Current understanding of ELF4 deficiency: a novel inborn error of immunity.

BACKGROUND: ELF4 deficiency has been recently recognized as a novel disorder within the spectrum of inborn errors of immunity (IEIs), specifically categorized as a "disease of immune dysregulation." Cases of this condition, reported by our team and others, are very limited worldwide. As such, our current knowledge of this new disease remains preliminary. This review aims to provide a brief overview of the clinical manifestations, pathogenesis, and treatment strategies for this novel IEI. DATA SOURCES: A comprehensive review was conducted after an extensive literature search in the PubMed/Medline database and websites concerning transcriptional factor ELF4 and reports concerning patients with ELF4 deficiency. Our search strategy was "ELF4 OR ETS-related transcription factor Elf-4 OR EL4-like factor 4 OR myeloid Elf-1-like factor" as of the time of manuscript submission. RESULTS: The current signature manifestations of ELF4 deficiency disorder are recurrent and prolonged oral ulcer, abdominal pain, and diarrhea in pediatric males. In some cases, immunodeficiency and autoimmunity can also be prominent. Targeted Sanger sequencing or whole exome sequencing can be used to detect variation in ELF4 gene. Western blotting for ELF4 expression of the patient's cells can confirm the pathogenic effect of the variant. To fully confirm the pathogenicity of the variant, further functional test is strongly advised. Glucocorticoid and biologics are the mainstream management of ELF4 deficiency disorder. CONCLUSIONS: Pediatric males presenting with recurring ulcerations in digestive tract epithelium with or without recurrent fever should be suspected of DEX. When atypical presentations are prominent, variations in ELF4 gene should be carefully evaluated functionally due to the complex nature of ELF4 function. Experience of treating DEX includes use of glucocorticoid and biologics and more precise treatment needs more patients to identify and further mechanistic study.

[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.

Yiqi Yangjing recipe stimulates apoptosis while suppressing the energy metabolism via under-expression of PFKFB3 in A549 cells.

Background: Lung cancer is a malignant tumor associated with high morbidity and mortality. Yiqi Yangjing recipe (YYR) is a formula of traditional Chinese medicine (TCM) that is commonly used for the treatment of lung cancer with good clinical efficacy. The specific anti-cancer mechanism of YYR is still unknown. We need to embark on a more in-depth pharmacological study of YYR to determine the complex compound ingredients, which could be promoted in clinical practice to achieve efficacy in prolonging recurrent metastasis of lung cancer. Methods: The cytotoxic effects of YYR on A549 cells were evaluated by Cell Counting Kit-8 (CCK-8) assay. The PFKFB3-under-expressed and overexpressed A549 cell lines were constructed via PFK15 treatment and transfection, respectively. The effects of YYR on PFKFB3 messenger RNA (mRNA) and protein expression were detected by reverse transcription quantitative polymerase chain reaction (RT-qPCR) and western blot. The pro-apoptotic and anti-glycolytic abilities of YYR were measured using flow cytometry assay and hippocampal XF96 extracellular flux analyzer. An in vivo tumorigenicity assay was performed on nude mice to confirm the anti-cancer effects of YYR. Results: YYR has a noticeable cytotoxic activity on A549 cells, with the treatment with both YYR and PFK15 significantly inducing apoptosis. YYR and PFK15 treatment reduced the extracellular acidification rate (ECAR) and oxygen consumption rate (OCR) in A549 cells. Similar to PFK15, YYR can down-regulate PFKFB3 expression, and PFKFB3 overexpression suppressed the apoptosis, which was reversed by YYR. Animal experiments confirmed that YYR was able to inhibit tumor growth, induce tumor cell apoptosis, and down-regulate PFKFB3 in tumor tissues. Conclusions: This study demonstrated that YYR promoted lung cancer cell apoptosis and inhibited energy metabolism by targeting PFKFB3. Furthermore, we believe that YYR may be a suitable supplement or alternative drug for lung cancer treatment.

Interfering with Rac1-activation during neonatal monocyte-macrophage differentiation influences the inflammatory responses of M1 macrophages.

