Astragaloside IV inhibits the proliferation, migration, invasion, and epithelial-mesenchymal transition of oral cancer cells by aggravating autophagy.

Oral cancer is one usual tumor that sorely affects the health of people and even result into death. Astragaloside IV (AS-IV) is one of the major components of Astragalus membranaceus extract, and has been identified to exhibit ameliorative functions in some cancers. Nevertheless, the regulatory impacts and correlative pathways of AS-IV in oral cancer remain vague. In this study, it was discovered that cell growth was gradually weakened with the increased dose of AS-IV (25, 50 and 100 µM). Additionally, it was uncovered that AS-IV restrained the EMT progress in oral cancer. The cell migration and invasion abilities were both gradually alleviated after AS-IV treatment in a dose-dependent manner. Moreover, AS-IV accelerated autophagy through intensifying LC3II/LC3I level and LC3B fluorescence intensity. At last, it was clarified that AS-IV triggered the AMPK pathway and retarded the AKT/mTOR pathway. In conclusion, AS-IV restrained cell proliferation, migration, invasion, and epithelial-mesenchymal transition (EMT) progress in oral cancer by aggravating autophagy through modulating the AMPK and AKT/mTOR pathways. This work may offer novel evidence on AS-IV in the treatment of oral cancer.

The impact of the COVID-19 pandemic on HIV treatment gap lengths and viremia among people living with HIV British Columbia, Canada, during the COVID-19 pandemic: Are we ready for the next pandemic?

The SARS-CoV-2 (COVID-19) pandemic has impacted the care of people living with HIV (PLWH). This study aims to characterize the impact of the pandemic on the length of HIV treatment gap lengths and viral loads among people living with HIV (PLWH) in British Columbia (BC), Canada, with a focus on Downtown Eastside (DTES), which is one of the most impoverished neighbourhoods in Canada. We analyzed data from the HIV/AIDS Drug Treatment Program from January 2019 to February 2022. The study had three phases: Pre-COVID, Early-COVID, and Late-COVID. We compared results for individuals residing in DTES, those not residing in DTES, and those with no fixed address. Treatment gap lengths and viral loads were analyzed using a zero-inflated negative binomial model and a two-part model, respectively, adjusting for demographic factors. Among the 8982 individuals, 93% were non-DTES residents, 6% were DTES residents, and 1% had no fixed address during each phase. DTES residents were more likely to be female, with Indigenous Ancestry, and have a history of injection drug use. Initially, the mean number of viral load measurements decreased for all PLWH during the Early-COVID, then remained constant. Treatment gap lengths increased for all three groups during Early-COVID. However, by Late-COVID, those with no fixed address approached pre-COVID levels, while the other two groups did not reach Early-COVID levels. Viral loads improved across each phase from Pre- to Early- to Late-COVID among people residing and not residing in DTES, while those with no fixed address experienced consistently worsening levels. Despite pandemic disruptions, both DTES and non-DTES areas enhanced HIV control, whereas individuals with no fixed address encountered challenges. This study offers insights into healthcare system preparedness for delivering HIV care during future pandemics, emphasizing community-driven interventions with a particular consideration of housing stability.

Structural family factors and bullying at school: a large scale investigation based on a Chinese adolescent sample.

BACKGROUNDS: Various family factors have been identified in association with school bullying and the involvement of children and adolescents in bullying behaviors. METHODS: A total of 11,919 participants (female = 6671, mean age = 15) from 22 middle schools in Suzhou City, China completed the questionnaire. The associations between structural family factors (family socio-economic status, living arrangement, number of siblings, whether they were local residents/migrants, had an urban/rural hukou [a household registration system in China], parental and maternal education levels, and other various bullying-related constructs (i.e. bullying witnessing, bullying involvement, bystander intervention, and fear of being bullied) were all examined. Odds ratios (ORs) adjusted for covariates were calculated for the four bullying-related constructs (bullying witness, bullying involvement, bystander intervention, and reactions to being bullied) using structural family factors. RESULTS: The result showed that all demographic household characteristics were associated with bullying at school except for being from a single-child family. Adolescents from rural families witnessed more bullying incidents than those from local families (OR = 1.35, 95% CI: [1.09, 1.68]). Adolescents who come from migrant families (OR = 1.12, 95% CI: [1.07, 1.43]) with a rural hukou (OR = 1.31, 95% CI: [1.00, 1.74]) and low parental education levels (OR = 1.42, 95% CI: [1.01, 2.57]) were more likely to be bullies. Adolescents who came from migrant families (OR = 1.37, 95% CI: [1.03, 1.82]), with low maternal education levels (OR = 1.42, 95% CI: [1.06, 1.91]) engaged in more negative bystander intervention behaviors. Furthermore, adolescents with less educated mothers experienced a higher fear of being bullied (never versus sometimes: OR = 1.33, 95% CI: [1.00, 1.85]; never versus usually OR = 1.39, 95% CI: [1.01, 1.20]). CONCLUSIONS: A systematic examination of the relationship between school bullying and demographic household characteristics may be used to inform school policies on bullying, such as training management on the importance of paying attention to adolescents from disadvantage household backgrounds. Identifying demographic factors that may predict bullying can also be used to prevent individuals from becoming involved in bullying and reduce the related negative consequences from being bullied.

