Relationship between effective blood flow rate and clinical outcomes in maintenance hemodialysis patients: a single-center study.

The association between blood flow rate (BFR) and clinical outcomes in patients undergoing maintenance hemodialysis (MHD) is inconclusive. This retrospective study included 175 patients undergoing MHD treatment between July 2015 and March 2022, divided into two groups based on time-averaged effective blood flow rate (eBFR) median value. We investigated arteriovenous fistula (AVF) outcomes and the association of eBFR with all-cause mortality and new major adverse cardiovascular events (MACE). Mean ± SD and median time-averaged eBFR values were 276 ± 24 and 275 mL/min, respectively. After adjusting for relevant factors including age, sex, vintage, diabetes, CVD, receiving hemodiafiltration (HDF) treatment and spKt/V, Cox models indicated a low time-averaged eBFR (≤ 275 ml/min) was associated with increased risks of all-cause mortality (hazard ratio [HR] 14.18; 95% confidence interval [CI], 3.14-64.1) and new MACE (HR 3.76; 95% CI, 1.91-7.40) in MHD patients. Continuous Cox models demonstrated each 20 ml/min increase in eBFR linked to a 63% decrease in the risk of all-cause mortality (HR: 0.37, 95% CI: 0.23-0.59) and a 38% decrease in the occurrence of new MACE (HR: 0.62, 95% CI: 0.46-0.84). There was no significant difference in AVF outcomes between the two groups. Our study noted higher eBFR (>275 mL/min) is associated with lower risks of both all-cause mortality and new MACE compared with low eBFR (≤275 mL/min). Increased eBFR is not associated with a higher risk of AVF failure.

Clinical characteristics and outcomes of maintenance hemodialysis patients with COVID-19 during the Omicron wave of the pandemic in Beijing: a single center retrospective study.

BACKGROUND: The clinical manifestations and prognosis of hemodialysis patients with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) during the Omicron wave of the pandemic infection were still unclear. This study investigated the clinical characteristics of patients undergoing maintenance hemodialysis (MHD) infected with it. METHODS: This retrospective single-center study included 151 patients undergoing MHD. Healthcare workers were selected as control group were assessed from December 1, 2022 to March 31, 2023. Clinical data, laboratory test results, treatment protocols, and prognoses were collected and analyzed. RESULTS: The study population included 146 patients with MHD, 93 (63.7%) of whom were infected with SARS-CoV-2. The number of non-severe, severe, and critical cases was 84 (90.3%), 4 (4.3%), and 5 (5.3%), respectively. Six patients (6.5%) died during the study period. The main symptoms of SARS-CoV-2 infection, including fever, cough, and fatigue, were less common in patients with MHD than the controls. During SARS-CoV-2 infection, the C-reactive protein (2.9 vs. 11.8 mg/dl, p < 0.0001) and ferritin levels(257.7 vs. 537 ng/l, p < 0.0001) were elevated. The hemoglobin(113vs 111 g/L, p = 0.0001) and albumin levels(39.4 vs. 36.1 g/L, p < 0.0001) decreased. Generally, it took two months for the hemoglobin levels to recover. Positivity rate for SARS-COV-2 serum immunoglobin G (IgG) antibodies and IgG titers were lower in dialysis patients than the controls. Age was positively associated with disease severity, while age and hyponatremia were associated with death. CONCLUSIONS: Patients with MHD and COVID-19 were primarily classified as non-severe. SARS-CoV-2 infection would soon lead to the increase of inflammation related acute response protein in dialysis patients, and then lead to the decrease of hemoglobin and albumin. About 9.6% in HD patients were severe cases and had poor prognosis. Advanced age and hyponatremia were associated with disease severity and prognosis.

Effects of the Omicron variant of coronavirus disease 2019 on anaemia treatment for patients undergoing peritoneal dialysis.

