[Role of programmed cell death in the diagnosis and treatment of prostate cancer：An update].

Prostate cancer（PCa）is the most common malignant tumor in male genitourinary system. In China, the incidence of PCa is increasing significantly, which seriously endangers the physical and mental health of Chinese men. Programmed cell death（PCD）is a kind of active and orderly cell death mode, which exists widely in the process of life activities. With the deepening understanding of PCD, more and more studies have found that different types of PCD are closely related to PCa.This article mainly reviews therole of programmed cell death in the diagnosis and treatment of prostate cancer.

[Cuproptosis-related lncRNAs to predict biochemical recurrence of prostate cancer].

OBJECTIVE: To construct a cuproptosis-related lncRNA model and obtain some new ideas and methods for predicting the biochemical recurrence (BCR) of PCa. METHODS: We identified cuproptosis-related lncRNAs from the gene expression data, mutation load data and clinical data on PCa patients in the Cancer Genome Atlas (TCGA) database and divided the patients into a training group and a verification group. We constructed a prognostic risk scoring model based on the cuproptosis -related lncRNAs, verified the validity of the model by BCR-free survival analysis, logistic regression analysis and independent prognosis analysis, and visualized the results using ROC curve analysis, Kaplan-Meier survival curves and the correlation heat map. We performed differential analysis and survival analysis of the tumor mutation burden (TMB), and assessed the value of the model and TMB in predicting the BCR of PCa. RESULTS: A prognostic risk scoring model was successfully constructed based on the 6 cuproptosis -related lncRNAs identified from the PCa cases in the training group, which were divided into a high- and a low-risk groups according to the median value. The incidence of BCR rose with the increase of the risk score, and the BCR-free time was significantly shorter in the high-risk group (P < 0.05). The model also exhibited a high differentiation value in different age groups (P < 0.05), which was shown to be a reliable and independent prognostic indicator for predicting the BCR of PCa, even more valuable than other clinicopathological indicators. TMB was differentially expressed in the high- and low-risk groups (P < 0.01) and significantly correlated with BCR. The highest rate of BCR-free survival was found in the patients with low risk scores and low TMB (P < 0.01). CONCLUSION: A cuproptosis -related lncRNA model was successfully constructed, which can accurately predict the risk of BCR in PCa patients. The higher the prognostic risk score, the greater the possibility of BCR. TMB is high in patients with a high risk, and the TMB level has certain suggestive significance for BCR.

[Clinical study of artificial intelligence-guided image fusion assisted transperineal prostate biopsy].

