The deubiquitinase OTUB2 promotes cervical cancer growth through stabilizing FOXM1.

OBJECTIVES: Ovarian tumor (OTU) domain-containing ubiquitin aldehyde-binding protein Otubain2 (OTUB2) is an important cysteine protease with deubiquitinase activity in the OTU family. However, the role of OTUB2 in cervical cancer (CC) has not been investigated. METHODS: OTUB2 expression was analyzed employing the CC data from The Cancer Genome Atlas (TCGA) database. Western blot and qRT-PCR analysis were performed to identify OTUB2 expression in CC. The oncogenic function of OTUB2 was identified through a series of in vitro and in vivo experiments. Tandem Mass Tag™ Quantitative Proteomics examination was used to identify potential targets of OTUB2. RESULTS: OTUB2 was overexpressed in CC and was related to poor prognosis of patients. In our in-house cohort, we also showed that OTUB2 was overexpressed in tumor tissues of CC compared to para-tumor. Knockdown of OTUB2 suppressed CC cell growth whereas OTUB2 upregulation fostered the proliferation of cancer cells. Forkhead box M1 (FOXM1) was found to be a target of OTUB2. FOXM1 can be positively regulated by OTUB2 in CC cells. In human CC tissues, protein level of FOXM1 was positively correlated with OTUB2. FOXM1 was found to play a critical role in OTUB2-mediated CC cell growth. Mechanistically, OTUB2 could bind FOXM1 and deubiquitinate FOXM1 to stabilize it. CONCLUSION: OTUB2 promotes CC progression through deubiquitinating and stabilizing FOXM1.

Efficacy of low-intensity pulsed ultrasound in the treatment of COVID-19 pneumonia.

PURPOSE: As a public health emergency of international concern, coronavirus disease 2019 (COVID-19) still lacks specific antiviral drugs, and symptomatic treatment is currently the mainstay. The overactivated inflammatory response in COVID-19 patients is associated with a high risk of critical illness or even death. Low-intensity pulsed ultrasound (LIPUS) can mitigate inflammation and inhibit edema formation. We aimed to investigate the efficacy of LIPUS therapy for COVID-19 pneumonia. MATERIALS AND METHODS: 62 patients were randomly assigned to a treatment group (LIPUS treatment area - Group 1; self-control area - Group 2) and an external control group (Group 3). The primary outcomes were the volume absorption rate (VAR) and the area absorption rate (AAR) of lung inflammation in CT images. RESULTS: After an average duration of treatment 7.2 days, there were significant differences in AAR and VAR between Group 1 and Group 2 (AAR 0.25 vs 0.12, p=0.013; VAR 0.35 vs 0.11, p=0.005), and between Group 1 and Group 3 (AAR 0.25 vs 0.11, p=0.047; VAR 0.35 vs 0.19, p=0.042). Neither AAR nor VAR was statistically different between Group 2 and Group 3. After treatment, C-reactive protein, interleukin-6, leukocyte, and fingertip arterial oxygen saturation (SaO2) improved in Group 1, while in Group 3 only fingertip SaO2 increased. CONCLUSION: LIPUS therapy reduced lung inflammation and serum inflammatory factor levels in hospitalized COVID-19 patients, which might be a major advancement in COVID-19 pneumonia therapy.

Three-dimensional pelvic ultrasound is a practical tool for the assessment of anal fistula.

OBJECTIVE: This study aims to investigate the diagnostic value of three-dimensional pelvic ultrasound in the preoperative assessment of anal fistula compared with findings of MRI and surgery. METHODS: A total of 67 patients (62 males) with suspected anal fistula were analyzed retrospectively. Preoperative three-dimensional pelvic ultrasound and magnetic resonance imaging were performed in all patients. The number of internal openings and the type of fistula were recorded. The accuracy of three-dimensional pelvic ultrasound was determined by comparing these parameters with surgical outcomes. RESULTS: At surgery, 5 (6%) were extrasphincteric, 10 (12%) were suprasphincteric, 11 (14%) were intersphincteric, and 55 (68%) were transsphincteric. There was no significant difference in the accuracy of pelvic 3D US and MRI, based on internal openings (97.92%, 94.79%), anal fistulas (97.01%, 94.03%), and those under Parks classification (97.53%, 93.83%). CONCLUSION: Three-dimensional pelvic ultrasound is a reproducible and accurate method for determining the type of fistula and detecting internal openings and anal fistulas.

