Flexible ureteroscopy in Chinese air force pilots with renal calculi: a cohort study at a single medical centre.

INTRODUCTION: Renal calculi are the predominant urological ailment in air force pilots. Flexible ureteroscopy (FURS) constitutes a valuable approach for renal calculi treatment. This study presents a decade-long exploration of using FURS for renal calculi treatment in air force pilots. Additionally, it investigates the safety and feasibility of granting waiver flights to pilots with renal parenchyma calcification. METHODS: From December 2009 to December 2019, a retrospective review was conducted on Chinese air force pilots undergoing treatment for renal calculi. Among the pilots assessed, a total of 71 individuals underwent FURS. Endoscopic methodology involved the insertion of a flexible ureteroscope into the ureter and renal pelvis, guided by a safety wire. Stone fragmentation was achieved using a holmium laser fibre, followed by extraction using a soft stone basket. Postoperative non-enhanced CT (NECT) scans was used to confirm stone clearance. Furthermore, clinical diagnoses were classified based on endoscopic findings and postoperative NECT results. All data were presented as mean (SD) or median (minimum-maximum) for continuous variables and frequency counts and percentages for categorical variables. RESULTS: FURS identified free kidney stones in 60 cases among all patients. The remaining 11 cases, without free stones detected during ureteroscopy, exhibited persistent high-density spots on postoperative NECT. Of the 60 cases with stones, renal calculi were successfully cleared in 30 pilots, while the remaining 30 exhibited persistent high-density spots on NECT postsurgery. Pilots with completely cleared free stones were deemed fit for flight. Pilots with diagnosed renal parenchyma calcification were granted permission to fly under waivers following a meticulous evaluation. CONCLUSIONS: FURS could not only effectively eliminate renal calculi but also accurately diagnose renal parenchyma calcification, facilitating a prompt return to flight for pilots. A protocol for managing pilot renal calculi, informed by FURS and our experience, is proposed.

[The prevalence and risk factors of diabetic peripheral artery disease in Chinese communities].

Objective: To investigate the prevalence and risk factors of diabetic peripheral artery disease (PAD) in patients with type 2 diabetes mellitus (T2DM) managed in primary health care in China. Methods: A total of 2 528 T2DM patients were selected using a two-stage cluster random sampling method based on the baseline survey of the "China Diabetic Foot Prevention Model Project." The study was conducted in 2015 among T2DM patients in 8 primary healthcare centers in Changshu county and Jiang'an district of Wuhan, China. Data collection methods included a questionnaire, body measurement, and blood glucose detection. The Ankle-Brachial Index (ABI) is the most widely used noninvasive vascular test. A binary logistic regression model was used to analyze the influence factors. Results: The prevalence of PAD was 11.2% among the diabetic patients managed in primary health care in the two cities. The prevalence of PAD under 55 years old, 55- years old, 65- years old, and ≥75 years old were 7.8%, 6.0%, 12.9% and 22.5%, respectively. Multivariate stepwise logistic regression identified influence factors included older age, higher education level, smoking, drinking, postprandial glucose uncontrol, and prior myocardial infarction or angina. Compared to age <55 years, the odds ratio for PAD were 0.74 for 55- years (95%CI: 0.43-1.28), 1.72 for 65- years (95%CI: 1.05-2.81), 3.56 for 75 years and above (95%CI: 2.07-6.11), respectively. Compared to patients with education in primary school and below, the odds ratio was 1.37 (95%CI: 0.97-1.94), 2.48 (95%CI: 1.73-3.55), 1.99 (95%CI: 1.26-3.13) for those with education levels of junior high school, senior high school, and college, respectively. Current smoking (OR=1.49, 95%CI: 1.02-2.17), current drinking (OR=0.45, 95%CI: 0.28-0.71), postprandial glucose uncontrol (2 h postprandial plasma glucose >10.0 mmol/L: OR=1.72, 95%CI: 1.22-2.43), and prior myocardial infarction or angina (OR=2.32, 95%CI: 1.50-3.61) were influencing factors of PAD. Conclusions: Despite the high prevalence of PAD in diabetes managed in primary health care; multiple risk factors are not effectively aware of and under control. It is urgent to promote ABI screening and standardized management for diabetes, especially in primary health care.

[Phenotypes and ATP7B gene variants in 316 children with Wilson disease].

