Abstract To understand the relationship between cardiovascular disease (CVD) and adverse childhood experiences (ACEs), the present review aims to describe the burden and influencing factors of CVD, epidemiological characteristics and burden of ACEs, current research on the relationship between ACEs and CVD, and the mechanism of ACEs leading to CVD. It is proposed that further assessment of the relationship is warranted through identifying blood biomarkers, conducting prospective cohort studies and intervention studies. Such efforts would provide valuable scientific insights for primary prevention strategies for cardiovascular disease.

Objective:To investigate the expression of signal recognition particle 14(SRP14)in hepatocellular carcinoma(HCC)and its clinical significance.Methods:The data of SRP14 expression in HCC were obtained from bioinformatics study,and from investigation with quantitative reverse transcription polymerase chain reaction(qRT-PCR),immunohistochemical staining and Western blotting in clinical samples.The Kaplan-Meier analysis was used to determine the associations between SRP14 mRNA expression and the overall survival,progression-free survival,and disease-specific survival of HCC patients.The effect of SRP14 on the proliferation and migration of HCC cells were determined by EdU staining,MTS,Transwell and wound-healing assays.The potential mechanism for SRP14 regulating HCC was explored through Kyoto Encyclopedia of Genes and Genomes(KEGG)and Gene Ontology(GO)enrichment analysis as well as qRT-PCR.Results:According to the data from GSE14520,TNMplot database and clinical samples,compared with paired tumor-adjacent tissues,non-paired tumor-adjacent tissues and normal tissues,the mRNA expression of SPR14 in HCC tissues was upregulated(all P<0.05).In clinical samples,compared with paired tumor-adjacent tissues,the protein expression of SPR14 in HCC tissues was increased(P<0.05).The increased mRNA expression of SRP14 was associated with good overall survival,progression-free survival,and disease-specific survival in HCC patients.SRP14 inhibited the proliferation and migration of HCC cells in vitro.According to the KEGG and GO enrichment analysis,in non-specific HCC,the genes co-expressed with SRP14 may predominantly regulate protein synthesis,processing,and transport,while in nonalcoholic fatty liver disease related HCC,the genes co-expressed with SRP14 could control multiple signaling pathways such as MAPK,cAMP,PI3K-Akt,and Wnt.Mechanistically,SRP14 up-regulated the mRNA expression of tumor suppressor gene GPRC5A in HCC cells(P<0.05).Conclusion:SRP14 may regulate HCC progression and influence patient prognosis.

Background::Heterotaxy (HTX) is a thoracoabdominal organ anomaly syndrome and commonly accompanied by congenital heart disease (CHD). The aim of this study was to analyze rare copy number variations (CNVs) in a HTX/CHD cohort and to examine the potential mechanisms contributing to HTX/CHD.Methods::Chromosome microarray analysis was used to identify rare CNVs in a cohort of 120 unrelated HTX/CHD patients, and available samples from parents were used to confirm the inheritance pattern. Potential candidate genes in CNVs region were prioritized via the DECIPHER database, and PNPLA4 was identified as the leading candidate gene. To validate, we generated PNPLA4-overexpressing human induced pluripotent stem cell lines as well as pnpla4-overexpressing zebrafish model, followed by a series of transcriptomic, biochemical and cellular analyses. Results::Seventeen rare CNVs were identified in 15 of the 120 HTX/CHD patients (12.5%). Xp22.31 duplication was one of the inherited CNVs identified in this HTX/CHD cohort, and PNPLA4 in the Xp22.31 was a candidate gene associated with HTX/CHD. PNPLA4 is expressed in the lateral plate mesoderm, which is known to be critical for left/right embryonic patterning as well as cardiomyocyte differentiation, and in the neural crest cell lineage. Through a series of in vivo and in vitro analyses at the molecular and cellular levels, we revealed that the biological function of PNPLA4 is importantly involved in the primary cilia formation and function via its regulation of energy metabolism and mitochondria-mediated ATP production. Conclusions::Our findings demonstrated a significant association between CNVs and HTX/CHD. Our data strongly suggested that an increased genetic dose of PNPLA4 due to Xp22.31 duplication is a disease-causing risk factor for HTX/CHD.

