Erratum: BMP4 augments the survival of hepatocellular carcinoma (HCC) cells under hypoxia and hypoglycemia conditions by promoting the glycolysis pathway.

[This corrects the article on p. 793 in vol. 11, PMID: 33791154.].

Status and correlates of children's exposure to secondhand smoke at home: A survey in Chongqing, China.

INTRODUCTION: The home is the primary source of children's exposure to secondhand smoke. This study investigated the status and influencing factors of child exposure to secondhand smoke at home when people smoke in the household. METHODS: Participants with at least one child living in their household from 10 communities in Chongqing were recruited and provided a self-administered questionnaire using a multistage proportional random sampling design from June to August 2021. The chi-squared test and binary logistic regression analyses were used to identify influencing factors. RESULTS: The questionnaire completed by 1345 families showed that 631 (46.9%) families lived with smokers in their household, and 509 (80.7%) of those families reported that smoking occurred within the home while the children were present. Binary logistic regression analyses demonstrated that the time between waking up and household smokers having the first cigarette of the day (OR=0.44; 95% CI: 0.22-0.85), changes to smoking habits and behaviors within the last six months (OR=1.76; 95% CI: 1.06-2.90), attitudes towards tobacco control in the household (OR=2.91; 95% CI: 1.72-4.92), self-efficacy in maintaining a smoke-free home (OR=2.27; 95% CI: 1.36-3.79), having rules to maintain a smoke-free home (OR=3.25; 95% CI: 1.68-6.29), and the status of providing cigarettes to guests at home (OR=11.0; 95% CI: 1.33-90.8) were associated with exposure to SHS. CONCLUSIONS: Education focusing on the impact of smoking on children's health should be encouraged. Smoke-free homes should be established, and smoking restrictions in the household should be enacted. Therefore, information about the available tobacco-control services should be given to family members and be used properly. It is an effective way to decrease the risk of at-home exposure to SHS for children, to overcome any obstacles in tobacco control.

Prokineticin 2 promotes macrophages-mediated antibacterial host defense against bacterial pneumonia.

OBJECTIVES: Bacterial pneumonia is a common serious infectious disease with high morbidity and mortality. Prokineticin 2 (PK2) has recently been identified as a novel immunomodulator in a variety of diseases; however, its role in bacterial pneumonia remains unclear. METHODS: The levels of PK2 were measured and analyzed in patients with pneumonia and healthy controls. The effects of PK2 on the host response to pneumonia were evaluated by in vivo animal experiments and in vitro cell experiments. RESULTS: PK2 levels dramatically decreased in patients with pneumonia compared with healthy controls, and PK2 levels were lower in patients with severe pneumonia than in pneumonia. In a mouse model of bacterial pneumonia, transtracheal administration of recombinant PK2 significantly alleviated lung injury and improved the survival, which was associated with increased host's bacterial clearance capacity, as manifested by decreased pulmonary bacterial loads. PK2 enhanced the chemotaxis, phagocytosis, and killing ability of macrophages, whereas the protective efficacy of PK2 was abolished after macrophage depletion. CONCLUSION: Impaired alveolar macrophage function caused by decreased PK2 is a new endogenous cause of the occurrence and development of bacterial pneumonia. The administration of recombinant PK2 may be a potential adjuvant therapy for bacterial pneumonia.

Status and correlates of home smoking bans after the implementation of the smoke-free legislation in public places: A survey in Chongqing.

INTRODUCTION: Secondhand smoke exposure in many countries decreased dramatically after the implementation of smoke-free legislation in public places, but the exposure at home did not change to the same degree. The aim of this study was to describe the status and correlates of a home smoking ban in Chongqing, China. METHODS: From June to August 2021, we selected two healthcare centers in the East, West, North, South and Middle regions of Chongqing. We investigated the family smoke-free situation in the selected region using a stratified random sampling method. A chi-squared test was performed to compare the totally and partially smoke-free homes, and a binary logistic regression model was used to analyze the correlates of smoke-free rules at home. RESULTS: The study investigated 2121 families, among which 884 (41.7%) implemented a total ban on smoking at home. The covariates included age (OR=1.54; 95% CI: 1.18-2.01), living with children aged <14 years (OR=1.51; 95% CI: 1.20-1.90), no smokers in the family (OR=2.37; 95% CI: 1.78-3.17), awareness of the hazards of secondhand smoke (OR=1.30; 95% CI: 1.07-1.59), worrying about the impact of smoking in the presence of children on health (OR=1.92; 95% CI: 1.25-2.95), no difficulty (OR=1.34; 95% CI: 1.07-1.67) and confidence (OR=1.73; 95% CI: 1.41-2.13) in stopping others from smoking, no smoking rules in cars (OR=3.67; 95% CI: 2.58-5.22), and frequency of entertaining guests with cigarettes (OR=0.41; 95% CI: 0.28-0.59). CONCLUSIONS: It is common for households in Chongqing to have smoking bans, especially those with children. If a family has members that are smokers, education researchers should pay more attention to the hazards of secondhand smoke on the health of family members, and to adopt more tobacco control measures and enhance the self-efficacy of implementing a home smoking ban. Helping smokers to quit is a vital way to decrease the hazards of cigarettes.

