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1.
Sci Rep ; 14(1): 15717, 2024 Jul 08.
Article in English | MEDLINE | ID: mdl-38977823

ABSTRACT

Obesity is a global health concern and independent risk factor for cancers including hepatocellular carcinoma (HCC). However, evidence on the causal links between obesity and HCC is limited and inconclusive. This study aimed to investigate the causal relationship between obesity-related traits and HCC risk and explore underlying mechanisms using bioinformatics approaches. Two-sample Mendelian randomization analysis was conducted leveraging publicly available genome-wide association study summary data on obesity traits (body mass index, body fat percentage, waist circumference, waist-to-hip ratio, visceral adipose tissue volume) and HCC. Associations of obesity with primary mechanisms (insulin resistance, adipokines, inflammation) and their effects on HCC were examined. Differentially expressed genes in obesity and HCC were identified and functional enrichment analyses were performed. Correlations with tumor microenvironment (TME) and immunotherapy markers were analyzed. Genetically predicted higher body mass index and body fat percentage showed significant causal relationships with increased HCC risk. Overall obesity also demonstrated causal links with insulin resistance, circulating leptin levels, C-reactive protein levels and risk of severe insulin resistant type 2 diabetes. Four differentially expressed genes (ESR1, GCDH, FAHD2A, DCXR) were common in obesity and HCC. Enrichment analyses indicated their roles in processes like RNA capping, viral transcription, IL-17 signaling and endocrine resistance. They exhibited negative correlations with immune cell infiltration and immunotherapy markers in HCC. Overall obesity likely has a causal effect on HCC risk in Europeans, possibly via influencing primary mechanisms. The identified differentially expressed genes may be implicated in obesity-induced hepatocarcinogenesis through regulating cell cycle, inflammation and immune evasion. Further research on precise mechanisms is warranted.


Subject(s)
Carcinoma, Hepatocellular , Genome-Wide Association Study , Liver Neoplasms , Obesity , Humans , Carcinoma, Hepatocellular/genetics , Liver Neoplasms/genetics , Obesity/complications , Obesity/genetics , Body Mass Index , Risk Factors , Insulin Resistance/genetics , Tumor Microenvironment/genetics , Mendelian Randomization Analysis
2.
Nat Commun ; 15(1): 5312, 2024 Jun 21.
Article in English | MEDLINE | ID: mdl-38906856

ABSTRACT

Drug exposure during pregnancy lacks global fetal safety data. The maternal drug exposure birth cohort (DEBC) study, a prospective longitudinal investigation, aims to explore the correlation of maternal drug exposure during pregnancy with pregnancy outcomes, and establish a human biospecimen biobank. Here we describe the process of establishing DEBC and show that the drug exposure rate in the first trimester of pregnant women in DEBC (n = 112,986) is 30.70%. Among the drugs used, dydrogesterone and progesterone have the highest exposure rates, which are 11.97% and 10.82%, respectively. The overall incidence of adverse pregnancy outcomes is 13.49%. Dydrogesterone exposure during the first trimester is correlated with higher incidences of stillbirth, preterm birth, low birth weight, and birth defects, along with a lower incidence of miscarriage/abortion. Due to the limitations of this cohort study, causative conclusions cannot be drawn. Further follow-up and in-depth data analysis are planned for future studies.


Subject(s)
Maternal Exposure , Pregnancy Outcome , Pregnancy Trimester, First , Premature Birth , Humans , Female , Pregnancy , China/epidemiology , Maternal Exposure/adverse effects , Adult , Premature Birth/epidemiology , Prospective Studies , Pregnancy Outcome/epidemiology , Dydrogesterone/adverse effects , Progesterone , Birth Cohort , Infant, Newborn , Abortion, Spontaneous/epidemiology , Abortion, Spontaneous/chemically induced , Stillbirth/epidemiology , Infant, Low Birth Weight , Longitudinal Studies , Incidence , Young Adult
3.
World J Gastroenterol ; 30(8): 833-842, 2024 Feb 28.
Article in English | MEDLINE | ID: mdl-38516241

ABSTRACT

The population of non-alcoholic fatty liver disease (NAFLD) patients along with relevant advanced liver disease is projected to continue growing, because currently no medications are approved for treatment. Fecal microbiota transplantation (FMT) is believed a novel and promising therapeutic approach based on the concept of the gut-liver axis in liver disease. There has been an increase in the number of pre-clinical and clinical studies evaluating FMT in NAFLD treatment, however, existing findings diverge on its effects. Herein, we briefly summarized the mechanism of FMT for NAFLD treatment, reviewed randomized controlled trials for evaluating its efficacy in NAFLD, and proposed the prospect of future trials on FMT.


