Albumin Levels Research Articles

Mechanisms by which Mettl3 regulates pericyte-myofibroblast transdifferentiation through PI3K/AKT signaling pathway

Objective: To investigate the role and underlying mechanisms of methyltransferase (Mettl) 3 in the process of angiotensin Ⅱ (Ang Ⅱ)-induced pericyte-to-myofibroblast transdifferentiation and renal fibrosis. Methods: C57BL/6J mice were used, in cell experiments, mouse renal pericytes were isolated and cultured using magnetic bead sorting. These pericytes were then induced to transdifferentiate into myofibroblasts with 1×106 mmol/L Ang Ⅱ, which was the Ang Ⅱ group, while pericytes cultured in normal conditions served as the control group. Successful transdifferentiation was verified by immunofluorescence staining, Western blotting, and real-time reverse transcription PCR (RT-qPCR) for α-smooth muscle actin (α-SMA). The levels of m6A modifications and related enzymes (Mettl3, Mettl14), Wilms tumor 1-associated protein (WTAP), fat mass and obesity protein (FTO), ALKBH5, YTHDF1, YTHDF2, YTHDC1, YTHDC2, YTHDC3 were assessed by Dot blot, RT-qPCR and Western blot. Mettl3 expression was inhibited in cells using lentivirus-mediated Mettl3-shRNA transfection, creating sh-Mettl3 and Ang Ⅱ+sh-Mettl3 groups, while lentivirus empty vector transfection served as the negative control (Ang Ⅱ+sh-NC group). The impact of Ang Ⅱ on pericyte transdifferentiation was observed, and the expression of downstream phosphatidylinositol 3-kinase (PI3K)/AKT signaling pathway proteins, including PI3K, AKT, phosphorylated AKT at serine 473 (p-AKT (S473)), and phosphorylated AKT at threonine 308 (p-AKT (T308)), were examined. PI3K gene transcription was inhibited by co-culturing cells with actinomycin D, and the half-life of PI3K mRNA was calculated by measuring residual PI3K mRNA expression over different co-culture time. The reversibility of Mettl3 inhibition on Ang Ⅱ-induced pericyte-to-myofibroblast transdifferentiation was assessed by adding the AKT activator SC79 to the Ang Ⅱ+sh-Mettl3 group. In animal experiments, mice were divided into these groups: sham group (administered 0.9% sterile saline), Ang Ⅱ group (infused with Ang Ⅱ solution), sh-Mettl3 group (injected with Mettl3 shRNA lentivirus solution), Ang Ⅱ+sh-Mettl3 group (infused with Ang Ⅱ solution and injected with Mettl3 shRNA lentivirus solution), and Ang Ⅱ+sh-Mettl3+SC79 group (administered Ang Ⅱ solution and Mettl3 shRNA lentivirus, with an additional injection of SC79). Each group consisted of six subject mice. Blood pressure was measured using the tail-cuff method before and after surgery, and serum creatinine, urea, and urinary albumin levels were determined 4 weeks post-surgery. Kidney tissues were collected at 28 days and stained using hematoxylin-eosin (HE) and Masson's trichrome to assess the extent of renal fibrosis. Results: Primary renal pericytes were successfully obtained by magnetic bead sorting, and intervened with 1×106 mmol/L Ang Ⅱ for 48 hours to induce pericyte-to-myofibroblast transdifferentiation. Dot blot results indicated higher m6A modification levels in the Ang Ⅱ group compared to the control group (P<0.05). RT-qPCR and Western blot results showed upregulation of Mettl3 mRNA and protein levels in the Ang Ⅱ group compared to the control group (both P<0.05). In the Ang Ⅱ+sh-Mettl3 group, Mettl3 protein expression was lower than that in the Ang Ⅱ group, with reduced expression levels of α-SMA, vimentin, desmin, fibroblast agonist protein (FAPa) and type Ⅰ collagen (all P<0.05). Compared to the control group, PI3K mRNA expression level was elevated in the Ang Ⅱ group, along with increased p-AKT (S473) and p-AKT (T308) expressions. In the Ang Ⅱ+sh-Mettl3 group, PI3K mRNA expression and p-AKT (S473) and p-AKT (T308) levels were decreased (all P<0.05). The half-life of PI3K mRNA was shorter in the Ang Ⅱ+sh-Mettl3 group than that in the Ang Ⅱ+sh-NC group (2.34 h vs. 3.42 h). The ameliorative effect of Mettl3 inhibition on Ang Ⅱ-induced pericyte-to-myofibroblast transdifferentiation was reversible by SC79. Animal experiments showed higher blood pressure, serum creatinine, urea, and 24-hour urinary protein levels, and a larger fibrosis area in the Ang Ⅱ group compared to the sham group (all P<0.05). The fibrosis area was smaller in the Ang Ⅱ+sh-Mettl3 group than that in the Ang Ⅱ group (P<0.05), but increased again upon addition of SC79. Conclusion: Mettl3-mediated RNA m6A epigenetic regulation is involved in Ang Ⅱ-induced pericyte-to-myofibroblast transdifferentiation and renal fibrosis, potentially by affecting PI3K stability and regulating the PI3K/AKT signaling pathway.