Objectives: To summarize the clinical phenotypes and the variation spectrum of ATP7B gene in Chinese children with Wilson's disease (WD) and to investigate their significance for early diagnosis. Methods: Retrospective analysis was performed on the clinical data of 316 children diagnosed as WD in Guangzhou Women and Children's Medical Center during the period from January 2010 to June 2021. The general situations, clinical manifestations, lab test results, imaging examinations, and ATP7B gene variant characteristics were collected. The patients were divided into asymptomatic WD group and symptomatic WD group based on the presence or absence of clinical symptoms at the time that WD diagnosis was made. The χ2 test, t test or Mann-Whitney U test were used to compare the differences between groups. Results: Among the 316 children with WD, 199 were males and 117 were females, with the age of 5.4 (4.0, 7.6) years at diagnosis; 261 cases (82.6%) were asymptomatic with the age of 4.9 (3.9, 6.4) years; whereas 55 cases (17.4%) were symptomatic with the age of 9.6 (7.3, 12.0) years. The main symptoms invloved liver, kidney, nervous system, or skin damage. Of all the patients, 95.9% (303/316) had abnormal liver function at diagnosis; 98.1% (310/316) had the serum ceruloplasmin lever lower than 200 mg/L; 97.7% (302/309) had 24-hour urine copper content exceeding 40 µg; only 7.4% (23/310) had positive corneal K-F rings, 8.2% (23/281) had abnormal MRI signals in the lenticular nucleus, and all of them had symptoms of damage in liver, kidney or nervous system. Compared with the group of symptomatic WD, asymptomatic group had higher levels of serum alanine aminotransferase and lower levels ceruloplasmin and 24-hour urine copper [(208±137) vs. (72±78) U/L, (55±47) vs. (69±48) mg/L, 103 (72, 153) vs. 492 (230, 1 432) µg; t=9.98, -1.98, Z=-4.89, all P<0.001]. Among the 314 patients completing genetic sequencing, a total of 107 mutations in ATP7B gene were detected, of which 10 are novel variants, and 3 cases (1.0%) had large heterozygous deletion (exons 10 to exon 11) in ATP7B gene. The percentage of missense mutation in asymptomatic WD children was significantly higher than that in symptomatic WD (81.5% (422/518) vs. 69.1% (76/110), χ²=8.47, P<0.05). WD patients carrying homozygous variant of c.2 333G>T had significantly low levels of ceruloplasmin than those not carrying this variant ((23±5) vs. (61±48) mg/L, t=-2.34, P<0.001). Conclusions: The elevation of serum ALT is an important clue for early diagnosis of WD in children, while serum ceruloplasmin and 24-hour urine copper content are specific markers for early diagnosis of WD. In order to confirm the diagnosis of WD, it is necessary to combine the Sanger sequencing with multiplex ligation-dependent probe amplification or other testing technologies.

[TRIM21 suppresses invasion of hepatocellular carcinoma cells by promoting ß-catenin ubiquitylation and degradation].

OBJECTIVE: To explore the role of TRIM21 in modulating the invasive phenotype of hepatocellular carcinoma (HCC) cells and its mechanism of action. METHODS: RNA interference technique was used to knock down the expression of TRIM21 and ß-catenin, alone or in combination, in HCC cell lines 97H and LM3, and the interfering efficiency and the activity of closely related pathways were determined using Western blotting. The two cells with TRIM21 knockdown (siTRIM21 97H and siTRIM21 LM3 cells) were assessed for their invasion ability in vitro using Transwell invasion assay, and the lung metastasis capacity of siTRIM21 LM3 cells following tail vein injection was evaluated in nude mice. The binding of TRIM21 with ß-catenin and the ubiquitylation level of ß-catenin in TRIM21-overexpressing HEK293 cells were determined with Western blotting and co-immunoprecipitation assay. We also compared the overall survival of patients with CTNNB1highTRIM21high and CTNNB1highTRIM21low HCC subtypes using Kaplan-Meier method based on filtrated and grouped HCC clinical data from TCGA database. RESULTS: TRIM21 knockdown significantly enhanced the invasion ability of 97H and LM3 cells in vitro (P < 0.01 or 0.05) and the lung metastasis ability of LM3 cells in nude mice (P < 0.01), and simultaneous knockdown of ß -catenin obviously suppressed the in vitro invasiveness of the cells (P < 0.0001 or 0.05). Co-immunoprecipitation assay showed that TRIM21 was capable of directly binding with ß-catenin protein to accelerate the ubiquitination and degradation of the latter, leading to inhibition of nuclear translocation of ß-catenin and hence reduced invasiveness of HCC cells. Bioinformatic analysis showed that compared patients with CTNNB1highTRIM21low HCC subtype where Wnt pathway was activated, the patients with CTNNB1highTRIM21high HCC subtype had a significantly better survival outcomes (P < 0.05). CONCLUSION: A high expression of TRIM21 suppresses the invasion of HCC cells by promoting ß-catenin ubiquitylation and degradation, which possibly explains the poor prognosis of CTNNB1highTRIM21low HCC patients.