Subject(s)
Gastrointestinal Microbiome , Non-alcoholic Fatty Liver Disease , Humans , Fecal Microbiota Transplantation/adverse effects , Non-alcoholic Fatty Liver Disease/therapy , Randomized Controlled Trials as Topic
4.
Risk Manag Healthc Policy ; 17: 269-277, 2024.
Article in English | MEDLINE | ID: mdl-38313395

ABSTRACT

Purpose: Temperature changes unfavorably impact on cardiovascular disease. However, the association between temperature changes and coronary artery disease (CAD) is not well documented. This study aimed to explore the association between daily mean temperature and daily CAD hospital admissions on the southeast coast of China (Fuzhou City). Methods: A total of 1883 CAD patients who underwent percutaneous coronary intervention between 2017 and 2019 were obtained. The severity of CAD was evaluated by the Gensini score. Distributed lag non-linear model (DLNM) combined with a quasi-Poisson regression model was used to examine the delayed effect between daily mean temperature and daily CAD hospital admissions. Stratified analyses were performed by Gensini score and severity of lesions. The relative risk (RR) with a 95% confidence interval (CI) was used to assess the relationship. Results: Extreme cold (8°C) (RR=0.49, 95% CI: 0.25-0.99) and moderate cold (10°C) (RR=0.56, 95% CI: 0.31-0.99) daily mean temperature with a lag of 0-20 days were correlated with lower risk of daily CAD hospital admissions. Moderate heat (30°C) (RR=1.80, 95% CI: 1.01-3.20) and extreme heat (32°C) (RR=2.02, 95% CI: 1.01-4.04) daily mean temperature with a lag of 0-20 days related to a higher risk of daily CAD hospital admissions. Similar results were observed for daily mean temperature with a lag of 0-25 days. Stratified analysis showed the lagged effect of daily mean temperature (lag 0, 0-5, 0-15, 0-20, and 0-25 days) on the daily CAD hospital admissions was observed only in patients with a Gensini score ≤39 (tertile 1). Conclusion: Cold temperatures may have a protective effect on daily CAD hospital admissions in the Fuzhou area, whereas hot temperatures can have an adverse effect.

5.
RSC Adv ; 13(37): 26160-26168, 2023 Aug 29.
Article in English | MEDLINE | ID: mdl-37671003

ABSTRACT

Bicyclic hydantoinothiolactone (1), as the key intermediate for production of (+)-biotin, has been efficiently and high-stereoselectively synthesized from the cheap starting material l-cystine via nine steps in 44% overall yield. In this new practical synthesis, there are two characteristic steps worthy of note. One step is TMSOTf-catalyzed efficient cyanation of (3S,7aR)-6-benzyl-5-oxo-3-phenyltetrahydro-1H,3H-imidazo[1,5-c]thiazol-7-yl acetate, the other step is DBU-catalyzed rapid isomerization of trans-isomer to cis-isomer of the bicyclic hydantoinothiolactone.

6.
J Cardiovasc Dev Dis ; 10(9)2023 Sep 06.
Article in English | MEDLINE | ID: mdl-37754813

ABSTRACT

PURPOSE: To construct and validate a nomogram for predicting depression after acute coronary stent implantation for risk assessment. METHODS: This study included 150 patients with acute coronary syndrome (ACS) who underwent stent implantation. Univariate analysis was performed to identify the predictors of postoperative depression among the 24 factors. Subsequently, multivariate logistic regression was performed to incorporate the significant predictors into the prediction model. The model was developed using the "rms" software package in R software, and internal validation was performed using the bootstrap method. RESULTS: Of the 150 patients, 82 developed depressive symptoms after coronary stent implantation, resulting in an incidence of depression of 54.7%. Univariate analysis showed that sleep duration ≥7 h, baseline GAD-7 score, baseline PHQ-9 score, and postoperative GAD-7 score were associated with the occurrence of depression after stenting in ACS patients (all p < 0.05). Multivariate logistic regression analysis revealed that major life events in the past year (OR = 2.783,95%CI: 1.121-6.907, p = 0.027), GAD-7 score after operation (OR = 1.165, 95% CI: 1.275-2.097, p = 0.000), and baseline PHQ-9 score (OR = 3.221, 95%CI: 2.065-5.023, p = 0.000) were significant independent risk factors for ACS patients after stent implantation. Based on these results, a predictive nomogram was constructed. The model demonstrated good prediction ability, with an AUC of 0.857 (95% CI = 0.799-0.916). The correction curve showed a good correlation between the predicted results and the actual results (Brier score = 0.15). The decision curve analysis and prediction model curve had clinical practical value in the threshold probability range of 7 to 94%. CONCLUSIONS: This nomogram can help to predict the incidence of depression and has good clinical application value. This trial is registered with ChiCTR2300071408.