Objective:To explore the effects of phased goal directed fluid therapy (GDFT) during anesthesia surgery on tissue perfusion and cognitive function in patients undergoing radical lung cancer surgery.Methods:A total of 108 lung cancer patients were prospectively selected and randomly divided into a control group and a study group using a random number table method. The control group received classical restrictive liquid therapy, while the study group received staged GDFT. We compared the surgical time, intraoperative blood loss, colloid fluid dosage, crystalloid fluid dosage, total output, and urine volume between two groups of patients; Two groups of patients were compared in terms of oxygenation index (OI), respiratory index (RI), central venous oxygen saturation (ScvO 2), lactate (Lac), central venous arterial carbon dioxide partial pressure difference (Pcv-aCO 2), oxygen supply index (DO 2I), and oxygen uptake rate (O 2ERe) before anesthesia induction (T 0), before single lung ventilation (T 1), 1 hour of single lung ventilation (T 2), immediate resumption of dual lung ventilation (T 3), 30 minutes of dual lung ventilation (T 4), and after surgery (T 5); The Mini Mental State Examination (MMSE) was used to evaluate the cognitive function scores of two groups of patients 1 day before surgery and 1 and 3 days after surgery, while recording the incidence of cognitive dysfunction (POCD) and pulmonary complications (including pulmonary infection, acute lung injury, pulmonary embolism, pulmonary edema, atelectasis, etc.) within 3 days after surgery. Results:The amount of crystal fluid and urine output in the research group was significantly lower than that in the control group, while the amount of colloidal fluid was significantly higher than that in the control group (all P<0.05). The OI of the study group T 1-T 5 was significantly higher than that of the control group, while the RI of T 2-T 5 was significantly lower than that of the control group (all P<0.05). The ScvO 2 of the study group T 1 to T 5 was significantly higher than that of the control group, and the Lac was significantly lower than that of the control group (all P<0.05); The MMSE scores of both groups of patients were significantly lower than those before surgery on day 1 and 3 after surgery, and the MMSE scores of the study group were significantly higher than those of the control group on day 1 and 3 after surgery (all P<0.05). The incidence of POCD within 3 days after surgery in the study group was 16.67%(9/54), lower than 37.04%(20/54) in the control group (χ 2=5.704, P=0.017); The incidence of pulmonary complications in the study group was lower than that in the control group (5.56% vs 22.22%, χ 2=4.955, P=0.026). Conclusions:The application of staged GDFT during anesthesia in patients undergoing radical lung cancer surgery can further improve tissue perfusion, improve microcirculation and oxygen supply-demand balance of systemic organs and tissues, including the brain, alleviate perioperative brain function damage, and reduce the occurrence of postoperative POCD compared to conventional liquid therapy.

