Cardiovascular disease (CVD) is one of the leading causes of death worldwide and poses a severe threat to human health. Recent years have witnessed a growing interest in how the gut microbiota regulates the cardiovascular system. Akkermansia muciniphila (A. muciniphila), a key constituent of this community, has become a focus of research on CVD prevention owing to its critical role in maintaining gut homeostasis, modulating metabolism, and regulating immunity. This review details the beneficial effects and mechanisms of action of A. muciniphila in CVD. A. muciniphila protects against conditions such as hypertension, atherosclerosis, heart failure, and abdominal aortic aneurysm by repairing the gut barrier, balancing glucose and lipid metabolism, regulating immune-inflammatory responses, and producing protective metabolites such as short-chain fatty acids. However, in pathological states, such as a damaged gut barrier or low-fiber diets, A. muciniphila can over-proliferate, accelerate mucus breakdown, and exacerbate inflammation and disease progression—revealing a “double-edged sword” character. Furthermore, diet, medications, and an individual’s baseline gut microbiota directly modulate their abundance, underscoring the need for personalized approaches. Future studies should focus on clarifying strain differences, establishing safe dosing, and optimizing delivery systems to advance the clinical application of A. muciniphila in CVD therapy.

INTRODUCTION:In recent years, increasing evidence has highlighted the potential of remote management in cardiovascular diseases, with growing recognition of its feasibility and clinical value supporting its broad future application. This study aimed to investigate the efficacy of remote management for patients with heart failure (HF) in Eastern China. METHODS:A single-center, prospective, nonrandomized controlled trial enrolled 433 patients with HF, comprising 52 opting for remote management and 381 receiving usual care. Propensity score matching (1:2) yielded 95 patients (37 intervention and 58 control) for analysis. The intervention comprised a multilevel digital health ecosystem (WeChat mini program and centralized digital health management platform), structured health monitoring (weight, blood pressure, heart rate, and oxygen saturation), and education. The primary outcome includes a composite of cardiovascular mortality and HF-related rehospitalization. RESULTS:The composite primary outcome occurred in 11 (30%) patients receiving intervention and 24 (41%) controls over a maximum 24-month follow-up period. The intervention group demonstrated a statistically significant reduction in the percentage of days lost due to unplanned HF rehospitalization or all-cause death (p = 0.049). Numerically lower rates were observed for HF-related rehospitalization, cardiovascular mortality, and all-cause mortality, along with higher quality of life scores, although with no statistical significance. CONCLUSION:Remote management demonstrated feasibility and potential clinical benefits, particularly in reducing the cumulative burden of illness. Further, it provides a foundation for integration into primary healthcare systems to optimize resource allocation and improve long-term patient outcomes.

Arterial stiffness is a critical determinant of cardiovascular risk and is influenced by various metabolic factors. The triglyceride-glucose (TyG) index, an emerging marker of insulin resistance, and visceral adiposity are both associated with arterial stiffness. However, the interaction between TyG index and visceral adiposity in relation to arterial stiffness has not been thoroughly explored. A total of 761 participants underwent health examinations, including measurements of fasting blood glucose, lipid profiles, visceral fat area (VFA), and arterial stiffness assessed by brachial-ankle pulse wave velocity (baPWV). Participants were stratified by TyG index and VFA. Logistics regression and interaction analyses were conducted to assess the combined effect of TyG and VFA on arterial stiffness. Both the high TyG index and high VFA were independently associated with arterial stiffness(OR, 3.786, 95

