Search

Mycobacterium tuberculosis /human immunodeficiency virus (MTB/HIV) coinfection has become an urgent problem in the field of prevention and control of infectious diseases in recent years. Adoptive cellular immunotherapy using antigen-specific T-cell receptor (TCR) engineered T cells which recognize the specific antigen artificially may have tremendous potential in anti-MTB/HIV coinfection. We have previously successfully identified a MTB Ag85B 199-207 and HIV-1 Env 120-128 peptide-bispecific TCR screened out from peripheral blood mononuclear cells of a HLA-A∗0201 + healthy individual and have further studied that how residues on the predicted complementarity determining region (CDR) 3 of the β chain contribute to the bispecific TCR contact with the peptide-MHC. However, it is not clear which amino acids in the predicted CDR3α of the bispecific TCR play a crucial role in ligand recognition.The variants in the CDR3α of the bispecific TCR were generated using alanine substitution. We then evaluated the immune effects of the five variants on T-cell recognition upon encounter with the MTB or HIV-1 antigen.Mutation of two amino acids (E112A, Y115A) in CDR3α of the bispecific TCR caused a markedly diminished T-cell response to antigen, whereas mutation of the other three amino acids (S113A, P114A, S116A) resulted in completely eliminated response.This study demonstrates that Ser 113 , Pro 114 and Ser 116 in CDR3α of the bispecific TCR are especially important for antigen recognition. These results will pave the way for the future development of an improved high-affinity bispecific TCR for use in adoptive cellular immunotherapy for MTB/HIV coinfected patients.

Myocardial ischemia/reperfusion (I/R) injury is associated with the poor outcome and higher mortality after myocardial infarction. Recent studies have revealed that miR-199a-5p participates in the process of myocardial I/R injury, but the precise roles and molecular mechanisms of miR-199a-5p in myocardial I/R injury remain not well-studied. Ferroptosis has been proposed to promote cardiomyocyte death, closely associated with myocardial I/R injury. Herein, the present study aimed to explore the function and mechanisms by which miR-199a-5p regulates whether miR-199a-5p contributes to ferroptosis-induced cardiomyocyte death responding to oxygen-glucose deprivation/reoxygenation (OGD/R) injury, an in vitro model of myocardial I/R injury focusing on Akt/eNOS signaling pathway. The results found that ferroptosis-induced cardiomyocyte death occurs and is accompanied by an increase in miR-199a-5p level in OGD/R-treated H9c2 cells. MiR-199a-5p inhibitor ameliorated ferroptosis-induced cardiomyocyte death as evidenced by the increased cell viability, the reduced reactive oxygen species (ROS) generation, lactate dehydrogenase (LDH) activity, malondialdehyde (MDA) and Fe

Oxidative DNA damage is tightly linked to the development of multiple age-related diseases. The prominent oxidation product is 8-oxo-7,8-dihydroguanine (OG), which has been proved to be an important epigenetic-like biomarker. Quantification of the locus-specific OG frequency includes quantitative and locating information, which is of great significance for exploring the functional roles of OG in disease induction and gene regulation. Herein, an ultrasensitive quantification of OG at single-base resolution was established using real-time fluorescence quantitative polymerase chain reaction as an amplification tool. Based on the coding property of

Refereed/Peer-reviewed Reducing lead (Pb) exposure via oral ingestion of contaminated soils is highly relevant for child health. Elevating dietary micronutrient iron (Fe) intake can reduce Pb oral bioavailability while being beneficial for child nutritional health. However, the practical performance of various Fe compounds was not assessed. Here, based on mouse bioassays, ten Fe compounds applied to diets (100–800 mg Fe kg−1) reduced Pb oral relative bioavailability (RBA) in two soils variedly depending on Fe forms. EDTA-FeNa was most efficient, which reduced Pb-RBA in a soil from 79.5 ± 14.7 % to 23.1 ± 2.72 % (71 % lower) at 100 mg Fe kg−1 in diet, more effective than other 9 compounds at equivalent or higher doses (3.6–68 % lower). When EDTA-FeNa, ferrous gluconate, ferric citrate, and ferrous bisglycinate were supplemented, Fe-Pb co-precipitation was not observed in the intestinal tract. EDTA-FeNa, ferrous gluconate, ferric citrate, and ferrous sulfate suppressed duodenal divalent metal transporter 1 (DMT1)mRNA relative expression similarly (27–68 % lower). In comparison, among ten compounds, EDTA-FeNa elevated Fe concentrations in mouse liver, kidney, and blood (1.50–2.69-fold higher) most efficiently, suggesting the most efficient Fe absorption that competed with Pb. In addition, EDTA was unique from other organic ligands, ingestion of which caused 12.0-fold higher Pb urinary excretion, decreasing Pb concentrations in mouse liver, kidney, and blood by 68–88 %. The two processes (Fe-Pb absorption competition and Pb urinary excretion with EDTA) interacted synergistically, leading to the lowest Pb absorption with EDTA-FeNa. The results provide evidence of a better inhibition of Pb absorption by EDTA-FeNa, highlighting that EDTA-FeNa may be the most appropriate supplement for intervention on human Pb exposure. Future researches are needed to assess the effectiveness of EDTA-FeNa for intervention on human Pb exposure.

Graphical abstract, Highlights • Skin cancer is a fatal public health concern rising continuously all over the world. • Several environmental and genetic risk factors are associated with cutaneous carcinogenesis. • Use of nanocarriers for targeted delivery of anticancer agents is the most advanced approach. • Polymeric structures are suitable for tumor selective delivery of drugs, genes and imaging agents. • Polymeric micro/nanostructures have successfully used for combination anticancer therapies., Background Skin cancer has been the leading type of cancer worldwide. Melanoma and non-melanoma skin cancers are now the most common types of skin cancer that have been reached to epidemic proportion. Based on the rapid prevalence of skin cancers, and lack of efficient drug delivery systems, it is essential to surge the possible ways to prevent or cure the disease. Aim of review Although surgical modalities and therapies have been made great progress in recent years, however, there is still an urgent need to alleviate its increased burden. Hence, understanding the precise pathophysiological signaling mechanisms and all other factors of such skin insults will be beneficial for the development of more efficient therapies. Key scientific concepts of review In this review, we explained new understandings about onset and development of skin cancer and described its management via polymeric micro/nano carriers-based therapies, highlighting the current key bottlenecks and future prospective in this field. In therapeutic drug/gene delivery approaches, polymeric carriers-based system is the most promising strategy. This review discusses that how polymers have successfully been exploited for development of micro/nanosized systems for efficient delivery of anticancer genes and drugs overcoming all the barriers and limitations associated with available conventional therapies. In addition to drug/gene delivery, intelligent polymeric nanocarriers platforms have also been established for combination anticancer therapies including photodynamic and photothermal, and for theranostic applications. This portfolio of latest approaches could promote the blooming growth of research and their clinical availability.