Mental Health Status of Cisgender and Gender-Diverse Secondary School Students in China.

Importance: Transgender or gender nonconforming (TGNC) adolescents face a wide range of physical and mental health concerns. However, there has been no school-based study to explore the prevalence and mental health status of these adolescents in mainland China. Objectives: To assess the mental well-being of TGNC adolescents in China by comparing them with their cisgender peers. Design, Setting, and Participants: This was a cross-sectional survey study. Of the 12 354 adolescents who completed the questionnaire, 246 did not specify to which sex they identified and were therefore excluded from further analysis. Therefore, a total of 12 108 adolescents were included from 18 secondary schools in Suzhou city, China, from June 2019 to July 2019. Participants provided consent and answered questions on sex assigned at birth and gender identity. Main Outcomes and Measures: All participants completed questionnaires, including the Patient Health Questionnaire for the measurement of depressive symptoms, a generalized anxiety disorder screening, the Pittsburgh Sleep Quality Index, and a self-harm and suicide risk checklist. The frequency of being bullied at school was also measured. Participants who reported their perceived gender as the opposite of their assigned sex at birth were classified as transgender, those who identified as neither male nor female were classified as nonbinary, and those who were not sure about their perceived gender were classified as questioning. All of these participants were categorized as TGNC adolescents. Results: A total of 12 108 adolescents (mean [SD] age, 15.8 [1.0] years; 6518 [53.8%] assigned male at birth [AMAB]) participated in the study. Of the 6518 participants AMAB in the sample, 5855 (89.8%) were classified as cisgender boys, 208 (3.2%) as transgender girls (transgender youth who perceive their current gender identity to be female), 138 (2.1%) as nonbinary youth AMAB, and 317 (4.9%) as questioning youth AMAB. Of the 5590 participants assigned female at birth (AFAB), 4142 (74.1%) were classified as cisgender girls, 861 (15.4%) as transgender boys (transgender youth who perceive their current gender identity to be male), 112 (2.0%) as nonbinary youth AFAB, and 475 (8.5%) as questioning youth AFAB. Compared with cisgender adolescents, TGNC adolescents reported significantly higher health concerns including lower overall health (t11 872 = -7.36; P < .001), poorer sleep (t11 683 = 10.49; P < .001), higher depression and anxiety symptoms (t11 830 = 12.43 and t11 847 = 11.47, respectively; P < .001), and higher rate of self-harm and suicide ideation (t11 860 = 12.22; P < .001). The TGNC youth who were AMAB were also more likely to be bullied at school than cisgender boys (transgender girls: odds ratio [OR], 2.34 [95% CI, 1.64-3.33]; nonbinary youth AMAB: OR, 1.97 [95% CI, 1.23-3.16]; and questioning youth AMAB: OR, 1.95 [95% CI, 1.43-2.67]). The TGNC groups also reported significantly greater amounts of thoughts of self-harm (transgender girls: OR, 3.06 [95% CI, 2.24-4.19]; transgender boys: OR, 4.06 [95% CI, 3.47-4.74]; nonbinary youth AMAB: OR, 2.86 [95% CI, 1.93-4.23]; nonbinary youth AFAB: OR, 3.71 [95% CI, 2.46-5.59]; questioning youth AMAB: OR, 2.61 [95% CI, 1.98-3.44]; and questioning youth AFAB: OR, 3.35 [95% CI, 2.70-4.16]), thoughts of suicide (transgender girls: OR, 3.93 [95% CI, 2.88-5.38]; transgender boys: OR, 3.71 [95% CI, 3.10-4.21]; nonbinary youth AMAB: OR, 3.13 [95% CI, 2.11-4.63]; nonbinary youth AFAB: OR, 3.78 [95% CI, 2.50-5.71]; questioning youth AMAB: OR, 2.53 [95% CI, 1.93-3.33]; and questioning youth AFAB: OR, 3.94 [95% CI, 3.17-4.88]), suicide plan formation (transgender girls: OR, 4.44 [95% CI, 2.88-6.83]; transgender boys: OR, 2.66 [95% CI, 2.03-3.50]; nonbinary youth AMAB: OR, 5.36 [95% CI, 3.22-8.93]; nonbinary youth AFAB: OR, 4.06 [95% CI, 2.25-7.30]; and questioning youth AFAB: OR, 2.36 [95% CI, 1.63-3.43]), deliberate self-harm during the last month (cisgender girls: OR, 1.49 [95% CI, 1.33-1.68]; transgender girls: OR, 2.74 [95% CI, 1.93-3.91]; transgender boys: OR, 3.06 [95% CI, 2.57-3.66]; nonbinary youth AMAB: OR, 2.56 [95% CI, 1.66-3.94]; nonbinary youth AFAB: OR, 3.06 [95% CI, 1.95-4.81]; questioning youth AMAB: OR, 2.14 [95% CI, 1.56-2.92]; and questioning youth AFAB: OR, 2.53 [95% CI, 2.00-3.01]), and attempts of suicide (transgender girls: OR, 4.35 [95% CI, 2.88-6.56]; transgender boys: OR, 2.92 [95% CI, 2.26-3.76]; nonbinary youth AMAB: OR, 3.94 [95% CI, 2.36-6.55]; nonbinary youth AFAB: OR, 3.06 [95% CI, 1.67-5.63]; questioning youth AMAB: OR, 2.61 [95% CI, 1.73-3.94]; and questioning youth AFAB: OR, 1.93 [95% CI, 1.33-2.81]) compared with cisgender boys. Conclusions and Relevance: Results of this cross-sectional survey study suggest poor mental health status among TGNC adolescents in China; in addition, findings suggest a compelling need for researchers, practitioners, and policy makers to address these mental health problems. Particular school-based interventions are recommended to support the mental health well-being of TGNC adolescents.