Objective:To investigate the incidence characteristics and influencing factors of non-alcoholic fatty liver disease (NAFLD) in rural Uyghur ethnic group residents in Xinjiang Production and Construction Corps and to provide scientific evidence for early identification and prevention of NAFLD for residents.Methods:A total of 10 158 participants were included from the Xinjiang Uygur ethnic group population cohort. A prospective cohort study and Cox proportional hazards regression model analysis were used to explore the influencing factors and clustering of NAFLD, and the dose-response relationship between related biochemical indicators and the risk of NAFLD was studied using a restricted cubic spline.Results:The cumulative incidence rate of NAFLD was 6.9%, and the incidence density of NAFLD was 12.06/1 000 person-years. The incidence density of NAFLD in females was higher than in males (14.72/1 000 person-years vs. 9.17/1 000 person-years, P<0.001). The incidence density of NAFLD gradually increased with age in the total population, both men and women (all P<0.001). In the general population, an education level of junior high school or above was a protective factor for NAFLD, while older age, divorce, widowhood, overweight, obesity, hypertension, increased glomerular filtration rate, decreased HDL-C, increased LDL-C, and increased ALT were risk factors for NAFLD. Estimated glomerular filtration rate (eGFR), HDL-C, LDL-C, and ALT were non-linearly correlated with the incidence of NAFLD, and there was a significant dose-response relationship between them. Only 19.1% of residents had no NAFLD risk factors; over 80.9% had ≥1 NAFLD risk factors. The risk of NAFLD increased with the number of risk factors. Conclusions:The incidence of NAFLD in rural Uygur ethnic group residents in Xinjiang Production and Construction Corps was relatively low, but most residents had one or more risk factors for NAFLD. Prevention and control of NAFLD in this population cannot be ignored. In addition, people of older age, divorced or widowed, low education level, overweight or obese, hypertension, and abnormal eGFR, HDL-C, LDL-C, and ALT were the high-risk groups of NAFLD that need to be paid attention to in this population.

Objective To investigate the relationship between interleukin-1β (IL-1β) and miR-185-5p in the process of joint injury in acute gouty arthritis (AGA). Methods The serum miR-185-5p levels of 89 AGA patients and 91 healthy volunteers were detected by real-time quantitative PCR. The correlation between miR-185-5p expression level and VAS score or IL-1β expression level was evaluated by Pearson correlation coefficient method. Receiver operating characteristic (ROC) curve was used to evaluate the diagnostic value of miR-185-5p in AGA. THP-1 cells were induced by sodium urate (MSU) to construct an in vitro acute gouty inflammatory cell model. After the expression level of miR-185-5p in THP-1 cells was upregulated or downregulated by transfection of miR-185-5p mimics or inhibitors in vitro, inflammatory cytokines of THP-1 cells, such as IL-1β, IL-8 and tumor necrosis factor α (TNF-α), were detected by ELISA. The luciferase reporter gene assay was used to determine the interaction between miR-185-5p and the 3'-UTR of IL-1β. Results Compared with the healthy control group, the expression level of serum miR-185-5p in AGA patients was significantly reduced. The level of serum miR-185-5p was negatively correlated with VAS score and IL-1β expression level. The area under the curve (AUC) was 0.905, the sensitivity was 80.17% and the specificity was 83.52%. Down-regulation of miR-185-5p significantly promoted the expression of IL-1β, IL-8 and tumor necrosis factor (TNF-α), while overexpression of miR-185-5p showed the opposite results. Luciferase reporter gene assay showed that IL-1β was the target gene of miR-185-5p, and miR-185-5p negatively regulated the expression of IL-1β. Conclusion miR-185-5p alleviates the inflammatory response in AGA by inhibiting IL-1β.
Humans ; 3' Untranslated Regions ; Arthritis, Gouty/genetics* ; Interleukin-1beta/genetics* ; Interleukin-8 ; Luciferases ; MicroRNAs/genetics* ; Tumor Necrosis Factor-alpha

