Search

This retrospective cohort study investigated older people living with HIV/AIDS (PLWHA) characteristics, HIV care, and treatment outcomes among all cases between 1996 and 2019 in Guangxi, China. Secondary data were extracted from two national surveillance databases. Older (≥50 years old) and younger (18-49 years old) PLWHA were compared regarding demographic and behavioral characteristics, HIV care, virologic failure, and all-cause mortality. Older PLWHA accounted for 41.6% of all HIV cases (N = 144,952) between 1996 and 2019. The proportion of older cases increased from 10.4% to 64.8% for men and from 2.4% to 66.7% for women between 2002 and 2019. Heterosexual contact accounted for 96.0% of older adults. Moreover, older PLWHA had a lower median CD4 count at the HIV diagnosis (193 vs. 212 cells/μL, p  < 0.0001) and were less likely to receive antiretroviral therapy (ART) than younger adults (72.1% vs. 86.1%, p  < 0.001). The all-cause mortality risk of older PLWHA was 2.87 times of younger adults [adjusted hazard ratio (AHR) 2.87; 95% confidence interval (CI) 2.76-2.98]. In addition, older PLWHA reported an 18% increase in odds for virologic failure than younger adults (AOR 1.18; 95% CI 1.08-1.30). Therefore, enhanced HIV prevention and care are urgently needed in older people.

Objective: To determine the significance of the nasopharyngeal cavity area (S) in diagnosing and treating adenoid hypertrophy (AH) in children by measuring it with cone beam computed tomography (CBCT). Methods: A retrospective analysis was conducted on the clinical data of eighty-five 5- to 6-year-old children with AH admitted to the Department of Otorhinolaryngology at Dalian Central Hospital between January 2022 and April 2023. Of the 85 patients, 48 were male and 37 were female; all had been diagnosed with AH and underwent surgery. Sleeping with open-mouth breathing was frequently accompanied by clinical manifestations such as chronic sinusitis in most patients. Every patient was subjected to a CBCT examination of the nasopharynx and 3D airway reconstruction. The adenoid thickness (A) and nasopharyngeal cavity width (N) were measured in the sagittal plane, while the S was measured in the coronal plane. The factors that had a significant impact on S's size was analyzed using linear regression. Results: S and age, A, N, height, weight, BMI, allergic rhinitis, deviated nasal septum, and enlarged turbinate hypertrophy did not differ significantly ( P > .05). However, there was a significant linear relationship between A/N and chronic sinusitis ( R 2 = 0.948, P < .01). Regression equation: S = -4.115 × A/N × 100-5.037 × 1/0 (with chronic sinusitis/without chronic sinusitis) +418. 097. The calculated S in individuals with A/N = 70% and no chronic sinusitis was 130 mm 2 . Conclusion: The S can be used as an important imaging index for diagnosing and evaluating the severity of AH in minors. When a child exhibits clinical signs of AH but A/N ≤ 70%, it is difficult to determine whether surgical intervention is necessary. At this time, CBCT is required to measure the nasopharyngeal cavity's size. When S ≤ 130 mm 2 , the patient should actively undertake surgical treatment., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

What Is Already Known About This Topic?: The effects of concurrent human immunodeficiency virus (HIV)/hepatitis C virus (HCV) infection on mortality and patient attrition in those undergoing antiretroviral therapy continue to be a contested area of research., What Is Added by This Report?: According to the propensity score-matched cohort, individuals with HIV/HCV co-infection exhibit an elevated risk of all-cause mortality [adjusted hazard ratio: 2.048, 95% confidence interval ( CI ): 1.526-2.749] and attrition (adjusted incidence rate ratio: 1.659, 95% CI : 1.4.8-1.961) compared to their counterparts who are mono-infected with HIV., What Are the Implications for Public Health Practice?: The pressing need for tailored testing and follow-up protocols for individuals co-infected with HIV/HCV cannot be overstated., Competing Interests: No conflicts of interest., (Copyright and License information: Editorial Office of CCDCW, Chinese Center for Disease Control and Prevention 2023.)

Background: Adenoidal hypertrophy (AH) is one of the most common causes of upper airway obstruction in children. Drug and surgical treatment are the typical treatment of AH. The study on the inflammatory mechanism of AH in children provides a new idea for preoperative intervention and non-surgical treatment with anti-inflammatory drugs such as montelukast sodium (a cysteine leukotriene receptor antagonist). The aim of this study is to evaluate the effect of montelukast sodium on adenoidal lymphoid tissue pathology in children with AH under light microscope. Objective: To study whether there is any change in pathology of the adenoidal lymphoid tissue under the light microscope compared with the control group in children with moderate to severe simple AH treated with montelukast sodium for 1 month before operation. Materials and methods: Twenty patients (8 males, 12 females, 3-8 years old) with moderate to severe AH who were prepared for surgical treatment were selected. All the patients were examined by Nasopharyngeal CT and hemocyte analysis before operation. 20 subjects were randomly divided into two groups: One group was given montelukast chewable tablets 5 mg/d, qn, for 4 weeks; The control group was given placebo 5 mg/d, qn, for 4 weeks. After 4 weeks, the adenoids were removed and examined histopathology. Results: Compared with the control group, the number of lymphocytes in the blood cell analysis of the study group was significantly reduced, with a statistically significant difference ( p < 0.05). And the number of germinal centers in adenoid tissue of the study group was relatively reduced, no small cyst was found in the epithelium, and the degree of inflammatory cell infiltration was reduced, with a statistically significant difference ( p < 0.05). Conclusion: Montelukast can reduce the number of reactive cells, the number of lymphocytes in blood cells and blood vessels in adenoid lymphoid tissue, which can provide a new idea for preoperative intervention and non-surgical treatment of adenoid hypertrophy in children. However, this is only a pilot study and a longer treatment period is needed to assess the long-term effects of montelukast sodium on adenoid lymphoid tissue. Clinical Trial Registration : www.Chictr.org.cn, identifier ChiCTR2300075040., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Wang, Wu, Liu, Wang, Zhang, Wu, Kang, Zhang, Li and Liu.)

Introduction: A combination of zidovudine (AZT), lamivudine (3TC) and lopinavir/ritonavir (LPV/r) is one of the most effective drugs for preventing mother-to-child transmission (PMTCT) of HIV. However, limited information is available regarding its systemic toxicity. This study aimed to investigate its potential toxicity., Method: An acute oral toxicity test was conducted to assess the potential acute toxicity of AZT + 3TC + LPV/r. Bacterial reverse mutation, mammalian erythrocyte micronucleus and mouse spermatogonia chromosomal aberration tests were conducted to assess its potential genotoxicity. A 28-day feeding test was conducted to assess the potential subacute toxicity., Results: In mice, the LD 50 of the AZT + 3TC + LPV/r mixture was greater than 2000 mg/kg body weight (BW). The rate of micronucleated polychromatic erythrocytes (PCEs) increased in a dose-dependent manner in mice (P < 0.01). After treatment with AZT + 3TC + LPV/r for 28 days, the BW gain of male and female rats in the high-dose group was lower than that in the control group (P < 0.05); the relative weights of the liver, kidney, spleen and brain increased (P < 0.05); and pathological abnormalities appeared in the thyroid and spleen of male and female rats in the high-dose group. The haemoglobin (HGB) and red blood cells (RBCs) count in male and female rats decreased, but the white blood cells (WBCs) and lymphocyte apoptosis rates in male and female rats in the high-dose group increased (P < 0.05). The total protein, albumin, cholesterol and blood glucose levels of male and female rats in the high-dose group were significantly decreased (P < 0.05). The alanine aminotransferase (ALT), alkaline phosphatase (ALP), lactate dehydrogenase (LDH), creatinine (Cr) and blood urea nitrogen (BUN) levels of male and female rats in the medium- and high-dose groups increased significantly (P < 0.05)., Conclusion: The results suggest that AZT + 3TC + LPV/r may exhibit genotoxicity and subacute toxicity under experimental conditions., (© 2023 The Authors. Basic & Clinical Pharmacology & Toxicology published by John Wiley & Sons Ltd on behalf of Nordic Association for the Publication of BCPT (former Nordic Pharmacological Society).)