Ultrasound image intelligent diagnosis in community-acquired pneumonia of children using convolutional neural network-based transfer learning.

Background: Studies show that lung ultrasound (LUS) can accurately diagnose community-acquired pneumonia (CAP) and keep children away from radiation, however, it takes a long time and requires experienced doctors. Therefore, a robust, automatic and computer-based diagnosis of LUS is essential. Objective: To construct and analyze convolutional neural networks (CNNs) based on transfer learning (TL) to explore the feasibility of ultrasound image diagnosis and grading in CAP of children. Methods: 89 children expected to receive a diagnosis of CAP were prospectively enrolled. Clinical data were collected, a LUS images database was established comprising 916 LUS images, and the diagnostic values of LUS in CAP were analyzed. We employed pre-trained models (AlexNet, VGG 16, VGG 19, Inception v3, ResNet 18, ResNet 50, DenseNet 121 and DenseNet 201) to perform CAP diagnosis and grading on the LUS database and evaluated the performance of each model. Results: Among the 89 children, 24 were in the non-CAP group, and 65 were finally diagnosed with CAP, including 44 in the mild group and 21 in the severe group. LUS was highly consistent with clinical diagnosis, CXR and chest CT (kappa values = 0.943, 0.837, 0.835). Experimental results revealed that, after k-fold cross-validation, Inception v3 obtained the best diagnosis accuracy, PPV, sensitivity and AUC of 0.87 ± 0.02, 0.90 ± 0.03, 0.92 ± 0.04 and 0.82 ± 0.04, respectively, for our dataset out of all pre-trained models. As a result, best accuracy, PPV and specificity of 0.75 ± 0.03, 0.89 ± 0.05 and 0.80 ± 0.10 were achieved for severity classification in Inception v3. Conclusions: LUS is a reliable method for diagnosing CAP in children. Experiments showed that, after transfer learning, the CNN models successfully diagnosed and classified LUS of CAP in children; of these, the Inception v3 achieves the best performance and may serve as a tool for the further research and development of AI automatic diagnosis LUS system in clinical applications. Registration: www.chictr.org.cn ChiCTR2200057328.

Renal blood perfusion in GK rats using targeted contrast enhanced ultrasonography.

OBJECTIVE: To explore application of targeted contrast enhanced ultrasonography in diagnosis of early stage vascular endothelial injury and diabetic nephropathy. METHODS: Targeted SonoVue-TM microbubble was prepared by attaching anti-TM monoclonal antibody to the surface of ordinary microbubble SonoVue by biotin - avidin bridge method and ultrasonic instrument was used to evaluate the developing situation of targeted microbubble in vitro. Twenty 12-week-old male GK rats and 20 Wistar rats were enrolled in this study, and were randomly divided into targeted angiography group and ordinary angiography group. Targeted microbubbles SonoVue-TM or general microbubble SonoVue were rapidly injected to the rats via tail vein; the developing situation of the two contrast agents in rats kidneys was dynamically observed. Time-intensity curve was used to analyze rat kidney perfusion characteristics in different groups. RESULTS: Targeted ultrasound microbubble SonoVue-TM was successfully constructed, and it could be used to develop an external image. Targeted microbubbles SonoVue-TM enabled clear development of experimental rat kidney. Time-intensity curve shapes of rat kidney of the two groups showed as single apex with steep ascending and slowly descending branch. Compared with the control group, the rising slope of the GK rat renal cortex, medulla in targeted angiography group increased (P < 0.05); the peak intensity of medulla increased (P < 0.05), and the total area under the curve of medulla increased (P < 0.05). Compared with control group, the ascending branch of the GK rat in renal cortex, medulla in ordinary angiography group increased (P < 0.05). The peak intensity of the curve increased (P < 0.05), and the total area under the curve increased (P < 0.05). Compared with the ordinary angiography group, the peak of GK rat medulla curve in targeted angiography group intensity increased (P < 0.05), and the total area under the curve increased (P < 0.05). CONCLUSIONS: Targeted microbubbles SonoVue-TM can make a clear development of experimental rat kidney, its stable performance meet the requirement of ultrasonic observation time limit, and it can reflect early changes of blood perfusion in GK rat kindey.