Umbilical cord blood as a substitute for neonatal blood in measuring serum albumin and immunoglobulin G levels.

In this study, we investigated the clinical feasibility of using umbilical cord blood as an alternative to neonatal blood for measuring serum albumin and immunoglobulin G (IgG) levels in newborns, including preterm newborns. Serum levels of albumin and IgG were measured in cord and neonatal blood from singleton newborns. We analyzed correlations and systematic errors between cord and neonatal blood measurements, stratifying the results for very preterm newborns (VPNs) born at a gestational age of less than 32 weeks and non-VPNs born at a gestational age of 32 weeks or later. Among all 494 newborns (78 VPNs and 416 non-VPNs), serum albumin and IgG levels were determined for 95.7% and 88.7% of them, respectively. Strong correlations between cord and neonatal blood were observed for the serum albumin and IgG levels (rs = 0.864 and 0.966, respectively). Moreover, the measurement errors between cord and neonatal blood were small for all newborns (0.2g/dL and 65mg/dL, respectively). These findings were consistent with both VPNs and non-VPNs. Umbilical cord blood is a suitable substitute for neonatal blood in measuring serum albumin and IgG levels in newborns, even in premature newborns.

Determinants of transthyretin levels and their association with adverse clinical outcomes among UK Biobank participants

Transthyretin is a transport protein whose misfolding has been implicated in the development of cardiac amyloidosis. Here, we examine the clinical correlates of transthyretin levels, the differences in transthyretin levels according to the pathogenic V142I TTR variant carrier status, and the association of transthyretin levels with outcomes among 35,206 UK Biobank participants who underwent plasma profiling and were free from prevalent cardiovascular disease and chronic renal disease. Transthyretin levels are lower in females, decrease with increasing C-reactive protein levels, and increase with body mass index, systolic blood pressure, diastolic blood pressure, total cholesterol, albumin levels, triglyceride levels, and creatinine levels. V142I non-carriers [n = 35,167, mean: −0.1 (0.3)] have higher adjusted transthyretin levels compared with the carriers [n = 39, mean: −0.5 (0.3)] (p:<0.001). A standard deviation decrease in transthyretin levels increases the risk of heart failure [HRadj: 1.17 (95% Confidence Interval = 1.08–1.26)] and all-cause mortality [HRadj: 1.18 (95% Confidence Interval = 1.14–1.24)]. This study shows that individuals with low transthyretin levels, such as those carrying the V142I variant, are at a higher risk of heart failure and mortality.

Melatonin mitigated methotrexate-induced hepatotoxicity through interrelated biological processes.

Hepatotoxicity associated with methotrexate (MTX) is mainly due to disruption of redox balance and development of oxidative injury to hepatocytes. Melatonin (MLT) is a potent antioxidant and regulates wide range of biological functions, processes and utilized as adjuvant for number of medical applications. The current study investigated the mitigating effect of MLT on the MTX-induced hepatotoxicity. Adult male rats received MLT (25mg/kg, orally) for seven days flowed by single injection of MTX (20mg/kg, ip) then treat with MLT continued for additional 7days. The present result showed MLT treatment mitigated histopathological changes in the liver that associated with normalization of ALT and AST activity as well as bilirubin, albumin and alfa-fetoprotein levels in serum of MLT + MTX-treated rat to comparable control level. MLT treatment significantly reduced MDA content and myeloperoxidase activity while enhanced the activity of superoxide dismutase, catalase and glutathione content in the liver indicating the empowerment of the antioxidant status. Amelioration of MLT-induced oxidative stress resulted in a reduction in the inflammatory response due to antioxidant restoration and inhibited apoptosis indicated by downregulation of caspase-3 expression. The replenishment of antioxidant content powers the defense system of the hepatocytes. As a result, apoptosis is reduced which might be due to the ability of MLT protect DNA integrity thus maintaining hepatocyte functions and structure. Consequently, liver histology was protected. In summary, MLT modulates liver function and structure by orchestrating linked processes, including redox balance, inflammatory response, suppression of caspase-3, and DNA damage.