Reversibly immortalized keratinocytes (iKera) facilitate re-epithelization and skin wound healing: Potential applications in cell-based skin tissue engineering.

Skin injury is repaired through a multi-phase wound healing process of tissue granulation and re-epithelialization. Any failure in the healing process may lead to chronic non-healing wounds or abnormal scar formation. Although significant progress has been made in developing novel scaffolds and/or cell-based therapeutic strategies to promote wound healing, effective management of large chronic skin wounds remains a clinical challenge. Keratinocytes are critical to re-epithelialization and wound healing. Here, we investigated whether exogenous keratinocytes, in combination with a citrate-based scaffold, enhanced skin wound healing. We first established reversibly immortalized mouse keratinocytes (iKera), and confirmed that the iKera cells expressed keratinocyte markers, and were responsive to UVB treatment, and were non-tumorigenic. In a proof-of-principle experiment, we demonstrated that iKera cells embedded in citrate-based scaffold PPCN provided more effective re-epithelialization and cutaneous wound healing than that of either PPCN or iKera cells alone, in a mouse skin wound model. Thus, these results demonstrate that iKera cells may serve as a valuable skin epithelial source when, combining with appropriate biocompatible scaffolds, to investigate cutaneous wound healing and skin regeneration.

Research on the factors that influence patients with colorectal cancer participating in the prevention and control of surgical site infection: Based on the extended theory of planned behaviour.

BACKGROUND: The most common and severe type of nosocomial infection in patients with colorectal cancer is surgical site infection (SSI). Patient-related factors are an important components of SSI. So it is necessary to participate in SSI prevention and control. It is important to identify the factors that influence patients' participation behaviour and to explore the mechanism of these effects. METHODS: A total of 580 patients with colorectal cancer completed relevant measures. Based on the extended theory of planned behaviour, a structural equation model was used to analyse the relationship among the influencing factors. RESULTS: The factors influencing participation of patients with colorectal cancer in SSI prevention and control were participation intention, participation ability, self-efficacy, participation attitude, perceived medical staff support, trust in physicians and social support. The direct effect coefficients of participation intention, participation ability and physician trust on SSI prevention and control behaviour were 0.67, 0.21 and 0.11, respectively. Self-efficacy, participation attitude, perceived medical staff support and social support indirectly affect participation behaviour through participation intention, and their effect values are 0.21, 0.11, 0.11 and 0.08, respectively. CONCLUSIONS: Based on the structural equation model developed in this study, targeted intervention measures should be implemented to mobilize the intention and enthusiasm of patients with colorectal cancer to participate in the prevention and control of SSI. PATIENT OR PUBLIC CONTRIBUTION: Patients or public contribute to spreading research findings, and promote broad participation in the implementation of policies or strategies.

BMP4 augments the survival of hepatocellular carcinoma (HCC) cells under hypoxia and hypoglycemia conditions by promoting the glycolysis pathway.

Hepatocellular carcinoma (HCC) is one of the leading causes of cancer death worldwide although its pathogenic mechanism remains to be fully understood. Unlike normal cells, most cancer cells rely on aerobic glycolysis and are more adaptable to the microenvironment of hypoxia and hypoglycemia. Bone Morphogenetic Protein 4 (BMP4) plays important roles in regulating proliferation, differentiation, invasion and migration of HCC cells. We have recently shown that BMP4 plays an important role in regulating glucose metabolism although the effect of BMP4 on glucose metabolic reprogramming of HCC is poorly understood. In this study, we found that BMP4 was highly expressed in HCC tumor tissues, as well as HCC cell lines that were tolerant to hypoxia and hypoglycemia. Mechanistically, we demonstrated that BMP4 protected HCC cells from hypoxia and hypoglycemia by promoting glycolysis since BMP4 up-regulated glucose uptake, the lactic acid production, the ATP level, and the activities of rate limiting enzymes of glycolysis (including HK2, PFK and PK). Furthermore, we demonstrated that BMP4 up-regulated HK2, PFKFB3 and PKM2 through the canonical Smad signal pathway as SMAD5 directly bound to the promoter of PKM. Collectively, our findings shown that BMP4 may play an important role in regulating glycolysis of HCC cells under hypoxia and hypoglycemia condition, indicating that novel therapeutics may be developed to target BMP4-regulated glucose metabolic reprogramming in HCC.