Thyroid cancer (TC) has increased globally, with a prominent increase in small, papillary thyroid cancers. PEST-containing nuclear protein (PCNP), a nuclear protein, has been found to be associated with human cancers in recent years. However, the role and molecular mechanism of PCNP in thyroid cancer remain underexplored. In the present study, the results showed that the expression levels of PCNP in human thyroid tissues were higher than those in adjacent non-tumor tissues. Overexpression of PCNP reduced the proliferation, migration, and invasion of human thyroid cancer cells and down-regulation of PCNP showed reverse effects. In addition, PCNP regulated cell cycle arrest through modifications in the expression of cell cycle regulating genes and PCNP affected apoptosis via activation of ERK/JNK/p38 pathway in thyroid cancer cells. Moreover, PCNP overexpression promoted autophagy by reducing the expression levels of Wnt/β-catenin pathway in TC cells, however, PCNP knockdown had opposite effects. Furthermore, PCNP overexpression reduced the growth of xenografted human thyroid cancer, whereas PCNP knockdown showed opposite trends. In conclusion

Background Previous reports have described hypogonadism associated with virus infection such as hantavirus, human immunodeficiency virus (HIV) or severe acute respiratory syndrome coronavirus 2 (SARS-COV-2). However, to our best knowledge there has been no case report of secondary hypogonadism following hand, foot, and mouth disease (HFMD). Case presentation A previously healthy 28-year-old man with no history of major physical and psychological trauma, presented with bilateral gynecomastia and erectile dysfunction 2 weeks after HFMD. Laboratory testament showed the level of gonadotropin hormones declined. Imaging examination demonstrated no major abnormal change in pituitary or reproductive system. The diagnosis of hypogonadism was established. Then the patient was ordered to maintain mental health outward of hospital without drug intervention. One month after presentation, his gonadotropin hormone level and sexual desire had recovered, while bilateral gynecomastia and erectile dysfunction symptoms disappeared. Conclusions Physicians should notice the possibility for hypogonadism in adult patients with a recent history of HFMD.

INTRODUCTION This study aimed to assess understanding of the potential risks associated with medical imaging among caregivers and adolescent patients in a paediatric emergency department (PED) in Singapore. METHODS A prospective convenience sample survey was performed involving adolescents and caregivers presenting to our PED from December 2015 to May 2016. The questionnaire examined demographic data, knowledge of imaging procedures and radiation risks, and expectations regarding information provided about medical radiation. RESULTS A total of 349 questionnaires were returned (caregivers 82.5%, adolescents 17.5%). A mean of 6.2 ± 2.4 (out of 11) questions were correctly answered. Those who had tertiary education fared better than those who did not (36.4% vs. 17.2% scoring above the mean, p = 0.001). Age, gender, history of previous imaging and imaging performed during the visit did not affect the score. Two-thirds of the participants did not associate medical radiation with any negative lifetime risk of cancers or know that different scans entailed differing amounts of radiation. Most were unaware that the radiation dose in medical imaging is adjusted to a child’s size. Among patients who underwent imaging, 90.1% received explanations on the need for scans, and 26.5% were informed of the risks involved. Almost all participants wished to be informed of imaging indications and risks. More preferred to learn this from physicians (75.6%) or technicians (51.6%) rather than through educational pamphlets (34.4%) or Internet resources (22.9%). CONCLUSION Awareness regarding medical radiation needs to be improved in our patient population. A mismatch exists between caregiver expectations and the actual procedure of disclosure of the risk associated with radiation.

Amyloid-β (Aβ) accumulating is considered as a causative factor for formation of senile plaque in Alzheimer’s disease (AD), but its mechanism is still elusive. The Nicotinamide mononucleotide adenylyltransferase 2 (Nmnat2), a key redox cofactor for energy metabolism, is reduced in AD. Accumulative evidence has shown that the decrease of α-secretase activity, a disintegrin and metalloprotease domain 10 (ADAM10), is responsible for the increase of Aβ productions in AD patient’s brain. Here, we observe that the activity of α-secretase ADAM10 and levels of Nmnat2 are significantly decreased, meanwhile there is a simultaneous elevation of Aβ in Tg2576 mice. Over-expression of Nmnat2 increases the mRNA expression of α-secretase ADAM10 and its activity and inhibits Aβ production in N2a/APPswe cells, which can be abolished by Compound C, an AMPK antagonist, suggesting that AMPK is involved in over-expression of Nmnat2 against Aβ production. The further assays demonstrate that Nmnat2 activates AMPK by up-regulating the ratio of NAD+/NADH, moreover AMPK agonist AICAR can also increase ADAM10 activity and reduces Aβ1-40/1-42. Taken together, Nmnat2 suppresses Aβ production and up-regulates ADAM10 in AMPK activity-dependent manner, suggesting that Nmnat2 may serve as a new potential target in arresting AD.

In recent decades, mass spectrometry-based lipidomics has provided a fertile environment for scientific investigations of biochemical and mechanistic processes in biological systems. Notably, this approach has been used to characterize physiological and pathological processes relevant to the central nervous system by identifying changes in the sphingolipid content in the brain, cerebral spinal fluid, and blood plasma. However, despite a preponderance of studies identifying correlations between specific lipids and disease progression, this powerful resource has not yet substantively translated into clinically useful diagnostic assays. Part of this gap may be explained by insufficient depth of the lipidomic profiles in many studies, by lab-to-lab inconsistencies in methodology, and a lack of absolute quantification. These issues limit the identification of specific molecular species and the harmonization of results across independent studies. In this chapter, we contextualize these issues with recent reports identifying correlations between brain lipids and neurological diseases, and we describe the workflow our group has optimized for analysis of the blood plasma sphingolipidome, adapted to the characterization of the human brain tissue.

Objective We aimed to investigate factors related to the 90-day poor prognosis (mRS≥3) in patients with transient ischemic attack (TIA) or minor stroke, construct 90-day poor prognosis prediction models for patients with TIA or minor stroke, and compare the predictive performance of machine learning models and Logistic model. Method We selected TIA and minor stroke patients from a prospective registry study (CNSR-III). Demographic characteristics,smoking history, drinking history(≥20g/day), physiological data, medical history,secondary prevention treatment, in-hospital evaluation and education,laboratory data, neurological severity, mRS score and TOAST classification of patients were assessed. Univariate and multivariate logistic regression analyses were performed in the training set to identify predictors associated with poor outcome (mRS≥3). The predictors were used to establish machine learning models and the traditional Logistic model, which were randomly divided into the training set and test set according to the ratio of 70:30. The training set was used to construct the prediction model, and the test set was used to evaluate the effect of the model. The evaluation indicators of the model included the area under the curve (AUC) of the discrimination index and the Brier score (or calibration plot) of the calibration index. Result A total of 10967 patients with TIA and minor stroke were enrolled in this study, with an average age of 61.77 ± 11.18 years, and women accounted for 30.68%. Factors associated with the poor prognosis in TIA and minor stroke patients included sex, age, stroke history, heart rate, D-dimer, creatinine, TOAST classification, admission mRS, discharge mRS, and discharge NIHSS score. All models, both those constructed by Logistic regression and those by machine learning, performed well in predicting the 90-day poor prognosis (AUC >0.800). The best performing AUC in the test set was the Catboost model (AUC=0.839), followed by the XGBoost, GBDT, random forest and Adaboost model (AUCs equal to 0.838, 0, 835, 0.832, 0.823, respectively). The performance of Catboost and XGBoost in predicting poor prognosis at 90-day was better than the Logistic model, and the difference was statistically significant(P Conclusion Machine learning algorithms were not inferior to the Logistic regression model in predicting the poor prognosis of patients with TIA and minor stroke at 90-day. Among them, the Catboost model had the best predictive performance. All models provided good discrimination.

Objectives To analyse the patterns of transition of health burden for 110 causes of death by stratification of age, sex and geographic regions in Guangdong between 2005 and 2015. Methods We analysed the age-specific, sex-specific, region-specific mortality in Guangdong based on assembled databases. County-level surveillance data were calculated to inform city-level changes. Results The age-standardised mortality of all causes, non-communicable diseases (NCDs), communicable diseases, maternal diseases, neonatal diseases, malnutrition and injury declined progressively. Despite declining mortality of NCDs, the overall burden of disease was dominated by NCDs (ie, cerebrovascular disease, chronic obstructive pulmonary disease) that still accounted for 86.93% and 88.12% of death in 2005 and 2015, respectively. Considerable variations across geographic regions were observed (lowest in Pearl River Delta and highest in west Guangdong). There was a modest shift to transport injuries at younger ages and unintentional injuries in the elderly. Conclusions We have documented a dramatic change in the overall mortality and age-specific, sex-specific and cause-specific mortality in Guangdong province between 2005 and 2015. The significant burden of NCDs remains a major healthcare issue despite the notable progress in reducing mortality in Guangdong, China. Our findings highlight important unmet needs to refine healthcare services by taking into account the inequity of age, sex and geographic regions. Identification of the ‘treatable’ risk factors and improved disease surveillance should be continuously improved to minimised the overall and cause-specific mortality.