AIM: Patients undergoing dialysis are at high risk for coronavirus disease 2019 (COVID-19). Haemoglobin (Hb) levels may be changed in patients infected with the Omicron variant of COVID-19 who are undergoing peritoneal dialysis (PD). Therefore, we aimed to explore the effect of anti-anaemia treatment on such patients. METHODS: This study enrolled patients undergoing PD who were infected with the Omicron variant of COVID-19 at our centre between November 2022 and February 2023. We retrospectively analysed changes in Hb levels and explored the effectiveness of roxadustat and recombinant human erythropoietin (rhEPO) for patients infected with the Omicron variant of COVID-19. RESULTS: Among 125 enrolled patients, 83 (66.4%) were infected with the Omicron variant and 75 (90.4%) patients mainly experienced mild or moderate disease. During infection, C-reactive protein (CRP) levels were higher than those before infection (p < .001). Additionally, their CRP levels were negatively correlated with Hb levels (p = .002). However, Hb levels were decreased 1 month after infection (109.61 ± 10.64 g/L vs. 115.69 ± 12.04 g/L; p < .001). The roxadustat treatment group did not exhibit significantly decreased Hb levels 1 month after infection (114.57 ± 14.11 vs. 117.51 ± 10.74 g/L; p = .225). Conversely, the rhEPO treatment group experienced a mild decrease in Hb levels (108.69 ± 11.20 vs. 115.03 ± 12.23 g/L; p = .001). Ferritin levels increased in both groups during infection (p = .495). Two months after infection, ferritin levels (median, 205.0 ng/mL) were significantly decreased compared with during infection (median, 377.4 ng/mL) (p < .001) in the roxadustat treatment group. CONCLUSION: Roxadustat was effective than rhEPO for treating anaemia in patients undergoing PD who were infected with the Omicron variant of COVID-19.

Evaluation of bioequivalence and safety analysis of capecitabine tablets and Xeloda® under postprandial dosing conditions in Chinese patients with solid tumor.

OBJECTIVES: To compare the pharmacokinetic and safety of the test group capecitabine tablets (0.5 g) and the reference group capecitabine tablets (0.5 g). METHODS: This study was registered at www.chinadrugtrials.org.cn under the registration number CTR20220138. 48 subjects with solid tumor were recruited and randomized to receive either the test group or the reference group at a dose of 2 g per cycle for three cycles of the entire trial. RESULTS: The point estimate of the geometric mean ratio of Cmax for the subject and reference groups was 1.0670, which was in the range of 80.00%-125.00%. And the upper limit of 95% confidence interval was -0.0450 < 0. The statistics of geometric mean ratio of AUC0-t and AUC0-∞ (test group/reference group) and their 90% confidence intervals were in the range of 80.00%-125.00%, thus the test group was bioequivalent to the reference group under the conditions of this postprandial test. There were no major or serious adverse events. Conclusion: The pharmacokinetic profiles of capecitabine under postprandial conditions were consistent between the two groups. The two groups were bioequivalent and had a similar favorable safety profile in Chinese patients with solid tumor.

A Novel Risk Score Model for the Differential Diagnosis of Type 2 Diabetic Nephropathy: A Multicenter Study.

Introduction: DN is a common complication of diabetes. However, diabetes combined with renal injury may involve DN or NDKD, with different treatment schemes. The purpose of our study was to determine the independent risk factors of DN and establish a risk score model to help differentiate DN and NDKD, providing a reference for clinical treatment. Methods: A total of 678 T2D patients who had undergone renal biopsy in four affiliated hospitals of Peking University were consecutively enrolled. Patients were assigned to the DN group and NDKD group according to histopathological results. Seventy percent of patients from PKUFH were randomly assigned to the training group, and the remaining 30% were assigned to the internal validation group. Patients from the other three centers were assigned to the external validation group. We used univariate and multivariate logistic regression analyses to identify independent risk factors of DN in the training group and conducted multivariate logistic regression analysis with these independent risk factors in the training group to find regression coefficients "ß" to establish a risk score model. Finally, we conducted internal and external validation of the model with ROC curves. Results: Diabetic retinopathy, diabetes duration ≥ 5 years, eGFR < 30 ml/min/1.73 m2, 24 h UTP ≥ 3 g, and no hematuria were independent risk factors (P < 0.05), and each factor scored 2, 1, 1, 1, and 1. We assigned the patients to a low-risk group (0-1 points), a medium-risk group (2-3 points), and a high-risk group (4-6 points), representing unlikely DN, possibly DN, and a high probability of DN, respectively. The AUCs were 0.860, 0.924, and 0.855 for the training, internal validation, and external validation groups, respectively. Conclusion: The risk score model could help differentiate DN and NDKD in a noninvasive manner, reduce the number of renal biopsies, and provide a reference for clinical treatment.

Conscious sedation anesthesia using different doses of remifentanil combined with dexmedetomidine for peritoneal dialysis catheter implantation.