Prophylactic Effects of Methanolic Leaf Extract of Momordica balsamina Against CCL4 Induced Liver Injury in Wistar Rats

Introduction: Liver injury can result from various causes, including alcohol consumption, viral infections (such as hepatitis), autoimmune diseases, metabolic disorders, and exposure to certain chemicals, drugs or toxins. It can manifest as inflammation, fatty liver disease, cirrhosis, or acute liver failure, depending on the cause and severity. Treatment often involves addressing the underlying cause, lifestyle changes (such as avoiding alcohol or certain medications), and sometimes medication to support liver function or manage specific conditions. Early detection and management are crucial for preventing further damage and promoting liver health. Studies have reported the effects of Momordica balsamina on liver injury. Aim: This study aim to evaluate the prophylactic effect of methanolic leaf extract of Momordica balsamina against CCL4-induced liver injury in Wistar Rats. Methodology: The fresh leaves of Momordica balsamina were purchased at Marina Market, Sokoto, the plant was air dry at room temperature for 2 weeks and the air-dried leaves were processed with methanol to obtain methanolic extract. An acute toxicity study of M. balsamina extract was conducted with six doses (10, 100, 1000, 1600, 2900 and 5000 mg/kg) to evaluate its safety. Phytochemical analysis of the extract was carried out to detect the presence or absence of carbohydrates, saponins, flavonoids, tannins, phenols, protein, alkaloids, cardiac glycosides and steroids. A total of 42 Wistar rats (170±20g) of either sex roughly of the same age (8-10 weeks) were used for the study. After two weeks of acclimatization, the rats were randomly divided into six groups of seven rats each; group 1 (normal control) treated with distilled water and vital feeds; groups 2 (Negative control) CCl4 treated with liver injury not on treatment; group 3 (Standard control) CCl4 liver injury treated with 50 mg/kg Silymarin; group 4 (500 mg/kg M. balsamina + 2mL CCl4); group 5 (1000 mg/kg M. balsamina + 2mL CCl4) and group 6 (1500 mg/kg M. balsamina + 2mL CCl4) for 4 weeks. On the last day, the rats were anaesthetized, and blood and liver organ were collected for biochemical and histomorphology study. Results: The prophylactic effects of methanolic leaf extract of Momordica balsamina against CCl4-induced liver injury were evaluated on liver function tests (LFTs) and Malondialdehyde (MDA). This study shows that Momordica balsamina extract significantly (P&lt; 0.05) decreased the level of serum AST, ALT, ALP, TB and DB positively by inhibiting their raise at dose-dependent manner compared to the negative control, equally, the extract increased the serum level of Albumin and total protein when compared to the negative control. On the other hand, the extract shows significant reduction of serum level of Malondialdehyde (MDA) near to normal at varying dose. The finding of the prophylactic effect of methanolic leaf extract of Momordica balsamina on histology shows significant improvement on liver cell with notable recovery and appearance of the histological architecture of the hepatocyte at the highest dose (1500 mg/kg+2mL CCl4) compared to negative control group. Conclusion: The presence of phytochemical compounds and antioxidant properties as well as a gene that is responsible for its prophylactic effect may be one of the mechanisms through which the plant extract was able to exert prophylactic effect on CCl4 induced liver injury in Wistar rats. This study suggests that M. balsamina extract may be considered as an affordable and non-invasive treatment option for liver injury in human.

Effects of L-Methionine and DL-Methionine on Growth Performance, Methionine-Metabolizing Enzyme Activities, Feather Traits, and Intestinal Morphology of Medium-Growing, Yellow-Feathered Chickens between 1 and 30 Days of Age