OBJECTIVE: To compare the diagnostic efficacy of AI-guided mpMRI-TRUS fusion assisted transperineal systematic biopsy, targeted biopsy and combined biopsy in the diagnosis of PCa, and to evaluate the clinical application value of combined biopsy. METHODS: From April 2022, the general personal information and clinical data of patients with suspicious prostate lesions (PI-RADS≥3) detected by 3.0T mpMRI were collected, then underwent AI-guided mpMRI-TRUS fusion-assisted transperineal prostate biopsy. The data included age, PSA level, PV, PSAD, PI-RADS score, Gleason score of biopsy tissue, etc. The mpMRI image data were imported into the real-time fusion imaging system before biopsy. After image fusion, the suspected PCa lesion was taken as the target, 2 to 3 cores of targeted biopsy were first performed, then 12 cores of systematic biopsy were continued. The results of targeted biopsy + systematic biopsy were defined as the results of combined biopsy. The detection rate of PCa, CsPCa and pathological Gleason score were compared among different biopsy methods, and the diagnostic efficacy in different PI-RADS score groups was further evaluated. RESULTS: A total of 118 PCa cases were detected in 220 patients enrolled in this study. The PCa detection rates of systematic biopsy and targeted biopsy were 40.45% and 43.64%, the result reveals no statistical significance (P=0.562). The PCa detection rate of combined biopsy was 53.64%, higher than single biopsy method and the differences were statistically significant (P<0.05). The detection rates of CsPCa in systematic biopsy and targeted biopsy were 28.18% and 37.27% which reveals significant statistical difference (P=0.042). The CsPCa detection rate of combined biopsy was 41.82%, higher than single biopsy method, the difference was statistically significant compared with systematic biopsy (P=0.003), but was not compared with targeted biopsy (P=0.330). In PI-RADS score 3 group, the PCa detection rate of systematic biopsy and targeted biopsy was 39.29% and 21.43%, which reveals no statistical significance (P=0.146). The PCa detection rate of combined biopsy was 50%, higher than single biopsy method, the difference was statistically significant compared with targeted biopsy (P=0.026), but was not compared with systematic biopsy (P=0.420). In PI-RADS 4 ~5 group, the PCa detection rate of systematic biopsy and targeted biopsy was 40.10%, and 46.88% which reveals no statistical significance (P=0.181). The PCa detection rate of combined biopsy was 54.17%, higher than single biopsy method, the difference was statistically significant compared with systematic biopsy (P=0.006), but was not compared with targeted biopsy (P=0.153). Among PCa patients detected by both systematic and targeted biopsy, 39 had concordant pathologic Gleason scores, 13 had escalating pathologic Gleason scores for systematic biopsy, and 18 had escalating pathologic Gleason scores for targeted biopsy. CONCLUSION: Compared with systematic biopsy, AI-guided mpMRI-TRUS image fusion assisted transperineal targeted prostate biopsy has a higher detection rate of CsPCa and is probably closer to the true pathological Gleason score. Compared with single biopsy, combined biopsy has higher diagnostic efficiency for PCa, which can be used as one of the options of prostate biopsy in clinical practice.

[Influence factors of erectile dysfunction in patients with localized prostate cancer after radical surgery].

OBJECTIVE: To analyze the influential factors of erectile dysfunction (ED) in patients with localized prostate cancer (LPC) after radical surgery. METHODS: The clinical data of 150 male patients diagnosed with LPC and normal erectile function (EF) before surgery admitted to the Department of Urology of the Eastern Theatre General Hospital from January 2021 to January 2023 were retrospectively analyzed. The EF status of the patients 6 months after surgery was assessed using the International Erectile Function Index -5(IIEF-5). Age, Gleason score, PSA level, TNM stage, preoperative International prostatic symptom score (IPSS), preoperative prostate volume, smoking index, alcohol consumption index, educational level, comorbidities, operation mode, and psychosexual state were used as influencing factors to analyze their effects on postoperative ED. RESULTS: Of the 150 patients, 88 had ED and 62 had normal EF. Univariate analysis showed that age, preoperative IPSS, preoperative prostate volume, comorbidities and sexual and psychological status were significantly correlated with postoperative ED. Further multivariate logistic regression analysis showed that age, preoperative prostate volume, comorbidities and sexual and psychological status were independent factors influencing the occurrence of ED after RP in LPC patients. CONCLUSION: The recovery of sexual function of patients with localized prostate cancer after radical surgery is generally poor, and the incidence of ED is high. Its independent influencing factors include age, preoperative prostate volume, comorbidities and sexual psychological state, etc. Correct intervention of different influencing factors is required in clinical work. In order to provide a better diagnosis and treatment scheme for LPC patients undergoing radical treatment, reduce the incidence of postoperative ED and improve the quality of life of patients after surgery.

[Difference between prostate cancer patients' Gleason scores from preoperative biopsy and those from postoperative pathology].