What Is Already Known About This Topic?: Migration has a significant impact on the transmission of human immunodeficiency virus (HIV). To date, there have been few studies examining the characteristics of migration among HIV-positive men who have sex with men (MSM)., What Is Added by This Report?: The prevalence of migrants among newly reported HIV-positive MSM in Guangxi Zhuang Autonomous Region increased from 2005 to 2021. Yulin Prefecture had the highest proportion of out-migrant MSM (12.6%), while Nanning Prefecture had the highest proportion of in-migrant MSM (55.9%). Risk factors associated with migration among MSM included being in the 18-24 age range, having a college education or higher, and being a student., What Are the Implications for Public Health Practice?: A complex prefecture-level network of HIV-positive MSM exists in Guangxi. To ensure effective follow-up management and antiretroviral therapy for migrant MSM, effective measures must be taken., (Copyright and License information: Editorial Office of CCDCW, Chinese Center for Disease Control and Prevention 2023.)

Background: Nearly one-third of new HIV infections occurred among youth in 2019 worldwide. Previous studies suggested that student youths living with HIV and nonstudent youths living with HIV might differ in some risk factors, transmission routes, HIV care, and disease outcomes., Objective: This study aimed to compare the HIV epidemic, disease outcomes, and access to care among student and nonstudent youths living with HIV aged 16 to 25 years in Guangxi, China., Methods: We performed a historical cohort study by extracting data on all HIV or AIDS cases aged 16 to 25 years in Guangxi, China, during 1996-2019 from the Chinese Comprehensive Response Information Management System of HIV or AIDS. We conducted analyses to assess possible differences in demographic and behavioral characteristics, HIV care, and disease outcomes between student and nonstudent youths living with HIV. Multivariate Cox regression was used to assess differences in mortality and virologic failure between student and nonstudent cases., Results: A total of 13,839 youths aged 16 to 25 years were infected with HIV during 1996-2019. Among them, 10,202 cases were infected through sexual contact, most of whom were men (n=5507, 54%); 868 (8.5%) were students, and 9334 (91.5%) were not students. The number of student youths living with HIV was lower before 2006 but gradually increased from 2007 to 2019. In contrast, the nonstudent cases increased rapidly in 2005, then gradually declined after 2012. Student cases were mainly infected through homosexual contact (n=614, 70.7% vs n=1447, 15.5%; P<.001), while nonstudent cases were more likely to be infected through heterosexual contact (n=7887, 84.5% vs n=254, 29.3%; P<.001). Moreover, nonstudent cases had a significantly lower CD4 count than student cases at the time of HIV diagnosis (332 vs 362 cells/μL; P<.001). Nonstudents also had a delayed antiretroviral therapy (ART) initiation compared to students (93 days vs 22 days; P<.001). Furthermore, the mortality rate of 0.4 and 1.0 deaths per 100 person-years were recorded for student and nonstudent youths with HIV, respectively. Overall, the mortality risk in nonstudent cases was 2.3 times that of student cases (adjusted hazard ratio [AHR] 2.3, 95% CI 1.2-4.2; P=.008). The virologic failure rate was 2.3 and 2.6 per 100 person-years among student and nonstudent youths living with HIV, respectively. Nonstudent cases had double the risk of virologic failure compared to student cases (AHR 1.9, 95% CI 1.3-2.6; P<.001)., Conclusions: Nonstudent youths living with HIV might face a low CD4 count at the time of HIV diagnosis, delayed ART initiation, and increased risk of death and virologic failure. Thus, HIV prevention and interventions should target youths who dropped out of school early to encourage safe sex and HIV screening, remove barriers to HIV care, and promote early ART initiation to curb the HIV epidemic among youths., (©Na Wang, Guanghua Lan, Qiuying Zhu, Huanhuan Chen, Jinghua Huang, Qin Meng, Zhiyong Shen, Shujia Liang, Xiuling Wu, Liuhong Luo, Rongyi Ye, Jinli Chen, Shengkui Tan, Hui Xing, Yiming Shao, Yuhua Ruan, Mei Lin. Originally published in JMIR Public Health and Surveillance (https://publichealth.jmir.org), 24.02.2023.)

The transport of the CagA effector into gastric epithelial cells by the Cag Type IV secretion system (Cag T4SS) of Helicobacter pylori (H. pylori) is critical for pathogenesis. CagA is recruited to Cag T4SS by the Cagβ ATPase. CagZ, a unique protein in H. pylori, regulates Cagβ-mediated CagA transport, but the underlying mechanisms remain unclear. Here we report the crystal structure of the cytosolic region of Cagβ, showing a typical ring-like hexameric assembly. The central channel of the ring is narrow, suggesting that CagA must unfold for transport through the channel. Our structure of CagZ in complex with the all-alpha domain (AAD) of Cagβ shows that CagZ adopts an overall U-shape and tightly embraces Cagβ. This binding mode of CagZ is incompatible with the formation of the Cagβ hexamer essential for the ATPase activity. CagZ therefore inhibits Cagβ by trapping it in the monomeric state. Based on these findings, we propose a refined model for the transport of CagA by Cagβ., (© 2023. The Author(s).)

Background: Currently, studies have shown that a high dose of radiotherapy to the throat have various harmful and adverse effects on the patients' laryngeal function, resulting in the development of pneumonia. This study aimed to explore how radiotherapy dose affected the probability of pneumonia following laryngeal cancer surgery., Materials and Methods: A retrospective analysis was done on patients diagnosed with laryngeal cancer between 2010 and 2020 and were treated surgically and with postoperative radiotherapy in the same institution. This study included 108 patients in total, 51 of who were in the low-dose group and 57 of whom were in the high-dose group. Age, gender, the location of laryngeal cancer, the presence or absence of lymph node metastasis, and other demographic and clinical characteristics were collected, and the prevalence of postoperative pneumonia was compared between the two groups., Results: The total prevalence of postoperative pneumonia was 59.3%, but there was a significant difference between the two groups(high-dose group 71.9% VS low-dose group 45.1%; p=0.005). A total of 9.3% (10/108) of the patients had readmission due to severe pneumonia, and the rate of readmission due to pneumonia was significantly different between the two groups (high-dose group 15.8% VS low-dose group 2.0%, p=0.032). Additionally, the high-dose group's prevalence of Dysphagia was significantly higher than the low-dose group's. According to multivariate logistic modeling, high-dose radiation was a risk factor for pneumonia (OR=4.224, 95%CI =1.603-11.131, p=0.004)., Conclusion: Pneumonia risk could increase with radiotherapy doses > 50 Gy in the treatment of laryngeal cancer. Therefore, we recommend that when the radiation dose surpasses 50Gy, doctors should pay particular attention to the lung health of patients with laryngeal cancer., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Lv, Wu, Wang, Wu, Ang, Cui, Shi, Wang and Liu.)