BACKGROUND:Atrial fibrillation/flutter (AF/AFL) is the most common clinically significant arrhythmias in older adults, with an increased burden of disease due to the aging of Chinese population. Identifying and predicting secular trends in the incidence and mortality of AF/AFL in Chinese residents is crucial to facilitate optimal healthcare planning and improve the management of AF/AFL. METHODS:The incidence and death data of AF/AFL in China from 1992 to 2021 were sourced from the Global Burden of Disease Study 2021 database. The time trends of AF/AFL from 1992 to 2021 was analyzed using the joinpoint regression model. Additionally, the age-period-cohort model was used to estimate the age, period, and cohort effects on disease burden of AF/AFL and the Bayesian age-period-cohort (BAPC) approach was employed to forecast future trends in the next 25 years. RESULTS:For 1992-2021, the age-standardized incidence rate of AF/AFL in China increased annually by 0.46% (95% CI: 0.39-0.52) in males, whiles the change in females was not statistically different. In addition, the incidence rate of AF/AFL in both females and males showed an increasing trend in all age groups under 65 years old, and a decreasing trend in the older groups. The age-standardized mortality rate of AF/AFL in China decreased annually by 1.00 (0.76-1.24) in females, while there is no statistically significant difference in males. The age-period-cohort fitting results showed that older age, present period and past cohort were risk factors for the incidence and mortality rate of AF/AFL. The BAPC predicts that, the incidence and mortality of AF/AFL are expected to rise rapidly among both males and females due to population aging, potentially reaching several times the figures recorded in 2021, particularly among females, owing to their longer life expectancy compared to males. CONCLUSION:Given China's large population and rapid aging, AF/AFL poses a significant public health challenge, particularly in the future. Targeted efforts to reduce the prevalence of risk factors, increase screening coverage rates and strengthen the management of AF/AFL are necessary to deal with the situation.

Background:Lower extremity peripheral arterial disease (PAD) reflects the overall condition of the cardiovascular system. Due to its often asymptomatic nature, PAD is frequently overlooked. We aimed to estimate the disease burden of PAD in China over the past 30 years and to project future trends over the next 25 years. Methods:The incidence and disability-adjusted life years (DALYs) of PAD was extracted from the Global Burden of Disease (GBD) database and subsequently described. Joinpoint regression was used to assess trends from 1990 to 2021, and an age-period-cohort model was constructed to examine the influence of period and cohort effects on incidence and DALYs of PAD. A Bayesian APC model was also applied to forecast trends through 2046. Results:In 2021, the annual number of new PAD cases in China was 2.45 (95% UI: 2.11-2.85) million, of which 1.74 (1.50-2.03) million were female and 0.71 (0.61-0.83) million were male. The number of new cases in 2021 was obviously higher than that in 1990 among females and males. The age-standardized incidence rate (ASIR) exhibited an increasing trend among males, while a decreasing trend was observed among females. Incidence number rose across all age groups, but rates declined in females. Period effects were identified as high-risk factors for PAD incidence and in both sexes, whereas the cohort effects appeared protective. The number of new cases is projected to rise from 2.45 million in 2021 to 4.04 million by 2046, while the ASIR remains stable. Trends in DALYs showed similar patterns. Conclusion:The burden of PAD in China has increased markedly from 1990 to 2021 and is expected to continue rising over the next 25 years. Efforts to reduce modifiable risk factors-such as smoking and metabolic diseases-and to enhance PAD prevention and management, including the establishment of Pan-Vascular Management Center, are urgently needed.

Isolated anti-HBc (IAHBc) is defined by the presence of anti-HBc in the absence of HBsAg and hepatitis B surface antibody (anti-HBs). IAHBc is of great clinical significance as a specific pattern of HBV infection, but IAHBc has not been fully clarified. This study aimed to explore the prevalence and influential factors of IAHBc from routine examination results of inpatients.A total of 61,247 individuals were included in the study, with a median age of 55 years (range: 43–68), and a male-to-female ratio of 0.90:1. The prevalence of current HBV infection (HBsAg positive) was 6.82%, while the prevalence of previous HBV infection (HBsAg negative but anti-HBc positive) was 48.63%. The prevalence of IAHBc was 12.31%. Among them, the rates for males were 7.10%, 52.16%, and 13.70%, respectively, which were significantly higher than the rates for females at 6.56%, 45.45%, and 11.06% (P < 0.05). The prevalence rates mentioned above were significantly reduced after vaccination (P < 0.05). The prevalence of IAHBc increases with age, rising from 0.23% in the age group of 15–29 years to 13.57% in individuals aged 80 and above. After the age of 50, the prevalence of IAHBc closely parallels the previous infection rate but shows no significant association with the current infection rate (P > 0.05). Among IAHBc individuals, approximately 33.83% tested positive for anti-HBe, and their anti-HBc absorbance values were significantly higher compared to anti-HBe negative individuals (7.08 and 5.31, P < 0.01). The prevalence of anti-HBe positivity among IAHBc individuals does not vary with changes in the previous infection rate and age (P > 0.05).

