General recommendation for assessment and management on the risk of glucocorticoid-induced osteonecrosis in patients with COVID-19.

BACKGROUND/OBJECTIVE: Coronavirus disease 2019 (COVID-19) is a disaster in human medical history and glucocorticoids remain the most promising therapy. Osteonecrosis is a disease caused by reduced intraosseous blood flow to bones in the joints, which will rapidly induce joint destruction. Approximately one-third patients with severe acute respiratory syndrome (SARS) who received high cumulative doses and long treatment durations of glucocorticoids occurred osteonecrosis. Considering the similarity of SARS and COVID-19 on their pathogen, clinical characteristics, and therapeutic strategies, it is particularly desirable to investigate whether osteonecrosis will become a common sequela among convalescent COVID-19 patients. METHODS: This multi-strategy study was designed by integrating different research methods, such as meta-analysis, systematic review, and cross-sectional investigations to address above study objectives. At first, two meta-analyses were performed on the osteonecrosis incidence among SARS patients and the clinical data of glucocorticoid exposure among COVID-19 patients. Then, a systematic review of low-dosage glucocorticoid associated osteonecrosis and a cross-sectional investigation of glucocorticoid exposure of COVID-19 patients in Wuhan city of China were also conducted. Moreover, the pathogenesis, diagnosis, prevention, and treatment options for osteonecrosis patients with COVID-19 infection were further presented and discussed. RESULTS: Our meta-analysis showed that 32% of SARS patients had developed osteonecrosis after receiving glucocorticoid treatment with high dose, and our system review supported that low level glucocorticoid exposure might also lead to the occurrence of osteonecrosis. Similarly, 40% of COVID-19 patients had undergone glucocorticoid treatment according to our meta-analysis. The cross-sectional investigation in Wuhan city of China found that the average of cumulative glucocorticoid exposure level was 504 â€‹mg calculated by the dosage of methylprednisolone. Notably, a confirmed osteonecrosis case was identified from 1406 patients with COVID-19 during our cross-sectional investigation, implying that preventive management of osteonecrosis should be better started with regular clinical follow-up observation. CONCLUSION: Growing evidence of the glucocorticoid therapy for COVID-19 patients prompts us to establish risk-classification-based early screening and to introduce early prevention protocol of its associated osteonecrosis that will be of clinical significance in favor of improved prognosis of this disease. THE TRANSLATIONAL POTENTIAL OF THIS ARTICLE: To establish risk-classification-based early screening and to introduce early prevention protocol of glucocorticoid-induced osteonecrosis will be of clinical significance in favor of improved prognosis of COVID-19.

Elevated neutrophil-lymphocyte ratio can be a biomarker for predicting the development of cervical intraepithelial neoplasia.

ABSTRACT: Cervical intraepithelial neoplasia (CIN) is the abnormal growth of cells on the surface of the cervix that could potentially lead to cervical cancer. In the present study, we investigated whether measuring the neutrophil-lymphocyte ratio (NLR) can be useful for predicting the risks of developing cervical lesions.This is a retrospective analysis of 212 women who were enrolled in this study. Among them, 106 patients with histologically confirmed CIN1-3 who were treated with loop electrosurgical excision procedure or cold knife cone in the Department of Gynecology, The Affiliated Hospital of Inner Mongolia Medical University between July 30th 2016 and January 30th 2019.Among the 106 patients in the CIN group, cytology showed minor abnormality which included atypical squamous cells of undetermined significance or low-grade squamous intraepithelial lesion in 42, high-grade squamous intraepithelial lesion in 62, and squamous cell carcinoma in 2 patients. We found that the NLR has no significant difference between the control group and the CIN1 group, while there were significant differences between CIN1 and CIN2, and CIN2 and CIN3 group. The median of the NLR was higher in the HPV16-persistent groups than in the HPV-negative group.In conclusion, a high NLR value independently predicts CIN and the stage of CIN. The NLR may help doctors evaluate outcomes of patients received conization and choose alternative therapies for patients with high NLR value.

