Identifying potential high-risk groups of oxaliplatin-induced liver injury (OILI) is valuable, but tools are lacking. So artificial neural network (ANN) and logistic regression (LR) models will be developed to predict the risk of OILI.

The medical information of patients treated with oxaliplatin between May and November 2016 at 10 hospitals was collected prospectively. We used the updated Roussel Uclaf causality assessment method (RUCAM) to identify cases of OILI and summarized the patient and medication characteristics. Furthermore, the ANN and LR models for predicting the risk of OILI were developed and evaluated.

The incidence of OILI was 3.65%. The median RUCAM score with interquartile range was 6 (4, 9). The ANN model performed similarly to the LR model in sensitivity, specificity, and accuracy. In discrimination, the area under the curve of the ANN model was larger (0.920>0.833, p=0.019). In calibration, the ANN model was slightly improved. The important predictors of both models overlapped partially, including age, chemotherapy regimens and cycles, single and total dose of OXA, glucocorticoid drugs, and antihistamine drugs.

When the discriminative and calibration ability was given priority, the ANN model outperformed the LR model in predicting the risk of OILI. Other chemotherapy drugs in oxaliplatin-based chemotherapy regimens could have different degrees of impact on OILI. We suspected that OILI may be idiosyncratic, and chemotherapy dose factors may be weakly correlated. Decision making on prophylactic medications needs to be carefully considered, and the actual preventive effect needed to be supported by more evidence.

Polymorphisms of the interleukin (IL)-17 proinflammatory cytokine family (IL17A and IL17F) have been associated with kidney chronic allograft failure (CAF). To date, the impact of heritable differences in IL17F genes and CAF among kidney transplant patients from North America has not been reported. The objective of the study was to assess the association of five distinct polymorphisms in the IL17F gene with histopathological changes in chronic kidney allograft failure.

Two hundred eighteen kidney transplant recipients were enrolled. Surveillance biopsies were performed to evaluate 11 distinct histological markers and the combined grade of interstitial fibrosis and tubular atrophy, 6 to 12 months post-transplant. Using direct sequencing, the IL17F polymorphisms (-1507C/T rs1889570, -1165A/G rs1266828, -5046C/T rs7771511, -6328G/A rs766748, and -7488A/G rs763780) were genotyped in the 10 healthy volunteer samples followed by all kidney transplant recipients were genotyped for five IL17F gene polymorphisms using polymerase chain reaction and sequence-specific primers. The association was evaluated using both univariate and multivariate logistic regression analysis.

We observed weak associations of TC genotype of IL17F-1165 (rs1266828) and allele of IL17F -1507C (rs1889570) with glomerular sclerosis and interstitial fibrosis and tubular atrophy (p = 0.017 and p = 0.03) respectively. Allele C of IL-17 -1165C/T (rs1266828) was associated with better glomerular sclerosis (p = 0.004, odds ratio = 0.39) score.

Our findings demonstrate that IL17F SNPs were not associated with CAF and support our prior published results that production of pro-inflammatory cytokines is not a strong predictor of CAF.

Accumulating evidence highlights the association between the gut microbiota and liver cirrhosis. However, the role of the gut microbiota in liver cirrhosis remains unclear.

We first assessed the differences in the composition of the bacterial community between CCl4-induced liver cirrhosis and control mice using 16S rRNA sequencing. We then performed a two-sample Mendelian randomization (MR) analysis to reveal the underlying causal relationship between the gut microbiota and liver cirrhosis. Causal relationships were analyzed using primary inverse variance weighting (IVW) and other supplemental MR methods. Furthermore, fecal samples from liver cirrhosis patients and healthy controls were collected to validate the results of the MR analysis.

Analysis of 16S rRNA sequencing indicated significant differences in gut microbiota composition between the cirrhosis and control groups. IVW analyses suggested that Alphaproteobacteria, Bacillales, NB1n, Rhodospirillales, Dorea, Lachnospiraceae, and Rhodospirillaceae were positively correlated with the risk of liver cirrhosis, whereas Butyricicoccus, Hungatella, Marvinbryantia, and Lactobacillaceae displayed the opposite effects. However, the weighted median and MR-PRESSO estimates further showed that only Butyricicoccus and Marvinbryantia presented stable negative associations with liver cirrhosis. No significant heterogeneity or horizontal pleiotropy was observed in the sensitivity analysis. Furthermore, the result of 16S rRNA sequencing also showed that healthy controls had a higher relative abundance of Butyricicoccus and Marvinbryantia than liver cirrhosis patients.

