Chromodomain-helicase-DNA-binding protein 1 (CHD1) deletion is among the most common mutations in prostate cancer (PCa), but its role remains unclear. In this study, RNA sequencing was conducted in PCa cells after clustered regularly interspaced palindromic repeat (CRISPR)/CRISPR-associated protein 9 (Cas9)-based CHD1 knockout. Gene set enrichment analysis (GSEA) indicated upregulation of hypoxia-related pathways. A subsequent study confirmed that CHD1 deletion significantly upregulated hypoxia-inducible factor 1α (HIF1α) expression. Mechanistic investigation revealed that CHD1 deletion upregulated HIF1α by transcriptionally downregulating prolyl hydroxylase domain protein 2 (PHD2), a prolyl hydroxylase catalyzing the hydroxylation of HIF1α and thus promoting its degradation by the E3 ligase von Hippel-Lindau tumor suppressor (VHL). Functional analysis showed that CHD1 deletion promoted angiogenesis and glycolysis, possibly through HIF1α target genes. Taken together, these findings indicate that CHD1 deletion enhances HIF1α expression through PHD2 downregulation and therefore promotes angiogenesis and metabolic reprogramming in PCa.
Male ; Humans ; Von Hippel-Lindau Tumor Suppressor Protein/metabolism* ; DNA-Binding Proteins/metabolism* ; Prolyl Hydroxylases/metabolism* ; Hypoxia ; Prostatic Neoplasms/pathology* ; Glycolysis ; Hypoxia-Inducible Factor 1, alpha Subunit/metabolism* ; Cell Line, Tumor ; DNA Helicases/metabolism*

Platelets are reprogrammed by cancer via a process called education, which favors cancer development. The transcriptional profile of tumor-educated platelets (TEPs) is skewed and therefore practicable for cancer detection. This intercontinental, hospital-based, diagnostic study included 761 treatment-naïve inpatients with histologically confirmed adnexal masses and 167 healthy controls from nine medical centers (China, n = 3; Netherlands, n = 5; Poland, n = 1) between September 2016 and May 2019. The main outcomes were the performance of TEPs and their combination with CA125 in two Chinese (VC1 and VC2) and the European (VC3) validation cohorts collectively and independently. Exploratory outcome was the value of TEPs in public pan-cancer platelet transcriptome datasets. The AUCs for TEPs in the combined validation cohort, VC1, VC2, and VC3 were 0.918 (95% CI 0.889-0.948), 0.923 (0.855-0.990), 0.918 (0.872-0.963), and 0.887 (0.813-0.960), respectively. Combination of TEPs and CA125 demonstrated an AUC of 0.922 (0.889-0.955) in the combined validation cohort; 0.955 (0.912-0.997) in VC1; 0.939 (0.901-0.977) in VC2; 0.917 (0.824-1.000) in VC3. For subgroup analysis, TEPs exhibited an AUC of 0.858, 0.859, and 0.920 to detect early-stage, borderline, non-epithelial diseases and 0.899 to discriminate ovarian cancer from endometriosis. TEPs had robustness, compatibility, and universality for preoperative diagnosis of ovarian cancer since it withstood validations in populations of different ethnicities, heterogeneous histological subtypes, and early-stage ovarian cancer. However, these observations warrant prospective validations in a larger population before clinical utilities.
Humans ; Female ; Blood Platelets/pathology* ; Biomarkers, Tumor/genetics* ; Ovarian Neoplasms/pathology* ; China

Objective To assess the effects of vascular endothelial growth factor-C (VEGF-C)/vascular endothelial growth factor receptor-3 (VEGFR-3) signaling on nitric oxide (NO) production and inducible nitric oxide synthase (iNOS) expression in human osteosarcoma MG63 cells and the subsequent impact on the proliferation of human umbilical vein endothelial cells (HUVECs). MethodsMG63 cells were treated with VEGF-C alone (VEGF-C group), VEGF-C + iNOS inhibitor aminoguanidine (AG; AG group), and VEGF-C + VEGFR-3 inhibitor MAZ51 (MAZ51 group); untreated MG63 cells were used as controls. NO production was evaluated by a colorimetric method involving nitrate reductase. Meanwhile, mRNA and protein levels of iNOS were examined by reverse transcription polymerase chain reaction (RT-PCR) and Western blot. To explore the effect of VEGF-C/VEGFR-3/iNOS signaling of MG63 cells on proliferation of HUVECs, we set up six groups: HUVECs, HUVECs+MG63, HUVECs+VEGF-C, HUVECs+MG63+VEGF-C, HUVECs+MG63+VEGF-C+AG, and HUVECs+MG63+VEGF-C+MAZ51 groups. The proliferation of HUVEC cells was assessed by Cell Counting Kit-8 (CCK-8), 5-ethynyl-2'-deoxyuridine (EdU) incorporation assay, and proliferating cell nuclear antigen (PCNA) expression quantitation. ResultsVEGF-C treatment enhanced iNOS expression at both gene and protein levels (mRNA: LSD-