Analysis of the social and clinical factors affecting the age of children when receiving surgery for hypospadias: a retrospective study of 1611 cases in a single center.

We aimed to explore the associations between the age at which children undergo surgery for hypospadias and a range of social and clinical factors in a single center. Our aim was to promote the early surgical treatment of children with hypospadias. For a 6-year period, social and clinical data were collected from all children undergoing surgery to repair hypospadias in Children's Hospital of Chongqing Medical University (Chongqing, China), located in southwest of China. We analyzed the correlations between age at surgery and a range of social and clinical factors. A total of 1611 eligible cases were recruited, with a mean age of 54.3 months and a median age of 42 months: 234 cases (14.5%) were classified into a "timely operation" group, 419 (26.0%) cases into a "subtimely operation" group, and 958 (59.5%) cases into a "delayed operation" group. According to multivariate regression analyses, the higher the regional economic level, the closer the urethral opening to the perineum, and the higher the educational level of the guardians was, the younger the children were when they underwent the initial surgery for hypospadias; this was also the case for families without other children. Our subgroup analysis showed that the primary educational level of the guardians was a risk factor for subtimely surgery in their children (odds ratio [OR] = 1.52, 95% confidence interval [CI]: 1.08-2.15, P < 0.05). A lower regional economic level (OR = 1.87, 95% CI: 1.26-2.78, P < 0.01), a lower educational level of the guardians (OR = 3.84, 95% CI: 2.31-6.41, P < 0.01), and an anterior-segment urethral opening (OR1 [vs middle hypospadias] = 2.07, 95% CI: 1.42-3.03; OR2 [vs posterior hypospadias] = 2.63, 95% CI: 1.75-3.95; P < 0.01) were all risk factors for delayed surgery in children.

The Effect of Tube Location on Corneal Endothelial Cells in Patients with Ahmed Glaucoma Valve.

PURPOSE: To compare the effects of the Ahmed glaucoma valve (AGV; New World Medical, Rancho Cucamonga, CA) with sulcus versus anterior chamber (AC) tube placement on the corneal endothelial density and morphology over time. DESIGN: Nonrandomized, interventional study. PARTICIPANTS: This study included 106 eyes from 101 pseudophakic patients who had the AGV tube placed in the AC (acAGV) and 105 eyes from 94 pseudophakic patients who had the AGV tube placed in the ciliary sulcus (sAGV). METHODS: All patients underwent preoperative specular microscopy, which was repeated postoperatively in 2019. The patients' demographic information, glaucoma diagnoses, and basic ocular information were obtained on chart review. Anterior segment OCT was conducted for patients who underwent sAGV to evaluate the sulcus tube position. Gonioscopy was performed to document peripheral anterior synechiae (PAS). Linear mixed-effects models were used to compare the different ocular and endothelial measurements between the 2 groups and to identify risk factors for endothelial cell density (ECD) loss over time. MAIN OUTCOME MEASURES: Monthly change in corneal endothelial measurements, including ECD and coefficient of variation (CV), calculated as the difference between preoperative and postoperative measurements divided by the number of months from the time of surgery to postoperative specular microscopy. RESULTS: The acAGV and sAGV groups were comparable in all baseline characteristics except that the acAGV group had longer follow-up (37.6 vs. 20.1 months, respectively, P < 0.001). Mean monthly loss in central ECD was significantly more in the acAGV group (mean ± standard deviation: 29.3±29.7 cells/mm2) than in the sAGV group (15.3±20.7 cells/mm2, P < 0.0001). Mean monthly change in CV was similar between the 2 groups (P = 0.28). Multivariate analyses revealed that younger age and tube location in the AC were associated with faster central ECD loss (P = 0.02, P < 0.0001, respectively). For patients with sAGV, while PAS was associated with faster central ECD loss (P = 0.002), a more forward tube position tenting the iris was not (P > 0.05). CONCLUSIONS: Compared with anterior segment placement, ciliary sulcus tube implantation may be a preferred surgery approach to reduce endothelial cell loss in pseudophakic patients.

Impact of tobacco control auxiliary resources on the 5As behavior in nursing interns: Self-reports from students.