To study the molecular mechanism of salt stress response of peanut small GTP binding protein gene AhRabG3f , a 1 914 bp promoter fragment upstream of the start codon of AhRabG3f gene ( 3f -P) from peanut was cloned. Subsequently, five truncated fragments ( 3f -P1- 3f -P5) with lengths of 1 729, 1 379, 666, 510 and 179 bp were obtained through deletion at the 5' end, respectively. Plant expression vectors where these six promoter fragments were fused with the gus gene were constructed and transformed into tobacco by Agrobacterium -mediated method, respectively. GUS expression in transgenic tobacco and activity analysis were conducted. The gus gene expression can be detected in the transgenic tobacco harboring each promoter segment, among which the driving activity of the full-length promoter 3f -P was the weakest, while the driving activity of the promoter segment 3f -P3 was the strongest. Upon exposure of the transgenic tobacco to salt stress, the GUS activity driven by 3f -P, 3f -P1, 3f -P2 and 3f -P3 was 3.3, 1.2, 1.9 and 1.2 times compared to that of the transgenic plants without salt treatment. This suggests that the AhRabG3f promoter was salt-inducible and there might be positive regulatory elements between 3f -P and 3f -P3 in response to salt stress. The results of GUS activity driven by promoter fragments after salt treatment showed that elements included MYB and GT1 between 1 930 bp and 1 745 bp. Moreover, a TC-rich repeat between 682 bp and 526 bp might be positive cis -elements responsible for salt stress, and an MYC element between 1 395 bp and 682 bp might be a negative cis -element responsible for salt stress. This study may facilitate using the induced promoter to regulate the salt resistance of peanut.

As an emerging class of organic contaminants, polyhalogenated carbazoles (PHCZs) have been increasingly detected all over the world since 1980s. Due to the environmental persistence, bioaccumulation, and dioxin-like toxicity, PHCZs have aroused widespread concerns in recent years. However, efficient approach for the degradation of PHCZs is quite limited so far. Therefore, in this study, an advanced oxidation process (AOP), sulfidated zero-valent iron/peroxymonosulfate (S-ZVI/PMS) system was used to degrade 3-chlorocarbazole (3-CCZ), which is one of the mostly detected PHCZs congeners. The degradation of 3-CCZ was systematically studied under different conditions by varying the molar ratio of S/Fe, the dosage of S-ZVI or PMS, pH and temperature. The results indicated that S-ZVI/PMS was an effective strategy for PHCZs treatment. The 20-min degradation efficiency of 3-CZZ was up to 96.6% with the pseudo-first-order rate constant of 0.168 min -1 under the conditions of 5 mg/L 3-CZZ, 0.3 g/L S-ZVI (S/Fe = 0.2), 1.0 mM PMS, pH 5.8 and 25 °C. HCO 3 - , Cl - and humic acid (HA) showed inhibitory effects to different degrees. Results of the electron paramagnetic resonance (EPR) and scavenging experiments clarified the dominant role of •OH, followed by 1 O 2 and SO 4 •─ . The product analysis and DFT calculation revealed three degradation pathways of 3-CCZ, namely hydroxylation, dechlorination and C-N bond cleavage, which largely alleviated the toxicity of the parent compound. This study showed the effectiveness of S-ZVI/PMS system in PHCZs treatment and provided a comprehensive investigation on the degradation behaviors of PHCZs in AOPs., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

We investigated the mechanism of erythropoietin (EPO) in brain injury in premature mice based on Akt/mTOR/p70S6K signaling pathway. The brain injury model group of premature mice was obtained by intraperitoneal injection of lipopolysaccharide during pregnancy. Normal mice were taken as the control group. The model mice were divided into low-dose EPO (1,000 IU/kg, L-EPO), medium-dose EPO (2,500 IU/kg, M-EPO), and high-dose EPO groups (5,000 IU/kg, H-EPO) by intraperitoneal injection. The levels of malondialdehyde (MDA) and total superoxide dismutase (T-SOD) were detected. TUNEL staining and Western blotting were used to detect the differences in neuronal apoptosis index (AI), microglial polarization marker protein, and Akt/mTOR/p70S6K-related protein expression levels in each group. Compared with the control group, the protein levels of AI, MDA, Bax, and iNOS in the model, L-EPO, and M-EPO groups were significantly increased, while the T-SOD level and Bcl-2, ARG1, p-Akt, p-mTOR, and p-70S6K protein levels were significantly decreased ( P < 0.05). Compared with the model group, AI, MAD levels and Bax, iNOS protein expression levels in L-EPO, M-EPO, and H-EPO groups were significantly decreased, while T-SOD level and Bcl-2, ARG1, p-Akt, p-mTOR, and p-70S6K protein levels were significantly increased. The changes were dose-dependent. In summary, EPO can activate microglia transformation from M1 to M2 through Akt/mTOR/p70S6K signaling pathway.

Background and Study Aims: Helicobacter pylori infection affects approximately 50% of the global population and has become a serious health concern related to gastric cancer, gastritis, and peptic ulcers. This organism acquires drug resistance through gene mutations, and its increasing resistance to antibiotics has severely influenced the effectiveness of eradication efforts. Therefore, we designed this study to determine the prevalence of H. pylori virulence- (cagA and vacA) and antibiotic resistance - associated genotypes in patients with gastric cancer infected with H. pylori in Whenzhou, China., Patients and Methods: We used polymerase chain reaction (PCR) to confirm H. pylori in cancerous and paracancerous tissue specimens from 225 patients. Then we tested the prevalence of virulence- and antibiotic resistance - associated genotypes in H. pylori using a PCR-based DNA-sequencing assay., Results: We observed H. pylori DNA in 222 of the 225 patients and found the most prevalent virulence-associated genotypes in cagA + (97.75%) and vacAs1m1 (93.25%). Metronidazole resistance - associated gene mutation was G616A in rdxA; levofloxacin resistance - associated gene mutations were N87K, N87I, and D91G in gyrA; clarithromycin resistance - associated gene mutations were A2143G and A2142G in 23SrRNA; and amoxicillin resistance - associated gene mutation was T556S in pbp1. The most prevalent mutation related to antibiotic resistance was present in rdxA (97.30%), followed by gyrA (41.44%) and 23SrRNA (16.67%); the least prevalent was in pbp1 (2.25%). We observed single-gene mutations in 102 patients (45.95%) and found mutations in multiple genes (≥2 genes) in 116 patients (52.25%)., Conclusion: Patients with gastric cancer in Wenzhou, China, have high incidence infection caused by H. pylori with high-toxicity virulence genotypes. The frequency of gene mutations associated with metronidazole, levofloxacin, and clarithromycin resistances was high and that associated with amoxicillin resistance was relatively low. The mutation patterns were diverse, and the rates of multiple gene mutations were high., Competing Interests: Declaration of competing interests The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 Pan-Arab Association of Gastroenterology. Published by Elsevier B.V. All rights reserved.)

Background: Accurate diagnosis of intrahepatic cholangiocarcinoma (ICC) caused by intrahepatic lithiasis (IHL) is crucial for timely and effective surgical intervention. The aim of the present study was to develop a nomogram to identify ICC associated with IHL (IHL-ICC)., Methods: The study included 2,269 patients with IHL, who received pathological diagnosis after hepatectomy or diagnostic biopsy. Machine learning algorithms including Lasso regression and random forest were used to identify important features out of the available features. Univariate and multivariate logistic regression analyses were used to reconfirm the features and develop the nomogram. The nomogram was externally validated in two independent cohorts., Results: The seven potential predictors were revealed for IHL-ICC, including age, abdominal pain, vomiting, comprehensive radiological diagnosis, alkaline phosphatase (ALK), carcinoembryonic antigen (CEA), and cancer antigen (CA) 19-9. The optimal cutoff value was 2.05 µg/L for serum CEA and 133.65 U/mL for serum CA 19-9. The accuracy of the nomogram in predicting ICC was 82.6%. The area under the curve (AUC) of nomogram in training cohort was 0.867. The AUC for the validation set was 0.881 from The Second Affiliated Hospital of Wenzhou Medical University, and 0.938 from The First Affiliated Hospital of Fujian Medical University., Conclusions: The nomogram holds promise as a novel and accurate tool to predict IHL-ICC, which can identify lesions in IHL in time for hepatectomy or avoid unnecessary surgical resection., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://dx.doi.org/10.21037/hbsn-20-332). The authors have no conflicts of interest to declare., (2021 Hepatobiliary Surgery and Nutrition. All rights reserved.)