Testicular cancer is the most common malignant tumor in young men, and its incidence has increased in recent years. The tumor microenvironment (TME) plays a crucial role in the development and progression of tumors; however, the TME of testicular germ cell tumor (TGCT) is poorly understood. In this study, we downloaded information for 156 TGCT cases from The Cancer Genome Atlas (TCGA) database, used the ESTIMATE method to determine immune and stromal scores, and used CIBERSORT to calculate the proportion of tumor-infiltrating immune cells (TICs). The differentially expressed genes were subjected to a COX regression analysis and used for the construction of a protein–protein interaction (PPI) network. Toll-like receptor 2 (TLR2) was identified as a predictive marker by combining the results of the Cox regression analysis and PPI network. A survival analysis showed that TLR2 was positively correlated with TGCT survival. A gene set enrichment analysis indicated that genes in the high TLR2 expression group were enriched for cell adhesion molecules (CAMs) and the chemokine signaling pathway, and genes in the low TLR2 expression group were mainly enriched in the spliceosome. Regarding proportions of TICs, naive B cells and follicular helper T cells were negatively correlated with the expression of TLR2. This suggests that as TLR2 expression increases, the immunocompetence of the TME decreases. The expression of TLR2 may affect the prognosis of TGCT, suggesting that this locus can be used as a prognostic factor for TGCT.

Background The aim of this study was to evaluate the in vivo confocal microscopic morphology of corneal subbasal nerves and its relationship with clinical parameters in patients with primary Sjögren’s syndrome in China. Methods This was a case control study of 22 dry eye disease (DED) patients with primary Sjögren’s syndrome (pSS) and 20 control subjects with non-Sjögren dry eye disease (NSDE). Each patient underwent an evaluation of ocular surface disease using the tear film break-up time (TBUT), noninvasive tear film break-up time (NIKBUT), noninvasive tear meniscus height (NIKTMH), corneal staining (National Eye Institute scale, NEI), Schirmer I test, meibography, and corneal subbasal nerve analysis with in vivo confocal microscopy (IVCM). The right eye of each subject was included in this study. Results SS patients showed a shorter TBUT (P = 0.009) and Schirmer I test results (P = 0.028) than the NSDE group. However, there was no significant difference in NIKBUT between the two groups (P = 0.393). The nerve density of subbasal nerves, number of nerves and tortuosity of the SS group were significantly lower than those of the NSDE group (P = 0.001, P P = 0.039, respectively). In the SS group, the mean nerve length was correlated with age and the Schirmer I test (r = − 0.519, P = 0.013 and r = 0.463, P = 0.035, respectively). Corneal staining was correlated with nerve density and the number of nerves (r = − 0.534, P = 0.013 and r = − 0.487, P = 0.025, respectively). Conclusions Sjögren syndrome dry eye (SSDE) patients have more severe clinical dry eye parameters than non-Sjögren dry eye disease (NSDE) patients. Compared with NSDE patients, we found that SSDE patients showed decreased corneal subbasal nerve density and numbers.

The implementation of lockdown measures to curb the transmission of Coronavirus disease-2019 (COVID-19) has brought about significant psychological impacts and older adults have been identified as one of the vulnerable groups. In the current COVID-19 context among older adults in the community, the fear of COVID-19, anxiety symptoms, compassion, resilience, and the practice of protective behaviors are possibly related to each other in several ways. How these factors relate to each other would have important implications in managing the spread of the disease and its mental health consequences. To this end, we modeled their interrelationships using a structural equation model. Older adults (N = 421), aged 60 and above completed various questionnairesCOVID-19 Fear Inventory, Short form of the Geriatric Anxiety Inventory, COVID-19 Risky and Protective Behaviours, Resilience Appraisals Scale, and Compassion Scale during a COVID-19 lockdown. The relationships between these variables were assessed within a structural equation model. The findings showed that older adults who are more compassionate engage in protective behaviors more frequently. Additionally, frequent practice of protective behaviors and greater resilience predicted lower anxiety among older adults. Greater fear predicted higher anxiety levels but did not significantly influence an individuals engagement in protective behaviors. Mental health services are crucial in fostering resilience and supporting older adults psychologically. Social services are also necessary in maintaining and enhancing social support for older adults. Importantly, these findings suggest that public health communications could promote compassion and avoid using a fear-based approach to increase engagement in protective behaviors., Lay Summary This study focused on the interrelations between various psychosocial factors (i.e., fear of COVID-19, compassion, and resilience) and the behavioral (i.e., engagement in protective health behaviors) and psychological responses (i.e., anxiety) to COVID-19 among community-dwelling older adults. The study analyzed self-reported data from 421 older adults who are aged 60 and above. The findings showed that older adults who are more compassionate engage in protective behaviors more frequently. Additionally, older adults who showed greater resilience and engage in protective health behaviors more frequently reported lower anxiety levels. Lastly, greater fear of COVID-19 predicted greater anxiety among older adults but did not significantly influence their engagement in protective health behaviors.

This study aimed to investigate the association between passive smoking and physical and psychological health in Chinese nurses. Participants of this cross-sectional study comprised 2,484 non-smoking nurses. Passive smoking and demographic information were assessed using a self-administered questionnaire. Physical, psychological, and overall health status of nurses were measured using the Cornell Medical Index (CMI) health questionnaire. Multivariate-adjusted odds ratio (OR) and 95% confidence interval (CI) for nurses' health were estimated by exposure to passive smoking using unconditional logistic regression models. A total of 1,219 nurses (49.07%) were exposed to passive smoking. Of these, 609 (24.52%), 160 (6.44%), and 587 (23.63%) nurses had poorer physical, mental, and overall health, respectively. After adjusting for other confounding factors, compared with the non-passive smoking group, passive smoking was associated with poor physical (OR = 1.51, 95% CI: 1.25–1.83), mental (OR = 1.48, 95% CI: 1.07–2.07), and overall (OR = 1.58, 95% CI: 1.30–1.93) health of nurses, respectively. We also carried out subgroup analyses stratified by age, department, and professional title, which showed that most findings supported the main results. This study demonstrated that exposure to passive smoking was a risk factor for overall decreased physical and mental health status among Chinese nurses.

Anesthesia and psychotropic drugs in pregnant women may cause long-term effects on the brain development of unborn babies. The authors set out to investigate the neurotoxicity of S-ketamine, which possesses anesthetic and antidepressant effects and may cause attention deficit hyperactivity disorder (ADHD)- and depression-like behaviors in offspring mice.Pregnant mice were administered with low-, medium-, and high-dose S-ketamine (15, 30, and 60 mg/kg) by intraperitoneal injection for 5 days from gestational day 14-18. At 21 days after birth, an elevated plus-maze test, fear conditioning, open field test, and forced swimming test were used to assess ADHD- and depression-like behaviors. Neuronal amount, glial activation, synaptic function indicated by ki67, and inhibitory presynaptic proteins revealed by GAD2 in the hippocampus, amygdala, habenula nucleus, and lateral hypothalamus (LHA) were determined by immunofluorescence assay.All the pregnant mice exposed to high-dose S-ketamine administration had miscarriage after the first injection. Both low-dose and medium-dose S-ketamine administration significantly increased the open-arm time and attenuated frozen time in the fear conditioning, which indicates impulsivity and memory dysfunction-like behaviors. Medium-dose S-ketamine administration reduced locomotor activity in the open field and increased immobility time in the forced swimming test, indicating depression-like behaviors. Changes in astrocytic activation, synaptic dysfunction, and decreased inhibitory presynaptic proteins were found in the hippocampus, amygdala, and habenula nucleus.These results demonstrate that S-ketamine may lead to detrimental effects, including ADHD-and depression-like behaviors in offspring mice. More studies should be promoted to determine the neurotoxicity of S-ketamine in the developing brain.