Necrotizing enterocolitis (NEC) is a life-threatening, inflammatory disease affecting premature infants with intestinal necrosis, but the mechanism remains unclear. Neonatal macrophages are thought to play an important role in the pathogenesis of NEC through the production of proinflammatory cytokines. Restriction of cytokine expression in macrophages of NEC tissues may be beneficial. In adult macrophages, interfering with Rac1 has been shown to influence the expression of cytokines. Here, we investigated whether interfering with Rac1 in neonatal macrophages affects their inflammatory responses. First, we found that Rac1-activation was upregulated in the macrophages of rats with NEC model induction compared to controls. The M1 macrophages derived from human neonatal monocytes showed greater Rac1-activation than the M2 macrophages derived from the same monocytes. Inhibition of Rac1-activation by NSC23766 potently reduced the production of proinflammatory cytokines in these M1 macrophages. While neonatal monocytes differentiated into M1 macrophages in vitro, NSC23766 significantly altered cell function during the first six days of incubation with GM-CSF rather than during the subsequent stimulation phase. However, the same effect of NSC23766 was not observed in adult macrophages. Using mass spectrometry, Y-box binding protein 1 (YB1) was identified as being downregulated upon inhibition of Rac1-activation in the neonatal macrophages. Moreover, we found that inhibition of Rac1-activation shortens the poly A tail of PABPC1 mRNA, thereby reducing the translation of PABPC1 mRNA. Consequently, the downregulation of PABPC1 resulted in a reduced translation of YB1 mRNA. Furthermore, we found that TLR4 expression was downregulated in neonatal macrophages, while YB1 expression was reduced. Adding resatorvid (TLR4 signaling inhibitor) to the macrophages treated with NSC23766 did not further reduce the cytokine expression. These findings reveal a novel Rac1-mediated pathway to inhibit cytokine expression in neonatal M1 macrophages and suggest potential targets for the prevention or treatment of NEC.

[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.

[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.

A superior articular process morphology of 5th lumbar vertebra prone to screws placement failure: an anatomical study of 299 patients.

PURPOSES: This study aimed to investigate whether the morphology of the superior articular processes of L5 vertebra affected the accuracy of pedicle screw placement by reviewing 299 patients who had undergone L5 pedicle screw fixation over the past 12 months and measuring relevant parameters. METHODS: We retrospectively analyzed patients who underwent L5 vertebra fixation at our spine surgery department from October 20, 2020 to October 20, 2021. Patients with spondylolisthesis, spondylolysis, and scoliosis were excluded. Parameters associated with the superior articular process were analyzed, including Mammillary process-Spinal canal Distance (MCD), Inter-Facet Distance (IFD), Inter-Pedicle Distance (IPD), Zygapophysial Joints Angle (ZJA), Superior Articular Width, and Lateral Recess Transverse Diameter. The L5 vertebral body was reconstructed by Mimics 21.0, and the simulated L5 screws were inserted at multiple entry points to measure the Maximum Safe Transverse Angle (STAmax). RESULTS: A total of 299 patients who underwent L5 vertebra fixation with 556 pedicle screws were analyzed. An MCD < 6 mm was associated with a significant increase in screw placement failure rate and decrease in ZJA. The MCD was positively correlated with IFD. No significant change in IPD was observed. Mimics software analysis showed that the STAmax decreased with a decrease of MCD. When WBV < 6 mm, 93% of the trans-mammillary vertical line was located within 50% of the pedicle. CONCLUSIONS: The superior articular process tended to narrow the spinal canal and exhibit a steep and a "cloverleaf" morphology when the MCD was < 6 mm. This morphology increased the risk of operator mis-judgement resulting in screw placement failure. Assessment of the relationship between the trans-mammillary vertical line and the pedicle represents a simple method to predict abnormal morphology of the superior articular process before surgery.

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.

[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.

[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.

[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.

[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.

A network meta-analysis protocol of efficacy and safety evaluation of different surgery regimens for varicocele patients with infertility: A study protocol.