This experiment investigated the effects of L-Methionine (L-Met) on growth performance, Met-metabolizing enzyme activity, feather traits, and small intestinal morphological characteristics, and compared these with DL-Methionine (DL-Met) for medium-growing, yellow-feathered broilers during the starter phase. Furthermore, the aim was to provide recommendations for the appropriate dietary Met levels in feed. A total of 1584 1-d broilers were randomly divided into 11 treatment groups with six replicates of 24 birds each: basal diet (CON, Met 0.28%), basal diet + L-Met (0.04%, 0.08%, 0.12%, 0.16%, 0.20%), and basal diet + DL-Met (0.04%, 0.08%, 0.12%, 0.16%, 0.20%). The total trial period was 30 days. Compared with broilers fed the basal diet, those fed 0.04 to 0.20% supplemental Met had higher final body weight (FBW), average daily feed intake (ADFI), average daily gain (ADG), and lower feed-to-gain ratio (F: G) (p &lt; 0.05). Compared with DL-Met groups, the L-Met group had higher FBW and ADG (p &lt; 0.05). The relative bioavailability (RBV) of L-Met in ADG of 1–30 d was 142.5%. Chicks fed diets supplemented with L-Met had longer fourth primary feather lengths compared to birds fed the control and diets supplemented with DL-Met (p &lt; 0.05). Compared to the control, birds supplemented with DL-Met or L-Met had an increased moulting score (p ≤ 0.05). Chicks fed diets supplemented with L-Met had lower activities of methionine adenosyl transferase (MAT) compared to those fed the basal diet or supplemented with DL-Met (p &lt; 0.05). Chicks supplemented with either DL-Met or L-Met had higher activities of cystathionine β-synthase (CBS) than those fed the basal diet (p &lt; 0.05). Compared with the control, chicks fed diets supplemented with either DL-Met or L-Met had an enhanced level of albumin in plasma (p &lt; 0.05). There were no obvious differences in the plasma content of uric acid and total protein among the treatments (p &gt; 0.05). Chicks fed diets supplemented with either DL-Met or L-Met had higher villus height and V/C in the duodenal than chicks fed the basal diet (p &lt; 0.05). The jejunum morphology was not affected by either L-Met or DL-Met supplementation (p &gt; 0.05). Therefore, dietary supplementation with DL-Met or L-Met improved the growth performance, feather traits, and intestinal morphological characteristics of medium-growing, yellow-feathered broiler chickens aged 1 to 30 d by decreasing the enzyme activities of Met methylation (MAT) and increasing the enzyme activities of the sulfur transfer pathway (CBS), and supplementation with L-Met showed a better improvement compared with DL-Met. The relative efficacy of L-Met to DL-Met was 142.5% for ADG of yellow-feathered broilers. The appropriate Met levels for medium-growing, yellow-feathered broilers are between 0.36~0.38% (supplementation with DL-Met) or 0.32~0.33% (supplementation with L-Met) when based on ADG and feed-to-gain ratio.

Evaluation of the follicular fluid thiol/disulfide balance among patients with poor ovarian response.

This study aimed to compare the thiol/disulfide balance, myeloperoxidase, and ischemia-modified albumin levels in the follicular fluid (FF) of poor ovarian response (POR) and normal ovarian response (NOR) women who received intracytoplasmic sperm injection (ICSI). The study was performed between March 2021 and April 2022 at the Department of Obstetrics and Gynecology, Center for Reproductive Medicine, Ankara City Hospital. The study included 27 POR and 35 NOR women who underwent ICSI. FF was obtained after the controlled ovarian stimulation cycle. The FF thiol/disulfide balance was detected using spectrophotometric methods. A correlation analysis was conducted to determine whether these oxidative stress markers could contribute to predicting oocyte quality. Disulfide levels were significantly higher in the NOR group than in the POR group (p=0.014). The number of fertilized egg (2PN) oocytes was positively correlated with the total thiol level (r=0.258, p=0.046). The disulfide level was positively correlated with the anti-Müllerian hormone level (r=0.262, p=0.039) and the total number of retrieved oocytes (r=0.335, p=0.008). The disulfide levels differed significantly between the NOR and POR groups. The statistically significant differences of fewer metaphase II oocytes and lower percentage of good-quality embryos in the NOR group compared to the POR group might have resulted from the NOR group's elevated disulfide levels. The total thiol levels correlated with the total of 2PN oocytes. Future studies should examine the thiol/disulfide balance at assisted reproductive technology centers to predict which oocytes could be fertilized.

Triiodothyronine (T3) suppresses hepatic tumorigenesis and development by inhibiting the phosphorylation of ERK.

The effect of triiodothyronine (T3) on the phosphorylation of ERK and the occurrence and development of hepatocellular carcinoma (HCC) is controversial and remains to be clarified. In the present study, both in vitro (hepatoma cell lines) and in vivo (wild-type mice [WT] and mouse models of HCC [HrasG12Vand KrasG12Dtransgenic mice (Hras-Tg and Kras-Tg)]) systems were used to investigate the effect of T3 on p-ERK and hepatocarcinogenesis. The results showed that, in vitro, T3 treatment elevated the levels of p-ERK in hepatoma cells within 30 min. However, p-ERK levels returned to normal after 1 h with no significant effects on cellular proliferation or apoptosis. Interestingly, in vivo, T3 induced early rapid and transient activation of ERK and later persistent downregulation of p-ERK in liver tissues of WT. In Hras-Tg, liver weight, liver/body weight ratio, hepatic tumor numbers and sizes were significantly reduced withT3treatment compared with the untreated group. Furthermore, the levels of albumin, HrasG12V, and p-ERK in hepatic precancerous and tumor tissues were all significantly downregulated with T3 treatment; however, the levels of endogenous Hras were not affected. In WT, T3 also induced downregulation of Albumin in liver tissues, but without influence on the expression of endogenous Hras and p-MEK. Especially, the inhibitory effect of T3 on p-ERK and hepatic tumorigenesis and development without influence on the levels of KrasG12D and p-MEK was further confirmed in Kras-Tg. In conclusion, T3 suppresses hepatic tumorigenesis and development by independently and substantially inhibiting the phosphorylation of ERK in vivo.