Contraception, unintended pregnancy, and induced abortion within 24 months of delivery in China: a retrospective cohort study.

OBJECTIVE: To explore the prevalence of contraceptive use, unintended pregnancy, and induced abortions within 24 months postpartum in eastern, central, and western regions of China and in China overall. STUDY DESIGN: We conducted a retrospective cohort study and selected women who delivered a live birth between 12 and 24 months before the survey at 60 hospitals in eastern, central, and western regions of China. We used structured questionnaires for data collection and applied life-table analyses to estimate the prevalence of contraception, unintended pregnancy, and abortions. We used clustered log-rank tests to compare trends and rate differences at each time interval between/among regions. RESULTS: A total of 19,939 postpartum women were contacted, and 18,045 (90.5%) of them agreed to be interviewed. The 6-, 12-, and 24-month rates for modern contraceptive methods were 62.7% (95% confidence interval [CI] 58.9-66.4), 72.4% (95% CI 68.8-75.7), and 73.2% (95% CI 69.6-76.6), respectively. Condoms accounted for 79% of contraceptive initiators. The 6-, 12-, and 24-month rates were 1.4% (95% CI 1.2-1.7), 5.3% (95% CI 4.5--6.1), and 13.1% (95% CI 11.3-14.8) for unintended pregnancy; and 1.1% (95% CI 0.8-1.3), 4.0% (95% CI 3.4-4.6), and 10.4% (95% CI 8.9-11.8) for induced abortion, respectively. By 24 months postpartum, 3-quarters of unintended pregnancies ended in abortion. The 24-month rates of modern contraceptive methods (75.2% vs73.4%, 71.1%), unintended pregnancy (15.3% vs 11.1%, 12.6%), and induced abortion (11.8% vs 9.9%, 9.4%) were higher in the western region relative to the eastern or central regions. CONCLUSION: Postpartum contraception use was relatively high in China but dominated by less-effective methods, and these may contribute to higher risks of unintended pregnancy and induced abortion during the postpartum period. Use of long-acting reversible contraceptives and effective and reliable short-acting methods should thus be fostered in postpartum family planning services in China. IMPLICATIONS: A national postpartum family planning program is needed in China. Service providers should work on counselling postpartum women and their partners with respect to long-acting reversible contraceptive methods, and to effectively and reliably use short-acting methods during the postpartum period.

Upregulation of ITGBL1 predicts poor prognosis and promotes chemoresistance in ovarian cancer.

BACKGROUND: Ovarian cancer remains one of the most lethal malignancies in women and the unfavorable prognosis and frequent recurrence are mainly due to the chemoresistance. However, the main mechanism underlying chemoresistance is still elusive. OBJECTIVE: To determine the role and biological function of ITGBL1 in ovarian cancer chemoresistance. METHODS: Immunohistochemical staining was used to determine the expression of ITGBL1 in ovarian cancer tissues. The association between ITGBL1 expression and clinicopathological features and survival was determined. Functional analysis including cell viability, apoptosis assays were performed after chemo drugs treatment to confirm the role of ITGBL1 in chemoresistance. In vivo tumor growth assay was used to detect the chemosensitivity of tumor cells. Western blot was used to detect the expression of indicated proteins. RESULTS: We noticed that ITGBL1 expression was significantly upregulated in ovarian cancer tissues compared to that in adjacent non-cancer tissues and high expression of ITGBL1 was significantly associated with lymph node invasion and advanced FIGO stage. More importantly, high ITGBL1 was an independent prognostic factor of ovarian cancer. Further experiments demonstrated that ITGBL1 promoted tumor cell resistant to chemo drugs both in vitro and in vivo. Mechanically, we found that ITGBL1 could activate PI3K/Akt signaling and using PI3K/Akt inhibitor could abrogate ITGBL1 induced chemoresistance. CONCLUSIONS: Our findings indicate that upregulation of ITGBL1 has important clinical significance and drives chemoresistance in ovarian cancer. Detection and depletion of ITGBL1 might be the potential approaches for diagnosis and therapy for ovarian cancer patients.