IntroductionMenstrual discomfort affects women's quality of life, which is an important public health issue. Evidence confirming the link between passive smoking and menstrual discomfort is limited. Therefore, the aim of this study is to investigate the aforementioned topic on the basis of a cross-sectional study of 2,571 non-smoking Chinese nurses.MethodsDemographic information and passive smoking were assessed using a self-administered questionnaire. Menstrual discomfort was characterized as dysmenorrhea, illness or weakness, bed rest, and restlessness during menstruation, which was assessed using a modified version of the Cornell Medical Index-Health Questionnaire. Multivariate-adjusted odds ratio (OR) and 95% confidence intervals (CIs) were estimated using the logistic regression model.ResultsA total of 1:195 nurses (46.48%) were exposed to passive smoking. Compared with non-passive smoking nurses, passive smoking nurses were more likely to have menstrual discomfort symptoms (72.38 vs. 64.39%), especially symptoms of dysmenorrhea (49.54 vs. 42.08%), illnesses or weakness (48.28 vs. 42.08%), and restlessness during menstruation (53.05 vs. 46.22%). Exposure to passive smoking was significantly associated with menstrual discomfort (OR = 1.41, 95%CI: 1.19–1.67), especially symptoms of dysmenorrhea (OR = 1.32, 95%CI: 1.13–1.56), illness or weakness (OR = 1.24, 95%CI: 1.06–1.46), and restlessness (OR = 1.26, 95%CI: 1.08–1.48) during menstruation. The subgroup analyses, stratified by age, children, and marital status, agreed with the main findings.ConclusionsExposure to passive smoking was related to symptoms of dysmenorrhea and menstrual discomfort.

Primary hyperparathyroidism (PHPT) is mainly caused by parathyroid adenoma, which produces excess parathyroid hormones. Its pathogenic mechanisms have not yet been fully understood. To investigate the mechanism in the pathogenesis of PHPT, the transcriptome and genome-wide DNA methylation profiles of parathyroid adenoma were analyzed. The candidate genes that may be involved in the PHPT were verified via qRT-PCR, immunohistochemistry, western blot, and methylation-specific PCR. A total of 1650 differentially expressed genes and 2373 differentially methylated regions were identified. After the integration of its transcriptome and DNA methylation data, IL6, SYP, GNA01, and pro-opiomelanocortin (POMC) were the candidate genes that demonstrated a similar pattern between their mRNA expression and DNA methylation status. Of the 4 candidate genes, POMC, a pro-peptide which is processed to a range of bioactive peptide products like ACTH, was further confirmed to be expressed at low levels at both the mRNA and protein levels, which may be due to POMC promoter hypermethylation. Hypermethylation of the POMC promoter may contribute to its low expression, which may be involved in the pathogenesis of PHPT.

Adolescence is the developmental process of becoming an adult. This journey of physical and psychological maturation is filled with challenges and hormonal chaos, and teenagers experience unhappiness at times. From a psychological perspective, this study aimed to examine the association between motivation, self-esteem and happiness; and to explore the mediating role of motivation in the association between self-esteem and happiness among adolescents in Malaysia. 480 secondary school students were recruited using a multistage cluster sampling method and answered the Malay versions of the Subjective Happiness, Brief Motivation and Rosenberg Self-esteem scales. Both self-esteem and motivation were found positively correlated to happiness. The hypothetical mediating role of motivation on the association between self-esteem and happiness was also supported, indicating that individuals with higher self-esteem have higher motivation which may result in greater happiness. Since the direct association between self-esteem and happiness remained significant, a partial mediation of adolescents’ motivation between self-esteem and happiness is indicated. The results showed that perceived self-esteem plays a role in predicting happiness and the presence of motivation enhances happiness, providing an insight to nurture happier adolescents for parents and educators in Malaysia.

Obesity is considered as a risk factor for chronic health diseases such as heart diseases, cancer, and diabetes 2. Reduced physical activities, lifestyle, poor nutritional diet, and genetics are among the risk factors associated with the development of obesity. In recent years, several studies have explored the link between the gut microbiome and the progression of diseases including obesity, with the shift in microbiome abundance and composition being the main focus. The alteration of gut microbiome composition affects both nutrients metabolism and specific gene expressions thereby disturbing body physiology. Specifically, the abundance of fiber-metabolizing microbes is associated with weight loss and that of protein and fat-metabolizing bacteria with weight gain. Various internal and external factors such as genetics, maternal obesity, mode of delivery, breastfeeding, nutrition, antibiotic use, and the chemical compounds present in the environment are known to interfere with the richness of the gut microbiota (GM), thereby influencing weight gain/loss and ultimately the development of obesity. However, the effectiveness of each factor in potentiating the shift in microbes' abundance to result in significant changes that can lead to obesity is not yet clear. In this review, we will highlight the factors involved in shaping gut microbiota, their influence on obesity and possible interventions. Understanding the influence of these factors on the diversity of the GM and how to improve their effectiveness on disease conditions could be key in the treatment of metabolic diseases.

Bladder cancer is one of the most common malignant tumors worldwide. Accordingly, its incidence and mortality are high. One of the characteristics of cancer is genomic instability. New studies suggest that long non-coding RNAs (lncRNAs) play an important role in maintaining genomic instability. This study aimed to identify a genomic instability-associated lncRNA signature to predict the outcome of patients with bladder cancer. We downloaded data for bladder cancer patients from The Cancer Genome Atlas database to obtain lncRNA expression profiles as well as somatic mutation profiles. Using the lncRNA computational framework, a genomic instability-related lncRNA signature (GIlncSig) was established and the prognostic value of this signature was assessed and validated. A five-lncRNA signature based on genomic instability (CFAP58-DT, MIR100HG, LINC02446, AC078880.3, and LINC01833) was obtained from 58 differentially expressed lncRNAs. Patients were divided into high-risk and low-risk groups, with the high-risk group having a substantially worse prognosis than the low-risk group. Univariate and multivariate Cox analyses indicated that GIlncSig may be an independent prognostic factor; this finding was subsequently validated. In addition, enrichment analysis indicated that GIlncSig is associated with genomic instability in bladder cancer. GIlncSig has a predictive value for the prognosis of bladder cancer patients and provides guidance for the clinical treatment of these patients.

In recent years, a vast number of potential cancer therapeutic targets have emerged. However, developing efficient and effective drugs for the targets is of major concern. Hydrogen sulfide (H2S), one of the three known gasotransmitters, is involved in the regulation of various cellular activities such as autophagy, apoptosis, migration, and proliferation. Low production of H2S has been identified in numerous cancer types. Treating cancer cells with H2S donors is the common experimental technique used to improve H2S levels; however, the outcome depends on the concentration/dose, time, cell type, and sometimes the drug used. Both natural and synthesized donors are available for this purpose, although their effects vary independently ranging from strong cancer suppressors to promoters. Nonetheless, numerous signaling pathways have been reported to be altered following the treatments with H2S donors which suggest their potential in cancer treatment. This review will analyze the potential of H2S donors in cancer therapy by summarizing key cellular processes and mechanisms involved.

To evaluate the functional and structural outcomes of intravitreal conbercept monotherapy using a "3 + pro re nata (PRN)" regimen in treatment-naïve subjects with polypoidal choroidal vasculopathy (PCV) up to 12 months.Thirty subjects (30 eyes) with PCV participated in this interventional, retrospective study. All subjects received intravitreal injections of 0.5 mg (0.05 ml) conbercept using a "3 + PRN" regimen for 12 months. The changes in best-corrected visual acuity (BCVA) and optical coherence tomography (OCT) parameters, polyp lesion area, and regression rate were evaluated at baseline, month 3, and month 12.At the study end-point, BCVA improved significantly from 52.80 ± 17.17 ETDRS letters at baseline to 62.20 ± 18.96 letters (P 0.001), with a mean gain of 9.40 ± 14.97 letters. The central retinal thickness (CRT) significantly reduced from 454.93 ± 147.31 μm at baseline to 308.73 ± 106.80 μm (P 0.001) at end-point, and the total macular volume (TMV) decreased from 9.51 ± 1.04 mmIntravitreal conbercept using the "3 + PRN" regimen was effective in the treatment of PCV.

