The sine oculis homeobox homolog (SIX) family, a group of transcription factors characterized by a conserved DNA-binding homology domain, plays a critical role in orchestrating embryonic development and organogenesis across various organisms, including humans. Comprising six distinct members, from SIX1 to SIX6 , each member contributes uniquely to the development and differentiation of diverse tissues and organs, underscoring the versatility of the SIX family. Dysregulation or mutations in SIX genes have been implicated in a spectrum of developmental disorders, as well as in tumor initiation and progression, highlighting their pivotal role in maintaining normal developmental trajectories and cellular functions. Efforts to target the transcriptional complex of the SIX gene family have emerged as a promising strategy to inhibit tumor development. While the development of inhibitors targeting this gene family is still in its early stages, the significant potential of such interventions holds promise for future therapeutic advances. Therefore, this review aimed to comprehensively explore the advancements in understanding the SIX family within gastrointestinal cancers, focusing on its critical role in normal organ development and its implications in gastrointestinal cancers, including gastric, pancreatic, colorectal cancer, and hepatocellular carcinomas. In conclusion, this review deepened the understanding of the functional roles of the SIX family and explored the potential of utilizing this gene family for the diagnosis, prognosis, and treatment of gastrointestinal cancers.

BACKGROUND:Yudantong decoction (YDTD) is a therapeutic prescription for cholestatic liver disease (CLD) and is clinically effective in our medical institution. However, the exact constituents and mechanisms of YDTD in treating CLD remain unknown. This project aimed to explore the primary constituents and mechanism of YDTD in the treatment of CLD through ultra-performance liquid chromatography-high resolution mass spectrometry (UPLC-HRMS), network pharmacology, molecular docking technology, and in vivo experiments. MATERIALS AND METHODS:The chemical constituents of YDTD were identified via UPLC-HRMS, and Bioinformatics analysis tool for molecular mechANism of traditional Chinese medicine (BATMAN-TCM) was employed to screen target proteins. Cytoscape 3.7.1 was used to build the herbal component-target network. The CLD targets were identified by querying the OMIM and DisGeNET databases and determining the overlap between the targets of the YDTD chemical constituents and those of CLD. The STRING database was utilized to construct a protein-protein interaction (PPI) network for subsequent analysis. Gene ontology (GO) biological process enrichment analysis and Kyoto encyclopedia of genes and genomes (KEGG) signaling pathway enrichment analysis were carried out using the database for annotation, visualization and integrated discovery (DAVID) database. Molecular docking validation against core targets with PyMOL software was conducted for the active compounds. Finally, in vivo experiments were performed to investigate the therapeutic effect of YDTD in a murine model of α-naphthyl isothiocyanate (ANIT)-induced CLD. RESULTS:YDTD has 112 major components, among which 59 have 1,478 potential targets. We identified a total of 1,957 potential therapeutic targets for CLD and 269 overlapping targets between CLD-associated targets and YDTD active component targets to construct a PPI network. Through topology analysis, IL-6, INS, IL1B, AKT1, BCL2, NFKB1, PTGS2, and TP53 were identified as key targets along with their corresponding primary chemical components. KEGG analysis revealed significant enrichment of the phosphoinositide 3-Kinase (PI3K)-Akt and nuclear factor Kappa-B (NF-κB) signaling pathways. The molecular docking results indicated strong binding affinities between glycyrrhizin-AKT1, l-arginine-IL1B, p-coumaric acid-IL1B, 2,4-dihydroxybenzoic acid-IL1B, p-coumaric acid-TNF, 2-hydroxycinnamic acid-TNF, uridine-AKT1, p-coumaric acid-IL6, and trigonelline-INS. In vivo experiments demonstrated that YDTD downregulated the expression of p-PI3K, p-AKT, p-NF-κB, IL-6, TNF-α, and IL-1β, and reduced immune cell infiltration in the liver to ameliorate liver damage in CLD patients. CONCLUSION:The present study clarified the active components and potential anti-inflammatory mechanism of YDTD in treating CLD, providing a solid foundation for future research on its therapeutic mechanisms.