The toxicity effects of imidacloprid and chlorpyrifos on oxidative stress and blood biochemistry in Cyprinus carpio

This study aimed to assess the toxicity effects of chlorpyrifos and imidacloprid, alone and in combination, on oxidative biomarkers and blood biochemistry of Cyprinus carpio. A total of 324 common carp (Cyprinus carpio) were distributed among 27 tanks and exposed to concentrations of 0.0, 100, and 200 μg L−1 of chlorpyrifos and 0.0, 10.0, and 20.0 μg L−1 of imidacloprid for 28 days. Changes in enzyme activities in the plasma of fish exposed to chlorpyrifos depended on the dose. In contrast, aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), lactate dehydrogenase (LDH), creatine phosphokinase (CPK), gamma-glutamyl transferase (GGT) activities were significantly increased in fish exposed to imidacloprid, alone and in combination with chlorpyrifos. However, the activity of butyrylcholinesterase (BChE) was significantly decreased. Exposure to imidacloprid and chlorpyrifos, alone and in combination, increased glucose, urea, cholesterol, triglycerides, and creatinine levels, whereas total protein and albumin levels were significantly decreased. The activity of superoxide dismutase (SOD), glutathione peroxidase (GPx), glutathione S-transferase (GST), and catalase (CAT) was significantly increased, while glutathione reductase (GR) was significantly decreased. Additionally, although the total antioxidant capacity (TAN) was significantly decreased, malondialdehyde (MDA) levels increased after exposure to imidacloprid and chlorpyrifos, alone and in combination. In conclusion, exposure to imidacloprid and chlorpyrifos, alone and in combination, induced oxidative stress and altered blood biochemistry in carp fish. Moreover, imidacloprid and chlorpyrifos had synergistic effects on some oxidative and biochemical biomarkers.

Associations between serum albumin level trajectories and clinical outcomes in sepsis patients in ICU: insights from longitudinal group trajectory modeling

Associations between serum albumin level trajectories and clinical outcomes in sepsis patients in ICU: insights from longitudinal group trajectory modeling

A novel prognostic model of de novo metastatic hormone-sensitive prostate cancer to optimize treatment intensity.

The treatment and prognosis of de novo metastatic hormone-sensitive prostate cancer (mHSPC) vary. We established and validated a novel prognostic model for predicting cancer-specific survival (CSS) in patients with mHSPC using retrospective data from a contemporary cohort. 1092 Japanese patients diagnosed with de novo mHSPC between 2014 and 2020 were registered. The patients treated with androgen deprivation therapy and first-generation anti-androgens (ADT/CAB) were assigned to the Discovery (N = 467) or Validation (N = 328) cohorts. Those treated with ADT and androgen-receptor signaling inhibitors (ARSIs) were assigned to the ARSI cohort (N = 81). Using the Discovery cohort, independent prognostic factors of CSS, the extent of disease score ≥ 2 or the presence of liver metastasis; lactate dehydrogenase levels > 250U/L; a primary Gleason pattern of 5, and serum albumin levels ≤ 3.7g/dl, were identified. The prognostic model incorporating these factors showed high predictability and reproducibility in the Validation cohort. The 5-year CSS of the low-risk group was 86% and that of the high-risk group was 22%. Approximately 26.4%, 62.7%, and 10.9% of the patients in the Validation cohort defined as high-risk by the LATITUDE criteria were further grouped into high-, intermediate-, and low-risk groups by the new model with significant differences in CSS. In the ARSIs cohort, high-risk group had a significantly shorter time to castration resistance than the intermediate-risk group. The novel model based on prognostic factors can predict patient outcomes with high accuracy and reproducibility. The model may be used to optimize the treatment intensity of de novo mHSPC.

The effect of human albumin administration on postoperative renal function following major surgery: a systematic review and meta-analysis

Optimal fluid management during major surgery is of considerable concern to anesthesiologists. Although crystalloids are the first choice for fluid management, the administration of large volumes of crystalloids is associated with poor postoperative outcomes. Albumin can be used for fluid management and may protect renal function. However, data regarding the effects of albumin administration on kidney function are conflicting. As such, the present study aimed to investigate the effect of albumin administration on renal function in patients undergoing major surgery and compare its effects with those of crystalloid fluid. The Embase, Medline, Web of Science, Cochrane Library, and KoreaMed databases were searched for relevant studies. The primary endpoint of the meta-analysis was the incidence of postoperative kidney injury, including acute kidney injury and renal replacement therapy. Twelve studies comprising 2311 patients were included; the primary endpoint was analyzed in four studies comprising 1749 patients. Perioperative albumin levels in patients undergoing major surgery did not significantly influence kidney dysfunction (p = 0.98). Postoperative fluid balance was less positive in patients who underwent major surgery and received albumin than in those who received crystalloids. Owing to the limitations of this meta-analysis, it remains unclear whether albumin administration during major surgery is better than crystalloid fluid for improving postoperative renal function.

