Downregulation of METTL14 improves postmenopausal osteoporosis via IGF2BP1 dependent posttranscriptional silencing of SMAD1.

Osteoporosis (OP) tends to occur in postmenopausal women, making them prone to fractures. N6-methyladenosine (m6A) methylation plays a crucial role in OP. Herein, we aimed to explore the effects of METTL14 on osteogenesis and the underlying mechanism. Osteogenic differentiation was assessed through osteoblast markers expression, cell proliferation, ALP activity, and mineralization, which were detected by qRT-PCR, CCK-8, EdU assay, ALP staining assay, and ARS staining assay, respectively. Osteoporosis was evaluated in OVX mice using qRT-PCR, microcomputed tomography, and H&E staining assay. The levels of METTL14 and SMAD1 were measured using qRT-PCR and western blot, and their interaction was assessed using RIP and luciferase reporter assay. M6A methylation was analyzed using the Me-RIP assay. The results indicated that m6A, METTL14, and SMAD1 levels were downregulated in patients with OP and OVX mice, and upregulated in osteogenic BMSCs. Knockdown of METTL14 suppressed osteogenesis of BMSCs and reduced bone mass of OVX mice. Moreover, silencing of METTL14 positively related to SMAD1 and inhibited m6A modification of SMAD1 by suppressing its stability. IGF2BP1 was identified as the methylation reader, and which knockdown reversed the upregulation induced by SMAD1. Overexpression of SMAD1 reversed the suppression of osteogenic differentiation induced by METTL14 knockdown. In conclusion, interference with METTL14 inhibited osteogenic differentiation of BSMCs by m6A modification of SMAD1 in an IGFBP1 manner, suggesting that METTL14 might be a novel approach for improving osteoporosis.

Surgical Selection of Unstable Intertrochanteric Fractures: PFNA Combined with or without Cerclage Cable.

Due to the instability of unstable intertrochanteric fractures, the selection of a suitable internal fixation has always been a challenge for orthopedic surgeons. This study is aimed at comparing the clinical efficacy of PFNA combined with cerclage cable and without cerclage cable and finally recommend a stable internal fixation method to provide the basis for clinical therapy. From January 2014 to January 2018, we retrospectively analyzed all cases of unstable intertrochanteric fractures who received treatment in the Orthopedics Department of our hospital and finally screened 120 cases, 51 of whom were treated with cerclage cable, 69 without cerclage cable. The follow-up period was one year. HHS, BI, and RUSH scores were given within the specified time. We divided the patients into the PFNA+cable (PFNA combined with cerclage cable) group and the PFNA group. The time of fracture healing and weight-bearing in the PFNA+cable group was shorter than that in the PFNA group. With regard to HHS, BI, and RUSH, the PFNA+cable group was higher than the PFNA group at 1 month, 3 months, 6 months, and 12 months after operation. For HHS rating, the PFNA+cable group has a higher excellent rate than the PFNA group, which was 96.1% and 84.1%, respectively. All the results mentioned above were statistically significant. Compared with the group without cerclage cable, the application of cerclage cable can reduce the incidence of complications. From the comparison between the two groups, it can be seen that the surgical method of PFNA combined with cerclage cable can not only help to improve the stability of fracture reduction, shorten the time of fracture healing and postoperative weight-bearing, and significantly improve patients' self-care ability but also reduce the incidence of postoperative complications. Therefore, we think PFNA combined with cerclage cable is a good choice.

[Evaluation of health education in primary school students from schistosomiasis-endemic areas around Poyang Lake by KAP hierarchical evaluation method].