Objective:To analyze the clinical efficacy of the Yuying powder combined with the Huanglian Shangqing pill for the treatment of subacute thyroiditis (SAT) with cervical anterior pain as the main complaint, as well as its impact on serum pain factors and oxidative stress levels in patients.Methods:A prospective selection of 100 SAT patients with anterior cervical pain as the main complaint admitted to the Hebei Provincial Hospital of Traditional Chinese Medicine from January 2020 to May 2022 was conducted. They were randomly divided into two groups, with 50 patients in each group. The control group was treated with sustained-release diclofenac sodium tablets, while the observation group was treated with external application of the Yuying powder and internal administration of the Huanglian Shangqing pill. After 2 weeks of continuous treatment, the analgesic efficacy and adverse drug reactions of both groups were observed. The analgesic onset time of two groups of anterior cervical pain was compared. Two simplified McGill pain questionnaires before and after treatment [the SF-MPQ scores, including Pain Rating Index (PRI), Visual Analog Scale (VAS), and Current Pain Intensity (PPI) ], were compared; the traditional Chinese Medicine Syndrome Score, Serum Pain Factors levels [ tumor necrosis factor (TNF)- α, interleukin-1 β(IL-1β), prostaglandin E 2 (PGE 2), and nitric oxide (NO) ] and oxidative stress indicators [the levels of malondialdehyde (MDA), superoxide dismutase (SOD), and glutathione peroxidase (GSH-Px) ] were also compared. Results:The total effective rate of analgesia in the observation group [98.00%(49/50)] was significantly higher than that in the control group [82.00%(41/50)] ( P<0.05). The analgesic onset time in the observation group was significantly shorter than that in the control group ( P<0.05). After treatment, the scores of various components (PRI, VAS, PPI) and traditional Chinese medicine syndrome scores in the two groups of SF-MPQ were significantly reduced compared to before treatment (all P<0.05); and the decrease was more significant in the observation group (all P<0.05). After treatment, the serum levels of TNF -α, IL-1β, PGE 2, and NO in both groups significantly decreased compared to before treatment (all P<0.05), and the levels of serum pain inducing factors in the observation group were significantly lower than those in the control group (all P<0.05). After treatment, both groups showed a significant decrease in serum MDA content (all P<0.05), and a significant increase in serum SOD and GSH-Px levels (all P<0.05); And the improvement was more significant in the observation group (all P<0.05). The incidence of adverse reactions in the observation group [4.00%(2/50)] was lower than that in the control group [16.00%(8/50)] ( P<0.05). Conclusions:The overall efficacy of external application of Yuying powder combined with oral administration of Huanglian Shangqing pill in the treatment of SAT with cervical anterior pain as the main complaint is definite, and its effect may be related to significantly downregulating the expression level of serum related pain inducing factors in patients and reducing the level of oxidative stress in the body.

Objective:To analyze the fail mode of neoadjuvant therapy combined with surgery for locally advanced esophageal squamous cell carcinoma (ESCC) after long-term follow-up.Methods:Clinical data of consecutive 238 patients with locally advanced resectable ESCC who underwent neoadjuvant therapy combined with surgery in Zhejiang Cancer Hospital from September 2012 to October 2019 were retrospectively analyzed. The failure mode in the whole cohort was analyzed after long-term follow-up. The overall survival (OS) and disease free survival (DFS) rates were analyzed by Kaplan-Meier method. Survival differences were determined by log-rank test.Results:The pathological complete response (pCR) rate was 42.0% in 238 patients. After a median follow-up of 46.1 months, tumor progression occurred in 96 patients (40.3%), including 25 patients (10.5%) with local recurrence, 61 patients (25.6%) with distant metastases, and 10 patients (4.2%) with simultaneous local recurrence and distant metastases. The median OS and DFS were 64.7 months and 49.9 months. And the 3-, 5-, and 7-year OS and DFS rates were 70.0%, 52.8%, 36.4% and 63.5%, 42.5%, and 30.0%, respectively. The 3-, 5-, and 7-year locoregional recurrence-free survival rates and distant metastasis-free survival rates were 86.0%, 71.4%, 61.2% and 70.6%, 55.9%, 43.0%. Compared with non-pCR patients, the overall progression rate and distant metastasis rate of pCR patients were lower (26.0% vs. 50.7%, 16.0% vs. 32.6%, both P<0.05). And the 3-, 5-, and 7-year OS (83.0% vs. 60.2%, 69.7% vs. 41.7%, 50.4% vs. 27.7%, all P<0.001) and DFS rates (80.4% vs. 51.4%, 63.9% vs. 31.2%, 45.9% vs. 20.3%, all P<0.001) were significantly better in pCR patients. Conclusions:Distant metastasis is the main failure mode of patients with locally advanced ESCC after neoadjuvant therapy. Patients with postoperative pCR can achieve better long-term survival.