7.
Front Pediatr ; 11: 1165477, 2023.
Article in English | MEDLINE | ID: mdl-37547102

ABSTRACT

Background: Birth defects (BDs) are associated with many potential risk factors, and its causes are complex. Objectives: This study aimed to explore the epidemiological characteristics of BDs in Guangxi of China and the associated risk factors of BDs. Methods: BDs data of perinatal infants (PIs) were obtained from the Guangxi birth defects monitoring network between 2016 and 2020. Univariate Poisson regression was used to calculate the prevalence-rate ratios (PRR) to explore the changing trends of BDs prevalence by year and the correlation between the regarding of characteristics of BDs (including infant gender, maternal age, and quarter) and BDs. Clinical characteristics of PIs with BDs and general characteristics of their mothers were documented, and Spearman correlation analysis was used to explore the potential associated risk factors of BDs. Results: Between 2016 and 2020, 44,146 PIs with BDs were monitored, with an overall BDs prevalence of 121.71 (95% CI: 120.58-122.84) per 10,000 PIs, showing a significant increase trend (PRR = 1.116, 95% CI: 1.108-1.123), especially the prevalence of congenital heart defects (CHDs) that most significantly increased (PRR = 1.300, 95% CI: 1.283-1.318). The 10 most common BDs were CHDs, polydactyly, congenital talipes equinovarus, other malformation of external ear, syndactyly, hypospadias, cleft lip with cleft palate, cleft lip, hemoglobin Bart's hydrops fetalis syndrome (BHFS), and congenital atresia of the rectum and anus. BDs were positively correlated with pregnant women's age (R = 0.732, P < 0.01) and education level (R = 0.586, P < 0.05) and having pre-gestational diabetes mellitus (PGDM)/gestational diabetes mellitus (GDM) (R = 0.711, P < 0.01), while when the pregnant women had a family history of a dead fetus (R = -0.536, P < 0.05) and a birth of a fetus with BDs (R = -0.528, P < 0.05) were negatively correlated with BDs. Conclusion: A significant increase in the prevalence of BDs was detected between 2016 and 2020 in Guangxi, especially the prevalence of CHDs that most significantly increased. Older maternal age, higher maternal education level, and having PGDM before pregnancy or GDM in early pregnancy were the risk factors for BDs.

8.
J Interv Med ; 6(2): 53-58, 2023 May.
Article in English | MEDLINE | ID: mdl-37409058

ABSTRACT

With the widespread adoption of ultrasound guidance, Seldinger puncture techniques, and intracardiac electrical positioning technology for the placement of peripherally inserted central catheters in recent years, an increasing number of medical staff and patients now accept peripheral placement of totally implantable venous access devices (TIVADs) in the upper arm. This approach has the advantage of completely avoiding the risks of hemothorax, pneumothorax, and neck and chest scarring. Medical specialties presently engaged in this study in China include internal medicine, surgery, anesthesiology, and interventional departments. However, command over implantation techniques, treatment of complications, and proper use and maintenance of TIVAD remain uneven among different medical units. Moreover, currently, there are no established quality control standards for implantation techniques or specifications for handling complications. Thus, this expert consensus is proposed to improve the success rate of TIVAD implantation via the upper-arm approach, reduce complication rates, and ensure patient safety. This consensus elaborates on the technical indications and contraindications, procedures and technical points, treatment of complications, and the use and maintenance of upper-arm TIVAD, thus providing a practical reference for medical staff.

9.
J Neurovirol ; 29(3): 283-296, 2023 06.
Article in English | MEDLINE | ID: mdl-37185939

ABSTRACT

A disintegrin and metalloproteinases (ADAMs) are involved in multiple neurodegenerative diseases. However, the roles and mechanisms of ADAMs in HIV-associated neurocognitive disorder (HAND) remain unclear. Transactivator of transcription (Tat) induces inflammatory response in astrocytes, thereby leading to neuronal apoptosis in the central nervous system. In this study, we determined that ADAM17 expression was upregulated during soluble Tat stimulus in HEB astroglial cells. Inhibition of ADAM17 suppressed Tat-induced pro-inflammatory cytokines production and rescued the astrocytes-derived conditioned media (ACM)-mediated SH-SY5Y neural cells apoptosis. Moreover, ADAM17 mediated Tat-triggered inflammatory response in a NF-κB-dependent manner. Conversely, Tat induced ADAM17 expression via NF-κB signaling pathway. In addition, pharmacological inhibition of NF-κB signaling inhibited Tat-induced inflammatory response, which could be rescued by overexpression of ADAM17. Taken together, our study clarifies the potential role of the ADAM17/NF-κB feedback loop in Tat-induced inflammatory response in astrocytes and the ACM-mediated neuronal death, which could be a novel therapeutic target for relief of HAND.


