[Acupoint application for Hashimoto's thyroiditis with liver-qi stagnation: a randomized controlled trial].

OBJECTIVE: To observe the clinical efficacy and safety of acupoint application for Hashimoto's thyroiditis (HT) with liver-qi stagnation. METHODS: One hundred and fifty patients of HT with liver-qi stagnation were randomly divided into an acupoint application group (75 cases, 11 cases were excluded, 5 cases dropped out) and a control group (75 cases, 12 cases excluded, 3 cases dropped out). Based on the health education combined with conventional western medicine treatment, the patients in the acupoint application group were treated with acupoint application, while the patients in the control group were treated with placebo acupoint application. Shenque (CV 8), bilateral Yongquan (KI 1), Yeshi, and ashi point were selected in both groups, with Yeshi treated once a week and the remaining acupoints treated every other day, for a total of 4 weeks. The serum levels of thyroglobulin antibody (TgAb), thyroid peroxidase antibody (TPOAb), free triiodothyronine (FT3), free thyroxine (FT4), and thyroid-stimulating hormone (TSH), as well as the thickness of thyroid left lobe, right lobe, and isthmus, TCM symptom score, hospital anxiety and depression scale (HADS) score, and MOS 36-item short form health survey (SF-36) score were compared between the two groups before and after treatment. Adverse reactions in both groups were observed. RESULTS: Compared with before treatment, in the acupoint application group, the serum levels of TgAb and TPOAb were reduced after treatment (P<0.05), and the scores of role physical (RP), body pain (BP), vitality (VT), role emotional (RE), and mental health (MH) in SF-36 were increased after treatment (P<0.01, P<0.001). The thickness of the thyroid isthmus after treatment was smaller than that before treatment (P<0.05), and the TCM symptom scores and HADS anxiety (HADS-A) scores after treatment were lower than those before treatment (P<0.001, P<0.01) in both groups. In the control group, the scores of physical function (PF), RP, BP, VT, and RE in SF-36 after treatment were higher than those before treatment (P<0.05, P<0.01, P<0.001). There was no statistically significant difference in serum FT3, FT4, and TSH levels within the groups (P>0.05). There was no statistically significant difference in the above indexes between the two groups (P>0.05). The incidence of adverse reactions in the acupoint application group and the control group was 20.0% (15/75) and 10.7% (8/75) respectively, with skin allergy being the main adverse reaction. CONCLUSION: Acupoint application could reduce the serum levels of TgAb and TPOAb in patients of HT with liver-qi stagnation, alleviate thyroid enlargement, improve TCM symptoms and anxiety, and improve quality of life, with safe and reliable clinical efficacy.

Life's Essential 8 and 10-Year and Lifetime Risk of Atherosclerotic Cardiovascular Disease in China.

INTRODUCTION: Cardiovascular health level according to the American Heart Association's Life's Essential 8 (LE8) in China and its effectiveness on the 10-year and lifetime risk of atherosclerotic cardiovascular diseases is unclear. METHODS: This prospective study included 88,665 participants in the China-PAR cohort (data from 1998 to 2020) and 88,995 in the Kailuan cohort (data from 2006 to 2019). Analyses were conducted by November 2022. LE8 was measured according to the American Heart Association's LE8 algorithm, and a high cardiovascular health status was defined as a LE8 score ≥80 points. Participants were followed for the primary composite outcomes, including fatal and nonfatal acute myocardial infarction, ischemic stroke, and hemorrhagic stroke. The lifetime risk was estimated from the cumulative risk of atherosclerotic cardiovascular diseases through ages 20-85 years, the association of LE8 and LE8 change with atherosclerotic cardiovascular diseases was assessed with the Cox proportional-hazards model, and partial population-attributable risks evaluated the proportion of atherosclerotic cardiovascular diseases that could be averted. RESULTS: The mean LE8 score was 70.0 in the China-PAR cohort and 64.6 in the Kailuan cohort, with 23.3% and 8.0% of participants having a high cardiovascular health status, respectively. Participants in the highest quintile had about 60% lower 10-year and lifetime risk of atherosclerotic cardiovascular diseases in the China-PAR and Kailuan cohorts than participants with the lowest quintile LE8 score. If everyone maintained the highest quintile of LE8 score, approximately half of the atherosclerotic cardiovascular diseases could be prevented. The participant with LE8 score that increased from the lowest to the highest tertile during 2006-2012 had a 44% (hazard ratio=0.56; 95% CI=0.45, 0.69) lower observed risk and a 43% (hazard ratio=0.57; 95% CI=0.46, 0.70) lower lifetime risk of atherosclerotic cardiovascular diseases than those remaining in the lowest tertile in the Kailuan cohort. CONCLUSIONS: The LE8 score was below optimal levels in Chinese adults. A high baseline LE8 score and an improving LE8 score were associated with decreased 10-year and lifetime risk of atherosclerotic cardiovascular diseases.