Methicillin-resistant Staphylococcus aureus nasal colonization and infection in an intensive care unit of a university hospital in China.

Objective This study was performed to determine the prevalence and risk factors associated with nasal methicillin-resistant Staphylococcus aureus (MRSA) colonization upon intensive care unit (ICU) admission and during the ICU stay in mainland China. Methods A prospective observational study was performed in a 50-bed general ICU of a 4300-bed teaching hospital in China from 2011 to 2013. Nasal swabs for MRSA detection were obtained upon ICU admission and at discharge for patients having stayed in the ICU for longer than 3 days. Results In total, 115 patients (4.1%; 95% confidence interval [CI], 3.4-4.9) were already colonized with MRSA on ICU admission, and another 185 patients (10.7%; 95% CI, 9.3-12.2) acquired MRSA during their ICU stay. Development of an MRSA infection was significantly more likely in patients with than without MRSA colonization on ICU admission (odds ratio [OR], 2.8; 95% CI, 1.1-7.3). Patients who acquired MRSA had significantly prolonged lengths of stay in the ICU (23.3 days) and higher hospital bills (135,171 RMB; about 19,590 USD) than those who tested negative for MRSA. Conclusion The MRSA colonization rate among ICU patients in mainland China is high. Patients with MRSA-positive nasal swabs are more likely to develop MRSA infections.

miR-125a induces apoptosis, metabolism disorder and migrationimpairment in pancreatic cancer cells by targeting Mfn2-related mitochondrial fission.