Association of diabetes with cardiovascular calcification and all-cause mortality in end-stage renal disease in the early stages of hemodialysis: a retrospective cohort study

BackgroundThe main goal of this study was to examine how diabetes, cardiovascular calcification characteristics and other risk factors affect mortality in end-stage renal disease (ESRD) patients in the early stages of hemodialysis.MethodsA total of 285 ESRD patients in the early stages of hemodialysis were enrolled in this research, including 101 patients with diabetes. Survival time was monitored, and general data, biochemical results, cardiac ultrasound calcification of valvular tissue, and thoracic CT calcification of the coronary artery and thoracic aorta were recorded. Subgroup analysis and logistic regression were applied to investigate the association between diabetes and calcification. Cox regression analysis and survival between calcification, diabetes, and all-cause mortality. Additionally, the nomogram model was used to estimate the probability of survival for these individuals, and its performance was evaluated using risk stratification, receiver operating characteristic, decision, and calibration curves.ResultsCardiovascular calcification was found in 81.2% of diabetic patients (82/101) and 33.7% of nondiabetic patients (62/184). Diabetic patients had lower phosphorus, calcium, calcium-phosphorus product, plasma PTH levels and lower albumin levels (p < 0.001). People with diabetes were more likely to have calcification than people without diabetes (OR 5.66, 95% CI 1.96–16.36; p < 0.001). The overall mortality rate was 14.7% (42/285). The risk of death was notably greater in patients with both diabetes and calcification (29.27%, 24/82). Diabetes and calcification, along with other factors, collectively predict the risk of death in these patients. The nomogram model demonstrated excellent discriminatory power (area under the curve (AUC) = 0.975 at 5 years), outstanding calibration at low to high-risk levels and provided the greatest net benefit across a wide range of clinical decision thresholds.ConclusionsIn patients with ESRD during the early period of haemodialysis, diabetes significantly increases the risk of cardiovascular calcification, particularly multisite calcification, which is correlated with a higher mortality rate. The risk scores and nomograms developed in this study can assist clinicians in predicting the risk of death and providing individualised treatment plans to lower mortality rates in the early stages of hemodialysis.

Preoperative Laboratory Values Predicting Periprosthetic Joint Infection in Morbidly Obese Patients Undergoing Total Hip or Knee Arthroplasty.

Morbidly obese patients are an ever-growing high-risk population undergoing total hip arthroplasty (THA) and total knee arthroplasty (TKA) for end-stage osteoarthritis. This study sought to identify preoperative laboratory values that may serve as predictors of periprosthetic joint infection (PJI) in morbidly obese patients undergoing THA or TKA. All morbidly obese patients with preoperative laboratory data before undergoing primary elective TKA or THA were identified using the Premier Healthcare Database. Patients who developed PJI within 90 days after surgery were compared with patients without PJI. Laboratory value thresholds were defined by clinical guidelines or primary literature. Univariate and multivariable regression analyses were utilized to assess the association between PJI and preoperative laboratory values, including total lymphocyte count, neutrophil-lymphocyte ratio (NLR), platelet-lymphocyte ratio (PLR), monocyte-lymphocyte ratio (MLR), systemic immune-inflammation index (SII), albumin level, platelet count, albumin-globulin ratio, hemoglobin level, and hemoglobin A1c. Of the 6,780 patients identified (TKA: 76.67%; THA: 23.33%), 47 (0.69%) developed PJI within 90 days after surgery. The rate of PJI was 1.69% for patients with a hemoglobin level of <12 g/dL (for females) or <13 g/dL (for males), 2.14% for those with a platelet count of <142,000/µL or >417,000/µL, 1.11% for those with an NLR of >3.31, 1.69% for those with a PLR of >182.3, and 1.05% for those with an SII of >776.2. After accounting for potential confounding factors, we observed an association between PJI and an abnormal preoperative NLR (adjusted odds ratio [aOR]: 2.38, 95% confidence interval [CI]: 1.04 to 5.44, p = 0.039), PLR (aOR: 4.86, 95% CI: 2.15 to 10.95, p < 0.001), SII (aOR: 2.44, 95% CI: 1.09 to 5.44, p = 0.029), platelet count (aOR: 3.50, 95% CI: 1.11 to 10.99, p = 0.032), and hemoglobin level (aOR: 2.62, 95% CI: 1.06 to 6.50, p = 0.038). This study identified preoperative anemia, abnormal platelet count, and elevated NLR, PLR, and SII to be associated with an increased risk of PJI among patients with a body mass index of ≥40 kg/m 2 . These findings may help surgeons risk-stratify this high-risk patient population. Prognostic Level III . See Instructions for Authors for a complete description of levels of evidence.