OBJECTIVE: To evaluate the consistency of the Gleason scores of PCa patients based on preoperative biopsy with those from postoperative pathology, identify the possible factors influencing results of scoring, and construct a risk scoring model. METHODS: We collected the demographic and clinical data on the patients with PCa confirmed by preoperative prostate biopsy or postoperative pathology and treated by radical prostatectomy within 6 months after diagnosis. Using paired sample t-test, we identified the difference between the Gleason scores based on preoperative biopsy and those from postoperative pathology, analyzed the demographic and clinical data on the patients for relevant factors affecting the consistency of the Gleason scores, and calculated and visualized the relative risk values of the factors through Poisson regression. From the continuous variables with statistical significance, we screened independent risk factors for the difference in the Gleason scores by Lasso regression analysis, established a risk scoring model, generated risk coefficients, and evaluated the predictive ability of the model using the ROC curve. Based on the results of imaging examination with statistically significant differences, we constructed a column chart by logistic regression and evaluated the predictive validity of the chart using calibration curves, decision curves and ROC curves. RESULTS: The results of paired sample t-test for 210 PCa patients showed statistically significant differences between the Gleason scores from preoperative biopsy and those from postoperative pathology (P < 0.001). There were significant differences in the body weight, BMI and PSA level as well as in all other factors but prostate calcification between the patients with consistent and those with inconsistent Gleason scores (all P < 0.05). An 8-factor prediction model was successfully constructed, which could predict the consistency of Gleason scores, with a better predicting performance than the single indicator within the model. The nomogram exhibited a C-index value of 0.85, with the calibration curve similar to the standard one, the threshold of the decision curve 0.10－0.92, and the area under the ROC curve higher than other predictive indicators. CONCLUSION: Based on the demographic and clinical data on PCa patients, a risk prediction model and a column chart were successfully constructed, which could effectively predict the difference between the Gleason scores from preoperative prostate biopsy and those from postoperative pathology.

[Low-intensity extracorporeal shockwave therapy improves symptoms of erectile dysfunction: A preliminary study].

OBJECTIVE: To verify the effect and safety of low-intensity extracorporeal shockwave therapy (Li-ESWT) in improving the symptoms of ED, and provide some reference for further related large-scale clinical trials. METHODS: Twenty-six patients diagnosed with ED received Li-ESWT with an energy of 0.09 mJ/mm2 for 20 minutes once a week for 6 four-week courses. Before and at 3, 6, 9, and 12 months after treatment, we obtained the IIEF-5 and Erectile Hardness Scale (EHS) scores of the patients using questionnaires, recorded the incidence of treatment-related adverse reactions, compared the erectile function of the patients before and after treatment, and evaluated the effect and safety of Li-ESWT in improving ED-related symptoms. RESULTS: Compared with the baseline, the IIEF-5 scores of the patients were significantly increased (P < 0.01) while the EHS scores slightly increased at 3 months after Li-ESWT treatment (P > 0.05), both IIEF-5 and EHS scores were dramatically increased at 6 months (P < 0.01), and both significantly higher than at 3 months. At 9 months, EHS scores remained remarkably higher than the baseline (P < 0.01) although IIEF-5 scores slightly lower than at 6 months. At 12 months, however, IIEF-5 scores decreased, though still significantly higher than the baseline (P < 0.01), and EHS scores became lower than at 6 and 9 months (P < 0.05) but still markedly higher than before treatment (P < 0.05). Adverse reactions observed during the intervention mainly included pruritus (4.35%), pain (2.90%), paresthesia (2.17%), and petechiae/ecchymosis (2.90%). CONCLUSION: Li-ESWT can increase the IIEF-5 and EHS scores and improve the clinical symptoms of ED patients, with a low incidence of adverse reactions during the treatment.

Genome-wide analysis of cell-Free DNA methylation profiling with MeDIP-seq identified potential biomarkers for colorectal cancer.

BACKGROUND: Colorectal cancer is the most common malignancy and the third leading cause of cancer-related death worldwide. This study aimed to identify potential diagnostic biomarkers for colorectal cancer by genome-wide plasma cell-free DNA (cfDNA) methylation analysis. METHODS: Peripheral blood from colorectal cancer patients and healthy controls was collected for cfDNA extraction. Genome-wide cfDNA methylation profiling, especially differential methylation profiling between colorectal cancer patients and healthy controls, was performed by methylated DNA immunoprecipitation coupled with high-throughput sequencing (MeDIP-seq). Logistic regression models were established, and the accuracy of this diagnostic model for colorectal cancer was verified using tissue-sourced data from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) due to the lack of cfDNA methylation data in public datasets. RESULTS: Compared with the control group, 939 differentially methylated regions (DMRs) located in promoter regions were found in colorectal cancer patients; 16 of these DMRs were hypermethylated, and the remaining 923 were hypomethylated. In addition, these hypermethylated genes, mainly PRDM14, RALYL, ELMOD1, and TMEM132E, were validated and confirmed in colorectal cancer by using publicly available DNA methylation data. CONCLUSIONS: MeDIP-seq can be used as an optimal approach for analyzing cfDNA methylomes, and 12 probes of four differentially methylated genes identified by MeDIP-seq (PRDM14, RALYL, ELMOD1, and TMEM132E) could serve as potential biomarkers for clinical application in patients with colorectal cancer.