[Proportion and related influencing factors of HIV-infected individuals that rejecting the antiretroviral therapy among all the HIV infections, Dehong prefecture, Yunnan province].

OBJECTIVE: To examine the proportion and influencing factors on HIV-infected individuals who rejecting the antiretroviral therapy among all the HIV positives, in Dehong prefecture, Yunnan province. METHODS: A cross-sectional analysis was conducted on all the local HIV-infected survivals aged over 16 year old who refused to receive antiretroviral therapy (ART) by the end of 2013 in Dehong prefecture. RESULTS: The proportion of those rejecting the ART among HIV-infected survivals and aged over 16 years old in Dehong prefecture, was 7.4% (605/8 136). Factors related to the 'rejection' among the 605 refusals would include: being male (72.9%), aged 31-45 years (57.2%), peasants (75.4%), married (52.2%), with minor ethnicity (41.3%), illiterate or only having primary school education (58.7%), infected through sexual contacts (61.2%), and with CD4(+)T cell counts >350 cells/mm(3) (66.6%). Data from the multiple logistic regression analysis indicated that rejecting the ART was significantly associated with areas, gender, age, ethnicity and CD4(+)T cell counts of the HIV patients. Those who were from Yingjiang county, female, aged 31-45 years old had lower proportions of ART refusals than those who were from Ruili city, male, aged ≤30 year old. Those who were of Dai minority and had no records on CD4(+)T cell counts, had higher proportions of ART refusals than those who were of Han ethnicity and had CD4(+)T cell counts ≤350 cells/mm(3). Reasons for the 605 HIV-infected patients with rejection to the ART would include fear of disclosure of HIV infection status (84, 13.9%), misunderstandings of the effectiveness and side effects of ART (111, 18.3%), self-realized wellness(340, 56.2%) and others (70, 11.6%). Of them, reasons for the 181 patients with CD4(+)T cell counts ≤350 cells/mm(3) that rejecting ART would include fearfulness on the disclosure of HIV infection status(40, 22.1%), misunderstandings of the effectiveness and side effects of ART (36, 19.9%), self-realized wellness (84, 46.4%) and others (21, 11.6%). Among those who rejected ART, reasons for that would vary by areas, gender, age, marital status and routes of HIV transmission, according to the results from Chi-squared tests. CONCLUSION: A substantial proportion of HIV-infected individuals rejected ART in Dehong prefecture of Yunnan province. It was urgently needed to enhance health education programs of ART tailored for those HIV-infected patients, according to different characteristics and reasons for rejection, so as to promote the ART in this prefecture.

[Study on the mortality and risk factors among HIV-infected individuals during 1989 - 2011 in Dehong prefecture, Yunnan province].

OBJECTIVE: To examine the mortality and risk factors among HIV-infected patients during 1989 - 2011 in Dehong prefecture, Yunnan province. METHODS: All HIV-infected patients reported during 1989 - 2011 in Dehong prefecture who held local residency were included in the study. Mortality rates and cumulative survival rates were calculated. Multiple regression analysis under Cox proportional hazard model was conducted to examine the risk factors for deaths. RESULTS: A total of 13 006 HIV-infected patients were included in this study including 73.2% males, 79.1% peasants and 48.7% married at the time of reporting. 64.5% of the patients were ethnic minorities, and 68.7% were illiterate or having received only primary school education. All the patients were followed-up for a total of 55 962.30 person-years with 4648 patients died, with overall mortality rate as 8.31/100 person-years. The mortality rate had been increasing from 1990 to 2004 but decreasing since 2005. The average survival time since the identification of HIV infection was 9.48 years overall, and was 16.65 years for those having received antiretroviral treatment (ART) and 7.67 years for those without ART. Data from multiple regression analysis indicated that ART and socio-demographic characteristics such as age, gender, ethnicity, occupation, marital status, education background etc. were significantly associated with death among HIV-infected patients. CONCLUSION: The comprehensive AIDS campaigns including ART had significantly reduced the deaths among HIV-infected patients in Dehong prefecture. More efforts on the scaling up program of ART as well as the enhanced management and follow-up program tailored for HIV-infected patients with different socio-demographic characteristics were needed to further reduce the deaths in the area.