BACKGROUND: Conscious sedation anesthesia (CSA) is an anesthetic method during peritoneal dialysis catheter implantation. However, lack of optimal CSA strategies for patients with end-stage renal disease (ESRD). This study aimed to evaluate the analgesic effects and safety of CSA using different doses of remifentanil combined with dexmedetomidine during peritoneal dialysis catheter insertion. METHODS: Patients who underwent peritoneal dialysis (PD) catheter placement via open surgical incision were retrospectively analyzed and divided into three groups based on the tertile dose of remifentanil. The bispectral index (BIS) was used to monitor the depth of anesthesia. Data regarding clinical findings, the effects of anesthesia, and the incidence of drug-related adverse effects were collected. RESULTS: In total, 102 patients completed the surgery successfully and safely. The dose of remifentanil was 0.02-0.07 µg/kg/min, 0.08-0.13 µg/kg/min, and 0.14-0.20 µg/kg/min in Groups A, B, and C, respectively. Only seven patients reported mild pain during the surgery. No significant differences were observed among the numeric rating scale scores of the three groups (p > 0.05). Intraoperative hemodynamics were stable. The incidence of respiratory depression was 8.3%, 20.0%, and 41.9% in Groups A, B, and C, respectively (p < 0.01). The incidence of gastrointestinal symptoms in Group C (51.6%) was higher than that in Groups A and B (p < 0.05). CONCLUSION: Low-dose remifentanil (0.02-0.07 µg/kg/min) combined with dexmedetomidine achieved satisfactory anesthetic effects with fewer adverse drug reactions during PD catheter implantation, indicating its potential for use in patients undergoing PD catheter placement.

Effects of sacubitril-valsartan in patients undergoing maintenance dialysis.

OBJECTIVES: Data on angiotensin receptor-neprilysin inhibitor (ARNI) sacubitril-valsartan (SV) in patients undergoing maintenance dialysis is scarce. Our study aimed to investigate the effect of SV on patients undergoing dialysis. METHODS: We retrospectively reviewed the data of end-stage kidney disease (ESRD) patients undergoing either peritoneal dialysis (PD) or hemodialysis (HD) in our center. A total of 51 patients receiving SV treatment were enrolled in the SV group. Another 51 age and sex-matched patients on dialysis without SV treatment were selected as the control group. All the patients were regularly followed up in the dialysis clinic. Their clinical, biochemical, and echocardiographic parameters were all recorded at baseline and during follow-up. The effect and safety of SV were further analyzed. RESULTS: A total of 102 ESRD patients on dialysis (51 patients in the SV group and 51 patients in the control group) were finally enrolled. The median follow-up time was 349 days (interquartile range [IQR]: 217-535 days). The level of B-type natriuretic peptide (BNP) (median [IQR] before and after SV treatment: 596.35 pg/ml [190.6-1714.85] vs. 188.7 pg/ml [83.34-600.35], p < 0.001) or N-terminal pro-B-type natriuretic peptide (NT-proBNP) (median [IQR]: 6316.00 pg/ml [4552.00-28598.00] vs. 5074.00 pg/ml [2229.00-9851.00], p = 0.022) were significantly decreased after treatment with SV. The variant rate of left ventricular ejection fraction (LVEF) was significantly higher in the SV group compared to the control group, especially in the PD subgroup. No significant difference was found in other echocardiographic parameters between SV and control group. Subgroup analysis of the PD group showed an increase in daily PD ultrafiltration (median [IQR]: 400 ml/d [200-500] vs. 500 ml/d [200-850], p = 0.114) after SV treatment. Variant rate of overhydration (OH) measured by the body composition monitor (BCM) of the SV group were significantly different from the control group (median [IQR]: -13.13% [-42.85%-27.84%] vs. 0% [-17.95%-53.85%], p = 0.049). The rate of hyperkalemia was slightly higher but without significant difference before and after the introduction of SV (19.6% vs. 27.5%, p = 0.350). No event of hypotension and angioedema were observed. CONCLUSIONS: SV might have a cardio-protective role in ESRD patients undergoing dialysis, especially in PD patients. Serum potassium should be monitored during the treatment.

Corrigendum: Association between hemoglobin glycation index and diabetic kidney disease in type 2 diabetes mellitus in China: a cross-sectional inpatient study.

[This corrects the article DOI: 10.3389/fendo.2023.1108061.].