Expression of miR-26b in ovarian carcinoma tissues and its correlation with clinicopathology.

The expression of microRNA (miR)-26b in ovarian carcinoma tissues, its correlation with clinicopathology, and its effect on diagnostic value and prognosis of ovarian cancer was investigated. A total of 74 patients with ovarian cancer (the study group) and 30 patients with benign ovarian tumors (the control group) in the Affiliated Hospital of Inner Mongolia Medical University from July 2011 to June 2013 were retrospectively analyzed. The expression of miR-26b in ovarian carcinoma tissues was detected by fluorescence reverse transcription-quantitative polymerase chain reaction (RT-qPCR), and the correlation between the expression of miR-26b and the pathological features of ovarian carcinoma tissues and prognosis of patients was analyzed. The expression level of miR-26b in the study group (0.28±0.07) was significantly lower than that in the control group (0.54±0.11; P<0.050). There was no significant correlation between miR-26b expression and age, tumor type, exercise habit, smoking habit of patients with ovarian cancer (P>0.050), but there was close correlation between the miR-26b expression and lymph node metastasis, differentiation degree and pathological stage of patients with ovarian cancer (P<0.001). ROC curve showed that the area under curve (AUC) was 0.839, and when the maximum cut-off value was 0.815, the sensitivity and specificity of miR-26b in diagnosing the ovary was 84.932% and 77.936%, respectively. The 5-year overall survival rate in the low-expression group (61.54%) was significantly lower than that in the high-expression group (84.85; P=0.028). miR-26b is under-expressed in the ovary and has a close relationship with pathological stage, differentiation degree, and lymph node metastasis of ovarian cancer, which indicates that miR-26b is involved in the occurrence and development of ovarian cancer and is expected to be an effective indicator for treatment and diagnosis of ovarian cancer and the prognosis of patients.

Potential proteins targeted by let-7f-5p in HeLa cells.

MicroRNAs are a class of small, endogenous, non-coding RNAs mediating posttranscriptional gene silencing. The current authors hypothesized that let-7f-5p is likely involved in cell invasion and proliferation by regulating the expression of target genes. The current study combined let-7f-5p with iTRAQ to assess its effect on gene expression in HeLa cells. Results indicated that 164 proteins were expressed at different levels in HeLa cells overexpressing let-7f-5p and negative controls and that 172 proteins were expressed at different levels in let-7f-5p-silenced HeLa cells and negative controls. Results indicated that let-7f-5p may suppress insulin-like growth factor 2 mRNA binding protein 1 (IGF2BP1) in HeLa cells.

E+ subgroup PPR protein defective kernel 36 is required for multiple mitochondrial transcripts editing and seed development in maize and Arabidopsis.

Mitochondria are semi-autonomous organelles that are the powerhouse of the cells. Plant mitochondrial RNA editing guided by pentatricopeptide repeat (PPR) proteins is essential for energy production. We identify a maize defective kernel mutant dek36, which produces small and collapsed kernels, leading to embryos and/or seedlings lethality. Seed filling in dek36 is drastically impaired, in line with the defects observed in the organization of endosperm transfer tissue. Positional cloning reveals that DEK36, encoding a mitochondria-targeted E+ subgroup PPR protein, is required for mitochondrial RNA editing at atp4-59, nad7-383 and ccmFN -302, thus resulting in decreased activities of mitochondrial complex I, complex III and complex IV in dek36. Loss-of-function of its Arabidopsis ortholog At DEK36 causes arrested embryo and endosperm development, leading to embryo lethality. At_dek36 also has RNA editing defects in atp4, nad7, ccmFN1 and ccmFN2 , but at the nonconserved sites. Importantly, efficiency of all editing sites in ccmFN1 , ccmFN2 and rps12 is severely decreased in At_dek36, probably caused by the impairment of their RNA stabilization. These results suggest that the DEK36 orthologue pair are essential for embryo and endosperm development in both maize and Arabidopsis, but through divergent function in regulating RNA metabolism of their mitochondrial targets.