Background: Anti-IgLON5 antibody-related encephalopathy is a recently discovered and rare autoimmune disease, and its diagnosis and treatment are more challenging than for other autoimmune encephalopathic diseases. Sleep disorder is the most prominent symptom of the disease. It can also present with gait instability, dysarthria, dysphagia, dementia, ataxia, autonomic nervous system dysfunction, chorea, vertical gaze paralysis, and other symptoms. Immunotherapy remains the primary treatment for this disease; however, there is no definitive conclusion regarding the effect of immunotherapy. The clinical symptoms of the reported cases of anti-IgLON5 antibody-related encephalopathy were generally severe. However, the symptoms in our patient were mild and relieved without immunotherapy, unlike the previously reported cases., Case Presentation: A 62-year-old man presented with behavioural abnormalities and involuntary movements after nearly 2 months of fever and headache. He also had symptoms of mild sleep disorder. Due to the abnormal levels of infection-related indicators, antiviral treatment was started on the day of admission. The serum analysis confirmed the presence of IgLON5 antibody, and the patient was found to be genetically susceptible. The patient's symptoms resolved rapidly without immunotherapy and did not recur., Conclusions: This case demonstrated that IgLON5 antibody-related encephalopathy might have mild manifestations. Infection and a genetic predisposition may be important causes for the disease. Patients with a mild disease may have a better prognosis.

Background: The widespread use of antiretroviral therapy (ART) has resulted in the development of transmitted drug resistance (TDR), which reduces ART efficacy. We explored TDR prevalence and its associated risk factors in newly diagnosed individuals in Guangxi., Methods: We enrolled 1324 participants who were newly diagnosed with HIV-1 and had not received ART at voluntary counselling and testing centres (VCT) in Guangxi, China, who had not received ART. Phylogenetic relationship, transmission cluster, and genotypic drug resistance analyses were performed using HIV-1 pol sequences. We analysed the association of demographic and virological factors with TDR., Results: In total, 1151 sequences were sequenced successfully, of which 83 (7.21%) showed evidence of TDR. Multivariate logistic regression analysis revealed that there was significant difference between the prevalence of TDR and unmarried status (adjusted odds ratio (aOR) = 2.41, 95% CI: 1.23-4.71), and CRF08&#95;BC subtype (aOR = 2.03, 95% CI: 1.13-3.64). Most cases of TDR were related to resistance to non-nucleoside reverse transcriptase inhibitors (4.87%) and V179E was the most common mutation detected. We identified a total of 119 HIV transmission clusters (n = 585, 50.8%), of which 18 (15.1%) clusters showed evidence of TDR (36, 41.86%). Three clusters were identified that included drug-resistant individuals having a transmission relationship with each other. The following parameters were associated with TDR transmission risk: Unmarried status, educational level of junior high school or below, and CRF08&#95;BC subtype may be a risk of the transmission of TDR., Conclusions: Our findings indicated that moderate TDR prevalence and highlighted the importance of continuous TDR monitoring and designing of strategies for TDR mitigation.

The prevalence of HIV-1 in Guangxi is very high, and the rate of HIV-1 infection among men who have sex with men (MSM) has been increasing. Therefore, it is necessary to explore the patterns and risk factors of HIV transmission in Guangxi. For this purpose, individuals diagnosed with HIV-1 during 2013-2018 in Guangxi were recruited. Phylogenetic relationship, transmission clusters, and genotypic drug resistance analyses were performed based on HIV-1 pol sequences. Related factors were analysed to assess for their association with HIV-1 transmission. CRF07&#95;BC (50.4%) and CRF01&#95;AE (33.4%) were found to be the predominant subtypes. The analysed 1633 sequences (50.15%, Guangxi; 49.85%, other provinces) were segregated into 80 clusters (size per cluster, 2-704). We found that 75.3% of the individuals were in three clusters (size ˃ 100), and 73.8% were high-risk spreaders (links ≥ 4). Infection time, marital status, and subtype were significantly associated with HIV-1 transmission. Additionally, 80.2% of recent infections were linked to long-term infections, and 46.2% were linked to other provinces. A low level of transmitted drug resistance was detected (4.8%). Our findings indicated superclusters and high-risk HIV-1 spreaders among the MSM in Guangxi. Effective strategies blocking the route of transmission should be developed.

Background: This study was conducted with the intent to develop and validate a radiomic model capable of predicting intrahepatic cholangiocarcinoma (ICC) in patients with intrahepatic lithiasis (IHL) complicated by imagologically diagnosed mass (IM)., Methods: A radiomic model was developed in a training cohort of 96 patients with IHL-IM from January 2005 to July 2019. Radiomic characteristics were obtained from arterial-phase computed tomography (CT) scans. The radiomic score (rad-score), based on radiomic features, was built by logistic regression after using the least absolute shrinkage and selection operator (LASSO) method. The rad-score and other independent predictors were incorporated into a novel comprehensive model. The performance of the Model was determined by its discrimination, calibration, and clinical usefulness. This model was externally validated in 35 consecutive patients., Results: The rad-score was able to discriminate ICC from IHL in both the training group (AUC 0.829, sensitivity 0.868, specificity 0.635, and accuracy 0.723) and the validation group (AUC 0.879, sensitivity 0.824, specificity 0.778, and accuracy 0.800). Furthermore, the comprehensive model that combined rad-score and clinical features was great in predicting IHL-ICC (AUC 0.902, sensitivity 0.771, specificity 0.923, and accuracy 0.862)., Conclusions: The radiomic-based model holds promise as a novel and accurate tool for predicting IHL-ICC, which can identify lesions in IHL timely for hepatectomy or avoid unnecessary surgical resection., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Xue, Wu, Zheng, Jiang, Chen, Jiang, Tian, Tu, Zhao, Shen, Ramen, Wu, Zhang, Zeng and Zheng.)

The Arabidopsis thaliana BON1 gene product is a member of the evolutionary conserved eukaryotic calcium-dependent membrane-binding protein family. The copine protein is composed of two C2 domains (C2A and C2B) followed by a vWA domain. The BON1 protein is localized on the plasma membrane, and is known to suppress the expression of immune receptor genes and to positively regulate stomatal closure. The first structure of this protein family has been determined to 2.5-Å resolution and shows the structural features of the three conserved domains C2A, C2B and vWA. The structure reveals the third Ca 2+ -binding region in C2A domain is longer than classical C2 domains and a novel Ca 2+ binding site in the vWA domain. The structure of BON1 bound to Mn 2+ is also presented. The binding of the C2 domains to phospholipid (PSF) has been modeled and provides an insight into the lipid-binding mechanism of the copine proteins. Furthermore, the selectivity of the separate C2A and C2B domains and intact BON1 to bind to different phospholipids has been investigated, and we demonstrated that BON1 could mediate aggregation of liposomes in response to Ca 2+ . These studies have formed the basis of further investigations into the important role that the copine proteins play in vivo., (© 2020 Society for Experimental Biology and John Wiley & Sons Ltd.)