INTRODUCTION: The help of healthcare professionals for smokers to quit is critically important to increase quit rates. In the future, internship nursing students will potentially become the largest population of medical professionals. This study explored the impact of the use and awareness of universal tobacco control auxiliary resources on nursing students' 5As behavior in helping patients to quit smoking during a 40-week clinical internship in the last year of nursing school in Chongqing, China. METHODS: A survey was conducted in 13 teaching hospitals selected from 29 in Chongqing, China, in 2019, by a random cluster sampling method. It investigated, by self-reported questionnaires, student 5As behavior in helping patients to quit smoking and use and knowledge of tobacco cessation auxiliary resources (tobacco cessation self-education manual, tobacco cessation guidelines, tobacco cessation drugs, tobacco cessation websites, and hotline). The relationship between tobacco cessation auxiliary resources and 5As behavior in helping patients to quit smoking was analyzed with a multivariate linear mixed-effect model. RESULTS: In all, 534 (39.3%) students, of a total of 1358, reported that the majority of internship units provided a tobacco control self-education manual; 674 (49.6%) ever skimmed through tobacco cessation guidelines; 641 (47.2%) browsed tobacco cessation websites; 738 (54.3%) knew some cessation-assistance drugs; and 93 (6.8%) knew of and could recall the tobacco cessation hotline. Except for tobacco cessation websites, tobacco cessation auxiliary resources affected nursing interns' 5As behavior in helping patients to quit (p<0.05). CONCLUSIONS: Tobacco cessation auxiliary resources influenced students' 5As behavior in helping patients to quit smoking. Students knew a little of tobacco cessation auxiliary resources. To improve students' 5As behavior for helping patients to quit, more tobacco cessation resources need to be developed and more students need to become acquainted with them.

Progress in the research of p53 tumour suppressor activity controlled by Numb in triple-negative breast cancer.

Numb is known as a cell fate determinant as it identifies the direction of cell differentiation via asymmetrical partitioning during mitosis. It is considered as a tumour suppressor, and a frequent loss of Numb expression in breast cancer is noted. Numb forms a tri-complex with p53 and E3 ubiquitin ligase HDM2 (also known as MDM2), thereby preventing the ubiquitination and degradation of p53. In this study, we examined Numb expression in 125 patients with triple-negative breast cancer (TNBC). The results showed that 61 (48.8%) patients presented with a deficient or decreased Numb expression. The percentage of Ki67 > 14% in the retained Numb group was significantly lower than that in the decreased and deficient Numb groups (86.00% vs. 98.40%, P = .0171). This study aimed to detect the expression and migration of Numb, HDM2 and p53 in the membrane, cytoplasmic and nuclear fractions of normal mammary epithelial cell line MCF-10A and basal-like TNBC cell line MDA-MB-231. We obtained the cell fractions to identify changes in these three protein levels after the re-expression of NUMB in the MDA-MB-231 cells and the knocking down of NUMB in the MCF-10A cells. Results showed that Numb regulates p53 levels in the nucleus where the protein levels of Numb are positively correlated with p53 levels, regardless if it is re-expressed in the MDA-MB-231 cells or knocked down in the MCF-10A cells. Moreover, HDM2 was remarkably decreased only in the membrane fraction of NUMB knock-down cells; however, its mRNA levels were increased significantly. Our results reveal a previously unknown molecular mechanism that Numb can migrate into the nucleus and interact with HDM2 and p53.

Facilitators and Barriers Associated with Uptake of HIV Self-Testing among Men Who Have Sex with Men in Chongqing, China: A Cross-Sectional Survey.

While studies on human immunodeficiency virus self-testing (HIVST) continue to accumulate after the World Health Organization's recommendation of HIVST as an additional approach to HIV testing services in 2016, few studies have focused on men who have sex with men (MSM) in Chinese cities. A cross-sectional study was conducted to describe the HIVST status of MSM in Chongqing, China. MSM participants were recruited by random sampling, and qualified interviewers collected data, using confidential self-administered questionnaires. Blood specimens were collected for HIV antibody detection. The survey evaluated the uptake and accuracy of HIVST kits and identified factors that may be associated with HIVST. The proportion of HIVST uptake was 15.6%. The sensitivity and specificity of HIVST were 74.2% (95% confidence interval [CI] 66.6%-80.7%) and 99.0% (95% CI 96.9%-99.7%), respectively. The consistency between the HIVST kit and antibody detection results was 90.5% (95% CI 87.5%-93.0%), and the Kappa value was 0.777 (p < 0.001). The positive predictive value of self-testing kits is 80.9% and the negative predictive value is 17.7%. Having been tested ≥2 times in the last year, higher educational levels, and higher scores of basic HIV/AIDS knowledge facilitated higher uptake of HIVST. Self-reported existing barriers for HIVST uptake included older age, marital status, and having resided in Chongqing for more than two years.