[Survey on contact tracing of newly reported HIV infections in 2009 in Dehong prefecture, Yunnan province].

OBJECTIVE: To explore a new method for finding more HIV/AIDS. METHODS: In September 2009, newly reported HIV-infected individuals from May to August, 2009 in Dehong prefecture were asked to participate in a survey which requested demographic characteristics, history of high-risk behaviors and contact information of individuals with whom they had high risky contacts. People with risky contacts with HIV-infected cases (index cases) were also approached to participate in this survey and HIV testing was provided. RESULTS: A total of 342 HIV-infected individuals were newly reported and served as index cases from May to August, 2009. Among them, 47.1% (161/342) were transmitted by regular sexual partners. Through three-round surveys, 218 contacts were traced and among them, 84.9% (185/218) were traced by regular heterosexual partners. HIV positive rate of the tested was 34.7% (60/173) in the first-round tracing and 12.5% (1/8) in the second one. Among the 560 individuals (index cases and their high-risk contacts), the proportions of having regular heterosexual partners, non-regular and non-commercial sexual partners, commercial sexual heterosexual partners and men having sex men were 87.9% (492/560), 18.9% (106/560), 22.3% (125/560) and 0.3% (1/318), respectively, while the proportion of having never used condoms when having sex with the above four types sexual partners were 73.8% (363/492), 72.6% (77/106), 63.2% (79/125) and 0.0% (0/1), respectively. CONCLUSION: As an epidemiological method for HIV/AIDS finding, contact tracing identified a large number of HIV infectors who were traced by newly reported HIV-infected individuals.

[Studies on the determinants and changes related to the natural CD4(+) T cell counts among antiretroviral treatment-naive HIV/AIDS patients in Dehong prefecture, Yunnan province].

OBJECTIVE: To explore the determinants and changes of CD4(+) T cell counts among antiretroviral treatment-naive HIV/AIDS patients in Dehong prefecture, Yunnan province. METHODS: A retrospective cohort analysis was conducted on HIV-infected local residents, being reported during 1989 through May 2010, in Dehong prefecture. The patients had received at least two CD4(+) T cell counting tests before receiving the antiretroviral treatment (ART). Difference between the first and the last CD4(+) T cell counts was calculated and described. Logistic regression analysis was conducted to examine the determinants of significant depletion of CD4(+) T cell counts among them. RESULTS: A total of 4487 HIV/AIDS patients were included in the study. The change of CD4(+) T cell counts between the first and the last CD4(+) T cell count tests had a median of -2.0 cells/µl in month (IQR: -8.2 - 3.6) and was significantly associated with socio-demographic characteristics, HIV transmission mode, the first or baseline CD4(+) T cell counts and the time interval between the first and the last CD4(+) T cell counting tests etc. About 60.0% (2693/4487) of the HIV/AIDS patients had deletions of CD4(+) T cell counts, and 31.2% (1400/4487) had significant (≥ 30%) deletions of CD4(+) T cell counts. Results from the multiple logistic regression analysis indicated that age, ethnicity, marital status, HIV transmission mode, the first CD4(+) T cell counts and the interval between the first and the last CD4(+) T cell counting tests were significantly associated with the significant depletion of CD4(+) T cell counts. CONCLUSION: The changing rate of CD4(+) T cell count among ART-naive local HIV-infected patients in Dehong prefecture, Yunnan province was relatively slow. However, substantial proportion of them showed significant decreases of CD4(+) T cell counts, which was determined by many factors. More efforts were needed to systematically and consistently follow-up those HIV-infected patients and measure their CD4(+) T cell counts in China, in order to instantaneously monitor the disease progression, and the initiation of ART, if necessary.

[Causes of death among HIV-infected patients in Dehong prefecture, Yunnan province: 1989-2010].