Visit-to-visit fasting blood glucose variability and lifetime risk of cardiovascular disease: a prospective study.

AIMS: Previous studies suggested an adverse association between higher fasting blood glucose (FBG) variability and cardiovascular disease (CVD). Lifetime risk provides an absolute risk assessment during the remainder of an individual's life. However, the association between FBG variability and the lifetime risk of CVD is uncertain. OBJECTIVE: We aimed to investigate the effect of the visit-to-visit FBG variability on the lifetime risk of CVD. METHODS: This study included participants from the Kailuan Study who did not have CVD at index ages 35, 45, and 55 years. The FBG variability was defined as the coefficient of variation (CV) of three FBG values that were measured during the examination periods of 2006-2007, 2008-2009, and 2010-2011. We used a modified Kaplan-Merrier method to estimate lifetime risk of CVD according to tertiles of FBG variability. RESULTS: At index age 35 years, the study sample comprised 46,018 participants. During a median follow-up of 7.0 years, 1889 participants developed CVD events. For index age 35 years, participants with high FBG variability had higher lifetime risk of CVD (32.5%; 95% confidence interval [CI]: 28.9-36.1%), compared with intermediate (28.3%; 95% CI: 25.5 -31.1%) and low (26.3%; 95% CI: 23.0-29.5%) FBG variability. We found that higher FBG variability was associated with increased lifetime risk of CVD in men but not women. Similar patterns were observed at index ages 45 and 55 years. CONCLUSIONS: Higher FBG variability was associated with increased lifetime risk of CVD at each index age. Focusing on the FBG variability may provide an insight to the clinical utility for reducing the lifetime risk of CVD.

Increased Stroke Risk in Metabolically Abnormal Normal Weight: a 10-Year Follow-up of 102,037 Participants in China.

The purpose of this study was to investigate the risks of stroke in subjects with metabolically abnormal normal weight (MANW) in China. We recruited 102,037 participants from the Zhejiang Metabolic Syndrome Cohort and the Kailuan cohort. The mean years of follow-up were 9.9 years. General obesity was defined by body mass index (BMI) ≥ 28, overweight by BMI < 28 and ≥ 24, and normal weight by BMI < 24 and ≥ 18.5. Metabolic abnormality was defined as two or more abnormal components (elevated triglycerides, low high-density lipoprotein cholesterol, elevated systolic blood pressure or diastolic blood pressure, or use of antihypertensive drug therapy, elevated fasting plasma glucose, or antidiabetic treatment). A multiple Cox regression model was used to calculate hazard ratio (HR) and its 95% confidence interval (CI), adjusted by potential confounding factors. Overall HR of the risks in two cohorts was calculated by a meta-analysis. Compared with the subjects who were metabolically normal with normal weight (MNNW), the pooled HR for stroke in MANW subjects was 1.82 (95% CI, 1.59-2.07). The risks of stroke in MANW subjects were significantly lower than that in subjects with metabolically abnormal obesity (MAO), but higher than that in those with metabolically normal obesity (MNO) (P < 0.05). These associations remained in the subtypes of cerebral infarction and cerebral hemorrhage. In normal-weight subjects, the HR for stroke was significantly positively correlated with the number of abnormal metabolic components (Ptrend < 0.001). In brief, metabolic abnormality increased the risk of stroke irrespective of obesity status. MANW individuals showed a greater risk of stroke, and this risk was positively correlated with the number of abnormal metabolic components.