Progranulin as a novel biomarker in diagnosis of early-onset neonatal sepsis.

BACKGROUND: Infections are leading causes of morbidity and mortality in neonates and may also have severe long-term consequences. As early diagnosis of neonatal sepsis improves prognosis, identification of new or complementary biomarkers is of great importance. In this study, we have evaluated the diagnostic value of progranulin (PGRN) in early-onset neonatal sepsis (EOS) and compare its effectiveness with other commonly used biomarkers, such as procalcitonin (PCT) and C-reactive protein (CRP). METHODS: A total of 121 infants with gestational age of >34 weeks admitted with suspected EOS were included in this study. Before initiating therapy, blood samples for whole blood count, CRP, PCT and PGRN were obtained from all neonates. Receiver-operating characteristic (ROC) curve and multivariate logistic regression analyses were performed. RESULTS: Serum PGRN level of infected group was significantly higher than uninfected group (median 47.72 vs. 37.86 ng/ml, respectively; Mann-Whitney p < 0.0001). The ROC area under the curve (AUC) was 0.786 [95% confidence interval (CI) 0.706-0.867; p < 0.0001] for PGRN, 0.699 (95% CI 0.601-0.797; p = 0.0001) for age adjusted PCT, and 0.673 (95% CI 0.573-0.773; p = 0.0007) for CRP. With a cut-off value of 37.89 ng/ml, the diagnostic sensitivity and negative predictive value of PGRN were 94.34% and 91.7%, respectively. PGRN could significantly predict EOS independently of PCT (p < 0.0001), and the combined use of PGRN and PCT could significantly improve diagnostic performance for EOS (0.806; 95% CI 0.73-0.88; p < 0.0001), with a specificity of 89.06% and a positive predictive value of 81.10%. CONCLUSIONS: PGRN may be used as a promising biomarker for the diagnosis of EOS, and the combined use of PGRN and PCT could improve the diagnosis of sepsis.

A simplified 3D liver microsphere tissue culture model for hepatic cell signaling and drug-induced hepatotoxicity studies.

Although a number of experimental models have been developed for liver research, each has its own advantages and disadvantages. The present study attempted to develop a simple and effective 3­dimensional mouse liver microsphere tissue culture (LMTC) model in vitro for the analysis of hepatic functions. Hepatic characteristics and potential applications of this model were compared with that of mouse model in vivo and mouse primary hepatocytes in vitro. Using freshly­perfused mouse liver tissue passed through 80­mesh sift strainer (sift80), it was demonstrated that under the optimal culture conditions, the sift80 microsphere tissue cultured in 2% bovine calf serum medium remained viable with marked proliferating cell nuclear antigen and anti­Myc proto­oncogene protein expression, exhibited normal hepatic functions including indocyanine green (ICG) uptake/release and periodic acid­Schiff staining, and expressed hepatocyte­specific genes for up to 2 weeks. The microsphere tissue was responsive to bone morphogenic protein 9 (BMP9) stimulation leading to upregulation of downstream targets of BMP9 signaling. Furthermore, 3 commonly­used liver­damaging drugs were indicated to effectively inhibit hepatic ICG uptake, and induce the expression of hepatotoxicity­associated genes. Therefore, this simplified LMTC model may be a useful in vitro tissue culture model to investigate drug­induced liver injury and metabolism, and hepatocyte­based cell singling.

Monitoring of the Effect of Cerebral Autoregulation on Delayed Cerebral Ischemia in Patients with Aneurysmal Subarachnoid Hemorrhage.

OBJECTIVE: To detect cerebral autoregulation (CA) in patients with aneurysmal subarachnoid hemorrhage (aSAH) by near-infrared spectroscopy and to assess its association with delayed cerebral ischemia (DCI). METHODS: From January to August 2017, 81 patients (average age 53.25 ± 10.27 years) were studied. Near-infrared spectroscopy was used to monitor CA, and associated factors were evaluated. Monitoring of CA was carried out at 5 time points (preoperative day 1 and postoperative days 1, 2, 3, and 7). Patients were sorted into 2 groups according to whether DCI occurred (DCI group and non-DCI group). The relationship between CA and DCI in patients with aSAH was analyzed. RESULTS: Among 81 patients, CA trended toward being impaired in patients with aSAH with a poorer grade. DCI occurred in 39 of 51 (48.15%) patients with impaired CA. DCI occurred in 6 of 30 (7.4%) patients with intact CA. CONCLUSIONS: Impaired CA monitored by near-infrared spectroscopy was shown in patients with aSAH before and after surgical intervention. Older age, smoking, hypertension, and especially impaired CA are independent risk factors for patients with DCI.