OBJECTIVES: To analyze the fatality and causes of death related to comprehensive prevention and care programs among HIV-infected patients in Dehong prefecture of Yunnan province, from 1989 to 2010. METHODS: Data on HIV/AIDS death cases in Dehong prefecture were extracted from the "Chinese National Comprehensive HIV/AIDS Prevention and Care Information System" and were analyzed. RESULTS: From 1989 to the end of 2010, a total of 13 493 HIV/AIDS cases registered as local residents or currently living in Dehong, had been reported. Among them, 8569 were reported as HIV cases with 2036 deaths and the other 4924 were reported as AIDS cases with 2251 deaths. A few of the cases had survived for 15 - 20 years. By the end of 2010, the number of deaths was higher than the number of survivors among HIV/AIDS cases reported before 2004, whereas the number of survivors was higher than the number of deaths among HIV/AIDS cases reported in 2004 and there after. During the twenty years' period, the proportion of reported HIV/AIDS cases died in the same year showed a secular trend of being low-highest-low, rising up to > 10.0% in 2001, peaking at 18.9% in 2003 and then continuously going down to 5.8% in 2010. The proportion of HIV/AIDS cases who survived at the beginning but died later in the year was going down since 2007. The proportion of HIV/AIDS deaths died directly from AIDS was increasing whereas the proportion of HIV/AIDS deaths dying directly from overuse of drugs was decreasing in the recent years. Among HIV/AIDS deaths, the proportion of ever received CD4(+) T-cell testing and the proportion of ever having received antiretroviral treatment were also increasing in the past years, reaching to 89.9% and 25.5% in 2010, respectively. CONCLUSION: The case fatality of HIV/AIDS was decreasing in the past years in Dehong prefecture. More efforts were needed to scale up the CD4(+) T-cell count testing and antiretroviral treatment in order to further reduce both morbidity and mortality among HIV/AIDS patients in Dehong prefecture. It is critical to improve surveillance program on HIV/AIDS deaths in the rural areas.

[Incidence and risk factors of HIV infection among sero-negative spouses of HIV patients in Dehong prefecture of Yunnan province].

OBJECTIVE: To study the HIV incidence and risk factors among sero-negative spouses of HIV patients in Dehong prefecture of Yunnan province. METHODS: A cohort of sero-negative spouses of the HIV patients had been developed and followed up since November, 2005. HIV new infections and related behaviors had been investigated every six months. RESULTS: By the end of June, 2008, 790 sero-negative spouses of HIV patients had been recruited, of whom 702 were followed-up for at least one time. During the total 1202.35 person-years, 31 new HIV infections were identified, with an overall incidence of 2.58/100 person-years. The HIV incidence rates were 2.22/100 person-years in 2006, 2.95/100 person-years in 2007 and 2.74/100 person-years in 2008. Data from the Cox proportional hazard regression model indicated that those who resided in Yingjiang county [hazard ratio (HR) = 4.37, 95%CI: 1.48 - 12.90, P = 0.008], ever using drugs (HR = 3.49, 95%CI: 1.09 - 11.18, P = 0.035), or having an HIV-infected spouse who never exposed to antiretroviral treatment (HR = 3.60, 95%CI: 1.41 - 9.16, P = 0.007) were at higher risk for HIV infection. CONCLUSION: Sero-negative spouses of HIV patients in Dehong prefecture of Yunnan province had a relatively high incidence of HIV new infection during 2006-2008. More efforts should put on those people living in these areas, having a history of drug use or having an HIV-infected spouse who had never been exposed to antiretroviral treatment.

[Tracing the sources of newly reported HIV infections in Dehong prefecture of Yunnan province].