[Characteristics and clinical significance of wideband tympanometry of otitis media with effusion in young children].

Objective: To study the characteristics of wideband tympanometry(WBT) and its application value in the diagnosis of otitis media with effusion(OME) in young children. Methods: We compared wideband acoustic energy absorbance(EA) under peak pressure in young children with OME(190 ears) and healthy control subjects(121 ears) from Ninth People's Hospital of Shanghai Jiaotong University School of Medicine between January 2018 and June 2020. Both groups were divided into three groups, 1-6 months, 7-36 months and 37-72 months. SPSS 20.0 statistical software was used to analyze and compare the EA parameters between OME children of different months and the control group. Receiver operating characteristic (ROC)curve was used to analyze the diagnostic value of WBT in young children with OME. Results: There were significant differences in EA among three OME groups from 500 Hz to 2 000 Hz(P<0.05).Compared with the control groups, EA of 1-6 m OME group decreased significantly below 4 000 Hz(P<0.05), EA of 7-36 m OME group decreased significantly at 545-1 600 Hz(P<0.05), EA of 37-72 m OME group decreased significantly above 545 Hz(P<0.05).ROC curve indicated that EA at 1 000 Hz had the greatest diagnostic value (AUC was 0.890), followed by 1 500 Hz and the range of 500-2 000 Hz (AUC was 0.883 and 0.881, respectively).EA at 1 000 Hz with a cutoff value of 0.55 had the best diagnostic sensitivity of 90.8%, which was higher than conventional tympanometry (85.8%). The maximum AUC (0.932) could be obtained by combining EA, peak pressure and admittance amplitude of 226 Hz tympanometry as predictors. Conclusions: EA is significantly decreased in young children with OME. Compared with the conventional single frequency tympanometry, WBT is more accurate in the diagnosis of OME in young children, and the prediction accuracy would be better if combined with 226 Hz tympanometry.

[Improved synthesis process of optical-magnetic bimodal probe of Gd-[4, 7-Bis-carboxymethyl-10-(2-fluoresceinthioureaethyl)-1, 4, 7, 10-tetraaza-cyclododec-1-yl]-acetic acid complexes].

OBJECTIVE: To improve the methods to synthesize and purify of optical-magnetic bimodal molecular probe of Gd-[4, 7-Bis-carboxymethyl-10-(2-fluorescein thioureaethyl)-1, 4, 7, 10-tetraaza-cyclododec-1-yl]-acetic acid complexes. METHODS: Target compound (7), optical-magnetic bimodal molecular molecular probe, was synthesized by the use of 1, 4, 7, 10-tetraazacyclododecane (1) as starting material via substitution reaction, hydrolysis reaction, coupling reaction and complexation reaction with metal. RESULTS: The synthetic route of Gd-[4, 7-Bis-carboxymethyl-10-(2-fluoresceinthioureaethyl)-1, 4, 7, 10-tetraaza-cyclododec-1-yl]-acetic acid complexes was improved. The optical-magnetic bimodal molecular probes were synthesized by substitution reaction, hydrolysis reaction, coupling reaction and complex reaction with metal respectively. For the improved route, the total yield could reach 34.6% which was higher than the original route (18.0%). The structures of those compounds were identified by 1H nuclear magnetic resonance, 13C nuclear magnetic resonance, and mass spectrometry. The improved route could avoid the uncontrollable disadvantage of the substitution reaction, this process could reduce the formation of impurities and made the purification process easier, and in the aspect of purification and separation, the preparative high-performance liquid chromatography with less sample loading and high cost was improved to a column chromatography with many sample loads and being easy to operate. Therefore, the use of column chromatography could be more conducive to mass production of the optical-magnetic bimodal molecular molecular probe. CONCLUSION: The improved synthetic route improves the controllability of the reaction conditions and makes it easier to purify and separate the compounds. At the same time, the improved synthetic route can increase the total yield significantly. The optical-magnetic bimodal molecular probe can combine the living magnetic resonance imaging with the in vitro optical imaging to realize the dual synchronous detection of magneto-optics, so that the detection results of the living magnetic resonance imaging and the in vitro optical imaging are mutually verified. In other words, this synthetic optical-magnetic bimodal molecular probe will make the experimental results more accurate and reliable. In subsequent biological experimental studies, the optical-magnetic bimodal molecular probe can be applied to related research of brain structure and function, and the probe can be used for the brain-related diseases researches, such as brain tumors. after intravenous administration, and thus the optical-magnetic bimodal molecular probe can play an important role in medical treatment of brain tumors and cerebrovascular diseases.