BACKGROUND: Surgical treatment of varicocele is still one of the most common important treatments for male infertility. Surgery regimens for varicocele (VC) is various, including high ligation, sub-inguinal, inguinal, retroperitoneal, laparoscopic, and microsurgery. The surgery regimens applied for VC patients are various in clinic, however, the significance, advantages, and disadvantages of different varicocelectomies for male infertility are still in controversial. Therefore, this network meta-analysis is mainly to assess the relative efficacy and safety of different surgery regimens for VC patients with infertility. METHODS: To compare the relative efficacy and safety among different varicocelectomies for VC patients, we systematic searched randomized controlled trials (RCTs) and non-RCTs were in five electronic databases: Pubmed, Web of Science, EMBASE database, Clinical Trials, and Cochrane Library. Using R-3.4.1 software to process and analyze data. The bias risk of RCTs and non-RCTs will be evaluated through the tool of Cochrane Handbook version 5.1.0 and non-randomized studies of interventions (ROBINS-I), respectively. RESULTS AND CONCLUSION: The result of this network meta-analysis aim is to evaluate the relative effectiveness and safety and rank the interventions among all surgery methods for VC patients and provide more evidence-based guidance in clinical practice. PROTOCOL REGISTRATION NUMBER: CRD42020162051.

[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.

NFAT Overexpression Correlates with CA72-4 and Poor Prognosis of Ovarian Clear-Cell Carcinoma Subtype.

Current biomarkers did not overcome the limitations of clinical application due to the heterogeneity of ovarian tumors. The role of nuclear factor of activated T cells (NFAT) in the prognosis of different histological subtypes of ovarian cancer remains unclear. NFAT expression was analyzed in 302 ovarian tumors from The Cancer Genome Atlas (TCGA) dataset and was further confirmed by 88 ovarian tumor specimens, including 30 clear-cell carcinoma, 34 serous carcinoma, and 24 papillary serous cystadenocarcinoma. The correlations between NFAT expression, cancer biomarkers, and clinical characteristics in different subtypes of ovarian tumors were analyzed. ALGGEN PROMO, reporter assay, and NFAT overexpression and knockdown were used to identify chondroadherin (CHAD) as the downstream target of NFAT. NFAT was significantly upregulated only in late-stage clear-cell carcinoma, but not in other two subtypes. NFAT levels were correlated with CA72-4 levels and poor overall survival and disease-free survival (P < 0.05), suggesting that NFAT together with CA72-4 were specific prognostic markers for clear-cell carcinoma. Pathological stage and lymph node metastasis were the prognostic factors affecting serous carcinoma (P < 0.05), while CA-125 was the prognostic factor affecting papillary serous cystadenocarcinoma (P < 0.05). PROMO and reporter assay indicated that CHAD was the downstream target of NFAT. In addition, NFAT overexpression and silencing increased and reduced CHAD expression, respectively. NFAT together with CA72-4 were specific tumor markers for risk assessment of unique clear-cell subtype of ovarian tumors. CHAD was identified as the downstream target gene of NAFT and was associated with poor survival of ovarian cancer.

[Several Common Respiratory Viral Pathogens in Hematopoietic Stem Cell Transplantion Patients with Primary Immunodeficiency Disease].

OBJECTIVE: To investigate the prevalence of respiratory viral infections in patients with primary immunodeficiency disease (PID) during hematopoietic stem cell transplantation. METHODS: 108 specimens of nasopharyngeal aspirate were collected from 22 PID patients before and after hematopoietic stem cell transplantation from July 2016 to July 2018 in the Department of Hematology. The TR-PCR was used to detect for respiratory viruses including respiratory syncytial virus(RSV)，human metapneumoviros(hMPV)，coronavirus(CoV) and parainfluenza 1-3 (PIV1-3). And the clinical characteristics and co-infection were analyzed. RESULTS: Among the total 108 specimens, viral pathogens were identified in 41 (37.96%) specimens. Among which the pathogens of highest detection rate was RSV (25.9%). Different types of PID showed different virus infection rates, among which the highest infection rate was severe combined immunodeficiency disease (SCID) patients, with the virus detection rate was 57.9%. The incidence of co-infection with two or more than two viruses was 19.5%. CONCLUSION: Patients with PID who undergo hematopoietic stem cell transplantation are more susceptible to respiratory viruses. RSV is an important respiratory tract virus pathogen after hematopoietic stem cell transplantation.

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.