Infantile and Very Early Onset Inflammatory Bowel Disease: A Multicenter Study.

This study described disease characteristics and long-term outcomes in patients diagnosed with very early onset inflammatory bowel disease (VEOIBD) (diagnosed before 6 years of age) and infantile-IBD (before 2 years). Cases from 21 centers worldwide diagnosed with VEOIBD (2008-2018), with minimum 2 years of follow-up, were retrospectively reviewed. The cohort included 243 patients (52% males, median follow-up of 5.8 [range 2-18] years, including 69 [28%]) with infantile-IBD. IBD subtypes included Crohn's disease (CD), ulcerative colitis (UC), or IBD-unclassified (IBDU) in 30%, 59%, and 11%, respectively. Among patients with CD, 94% had colonic involvement, and among patients with UC/IBDU, 75% had pancolitis. Patients with infantile-IBD presented with higher rates of IBDU, lower hemoglobin and albumin levels, and higher C-reactive protein, and had lower response rates to first-induction therapy and corticosteroids therapy (P < .05 for all). Colectomy and diversion surgeries were performed in 11% and 4%, respectively, with no significant differences between age groups. Corticosteroid-free remission rates were 74% and 78% after 3 and 5 years, respectively, and 86% at end of follow-up. Genetic testing was performed in 96 (40%) patients. Among tested population, 15 (16%) were identified with monogenic disease. This group demonstrated lower response rates to induction therapies, higher rates of surgical intervention, and higher rates of major infections (P < .05 for all). Patients with VEOIBD, including infantile-IBD, exhibit low rate of complications and surgical interventions at the long term. Patients with monogenic IBD are at risk for more severe disease course.

Nutritional status affects immune function and exacerbates the severity of pulmonary tuberculosis

AimTo comprehensively evaluate the association and impact of nutritional status and immune function on the severity of pulmonary tuberculosis (PTB).MethodsThis descriptive cross-sectional study involved 952 participants who were diagnosed with active PTB. Severe PTB involves three or more lung field infections based on chest radiography. Nutritional status was evaluated using various indicators, including body mass index (BMI), the nutritional risk screening score (NRS-2002), total protein (TP), prealbumin (PA), transferrin (TRF), and serum albumin (ALB) levels and the prognostic nutritional index (PNI). Immune dysfunction was defined as a CD4+ count &amp;lt;500 cells/µl or a CD4+/CD8+ ratio &amp;lt;1. Neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) were also calculated. Multivariate logistic and generalized linear regression were used to assess the associations between nutritional status, immune function, the severity of PTB, and the number of infected lung fields, adjusting for age, sex, and diabetes. Mediation analysis was conducted to evaluate the extent to which immune function mediated the impact of nutritional status on the severity of PTB. Sensitivity analysis was performed to enhance the robustness of the results.ResultsCompared to those in the general PTB group, patients in the severe PTB group tended to be older men with diabetes. Higher nutritional risk, higher proportion of immune dysfunction and lower lymphocyte counts were observed in the severe group. BMI and the PNI were found to be protective factors, while PLR was identified as a risk factor for disease severity. Immune dysfunction and the PLR are mediators of the relationship between nutritional status and PTB severity. When BMI, the PNI, and the PLR were combined with traditional clinical indicators, these parameters showed promising diagnostic value, and the AUC reached 0.701 (95% CI: 0.668–0.734).ConclusionThe findings suggest that nutritional status is significantly associated with the severity of PTB, and immune function mediates the effects of nutritional status on the severity of PTB. Maintaining adequate BMI, PNI levels, and immune function or reducing PLR levels helps reduce the risk of severe PTB.

The association of umbilical cord blood oxidative stress with maternal iron deficiency anemia: A tertiary center experience.

To compare the levels of oxidative stress markers in the umbilical cord blood between pregnant women diagnosed with iron deficiency anemia (IDA) and low-risk controls. The sample consisted of 131 patients, including 55 pregnant women with IDA and 76 controls with similar demographic characteristics. Participants were selected from patients delivered at ≥37 weeks. We compared the two groups in terms of the native thiol, total thiol, disulfide, and ischemia-modified albumin (IMA) levels measured in pregnant women's umbilical cord venous blood. The native thiol and total thiol values were statistically significantly lower in the anemia group, and the disulfide and IMA values were statistically significantly higher in the IDA group (P < 0.001). Perinatal outcomes were similar between the groups. In the present study, pregnant women with IDA had lower native and total thiol values and higher disulfide and IMA values in umbilical cord blood. Iron deficiency anemia in pregnancy may be a potential cause of increased oxidative stress.