Anaplastic thyroid carcinoma (ATC) is a highly malignant and aggressive thyroid malignancy with rapid onset and poor prognosis. There is no effective treatment for ATC yet. Molecular targeted therapy provides a new idea for ATC treatment. Tyrosine kinase inhibitor lenvatinib has potential in treating ATC patients with favorable efficacy in clinical trials. The effectiveness of the v-raf murine sarcoma viral oncogene homologue B1 ( BRAF) gene inhibitor dabrafenib in combination with trametinib for the treatment of BRAF (V600E) positive ATC patients has been demonstrated in clinical trials. The NCCN clinical practice guidelines in oncology has proposed dabrafenib in combination with trametinib as the preferred modality for the treatment of patients with BRAF (V600E) positive ATC. The immune checkpoint inhibitor pembrolizumab can be applied to treat thyroid cancer with high tumor mutational load and may be considered as the preferred modality for the treatment of ATC patients with high programmed death ligand-1 expression. The mammalian target of rapamycin pathway inhibitors, peroxisome proliferators-activated receptor γ agonists, endothelial growth factor receptors-targeting monoclonal antibody cetuximab and novel vascular blocker fosbretabulin are still in the clinical research stage, which are expected to provide new directions for the development of novel targeted drugs. This article reviews the current research progress on targeted drugs for the treatment of ATC.

Signal transducer and activator of transcription (STAT) is a unique protein family that binds to DNA and plays a vital role in regulating major physiological cellular processes. Seven STAT genes have been identified in the human genome. Several studies suggest STAT family members to be involved in cancer development, progression, and metastasis. However, the predictive relationship between STAT family expression and immune cell infiltration in endometrial cancer remains unknown.We explored STAT family expression and prognosis in endometrial cancer using various databases. The STRING, GeneMANIA, and DAVID databases, along with GO and KEGG analyses, were used to construct a protein interaction network of related genes. Finally, the TIMER database and ssGSEA immune infiltration algorithm were used to investigate the correlation of STAT family expression with the immune infiltration level in uterine corpus endometrial carcinoma (UCEC).Our study showed that different STAT family members are differentially expressed in UCEC. STAT1 and STAT2 expression increased at various stages of UCEC, and STAT5A, STAT5B, and STAT6 levels were decreased. STAT3 and STAT4 expression was not significantly different between UCEC and normal tissues. High STAT1 expression may be a prognostic disadvantage of UCEC, and high STAT6 expression may improve UCEC patient prognosis. The STAT family-associated genes were significantly enriched in signal transduction, protein binding, DNA binding, and ATP binding upon GO analysis. Related genes in the KEGG analysis were mainly enriched in pathways in cancer, viral carcinogenesis, chemokine signaling pathway, JAK/STAT signaling pathway, and regulation of the actin cytoskeleton. In terms of immune infiltration, STAT1 and STAT2 were positively correlated with B, CD8+ T, CD4+ T, and dendritic cells, and neutrophils (p 0.05). All STAT family members were positively correlated with neutrophils and dendritic cells (p 0.05). STAT1 and STAT2 showed similar correlations with all immune cell types, whereas STAT1 and STAT6 showed opposite correlations.These findings suggest that the STAT family is a prognostic marker, and the immune infiltration level, a therapeutic target, for endometrial cancer.

Hydrogen sulfide (H2S), a gaseous signaling molecule, is associated with the development of various malignancies via modulating various cellular signaling cascades. Published research has established the fact that inhibition of endogenous H2S production or exposure of H2S donors is an effective approach against cancer progression. However, the effect of pharmacological inhibition of endogenous H2S-producing enzymes (cystathionine-γ-lyase (CSE), cystathionine-β-synthase (CBS), and 3-mercaptopyruvate sulfurtransferase (3-MPST)) on the growth of breast cancer (BC) remains unknown. In the present study, DL-propargylglycine (PAG, inhibitor of CSE), aminooxyacetic acid (AOAA, inhibitor of CBS), and L-aspartic acid (L-Asp, inhibitor of 3-MPST) were used to determine the role of endogenous H2S in the growth of BC by in vitro and in vivo experiments. An in silico study was also performed to confirm the results. Corresponding to each enzyme in separate groups, we treated BC cells (MCF-7 and MDA-MB-231) with 10 mM of PAG, AOAA, and L-Asp for 24 h. Findings reveal that the combined dose (PAG + AOAA + L-Asp) group showed exclusive inhibitory effects on BC cells’ viability, proliferation, migration, and invasion compared to the control group. Further, treated cells exhibited increased apoptosis and a reduced level of phospho (p)-extracellular signal-regulated protein kinases such as p-AKT, p-PI3K, and p-mTOR. Moreover, the combined group exhibited potent inhibitory effects on the growth of BC xenograft tumors in nude mice, without obvious toxicity. The molecular docking results were consistent with the wet lab experiments and enhanced the reliability of the drugs. In conclusion, our results demonstrate that the inhibition of endogenous H2S production can significantly inhibit the growth of human breast cancer cells via the AKT/PI3K/mTOR pathway and suggest that endogenous H2S may act as a promising therapeutic target in human BC cells. Our study also empowers the rationale to design novel H2S-based anti-tumor drugs to cure BC.

Background Biochemical markers are crucial for determining risk in coronary artery disease (CAD) patients; however, the relationship between fasting blood glucose to high-density lipoprotein cholesterol (FG/HDL-C) ratio and short-term outcomes in acute coronary syndrome (ACS) patients remains unknown. Therefore, we have investigated the relationship between the FG/HDL-C ratio and short-term outcomes in ACS patients. Methods We used data from a pragmatic, stepped-wedge, cluster-randomized clinical trial to perform a post hoc analysis. A total of 11,284 individuals with ACS were subdivided into quartiles according to their FG/HDL-C ratios. We used a multivariate logistic regression model, two-piecewise linear regression model, and generalized additive model (GAM) to evaluate the relationship between the FG/HDL-C ratio and short-term outcomes (major adverse cardiovascular events [MACEs] and cardiovascular [CV] death within 30 days). Results The FG/HDL-C ratio was remarkably linked to an enhanced risk of MACEs and CV death in individuals with ACS in the highest quartile (MACEs, odds ratio [OR]: 1.49; 95% confidence interval [CI], [1.11, 1.99]; P P = 0.04). The GAM suggested that the relationship between the FG/HDL-C ratio and MACEs and CV death was non-linear. The two-piecewise linear regression model demonstrated that the threshold values were 3.02 and 3.00 for MACEs and CV death, respectively. Conclusions A higher FG/HDL-C ratio is associated with a higher risk of MACEs and CV death in patients with ACS.