MiR-429-5p attenuates the migration and invasion of malignant melanoma by targeting LIMK1.

OBJECTIVE: To investigate the potential effects of microRNA-429-5p (miR-429-5p) on the development of malignant melanoma (MM) and the relevant mechanism. PATIENTS AND METHODS: Quantitative Real Time-Polymerase Chain Reaction (qRT-PCR) was used to detect the differential expression of miR-429-5p in MM tissues. The relationship between miR-429-5p expression and clinical pathological data of MM patients was analyzed. LIM kinase 1 (LIMK1) was verified as a downstream target of miR-429-5p by online prediction software, and the interaction between LIMK1 and miR-429-5p was verified by Dual-Luciferase reporter assay. RESULTS: Compared with normal skin tissues, miR-429-5p was downregulated in MM tissues. MiR-429-5p expression was correlated with tumor size and stage of MM. Upregulation of miR-429-5p significantly inhibited protein expression of LIMK1 and reduced migration and invasion ability of MM cells. LIMK1 was involved in MM progression regulated by miR-429-5p. CONCLUSIONS: MiR-429-5p attenuates migration and invasion in MM by targeting LIMK1. Hence, miR-429-5p/LIMK1 axis might be a potential therapeutic target for the treatment of MM.

[Expression and distribution of programmed death receptor 1 and T cell immunoglobulin mucin 3 in breast cancer microenvironment and its relationship with clinicopathological features].

Objective: To explore the expression and distribution of programmed death receptor 1 (PD-1) and T-cell immunoglobulin mucin 3 (TIM-3) in breast cancer microenvironment and analyze the their correlation with the clinicopathological features. Methods: The specimens of tumor tissue and adjacent tissues from 30 patients with infiltrative breast cancer who were diagnosed as breast cancer from June 2016 to May 2017 in The First Hospital of Jiaxing were collected, and the specimen were divided into two parts along the center. After embedding and cryosectioning, the expression and distribution of PD-1 and TIM-3 protein in tumor tissues were observed by immunofluorescence staining. Another part of the specimen was cut and digested, and non-continuous density gradient centrifugation was used to extract tumor-infiltrating lymphocytes (TILs), real-time quantitative PCR (qRT-PCR) was used to detect the mRNA expression of PD-1 and TIM-3 in TILs. Meanwhile, the protein expression was determined by Western blotting. The relationship between the expression of PD-1 and TIM-3 and pathological parameters of breast cancer was analyzed with correlation analysis. Results: Immunofluorescence results showed that more PD-1 and TIM-3 positive cells were observed in the tumor tissues compared with the tumor-adjacent tissues. The qRT-PCR showed that the expression of PD-1 and TIM-3 mRNA in TILs were both significantly higher than those in paracancerous tissues (3.09±0.38 vs 1.26±0.23, 3.42±0.31 vs 1.57±0.29, t=4.16, 4.37, both P<0.05). At the protein level, the expression of PD-1 and TIM-3 in tumor tissue lymphocytes(0.66±0.08, 0.80±0.11) was significantly higher than those in cancerous tissues(0.10±0.01, 0.26±0.02) (t=6.79, 4.57, both P<0.05). There were significant differences in the expression of PD-1, TIM-3 mRNA in the TILs between the different tumor histological grades, tumor sizes, lymph node metastasis (t=2.22-2.99, all P<0.05). Correlation analysis showed that there was a significant positive correlation between the expression of PD-1 and TIM-3 in tumor tissues (r=0.616, P<0.01). Conclusions: In the breast cancer microenvironment, PD-1, TIM-3-mediated signaling pathway plays an important role in the occurrence and development of breast cancer, it provides a new basis for the combination therapy of breast cancer.