In the past 37 years, human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS) has undergone various major transmission routes in China, with the world most complex co-circulating HIV-1 subtypes, even the prevalence is still low. In response to the first epidemic outbreak of HIV in injecting drug users and the second one by illegal commercial blood collection, China issued the Anti-Drug Law and launched the Blood Donation Act and nationwide nucleic acid testing, which has avoided 98,232 to 211,200 estimated infections and almost ended the blood product-related infection. China has been providing free antiretroviral therapy (ART) since 2003, which covered >80% of the identified patients and achieved a viral suppression rate of 91%. To bend the curve of increasing the disease burden of HIV and finally end the epidemic, China should consider constraining HIV spread through sexual transmission, narrowing the gaps in identifying HIV cases, and the long-term effectiveness and safety of ART in the future.
Acquired Immunodeficiency Syndrome/prevention & control* ; China/epidemiology* ; Disease Outbreaks ; HIV Infections/prevention & control* ; Humans ; Prevalence

Objective To study the distribution of sleep duration in mid－pregnancy women and examine its association with prehypertension ( PHT) ． Methods In the baseline survey of a prospective cohort study，943 women in mid－pregnancy were recruited in Guangzhou，China in 2017－2018． A standardized questionnaire was used to assess demographic characteristics，sleep duration and other lifestyles． We obtained maternal blood pressure values，weights，heights，and medical histories from medical records． Multivariate logistic regression was conducted to examine the association between sleep duration and PHT． Ｒesults The average daily sleep duration of women in mid －pregnancy was ( 10. 41 ± 1. 67 ) hours，and it was negatively related to age and educational level． Overall，98. 33% of pregnant women had a daily sleep duration ≥ 7 h and the distribution was related to passive smoking． The average night time sleep duration was ( 9. 48±1. 21 ) hours，and it was negatively related to age and educational level． The daytime sleep duration was ( 0. 93 ± 0. 69 ) hours，and it was positively associated with physical activity． The average bedtime was( 22 ∶ 42 ± 1．24) ，and it was positively associated with passive smoking． The prevalence of PHT was 9. 61%． We did not observe any significant association between sleep duration and PHT． Conclusions The mid－pregnancy women in Guangzhou had relatively long sleep duration， and it differed by maternal age，educational level，physical activity，and passive smoking． There was no significant association between sleep duration and PHT．