Subject(s)
HIV-1 , Neuroblastoma , Humans , NF-kappa B/genetics , NF-kappa B/metabolism , HIV-1/metabolism , Astrocytes/metabolism , Trans-Activators/metabolism , Feedback , Neuroblastoma/metabolism , tat Gene Products, Human Immunodeficiency Virus/metabolism , ADAM17 Protein/genetics , ADAM17 Protein/metabolism
10.
Brain ; 146(8): 3347-3363, 2023 08 01.
Article in English | MEDLINE | ID: mdl-36869767

ABSTRACT

Recurrent proximal 16p11.2 deletion (16p11.2del) is a risk factor for diverse neurodevelopmental disorders with incomplete penetrance and variable expressivity. Although investigation with human induced pluripotent stem cell models has confirmed disruption of neuronal development in 16p11.2del neuronal cells, which genes are responsible for abnormal cellular phenotypes and what determines the penetrance of neurodevelopmental abnormalities are unknown. We performed haplotype phasing of the 16p11.2 region in a 16p11.2del neurodevelopmental disorders cohort and generated human induced pluripotent stem cells for two 16p11.2del families with distinct residual haplotypes and variable neurodevelopmental disorder phenotypes. Using transcriptomic profiles and cellular phenotypes of the human induced pluripotent stem cell-differentiated cortex neuronal cells, we revealed MAPK3 to be a contributor to dysfunction in multiple pathways related to early neuronal development, with altered soma and electrophysiological properties in mature neuronal cells. Notably, MAPK3 expression in 16p11.2del neuronal cells varied on the basis of a 132 kb 58 single nucleotide polymorphism (SNP) residual haplotype, with the version composed entirely of minor alleles associated with reduced MAPK3 expression. Ten SNPs on the residual haplotype were mapped to enhancers of MAPK3. We functionally validated six of these SNPs by luciferase assay, implicating them in the residual haplotype-specific differences in MAPK3 expression via cis-regulation. Finally, the analysis of three different cohorts of 16p11.2del subjects showed that this minor residual haplotype is associated with neurodevelopmental disorder phenotypes in 16p11.2del carriers.


Subject(s)
Chromosome Deletion , Induced Pluripotent Stem Cells , Humans , Haplotypes , Phenotype , Cell Differentiation
11.
BMJ Open ; 13(3): e069772, 2023 03 22.
Article in English | MEDLINE | ID: mdl-36948557

ABSTRACT

OBJECTIVES: The upper arm infusion ports have been proven to be advanced and safe, but the experience from the perspective of patients is lacking. This study explored the indwelling experience and coping strategies of upper arm infusion ports in patients with cancer. DESIGN: Qualitative exploratory study. SETTING: This study was conducted between May 2021 and August 2021 at a level III-A general hospital in Shanghai, China. PARTICIPANTS: The participants, who are patients with cancer implanted with the upper arm infusion ports, included 10 women and 6 men, and the average age was 54.4±8.3 years old. METHODS: Data were selected from semistructured in-depth interviews and analysed by thematic analysis. RESULTS: There were 10 descriptive topics and 4 analytical topics in 2 parts. The indwelling experience includes positive experience (treatment benefit, life convenience) and negative experience (physical discomfort, social anxiety, psychological distress). Coping strategies include emotional-focused strategies (self-acceptance, avoidance and self-protection) and problem-focused strategies (information seeking, functional exercise and remove as soon as possible). CONCLUSION: The infusion port in the upper arm is beneficial to the safety and quality of life of patients with cancer. At the same time, there are challenges in physical, psychological and social adaptation. Patients respond with some measures, but obstacles may arise during implementation.