Objectives: To investigate the relationship between the lesion location and post-stroke restless legs syndrome (RLS)., Methods: A total of 376 patients with acute cerebral infarction were recruited from Tangshan Gongren Hospital, Department of Neurology between May 2016 and May 2017, all of whom were evaluated for RLS. Established RLS was diagnosed according to the criteria of the International Restless Legs Syndrome Study Group (IRLSSG) in 2012. Neurological functions were assessed according to the National Institutes of Health Stroke Scale (NIHSS). The lesion location was evaluated with magnetic resonance imaging (MRI). The associations between the lesion location and post-stroke RLS were then analyzed by logistic regression., Results: A total of 49 patients (13.03%) had RLS. The multivariate logistic regression model adjusting for post-stroke RLS risk factors including gender, age, history of hypertension, history of diabetes, history of stroke, smoking, drinking, body mass index (BMI), NIHSS, hemoglobin, platelet and homocysteine determined that body of caudate nucleus and pontine were significantly associated with post-stroke RLS with odds ratio (OR) of 26.26 (95% confidence interval (CI): 9.41-73.28,p < 0.001) and OR of 4.37 (95% CI: 1.24-15.34, p = 0.021). The stepwise logistic regression model with temporal lobe, parietal lobe, occipital lobe, frontal lobe, callosum, body of caudate nucleus, thalamus, lenticulo capsule, corona radiata, centrum semi-ovale and pontine as potential predictors yielded a predictor mode. The stepwise logistic regression predictor mode indicated that body of caudate nucleus and pontine predicted post-stroke RLS with similar OR to multivariate models of 23.61 (95% CI: 9.53-58.51, p < 0.001) and 4.46 (95% CI: 1.38-14.4, p = 0.012)., Conclusions: The ischemic infarcts located in body of caudate nucleus, pontine are significantly associated with post-stroke RLS. Body of caudate nucleus acute infarcts may play a role in the development of post-stroke RLS., (Copyright © 2019 Elsevier B.V. All rights reserved.)

The Teosinte branched 1/Cycloidea/Proliferating cell factor (TCP) domain is an evolutionarily conserved DNA binding domain unique to the plant kingdom. To date, the functions of TCPs have been well studied, but the three-dimensional structure of the TCP domain is lacking. Here, we have determined the crystal structure of the TCP domain from OsPCF6. The structure reveals that the TCP domain adopts three short β-strands followed by a helix-loop-helix structure, distinct from the canonical basic helix-loop-helix structure. This folded domain shows high structural similarity to the ribbon-helix-helix (RHH) transcriptional repressors, a family of DNA binding proteins with a conserved 3D structural motif (RHH fold), indicating that TCPs could be reclassified as RHH proteins. Our work will provide insight toward a better understanding of the mechanisms underlying TCP protein function., (© 2020 Federation of European Biochemical Societies.)

RGLG1 is an E3 ubiquitin ligase in Arabidopsis thaliana that participates in ABA signaling and regulates apical dominance. Here, we present crystal structures of RGLG1 VWA domain, revealing two novel calcium ions binding sites (NCBS1 and NCBS2). Furthermore, the structures with guided mutagenesis in NCBS1 prove that Ca 2+ ions play important roles in controlling conformational change of VWA, which is stabilized in open state with Ca 2+ bound and converted to closed state after Ca 2+ removal. This allosteric regulation mechanism is distinct from the ever reported one involving the C-terminal helix in integrin α and β I domains. The mutation of a key residue in NCBS2 do not abolish its Ca 2+ -binding potential, with no conformational change. MD simulations reveals that open state of RGLG1 VWA has higher ligand affinity than its closed state, consisting with integrin. Structural comparison of ion-free-MIDAS with Mg 2+ -MIDAS reveals that Mg 2+ binding to MIDAS does not induce conformational change. With acquisition of first structure of plant VWA domain in both open state and closed state, we carefully analyze the conformational change and propose a totally new paradigm for its transition of open-closed states, which will be of great value for guiding future researches on VWA proteins and their important biological significance., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2020 The Authors.)

The VirB/D type IV secretion system (T4SS) plays an essential role in materials transport between host cells and pathogenic Helicobacter pylori and is considered the major pathogenic mediator of H. pylori-associated gastric disease. VirB8, an inner membrane protein that interacts with many other proteins, is a crucial component for secretory function. Here, we present a crystal structure of the periplasmic domain of CagV, the VirB8 counterpart in the H. pylori Cag-T4SS. The structure reveals a fold similar to that of other VirB8 members except for the absence of the α5 helix, a discontinuous β1 strand, a larger angle between the α2 and α3 helices, a more hydrophobic surface groove, but exhibits a different dimer interface. Whether the dimerization occurs in solution was proved by mutagenesis, size-exclusion chromatography and cross-linking assays. Unlike the classical dimerization mode, the interface of the CagV dimer is principally formed by several hydrogen bonds, which indicates instability of dimerization. The structure here demonstrates the difference in dimerization among VirB8 homologues and indicates the considerable compositional and functional diversity of them in T4SS. DATABASE: Coordinates and structure factors have been deposited in the Protein Data Bank under accession codes 6IQT., (© 2019 Federation of European Biochemical Societies.)

Diffusion magnetic resonance imaging has been demonstrated to be a simple, noninvasive and accurate method for the detection of renal microstructure and microcirculation, which are closely linked to renal function. Moreover, serum endothelin-1 (ET-1) was also reported as a good indicator of early renal injury. The aim of this study was to evaluate the feasibility and capability of diffusion MRI and ET-1 to detect acute kidney injury by an operation simulating high-pressure renal pelvic perfusion, which is commonly used during ureteroscopic lithotripsy. Histological findings were used as a reference. Fourteen New Zealand rabbits in an experimental group and 14 in a control group were used in this study. Diffusion tensor imaging and intravoxel incoherent motion diffusion-weighted imaging were acquired by a 3.0 T MRI scanner. Significant corticomedullary differences were found in the values of the apparent diffusion coefficient (ADC), pure tissue diffusion, volume fraction of pseudo-diffusion (fp) and fractional anisotropy (FA) (P < 0.05 for all) in both preoperation and postoperation experimental groups. Compared with the control group, the values of cortical fp mean , medullary ADC mean and FA mean decreased significantly (P < 0.05) after the operation in the experimental group. Also, the change rate of medullary ADC mean in the experimental group was more pronounced than that in the control group (P = 0.018). No significant change was found in serum ET-1 concentration after surgery in either the experimental (P = 0.80) or control (P = 0.17) groups. In the experimental group, histological changes were observed in the medulla, while no visible change was found in the cortex. This study demonstrated the feasibility of diffusion MRI to detect the changes of renal microstructure and microcirculation in acute kidney injury, with the potential to evaluate renal function. Moreover, the sensitivity of diffusion MRI to acute kidney injury appears to be superior to that of serum ET-1., (© 2019 John Wiley & Sons, Ltd.)

The phosphate starvation response 1 (PHR1) protein has a central role in mediating the response to phosphate starvation in plants. PHR1 is composed of a number of domains including a MYB domain involved with DNA binding and a coiled-coil domain proposed to be involved with dimer formation. PHR1 binds to the promoter of phosphate starvation-induced genes to control the levels of phosphate required for nutrition. Previous studies have shown that both the MYB domain and the coiled-coil domain of PHR1 are required for binding the target DNA. Here, we describe the crystal structure of the PHR1 MYB domain and two structures of its complex with the PHR1-binding DNA sequence (P1BS). Structural and isothermal titration calorimetry has been carried out showing that the MYB domain of PHR1 alone is sufficient for target DNA recognition and binding. Two copies of the PHR1 MYB domain bind to the same major groove of the P1BS DNA with few direct interactions between the individual MYB domains. In addition, the PHR1 MYB-P1BS DNA complex structures reveal amino acid residues involved in DNA recognition and binding. Mutagenesis of these residues results in lost or impaired ability of PHR1 MYB to bind to its target DNA. The results presented reveal the structural basis for DNA recognition by the PHR1 MYB domain and demonstrate that two PHR1 MYB domains attach to their P1BS DNA targeting sequence. DATABASE: Coordinates and structure factors have been deposited in the Protein Data Bank under accession codes 6J4K (PHR1 MYB), 6J4R (PHR1 MYB-R-P1BS), 6J5B (MYB-CC-R2-P1BS)., (© 2019 Federation of European Biochemical Societies.)