OBJECTIVE: To quantitatively evaluate the intervention effect of schistosomiasis health education on the knowledge, attitude and behavior (KAP) among the primary school students. METHODS: A questionnaire was designed to collect baseline data. Questionnairing was conducted among students of grades 3 and 4 from the Central Primary School, Liyuzhou Primary School, and Meichi Primary School in Wuxing Farm of Nanchang City in June 2010. Eighty-four students from Central Primary School were selected as experiment group, and 62 students in the other two schools served as control group. Health education intervention (knowledge lectures, information dissemination, intensive education and so on) was conducted for the students in experiment group from September 2010 to October 2011. Final KAP questionnaire survey was carried out after intervention. A KAP hierarchical evaluation method was used to calculate the KAP scores in the two groups before and after intervention. RESULTS: After health education, the total KAP score in experiment group increased from 8.40 before education to 9.36 (t = 2.994 4, P < 0.01), higher than that of the control (8.53, t = 5.335 5, P < 0.01). The scores of knowledge, attitude and behavior of schistosomiasis control increased from 6.16, 9.10, and 8.67 before education to 8.12, 9.86, and 9.45 after education in experiment group (t = 5.716 8, P < 0.01; t = 3.2764, P < 0.01; t = 3.276 4, P < 0.01), respectively. Compared to the experiment group, after health education the scores of knowledge (6.34, t = 3.517 5, P < 0.01) and attitude of schistosomiasis control (9.43, t = 2.311 9, P < 0.05) were lower in control group; but no significant difference was found on the score of behavior between the two groups. After health education, the scores of 26 indices in experiment group were higher than that of the control and before education. CONCLUSION: The health education intervention is effective for schistosomiasis control in the experiment school.

[Evolution of spatial-temporal pattern of schistosome infection rates in Nanchang County, Jiangxi Province].

OBJECTIVE: To explore the evolution of spatial-temporal pattern of schistosome infection rates in Nanchang County, Jiangxi Province. METHODS: Based on the data of schistosome infection rates at unit of administrative villages during 2006 to 2009, the evolution of spatial-temporal pattern of schistosome infection rates was analyzed by means of global Moran's I, Getis-Ord General G, local Getis-Ord Gi and variogram. RESULTS: Since 2006, the global Moran's I index increased, and all the Getis-Ord General G index G (d) values were 0.02, all the Z(d) values were of statistic significance (all P values were < 0.01). The hotspots mainly distributed in the northeast and southeast of the county, while the cold spots and secondary cold spots mainly distributed in the southwest. The optimal fitted variograms of the 3 years were all Gaussian model, the Nugget coefficient decreased from 0.026 to 0.006. The spatial autocorrelation of schistosome infection rates got stronger, the ranges shrank by 9.04%. CONCLUSION: The schistosome infection rates in Nanchang County have a tendency of clustering towards the areas along the lake, and the impact of the structural factors is increasing, but the effect range of spatial correlation is decreasing.

Induction of apoptosis by Icariside II through extrinsic and intrinsic signaling pathways in human breast cancer MCF7 cells.

The anti-tumor effect of Icariside II (IcaS), a natural prenylated flavonol glycoside, was studied on human breast cancer MCF7 cells to unveil the underlying mechanisms involved. IcaS in MCF7 cells produced a loss of mitochondrial membrane potential and release of cytochrome c and apoptosis-inducing factor (AIF), and activation of caspase-9 revealed the involvement of the intrinsic apoptosis pathway. In contrast, IcaS enhanced the expression level of Fas and the Fas-associated death domain (FADD), and activated caspase-8, suggesting the involvement of the extrinsic apoptosis pathway. IcaS also increased the expression of Bax and BimL without affecting the expression status of Bcl-2 and Bid, suggesting that the apoptosis induced by IcaS was related to Bcl-2 family protein regulation. IcaS thus induced apoptosis in MCF7 cells involving both the intrinsic and extrinsic signaling pathways. Its potential as a candidate for an anti-cancer agent warrants further investigation.

[Comparison of knowledge, attitude and practice of students left at home or not on schistosomiasis prevention and control].

The questionnaire survey on knowledge, attitude and practice (KAP)of students left at home or not about schistosomiasis prevention and control showed that there were no statistically significant differences of the scores of KAP between the two groups of students (all P values were above 0.05).

[Systematic surveillance of water body in schistosomiasis susceptible areas in Nanchang County by sentinel mice].