Background: Fatty acid-binding protein 4 (FABP4) is an adipokine that is critically involved in inflammatory, metabolic, and immune diseases. The current study aimed to investigate the role of FABP4 in patients with antineutrophil cytoplasmic antibody-associated glomerulonephritis (ANCA-GN). Methods: Patients with biopsy-proven ANCA-GN and with clinical data, plasma, urine and kidney samples from a single clinical center was enrolled. Plasma FABP4 and urinary FABP4 expression level were measured at the time of kidney biopsy and during follow-ups. Human kidney tissue samples (n = 56) were stained for FABP4 using immunohistochemistry and immunofluorescence, and the correlation between renal FABP4 expression and clinical parameters of patients were analyzed. The effect of FABP4 inhibition in ANCA-GN was further investigated in a recognized rat model of experimental autoimmune vasculitis (EAV). Results: The levels of FABP4 were abnormally increased in the urine, plasma, and kidney samples of patients with active ANCA-GN comparing to those of healthy controls. U-FABP4 level reduced dramatically with the remission of disease and showed association with the activity, severity, and prognosis of ANCA-GN. Furthermore, FABP4 inhibition by BMS309403 ameliorated renal pathological injury, improved hematuria, and lowered proteinuria in EAV rats. Interpretation: U-FABP4 was a potential noninvasive biomarker of disease activity and severity in ANCA-GN, and FABP4 might act as a promising therapeutic target against ANCA-GN. Funding: This work was supported by the National Natural Science Foundation of China (No. 82102260 and No.82300837) and the China Postdoctoral Science Foundation (No. 2023M742479). Declaration of Interest: The authors declare that they have no competing interests. Ethical Approval: The animal procedures and experimental protocols were approved by the Experimental Animal Ethics Committee of West China Hospital of Sichuan University.

BackgroundPlasma oxidized lipids are intimately linked to immune regulation as bioactive mediators. However, it is not clear whether they are related to the progression of sepsis-associated acute kidney injury (SA-AKI) and the effect of continuous renal replacement therapy (CRRT). This study intends to explore the changes in certain oxidized lipid during CRRT treatment and their correlation with the immune microenvironment and prognosis by analyzing plasma oxidative lipidomics.MethodsA total of 48 SA-AKI patients undergoing CRRT for more than 72 h were enrolled in this prospective cohort study. Oxidative lipidomics was analyzed by ultra performance liquid chromatography coupled with tandem mass spectrometric (UPLC-MS/MS) detection at the beginning of CRRT (T0) and 72 h later (T72), respectively.ResultsCompared with survivors, plasma EETs, EpOMEs and EpDPEs in non-survivors were significantly down-regulated at T0, while PGFs, TXB and HEPEs were up-regulated. After 72 h of CRRT, DiHETEs were significantly up-regulated and PGFs were down-regulated in non-survivors, while HEPEs and EpOMEs were up-regulated and 6keto-PGF1α was down-regulated in survivors. KEGG annotation showed that the differential lipids of survivors before and after CRRT were mainly enriched and up-regulated in metabolic pathway.ConclusionThis study provided a comprehensive overview of plasma oxidized lipids in SA-AKI patients undergoing CRRT and further elucidated the lipids and pathways linked to patient severity and prognosis. Additionally, we unveiled the potential mechanisms by which CRRT improves the prognosis of SA-AKI patients by removing PGFs and TXs while simultaneously upregulating HEPE to ameliorate the immune microenvironment, as well as the potential significance of adjusting CRRT prescriptions based on plasma oxidized lipidomics.