OBJECTIVE: To investigate the clinical application and efficacy of ¹²⁵Ⅰ radioactive seeds implantation in the treatment of recurrent salivary gland carcinoma after external radiotherapy. METHODS: From July 2004 to July 2016, 43 cases of recurrent salivary gland carcinoma of the neck after external radiotherapy or surgery combined with external radiotherapy were treated. According to the conventional segmentation radiotherapy for head and neck cancer (once a day, 1.8-2.0 Gy each time, 5 days per week), the cumulative radiation dose of the patients in this group was calculated. In the study, 26 patients received 50-60 Gy, 7 patients received less than 50 Gy, 4 patients received 60-70 Gy, and 6 patients received more than 80 Gy (range: 80-120 Gy). The interval between the last external irradiation and local recurrence was 4-204 months, and the median interval was 48 months. Among them, 25 cases were treated with ¹²⁵Ⅰ radioactive seeds implantation only and 18 cases were treated with ¹²⁵Ⅰ radioactive seeds implantation after operation. The prescription dose was 100-140 Gy. The control rate, survival rate and disease-free survival rate were recorded to evaluate the side effects. RESULTS: The median follow-up time was 27 months (ranging from 2.5 to 149.0 months). Among them, the median follow-up time of adenoid cystic carcinoma patients was 31 months (range: 2.5-112.0 months), and the median follow-up time of mucoepidermoid carcinoma patients was 18 months (range: 5-149 months). The local control rates for 1, 3 and 5 years were 66.5%, 48.8% and 42.7%, respectively. The 1-, 3- and 5- year survival rates were 88.0%, 56.7% and 45.8%, respectively. The disease-free survival rates of 1, 3 and 5 years were 58.3%, 45.4% and 38.1%, respectively. There was no statistically significant difference in local control rate, survival rate, and disease-free survival between the radioactive seeds implantation group and the radioactive seeds implantation group after surgical resection. There were 2 cases of acute radiation reaction Ⅰ/Ⅱ and 3 cases of reaction Ⅲ or above. In the late stage of radiotherapy, there were 8 cases with Ⅰ/Ⅱ grade reaction and 3 cases with Ⅲ grade or above reaction. The incidence of radiation reactions of Grade Ⅲ and above was 7%. CONCLUSION ¹²⁵Ⅰ radioactive seeds implantation provides an alternative method for the treatment of recurrent salivary gland carcinoma after external radiotherapy. The local control rate and survival rate are improved on the premise of low incidence of side effects.
Brachytherapy/adverse effects* ; Humans ; Iodine Radioisotopes/therapeutic use* ; Neoplasm Recurrence, Local/radiotherapy* ; Salivary Gland Neoplasms/radiotherapy* ; Salivary Glands

Objective Angiotensin Ⅱ (Ang Ⅱ)-induced vascular damage is a major risk of hypertension. However, the underlying molecular mechanism of AngⅡ-induced vascular damage is still unclear. In this study, we explored the novel mechanism associated with Ang II-induced hypertension. Methods We treated 8- to 12-week-old C57BL/6J male mice with saline and Ang Ⅱ(0.72 mg/kg·d) for 28 days, respectively. Then the RNA of the media from the collected mice aortas was extracted for transcriptome sequencing. Principal component analysis was applied to show a clear separation of different samples and the distribution of differentially expressed genes was manifested by Volcano plot. Functional annotations including Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway were performed to reveal the molecular mechanism of Ang Ⅱ-induced hypertension. Finally, the differentially expressed genes were validated by using quantitative real-time PCR. Results The result revealed that a total of 773 genes, including 599 up-regulated genes and 174 down-regulated genes, were differentially expressed in the aorta of Ang Ⅱ-induced hypertension mice model. Functional analysis of differentially expressed genes manifested that various cellular processes may be involved in the Ang Ⅱ-induced hypertension, including some pathways associated with hypertension such as extracellular matrix, inflammation and immune response. Interestingly, we also found that the differentially expressed genes were enriched in vascular aging pathway, and further validated that the expression levels of insulin-like growth factor 1 and adiponectin were significantly increased (P<0.05). Conclusion We identify that vascular aging is involved in Ang Ⅱ-induced hypertension, and insulin-like growth factor 1 and adiponectin may be important candidate genes leading to vascular aging.
Aging ; Angiotensin II ; Animals ; Aorta/physiopathology* ; Blood Pressure/genetics* ; Gene Expression Profiling/methods* ; Gene Ontology ; Hypertension/genetics* ; Male ; Mice, Inbred C57BL ; Reverse Transcriptase Polymerase Chain Reaction

Objective To investigate whether elevated baseline levels of high sensitivity C-Reactive Protein (hsCRP) and neutrophil (NE) are associated with an increased risk of breast cancer in Kailuan female cohort. Methods Females from Kailuan cohort (2006-2007) were included in this study. Information on check-up, hsCRP and NE were collected at baseline for all subjects. Multivariable Cox proportional hazards regression models were used to calculate hazard ratios (HR) and 95% confidence intervals (95%CI) of association between baseline hsCRP and NE values and breast cancer risk. Results By December 31, 2015, a total of 18 866 participants were enrolled in this study. During the follow-up, 183 new cases of breast cancer were observed. All participants were divided into three groups according to the level of hsCRP (<1 mg/L, 1-3 mg/L and >3 mg/L). The cumulative incidence of breast cancer were 829/105, 1 211/105 and 1 495/105 in these 3 groups, respectively ( 2=12.08， P=0.002). Compared with participants with lower hsCRP levels (<1 mg/L), individuals with the highest hsCRP (>3 mg/L) levels had significantly increased risk of breast cancer (HR=1.71,95%CI: 1.18-2.47, P=0.005), howerver, we didn’t find the statistically significant association between NE level (<3.70×109/Lvs. ≥3.70×109/L) and the risk of brease cancer (P>0.05). Conclusions Elevated levels of hsCRP at baseline might increase the risk of breast cancer in females.