In the era of personalized medicine, lung cancer is a typical disease which can be treated strategically based on the patient's histological and molecular diagnosis. Immunohistochemistry (IHC), fluorescence in-situ hybridization (FISH), Sanger sequencing and real-time PCR are techniques commonly used in clinical laboratories. Many patients are required to use several of the above technologies to get a complete diagnosis, which is expensive and timeconsuming. Next generation of sequencing (NGS) has the advantage to simultaneously analyze multigene mutations. The average cost for each patient is affordable if each run contains a certain number of samples. In this study, we tested a 10-gene, 32-mutation detection NGS method, which was used to test 195 samples from non-small cell lung cancer (NSCLC). Sanger sequencing and Amplification-refractory Mutation System (AMRS) PCR were employed to verify Epidermal Growth Factor Receptor (EGFR) and Anaplastic Lymphoma Kinase (ALK) results. This NGS method was partially proved to have a higher sensitivity to detect mutations with low abundance than Sanger sequencing and even ARMS PCR. Using genomic DNA to detect gene fusions may have some disadvantages to miss low abundance or large fragment fusions. As compared to using a few different technologies to analyze multigene mutations, small NGS analysis panel is a clinically applicable, efficient and affordable choice for NSCLC patients., (Copyright © 2019 Elsevier GmbH. All rights reserved.)

Gefitinib is effective for patients with non-small cell lung cancer (NSCLC) with a mutation in the epidermal growth factor receptor (EGFR) gene, which makes the detection of EGFR mutations a critical step prior to determining a treatment schedule. Therefore, the present study determined the EGFR mutation status in patients with NSCLC using an allele refractory mutation system (ARMS) and analyzed the detection ratio for different specimen types. A total of 1,596 NSCLS samples were collected and EGFR gene mutations were detected on exons 18-21 using ARMS and direct sequencing. The concordance of two methods reached 89.21%, with a total mutation rate of 45.55% (727/1,596), in which the mutation rate in lung adenocarcinoma samples was markedly increased compared with squamous cell carcinoma (51.77 vs. 8.68%). In patients with lung adenocarcinoma, EGFR mutations were more frequent in female patients than male patients (65.53 vs. 39.80%, P<0.01); there was no observable difference depending on age. Similar results were obtained for squamous cell carcinoma. In the present study, certain rare mutations were also identified; these may be subjects for further study. The impact of different sample types on the consistency between the methods was determined to be insignificant. ARMS is a more applicable approach for large-scale clinical detection than direct sequencing, and we hypothesize that ARMS may replace direct sequencing if the drawbacks of ARMS, including its narrow detection range, can be amended.

Background: Accurate preoperative diagnosis of intrahepatic cholangiocarcinoma (ICC) among patients with imagiologically intrahepatic lithiasis (IHL) complicated by mass is crucial for timely and effective surgical intervention. The aim of the present study was to develop a nomogram to identify ICC associated with IHL (IHL-ICC)., Patients and Methods: Data were obtained from a total of 252 consecutive patients with IHL complicated by mass. Multivariate logistic regression analysis was conducted to identify the clinicopathologic and imagiological characteristics that were potentially associated with ICC. A nomogram was developed based on the results of the multivariate analysis, and the value for prediction of ICC was assessed., Results: The study revealed six potential predictors for IHL-ICC, including comprehensive imagiological diagnosis, biliary tract operation history, fever, ascites, cancer antigen (CA) 19-9, and carcinoembryonic antigen (CEA). The optimal cutoff value was 3.75 μg/L for serum CEA and 143.15 U/mL for serum CA 19-9. The accuracy of the nomogram in predicting ICC was 78.5%. The Youden index provided a value of 0.348, corresponding to a cutoff of 95 points, with an area under the curve of 0.863., Conclusion: The nomogram holds promise as a novel and accurate tool in identifying IHL-ICC for hepatectomy, and in the differentiation of benign occupying lesions in IHL patients, resulting in the avoidance of unnecessary surgical resection., Competing Interests: Disclosure The authors report no conflicts of interest in this work.

Objectives: IgG4-related sclerosing cholangitis (IgG4-SC), a recently defined disease entity, has been classified into four types based on the stricture regions revealed by cholangiography. However, localized intrahepatic IgG4-SC is not included into the classification. This study aimed to analyze and characterize localized intrahepatic IgG4-SC and justify the inclusion of this type into the classification., Methods: PubMed and Embase were searched for studies published from March 2001 to June 2017 reporting localized intrahepatic IgG4-SC. Data were obtained and analyzed from the included articles., Results: Twelve cases of localized intrahepatic IgG4-SC were included. All patients were adults with the median age of 73 years (range 46-78), and had a male preponderance (88.9%). The most common clinical presentation was obstructive jaundice (50%), abdominal pain (25%) and absence of symptoms (25%). On imaging and macroscopically, localized intrahepatic IgG4-SC presented with three subtypes, i.e., mass-forming (n = 6, 50%), stricture (n = 5, 41.7%) and periductal infiltrating (n = 1, 8.3%) subtypes. Among the eight cases with diagnoses reported, six patients were misdiagnosed as intrahepatic cholangiocarcinoma; one was diagnosed as hepatic mass and one as IgG4-SC before biopsy or operation. Information on treatment was available on 10 cases; eight underwent surgical resection, one received steroid treatment alone and one underwent endoscopic biliary drainage. No relapse was noted in patients with surgical resection during a period of followed up., Conclusions: The localized intrahepatic IgG4-SC presents with mass-forming, stricture and periductal infiltrating subtypes, and should be recognized as an additional type of IgG4-SC according to the cholangiographic classification or anatomic site.

One clone (Lip906) exhibiting lipase activity was screened from a metagenomic library by using a medium containing tricaprylin. A novel lipase gene from the inserted fragment of Lip906 was obtained by sequencing. The phylogenetic analysis of Lip906 lipase exhibited 34% and 32% homologue to lipases from Streptomyces sp. MspMP-M5 and Rhodopirellula europaea. This gene was expressed in Escherichia coli (E. coli) BL21 (DE3), and the recombinant protein was purified and characterized. The best substrate of the recombinant Lip906 lipase was p-nitrophenyl myristate (C14). The lipase expressed maximum activity at 74°C and pH7.8, and it was found to be stable at pH values and temperatures ranging from 6.0-8.0 and 4-78°C, respectively. Furthermore, the lipase was found to be highly resistant to commercial detergent, DMSO, and EDTA, whereas its activity was stimulated in the presence of methanol and ethanol at low concentrations. The lipase showed enhanced activity in the presence of Hg 2+ , whereas the presence of the metal ions Fe 2+ , Ca 2+ , Co 2+ , and Mg 2+ inhibited the activity. These beneficial characteristics of Lip906 lipase provide some advantages for its potential application in industry., (Copyright © 2017. Published by Elsevier B.V.)

Previous studies have indicated that, in lung cancers, the gene rearrangement of ALK is mutually exclusive with mutations in the epidermal growth factor receptor ( EGFR ) gene. However, the coexistence of EML4-ALK fusions and EGFR mutations (double positive) has been occasionally reported, with frequencies ranging from 0-8%. Currently, no consensus standard therapy exists for tumors with double positive mutations. In the present case report, the case is described of a 53-year-old woman with stage IV lung adenocarcinoma, harboring a concomitant EGFR mutation and ALK gene rearrangement, who was refractory to gefitinib administration but demonstrated a good response to crizotinib and pemetrexed chemotherapy. A review of the literature revealed a total of 65 cases, including our case, harboring double positive mutations, and of these cases, 39 (60.0%) patients had received an EGFR tyrosine kinase inhibitor (EHGR-TKI), and 15 (23%) patients had received crizotinib treatment, the majority of whom had crizotinib selected for them as a second-line or third-line therapy. The disease control rate (DCR) of EGFR-TKI was 72.2%, with the progression-free survival (PFS) being 11.9 months, whereas the DCR of crizotinib was 93.3%, with the PFS being 10 months.