Visit-to-Visit Variability of Lipids Measurements and the Risk of Stroke and Stroke Types: A Prospective Cohort Study.

BACKGROUND AND PURPOSE: Previous studies suggested increased visit-to-visit variability of total cholesterol (TC) is associated with stroke. This study aimed to investigate the associations of various lipids measurements variability and the risk of stroke and stroke type (ischemic and hemorrhagic stroke). METHODS: Fifty-one thousand six hundred twenty participants in the Kailuan Study without history of myocardial infarction, stroke, and cancer who underwent three health examinations during 2006 to 2010 were followed for incident stroke. Variability in TC, triglycerides, high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C) measurements were measured using the coefficient of variation (CV), standard deviation (SD), variability independent of the mean (VIM), and average real variability (ARV). RESULTS: During a median of 6.04 years of follow-up, 1,189 incident stroke (1,036 ischemic and 160 hemorrhagic stroke) occurred. In the multivariable-adjusted model, the hazard ratio (HR) comparing participants in the highest versus lowest quartile of CV of HDL-C were 1.21 (95% confidence interval [CI], 1.02 to 1.45; P for trend=0.013) for ischemic stroke. The highest quartile of CV of LDL-C was associated with 2.17-fold risk of hemorrhagic stroke (HR, 2.17; 95% CI, 1.25 to 3.75; P for trend=0.002) compared with the lowest quartile. We did not observe any significant association between TC and triglycerides variability with any of stroke. Consistent. RESULTS: were obtained when calculating variability index using SD, VIM, or ARV. CONCLUSIONS: These findings suggest the high visit-to-visit HDL-C and LDL-C variability were associated with an increased incidence of ischemic and hemorrhagic stroke, respectively.

Competing endogenous RNA regulatory network in papillary thyroid carcinoma.

The present study aimed to screen all types of RNAs involved in the development of papillary thyroid carcinoma (PTC). RNA­sequencing data of PTC and normal samples were used for screening differentially expressed (DE) microRNAs (DE­miRNAs), long non­coding RNAs (DE­lncRNAs) and genes (DEGs). Subsequently, lncRNA­miRNA, miRNA­gene (that is, miRNA­mRNA) and gene­gene interaction pairs were extracted and used to construct regulatory networks. Feature genes in the miRNA­mRNA network were identified by topological analysis and recursive feature elimination analysis. A support vector machine (SVM) classifier was built using 15 feature genes, and its classification effect was validated using two microarray data sets that were downloaded from the Gene Expression Omnibus (GEO) database. In addition, Gene Ontology function and Kyoto Encyclopedia Genes and Genomes pathway enrichment analyses were conducted for genes identified in the ceRNA network. A total of 506 samples, including 447 tumor samples and 59 normal samples, were obtained from The Cancer Genome Atlas (TCGA); 16 DE­lncRNAs, 917 DEGs and 30 DE­miRNAs were screened. The miRNA­mRNA regulatory network comprised 353 nodes and 577 interactions. From these data, 15 feature genes with high predictive precision (>95%) were extracted from the network and were used to form an SVM classifier with an accuracy of 96.05% (486/506) for PTC samples downloaded from TCGA, and accuracies of 96.81 and 98.46% for GEO downloaded data sets. The ceRNA regulatory network comprised 596 lines (or interactions) and 365 nodes. Genes in the ceRNA network were significantly enriched in 'neuron development', 'differentiation', 'neuroactive ligand­receptor interaction', 'metabolism of xenobiotics by cytochrome P450', 'drug metabolism' and 'cytokine­cytokine receptor interaction' pathways. Hox transcript antisense RNA, miRNA­206 and kallikrein­related peptidase 10 were nodes in the ceRNA regulatory network of the selected feature gene, and they may serve import roles in the development of PTC.