Detection of Abnormal Wall Shear Stress and Oscillatory Shear Index via Ultrasound Vector Flow Imaging as Possible Indicators for Arteriovenous Fistula Stenosis in Hemodialysis.

OBJECTIVE: The arteriovenous fistula (AVF) is an essential vascular access for hemodialysis patients. AVF stenosis may occur at sites with abnormal wall shear stress (WSS) and oscillatory shear index (OSI), which are caused by the complex flow in the AVF. At present, an effective method for rapid determination of the WSS and OSI of the AVF is lacking. The objective of this study was to apply an ultrasound-based method for determination of the WSS and OSI to explore the risk sites of the AVF. METHODS: In this study, the ultrasound vector flow imaging technique V Flow was applied to measure the WSS and OSI at four different regions of the AVF to detect and analyze the risk sites: (i) anastomosis region, (ii) curved region, (iii) proximal vein and (iv) distal vein. Twenty-one patients were included in this study. The relative residence time was calculated based on the measured WSS and OSI. RESULTS: The curved region had the lowest WSS; the anastomosis region had a significantly higher OSI (p < 0.05) compared with the venous regions, and the curved region had a significantly higher RRT (p < 0.05) compared with the proximal vein region. CONCLUSION: V Flow is a feasible tool for studying WSS variations in AVF. The possible risk site in the AVF may be located in the anastomosis and curved regions, where the latter could present a higher risk for AVF stenosis.

Drug-drug interaction potential of SH-1028, a third-generation EGFR-TKI: in vitro and clinical trials.

SH-1028 is an irreversible third-generation EGFR tyrosine kinase inhibitor (EGFR-TKI) for the treatment of locally advanced or metastatic non-small cell lung cancer (NSCLC). Considering the possibility of combination therapy in patients with NSCLC, we investigated the drug-drug interaction (DDI) potential of SH-1028 both in vitro and in clinical trials. The in vitro studies were conducted to determine the potential of SH-1028 as a substrate, inducer, or inhibitor of cytochrome P450 (CYP) subtypes. A phase I drug-drug interaction study in healthy volunteers was performed to evaluate the impact of co-administering rifampicin (a strong CYP3A4 inducer) and itraconazole (a strong CYP3A4 inhibitor) on the pharmacokinetics of SH-1028. The in vitro experiments showed that SH-1028 was mainly metabolized by CYP3A4. The activities of CYP1A2, 2B6, 2C19, 2D6 and 3A4 enzymes were slightly inhibited in vitro with SH-1028. SH-1028 has no obvious induction effect on CYP1A2 and CYP2B6 activities, but has potential induction effect on CYP3A4 mRNA expression. However, SH-1028 may not induce or inhibit human CYPs significantly at the clinically expected dose (200 mg). The geometric mean ratios of pharmacokinetic parameters and their corresponding 90% confidence intervals for SH-1028 in combination and alone did not fall within the range of 80-125%. It is speculated that itraconazole and rifampicin affect the metabolism of SH-1028. In the clinical application of SH-1028, special attention should be paid to the interaction between SH-1028 and drugs or foods that affect the activity of CYP3A4. (Clinical trial registration number: CTR20210558).

A phase I study comparing the biosimilarity of the pharmacokinetics and safety of recombinant humanized anti-vascular endothelial growth factor monoclonal antibody injection with Avastin® in healthy Chinese male subjects.