[miR-129 in the diagnosis, treatment and prediction of clinical prognosis of prostate cancer].

OBJECTIVE: To explore the value of miR-129 in the diagnosis, treatment and prediction of the clinical prognosis of PCa by observing the correlation between miR-129 and the progression of the malignancy. METHODS: This retrospective analysis included 310 male patients who visited the Department of Urology of the General Hospital of Eastern Theater Command from January 2014 to January 2022, 80 as normal healthy men, 80 with BPH, and the other 150 with PCa treated by radical prostatectomy without chemotherapy, radiotherapy or androgen-deprivation therapy. We determined the miR-129 expression in the serum and prostatic tissue of all the subjects by real-time quantitative PCR (RT-qPCR), performed pathological grading of the primary cancerous and pericancerous (≥ 3 cm from the focus) prostate tissues from the 150 PCa patients, collected the demographic and clinical data on all the subjects, and analyzed the correlation of their demographic data with the clinical parameters. We selected and transfected PC-3 and DU-145 cell lines with miR-129 precursor or miR-129 scramble, assessed the proliferation ability of each cell line and detected the expression levels of related proteins by cell proliferation assay and Western blot. RESULTS: The expression of miR-129 was significantly decreased in the serum of the PCa patients compared with that in the normal healthy men and BPH patients (P < 0.01), so was it in the PCa tissue in comparison with that in the pericancerous prostatic tissue (P < 0.01), and it was negatively correlated with the preoperative serum PSA level (P < 0.001), histological grade (P < 0.001), pathological stage (P < 0.001), Gleason score (P < 0.001), lymph node metastasis (P = 0.02), angiolymphatic invasion (P = 0.021) and biochemical recurrence (BCR) (P=0.001). Kaplan-Meier analysis showed a strong correlation of down-regulated miR-129 expression with a lower BCR-free survival rate, while multivariate survival analysis indicated that the expression of miR-129 was an independent prognostic indicator of BCR-free survival of the PCa patients (P < 0.001). Highly expressed miR-129 significantly inhibited the proliferation of PCa cells by regulating the expressions of cell cycle-regulatory proteins. CONCLUSION: The expression of miR-129 is significantly down-regulated in PCa tissues, which plays an important role in inhibiting the proliferation of PCa cells and tumor progression and improving BCR-free survival. Therefore, miR-129 can be considered as a new independent biomarker for the diagnosis, treatment and prediction of the clinical prognosis of PCa.

[Exosomes in the diagnosis of prostate cancer: Advances in studies].

In recent years, the incidence of PCa in China has been increasing year by year. Early diagnosis of the malignancy and monitoring of its progression are keys to the reduction of mortality. Currently, early diagnosis of PCa is mainly achieved by determining the level of PSA. Due to the insufficient specificity of PSA, definite diagnosis necessitates needle biopsy, which, as an invasive procedure, causes injury to the patients. Therefore biomarkers seem to be a significant option for the improvement of diagnostic accuracy. Exosomes are 30－150 nm extracellular vesicles secreted by various types of cells in normal and pathological conditions and exist stably in circumcision. Studies show that exosomes contain miRNAs and proteins critical to the progression and metastasis of PCa and have a great potential in the diagnosis of the malignancy. This review outlines the advances in the application of exosomes as novel biomarkers in the diagnosis of PCa.

[Prostate-specific membrane antigen-targeted drug delivery system for prostate cancer].