A bioinspired photocatalytic nanocomposite membrane was successfully prepared via polydopamine (pDA)-coated poly(vinylidene fluoride) (PVDF) membrane, as a secondary platform for vacuum-filtrated Au-TiO 2 nanocomposites, with enhanced photocatalytic activity. The degradation efficiency of Au-TiO 2 /pDA/PVDF membranes reached 92% when exposed to visible light for 120 min, and the degradation efficiency of Au-TiO 2 /pDA/PVDF membranes increased by 26% compared to that of Au-TiO 2 powder and increased by 51% compared to that of TiO 2 /pDA/PVDF nanocomposite membranes. The degradation efficiency remained about 90% after five cycle experiments, and the Au-TiO 2 /pDA/PVDF nanocomposite membranes showed good stability, regeneration performance, and easy recycling. The pDA coating not only served as a bioadhesion interface to improve the bonding force between the catalyst and the membrane substrate but also acted as a photosensitizer to broaden the wavelength response range of TiO 2 , and the structure of Au-TiO 2 /pDA/PVDF also improves the transfer rate of photogenerated electrons; the surface plasmon resonance effect of Au also played a positive role in improving the activity of the catalyst. Therefore, we believe that this study opens up a new strategy in preparing the bioinspired photocatalytic nanocomposite membrane for potential wastewater purification, catalysis, and as a membrane separation field.

GRAS proteins belong to a plant-specific protein family with many members and play essential roles in plant growth and development, functioning primarily in transcriptional regulation. Proteins in the family are minimally defined as containing the conserved GRAS domain. Here, we determined the structure of the GRAS domain of Os-SCL7 from rice (Oryza sativa) to 1.82 Å. The structure includes cap and core subdomains and elucidates the features of the conserved GRAS LRI, VHIID, LRII, PFYRE, and SAW motifs. The structure is a dimer, with a clear groove to accommodate double-stranded DNA. Docking a DNA segment into the groove to generate an Os-SCL7/DNA complex provides insight into the DNA binding mechanism of GRAS proteins. Furthermore, the in vitro DNA binding property of Os-SCL7 and model-defined recognition residues are assessed by electrophoretic mobility shift analysis and mutagenesis assays. These studies reveal the structure and preliminary DNA interaction mechanisms of GRAS proteins and open the door to in-depth investigation and understanding of the individual pathways in which they play important roles., (© 2016 American Society of Plant Biologists. All rights reserved.)

Human DAB2 interaction protein (DAB2IP) is a member of Ras-GTPase activating protein family and functions as a tumor suppressor, implying it could serve as a prognostic biomarker in cancers. Here we generated a mouse monoclonal antibody, 2A4, directed against human DAB2IP. This antibody was identified as IgG1 and specifically recognizes DAB2IP in both its native and denatured forms. It will serve as a useful and versatile tool for further mechanistic study and development of the potential prognostic significance of DAB2IP.

Bladder cancer (BCa) is the most common tumor of the urinary system. Chronic inflammation in the papillary urothelial neoplasm of low malignant potential (PUNLMP)may contribute to carcinogenesis, including that of BCa, via poorly understood mechanisms. In this study, we show that the lymphotoxin β receptor (LTβR) is upregulated in BCa via activation of the canonical and non-canonical nuclear factor-κB (NF-κB) pathways. The mRNA expression of LTβR in 81 BCa, 10 chronic cystitis and 23 healthy bladder mucosa tissues was investigated by reverse transcription-fluorescent quantitative polymerase chain reaction (RT-FQ-PCR), and protein expression was studied in 73 BCa, 30 cystitis and 15 healthy paraffin-embedded tissue sections by immunohistochemistry. Both LTβR mRNA and protein were upregulated in BCa and cystitis compared to the healthy group (P<0.05). The mRNA level of the downstream NF-κB canonical pathway p65 gene and of the non-canonical pathway RelB gene were higher in the BCa and cystitis groups compared to the healthy one. The level of phosphorylated p65 (p-p65) protein of the canonical NF-κB pathway and that of p52, a protein of the non-canonical NF-κB pathway, were also higher in the BCa and cystitis group compared to the healthy group. The levels of these proteins significantly correlated to the pathological grade, clinical stage and lymph node metastasis of BCa patients (P<0.05). In addition, there was a positive correlation between LTβR and NF-κB pathway proteins. Thus, LTβR signaling may be involved in promoting BCa through the NF-κB pathway, and which may represent the molecular link between inflammation and BCa.

We report an extremely rare case of an unruptured non-communicating rudimentary horn full-term pregnancy. A woman who had a uterine malformation was misdiagnosed as uterus didelphys and gave birth to a live, healthy fetus. The correct diagnosis was not made until cesarean section at 37 4/7 weeks. The case suggests that women who are pregnant in a rudimentary horn could obtain a full-term delivery and give birth to a live and healthy baby.

Purpose: To investigate the expressions of FOXP1, hypoxia inducible factor (HIF)-1a and vascular endothelial growth factor (VEGF) in renal cell carcinoma of the clear type (CCRCC) and their relationship with the patient clinicopathological features., Methods: The expressions of forkhead box-P1 (FOXP1), HIF-1a and VEGF in 55 cases of CCRCC tissues were determined using immunohistochemistry. Then, their correlations with clinical stage, histological grade and lymph node metastasis were analyzed using chi-square test., Results: Thirty-seven of the 55 cases (67.3%) of CCRCC expressed FOXP1 with an abnormal expression rate of 38.2% (21/55), in which there were 10 cases with positive FOXP1 both in the nucleus and the cytoplasm and 11 cases with positive FOXP1 in cell membrane. The abnormal expression rate of FOXP1 inhigh grade CCRCC (G3/G4) was significantly higher than that in low grade CCRCC (G1/G2, p<0.05). FOXP1 expression was significantly correlated with the expression of HIF1 and VEGF (r=0.54, p<0.01 and r=0.37, p<0.05, respectively), but was not obviously correlated with clinical stage, lymph node metastasis and 5-year overall patient survival (p>0.05)., Conclusion: Abnormal expression of FOXP1 and its deficiency are common events in CCRCC. Abnormal expression of FOXP1 may create progression of tumor from low grade to high grade by regulating the HIF-1-VEGF pathway.