BACKGROUND: The biosimilar landscape for malignancies continues to grow, with several biosimilars for reference product bevacizumab currently available. Bevacizumab has been shown to be well tolerated; however, the safety of recombinant humanized anti-vascular endothelial growth factor (VEGF) monoclonal antibody injection remains unclear. This study aimed to compare the pharmacokinetics (PK), safety, and immunogenicity of recombinant humanized anti-VEGF monoclonal antibody injection to that of Avastin® in healthy Chinese male volunteers. METHODS: A randomized, double-blind, single-dose, and parallel-group study was performed on 88 healthy men who randomly (1:1) received either the test drug as an intravenous infusion of 3 mg/kg or Avastin®. The primary PK parameter was area under the serum concentration-time curve (AUC) from time zero to last quantifiable concentration (AUC0-t). Secondary endpoints included maximum observed serum concentration (Cmax), AUC from 0 extrapolated to infinity (AUCinf), safety, and immunogenicity. Serum bevacizumab concentrations were measured using a validated enzyme-linked immunosorbent assay (ELISA). RESULTS: The baseline characteristics were similar among the two groups. The 90% confidence interval (CI) for the geometric mean ratio of AUC0-t, Cmax and AUCinf between the test group and reference group were 91.71%-103.18%, 95.72%-107.49% and 91.03%-103.43%, respectively. These values were within the predefined bioequivalence margin of 80.00%-125.00%, demonstrating the biosimilarity of the test drug and Avastin®. Eighty-one treatment-emergent adverse events were reported, with a comparable incidence among the test group (90.91%) and the reference group (93.18%). No serious adverse events were reported. The incidence of ADA antibodies in the two groups was low and similar. CONCLUSION: In healthy Chinese men, PK similarity of recombinant humanized anti-VEGF monoclonal antibody injection to Avastin® was confirmed, with comparable safety and immunogenicity. Subsequent studies should investigate recombinant humanized anti-VEGF monoclonal antibody injection in patients setting. TRIAL REGISTRATION: Registered 08/10/2019, CTR20191923.

Association between hemoglobin glycation index and diabetic kidney disease in type 2 diabetes mellitus in China: A cross- sectional inpatient study.

Objective: To investigate the association between Hemoglobin Glycation Index (HGI) and Diabetic Kidney Disease (DKD) in Chinese type 2 diabetic individuals and to construct a risk score based on HGI to predict a person's risk of DKD. Methods: We retrospectively analyzed 1622 patients with type 2 diabetes mellitus (T2DM). HGI was obtained by calculating the fasting plasma glucose (FPG) level into the formula, and they were grouped into low HGI group (L-HGI), medium HGI group (H-HGI) and high HGI group (H-HGI) according to tri-sectional quantile of HGI. The occurrence of DKD was analyzed in patients with different levels of HGI. Multivariate logistics regression analysis was used to analyze the risk factors of DKD in patients with T2DM. Results: A total of 1622 patients with T2DM were enrolled in the study. Among them, 390 cases were DKD. The prevalence of DKD among the three groups was 16.6%, 24.2% and 31.3%. The difference was statistically significant (P = 0.000). There were significant differences in age (P=0.033), T2DM duration (P=0.005), systolic blood pressure (SBP) (P=0.003), glycosylated hemoglobin (HbA1c) (P=0.000), FPG (P=0.032), 2-hour postprandial plasma glucose (2h-PPG) (P=0.000), fasting C-peptide FCP (P=0.000), 2-hour postprandial C-peptide (2h-CP) (P=0.000), total cholesterol (TC) (P=0.003), low density lipoprotein cholesterol (LDL-C) (P=0.000), serum creatinine (sCr) (P=0.001), estimated glomerular filtration rate (eGFR) (P=0.000) among the three groups. Mantel-Haenszel chi-square test showed that there was a linear relationship between HGI and DKD (x2=177.469, p < 0.001). Pearson correlation analysis showed that with the increase of HGI level the prevalence of DKD was increasing (R= 0.445, P=0.000). It was indicated by univariate logistic regression analysis that individuals in H-HGI was more likely to develop DKD (OR: 2.283, 95% CI: 1.708~ 3.052) when compared with L-HGI. Adjusted to multiple factors, this trend still remained significant (OR: 2.660, 95% CI: 1.935~ 3.657). The combined DKD risk score based on HGI resulted in an area under the receiver operator characteristic curve (AUROC) of 0.702. Conclusions: High HGI is associated with an increased risk of DKD. DKD risk score may be used as one of the risk predictors of DKD in type 2 diabetic population.

Oseltamivir phosphate for suspension is bioequivalent to TAMIFLU in healthy volunteers: a randomized, open-label clinical study.