OBJECTIVE: To retrospectively analyze the results of treatment outcome by surgery combined with ₁₂₅I brachytherapy and correlative factors of adenoid cystic carcinoma (ACC). METHODS: In the study, 75 patients with primary ACC of oral and maxillofacial region were treated by surgery combined with ₁₂₅I seeds brachytherapy. Radical resection or subtotal resection was applied for the tumor. The brachytherapy treatment planning system was used to create implant plans with the prescribed dose of 60 Gy to 120 Gy. The ₁₂₅I seeds were implanted intraoperatively or postoperatively. The regular follow-up was required. The Kaplan-Meier method was used to assess the tumor control rate and the patients' survival rates. Meanwhile, the Cox regression analysis was used to find out the prognostic factors. RESULTS: Local control rates at the end of 3 and 5 years were as follows: T1-T2, 92.2% and 82.0%; T3-T4, 82.6% and 82.6%; and overall, 90.0% and 78.8%. The disease-free survival rates were 74.9% and 54.3%, respectively. The overall survival rates for all the patients were 86.0% and 79.6%, respectively at the end of 3 and 5 years and were 91.3% and 91.3% for T1-T2 patients vs. 73.9% and 59.7% for T3-T4 patients. Distant metastasis-free survival rates at the end of 3 and 5 years were 84.4% and 76.7%, respectively. The distant metastasis-free survival rates at the end of 3 and 5 years were 83.4% and 79.6% with T1-T2 lesion compared with 86.0% and 67.8% with T3-T4 lesion. According to the COX univariate analysis and multivariate analysis, the risk of local recurrence would be raised by the age. Tumor stage and tumor site were the prognostic factors of the overall survival rates. CONCLUSION ₁₂₅I brachytherapy conducted as an adjuvant therapy postoperatively of ACC of oral and maxillofacial region can acquire satisfactory localregional control, distant metastasis-free survival, disease-free survival and overall survival. Tumors are prone to recur on the older patients. Patients having advanced tumor stage or tumor located in the nasal cavity or sinuses will suffer lower survival rates.
Brachytherapy ; Carcinoma, Adenoid Cystic ; Combined Modality Therapy ; Humans ; Iodine Radioisotopes ; Neoplasm Recurrence, Local ; Neoplasm Staging ; Retrospective Studies ; Survival Rate

BACKGROUND: Preliminary studies have found that the oral intake of contraceptives reduces the rate of orthodontic tooth movement. This study mainy explores the effects of oral contraceptives on periodontium remodeling during orthodontic tooth movement in a female rat model. OBJECTIVE: To investigate the effects of combined oral contraceptives (COCs) on the expression levels of progesterone receptor and osteoprotegerin, as well as the number of osteoclasts in the periodontium during orthodontic tooth movement. METHODS: Eighty 3-month-old female Sprague-Dawley rats were randomly divided into two groups (n=40 per group), and COCs (marvelon, experimental group) or normal saline (control group) was then given by gavage. At 7 days after administration, the right maxillary first molars were moved mesially under a force of 50 g delivered by nickel-titanium coil springs, and 10 rats were killed on day 7, 14, 21 and 28 after loading, respectively. The expression levels of progesterone receptor and osteoprotegerin in the periodontium were detected by immunohistochemistry, and the number of activated osteoclasts was measured by tartrate-resistant acid phosphatase staining. RESULTS AND CONCLUSION: At 28 days after force loading, the expression level of progesterone receptor in the periodontium in the experimental group (0.307±0.03) was significantly higher than that in the control group (0.194±0.11), (P < 0.01). The number of osteoclasts in the maxillary first molars in the experimental group was significantly less than that in the control group at 7, 14, 21 and 28 days after force loading (P < 0.05). The average absorbance value of osteoprotegerin in the experimental group was significantly higher than that in the control group (P < 0.01). These results show that COCs are able to promote osteogenesis and slow bone absorption during periodontal reconstruction, indicating that the course of orthodontic treatment for female patients with a history of COCs intake may be extended.