A cell line expressing the CD2v protein of ASFV was generated. The efficient expression of CD2v protein was determined by immunofluorescence and Western blotting. The CD2v protein was Ni-affinity purified from the supernatant of cell cultures. The CD2v-expressing cells showed properties of hemadsorption, and the secreted CD2v protein exhibited hemagglutinating activity. The antigenicity and immunoprotection ability of CD2v were evaluated by immunizing pigs alone, combined with a cell-line-expressed p30 protein or triple combined with p30 and K205R protein. Immunized pigs were challenged with the highly virulent ASFV strain HLJ/18. Virus challenge results showed that CD2v immunization alone could provide partial protection at the early infection stage. Protein p30 did not show synergistic protection effects in immunization combined with CD2v. Interestingly, immunization with the triple combination of CD2V, p30 and K205R reversed the protection effect. The viremia onset time was delayed, and one pig out of three recovered after the challenge. The pig recovered from ASFV clinical symptoms, the rectal temperature returned to normal levels and the viremia was cleared. The mechanism of this protection effect warrants further investigation.

Objective According to the latest consensus statement, fatty liver complicated by specific metabolic abnormalities can be diagnosed as metabolic dysfunction-associated fatty liver disease (MAFLD) in nonobese patients without type 2 diabetes mellitus (T2DM). However, hyperuricemia (HUA), a manifestation of metabolic disorders, is excluded from diagnostic criteria. This study explored the association between HUA and MAFLD in nonobese patients without T2DM. Methods A total of 28187 participants were recruited from the Examination Center of the China-Japan Friendship Hospital from 2018 to 2022 and divided into 4 subgroups: nonobese patients without T2DM, obese patients without T2DM, nonobese patients with T2DM, and obese patients with T2DM. MAFLD was diagnosed by ultrasound combined with laboratory examinations. The association of HUA with MAFLD subgroups was performed by logistical regression analysis. The predictive ability of UA for MAFLD subgroups was assessed by receiver operating characteristics (ROC). Results HUA was positively associated with MAFLD in nonobese patients without T2DM in both males and females, even after adjusting for sex, BMI, dyslipidemia, and abnormal liver function. The association increased gradually with aging, especially in those over 40 years old. Conclusions HUA was an independent risk factor for MAFLD in nonobese patients without T2DM. We suggest that UA abnormalities might be considered in the diagnosis of MAFLD.in nonobese patients without T2DM.

Silver sulfadiazine is commonly used to treat local burn wounds. Aquacel‐Ag is a hydrogen fiber dressing containing ionic silver that reduces burn wound infection and promotes antimicrobial activity. It is necessary to compare the efficacy of the two in the healing of burns.

Purpose . As one of the most common chronic liver diseases, metabolic dysfunction-associated fatty liver disease (MAFLD) had different prognoses between mild and moderate-severe levels. Serum uric acid to serum creatinine ratio (sUA/Cr) can reflect the overall metabolic status of the body. To explore a convenient indicator to screen MAFLD and distinguish the severity of the disease, this study analyzed the correlation between sUA/Cr and the severity of MAFLD. Methods . 228 participants were enrolled and divided into 2 groups, including mild MAFLD and non-MAFLD group and moderate-severe MAFLD group, based on liver/spleen computed tomography (CT) ratios. The correlations between sUA/Cr and the severity of MAFLD were analyzed by logistic and linear regression. Receiver operating characteristics (ROCs) analyzed the predictive ability of sUA/Cr for the severity of MAFLD expressed by the area under curve (AUC). Results . The level of sUA/Cr was higher in themoderate-severe MAFLD group than mild MAFLD and non-MAFLD group (6.14 ± 1.55 vs. 5.51 ± 1.19, P = 0.008). After adjustment for confounders, the correlation analysis showed that patients with elevated sUA/Cr had a higher risk of moderate-severe MAFLD (OR: 1.350, P = 0.036). A higher sUA/Cr level was associated with lower liver CT values ( β  = −0.133, P = 0.039) and liver/spleen CT ratio ( β  = −0.154, P = 0.016). sUA/Cr had the ability to discriminate the severity of MAFLD (AUC: 0.623). Conclusion . sUA/Cr was positively associated with the risk of moderate-severe MAFLD and had the predictive ability to discriminate the moderate-severe MAFLD from mild MAFLD and non-MAFLD. The sUA/Cr level was suggested to be monitored and controlled in the screening and treatment of MAFLD.