Prostate cancer (PCa) is a most common malignancy in the genitourinary system, which imposes a huge burden on the patients and society. Various traditional medication methods fail to achieve satisfactory effects, and therefore it is imperative to develop innovative and effective routes of administration. Drug delivery systems have the characteristics of both delivery and controlled release and are widely used clinically. Prostate-specific membrane antigen (PSMA) is one of the most characteristic and highly selective biomarkers of PCa with a good PCa-targetability. Many drug delivery systems targeting PSMA have been explored, including drug-ligand conjugates and nano-drug delivery systems (polymer nanoparticles, inorganic nanoparticles, liposomes, and biological nanoparticles, etc.). This article reviews the recent studies on the role of the PSMA-targeting drug delivery system in PCa, in order to provide some reference for the precise and effective treatment of the malignancy.

[Trace elements and sperm quality: An update].

With changes in the modes of life and work, infertility is becoming a serious international problem. The incidence of infertility is 10－15% of the couples of childbearing age in China and is increasing year by year, and 30－50% of the cases are related to male factors. Trace elements refer to the chemical elements that account for less than 1/10,000 of the total weight of the human body, of which less than 100 mg is required per person per day. They are important biochemical components in the semen. Trace elements are essential for normal spermatogenesis, sperm maturation and capacitation, and maintenance of normal sperm function, though sperm quality can be affected by genetic, epigenetic, environmental and lifestyle-related factors. This focuses on the latest progress in the studies of the effects of trace elements on sperm quality.

[Basement membrane-related gene signature to predict biochemical recurrence in patients with prostate cancer after radical prostatectomy].

OBJECTIVE: To construct and verify a key gene signature of the basement membrane of prostate cancer (PCa) to predict the progression and biochemical recurrence of the malignancy after radical prostatectomy. METHODS: Based on the PCa-related transcriptome, gene mutation and clinical data from the Cancer Genome Atlas Project (TCGA) database, we analyzed the differentially expressed genes (DEG) related to the basement membrane in the PCa and adjacent normal prostate tissues, and subjected them to GO function enrichment and KEGG pathway enrichment analyses. We identified prognosis-related genes from the DEGs and analyzed their mutations. According to the follow-up data and biochemical recurrence after prostatectomy, we established a prognostic risk scoring model, verified its accuracy using the Gene Expression Omnibus (GEO) database, and performed survival analysis, principal component analysis (PCA), independent prognostic analysis and ROC curve analysis of the model. We constructed a protein-protein interaction network after verifying the correctness of the model by immunohistochemistry. We also established a nomogram and tested its accuracy using ROC and calibration curves. RESULTS: Totally, 85 DEGs were identified, among which 18 were up-regulated and 67 down-regulated. The prognostic risk scoring model was established with 11 of the genes. The risk of biochemical recurrence PCa was significantly higher in the high-risk than in the low-risk group (HR: 3.51, 95% CI: 2.32－5.32, P < 0.01), which was verified with the GEO database data (P < 0.01). In addition, the patients in the high-risk group were older with higher clinical T-stage, higher Gleason score, higher positive rate, larger numbers of positive lymph nodes, and a larger proportion of residual tumors than those in the low-risk group (P < 0.05). The nomogram constructed with the patients' age, pN, pT and cT stages, Gleason score and prognostic risk score manifested that the area under the ROC curve was higher than the other predictors. The calibration chart showed consistency of the predicted outcomes to the actual results. CONCLUSION: A prognostic risk scoring model of basement membrane-related genes and an effective nomogram were successfully constructed, which can predict the risk of biochemical recurrence in PCa patients after radical prostatectomy.

[Erectile function of renal failure patients after hemodialysis or kidney transplantation: A comparative study].