Abstract Objective To analyze the correlation between antimicrobial resistance of Klebsiella pneumoniae in ICU and the use of antibiotics, to provide evidence and reference for rational use of antibiotics and prevention and control of multi-drug resistant bacteria. Methods The composition ratio and the antibiotic resistance rate of Klebsiella pneumoniae isolated in ICU from 2020 to 2022 was analyzed retrospectively, as well as the correlation between the antibiotic use density and antibiotic resistance were analyzed. Results 971 strains of Klebsiella pneumoniae isolated from ICU for three years were selected. The samples were mainly derived from sputum (72.50%), urine (10.40%), drainage fluid (7.00%), blood (6.80%). The antibiotic resistance rate of Klebsiella pneumoniae was 48.6%, and there was significant difference in the antibiotic resistance rate of all kinds of antibiotics (P < 0.001).The resistance rate of Klebsiae pneumoniae to β-lactam and quinolone antibiotics was higher (> 50%). The resistance rate to Carbapenems, aminoglycosides and sulfonamides was relatively low (< 40%). There was a significant positive correlation between the resistance rate of Klebsiella pneumoniae and the antibiotics use density (P < 0.05). Conclusion The antibiotic resistance of Klebsiella pneumoniae is severe, which is significantly related to the antibiotic use density. We should strengthen the management of antibiotic, and strictly implement the prevention and control measures of multi-drug resistant bacteria to reduce the spread of resistant.

目的 观察超体重(孕前体质量指数≥25 kg/m2)产妇剖宫产术中应用超声引导下椎管内麻醉联合腹横肌平面神经阻滞的效果,探讨其在术后康复中的作用.方法 行剖宫产手术超体重产妇240例,随机分为观察组和对照组各120例.对照组椎管内麻醉采用常规髂嵴最高点连线定位法,于L2-3间隙穿刺后注射质量分数0.75％布比卡因1.2～1.5 mL;观察组在超声引导下于L2-3间隙穿刺后注射质量分数0.75％布比卡因1.2～1.5 mL,手术结束时于超声引导下行双侧腹横肌平面神经阻滞,注射质量分数0.375％盐酸罗哌卡因15 mL+盐酸右美托咪定0.75 μg/kg;2组术后自控静脉镇痛均应用舒芬太尼+酮洛酸氨丁三醇+盐酸阿扎司琼.记录2组麻醉穿刺时间、穿刺次数、首次自控镇痛时间、自控镇痛次数、术后泌乳时间、住院时间等;采用40项恢复质量量表(quality of recovery-40 questionnaire,QoR-40)评分评估2组术后24 h恢复情况;比较2组术前及术后24 h催乳素、空腹血糖、去甲肾上腺素、白细胞介素-6(interleukin 6,IL-6)水平;多因素线性回归分析影响超体重产妇剖宫产术后QoR-40评分的因素.结果 2组年龄、孕周、体质量指数、手术时间及术后下床时间比较差异均无统计学意义(P＞0.05).观察组麻醉穿刺时间[(78.1±20.2)s]、术后泌乳时间[(25.3±10.2)h]、术后通气时间[(10.7±6.1)h]、住院时间[(4.8±0.8)d]均短于对照组[(117.6±79.1)s、(33.1±12.9)h、(12.8±9.4)h、(5.0±0.8)d](t=5.300,P＜0.001;t=5.177,P＜0.001;t=2.046,P=0.040;t=2.023,P=0.040),穿刺次数[(1.3±0.5)次]、自控镇痛次数[(1.9±1.3)次]均少于对照组[(1.8±0.9)、(2.8±1.6)次](t=5.610,P＜0.001;t=4.893,P＜0.001),术后 24 h QoR-40 评分[(192.0±9.8)分]高于对照组[(180.1±21.8)分](t=5.443,P＜0.001).观察组术前 24 h 空腹血糖[5.20(4.50,5.60)mmol/L]、去甲肾上腺素[442.50(382.25,462.00)ng/L]、IL-6[5.37(4.56,5.90)ng/L]、催乳素[226.00(206.25,245.00)μg/L]水平与对照组[5.20(4.50,5.60)mmol/L、445.00(376.00,467.75)ng/L、5.37(4.56,5.82)ng/L、226.00(215.00,245.00)μg/L]比较差异均无统计学意义(P＞0.05);观察组术后24 h催乳素[400.50(387.00,418.00)μg/L]水平高于对照组[367.00(355.00,390.00)μg/L](U=8.26,P＜0.001),空腹血糖[5.60(5.50,5.90)mmol/L]、去甲肾上腺素[521.00(467.00,545.75)ng/L]、IL-6[16.82(15.15,19.85)ng/L]水平均低于对照组[6.25(5.90,6.68)ng/L、606.00(556.00,645.00)ng/L、24.42(19.88,27.55)ng/L](U=-7.73,P＜0.001;U=-8.76,P＜0.001;U=-8.98,P＜0.001);2 组术后 24 h 各指标均高于术前 24 h(P＜0.05).术后 IL-6(β=-0.58,95％CI:-0.96～0.20,P=0.003)、麻醉穿刺时间(β=-0.04,95％CI:-0.07～0.01,P=0.021)、麻醉方式(β=5.36,95％CI:0.55～10.18,P=0.029)是超体重产妇剖宫产后QoR-40评分的影响因素.结论 超体重产妇剖宫产术中应用超声引导下椎管内麻醉联合腹横肌平面神经阻滞可缩短术中麻醉穿刺时间,减少穿刺次数,减轻术后疼痛,促进术后快速康复.