Background and Objective: Heart failure is the end-stage of various cardiovascular diseases. Recent progress in molecular biology has facilitated the understanding of the mechanisms of heart failure development at the molecular level. N6-adenosine methylation (m6A) is a post-transcriptional modification of RNA. Recent research work reported that m6A regulates gene expression and subsequently affects the activation of cell signaling pathways related to heart failure. Moreover, m6A regulators like methyltransferase-like 3 (METTL3) were reported to participate in myocardium hypertrophy. However, the current research work related to the role of m6A participating in the occurrence of heart failure is rare in some aspects like immune cell infiltration and diabetic heart diseases. Thus, it is reasonable to review the current achievements and provide further study orientation. Methods: We searched related literature using the keywords: m6A AND heart failure in PubMed, Web of Science and Medline. The language was confined to English. The published year of searched literature ranged from 2012 to 2022. The searched results were put into Endnote software for management. Two authors investigated the searching terms and reviewed the full text of selected terms. Key Content and Findings: m6A and its regulators are involved in the metabolism of various types of RNAs. m6A modification can regulate various types of cell signaling pathways related to the heart failure via interaction with m6A regulators. m6A and its regulators broadly participate in the myocardium fibrosis, myocardium hypertrophy, myocardial cell apoptosis, and ischemic reperfusion injury. Specifically, m6A participates in the cell apoptosis via regulation of autophagy flux. However, the current research work does not have enough evidence to prove that m6A regulator played its specific effect on the target transcript via regulating the m6A level. Conclusions: m6A and its regulators participates in the progression of heart failure via modifying the RNA level. Future investigation of m6A should focus on the interaction between the m6A regulators and targeted transcript. Besides, the regulation role of m6A in immune cell infiltration and diabetic heart diseases should also be focused.

Objective Metabolic dysfunction-associated fatty liver disease (MAFLD) affects 25% of the population without approved drug therapy. According to the latest consensus, MAFLD is divided into three subgroups based on different diagnostic modalities, including Obesity, Lean, and Type 2 diabetes mellitus (T2DM) MAFLD subgroups. This study aimed to find out the optimum non-invasive metabolism-related indicators to respectively predict MAFLD and its subgroups. Design 1058 Chinese participants were enrolled in this study. Anthropometric measurements, laboratory data, and ultrasonography features were collected. 22 metabolism-related indexes were calculated, including fatty liver index (FLI), lipid accumulation product (LAP), waist circumference-triglyceride index (WTI), etc. Logistic regression analyzed the correlation between indexes and MAFLD. Receiver operating characteristics were conducted to compare predictive values among 22 indicators for screening the best indicators to predict MAFLD in different subgroups. Results FLI was the best predictor with the maximum odds ratio (OR) values of overall MAFLD (OR: 6.712, 95%CI: 4.766-9.452, area under the curve (AUC): 0.879, P < 0.05) and T2DM MAFLD subgroup (OR: 14.725, 95%CI: 3.712-58.420, AUC: 0.958, P < 0.05). LAP was the best predictor with the maximum OR value of Obesity MAFLD subgroup (OR: 2.689, 95%CI: 2.182-3.313, AUC: 0.796, P < 0.05). WTI was the best predictor with the maximum OR values of Lean MAFLD subgroup (OR: 3.512, 95%CI: 2.286-5.395, AUC: 0.920, P < 0.05). Conclusion The best predictors of overall MAFLD, Obesity, Lean, and T2DM MAFLD subgroups were respectively FLI, LAP, WTI, and FLI.