Elementary screening of lymph node metastatic-related genes in gastric cancer based on the co-expression network of messenger RNA, microRNA and long non-coding RNA.

Gastric cancer (GC) is the fifth most common cancer and the third leading cause of cancer-related deaths worldwide. The high mortality might be attributed to delay in detection and is closely related to lymph node metastasis. Therefore, it is of great importance to explore the mechanism of lymph node metastasis and find strategies to block GC metastasis. Messenger RNA (mRNA), microRNA (miRNA) and long non-coding RNA (lncRNA) expression data and clinical data were downloaded from The Cancer Genome Atlas (TCGA) database. A total of 908 differentially expressed factors with variance >0.5 including 542 genes, 42 miRNA, and 324 lncRNA were screened using significant analysis microarray algorithm, and interaction networks were constructed using these differentially expressed factors. Furthermore, we conducted functional modules analysis in the network, and found that yellow and turquoise modules could separate samples efficiently. The groups classified in the yellow and turquoise modules had a significant difference in survival time, which was verified in another independent GC mRNA dataset (GSE62254). The results suggested that differentially expressed factors in the yellow and turquoise modules may participate in lymph node metastasis of GC and could be applied as potential biomarkers or therapeutic targets for GC.

Elementary screening of lymph node metastatic-related genes in gastric cancer based on the co-expression network of messenger RNA, microRNA and long non-coding RNA

Gastric cancer (GC) is the fifth most common cancer and the third leading cause of cancer-related deaths worldwide. The high mortality might be attributed to delay in detection and is closely related to lymph node metastasis. Therefore, it is of great importance to explore the mechanism of lymph node metastasis and find strategies to block GC metastasis. Messenger RNA (mRNA), microRNA (miRNA) and long non-coding RNA (lncRNA) expression data and clinical data were downloaded from The Cancer Genome Atlas (TCGA) database. A total of 908 differentially expressed factors with variance >0.5 including 542 genes, 42 miRNA, and 324 lncRNA were screened using significant analysis microarray algorithm, and interaction networks were constructed using these differentially expressed factors. Furthermore, we conducted functional modules analysis in the network, and found that yellow and turquoise modules could separate samples efficiently. The groups classified in the yellow and turquoise modules had a significant difference in survival time, which was verified in another independent GC mRNA dataset (GSE62254). The results suggested that differentially expressed factors in the yellow and turquoise modules may participate in lymph node metastasis of GC and could be applied as potential biomarkers or therapeutic targets for GC.

Changes in Cardiovascular Health Status and the Risk of New-Onset Hypertension in Kailuan Cohort Study.

American Heart Association cardiovascular health metrics are intimately related to cardiovascular diseases. Acting as a key independent risk factor for high morbidity and mortality of cardiovascular diseases, hypertension and its relationship between health status get urgent attention. While the influence of individual health status changes and the future risk of new-onset hypertension is rarely understood, the present study applied this construct to assess the changes of cardiovascular health status and the morbidity of hypertension in Kailuan cohort study in north China. The Cardiovascular Health Score (CHS) was evaluated by the follow-ups of 2006-2007, 2008-2009, 2010-2011 and 2012-2013. The study population (n = 19381) was divided into 5 groups based on the changes in their CHS score between the first two follow-ups (△CHS) of 2006-2007 and 2008-2009 (≤-2, -1, 0, 1, ≥2). The morbidity of hypertension was collected during 2010-2011 and 2012-2013 follow-ups. Data analysis showed that during a median follow-up of 3.79±0.96 years, morbidity of hypertension had a graded relationship with △CHS. As △CHS scored from low to high, the standardized morbidity of hypertension for all participants were 81.40, 75.47, 68.37, 71.43 and 83.13 per 1000 person-year, respectively. An increased △CHS score of 1 was associated with a 10% decrease in the future risk of new-onset hypertension(HR: 0.90, 95% CI: 0.88-0.92). In conclusion, there was a strong inverse relationship between the incidence of new-onset hypertension and elevation of cardiovascular health metrics. Population-wide prevention, especially the promotion of lifestyle improvements, is critical to reducing the morbidity of new-onset hypertension.