OBJECTIVE: To trace and provide HIV-testing among those having contacts with HIV-infected individuals at various levels in Dehong prefecture, Yunnan province and to evaluate the effectiveness and feasibility of such investigation as a supplemental strategy for HIV testing and control. METHODS: Newly reported HIV infections from August throughout October in Dehong prefecture, in 2008 were asked to provide contact information of persons whom they had high risk contacts with. Persons having had risk contacts with HIV-infected cases were here of interviewed and their blood tested on the sero-status of HIV. RESULTS: A total of 335 HIV cases were newly reported during this three-month period. A total of 309 cases of them and 148 HIV infections identified thereafter from their risk contacts were under informed consent, to participate in this study. A total number of 3395 risk contacts were reported, of whom only 20.7% (704/3395) had 'contact information' and 51.3% (361/704) were successfully located and interviewed, including 117 previously confirmed HIV infections and 244 people with unknown HIV status. The majority of them (203 or 83.2% of 244) were then tested for HIV and 56 (27.6% of 203) were tested positive for HIV. The proportion of having detailed contact information and the proportion of being traced or followed among reported risk contacts of HIV infections were 68.8% and 68.2% for spouses of HIV patients, respectively, which were much higher than those among commercial sex partners (1.2% and 16.7%), casual sex partners (37.3% and 22.3%) and peers who sharing needles (34.1% and 56.4%). CONCLUSION: Newly reported HIV infections reported a large number of risk contacts and new HIV infections were identified among them. It was extremely difficult to trace commercial sex partners or casual sex partners on their HIV infection status. Nevertheless, tracing the risk contacts of newly reported HIV infections seemed to be helpful in identifying new HIV infections and in understanding the nature of transmission towards controlling the HIV epidemics.

[Application of automated identification and quantification system with a database (AIQS-DB) to screen organic pollutants in surface waters from Yellow River and Yangtze River].

Approximately 1 000 chemicals were screened in surface waters from downstreams of Yellow River and Yangtze River using GC-MS coupled with Automated Identification and Quantification System with a Database (AIQS-DB). 95 pollutants were detected in water samples from Yellow River in Shandong Province and 121 in those from Yangtze River in Jiangsu Province. The pollutants involved n-alkanes, PAHs, phenols, nitro compounds, phthalates esters (PAEs), pesticides and pharmaceuticals, etc. The average concentrations of n-alkanes, 16 priority PAHs and 6 priority PAEs were 1 806 ng/L, 27 ng/L, 77 ng/L in water samples from Yellow River and 720 ng/L, 30 ng/L, 2 166 ng/L in water samples from Yangtze River respectively. Besides, 9 and 11 pesticides were detected in water samples from Yellow River and Yangtze River respectively. The levels of pollutants showed stronger site dependence in samples from Yellow River than those from Yangtze River. Combination of GC-MS and AIQS-DB shows high efficiency in regional pollutants survey.

[Incidence and risk factors on HIV infection among injection drug users in Dehong prefecture area of Yunnan province].

OBJECTIVE: To determine the incidence and risk factors on HIV infection among injection drug users (IDU) in Dehong prefecture area of Yunnan province. METHODS: An epidemiological cohort of HIV-negative IDU had been developed and followed since October, 2004. HIV new infections and related behaviors had been investigated every six months. RESULTS: By the end of 2008, 760 HIV-negative IDU had been recruited and followed for a total of 1153.6 person-years. 47 new HIV infections were identified, with an overall incidence of 4.07/100 person-years during the follow-up period. The HIV incidence was 4.45/100 person-years during 2004 - 2006, 4.50/100 person-years in 2007 and 2.54/100 person-years in 2008. Both the behavior of drug injection and the HIV incidence among the cohort had substantially decreased during the follow-up period. Multiple regression analysis using Cox proportional hazard model indicated that people with Jing-po ethnicity (Hazard ratio, HR = 2.56, 95%CI: 1.06 - 6.19) and other minorities except for Dai (HR = 3.26, 95%CI: 0.89 - 11.96) were at higher risk for HIV infection than the people with Han ethnicity. People injecting drugs with (HR = 2.27, 95%CI: 0.98 - 5.25) or without (HR = 5.27, 95%CI: 2.25 - 12.34) needle sharing were at higher risk for HIV infection than those reporting having no drug injection behavior during the follow-up period. CONCLUSION: Both the behavior of drug injection and the HIV incidence among former IDU in Dehong prefecture area of Yunnan province had been decreasing during the four years. However, needle sharing remained the most important risk factor for HIV new infection among IDUs. IDUs with different ethnicities seemed to have different risks towards HIV infection.