What is already known about this topic? Healthcare workers (HCWs) and previously infected patients (PIPs) may experience a wave of epidemic following the modification of the country's coronavirus disease (COVID)-zero policy in China. What is added by this report? As of early January 2023, the initial wave of the COVID-19 pandemic among HCWs had effectively subsided, with no statistically significant differences observed in infection rates compared to those of their co-occupants. The proportion of reinfections among PIPs was relatively low, particularly in those with recent infections. What are the implications for public health practice? Medical and health services have resumed normal operations. For patients who have recently experienced severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections, appropriate relaxation of policies may be considered.

Background Patients infected with SARS-CoV-2 Delta VOC have a longer course of disease. We detected the air, surfaces, and patient’s personal items in the wards of the second hospital of Nanjing during the outbreak of the COVID-19 Delta Variant to identify the environmental contamination, which provides a theoretical basis for the prevention and control of COVID-19 variation beads in the future. Methods In the cross-sectional study, we collected and analyzed clinical features, demographic and epidemiological data, laboratory and swab test results, and surface and air samples of 144 COVID-19 cases. Results The time from symptom onset to surface sampling was 25 days (IQR, 21 to 33 days). Positive throat swabs were detected in 52(36.1%) patients, of which only 8(5.6%) patients had N or ORF1a/b genes Ct value <35 on the surface sampling day. Among the 692 environmental surface and air specimens collected from 144 COVID-19 cases, 3 specimens (3/692, 0.4%) related to 5 cases (3.5%, 5/144) were detected positive on RT-PCR. Overall, bedside tables (2/144, 1.4%) were most likely to be contaminated, followed by toilet seats (1/81, 1.2%). Conclusion The environmental contamination by SARS-CoV-2 Delta VOC-infected cases with disease duration of more than two weeks is limited.

Objectives C1s activation is associated with the pathogenesis of various diseases, indicating the potential value of C1s activation detection in clinic. Here we aimed to establish fluorescence resonance energy transfer (FRET)-based immunoassay for the quantitative detection of activated C1s in serum. Methods FRET-based fluorogenic peptides, sensitive to the enzymatic activity of activated C1s, were prepared and labeled with the fluorophore ortho-aminobenzoic acid (Abz) and quencher 2,4-dinitrophenyl (Dnp), and then were further selected depending on its Kcat/Km value. C1s in the samples was captured and separated using anti-C1s-conjugated magnetic microbeads. Next, enzymatic activity of activated C1s in samples and standards was examined using fluorescent quenched substrate assays. Limit of detection (LOD), accuracy, precision, and specificity of FRET-based immunoassay were also investigated. Results This method presented a linear quantification range for the enzymatic activity of activated C1s up to 10 μmol min -1 mL -1 and LOD of 0.096 μmol·min -1 ·mL -1 for serum samples. The recovery of the method was in the range of 90% ~ 110%. All CV values of the intra-analysis and inter-analysis of three levels in samples were less than 10%. The cross-reaction rates with C1r enzyme, MASP1, and MASP2 were less than 0.5%. No significant interferences were found with bilirubin (0.2 mg mL -1 ), Chyle (2000 FTU), and haemoglobin (5 mg mL -1 ), but anticoagulants (EDTA, citrate and heparin) inhibited the enzymatic ability of activated C1s. Thus, this established method can be used for the determination of active C1s in human serum samples in the concentration interval of 0.096-10.000 μmol min -1 mL -1 . Conclusions One anti-C1s-based FRET immunoassay for activated C1s detection in serum samples were established, and it will be useful to explore the role of C1s activation in the pathogenesis, diagnosis and treatment in complement-related diseases.