OBJECTIVE: To determine the status of cercariae of Schistosoma japonicum in water bodies of the Nanchang County section of Poyang Lake region. METHODS: By using sentinel mice, the schistosome infectivity of water bodies was detected in 8 surveillance areas (59 experimental points in total) along the Fu River, Wuxing Farm, south branch of the Ganjiang River, and middle branch of the Ganjiang River from June to July 2011. RESULTS: A total of 600 sentinel mice were placed in the experimental areas and 584 were retrieved, among which 577 mice were dissected and 1 mouse was infected with S. japonicum (4 worms collected), with the infection rate of 0.17%. CONCLUSION: By using the sentinel mouse method to survey the water body schistosome infectivity, the status of Oncomelania snails should be mainly considered, and the infection rate of sentinel mice is affected by water situation, water level, flow velocity, etc.

[Spatial clustering detecting for schistosomiasis in Nanchang County].

OBJECTIVE: To explore the cluster of schistosomiasis in Nanchang County, Jiangxi Province. METHODS: Based on the data of schistosome infection cases and population, the spatial analysis technology, global autocorrelation and hotspot detection methods in ArcGIS 9.2 software were used to render the spatial autocorrelation coefficient graph. The autocorrelation index change trend of schistosome infection rates in different spatial scales was described. In addition, the hotspot area of schistosome infection rates in study area was detected by using the representative distance for pace parameters combined with actual situation. RESULTS: The spatial distribution of schistosome infection in study area was characteristic of clusters in 2009. The spatial autocorrelation coefficient graph indicated that the peak of wave happened in the distances of 1 900 m, 2 600 m, 3 800 m and 5 000 m, respectively. Comparing with the geographical conditions, the hotspots in 5 000 m spatial scale were more realistic than other distances. In this scale, 2 hotspots and 2 second hotspots were explored. CONCLUSION: The spatial clustering analysis combined with the spatial autocorrelation analysis can explore the schistosomiasis gathering area more precisely.

Triterpenoid saponins from Dipsacus asper and their activities in vitro.

Two new triterpenoid saponins 1 and 2, along with six known saponins 3-8, were isolated from the roots of Dipsacus asper. The structures of new compounds were established as 3-O-ß-d-glucopyranosyl-(1 â†’ 4)-[α-l-rhamnopyranosyl-(1 â†’ 3)]-ß-d-glucopyranosyl-(1 â†’ 3)-α-l-rhamnopyranosyl-(1 â†’ 2)-α-l-arabinopyranosyl-hederagenin-28-O-ß-d-glucopyranoside (dipsacus saponin J, 1) and 3-O-α-l-arabinopyranosyl-hederagenin-28-O-ß-d-glucopyranosyl-(1 â†’ 6)-ß-d-glucopyranosyl-(1 â†’ 6)-ß-d-glucopyranoside (dipsacus saponin K, 2). The structures were determined by extensive analysis of their spectroscopic data. Compounds 6 and 7 could significantly stimulate UMR106 cell proliferation and increase alkaline phosphatase activities in UMR106 cell at the concentration of 4 µM.

Protective effect of the methanolic extract from Duchesnea indica against oxidative stress in vitro and in vivo.

Duchesnea indica (Rosaceae family) is herb used extensively in traditional Chinese medicine. In this study we investigated its protective activity against hydrogen peroxide (H(2)O(2))-induced cytotoxicity in human skin fibroblast (CCD-986Sk) cells and 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced H(2)O(2) in the skin of hairless mice. Pretreatment of CCD-986Sk cells with methanolic extract of D. indica (DIM) improved the cell viability, enhanced activity of catalase, and decreased the leakage of lactate dehydrogenase (LDH) and the levels of malondialdehyde (MDA) and intracellular reactive oxygen species (ROS) in H(2)O(2) injured cells. Furthermore, DIM inhibited cell apoptosis and Bax expression induced by H(2)O(2). In addition, the level of H(2)O(2) stimulated by TPA was decreased by DIM in the skin of hairless mice. These results suggest that DIM offers protection against oxidative stress in vitro and in vivo, and this ability suggests potential use for protection against oxidation-induced skin damage.