Background A simple and readily available biomarker can provide an effective approach for the surveillance of type 2 diabetes mellitus (T2DM) in the elderly. In this research, we aim to evaluate the role of triglyceride to high-density lipoprotein cholesterol (TG/HDL-C) ratio as an indicator for new-onset T2DM in an elderly Chinese population aged over 75 years. Methods This longitudinal retrospective cohort study was conducted using a free database from a health check screening project in China. Participants with baseline TG and HDL measurements were enrolled, and the data of T2DM development were collected. The cumulative incident T2DM rates in different quintile groups of TG/HDL-C ratio (Q1 to Q5) were calculated and plotted. The independent effect of baseline TG/HDL-C ratio on T2DM risk during the follow-up period was tested by the Cox proportional hazard model. Subgroup analysis was also conducted to clarify the role of TG/HDL-C ratio in specific populations. Results A total of 231 individuals developed T2DM among 2,571 subjects aged over 75 years during follow-up. Regardless of adjustment for potential confounding variables, elevated TG/HDL-C ratio independently indicated a higher risk of incident T2DM [hazard ratio (HR) = 1.29; 95% confidence interval (CI), 1.14–1.47; P < 0.01. As compared with the lowest quintile (Q1), elevated TG/HDL-C ratio quintiles (Q2 to Q5) were associated with larger HR estimates of incident T2DM [HR (95% CI), 1.35 (0.85–2.17), 1.31 (0.83–2.06), 1.85 (1.20–2.85), and 2.10 (1.38–3.20), respectively]. In addition, a non-linear correlation was found between TG/HDL-C ratio and the risk of T2DM, and the slope of the curve decreased after the cutoff point of 2.54. Subgroup analysis revealed a stronger positive correlation among male individuals and those with body mass index <24 kg/m2. Conclusions Increased TG/HDL-C ratio indicates a greater risk of new-onset T2DM regardless of confounding variables. TG/HDL-C ratio is a simple but effective indicator in predicting T2DM in older adults. More future investigations are warranted to further promote the clinical application of TG/HDL-C ratio.