Subject(s)
Arm , Neoplasms , Male , Humans , Female , Middle Aged , Quality of Life/psychology , China , Adaptation, Psychological , Neoplasms/drug therapy
12.
Medicine (Baltimore) ; 101(42): e31163, 2022 Oct 21.
Article in English | MEDLINE | ID: mdl-36281159

ABSTRACT

Fecal calprotectin (FC) has been proposed as a noninvasive surrogate marker of intestinal inflammation in inflammatory bowel disease. This study aimed to assess the capability of FC in predicting small bowel capsule endoscopy (SBCE) findings in pediatric patients with known Crohn's disease (CD). We retrieved data of consecutive patients aged 2 to 17 years old with established CD who underwent SBCE from Janurary 2017 to April 2020 and had endoscopic remission on ileocolonoscopy. Sixty-eight patients were included in the analysis. There were 13 patients with a weighted pediatric CD activity index ≥ 12.5, 47 patients with FC ≥ 200 µg/g, and 45 patients with significant small bowel (SB) inflammation [Lewis score (LS) ≥ 135]. The LS correlated weakly with FC (R = 0.30, P < .05). The area under the curve of FC as a surrogate diagnostic test for LS ≥ 135 was 0.691, and the optimal FC cutoff values were 242 µg/g with the corresponding sensitivity and specificity of 78% and 65%, respectively. The area under the curve of FC for moderate-to-severe inflammatory activity in the SB was 0.718. In patients with FC level ≥ 670 µg/g, LS ≥ 790 was found in 33% (9/27) of patients, with the sensitivity and specificity of 69% and 67%, respectively. FC may be used to predict SB mucosal inflammation in pediatric patients with confirmed CD having endoscopic remission on ileocolonoscopy.


Subject(s)
Capsule Endoscopy , Crohn Disease , Humans , Child , Child, Preschool , Adolescent , Leukocyte L1 Antigen Complex/analysis , Crohn Disease/diagnosis , Feces/chemistry , Biomarkers/analysis , Inflammation , Severity of Illness Index
13.
Contrast Media Mol Imaging ; 2022: 6112659, 2022.
Article in English | MEDLINE | ID: mdl-36072640

ABSTRACT

Based on hypoxia-inducible factor-1α (HIF-1α), follicle-stimulating hormone (FSH), luteinizing hormone (LH), estradiol (E2), and anti-Mullerian hormone (AMH), the antral follicle is explored. The expression of count (AFC) in females at lofty elevation and its clinical significance are analyzed. A total of 82 females in lofty elevation areas and in low-elevation areas who received health checks from April 2020 to May 2021 are selected as the lofty elevation set and the low-elevation set, respectively. In addition, 76 females are served as the routine set. By comparing the serum HIF-1α standards, the standards of sex hormone indexes FSH, LH, and E2, and the expressions of AMH and AFC between the two sets of females, the correlation between HIF-1α and sex hormone indexes and ovarian reserve function is analyzed. The experimental results show that the lofty standard of HIF-1α in females at lofty elevation may lead to abnormal standards of sex hormones and weakened ovarian reserve. The detection of HIF-1α in females in lofty elevation areas is of great significance for evaluating their sex hormone standards, ovarian function, and preventing the occurrence of female gynecological diseases.


Subject(s)
Altitude , Anti-Mullerian Hormone , Follicle Stimulating Hormone , Estrogens , Female , Gonadal Steroid Hormones , Humans , Hypoxia-Inducible Factor 1, alpha Subunit , Luteinizing Hormone
14.
BMC Pediatr ; 22(1): 522, 2022 09 02.
Article in English | MEDLINE | ID: mdl-36056317

ABSTRACT

BACKGROUND: Large-scale data on esophagogastroduodenoscopy (EGD) in China are scarce. This study aimed to assess the indications and diagnostic yield of EGD in children and the relationship between factors (such as age, sex, and indications) and diagnostic yield. METHODS: We performed a prospective cross-sectional observational study involving patients aged < 18 years who underwent diagnostic EGD. The study was conducted in five children's hospitals, each in a different city. Demographic features, indications for endoscopy, and endoscopic and histopathological findings were collected. Univariable and multivariable ordinal logistic regression analyses of the relationship between the factors and diagnostic yield were performed. RESULTS: The study included 2268 patients (male/female ratio, 1.3:1) with a median age of 8.68 years. Among the 2268 children, the most frequent indications were abdominal pain in 1954 (86.2%), recurrent vomiting in 706 (31.1%), weight loss in 343 (15.1%), and others. The endoscopic yield was 62.5% and was the highest in patients with dysphagia (90.9%). The histologic yield was 30.4% and was the highest in patients with unexplained anemia (45.5%). On multivariable regression analysis, the endoscopic yield was associated with dysphagia, gastrointestinal (GI) bleeding, and recurrent vomiting, and the histologic yield was associated with age. Different groups of patients with abdominal pain had variable probabilities of abnormal endoscopic findings. CONCLUSIONS: The most frequent indication of pediatric EGD is abdominal pain, with variable probabilities of abnormal endoscopic findings in different groups. Endoscopic yield and histologic yield are associated with certain alarming features. TRIAL REGISTRATION: The trial registration number (ClinicalTrials. gov): NCT03603093 (The study was registered on 27/07/2018).