Abstract Background This study aims to investigate differences in sex hormone levels and brain morphology among women with offspring and nulliparous to explore the changes that the reproduction induces. Methods A total of 66 females of reproductive age range 20–40 years were enrolled, including 35 offspring women, and 31 nulliparous. Participants’ sex hormone levels were assessed. T1 structural images were obtained using a 3.0 Tesla MRI scanner, and voxel-based morphometry (VBM) was implemented to investigate gray matter changes between the two groups and extract brain volume including gray matter volume (GMV), white matter volume (WMV), cerebrospinal fluid (CSF). Results Analysis of sex hormones revealed no significant differences in E2 (z = − 0.28,p = 0.782), LH (z = − 0.62,p = 0.537), and P (z = − 1.34,p = 0.181), whereas significant differences were found in FSH (z = 3.86,p < 0.001), T (z = − 3.92,p < 0.001), and PRL (z = − 3.27, p = 0.018). Differences in brain volumes, including GMV (t = − 3.53,p = 0.001), CSF (t = − 2.39,p = 0.020), were observed. VBM analysis showed that compared with nulliparous women, those with offspring exhibited decreased cortical areas in the left superior frontal gyrus and right putamen, but no increased cortical areas were found. Conclusion Females of reproductive age in the 20–40 years group, compared with nulliparous female, sex hormones of female with offspring changed, and the volume of the cerebral cortex decreased, which indicated that females were developing in the direction of functional decline. Further research should explore the mechanism underlying these discrepancies, and their potential consequences for female health.

To analyze the diagnostic value of CD40 ligand (CD40L), soluble growth stimulating expression gene 2 protein (ST2), interleukin-6 (IL-6), and C-reactive protein (CRP) are used in patients with acute coronary syndrome (ACS). Serum samples were collected from 259 ACS patients admitted to our hospital. Additionally, 119 healthy individuals who received physical examination in the hospital at the same time period were included as normal control. The levels of CD40L, ST2, IL-6, and CRP in 259 patients with ACS and 119 healthy subjects were detected by ELISA. The levels of CD40L, ST2, IL-6, and CRP were significantly increased in unstable angina (UA) patients, while ST2, CRP, and IL-6 were significantly elevated in acute myocardial infarction (AMI) patients. Pearson correlation analysis showed that ST2 was also closely related to CRP in ACS patients, while ST2 was positively correlated with creatine kinase (CK), creatine kinase isoenzyme (CK-MB), and troponin I (cTnI) in AMI patients. The levels of glucose (GLU) and low-density lipoprotein cholesterol (LDL-c) were significantly decreased, while the levels of high-density lipoprotein cholesterol (HDL-c) were significantly increased in AMI patients treated with stent implantation. Furthermore, the level of serum CD40 L was significantly elevated in coronary heart disease (CHD) patients treated with stent implantation, while the levels of ST2 and IL-6 in AMI patients treated with the stent implantation decreased significantly. The levels of inflammatory factors significantly changed in patients with ACS. These inflammatory factors may involve in the pathological progression of ACS and can be used as diagnostic indexes for ACS.

Background: Cumulative evidence suggests that A-kinase interacting protein 1 (AKIP1) plays an important role in tumor progression. However, the prognostic value of AKIP1 expression in various cancers remains unclear. Here, we conducted a meta-analysis to evaluate the prognostic value of AKIP1 expression in patients with cancer. Methods: The PubMed, Web of Science, EMBASE, CNKI, and Wanfang databases were systematically searched to identify studies in which the effect of AKIP1 expression on prognosis (overall survival or disease-free survival) was investigated. Hazard ratios (HRs) with 95% confidence intervals (CIs) were combined to assess the effect of AKIP1 expression on patient survival. Odds ratios (ORs) with 95% CIs were pooled to estimate the association between AKIP1 expression and clinicopathological characteristics of patients with cancer. Results: Nineteen eligible studies, encompassing 3979 patients, were included in the meta-analysis. AKIP1 expression was negatively associated with overall survival (HR=1.86, 95% CI: 1.58-2.18, P<.001) and disease-free survival (HR= 1.69, 95% CI: 1.53-1.87, P<.001) in patients with cancer. Moreover, AKIP1 overexpression was positively correlated with adverse clinicopathological features, such as tumor size (OR=2.22, 95% CI: 1.67-2.94, P<.001), clinical stage (OR=2.05, 95% CI: 1.45-2.90, P<.001), depth of tumor invasion (OR=2.98, 95% CI: 2.21-4.02, P<.001), and degree of lymph node metastasis (OR=2.12, 95% CI: 1.75-2.57, P<.001). Conclusions: High AKIP1 expression is an unfavorable prognostic biomarker and may serve as a potential therapeutic target in patients with cancer.