Thyroid cancer is considered to be one of the most common endocrine tumors worldwide. Cystathionine

Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP) and Bioinformatics Analysis Tool for Molecular Mechanism of Traditional Chinese Medicine(BATMAN-TCM) were searched for the effective components and targets of Shaofu Zhuyu Decoction. The relevant targets for endometriosis(EMT) and dysmenorrhea were retrieved from the Comparative Toxicogenomics Database(CTD), Therapeutic Target Database(TTD), GeneCards, and DisGeNET with the terms ofquot;endometriosisquot; andquot;dysmenorrheaquot;. Cytoscape 3.8.0 was employed to construct the drug-active component-therapeutic target network. A protein-protein interaction(PPI) network was established by STRING 11.0. Analyze Network, the plug-in in the Cytoscape 3.8.0, was used to calculate the topological parameters of the nodes and screen out the critical proteins in the network. The potential therapeutic targets were imported into RStudio and subjected to Gene Ontology(GO) and Kyoto Encyclopedia of Genes and Genomes(KEGG) enrichment analyses with clusterProfiler package. Finally, the AutoDock Vina(Vina) platform was used for molecular docking to predict the binding degree of the main active components of Shaofu Zhuyu Decoction to key targets. As revealed by the screening results, 136 active components and 380 targets of Shaofu Zhuyu Decoction were obtained. Additionally, there were 1 627 targets related to EMT and 142 targets related to dysmenorrhea with 107 common targets, and 42 potential therapeutic targets of Shaofu Zhuyu Decoction for the treatment of EMT-induced dysmenorrhea. The targets such as interleukin 6(IL6) and prostaglandi-nendoperoxide synthase-2(PTGS2) were pivotal in the biological network of Shaofu Zhuyu Decoction intervention in EMT-induced dysmenorrhea, which involved multiple signaling pathways, including inflammation, hormones, and those promoted cell proliferation [e.g., mitogen-activated protein kinase(MAPK) and phosphatidylinositol-3 kinase(PI3 K)-protein kinase B(AKT)]. The results of molecular docking showed that the active components of Shaofu Zhuyu Decoction had good binding capacities to key targets such as IL6 and PTGS2. The findings of this study demonstrated that Shaofu Zhuyu Decoction could treat EMT-induced dysmenorrhea through multiple targets and multiple pathways, which could provide new ideas for investigating the underlying mechanism of Shaofu Zhuyu Decoction in the treatment of EMT-induced dysmenorrhea.

Centrosome amplification is a phenomenon frequently observed in human cancers, so centrosome depletion has been proposed as a therapeutic strategy. However, despite being afflicted with a lack of centrosomes, many cancer cells can still proliferate, implying there are impediments to adopting centrosome depletion as a treatment strategy. Here, we show that TFEB- and TFE3-dependent autophagy activation contributes to acentrosomal cancer proliferation. Our biochemical analyses uncover that both TFEB and TFE3 are novel PLK4 (polo like kinase 4) substrates. Centrosome depletion inactivates PLK4, resulting in TFEB and TFE3 dephosphorylation and subsequent promotion of TFEB and TFE3 nuclear translocation and transcriptional activation of autophagy- and lysosome-related genes. A combination of centrosome depletion and inhibition of the TFEB-TFE3 autophagy-lysosome pathway induced strongly anti-proliferative effects in cancer cells. Thus, our findings point to a new strategy for combating cancer. Abbreviations: AdCre: adenoviral Cre recombinase; AdLuc: adenoviral luciferase; ATG5: autophagy related 5; CQ: chloroquine; DAPI: 4’,6-diamidino-2-phenylindole; DKO: double knockout; GFP: green fluorescent protein; KO: knockout; LAMP1: lysosomal associated membrane protein 1; LAMP2: lysosomal associated membrane protein 2; LTR: LysoTracker Red; MAP1LC3B/LC3B: microtubule associated protein 1 light chain 3 beta; MITF: melanocyte inducing transcription factor; PLK4: polo like kinase 4; RFP: red fluorescent protein; SASS6: SAS-6 centriolar assembly protein; STIL: STIL centriolar assembly protein; TFEB: transcription factor EB; TFEBΔNLS: TFEB lacking a nuclear localization signal; TFE3: transcription factor binding to IGHM enhancer 3; TP53/p53: tumor protein p53

Oral diseases are among the most common human diseases yet less studied. These diseases affect both the physical, mental, and social health of the patients resulting in poor quality of life. They affect all ages, although severe stages are mostly observed in older individuals. Poor oral hygiene, genetics, and environmental factors contribute enormously to the development and progression of these diseases. Although there are available treatment options for these diseases, the recurrence of the diseases hinders their efficiency. Oral volatile sulfur compounds (VSCs) are highly produced in oral cavity as a result of bacteria activities. Together with bacteria components such as lipopolysaccharides, VSCs participate in the progression of oral diseases by regulating cellular activities and interfering with the immune response. Hydrogen sulfide (H2S) is a gaseous neurotransmitter primarily produced endogenously and is involved in the regulation of cellular activities. The gas is also among the VSCs produced by oral bacteria. In numerous diseases, H2S have been reported to have dual effects depending on the cell, concentration, and donor used. In oral diseases, high production and subsequent utilization of this gas have been reported. Also, this high production is associated with the progression of oral diseases. In this review, we will discuss the production of H2S in oral cavity, its interaction with cellular activities, and most importantly its role in oral diseases.

Background There has been ongoing research impetus to uncover novel blood-based diagnostic and prognostic biomarkers for Alzheimer’s disease (AD), vascular dementia (VaD), and related cerebrovascular disease (CEVD)-associated conditions within the spectrum of vascular cognitive impairment (VCI). Sphingosine-1-phosphates (S1Ps) are signaling lipids which act on the S1PR family of cognate G-protein-coupled receptors and have been shown to modulate neuroinflammation, a process known to be involved in both neurodegenerative and cerebrovascular diseases. However, the status of peripheral S1P in AD and VCI is at present unclear. Methods We obtained baseline bloods from individuals recruited into an ongoing longitudinal cohort study who had normal cognition (N = 80); cognitive impairment, no dementia (N = 160); AD (N = 113); or VaD (N = 31), along with neuroimaging assessments of cerebrovascular diseases. Plasma samples were processed for the measurements of major S1P species: d16:1, d17:1, d18:0, and d18:1, along with pro-inflammatory cytokines interleukin (IL)-6, IL-8, and tumor necrosis factor (TNF). Furthermore, in vitro effects of S1Ps on cytokine expression were also studied in an astrocytoma cell line and in rodent primary astrocytes. Results Of the S1Ps species measured, only d16:1 S1P was significantly reduced in the plasma of VaD, but not AD, patients, while the d18:1 to d16:1 ratios were increased in all cognitive subgroups (CIND, AD, and VaD). Furthermore, d18:1 to d16:1 ratios correlated with levels of IL-6, IL-8, and TNF. In both primary astrocytes and an astroglial cell line, treatment with d16:1 or d18:1 S1P resulted in the upregulation of mRNA transcripts of pro-inflammatory cytokines, with d18:1 showing a stronger effect than d16:1. Interestingly, co-treatment assays showed that the addition of d16:1 reduced the extent of d18:1-mediated gene expression, indicating that d16:1 may function to “fine-tune” the pro-inflammatory effects of d18:1. Conclusion Taken together, our data suggest that plasma d16:1 S1P may be useful as a diagnostic marker for VCI, while the d18:1 to d16:1 S1P ratio is an index of dysregulated S1P-mediated immunomodulation leading to chronic inflammation-associated neurodegeneration and cerebrovascular damage.

The amino acid sequence enriched with proline (P), glutamic acid (E), serine (S), and threonine (T) (PEST) is a signal-transducing agent providing unique features to its substrate nuclear proteins (PEST-NPs). The PEST motif is responsible for particular posttranslational modifications (PTMs). These PTMs impart distinct properties to PEST-NPs that are responsible for their activation/inhibition, intracellular localization, and stability/degradation. PEST-NPs participate in cancer metabolism, immunity, and protein transcription as oncogenes or as tumor suppressors. Gene-based therapeutics are getting the attention of researchers because of their cell specificity. PEST-NPs are good targets to explore as cancer therapeutics. Insights into PTMs of PEST-NPs demonstrate that these proteins not only interact with each other but also recruit other proteins to/from their active site to promote/inhibit tumors. Thus, the role of PEST-NPs in cancer biology is multivariate. It is hard to obtain therapeutic objectives with single gene therapy. An especially designed combination gene therapy might be a promising strategy in cancer treatment. This review highlights the multifaceted behavior of PEST-NPs in cancer biology. We have summarized a number of studies to address the influence of structure and PEST-mediated PTMs on activation, localization, stability, and protein-protein interactions of PEST-NPs. We also recommend researchers to adopt a pragmatic approach in gene-based cancer therapy.

