. In addition, serum from KD patients promoted apoptosis, whereas serum after IVIG treatment inhibited apoptosis. KD patient serum downregulated the expression of FOXP3, Bcl2, TGF-ß1 and IL-10 in cells, and upregulated the expression of caspase3, Bax, IL-17, IL-6, and IL-23. The opposite results were obtained with IVIG-treated sera. CONCLUSION: miR-223-3p secreted in serum of KD patients can regulate the expression of FOXP3 and affect the proliferation, apoptosis, and inflammation of cells.

[The epidemiological impact of varicella vaccination in kindergartens, primary and secondary schools in Beijing].

OBJECTIVE: To study the epidemiological impact of varicella vaccine vaccination on kindergartens and school children in Beijing. METHODS: According to "China Information System for Diseases Control and Prevention", the reported clinical diagnosis varicella cases were tracked in kindergartens, primary and secondary schools whose onset date were from 2008 to 2010. Epidemiological survey was conducted and epidemiological features were analyzed. RESULTS: A total of 21 474 varicella cases were investigated: 55.3% (11 883 cases) had been vaccinated by varicella vaccine. Of cases with definite immunization history, interval between vaccination date and onset date were from 30 days to 1 year accounted for 3.4% (286/8510), 1 to 3 years accounted for 18.2% (1551/8510), 3 to 5 years accounted for 28.6% (2431/8510), 5 to 10 years accounted for 34.3% (2916/8510) (left-closed right-open interval); The peak age of onset was 4 years old in cases without immunization history, which was 6 years old in cases with immunization history; The proportion of cases with immunization history (≥ 30 days) had increased from 42.4% (2862/6754) in 2008 to 56.3% (4327/7679) in 2010. The cases with no fever had a higher proportion (54.9%, 6413/11 679) of immunization history (≥ 30 days) than cases with fever (47.7%, 4533/9500) (P < 0.01); The cases with rashes less than 50 had a higher proportion (57.4%, 8045/14 020) of immunization history (≥ 30 days) than cases with rashes more than 50 (40.2%, 2902/7216) (P < 0.01). CONCLUSION: Varicella vaccine delays the peak age of onset, alleviates the symptoms. The current immunization strategy can not block varicella spread in kindergartens, primary and secondary schools.