目的 探讨乙型肝炎病毒e抗原(hepatitis B virus e antigen,HBeAg)阳性慢性乙型肝炎(chronic hepatitis B,CHB)患者恩替卡韦(entecavir,ETV)治疗中乙型肝炎病毒核心相关抗原(hepatitis B virus core-related antigen,HBcrAg)水平变化及其对治疗效果的预测价值.方法 选取2019年1月至2019年9月保定市人民医院收治的133例HBeAg阳性CHB患者为研究对象.所有患者均给予ETV治疗至少48周.以治疗48周内是否完全应答分为完全应答(59例)和非完全应答(74例).采用荧光定量PCR检测HBV DNA水平,采用全自动免疫分析仪检测HBeAg和HBsAg水平,采用化学发光酶免疫法检测H B c rAg水平,采用全自动生化分析仪检测丙氨酸氨基转移酶(alanine aminotransferase,ALT)、天门冬氨酸氨基转移酶(aspartate aminotransferase,AST)、白蛋白(albumin,ALB)及肌酐(creatinine,Cr)水平.HBcrAg与HBV DNA、HBeAg、HBsAg的相关性采用Pearson相关性分析.采用受试者工作特征(receiver operator characteristic,ROC)曲线分析HBcrAg对HBeAg阳性CHB患者完全应答的预测价值.结果 完全应答组患者基线HBV DNA[(5.22±1.25)lg IU/ml vs(6.57±1.50)lg IU/ml]、HBeAg[(2.53±0.56)lg S/CO vs(3.82±0.46)lg S/CO]、HBsAg[(3.34±0.77)lg IU/ml vs(3.91±0.83)lg IU/ml]、HBcrAg[(7.69±2.33)lg U/ml vs(8.36±2.67)lg U/ml]水平显著低于非完全应答组患者(P均<0.05).Logistic多因素回归分析表明,HBV DNA(OR=27.139,95％CI:8.760～84.077,P<0.001)、HBeAg(OR=2.382,95％CI:1.505～3.768,P<0.001)、HBsAg(OR=1.197,95％CI:1.043～1.374,P=0.011)、HBcrAg(OR=1.962,95％CI:1.478～2.605,P<0.001)均为HBeAg阳性CHB患者48周内非完全应答的危险因素(P<0.05).完全应答组患者基线、治疗12周、治疗24周、治疗48周HBcrAg水平分别为(7.20±2.33)lg U/ml、(6.12±2.10)lg U/ml、(5.73±2.01)lg U/ml、(5.51±1.52)lg U/ml,非完全应答组分别为(8.36±2.67)lg U/ml、(7.83±2.43)lg U/ml、(7.16±1.87)lg U/ml、(6.43±1.73)lg U/ml.重复测量方差分析表明,两组间差异有统计学意义(F组别=23853,P组别<0.001),各时间点差异有统计学意义(F时间=73.134,P时间<0.001),组别和时间无交互作用(F交互=0.514,P交互=0.084).完全应答组基线、治疗12周、治疗24周及治疗48周HBcrAg水平均显著低于非完全应答组(P均<0.05).完全应答组治疗12周、治疗24周及治疗48周HBcrAg水平均显著低于基线(P<0.05);非完全应答组治疗24周、治疗48周HBcrAg水平显著低于基线(P<0.05).Pearson相关性分析表明,HBcrAg与HBV DNA、HBeAg和HBsAg均呈显著正相关(r值分别为0.804、0.875、0.863,P均<0.001).基线HBcrAg预测HBeAg阳性CHB患者完全应答的ROC曲线下面积为0.783(渐进95％CI:0.704～0.861),HBcrAg为7.695 lg U/ml时预测价值最高,敏感度为0.730、特异度为0.729.结论 HBV DNA、HBeAg、HBsAg、HBcrAg等HBV相关标志物均为ETV治疗48周后HBeAg阳性CHB患者非完全应答的危险因素,且在治疗过程中伴随着HBcrAg的变化,HBcrAg对于患者非完全免疫应答具有预测价值.

Objective: To investigate the clinical efficacy and safety of compound wild chrysanthemum eye masks for mild and moderate dry eye. Methods: In this double-masked, multicenter, placebo-controlled, randomized trial, middle-aged and elderly patients with mild and moderate dry eye were enrolled from six hospitals (Xiamen Eye Center of Xiamen University, China-Japan Friendship Hospital, Peking Union Medical College Hospital, Wangjing Hospital of China Academy of Chinese Medical Sciences, Affiliated Eye Hospital of Shandong University of Traditional Chinese Medicine and Hebei Eye Hospital). The patients were assigned to the compound wild chrysanthemum eye mask group and the eye mask simulator group based on the random number table. Subjective symptoms of dry eye, visual acuity, break-up time (BUT), Schirmer Ⅰ test, and corneal fluorescent staining were evaluated in all patients before treatment and at 1 and 2 weeks after treatment. All adverse reactions during the treatment and follow-up were recorded. Results: A total of 120 patients were enrolled. Among them, 112 subjects were included for statistical analyses after the exclusion of 8 subjects who were lost for follow-up or had an adverse event, with an age of (54.26±7.44) years. All the indicators were equally comparable between the two groups. Before treatment and at 1 and 2 weeks after treatment, the median (lower quartile, upper quartile) of total score of questionnaires in the eye mask group was 14.50 (10.00, 19.00), 9.00 (5.00, 14.00) and 7.00 (4.00, 10.00), respectively, and that in the control group was 14.00 (9.00, 22.50), 12.00 (6.00, 20.00) and 10.00 (3.50, 17.00), respectively. The score decreased significantly in both groups after 1 week (t=9.1604, S=398.00; P<0.01) and 2 weeks (S=681.00, 575.50; P<0.05) of treatment. The total score of questionnaires in the eye mask group was significantly lower than that in the control group (Z=3.27, 2.81; P<0.05) after treatment. After 1 week of treatment, the average BUT of the eye mask group was (5.71±2.31) s, which was significantly longer than that before treatment (5.06±2.00) s (S =208.50, P<0.05). But there was no significant difference in the control group (S=150.00, P>0.05). After 2 weeks of treatment, there was statistically significant difference in BUT between the two groups (S=407.00, t=3.07; P<0.01). After 1 week of the treatment, the amount of tear secretion in the eye mask group [(6.88±4.78) mm] was significantly larger than that before treatment (S=196.50, P<0.05), while the control group [(6.80±5.85) mm] showed no significant difference (S=55.00, P<0.05). After 2 weeks of the treatment, the amount increased significantly to (7.43±4.86) mm and (7.29±4.56) mm, respectively, in both groups (t=-3.29, -2.26; P<0.05). The difference in the average BUT, Schirmer Ⅰ test result and corneal fluorescent staining between both groups was not statistically significant at each time point. Five mild adverse events occurred, including 2 adverse events (2 times, 3.51%) in the eye mask group and 3 adverse events (4 times, 5.36%) in the control group. Conclusions: Compound wild chrysanthemum eye masks can effectively improve the symptoms and physical signs of mild and moderate dry eye and can be used as an auxiliary treatment. (Chin J Ophthalmol, 2021, 57: 601-607).