Association between high sensitivity C-Reactive protein and prevalence of asymptomatic carotid artery stenosis.

INTRODUCTION: Inflammation plays a key role in the pathophysiology of atherosclerosis. Little is known about the association between high sensitivity C-reactive protein (hs-CRP) especially long-term hs-CRP and asymptomatic carotid artery stenosis (ACAS) in healthy Chinese adults. The aim of this study was to assess the relationship between hs-CRP levels and the prevalence of ACAS in a Chinese community-based cohort. METHODS: A sample of 5349 participants aged ≥ 40 years (40.36% women) were enrolled in this study, all without preexisting stroke. Ultrasonography of the bilateral carotid arteries was performed for the evaluation of carotid stenosis. Participants were stratified into three groups according to hs-CRP levels. We used both baseline (hs-CRP levels analyzed during 2010) and average hs-CRP values for the last four years (the average of hs-CRP levels analyzed at the year of 2006, 2008 and 2010) in the analysis. Multivariable logistic regression models were used to analyze the association between hs-CRP levels and ACAS. RESULTS: A total of 356 (6.66%) subjects showed evidence of ACAS. Multivariate analysis showed that both baseline and average hs-CRP values for the last four years were independent indicators for the presence of ACAS (P for trend = 0.007, 0.001, respectively). Stratified by age and sex, higher baseline hs-CRP levels were associated with ACAS in old adults (≥ 60 y) (multivariate-adjusted, odds ratio [OR] = 1.03, 95% confidence interval [CI]: 1.01-1.05) and male (multivariate-adjusted, OR = 1.03, 95%CI: 1.01-1.05), but not in middle-aged adults (40-59 y) and female. Similarly, higher average hs-CRP values for the last four years were associated with ACAS in old adults and male, but not in middle-aged adults and female. CONCLUSION: Both baseline and chronic elevation of serum hs-CRP were associated with ACAS, especially in older or male adults. hs-CRP might be used as a useful marker and a potential therapeutic target for carotid atherosclerosis.

Expression of leucine aminopeptidase 3 (LAP3) correlates with prognosis and malignant development of human hepatocellular carcinoma (HCC).

Leucine aminopeptidases (LAPs) were associated with tumor cell proliferation, invasion and/or angiogenesis. LAP3 is one important member of this family. However, its clinical significance and biological function in hepatocellular carcinoma (HCC) remains unknown. In the present study, we demonstrated that LAP3 expression was significantly up-regulated in HCC tissues as well as cells and was closely correlated with lower differentiation, positive lymph node metastasis and high Ki-67 expression, indicating a poor prognosis. Then cell viability assays, flow cytometry assays, wound-healing assays and matrigel invasion assays were performed to demonstrate that LAP3 promoted HCC cells proliferation by regulating G1/S checkpoint in cell cycle and advanced HCC cells migration. Furthermore, we discovered that knockdown LAP3 will enhance the sensitivity of HCC cells to cisplatin, thus promoting the cell death of HCC cells. Collectively, our results indicated that up-regulated expression of LAP3 might contribute to the proliferation and metastasis of HCC. Our data gains greater insight into the cancer-promoting role of LAP3 and its functions in HCC cells, possibly providing potential therapeutic strategies for clinical trials.