Subject(s)
Deglutition Disorders , Abdominal Pain/diagnosis , Child , China , Cross-Sectional Studies , Endoscopy, Gastrointestinal , Female , Gastrointestinal Hemorrhage/diagnosis , Humans , Male , Prospective Studies , Retrospective Studies , Vomiting
15.
Brain Dev ; 44(8): 540-545, 2022 Sep.
Article in English | MEDLINE | ID: mdl-35491272

ABSTRACT

PURPOSE: Mutations in ASPM are the most common causes of primary microcephaly (MCPH), which is a rare brain developmental disorder with few studies in Chinese population so far. This study aimed to identify the common pathogenic variants of ASPM and estimated the incidence of MCPH5 in Guangxi population. METHODS: We ascertained six MCPH cases caused by ASPM mutations in Guangxi Zhuang Autonomous Region, Whole-exome sequencing (WES) was performed to uncover the causal variants. The haplotype analysis was used to estimate the age of the recurrent variation. RESULTS: Five different pathogenic variants were identified in this batch of MCPH5 cases, including two novel variants p.Ser842fs*9 and p.Lys1340Argfs*29. An rarely reported pathogenic variant, c.1789C>T/p.Arg597* was found to be a founder mutation in local population. We evaluated all ASPM variants detected among 2674 non-microcephalic individuals and estimated the MCPH5 incidence to be 5.03/1,000,000 in Guangxi population. CONCLUSIONS: We reported the first case series of Chinese MCPH cases with ASPM mutation and revealed a highly recurrent founder mutation in this local population. MCPH5 may be the major type of congenital microcephaly in Chinese population.


Subject(s)
Microcephaly , Nerve Tissue Proteins , China/epidemiology , Founder Effect , Humans , Microcephaly/epidemiology , Microcephaly/genetics , Mutation , Nerve Tissue Proteins/genetics
16.
Support Care Cancer ; 30(6): 4927-4934, 2022 Jun.
Article in English | MEDLINE | ID: mdl-35175418

ABSTRACT

OBJECTIVE: This study is designed to investigate the status of kinesiophobia and related factors in cancer patients with totally implantable venous access ports (TIAPs). METHODS: This is a cross-sectional study; all the participants were recruited from the Oncology Department and the Daytime Chemotherapy Center, Renji Hospital, Shanghai Jiao Tong University School of Medicine, from April 1 to May 31, 2021. The participants were interviewed by researchers using the self-made general information questionnaire and the Tampa Scale of Kinesiophobia-11 (TSK-11) scale, which allows the fear of movement to be quantified. Eligible patients were aged ≥ 18 years, confirmed with cancer, and implanted with a port. The logistic regression model was used to evaluate clinical factors and the risk of kinesiophobia. RESULTS: A total of 282 patients were recruited (aged 58.0 ± 11.5 years), of which gastrointestinal cancer accounted for 54.6%, breast cancer accounted for 22.7%, lung cancer accounted for 11.3%, and other types accounted for 11.3%. The TSK-11 score of the 282 patients was 17.84 ± 6.06 points, 45.7% of the patients reported mild kinesiophobia (TSK-11 ≥ 18), 18.4% of the patients reported moderate to severe kinesiophobia (TSK-11 ≥ 25), and the highest score reached 34 points. Results of logistic regression analysis showed that exercise habits (P = 0.025), pain (P = 0.023), and foreign body sensation (P = 0.003) were the risk factors of kinesiophobia. CONCLUSION: Kinesiophobia is common in cancer patients with TIAPs, and it is closely related to the subjective experience of daily activities, which requires more attention and early intervention to reduce the potential adverse effects.