A systematic review and meta‐analysis was conducted to determine the association between the serum vitamin D level and dry eye. A systematic literature search was performed using the PubMed, Embase, Web of Science and Cochrane Library databases to identify clinical studies evaluating the association between vitamin D levels and dry eye. The random‐effect model was used to combine the results. Possible sources of heterogeneity across studies were determined by meta‐regression and sensitivity analysis. Overall, 10 studies ( n = 18 919) were included. Patients with dry eye had a mean serum vitamin D level that was lower than that in healthy controls by 3.99 ng/ml (95% CI −6.57, −1.40; p = 0.002). The mean Ocular Surface Disease Index score was higher (mean difference 10.70, 95% CI 1.55–19.86; p = 0.02) and Schirmer’s test without anaesthesia result was lower (mean difference 6.38 mm/5 min, 95% CI −10.48, −2.28; p = 0.002) in patients with vitamin D deficiency than in controls. Tear break‐up time was comparable in the vitamin D deficiency and control groups (p = 0.15). Sensitivity analyses indicated that the results obtained were robust. This meta‐analysis suggested that vitamin D deficiency is associated with worse subjective symptoms and less tear production in patients with dry eye. Vitamin D deficiency may be a risk factor for dry eye syndrome. Prospective cohort and intervention studies are warranted to determine if vitamin D has a protective role in the development of dry eye.

Objective This report was designed to assess the functional role of miR-218/dachshund family transcription factor 1 (DACH1) in diabetic kidney disease (DKD) and investigate its possible molecular mechanism. Materials and Methods From the GEO database, we downloaded different datasets for analyzing the expression of miR-218 and DACH1 in DKD. TargetScan was adopted to predict the binding sites between miR-218 and DACH1, which was further verified by dual-luciferase reporter assays. The renal proximal tubule cells (HK-2) treated with high glucose (HG) were used as an in vitro model. QRT-PCR and western blot were used to determine the expression of DACH1 and other relative factors. Cell counting kit-8 and flow cytometer were applied to detect cell viability and apoptosis. The levels of inflammatory cytokines were determined by an ELISA assay. Results A prominent raise of miR-218 was observed in DKD through bioinformatics analysis, which was further confirmed in the HG-induced model. DACH1 is a target of miR-218. miR-218 reduced cell viability and induced apoptosis by negatively regulating DACH1. Moreover, upregulating miR-218 in HG models increased the concentrations of pro-inflammatory cytokines TNF-α and IL-1β, reduced the level of anti-inflammatory cytokine IL-10, and promoted the epithelial-mesenchymal transition (EMT) process, which is possibly achieved by targeting DACH1. While downregulating miR-218 showed the opposite results. Conclusion These data demonstrated that, under an in vitro HG environment, miR-218 suppressed the HK-2 cells proliferation, promoted apoptosis, caused an inflammatory response, and facilitated the EMT process largely by targeting DACH1, providing an insight into the therapeutic intervention of DKD.