PURPOSE: The study was aimed at evaluating the bioequivalence and safety of oseltamivir phosphate for suspension, provided by Shenzhen Beimei Pharmaceutical Co. Ltd. and manufactured by Hetero Labs Limited, and the reference product TAMIFLU® in healthy Chinese subjects. METHODS: A single-dose, randomized, two-phase, self-crossed model was adopted. Among 80 healthy subjects, 40 subjects in the fasting group and 40 subjects in the fed group. Subjects in the fasting group were randomized into two sequences according to the proportion of 1:1, each given 75 mg/12.5 mL of Oseltamivir Phosphate for Suspension or TAMIFLU®, and cross-administered after 7 days. Postprandial group is the same as fasting group. RESULTS: The Tmax of TAMIFLU® and Oseltamivir Phosphate for Suspension in the fasting group were 1.50 h and 1.25 h, which in the fed group were both 1.25 h. Geometrically adjusted mean ratios of the PK parameters of Oseltamivir Phosphate for Suspension along with TAMIFLU® under fasting and postprandial conditions were in the range of 80.00-125.00% at the 90% confidence interval (CI). The 90% CI of Cmax, AUC0-t, AUC0-∞ for fasting group and postprandial group were (92.39,106.50), (94.26,100.67), (94.32,100.89) and (93.61,105.83),(95.64,100.19),(96.06,102.66). Among the subjects on medication, a total of 18 subjects reported 27 adverse events, all of which were treatment-emergent adverse events (TEAEs), six of these TEAEs were rated as grade 2 in severity and the rest were as grade 1. The number of TEAEs in the test product and the reference product were 14,13 respectively. CONCLUSION: Two Oseltamivir phosphate for suspensions are safe and bioequivalent.

Mass balance, metabolic disposition, and pharmacokinetics of a novel selective inhibitor of PI3Kδ [14C] SHC014748M in healthy Chinese subjects following oral administration.

PURPOSE: SHC014748M is a potent, novel selective PI3Kδ isoform inhibitor and is proposed for the treatment of non-Hodgkin lymphoma and chronic lymphocytic leukemia/small lymphocytic lymphoma. This study investigated the pharmacokinetics, mass balance, metabolism and excretion of SHC014748M in Chinese male subjects following a single oral dose of 150 mg (100 µCi) [14C] SHC014748M. METHODS: Six healthy Chinese male subjects administrated an oral suspension of 150 mg (100 µCi) [14C] SHC014748M and the samples of blood, urine and feces were collected for measuring. Liquid chromatography-tandem mass spectrometry and liquid scintillation counter were utilized to obtain mass balance and the pharmacokinetic data. RESULTS: The median Tmax for [14C]-radioactivity was 1.6 ± 0.5 h after the oral administration of [14C] SHC014748M and the mean Cmax was 3863 ± 354 ng Eq./mL in plasma, while the mean Cmax, t1/2 values and AUC0-∞ values for total radioactivity in whole blood were 2466 ± 518 ng Eq./mL, 32.2 ± 30.5 h and 66,236 ± 44,232 h * ng Eq./mL, respectively. Fecal excretion was proposed as the predominant elimination route, accounting for a mean of 90.68 ± 11.38% of the administered dose, whereas the mean urine excretion was 6.00 ± 1.48% within 336 h post-dose. The proposed major metabolic pathway of [14C] SHC014748M in the human body were as follows: (I) monooxidation, (II) glucuronide acid conjugation, and (III) monoxide-hydrogenation. CONCLUSIONS: SHC014748M was absorbed, metabolized and excreted with unchanged SHC014748M as its main circulating component in plasma following oral administration. In addition, it was speculated that fecal excretion was the principal excretion pathway; meanwhile, monohydroxy, glucuronide conjugation, oxygen, and hydrogenation were the major clearance pathways of SHC014748M through urine and/or feces. TRIAL REGISTRATION: The trial registration number: CTR20202505.

The role of CSTF2 in cancer: from technology to clinical application.

A protein called cleavage-stimulating factor subunit 2 (CSTF2, additionally called CSTF-64) binds RNA and is needed for the cleavage and polyadenylation of mRNA. CSTF2 is an important component subunit of the cleavage stimulating factor (CSTF), which is located on the X chromosome and encodes 557 amino acids. There is compelling evidence linking elevated CSTF2 expression to the pathological advancement of cancer and on its impact on the clinical aspects of the disease. The progression of cancers, including hepatocellular carcinoma, melanoma, prostate cancer, breast cancer, and pancreatic cancer, is correlated with the upregulation of CSTF2 expression. This review provides a fresh perspective on the investigation of the associations between CSTF2 and various malignancies and highlights current studies on the regulation of CSTF2. In particular, the mechanism of action and potential clinical applications of CSTF2 in cancer suggest that CSTF2 can serve as a new biomarker and individualized treatment target for a variety of cancer types.

Research progress on microRNA in gout.