[Effects of bimodal intervention on the development of auditory and speech ability in infants with unilateral cochlear implantation].

Objective: To explore the effects of bimodal intervention on the development of auditory and speech ability in the infants with unilateral cochlear implantation(CI). Methods: Total 35 bilateral profound sensorineural hearing loss infants with unilateral CI, aged 0.7 to 2.8 years old, were selected. The subjects were divided into two groups: the group with unilateral CI(cochlear implant alone, n= 15), and the bimodal group with CI and contralateral fitting hearing aid(n= 20). Their auditory and speech abilities were estimated at the different time points after switch-on(the 0th, 0.5th, 1st, 3rd, 6th, 12th, 18th, and 24th month, respectively) using Infant Toddler-Meaningful Auditory Integration Scale(IT-MAIS), Meaningful Use of Speech Scale(MUSS), Categories of Auditory Performance(CAP), and Speech Intelligibility Rating(SIR) scores. Results: The IT-MAIS scores of bimodal group after switch-on were higher than unilateral CI group(the 0.5th, 1st, 3rd, 6th, 12th, and 18th month), the statistical significances were identified at the 0.5th, 1st, 3rd, 6th, and 12th month, respectively(P<0.05). The CAP scores of bimodal group before CI operation and after switch-on(the 0.5th, 1st, 3rd, 6th, 12th, 18th and 24th month)were higher than unilateral CI group, the statistical significances were seen at the 3rd, 6th, 12th, 18th and 24th month after switch-on(P<0.05). The MUSS scores of bimodal group after switch-on were higher than unilateral CI group(the 1st, 3rd, 6th, 12th, 18th and 24th month), the statistical significances were found at the 12th, 18th and 24th month, respectively(P<0.05). The SIR scores of bimodal group after switch-on were higher than unilateral CI group(the 3rd, 6th, 12th, 18th and 24th month), and significant differences appeared at the 12th, 18th and 24th month after switch-on(P<0.05). Conclusion: Bimodal intervention could be helpful to the development of auditory and speech ability of infants.

Tanshinone IIA ameliorates chronic arthritis in mice by modulating neutrophil activities.

Rheumatoid arthritis (RA) is a chronic immune inflammatory disease mediated by the influx of immune cells into the synovial joint space. As Tanshinone IIA (TIIA) has potent anti-oxidant and anti-inflammatory activities, we used the adjuvant-induced arthritis (AA) murine model of RA to investigate the impact of TIIA on RA and immune cell activation. The anti-arthritic activity of TIIA was investigated in an adjuvant-induced arthritis model of RA in mice. Myeloperoxidase and neutrophil elastase expression levels were assessed in ankle joints by immunohistochemistry analysis. Immune cell infiltration was evaluated in air pouch experiments. Proinflammatory cytokines expression levels were determined by quantitative real-time polymerase chain reaction (PCR) and enzyme-linked immunosorbent assays. Neutrophil extracellular traps (NETs) were assessed by immunostaining and confocal microscopy. Treatment with TIIA alleviated cartilage erosion and neutrophil infiltration in the ankle joints of AA mice and reduced proinflammatory cytokine expression levels in sera. TIIA suppressed interleukin-6 and tumour necrosis factor-α expression and release in neutrophils and promoted neutrophil apoptosis. TIIA also inhibited the NET formation of neutrophils. Our findings demonstrated that TIIA can ameliorate RA effectively by targeting neutrophils, indicating that TIIA may act as a potential therapeutic for RA.

Clinical and molecular characteristics in 15 patients with androgen receptor gene mutations from South China.