The dysfunction of long non-coding RNAs (lncRNAs), without protein-coding potential, has been implicated in drug resistance against treatment in various human diseases, especially in malignant tumors. As the most common-diagnosed female malignancy worldwide, breast cancer is also the second-leading cause of cancer-related mortality in women. Despite the improvement in neo-adjuvant therapy, endocrine therapy, molecular-targeted treatment, and chemotherapy, drug resistance to various treatment regimens is still quite prevalent. This article focused on the lncRNAs and their functions in drug resistance against breast cancer therapeutic agents, in order to develop new precise treatment strategies for patients with breast cancers. The discovery of lncRNA opened new doors to the molecular mechanisms of the biological processes, and has provided new pathways to regulate biochemical events. Thus, lncRNAs may be developed as a biomarker for the detection and/or prevention of breast cancer. Additionally, lncRNA-based approaches may provide an additional treatment modality in personalized medicine alone or in combination with existing tumor-directed interventions to improve patient outcomes. In conclusion, lncRNAs molecules may represent the next generation therapy option for breast cancer patients.

Type 2 diabetes mellitus (T2DM) has a rising prevalence and gut microbiota involvement is increasingly recognized. Diabetic nephropathy (DN) is a major complication of T2DM. The aim of the study was to understand the gut–kidney axis by an analysis of gut microbiota composition among biopsy-proven DN, T2DM without kidney disease, and healthy control.

Rubus alceaefolius Poir. has been used for the treatment of nasopharyngeal carcinoma (NPC) in China for many years. Euscaphic acid is an active component of Rubus alceaefolius Poir. However, the mechanism of action of euscaphic acid in NPC remains unclear. In this study, Euscaphic acid inhibited the proliferation of NPC cells, induced apoptosis, and led to cell cycle arrest in the G1/S phase. In addition, euscaphic acid inhibited the expression of phosphatidylinositide 3-kinases (PI3K), phosphorylated protein kinase B (p-AKT), and phosphorylated mammalian target of rapamycin (p-mTOR) p-mTOR in NPC cells. The activation of the PI3K/AKT/mTOR signaling pathway by IGF-1 promoted cell proliferation, inhibited apoptosis, and cell cycle arrest in NPC cells. In conclusion, we demonstrated that euscaphic acid reduced cell proliferation and induced apoptosis and cell cycle arrest in NPC cells by suppressing the PI3K/AKT/mTOR signaling pathway.

BACKGROUND:Overhydration is common among peritoneal dialysis (PD) patients and can affect PD-related outcomes. This paper aims to systematically investigate whether bioimpedance-assessed overhydration is a predictor for mortality and technique failure in PD patients.METHODS:We conducted a systematic review and meta-analysis of cohort studies on overhydration and prognosis in PD patients, strictly complying with the Preferred Reporting Items for Systematical Reviews and Meta-analyses.RESULTS:Eight articles met the selection criteria and 5 studies were included in the meta-analysis. Meta-analyses-revealed overhydration, defined as a high ratio of extracellular water/total body water (ECW/TBW), was significantly associated with higher risk for all-cause mortality and technique failure. Other higher dichotomized overhydration indicators and continuous hydration variables all indicated overhydration as a significant risk factor for all-cause mortality.CONCLUSION:Overhydration, defined by a higher ratio of ECW/TBW, might be an independent predictor for all-cause mortality and technique failure among PD patients. However, more studies are needed to confirm this conclusion. Video Journal Club 'Cappuccino with Claudio Ronco' at https://www.karger.com/Journal/ArticleNews/223997?​sponsor=52.