Introduction We evaluated the risk factors associated with Type 1 retinopathy of prematurity (ROP) in very low birth weight (VLBW) infants and compared ophthalmologic outcomes between cases with Type 1 ROP who received treatment and gestational age-matched controls with mild or no ROP not requiring treatment. Methods This was a retrospective case-control study of VLBW infants born in National University Hospital, Singapore, from January 2001 to December 2013. 17 cases with Type 1 ROP were each matched for gestational age with controls who had either mild (below Stage 2) or no ROP. Antenatal, perinatal and postnatal variables, as well as childhood ophthalmologic outcomes, were collected from their clinical records and analysed. Results The number of packed cell transfusions and highest fraction of inspired oxygen given at weeks 7-10 were found to be statistically significant on multivariate analysis (p = 0.045 and p = 0.049, respectively). None of the infants had blindness or retinal detachment, and there were no significant differences in refractive errors between the groups at 1-4 years of age. Strabismus at four years of age was more common in the group with Type 1 ROP (p = 0.023). Conclusion Increased episodes of blood transfusions and chronic lung disease requiring high oxygen supplementation at 7-10 weeks of life are significant risk factors associated with Type 1 ROP in VLBW infants in our study. Strabismus at four years is more common in this group of patients. This study highlights the importance of long-term ophthalmologic surveillance for these high-risk children.

Inherent and/or acquired multi-drug resistance might be the instigator of treatment failure for acute myeloid leukemia (AML). In the current study, we aimed to explored the chemosensitizing effect of 4-HPR on AML therapy. Luciferase reporter assays were used to test the effect of 4-HPR on transcriptional signaling pathways. The quantitative real-time polymerase chain reaction and immunoblots were used to confirm the role of 4-HPR in NF-κB inhibition, apoptosis, and drug resistance. MTT and flow cytometry assays were applied to test the drug response and chemosensitizing effect of 4-HPR with AML cell lines and primary AML samples. 4-HPR suppressed tumor necrosis factor-α- and daunorubin-induced NF-κB activation in AML cell lines. The expression of anti-apoptotic gene, BCL2, was downregulated, while expressions of pro-apoptotic genes, cIAP, XIAP, and BID, were increased after 4-HPR treatment. Immunoblots showed decreased p65-NF-κB, IκBα, and MDR1, but increased cleaved poly (ADP-ribose) polymerase and BIM. A low concentration of 4-HPR chemosensitized AML cells to daunorubin treatment in vitro. 4-HPR-induced NF-κB inhibition was the main driver of the chemosensitizing effect observed in AML cell lines and primary AML samples. These results highlight that 4-HPR might be a promising chemosensitizing agent in AML therapy.

Ever reports showed that PCNP is associated with human cancers including neuroblastoma and lung cancer. However, the role and underlying molecular mechanism of PCNP in ovarian cancer have not been plenty elucidated. Herein, we first investigated the expression of PCNP in ovarian cancer tissues and cells, the effects of PCNP in ovarian cancer proliferation, apoptosis, migration and invasion, and determined the molecular mechanism of PCNP in ovarian cancer progression. The results indicated that PCNP was significantly overexpressed in human ovarian cancer tissues and cells, and related to poor prognosis in ovarian cancer patients. In addition, we also detected that PCNP promoted ovarian cancer cells growth, migration and invasion, as well as inhibited ovarian cancer cells apoptosis. Mechanistically, PCNP binding to β‐catenin promoted β‐catenin nuclear translocation and further activated Wnt/β‐catenin signalling pathway. Moreover, PCNP regulated the expression of genes involved in EMT and further triggered EMT occurrence. Conclusionally, PCNP may promote ovarian cancer progression through activating Wnt/β‐catenin signalling pathway and EMT, acting as a novel and promising target for treating ovarian cancer.

Background Breast cancer is the leading cause of death among women worldwide. Studies have identified breast density as a controversial risk factor of breast cancer. Moreover, studies found that breast density reduction through Tamoxifen could reduce risk of breast cancer significantly. To date, no study on the association between breast density and breast cancer has been carried out in Malaysia. If breast density is proven to be a risk factor of breast cancer, intervention could be carried out to reduce breast cancer risk through breast density reduction. Purpose To determine if density of breast is an independent risk factor which will contribute to development of breast cancer. Materials and Methods A prospective cohort study is carried out in two hospitals targeting adult female patients who presented to the Breast Clinic with symptoms suspicious of breast cancer. Participants recruited were investigated for breast cancer based on their symptoms. Breast density assessed from mammogram was correlated with tissue biopsy results and final diagnosis of benign or malignant breast disease. Results Participants with dense breasts showed 29% increased risk of breast cancer when compared to those with almost entirely fatty breasts (odds ratio [OR] 1.29, 95% CI 0.38‐4.44, P = .683). Among the postmenopausal women, those with dense breasts were 3.1 times more likely to develop breast cancer compared with those with fatty breasts (OR 3.125, 95% CI 0.72‐13.64, P = .13). Moreover, the chance of developing breast cancer increases with age (OR 1.046, 95% CI 1.003‐1.090, P, There are many established risk factors of breast cancer, and density of breast is a controversial risk factor which we wanted to evaluate. Our study shows that postmenopausal women with dense breasts are 3 times more likely to develop breast cancer compared to those with low breast density.

Background and aims The SPINK1 c.194 + 2T > C variant has been increasingly recognized as an important risk factor for chronic pancreatitis (CP). However, there is no clear agreement on its contribution to different ethnicities and CP etiologies. To address this issue, a meta-analysis of literature was performed. Methods Studies addressing the presence of the SPINK1 c.194 + 2T > C variant in CP patients and controls were retrieved from the PubMed, EMBASE and Cochrane databases. Initial analysis included all CP patients, followed by subgroup analyses for East Asian and non-East Asian patients, and for idiopathic CP (ICP) and non-ICP. Results A total of 13 studies were retrieved for analysis, comprising 2097 cases and 4019 controls. There were 126 cases (10.01%) carrying the SPINK1 c.194 + 2T > C variant in cases, while only two controls were carriers (0.05%). Overall, the variant was significantly associated with an increased risk of CP (OR = 25.73). In the subgroup, the variant was significantly associated with increased risk of CP in East Asians (OR = 73.16), and in non-East Asians (OR = 10.21). Further, the contribution of the variant in ICP (OR = 35.31) was found to be higher than in non-ICP (25.75). Conclusions The SPINK1 c.194 + 2T > C variant is a strong risk factor for CP, especially in East Asian patients with ICP.

Since the end of 2019, a new type of coronavirus pneumonia (COVID-19) caused by the Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) has been spreading rapidly throughout the world. Previously, there were two outbreaks of severe coronavirus caused by different coronaviruses worldwide, namely Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV) and the Middle East Respiratory Syndrome Coronavirus (MERS-CoV). This article introduced the origin, virological characteristics and epidemiological overview of SARS-CoV-2, reviewed the currently known drugs that may prevent and treat coronavirus, explained the characteristics of the new coronavirus and provided novel information for the prevention and treatment of COVID-19.