A variety of mutations in the androgen receptor (AR) gene are linked to androgen insensitivity syndrome (AIS) or sexual development disorder. Here, we studied 15 patients with various degrees of disorders of genital hypoplasia from South China. Clinical data including basal hormone level, phenotype, karyotyping and SRY gene identification were documented. Exons with flanking intronic region of the AR gene were sequenced and analysed for mutations, and a total of eight mutations were identified in the AR gene. Of eight mutations, two novel mutations c.2518G>T (p.Asp840Tyr) and c.1186G>C (p.Gly396Arg) were predicted to be damaging by SIFT and Polyphen2 online software. Previously reported mutations: c.528C>A (p.Ser176Arg), c.1789G>A (p.Ala597Thr), c.2612C>T (p.Ala871Val), c.1752C>A (p.Phe584Leu), c.171_172insCTG (p.57_58insLeu) and c.2659A>G (p.Met887Val) were also detected in our subjects. Most of them are involved in hypospadias, penis dysplasia or other disorders of sexual development. A complete AIS case (p.Phe584Leu) with female phenotype and high serum concentrations of dihydrotestosterone (DHT) was also found. This study presented a wide range of spectrum of AIS (from partial AIS to complete AIS) caused by AR mutations in South China population. It suggests that further study with larger data set need to be performed to elucidate the differences of the phenotypes in our study.

The Prevalence, Clinical, and Molecular Characteristics of Congenital Hypothyroidism Caused by DUOX2 Mutations: A Population-Based Cohort Study in Guangzhou.

Thyroid dyshormonogenesis (DH) has recently been reported to be more frequently associated with mutations in the dual oxidase 2 (DUOX2) gene. The present study was aimed to investigate the prevalence, clinical, and molecular characteristics of congenital hypothyroidism (CH) caused by DUOX2 mutations in Guangzhou. A population-based cohort of 156 patients with CH was recruited based on neonatal screening among 433 578 newborns born in Guangzhou from 2011 to 2012. Genetic analysis of DUOX2 was performed in 96 patients with suspected thyroid dyshormonogenesis (SDH) by PCR-amplified direct sequencing. Apart from 2 cases without ultrasonographic data, 118 (76.6%) of the 156 patients were classified as SDH and 36 (23.4%) as thyroid dysgenesis (TD) according to thyroid ultrasound at diagnosis. Genetic analysis revealed 23 different variants in 60 unrelated individuals (60/96, 62.5%), including 13 novel variants that were absent from HGMD, dbSNP databases, and the 50 normal controls. The novel missense variants were predicted to be pathogenic by SIFT and PolyPhen-2. The p.K530X was the most common mutation. Ninety-three percent of mutant alleles occurred in exons 5, 6, 9, 14, 17, 20, 25, 27, and 28. There were no significant differences in phenotypes between biallelic and monoallelic variants cases or between with-DUOX2 and non-DUOX2 variants cases. Most patients with DUOX2 defects (78.2%) were transient CH. In conclusion, the prevalence of DUOX2 pathogenic variants was high (62.5%) in this cohort. Thirteen novel probably pathologic variants were reported. The p.K530X was the most common mutation in the Chinese population. There was no correlation between DUOX2 genotypes and clinical phenotypes.

Positive Correlation between Serum Osteocalcin and Testosterone in Male Hyperthyroidism Patients with High Bone Turnover.

PURPOSE: Animal studies suggested that there is an independent bone-osteocalcin-gonadal axis, except of the hypothalamic-pituitary-gonadal axis. Based on this hypothesis, the higher osteocalcin during the high bone turnover should be followed by higher testosterone formation. Yet such clinical evidence is limited. The patients with uncontrolled hyperthyroidism are proper model with high bone turnover. If this hypothesis is true, there should be high testosterone level in patients with uncontrolled hyperthyroidism. Therefore, Graves' disease patients were recruited to study the correlation between osteocalcin and testosterone. MATERIALS AND METHODS: 50 male hyperthyroidism patients with Graves' disease and 50 health persons matched by age and gender were enrolled in our cross-section study. Serum markers for thyroid hormone, sex hormone and bone metabolic markers including free triiodothyronine (FT3), free thyroxine (FT4), thyroid-stimulating hormone (TSH), testosterone, luteinizing hormone (LH), follicle-stimulating hormone (FSH) and osteocalcin (OC), C-terminal telopeptide fragments of type I collagen (CTX) were examined. The demographic parameters such as duration of disease were also collected. All data was analyzed by SPSS 20.0. RESULTS: High testosterone and osteocalcin level was observed in the hyperthyroidism patients (T 36.35±10.72 nmol/l and OC 46.79±26.83 ng/ml). In simple Pearson correlation, testosterone was positively associated with OC (r=0.486, P<0.001), and this positive relation still existed after adjusted for age, BMI, smoking, drinking, duration of disease, FT3, FT4, LH, FSH, CTX in multi-linear regression analysis (See Model 1-4). CONCLUSION: In male hyperthyroidism patients, osteocalcin was positively correlated with serum testosterone, which indirectly supports the hypothesis that serum osteocalcin participates in the regulation of sex hormone.