目的 基于流程优化理论再造智慧门诊服务流程,并探讨其实践效果.方法 选取2020年1月至2021年12月在我院门诊救治的2175559例患者,比较再造前后患者门诊挂号总人数、预约数、在线咨询及预约就诊率,患者就诊时间、候诊时间及检查等待时间,门诊各部门人流密度及医患满意度.结果 再造后,门诊预约挂号及在线咨询人数显著提高,且门诊预约就诊率及在线咨询率提升,门诊患者就诊时间、候诊时间及检查等待时间均低于再造前(P<0.05).门诊各部门人流密度均有所降低,但差异在统计学上无意义(P>0.05).再造后患者满意度89.34％及医生满意度92.31％,均显著优于再造前(P<0.05).结论 智慧门诊服务流程的再造,实现了门诊预约及诊疗服务在时间及空间方面分布合理,提高了门诊预约就诊率,加快患者门诊就医周转,控制人流密度,有效提升医患满意度,实现自理智治,值得临床推广应用.

Coronavirus disease 2019 (COVID-19), caused by SARS-CoV-2, has induced a worldwide pandemic since early 2020. COVID-19 causes pulmonary inflammation, secondary pulmonary fibrosis (PF); however, there are still no effective treatments for PF. The present study aimed to explore the inhibitory effect of dihydroartemisinin (DHA) on pulmonary inflammation and PF, and its molecular mechanism. Morphological changes and collagen deposition were analyzed using hematoxylin-eosin staining, Masson staining, and the hydroxyproline content. DHA attenuated early alveolar inflammation and later PF in a bleomycin-induced rat PF model, and inhibited the expression of interleukin (IL)-1β, IL-6, tumor necrosis factor α (TNFα), and chemokine (C-C Motif) Ligand 3 (CCL3) in model rat serum. Further molecular analysis revealed that both pulmonary inflammation and PF were associated with increased transforming growth factor-β1 (TGF-β1), Janus activated kinase 2 (JAK2), and signal transducer and activator 3(STAT3) expression in the lung tissues of model rats. DHA reduced the inflammatory response and PF in the lungs by suppressing TGF-β1, JAK2, phosphorylated (p)-JAK2, STAT3, and p-STAT3. Thus, DHA exerts therapeutic effects against bleomycin-induced pulmonary inflammation and PF by inhibiting JAK2-STAT3 activation. DHA inhibits alveolar inflammation, and attenuates lung injury and fibrosis, possibly representing a therapeutic candidate to treat PF associated with COVID-19.

Background and Aim. Sphingosine kinase 1 (SPHK1) is a key enzyme of sphingolipid metabolism which is involved in the pathogenesis and progression of human cancer. It has been demonstrated to be upregulated in various types of human malignancies. However, the prognostic value of SPHK1 remains unclear. Therefore, we performed this meta-analysis to assess its predictive value in the prognosis of cancer patients. Methods. PubMed, Web of Science, Embase, CNKI, and Wanfang databases were thoroughly searched for eligible studies, in which the relationship between SPHK1 expression and cancer prognosis was evaluated. Hazard ratios (HRs) and 95% confidence intervals (CIs) were pooled to estimate the impact of SPHK1 expression on cancer patients’ survival. Odds ratios (ORs) and 95% CIs were combined to assess the association between SPHK1 expression and clinicopathological characteristics of cancer patients. The certainty of evidence was evaluated by Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) criteria. Results. Thirty studies comprising 32 cohorts with 5965 patients were included in this meta-analysis. The outcomes indicated that elevated SPHK1 expression was associated with worse overall survival (OS) (HR=1.71, 95% CI: 1.45-2.01, P<0.001) and disease-free survival (DFS) (HR=1.34, 95% CI: 1.13-1.59, P=0.001). What is more, SPHK1 overexpression was significantly correlated with certain phenotypes of tumor aggressiveness, such as clinical stage (OR=2.07, 95% CI: 1.39-3.09, P<0.001), tumor invasion (OR=2.16, 95% CI: 1.47-3.18, P<0.001), lymph node metastasis (OR=2.04, 95% CI: 1.71-2.44, P<0.001), and distant metastasis (OR=3.16, 95% CI: 2.44-4.09, P<0.001). The quality of the evidence for both OS and DFS was low. Conclusions. Increased SPHK1 expression is related to poor prognosis in human cancers and may serve as a promising prognostic marker and therapeutic target for malignant patients. However, conclusions need to be treated with caution because of lack of high quality of evidence.