OBJECTIVE: To study the changes in the erectile function of the male patients with renal failure after hemodialysis (HD) or kidney transplantation (KT) and explore the causes of these changes. METHODS: From January 2015 to January 2021, 160 male patients with renal failure complaining of ED underwent HD (n = 80) or KT (n = 80) in the General Hospital of Eastern Theater Command. The patients were aged 25－45 (31.7 ± 4.8) years, 32 ± 4.5 years in the HD group and 31.4 ± 5.1 years in the KT group. We recorded the levels of serum T, E2, FSH and LH and the scores on IIEF-5, Self-Rating Anxiety Scale (SAS) and Self-Rating Depression Scale (SDS) of the patients, and compared them between the two groups. RESULTS: Compared with the patients in the HD group, those in the KT group showed a significantly higher T level (ï¼»7.45 ± 3.54ï¼½ vs ï¼»17.75 ± 7.32ï¼½ nmol/L, P < 0.01) and a lower E2 level (ï¼»151.37 ± 20.89ï¼½ vs ï¼»94.17 ± 40.79ï¼½ pmol/L, P < 0.01), but no statistically significant difference from the former group in the levels of FSH (ï¼»8.12 ± 5.12ï¼½ vs ï¼»8.97 ± 2.36ï¼½ IU/L, P > 0.05) and LH (ï¼»5.16 ± 3.87ï¼½ vs ï¼»4.69 ± 2.18ï¼½ IU/L, P > 0.05). There were fewer cases of severe ED in the KT than in the HD group (3.75% vs 16.25%, P < 0.05). Different degrees of anxiety and depression were observed in both groups, with fewer severe cases of anxiety (6.25% vs 30.00%, P < 0.05) and depression (6.25% vs 31.25%, P < 0.05) and more mild cases of anxiety (68.75% vs 47.50%, P < 0.05) and depression (70.00% vs 48.75%, P < 0.05) in the KT than in the HD group, but no statistically significant difference in the incidence of moderate anxiety (25.00% vs 22.50%, P > 0.05) and depression (23.75% vs 20.00%, P > 0.05) between the KT and HD groups. CONCLUSION: For male patients with renal failure, kidney transplantation can evidently improve erectile function, while hemodialysis has a poorer effect. The altered hormone levels, anxiety and depression of the patients are important causes of the changes in their erectile function.

Identification of Serum Biomarkers for Systemic Lupus Erythematosus Using a Library of Phage Displayed Random Peptides and Deep Sequencing.

Systemic lupus erythematosus (SLE) is one of the most serious autoimmune diseases, characterized by highly diverse clinical manifestations. A biomarker is still needed for accurate diagnostics. SLE serum autoantibodies were discovered and validated using serum samples from independent sample cohorts encompassing 306 participants divided into three groups, i.e. healthy, SLE patients, and other autoimmune-related diseases. To discover biomarkers for SLE, a phage displayed random peptide library (Ph.D. 12) and deep sequencing were applied to screen specific autoantibodies in a total of 100 serum samples from 50 SLE patients and 50 healthy controls. A statistical analysis protocol was set up for the identification of peptides as potential biomarkers. For validation, 10 peptides were analyzed using enzyme-linked immunosorbent assays (ELISA). As a result, four peptides (SLE2018Val001, SLE2018Val002, SLE2018Val006, and SLE2018Val008) were discovered with high diagnostic power to differentiate SLE patients from healthy controls. Among them, two peptides, i.e. SLE2018Val001 and SLE2018Val002, were confirmed between SLE with other autoimmune patients. The procedure we established could be easily adopted for the identification of autoantibodies as biomarkers for many other diseases.

[Primary testicular mucinous cystadenoma: A case report and literature review].

Objective: To investigate the tissue source, clinical diagnosis, treatment and prognosis of primary testicular mucinous cystadenoma (PTMC). METHODS: We retrospectively analyzed the clinical data on a case of PTMC and reviewed relevant literature. RESULTS: The patient underwent radical resection of the right testis after relevant preoperative examinations. Postoperative pathology indicated mucinous cystadenoma with low-grade intraepithelial neoplasia of the glandular epithelium. No recurrence was observed during an 11-month follow-up. CONCLUSIONS: PTMC is an extremely rare testicular and ovarian surface epithelial tumor, usually benign, rarely malignant. For the treatment of localized PTMC, radical orchiectomy is mostly recommended, while for the cases with invasion, metastasis or recurrence tendency, chemotherapy protocols for ovarian tumors can be considered.