Subject(s)
Fear , Neoplasms , China/epidemiology , Cross-Sectional Studies , Humans , Neoplasms/epidemiology , Surveys and Questionnaires
17.
Diabetes ; 71(4): 795-811, 2022 04 01.
Article in English | MEDLINE | ID: mdl-35043173

ABSTRACT

Methazolamide (MTZ), a carbonic anhydrase inhibitor, has been shown to inhibit cardiomyocyte hypertrophy and exert a hypoglycemic effect in patients with type 2 diabetes and diabetic db/db mice. However, whether MTZ has a cardioprotective effect in the setting of diabetic cardiomyopathy is not clear. We investigated the effects of MTZ in a mouse model of streptozotocin-induced type 1 diabetes mellitus (T1DM). Diabetic mice received MTZ by intragastric gavage (10, 25, or 50 mg/kg, daily for 16 weeks). In the diabetic group, MTZ significantly reduced both random and fasting blood glucose levels and improved glucose tolerance in a dose-dependent manner. MTZ ameliorated T1DM-induced changes in cardiac morphology and dysfunction. Mechanistic analysis revealed that MTZ blunted T1DM-induced enhanced expression of ß-catenin. Similar results were observed in neonatal rat cardiomyocytes (NRCMs) and adult mouse cardiomyocytes treated with high glucose or Wnt3a (a ß-catenin activator). There was no significant change in ß-catenin mRNA levels in cardiac tissues or NRCMs. MTZ-mediated ß-catenin downregulation was recovered by MG132, a proteasome inhibitor. Immunoprecipitation and immunofluorescence analyses showed augmentation of AXIN1-ß-catenin interaction by MTZ in T1DM hearts and in NRCMs treated with Wnt3a; thus, MTZ may potentiate AXIN1-ß-catenin linkage to increase ß-catenin degradation. Overall, MTZ may alleviate cardiac hypertrophy by mediating AXIN1-ß-catenin interaction to promote degradation and inhibition of ß-catenin activity. These findings may help inform novel therapeutic strategy to prevent heart failure in patients with diabetes.


Subject(s)
Diabetes Mellitus, Experimental , Diabetes Mellitus, Type 1 , Diabetes Mellitus, Type 2 , Diabetic Cardiomyopathies , Animals , Axin Protein/metabolism , Diabetes Mellitus, Experimental/drug therapy , Diabetes Mellitus, Experimental/metabolism , Diabetes Mellitus, Type 1/drug therapy , Diabetes Mellitus, Type 1/metabolism , Diabetes Mellitus, Type 2/metabolism , Diabetic Cardiomyopathies/drug therapy , Diabetic Cardiomyopathies/metabolism , Diabetic Cardiomyopathies/prevention & control , Glucose/metabolism , Humans , Methazolamide/metabolism , Methazolamide/pharmacology , Methazolamide/therapeutic use , Mice , Mice, Inbred C57BL , Myocytes, Cardiac/metabolism , Rats , beta Catenin/metabolism
18.
Bioengineered ; 12(2): 9561-9574, 2021 12.
Article in English | MEDLINE | ID: mdl-34719307

ABSTRACT

Preeclampsia (PE), a pregnancy-specific syndrome, is the primary cause of maternal mortality. This work was designed to investigate the specific functions of PTPRO/ ERp44 in the biological behaviors of trophoblast cells and elucidate the underlying molecular mechanism. Constructed siRNA-PTPRO and ERp44 overexpression plasmids were transfected into HTR-8/SVneo and JEG-3 cells for further functional experiments. Subsequently, the proliferation and invasion of trophoblast cells were identified by performing CCK-8, flow cytometry and transwell assay. In addition, tube formation assay was employed to estimate the angiogenic ability of HUVECs incubated with the conditioned media (CM) of HTR-8/SVneo or JEG-3 cells. Importantly, the interaction between PTPRO and ERp44 was analyzed through Co-IP. In the current investigation, it was discovered that downregulation of PTPRO notably facilitated the proliferation and invasion of trophoblast cells and induced a stronger in vitro angiogenesis. Moreover, PTPRO interacted with ERp44 to regulate ERp44 expression. ERp44 overexpression suppressed the proliferative, invasive and angiogenic activities of trophoblast cells. As a result, functions of PTPRO knockdown in the biological behaviors of trophoblast cells were partially abrogated upon elevation of ERp44. To sum up, this current research systematically evidenced that PTPRO could regulate the biological behaviors of trophoblast cells by modulating ERp44. Findings may contribute to a novel therapeutic strategy for PE.