Objective The prevalence of inflammatory bowel disease (IBD) has been increasing worldwide, and the risk of infection has increased due to the use of immunosuppressive and biologic medications. Some of these infections can be prevented with vaccinations. The aim of this study was to evaluate the vaccination practices of Chinese gastroenterologists for patients with IBD. Methods Questionnaires based on quick response codes were sent using email and the WeChat platform to gastroenterologists at 20 hospitals in China. The vaccination practices of the gastroenterologists, including vaccinating for hepatitis B, hepatitis A, and varicella, were assessed. Results Of the 468 gastroenterologists who received the questionnaire, 307 (65.6%) completed it. Of the gastroenterologists who were most concerned about hepatitis B; 83.4% always or frequently asked about an infection history, 53.7% took an immunization history, and 73.6% tested patients for hepatitis B infection. However, few gastroenterologists did so for hepatitis A or varicella. The proportion of patients who were asked about an infection and immunization history and tested for varicella infection was 16.0%, 15.0%, and 9.4%, respectively. Only a few gastroenterologists recommended vaccination for patients without an infection before IBD medical treatment (26.7% for hepatitis A, 45.6% for hepatitis B, and 28% for varicella vaccination). Conclusion Vaccination practices for patients with IBD used by Chinese gastroenterologists vary greatly, suggesting that education about immunization is needed.

To compare the clinical effect of acupuncture combined with wheat-grain moxibustion and oral sertraline hydrochloride dispersible tablets in the treatment of mild to moderate postpartum depression.Sixty patients with mild to moderate postpartum depression were randomly divided into an observation group and a control group, 30 cases in each group. Both groups were treated with psychotherapy. The control group was treated with oral sertraline hydrochloride dispersible tablets, 50 mg each time, once a day; the observation group was treated with acupuncture at Qihai (CV 6), Zusanli (ST 36), Xuehai (SP 10), Hegu (LI 4), Sanyinjiao (SP 6), Taixi (KI 3), etc. combined with wheat-grain moxibustion at Xinshu (BL 15), Pishu (BL 20), Ganshu (BL 18) and Shenshu (BL 23), once every other day, 3 times a week. Both groups were treated for 4 weeks as a course, with 2 consecutive courses of treatment. Before and after treatment and follow-up of 3 months after the end of treatment, the Hamilton depression scale (HAMD), Edinburgh postnatal depression scale (EPDS) and World Health Organization quality of life-BREF (WHOQOL-BREF) score of the two groups were compared, and the clinical effect was assessed.After treatment and during follow-up, the HAMD and EPDS scores of the two groups were lower than before treatment (Acupuncture combined with wheat-grain moxibustion can improve the depressive symptoms of patients with mild to moderate postpartum depression and improve their quality of life, and the clinical effect is more lasting and stable than oral sertraline hydrochloride dispersible tablets.

Esophageal squamous cell carcinoma (ESCC) is a major cause of cancer-related deaths. We have previously connected a non-sulfated glycosaminoglycan, hyaluronic acid (HA), with a common hydrogen sulfide (H

The appearance of the intestinal mucosa during endoscopy varies among patients with primary intestinal lymphangiectasia (PIL).To classify the endoscopic features of the intestinal mucosa in PIL under endoscopy, combine the patients' imaging and pathological characteristics of the patients, and explain their causes.We retrospectively analyzed the endoscopic images of 123 patients with PIL who were treated at the hospital between January 1, 2007 and December 31, 2018. We compared and analyzed all endoscopic images, classified them into four types according to the endoscopic features of the intestinal mucosa, and analyzed the post-lymphographic computed tomography (PLCT) and pathological characteristics of each type.According to the endoscopic features of PIL in 123 patients observed during endoscopy, they were classified into four types: nodular-type, granular-type, vesicular-type, and edematous-type. PLCT showed diffuse thickening of the small intestinal wall, and no contrast agent was seen in the small intestinal wall and mesentery in the patients with nodular and granular types. Contrast agent was scattered in the small intestinal wall and mesentery in the patients with vesicular and edematous types. Analysis of the small intestinal mucosal pathology revealed that nodular-type and granular-type lymphangiectasia involved the small intestine mucosa in four layers, whereas ectasia of the vesicular- and edematous-type lymphatic vessels largely involved the lamina propria mucosae, submucosae, and muscular layers.Endoscopic classification, combined with the patients' clinical manifestations and pathological examination results, is significant and very useful to clinicians when scoping patients with suspected PIL.

Secreted protein, acidic and rich in cysteine (SPARC, also known as osteonectin), is a small molecule glycoprotein associated with cell secretions. The purpose of our research is to clarify the clinicopathological and prognostic significance of SPARC expression in breast cancer. In this study, we performed a meta-analysis and bioinformatics analysis using the PubMed, Web of Science, Wanfang Data, and CNKI databases. The meta-analysis showed that SPARC expression was elevated in breast cancer tissue, compared with normal tissue, while SPARC expression in tumor stromal cells was higher than that of tumor cells. The expression of SPARC was positively correlated with histological grade and TNM staging. The Kaplan-Meier plotter showed that low SPARC expression was negatively correlated with the overall, postprogression, and distant metastasis survival rates of patients. According to Oncomine database, SPARC expression was upregulated in breast cancer than normal tissues. In TCGA database, univariate analysis showed that lymph node metastasis, distant metastasis, and TNM staging were negatively correlated with patient prognosis in breast cancers. Cox multivariate analysis showed that age, lymph node metastasis, distant metastasis, and TNM staging were important factors affecting the survival time of breast cancer patients. SPARC expression can be employed as a good indicator of prognosis of breast cancer patients, which will provide new methods and ideas of preventive treatment.

Background Under the outbreak of Coronavirus disease 2019 (COVID-19), a structural equation model was established to determine the causality of important factors that affect Chinese citizens’ COVID-19 prevention behavior. Methods The survey in Qingdao covered several communities in 10 districts and used the method of cluster random sampling. The research instrument used in this study is a self-compiled Chinese version of the questionnaire. Of the 1215 questionnaires, 1188 were included in our analysis. We use the rank sum test, which is a non-parametric test, to test the influence of citizens’basic sociodemographic variables on prevention behavior, and the rank correlation test to analyze the influencing factors of prevention behavior. IBM AMOS 24.0 was used for path analysis, including estimating regression coefficients and evaluating the statistical fits of the structural model, to further explore the causal relationships between variables. Results The result showed that the score in the prevention behavior of all citizens is a median of 5 and a quartile spacing of 0.31. The final structural equation model showed that the external support for fighting the epidemic, the demand level of health information, the cognition of (COVID-19) and the negative emotions after the outbreak had direct effects on the COVID-19 prevention behavior, and that negative emotions and information needs served as mediating variables. Conclusions The study provided a basis for relevant departments to further adopt epidemic prevention and control strategies.

BackgroundThis is the first study to investigate the effect of parental psychological abuse on potential psychopathological symptoms in gender minority youth subgroups, including transgender women, transgender men, and gender queer individuals.MethodsData was analysed from the Chinese National Transgender Survey in 2017; the survey was distributed through community-based organizations to transgender adolescents and adults residing in China, with representation from all 32 provinces and autonomous regions. A total of 1293 youth that self-identified as transgender or gender queer completed the study. Measures covered psychopathological symptoms including depression, anxiety, risk of suicideand self-harm. Parental psychological abuse was assessed in terms of neglect and avoidance, force to change, and verbal insults. Both the edges and centralities were computed via network analysis, and the network properties were then compared among the three gender minority subgroups. In addition, linear regression was adopted to test the predictive ability of node centrality for low self-esteem.ResultsDescriptive analysis revealed that among the three subgroups, transgender women had more severe psychopathological symptoms and reported the most psychological abuse. Network analysis revealed that the risk of suicide and self-harm was directly connected with one type of parental psychological abuse (“neglect and avoidance”). Node centrality was significantly associated with the predicting value of the nodes on low self-esteem (r2= 0.25, 0.17, 0.31) among all three gender minority subgroups.ConclusionsThe distinctive core psychopathological symptoms, within the networks of the gender minority subgroups, revealed specific symptoms across each group. The significant association between node centrality and low self-esteem indicated the extent of parental psychological abuse. Parental psychological abuse directed towards gender minority youth should be recognized as a form of family cold violence. It is recommended that schools and local communities should support early intervention to improve psychological well-being.