Musashi 2 (MSI2) is an RNA-binding protein that regulates mRNA translation of numerous intracellular targets and plays an important role in the development of cancer. However, the prognostic value of MSI2 in various cancers remains controversial. Herein, we conducted this meta-analysis including 21 studies with 2640 patients searched from PubMed, Web of Science, EMBASE, Chinese National Knowledge Infrastructure databases, and WanFang databases to accurately assess the prognostic significance of MSI2 in various cancers. Our results indicated that high MSI2 expression was significantly related to poor overall survival (HR = 1.84, 95% CI: 1.66-2.05, P < 0.001) and disease-free survival (HR = 1.73, 95% CI: 1.35-2.22, P < 0.001). In addition, MSI2 positive expression was associated with certain phenotypes of tumor aggressiveness, such as clinical stage, depth of invasion, lymph node metastasis, liver metastasis and tumor size. In conclusion, elevated MSI2 expression is closely correlated with poor prognosis in various cancers, and may serve as a potential molecular target for cancer patients.

BACKGROUND Colorectal cancer (CRC) is one of the most common malignancies worldwide. Given its insidious onset, the condition often already progresses to advanced stage when symptoms occur. Thus, early diagnosis is of great significance for timely clinical intervention, efficacy enhancement, and prognostic improvement. Featuring high throughput, fastness, and rich information, next generation sequencing (NGS) can greatly shorten the detection time, which is a widely used detection technique at present. AIM To screen specific genes or gene combinations in fecal DNA that are suitable for diagnosis and prognostic prediction of CRC, and to establish a technological platform for CRC screening, diagnosis, and efficacy monitoring through fecal DNA detection. METHODS NGS was used to sequence the stool DNA of patients with CRC, which were then compared with the genetic testing results of the stool samples of normal controls and patients with benign intestinal disease, as well as the tumor tissues of CRC patients. Specific genes or gene combinations in fecal DNA suitable for diagnosis and prognostic prediction of CRC were screened, and their significances in diagnosing CRC and predicting patients' prognosis were comprehensively evaluated. RESULTS High mutation frequencies of TP53, APC, and KRAS were detected in the stools and tumor tissues of CRC patients prior to surgery. Contrastively, no pathogenic mutations of the above three genes were noted in the postoperative stools, the normal controls, or the benign intestinal disease group. This indicates that tumor-specific DNA was detectable in the preoperative stools of CRC patients. The preoperative fecal expression of tumor-associated genes can reflect the gene mutations in tumor tissues to some extent. Compared to the postoperative stools and the stools in the two control groups, the pathogenic mutation frequencies of TP53 and KRAS were significantly higher for the preoperative stools (χ2 = 7.328, P < 0.05; χ2 = 4.219, P < 0.05), suggesting that fecal TP53 and KRAS genes can be used for CRC screening, diagnosis, and prognostic prediction. No significant difference in the pathogenic mutation frequency of the APC gene was found from the postoperative stools or the two control groups (χ2 = 0.878, P > 0.05), so further analysis with larger sample size is required. Among CRC patients, the pathogenic mutation sites of TP53 occurred in 16 of 27 preoperative stools, with a true positive rate of 59.26%, while the pathogenic mutation sites of KRAS occurred in 10 stools, with a true positive rate of 37.04%. The sensitivity and negative predictive values of the combined genetic testing of TP53 and KRAS were 66.67% (18/27) and 68.97%, respectively, both of which were higher than those of TP53 or KRAS mutation detection alone, suggesting that the combined genetic testing can improve the CRC detection rate. The mutation sites TP53 exon 4 A84G and EGFR exon 20 I821T (mutation start and stop positions were both 7579436 for the former, while 55249164 for the latter) were found in the preoperative stools and tumor tissues. These "undetected" mutation sites may be new types of mutations occurring during the CRC carcinogenesis and progression, which needs to be confirmed through further research. Some mutations of "unknown clinical significance" were found in such genes as TP53, PTEN, KRAS, BRAF, AKT1, and PIK3CA, whose clinical values is worthy of further exploration. CONCLUSION NGS-based fecal genetic testing can be used as a complementary technique for the CRC diagnosis. Fecal TP53 and KRAS can be used as specific genes for the screening, diagnosis, prognostic prediction, and recurrence monitoring of CRC. Moreover, the combined testing of TP53 and KRAS genes can improve the CRC detection rate.