Subject(s)
Cell Proliferation/genetics , Gene Expression Regulation , Gene Knockdown Techniques , Membrane Proteins , Molecular Chaperones , Neovascularization, Pathologic , Pre-Eclampsia , Receptor-Like Protein Tyrosine Phosphatases, Class 3/deficiency , Trophoblasts/metabolism , Cell Line , Female , Human Umbilical Vein Endothelial Cells , Humans , Membrane Proteins/genetics , Membrane Proteins/metabolism , Molecular Chaperones/genetics , Molecular Chaperones/metabolism , Neovascularization, Pathologic/genetics , Neovascularization, Pathologic/metabolism , Pre-Eclampsia/genetics , Pre-Eclampsia/metabolism , Pregnancy , Receptor-Like Protein Tyrosine Phosphatases, Class 3/metabolism
19.
Medicine (Baltimore) ; 100(22): e26245, 2021 Jun 04.
Article in English | MEDLINE | ID: mdl-34087912

ABSTRACT

BACKGROUND: Breast cancer was the second cause of cancer death and approximately accounted for 30% of all newly diagnosed cancer in American women. Adjuvant chemotherapy is the preferred treatment approach for breast patients. Kanglaite injection (KI) was commonly used as adjuvant chemotherapy combined with chemotherapy for women breast cancer which could increase chemotherapy efficacy and alleviate chemotherapy drugs induced adverse events, however, the efficacy and safety for KI combined western medicine remains controversial. Thus, we conducted this protocol of systematic review and meta-analysis to estimate the efficacy and safety of KI combined with western medicine for women breast cancer. METHODS: This study will search electronic database included English medicals databases and Chinese databased up to May 2021. The main outcomes of this study include clinical efficacy rate. Adverse reaction rate, Karnofsky Performance Status and immune function were defined as the secondary outcomes. RESULTS: This protocol study will comprehensively evaluate the efficacy and safety of KI combined with chemotherapy for women breast cancer. CONCLUSION: This protocol for systematic review and meta-analysis will evaluate the efficacy and safety of KI combined with chemotherapy for women breast cancer, aiming to provide optimal therapy for women breast cancer patients.


Subject(s)
Antineoplastic Agents/therapeutic use , Breast Neoplasms/drug therapy , Carcinoma/drug therapy , Drugs, Chinese Herbal/therapeutic use , Adult , Antineoplastic Agents/administration & dosage , Antineoplastic Agents/adverse effects , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Breast Neoplasms/epidemiology , Breast Neoplasms/mortality , Carcinoma/diagnosis , Chemotherapy, Adjuvant/methods , Data Management , Drugs, Chinese Herbal/administration & dosage , Drugs, Chinese Herbal/adverse effects , Esophageal Neoplasms/pathology , Female , Humans , Karnofsky Performance Status , Randomized Controlled Trials as Topic , Safety , Treatment Outcome , Meta-Analysis as Topic
20.
Cancer Sci ; 112(4): 1457-1470, 2021 Apr.
Article in English | MEDLINE | ID: mdl-33511729

ABSTRACT

Resident adipocytes under a hypoxic tumor microenvironment exert an increasingly important role in cell growth, proliferation, and invasion in cancers. However, the communication between adipocytes and cancer cells during nasopharyngeal carcinoma (NPC) progression is poorly understood. Here, we demonstrate that hypoxic adipocyte-derived exosomes are key information carriers that transfer low expression of miR-433-3p into NPC cells. In addition, luciferase reporter assays detected that hypoxia inducible factor-1α (HIF-1α) induced miR-433-3p transcription through five binding sites at its promoter region. Concordantly, the low expression of miR-433-3p promoted proliferation, migration, and lipid accumulation in NPC cells via targeting stearoyl-CoA desaturase 1 (SCD1) are suggested by functional studies. Consistent with these findings, in tumor-bearing mice, NPC cells with low HIF-1α expression, high miR-433-3p expression, and low SCD1 expression were equally endowed with remarkably reduced potential of tumorigenesis. Collectively, our study highlights the critical role of the HIF-1α-miR-433-3p-SCD1 axis in NPC progression, which can serve as a mechanism-based potential therapeutic approach.


Subject(s)
Adipocytes/pathology , Down-Regulation/genetics , Exosomes/genetics , Hypoxia-Inducible Factor 1, alpha Subunit/genetics , MicroRNAs/genetics , Nasopharyngeal Carcinoma/genetics , Nasopharyngeal Neoplasms/genetics , Stearoyl-CoA Desaturase/genetics , Animals , Cell Movement/genetics , Cell Proliferation/genetics , Gene Expression Regulation, Neoplastic/genetics , Humans , Hypoxia/genetics , Hypoxia/pathology , Lipid Metabolism/genetics , Male , Mice , Mice, Inbred BALB C , Mice, Nude , Nasopharyngeal Carcinoma/pathology , Nasopharyngeal Neoplasms/pathology , Promoter Regions, Genetic/genetics
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