Gout is a common form of arthritis caused by the deposition of sodium urate crystals in the joints and tissues around them. MicroRNAs (miRNAs) are noncoding RNAs that have been shown to be involved in regulating the pathogenesis of gout through multiple cellular signaling pathways, which may be potential targets for the treatment of gout. In this review, we systematically discuss the regulatory roles of related miRNAs in gout, which will provide help for the treatment of gout and miRNAs is expected to become a potential biomarker for gout diagnosis.

The regulatory role of PDE4B in the progression of inflammatory function study.

Inflammation is a response of the body to external stimuli (eg. chemical irritants, bacteria, viruses, etc.), and when the stimuli are persistent, they tend to trigger chronic inflammation. The presence of chronic inflammation is an important component of the tumor microenvironment produced by a variety of inflammatory cells (eg. macrophages, neutrophils, leukocytes, etc.). The relationship between chronic inflammation and cancer development has been widely accepted, and chronic inflammation has been associated with the development of many cancers, including chronic bronchitis and lung cancer, cystitis inducing bladder cancer. Moreover, chronic colorectitis is more likely to develop into colorectal cancer. Therefore, the specific relationship and cellular mechanisms between inflammation and cancer are a hot topic of research. Recent studies have identified phosphodiesterase 4B (PDE4B), a member of the phosphodiesterase (PDEs) protein family, as a major cyclic AMP (cAMP) metabolizing enzyme in inflammatory cells, and the therapeutic role of PDE4B as chronic inflammation, cancer. In this review, we will present the tumors associated with chronic inflammation, and PDE4B potential clinical application.

pH Programmed Optical Sensor Arrays for Cancer Plasma Straightforward Discrimination Based on Protein-Responsive Patterns.

Optical cross-reactive sensor arrays inspired by the mammalian olfactory system that can realize straightforward discrimination of plasma from cancer patients hold great potential for point-of-care diseases diagnostics. Herein, a pH programmed fluorescence sensor array based on protein-responsive patterns was designed for straightforward discrimination of different types of cancer plasma. It is worth noting that plasma discrimination can be realized only by programming one nanomaterial using different pH values, which greatly simplifies the programmable design of the sensor array, making it an important highlight of this work. In addition, the mechanism of the pH programmed fluorescence sensor array for protein responsiveness was systematically investigated through molecular docking simulation, fluorescence resonance energy transfer (FRET), and fluorescence lifetime experiments. Most importantly, not only can the differences between plasma from healthy people and and from patients with different cancer species including gastric cancer, liver cancer, breast cancer, and cervical cancer be discriminated by this pH programmed fluorescence sensor array, but also the blind test of unknown plasma samples can be well identified with 100% accuracy, indicating its promising prospect in clinical application.

TMEM88 Modulates Lipid Synthesis and Metabolism Cytokine by Regulating Wnt/ß-Catenin Signaling Pathway in Non-Alcoholic Fatty Liver Disease.

Objective: To clarify the molecular mechanism of TMEM88 regulating lipid synthesis and metabolism cytokine in NAFLD. Methods: In vivo, NAFLD model mice were fed by a Methionine and Choline-Deficient (MCD) diet. H&E staining and immunohistochemistry experiments were used to analyze the mice liver tissue. RT-qPCR and Western blotting were used to detect the lipid synthesis and metabolism cytokine. In vitro, pEGFP-C1-TMEM88 and TMEM88 siRNA were transfected respectively in free fat acid (FFA) induced AML-12 cells, and the expression level of SREBP-1c, PPAR-α, FASN, and ACOX-1 were evaluated by RT-qPCR and Western blotting. Results: The study found that the secretion of PPAR-α and its downstream target ACOX-1 were upregulated, and the secretion of SREBP-1c and its downstream target FASN were downregulated after transfecting with pEGFP-C1-TMEM88. But when TMEM88 was inhibited, the experimental results were opposite to the aforementioned conclusions. The data suggested that it may be related to the occurrence, development, and end of NAFLD. Additionally, the study proved that TMEM88 can inhibit Wnt/ß-catenin signaling pathway. Meanwhile, TMEM88 can accelerate the apoptotic rate of FFA-induced AML-12 cells. Conclusion: Overall, the study proved that TMEM88 takes part in regulating the secretion of lipid synthesis and metabolism cytokine through the Wnt/ß-catenin signaling pathway in AML-12 cells. Therefore, TMEM88 may be involved in the progress of NAFLD. Further research will bring new ideas for the study of NAFLD.