Mitochondrial fission is important for the development and progression of pancreatic cancer (PC). However, little is known regarding its role in pancreatic cancer apoptosis, metabolism and migration. In the current study, the mechanism by which mitochondrial fission modifies the biological characteristics of PC was explored. MicroRNA­125a (miR­125a) had the ability to inhibit mitochondrial fission and contributed to cellular survival. Suppressed mitochondrial fission led to a reduction in mitochondrial debris, preserved the mitochondrial membrane potential, inhibited mitochondrial permeability transition pore opening, ablated cytochrome c leakage into the cytoplasm and reduced the pro­apoptotic protein contents, finally blocking mitochondria related apoptosis pathways. Furthermore, defective mitochondrial fission induced by miR­125a enhanced mitochondria­dependent energy metabolism by promoting activity of electron transport chain complexes. Furthermore, suppressed mitochondrial fission also contributed to PANC­1 cell migration by preserving the F­actin balance. Furthermore, mitofusin 2 (Mfn2), the key defender of mitochondrial fission, is involved in inhibition of miR125a­mediated mitochondrial fission. Low contents of miR­125a upregulated Mfn2 transcription and expression, leading to inactivation of mitochondrial fission. Ultimately, the current study determined that miR­125a and Mfn2 are regulated by hypoxia­inducible factor 1 (HIF1). Knockdown of HIF1 reversed miR­125a expression, and therefore, inhibited Mfn2 expression, leading to activation of mitochondrial fission. Collectively, the present study demonstrated mitochondrial fission as a tumor suppression process that is regulated by the HIF/miR­125a/Mfn2 pathways, acting to restrict PANC­1 cell survival, energy metabolism and migration, with potential implications for novel approaches for PC therapy.

Infection prevention and control in outpatient settings in China-structure, resources, and basic practices.

BACKGROUND: More than 7 billion visits are made by patients to ambulatory services every year in mainland China. Healthcare-associated infections are becoming a new source of illness for outpatients. Little is known about infection prevention, control structure, resources available, and basic practices in outpatient settings. METHODS: In 2014, we conducted a multisite survey. Five provinces were invited to participate based on geographic dispersion. Self-assessment questionnaires regarding the structure, infrastructure, apparatus and materials, and basic activities of infection prevention and control were issued to 25 hospitals and 5 community health centers in each province. A weight was assigned to each question according to its importance. RESULTS: Overall, 146 of 150 facilities (97.3%) participated in this study. The average survey score was 77.6 (95% confidence interval 75.7-79.5) and varied significantly between the different gross domestic product areas (P < .01), but scores were not significantly different between the 5 facility types (P = .07). The main lapse of infrastructure was in providing hand hygiene equipment (43.4%) and masks (38.7%) for patients in the waiting areas and main entrances. CONCLUSION: In a sample of ambulatory facilities in 5 provinces in China, infection prevention and control was practiced consistently, although there were lapses in some areas.

Molecular epidemiological analysis of methicillin-resistant Staphylococcus aureus isolates from a medical intensive care unit: a comparison of nasal and clinical isolates.

BACKGROUND: The control of nosocomial transmission of methicillin-resistant Staphylococcus aureus (MRSA) represents a significant challenge to infection control professionals. Nasal carriage colonization by MRSA plays a crucial role in the epidemiology and pathogenesis of this infection. METHODS: Patients in the medical intensive care unit (ICU) between November 2010 and March 2011 were swabbed when hospitalized, reswabbed 1 week later and for a third time, when they were discharged from the ICU. All swabs were examined within 2 hours of collection using ChromID MRSA-Select agar plates to detect MRSA. Positive specimens were determined to have the mecA and femB gene through amplification with duplex polymerase chain reaction. Repetitive element sequence-based polymerase chain reaction was used to investigate the epidemiological types of MRSA isolates in the third screening and clinical isolates obtained from 2007 to 2010 in West China Hospital. A comparison of molecular types was performed to investigate the genetic relationship between nasal and clinical isolates. RESULTS: After the third screening, 16 nasal MRSA isolates were identified. Epidemiological analysis revealed that 16 nasal MRSA isolates and 37 clinical MRSA isolates differentiated into 2 clusters, comprising 9 subclusters. Of the 16 nasal strains, 11 (68.8%) belonged to subcluster I of cluster I; 3 of 9 subclusters consisted of both nasal and clinical isolates, while 4 of 9 subclusters consisted of clinical isolates and only 2 of 9 consisted of nasal isolates. CONCLUSIONS: Our study indicated a high degree of genetic relatedness between nasal and clinical MRSA isolates. The molecular typing of MRSA is critical for controlling the nosocomial transmission of this pathogen in ICU setting and defining a nosocomial infection control policy.