Introduction: Long noncoding RNA prostate cancer gene antigen 3 (PCA3) is one of the most prostate cancer-specific genes at present. Consequently, the prostate-specific expression and the sharp up-regulation of PCA3 RNA in prostate cancer suggest a unique transcriptional regulation, which possibly can be attributed to promoter polymorphism. In this study, we investigated a short tandem repeat (STR) polymorphism of TAAA in the promoter region of PCA3 gene found in our previous study in prostate cancer (PCa) patients and benign prostatic hypertrophy (BPH) patients, aiming to evaluate the association between the STR and increased risk for PCa., Material and Methods: 120 PCa cases and 120 benign prostatic hypertrophy (BPH) cases were identified among participants. The region encompassing the TAAA repeat was amplified with a specific primer set we designed and screened by PCR-based cloning and sequencing in paired peripheral blood leukocytes and prostate tissues. Genotype-specific risks were estimated as odds ratios (ORs) associated with 95% confidence intervals (CIs) and adjusted for age by means of unconditional logistic regression., Results: 5 PCA3 TAAA STR polymorphisms and 8 genotypes were found in both peripheral blood leukocytes and prostate tissues, the carriers with more TAAA repeats were associated with increased risk for PCa than individuals having less TAAA repeats. Interestingly, 18 (15.0%) of 120 PCa patients had more (TAAA)n repeats in prostate tissues than that in peripheral blood leukocytes, and 3 (2.5%) of 120 had less (TAAA)n repeats in prostate tissues., Conclusions: The results of this study suggest that short tandem repeat polymorphism of TAAA in the promoter region of PCA3 gene is a risk-increasing factor for prostate cancer in the Chinese population. In addition to the hereditary factor, the insertion mutation of (TAAA)n in a local tissue maybe another mechanism of the onset of PCa., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Background: Risk factors of anxiety and depression symptoms in patients with chronic obstructive pulmonary disease (COPD) have been widely researched, but most of them cannot be addressed clinically. The aim of this study was to investigate whether COPD knowledge level is a risk factor of anxiety and/or depression in COPD patients in addition to functional capacity and quality of life, and to determine the key topics of COPD knowledge., Methods: A total of 364 COPD patients from four centers were recruited into this cross-sectional survey. Subjects' general medical information, assessments of lung function, dyspnea, quality of life, and exercise capacity, and responses to the Hospital Anxiety and Depression Scale (HAD) and the Bristol COPD Knowledge Questionnaire (BCKQ) were collected. Partial correlation analysis was performed, and a multivariable model testing risk factors of anxiety and depression as well as a multivariable model of 13 topics of knowledge derived from BCKQ were constructed., Results: Subjects with anxiety or depression were more likely to have less COPD knowledge. Partial correlation analysis revealed that HAD score was negatively correlated with BCKQ score (rho = -0.153, P = 0.004). BCKQ score was significant in the multivariable model that tested risk factors of anxiety and depression (P = 0.001, OR = 0.944). Topics of epidemiology (P < 0.001, OR = 0.653) and infections (P = 0.006, OR = 0.721) were significant in the multivariable model evaluating 13 topics., Conclusions: The level of patients' disease knowledge is a significant risk factor of anxiety and depression in COPD patients. Epidemiology and infections are key topics of COPD knowledge to target in the Chinese population., Trial Registration: ChiCTR-OCS-12002518.

Objective: To investigate the expression of Jade-1 and β-catenin and their effect in the development of renal cell carcinoma (RCC)., Methods: The expression of Jade-1 and β-catenin in 11 normal kidney tissue specimens (normal group) and 60 RCC specimens (RCC group) was determined using real-time polymerase chain reaction and immunohistochemistry. Also, their effect on early relapses of RCC was analyzed after 5 years of follow-up., Results: The expression of Jade-1 protein in the RCC group was significantly lower than that in the normal group (0.1655 vs 0.7438, P < .05), and the expression of β-catenin protein was significantly greater than that in the normal group (0.2756 vs 0.0855, P < .05). The expression of Jade-1 mRNA in the RCC group was 0.202 times that in the normal group, which were lower (P < .05). The expression of β-catenin mRNA was 1.014 times that in the normal group (P > .05). The expression of Jade-1 protein and β-catenin protein in poorly differentiated RCC specimens was significantly lower and higher than the expression in the well-differentiated RCC specimen (P < .05), respectively. Patients with negative Jade-1 expression and positive β-catenin expression were found to have shorter survival on univariate analysis (P < .05)., Conclusion: RCC with a low expression of Jade-1 and high expression of β-catenin is associated with a poor outcome and decreased survival., (Copyright © 2012. Published by Elsevier Inc.)

Prostate cancer gene 3 (PCA3) encodes a prostate-specific mRNA that has shown promise as a prostate cancer (PCa) diagnostic tool and is detectable in prostate cancer cells shedding into urine after digital rectal examination (DRE). In our earlier studies, a tissue test for PCA3 appeared to have greater specificity for PCa. There, we performed a clinical evaluation of PCA3 mRNA assay in urine sediments after DRE enriched with prostate cells in a Chinese population. PCA3 mRNA was detected by real-time fluorescent quantitative reverse transcription-polymerase chain reaction (FQ-RT-PCR) in the urine sediments. PSA mRNA detected also by real-time FQ-RT-PCR was used to confirm the yield of prostate cells in the urine sediments beforehand and normalize PCA3 mRNA signals. The data were summarized in a receiver operating characteristic (ROC) curve to visualize the efficacy of ratio PCA3/PSA mRNA as a marker; sensitivity and specificity were calculated also. We also correlated the ratio PCA3/PSA mRNA to the biopsy results (including the presence or absence of malignancy and the Gleason score of the malignancy cases) and to the bone metastasis to evaluate its clinical value. The PCA3 mRNA expression (PCA3/PSA mRNA) in the PCa group was significantly higher than that in the BPH group. The AUC-ROC was 0.786 (95% CI: 0.683-0.889). When the cutoff value was set as 0.107, the sensitivity and specificity were 62.9% and 90.6%, respectively. The positive predictive value and negative predictive value of the PCA3 urine test was 78.6% and 81.7%, respectively. No significant correlation was found between urine PCA3 expression and Gleason score or bone metastasis. Results indicated the clinical usefulness of the PCA3/PSA mRNA of urine sediments after DRE as a molecular marker in the early diagnosis of prostate cancer, which appears to be highly specific for PCa. As a non-invasive and sample accessible assay, the PCA3/PSA mRNA may therefore be useful as an aid in the diagnosis of PCa., (Copyright © 2010 Elsevier Inc. All rights reserved.)

Background: PCA3 (prostate cancer antigen 3) gene is one of the most prostate cancer-specific genes at present. Consequently, the prostate-specific expression and the sharp up-regulation of PCA3 mRNA in prostate cancer suggest a unique transcriptional regulation, which possibly can be attributed to promoter polymorphism. In our study, we evaluated whether there is polymorphism in PCA3 promoter region and also assess the association of the polymorphism with prostate cancer., Methodology/principal Findings: We designed a specific primer set to screen the promoter of PCA3 gene by polymerase chain reaction (PCR)-based cloning and sequencing with the DNA extracted from peripheral blood samples of prostate cancer (PCa) cases (n = 186) and healthy control cases (n = 135). Genotype-specific risks were estimated as odds ratios (ORs) with associated 95% confidence intervals (CIs) by chi-square test. Possible deviation of the genotype frequencies from controls and PCa cases expected under Hardy-Weinberg equilibrium was assessed by the chi-square test. Short tandem repeat polymorphism of TAAA was found in the promoter region of PCA3 gene, five polymorphisms and eight genotypes were identified. The eight genotypes were divided into three groups: ≤10TAAA, 11TAAA, ≥12TAAA. The group 11TAAA and ≥12TAAA were associated with higher relative risk for prostate cancer than group ≤10TAAA (OR = 1.76, 95%CI = 1.07-2.89[for group 11TAAA]; OR = 5.28, 95%CI = 1.76-15.89[for group ≥12TAAA])., Conclusions/significance: The presence of the (TAAA)n short tandem repeat polymorphisms in the PCA3 promoter region may be a risk factor for prostate cancer in the Chinese population.

Prostate cancer (PCa) is the second most common cancer in men, and its incidence is still increasing. PCA3 is the most prostate cancer specific biomarker. Here we confirmed that both exon 3 and exon 4 are in the prostate-specific region of the PCA3 gene, and established the methodology of real-time fluorescent quantitative RT-PCR (FQ-RT-PCR) detecting PCA3 mRNA with primer spanning exons 1 and 3, and evaluated its clinical utility in a Chinese population. What disclosed that PCA3 mRNA is prostate cancer specific and shows increased expression in prostate cancer. It could be a reliable molecular marker in prostate cancer diagnosis. Exon 3-based real-time FQ-RT-PCR may prove useful in prostate cancer diagnosis, given that the associated primer would span only exons 1 and 3, relative to other models spanning exons 1 to 4. A shorter amplicon would not only enhance the efficiency of real-time FQ-RT-PCR, but may also simplify the quantification of PCA3 mRNA., (Copyright 2010. Published by Elsevier Inc.)