Methylene blue-based 7-nitro-1,2,3-benzoxadiazole NIR fluorescent probe triggered by H2S.

A new Methylene blue-based 7-nitro-1,2,3-benzoxadiazole NIR fluorescent probe 3, 7-bis-dimethylamino-10-(7-nitrobenzo[c][1,2,5]oxadiazol-4-yl)-10H-phenothiazine (leuco-MB-NBD) was designed and synthesized. Leuco-MB-NBD showed high sensitivity and selectivity for H2S as a fluorescent probe in C2H5OH-PBS (9:1, v/v, pH = 7.4) solution, this fluorescent assay showed a linear range of 0-50.0 µM and a LOD (limit of detection) of 0.43 µM. Moreover, the probe leuco-MB-NBD has lower toxicity at low concentrations to HCT-116 cells and can be used for cell imaging. Additionally, Leuco-MB-NBD is triggered by hydrogen sulfide to generate methylene blue, methylene blue which has potential rescuing effects on the mitochondrial activity can act as an antidote against sulfide intoxication.

Chromatin accessibility analysis reveals that TFAP2A promotes angiogenesis in acquired resistance to anlotinib in lung cancer cells.

Anlotinib, a multitarget tyrosine kinase inhibitor, is effective as a third-line treatment against non-small cell lung cancer (NSCLC). However, acquired resistance occurs during its administration. To understand the molecular mechanisms of anlotinib resistance, we characterized chromatin accessibility in both the parental and anlotinib-resistant lung cancer cell line NCI-H1975 through ATAC-seq. Compared with the parental cells, we identified 2666 genomic regions with greater accessibility in anlotinib-resistant cells, in which angiogenesis-related processes and the motifs of 21 transcription factors were enriched. Among these transcription factors, TFAP2A was upregulated. TFAP2A knockdown robustly diminished tumor-induced angiogenesis and partially rescued the anti-angiogenic activity of anlotinib. Furthermore, transcriptome analysis indicated that 2280 genes were downregulated in anlotinib-resistant cells with TFAP2A knocked down, among which the PDGFR, TGF-ß, and VEGFR signaling pathways were enriched. Meanwhile, we demonstrated that TFAP2A binds to accessible sites within BMP4 and HSPG2. Collectively, this study suggests that TFAP2A accelerates anlotinib resistance by promoting tumor-induced angiogenesis.

Two paternal mosaicism of mutation in ELANE causing severe congenital neutropenia exhibit normal neutrophil morphology and ROS production.

Severe congenital neutropenia caused by ELANE gene mutation is a rare disease. To date, only four families were reported with mosaicism. Here we examined the morphology and function of granulocytes isolated from two patients and their mosaic fathers. Analysis of granulocytes isolated from the fathers revealed no genetic mutations. DNA extracted from fractionated peripheral blood mononuclear cells (PBMCs) and fingernails obtained from both fathers did harbor the mutation, suggesting mosaicism. Granulocytes isolated from the patients displayed significantly weaker ionomycin-induced intracellular reactive oxygen species (ROS) responses than those isolated from the fathers. Both patients showed increased expression of neutrophil elastase, whereas the mosaic fathers showed normal expression. Taken together, the results suggest that granulocytes from these SCN patients are immunocompromised, whereas those from the mosaic fathers are normal. These findings may provide new insight into disease diagnosis, prognosis, therapy and genetic counseling.

How does hard-to-reach status affect antiretroviral therapy adherence in the HIV-infected population? Results from a meta-analysis of observational studies.