A Four-Year Follow-up Study of Renal Epithelioid Angiomyolipoma: A Multi-Center Experience and Literature Review.

In this study, we systematically explored the clinical manifestations, diagnosis, treatment, and prognosis of renal epithelioid angiomyolipoma (EAML) retrospectively by analyzing data of 52 patients diagnosed with EAML at four centers. Our results showed that the onset of EAML was usually inconspicuous, and so no obvious symptoms or signs had occurred in most patients at diagnosis. Its diagnoses always depended on postoperative pathological examination. The immunohistochemical (IHC) results [HMB45 ( + ), cytokeratin (-), and S100 (-)] could be used to differentiate EAML from other malignancies such as renal cell cancer (RCC) and sarcomas. For treatment, surgery resulted in satisfactory short-term prognosis. The long-term prognosis of patients with EAML was poor, particularly when a large size, a high percentage of epithelioid component, tumor thrombus formation, and necrosis were present. In conclusion, EAML is a tumor with malignant potential. Once diagnosed, integrated approaches, including surgery, chemotherapy, and targeted therapy, should be considered; a close follow-up regimen is necessary for cases that met: 1) tumor size>9 cm, 2) tumor thrombus formation in the vein, 3) epithelioid cells>70% or atypia cells>60%, and 4) necrosis.

Hyperthyroidism caused by acquired immune deficiency syndrome.

BACKGROUND: Acquired immune deficiency syndrome (AIDS) is an immune deficiency disease. The etiology of hyperthyroidism, which can also be immune-related, is usually divided into six classical categories, including hypophyseal, hypothalamic, thyroid, neoplastic, autoimmune and inflammatory hyperthyroidism. Hyperthyroidism is a rare complication of highly active antimicrobial therapy (HAART) for human immunodeficiency virus (HIV). Hyperthyroidism caused directly by AIDS has not been previously reported. PATIENT FINDINGS: A 29-year-old man who complained of dyspnea and asthenia for 1 month, recurrent fever for more than 20 days, and breathlessness for 1 week was admitted to our hospital. The thyroid function test showed that the level of free thyroxine (FT4) was higher than normal and that the level of thyroid-stimulating hormone (TSH) was below normal. He was diagnosed with hyperthyroidism. Additional investigations revealed a low serum albumin level and chest infection, along with diffuse lung fibrosis. Within 1 month, he experienced significant weight loss, no hand tremors, intolerance of heat, and perspiration proneness. We recommended an HIV examination; subsequently, AIDS was diagnosed based on the laboratory parameters. SUMMARY: This is the first reported case of hyperthyroidism caused by AIDS. CONCLUSIONS: AIDS may cause hyperthyroidism by immunization regulation with complex, atypical, and easily ignored symptoms. Although hyperthyroidism is rare in patients with AIDS, clinicians should be aware of this potential interaction and should carefully monitor thyroid function in HIV-positive patients.

Estrogen combined with progesterone decreases cell proliferation and inhibits the expression of Bcl-2 via microRNA let-7a and miR-34b in ovarian cancer cells.

PURPOSE: This study evaluated the effect of estrogen (E(2)), progesterone (P4), and the combination of them (E(2) + P4) on survival rate, apoptosis, and the expressions of Bcl-2, hsa-let-7a and has-miR-34b in primary ovarian cancer cells to provide new clues for the clinical treatments of ovarian cancer. METHODS: The primary ovarian cancer cells from 60 cases of clinical ovarian cancer tissues were isolated and then cultured. The survival rate of ovarian cancer cells after the treatment of E(2), P4 and E(2) + P4 was analyzed by MTT assay. Cell apoptosis rate and cell cycle were measured by FACS analysis. Moreover, the relative abundance of Bcl-2 and microRNAs (let-7a, miR-34b) expressions were detected by quantitative real-time PCR (qRT-PCR) and Western blotting. RESULTS: Low concentrations of estrogen (10(-10), 10(-8), 10(-6 )mol/L) did not affect the proliferation of ovarian cancer cells. However, the high concentration of estrogen (10(-4 )mol/L) inhibited survival rate of ovarian cancer cells. Progesterone (10(-4 )mol/L) inhibited the proliferation of cancer cells. The combination of estrogen and progesterone significantly inhibited the survival rate of ovarian cancer cells with a time- and dose-dependent manner. High concentration of estrogen combined with progesterone (E(2) + P4) induced apoptosis of ovarian cancer cells. E(2) + P4 promoted the expression of let-7a and miR-34b and reduced the expression of Bcl-2 in ovarian cancer cells. When the expression of let-7a or/and miR-34b was inhibited using miRNA inhibitors, E(2) + P4 treatment did not change the protein level of Bcl-2. CONCLUSION: E(2) + P4 significantly inhibited the cell survival, promoted the cell apoptosis, induced the expression of let-7a and miR-34b, and reduced the expression of Bcl-2 in ovarian cancer cells.