Objective:To analyze the failure patterns and survival after stereotactic body radiotherapy (SBRT) in patients with T 1-2N 0M 0 non-small cell lung carcinoma (NSCLC). Methods:Clinical data of early-stage NSCLC patients who received SBRT at Zhejiang Cancer Hospital from January 2012 to September 2018 were retrospectively analyzed. The primary observed endpoint was the pattern of disease progression, which was divided into intra-field recurrence, regional lymph node recurrence and distant metastasis. Overall survival (OS) and progression-free survival (PFS) were calculated by Kaplan-Meier method. Univariate analysis was conducted by log-rank test, and multivariate analysis was performed by Cox's model.Results:A total of 147 patients with 156 lesions were included. The median follow-up time was 44.0 months (16.5-95.5 months). A total of 57 patients (38.8%) progressed: 14 patients (24.5%) had recurrence with the 1-, 3-, and 5-year local recurrence rates of 2.0%, 10.9%, and 14.3%, respectively; 36 patients (63.2%) had Distant metastasis with the 1-, 3- and 5-year distant metastasis rates of 12.2%, 22.4% and 28.6%, respectively; and 7 patients (12.3%) had recurrence complicated with distant metastasis. The 3-, 5- and 7-year OS rates were 80.5%, 64.2% and 49.9% for all patients, respectively. The median OS was 78.4 months. The 3-, 5- and 7-year PFS rates were 64.8%,49.5% and 41.5%, with a median PFS of 57.9 months (95% CI: 42.3-73.5 months). Univariate and multivariate analyses showed that biologically equivalent dose and age were the factors affecting the efficacy of SBRT (both P<0.05). Conclusion:Distant metastasis is the main failure pattern in patients with T 1-2N 0M 0 NSCLC after SBRT. High-risk population should be selected for further systematic treatment to improve the efficacy.

ObjectiveTo investigate the association between ZJU index and the onset of nonalcoholic fatty liver disease （NAFLD） in the Uygur population and the value of ZJU index in predicting the risk of NAFLD. MethodsThe Uighur community of The 51st Regiment of The Third Division of Xinjiang Kashgar Corps was selected as the investigation site， and the Uygur residents who lived in this area and had an age of >18 years were selected as subjects. Follow-up studies were conducted in 2019， 2020， and 2021， and the investigation of outcomes was completed in June to August of 2021. Finally 10 597 subjects were enrolled for analysis. The Kruskal-Wallis H test was used for comparison of continuous variables between groups， and the chi-square test was used for comparison of categorical variables between groups. The subjects were divided into Q1-Q4 groups according to the level of ZJU index. The Kaplan-Meier curve was used to predict the incidence rate of NAFLD， and the Cox regression model was used to analyze the association between ZJU index and the risk of NAFLD； the area under the ROC curve （AUC） was used to evaluate the value of ZJU index in predicting the risk of NAFLD. ResultsDuring the median follow-up time of 4.92 years， the incidence rate of NAFLD was 9.4% （992/10 597） among the study population. After adjustment for multiple factors， there was a significant increase in the risk of NAFLD with the increase in ZJU index， with a hazard ratio of 2.55 （95% confidence interval ［CI］： 1.60‍ — ‍4.06）， 7.32 （95%CI： 4.78‍ — ‍11.20）， and 21.74 （95%CI： 14.32‍ — ‍33.00）， respectively （all P_trend<0.001）. The ROC curve showed that ZJU index had a higher value in predicting NAFLD （AUC=0.816）， and the male subgroup had a significantly higher predictive accuracy of ZJU index than the female subgroup （AUC： 0.829 vs 0.809）. ConclusionZJU index is a predictive factor for the onset of NAFLD in the Uygur population in rural areas of Xinjiang and has a good value in predicting the risk of NAFLD.