Objective:To explore the expression of long-chain noncoding RNA (lncRNA) and myocardial infarction-associated transcription (MIAT) in Leukocyte differentiation antigen (CD)4+T cells in peripheral blood of gastric cancer patients and its value of clinical application.Methods:Peripheral blood CD4+T cells were collected from 124 patients with gastric cancer, 90 benign gastric diseases patients and 80 healthy controls enrolled in Taizhou People′s Hospital from January 2019 to April 2021. The expression levels of MIAT and N6-methyladenosine(m6A) binding to MIAT promoter in CD4+T cells were detected by real-time fluorescent quantitative polymerase chain reaction (qPCR) and Chromatin immunoprecipitation (ChIP)-qPCR, respectively. Spearman test was used to analyze the correlation between MIAT and clinicopathological features, as well as between MIAT and regulatory T cell levels. The receivor operating characteristic curve (ROC) of the subjects was used to evaluate the MIAT expression level in the auxiliary diagnostic value of gastric cancer.Results:The relative expression levels of MIAT in the gastric cancer patients, the benign gastric diseases patients, and the healthy controls were 2.849 (2.131, 4.062), 1.511 (0.916, 1.855) and 0.963 (0.729, 1.432), respectively. The difference among the three groups was statistically significant ( H=158.25, P<0.001). The relative expression level of MIAT in the gastric cancer patients was significantly higher than the levels in the benign gastric diseases patients and healthy controls. The difference was statistically significant ( Z=100.63, 145.14, P<0.001). The binding activity of m6A to MIAT promoter in patients with early stage (stage Ⅰ and Ⅱ) and end stage (stage Ⅲ and Ⅳ) gastric cancer was 8.590±1.483 and 4.274±0.425, respectively. The difference was statistically significant ( t=6.255, P=0.002). Furthermore, the binding activity of m6A to MIAT promoter in the gastric cancer patients was significantly lower than that in patients with benign gastric diseases (17.267±3.106) and healthy controls (27.637±3.945) ( t=-7.331,-12.832, P<0.001). The relative expression of MIAT in CD4+T cells in peripheral blood of the gastric cancer patients had no significant difference in age(χ2=0.000, P=1.000), gender(χ2=0.000, P=1.000), CEA (χ2=0.648, P=0.421) and CA199(χ2=1.554, P=0.213), but had significant difference with tumor size expression(χ2=9.443, P<0.01), TNM stage(χ2=23.571, P=0.002) and lymph node metastasis (χ2=45.248, P<0.01). In addition, there was a significant positive correlation between the relative expression of MIAT in CD4+T cells and Treg level ( r2=0.76, P<0.001). The diagnostic efficacies of MIAT in CD4+T cells, CEA and CA199 in the gastric cancer patients were analyzed by ROC curve. When compared with patients with benign gastric diseases, the areas under the curve were 0.879, 0.635 and 0.611, respectively. When compared with healthy patients, the areas under the curve were 0.953, 0.784 and 0.598, respectively. Conclusions:The level of MIAT in CD4+T cells in peripheral blood of patients with gastric cancer is significantly higher than the levels in patients with benign gastric diseases and the healthy controls, which may be related with the decreased activity of m6A binding to the promoter of MIAT. The level of MIAT in CD4+T cells may be a relevant biomarker for the diagnosis and prognosis of gastric cancer.