Prognostic significance of TMPRSS4 in gastric cancer.

Transmembrane protease, serine 4 (TMPRSS4), is a novel type of II transmembrane serine protease that is highly expressed in multiple cancers. However the expression pattern and clinical significance of TMPRSS4 in gastric cancer (GC) remain unclear. We aimed to investigate the clinical and prognostic importance of TMPRSS4 in GC. We performed an analysis of TMPRSS4 expression in 200 consecutive GC patients by immunohistochemistry. Based on TMPRSS4 positivity, the GC tissues were divided into TMPRSS4-positive group and TMPRSS4-negative group. The relationships between TMPRSS4 expression and clinicopathological parameters or prognosis were explored.The positivity of TMPRSS4 expression was significantly higher in GC tissues than in adjacent normal tissues (44.5% versus 9.5%, P<0.001). TMPRSS4 positivity was significantly correlated with depth of invasion, lymph node metastasis, and vessel invasion (all p<0.01). Survival analysis indicated that the TMPRSS4-positive group showed poorer survival than the TMPRSS4-negative group (p<0.01). In terms of clinical stages, significantly different TMPRSS4 positivity was found only in stages II and III. Multivariate analysis showed that TMPRSS4 expression was an independent prognostic factor (p=0.013). Our data suggest that TMPRSS4 positivity is associated with GC invasion and lymph node metastasis. We propose TMPRSS4 expression as an indicator of poor prognosis in GC patients.

Endometrial cancer metastasize to the skin of lower leg and vagina: case report and literature review.

Endometrial cancer is the most frequent malignancy of the female reproductive system, while cutaneous metastasis is extremely rare in endometrial cancer. The authors herein report a case ofendometrial adenocarcinoma (FIGO Stage IIIC2, Grade 2) with metastasis to the skin of right lower leg and vaginal orifice. The patient was treated with local excision and combination chemotherapy, but she did not respond to therapy and died within 11 months. The authors reviewed the clinico-pathologic features, treatment, and prognosis of such case with cutaneous metastasis.

An antiapoptotic Bcl-2 family protein index predicts the response of leukaemic cells to the pan-Bcl-2 inhibitor S1.

BACKGROUND: Bcl-2-like members have been found to be inherently overexpressed in many types of haematologic malignancies. The small-molecule S1 is a BH3 mimetic and a triple inhibitor of Bcl-2, Mcl-1 and Bcl-XL. METHODS: The lethal dose 50 (LD(50)) values of S1 in five leukaemic cell lines and 41 newly diagnosed leukaemia samples were tested. The levels of Bcl-2 family members and phosphorylated Bcl-2 were semiquantitatively measured by western blotting. The interactions between Bcl-2 family members were tested by co-immunoprecipitation. The correlation between the LD(50) and expression levels of Bcl-2 family members, alone or in combination, was analysed. RESULTS: S1 exhibited variable sensitivity with LD(50) values ranging >2 logs in both established and primary leukaemic cells. The ratio of pBcl-2/(Bcl-2+Mcl-1) could predict the S1 response. Furthermore, we demonstrated that pBcl-2 antagonised S1 by sequestering the Bak and Bim proteins that were released from Mcl-1, andpBcl-2/Bak, pBcl-2/Bax and pBcl-2/Bim complexes cannot be disrupted by S1. CONCLUSION: A predictive index was obtained for the novel BH3 mimetic S1. The shift of proapoptotic proteins from being complexed with Mcl-1 to being complexed with pBcl-2 was revealed for the first time, which is the mechanism underlying the index value described herein.