Classifications of clinical and bowel morphological changes and their relationship with characteristics of patients with incarcerated groin hernias.

BACKGROUND: There is currently no grading standard for the degree of clinical and bowel morphological changes. The objective of this study was to define clinical and bowel morphological classifications and investigate the possible relationship with the characteristics of patients with incarcerated groin hernias. MATERIAL AND METHODS: We retrospectively studied 195 patients who underwent emergency hernia repair with simultaneous bowel resection between January 1992 and January 2012. We classified the degree of clinical and bowel morphological changes into 3 grades based on the incarceration time, intestinal morphology after damage, hernia sac integrity, degree of inflammation, and the presence/absence of bacterial growth, peritonitis signs, mechanical obstruction, cellulitis, and systemic shock. We also recorded patient characteristics and analyzed their relationships with these degrees according to our grading system. RESULTS: We identified 134, 42, and 19 cases of Grades I, II, and III of clinical and bowel morphological changes, respectively. Pearson's chi-squared tests revealed that advanced age (P=0.001), presence of comorbid disease (P=0.002), and high American Society of Anesthesiologists (ASA) score (P=0.017) were related to the degree. Morbidity and mortality also showed significant relationships with the degree (P<0.001, P=0.005, respectively), especially with regard to post-operative infection. CONCLUSIONS: The proposed 3-stage classifications of clinical and bowel morphological changes can be used to objectively reflect the degree of bowel damage. Greater levels of the changes were associated with higher incidences of complications and increased mortality, especially for older patients with comorbid diseases and poor ASA scores. Urgent surgery should be performed to avoid bowel damage exacerbation.

Identification of a germline mutation in the HRPT2 gene in a Chinese family with parathyroid carcinomas.

This study reported a family with primary hyperparathyroidism due to parathyroid carcinoma and investigated the pathological and genetic features of family members. Three members of the family had clinical manifestation of primary hyperparathyroidism and tumors in the neck. All three patients underwent parathyroidectomy, thyroidectomy and level-VI neck dissection and were definitively diagnosed based on pathology. The index case was a patient that was found to have parathyroid carcinoma on the right side and parathyroid adenoma on the left side. The other two patients had local tumor recurrence and metastasis to distant organs. A germline mutation in the HRPT2 gene (Arg91Pro) was identified in all of the patients in this family. Study of the literature indicated that this is the first report of familial parathyroid carcinomas with an HRPT2 gene missense mutation. Results also indicated that HRPT2 may play an important role in the development of parathyroid carcinoma.

Identification of potential markers related to neoadjuvant chemotherapy sensitivity of breast cancer by SELDI-TOF MS.

Neoadjuvant chemotherapy (NACT) is known to be beneficial for patients with locally advanced breast cancer. However, there is still no unified standard on the evaluation of NACT. To identify the potential markers related to NACT sensitivity of breast cancer, in the present study, we examined the protein spectrum of breast cancer tissues before and after NACT using surface-enhanced laser desorption/ionization time-of-flight mass spectrometry (SELDI-TOF MS). Totally, 87 protein samples were extracted from tissues of breast cancer, with 30 from patients before NACT, 30 from patients after NACT, and 27 from patients without any treatment. To eliminate confounding factors a couple of tissue samples from the same patient were mixed. SELDI-TOF MS analysis demonstrated that the intensities of eight different protein peaks, i.e., 26,055.46, 17,898.94, 8,949.50, 11,652.02, 11,053.48, 38,546.56, 5,825.89, and 22,250.63 Da, were higher in samples after NACT than those before NACT. Although further experiments are needed to prove the reliability of the proteins identified in this study, our results will help the establishment of protein model based on drug resistance-related protein peaks to screen whether a patient is suitable for adopting NACT and to improve cancer treatment.