Biomarker of severity in hospitalised patients with COVID-19: a retrospective study

BackgroundThe novel COVID-19 was rapidly spreading and was highly contagious. COVID-19 caused over 6 million deaths worldwide, with high mortality rates, particularly in severe cases.ObjectiveThis study aimed to investigate whether...

Factors associated with skeletal muscle mass in middle-aged men living with HIV.

Despite extensive research on muscle loss in people living with HIV (PLWH), the prevalence and contributing factors specifically among middle-aged men remain unclear. This study aimed to determine the prevalence of low muscle mass within this demographic and to identify associated factors. A total of 378 men living with HIV were enrolled in the study. They were classified into low muscle mass group if they displayed a skeletal muscle index (SMI) <7.00kg/m2 or fell within the lowest quintile of SMI based on the criteria established by the Asian Working Group for Sarcopenia 2019. Out of the 378 men living with HIV enrolled, 351 had normal muscle mass, while 27 (7.1%) had low muscle mass. Antiretroviral drugs Zidovudine (AZT) (OR=0.246, P=0.022) and higher serum albumin levels (OR=0.899, P=0.026) were found to be protective factors against low muscle mass according to quintile grouping. Strong positive associations between SMI and body mass index (BMI), nutritional risk index (NRI), oedema index and fat-free mass index (FFMI) (R>0.5, P<0.001) were observed. In addition, both BMI (sensitivity=0.741, specificity=0.906) and NRI (sensitivity=0.963, specificity=0.601) had high sensitivity and specificity in diagnosing low muscle mass, with critical values of 19.85 and 114.177 for BMI and NRI, respectively. The oedema index was the most effective measure of body composition in detecting abnormal fluid retention with high sensitivity (92.6%) and moderate specificity (71.8%) in identifying individuals with low muscle mass. Notably, PLWH with low muscle mass participants had a significantly higher prevalence (92.6%) of a high oedema index compared with those with normal muscle mass (28.2%). This observation indicates that individuals with HIV who experience reduced muscle mass is commonly accompanied with abnormal fluid retention within the body. Antiretroviral medication types, specifically Zidovudine, BMI and NRI can be independent risk factors for low muscle mass in men with HIV. These factors, along with BMI, could be used conveniently to predict low muscle mass. Furthermore, the association between the oedema index and muscle mass suggests that observing signs of oedema may indicate a risk of low muscle mass in PLWH.

Clinical features and risk factors for Sjogren’s syndrome patients suffering from oral candidiasis in Shanxi, China

ObjectivesTo investigate the clinical features and risk factors of Sjogren’s Syndrome (SS) patients suffering from oral candidiasis and to provide a foundation for the prevention and treatment of oral candidiasis in SS patients.MethodsThe medical records of 479 SS patients admitted to the Second Hospital of Shanxi Medical University from 2018 to 2020 were analysed to determine the clinical characteristics and risk factors that influence the occurrence of oral candidiasis infection in SS patients.ResultsPatients with oral candidiasis were older than those without oral candidiasis (P < 0.05). Male SS patients had greater oral candidiasis rates (P < 0.05). Unstimulated whole saliva (UWS) and stimulated whole saliva (SWS) were both shown to be adversely associated with oral Candida infections (P < 0.001). Logistic regression revealed that a low UWS was an independent risk factor for oral Candida infections in SS patients (OR: 0.004, P = 0.023). Greater WBC counts (OR: 1.22, P < 0.001), lower haemoglobin levels (OR: 0.97, P = 0.007), lower serum albumin levels (OR: 0.88, P < 0.001), lower IgG levels (OR: 0.91, P = 0.011), lower IgA levels (OR: 0.75, P = 0.011), and lower IgM levels (OR: 0.91, P = 0.015) were found in patients with oral Candida infections. Patients on immunosuppressive medications (OR: 0.32, P = 0.011), particularly rapamycin (P < 0.001), had a decreased rate of oral Candida infections.ConclusionsPatients with oral candidiasis were older than those without oral candidiasis. Male SS patients are more likely to have oral candidiasis. Individuals with lower UWS and SWS are more susceptible to oral Candida infection. Oral Candida infections in SS patients depend on their immunological status. Rapamycin may increase the abundance of Treg cells to reduce oral Candida infection in SS patients.