BACKGROUND: Socially disadvantaged groups, such as drug users, sex workers and homeless individuals, are labelled as "hard-to-reach" (HTR) in public health and medical research. HIV disproportionately impacts these populations, but data on how the HTR status could affect antiretroviral therapy (ART) adherence among HIV-positive people are limited and have not been previously synthesized in a systematic manner. We performed a meta-analysis to explore the association between HTR status and optimal antiretroviral therapy adherence in the HIV-infected population to provide evidence and recommendations regarding ART adherence improvement and HIV infection control and prevention among HTR people. METHODS: The PubMed, EMBASE, and Cochrance Library databases and the bibliographies of relevant studies were systematically searched up to December 2018. Full-text studies published in English were included, and no geographic or race restrictions were applied. Studies that quantitatively assessed the association between HTR status and optimal ART adherence among HIV-infected populations with a status of homelessness, sex work, or drug use were eligible for inclusion. We estimated the pooled odds ratios (ORs) of HTR characteristics related to ART adherence from each eligible study using a random effects model. The sensitivity, heterogeneity and publication bias were assessed. RESULTS: Our search identified 593 articles, of which 29 studies were eligible and included in this meta-analysis. The studies were carried out between 1993 and 2017 and reported between 1999 and 2018. The results showed that HTR status resulted in a 45% reduction in the odds of achieving optimal ART adherence compared to odds in the general population (OR = 0.55, 95% confidential intervals (CIs) 0.49-0.62), and this significant inverse association was consistently found regardless of study design, exposure measurement, adherence cut-off points, etc. Subgroup analyses revealed that the HTRs tend to be suboptimal adhering during a longer observational period. CONCLUSIONS: HIV treatment adherence is extremely negatively affected by HTR status. It is crucial to develop appropriate interventions to improve ART adherence and health outcomes among HTR people who are HIV-infected.

[Influence of body fat percentage and body mass index on semen parameters in adult males].

OBJECTIVE: To explore the influence of body fat percentage (BF%) and body mass index (BMI) on the semen quality of adult males. METHODS: A total of 125 randomly selected male infertility patients underwent examinations of semen quality, BMI and BF% on the day of enrollment. With BMI ≥28 kg/m2 as the criterion of obesity, 50 of the patients fell into the category of obesity and 75 into that of non-obesity, while with BF% >25% as the criterion, 69 belonged to the obesity and 56 to the non-obesity type. We compared the semen parameters of the subjects between the obesity and non-obesity groups based on the two criteria and analyzed the correlation of semen quality with age, BF% and BMI. RESULTS: With BF% as the criterion, the obesity patients, as compared with the non-obesity men, showed significantly lower semen volume (ï¼»2.94 ± 1.15ï¼½ vs ï¼»3.51 ± 1.27ï¼½ ml, P < 0.05), percentage of grade a+b sperm (ï¼»33.37 ± 19.80ï¼½% vs ï¼»41.87 ± 15.43ï¼½%, P < 0.05) and sperm motility (ï¼»56.31 ± 22.26ï¼½% vs ï¼»64.95 ± 18.22ï¼½%, P < 0.05). Similar results were observed with BMI as the criterion in the semen volume (ï¼»2.86 ± 1.11ï¼½ vs ï¼»3.34 ± 1.26ï¼½ ml, P < 0.05), percentage of grade a sperm (ï¼»16.33 ± 13.80ï¼½% vs ï¼»25.09 ± 15.06ï¼½%, P < 0.05), percentage of grade a+b sperm (ï¼»30.10 ± 18.43ï¼½% vs ï¼»39.80 ± 17.50ï¼½%, P < 0.05) and sperm motility (ï¼»53.62 ± 21.56ï¼½% vs ï¼»62.83 ± 20.47ï¼½%, P < 0.05). Age was correlated negatively with sperm motility (r = －0.20,P < 0.05), BF% negatively with the semen volume (r = －0.21, P < 0.05), the percentage of grade a sperm (r = －0.21, P < 0.05) and the percentage of grade a+b sperm (r = －0.18, P <0.05), and BMI negatively with the semen volume (r = －0.26, P < 0.01), percentage of grade a sperm (r = －0.23, P<0.01) and percentage of grade a+b sperm (r = －0.18, P < 0.05). Further multivariate analysis also showed that BF% was negatively correlated with the semen volume and percentage of grade a+b sperm after exclusion of age and other factors. CONCLUSIONS: Obesity affects the semen volume, percentage of grade a sperm, percentage of grade a+b sperm and sperm motility in male infertility patients. And BF% can be used as an indicator in the diagnosis of obesity.