Our study provides new causal evidence for the link between gut microbiota and liver cirrhosis, which may contribute to the discovery of novel strategies to prevent liver cirrhosis.

Visceral adipocytes, typically larger and more pro-inflammatory, are less sensitive to insulin action and more susceptible to apoptosis than subcutaneous adipocytes. Melatonin is an anti-inflammatory, anti-apoptotic, and temporal cue to several tissues, including adipose tissue. The modern lifestyle often involves irregular sleep-wake cycles, exposure to artificial light at night, and shift work, all of which suppress nocturnal melatonin secretion and could disrupt adipose tissue homeostasis. This study aimed to determine the effects of pinealectomy on the temporal expression of core clock components and apoptosis-related transcripts and proteins in rat retroperitoneal (RP) adipose tissue.

In silico analysis predicted putative binding sites of core clock components for Caspase genes. Eighty male Wistar rats were divided into either Sham-operated or Pinealectomized groups. Four weeks post-surgery, the animals were euthanized every 4 h over 24 h, and the RP tissue was processed for qRT-qPCR and ELISA.

The promoter and regulatory regions of caspases 3, 8, and 9 were predicted. The expression of apoptosis-related genes exhibited circadian rhythmicity in control animals. Pinealectomy resulted in a loss of Fas rhythmicity, altered the cosinor parameters of Bax, Bcl2, Casp3, and Casp9 expression, and increased the protein content of BAX, BCL2, CASP3, and CASP8 in the late dark phase. The daily expression of core clock components (Clock, Bmal1, Per2, Cry1, and Nr1d1) was significantly altered by the time main effect, while pinealectomy did not change their expression.

Melatonin plays important roles in the daily regulation of apoptosis in RP fat, suggesting that melatonin suppression due to a desynchronized modern lifestyle might contribute to the development of obesity and metabolic syndrome.

Inflammation is a natural reaction of the innate immune system that evolved primarily to protect the human body from invading pathogens and to heal injuries. There are two different types of inflammation, acute and chronic inflammation, differing in duration, underlying causes, and characteristics. The acute-to-chronic transition can be determined by several pathomechanisms, including dysregulation of immune response and failure to eliminate the underlying cause. Emerging evidence suggests that dysfunctional mitochondria can promote the development of chronic inflammation. In this respect, the mechanisms triggering defective mitophagy, a selective form of autophagy that exterminates dysfunctional mitochondria to maintain cellular homeostasis, attracted special attention. This review aims to summarize current evidence underlining the role and mechanisms of mitochondria in inflammation chronification, which will contribute to develop targeted therapeutic approaches to restore mitochondrial health and alleviate chronic inflammation that can be used for a wide range of chronic inflammatory diseases.

The coronavirus disease 2019 (COVID-19) pandemic continues to affect global health, and the emergence of new variants has added a layer of uncertainty to medical practice. Although elective surgeries are recommended to be postponed for at least 7 weeks after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection to be considered safe, the safety and optimal timing for pancreatic surgery after this infection remains unknown.

Conducted in four high-volume pancreas centers in China, this prospective, multicenter clinical trial aimed to provide a realistic representation of the key perioperative parameters for pancreatic surgery after SARS-CoV-2 infection. The primary outcome was 30-day perioperative survival, and the secondary outcomes included major complications, pulmonary complications, and surgical complications.

Our results revealed that elective pancreatic surgery within 4 weeks of SARS-CoV-2 infection may be correlated with a prolonged hospital stay. Specifically, patients who underwent surgery within 0–2 weeks (24.7 days average) or 3–4 weeks (21.8 days average) after infection had obviously longer hospital stays compared to those without prior infection (15.5 days average) or those who underwent surgery more than 4 weeks after infection. However, there was no apparent increase in the total postoperative complications classified as Clavien-Dindo grade ≥ 3, even among patients who underwent surgery within 2 weeks after SARS-CoV-2 infection.

No significant increase in major complications is observed among patients undergoing pancreatic surgery following a diagnosis of SARS-CoV-2. However, it would be safer to perform pancreatic surgery at least 4 weeks after SARS-CoV-2 infection.

Gremlin-1 (GREM1) was recently reported to maintain the cellular heterogeneity of pancreatic cancer. However, the function of GREM1 in endometrial cancer remains elusive. The purpose of this study was to investigate the underlying mechanisms of GREM1 in endometrial cancer using an ensemble learning-based framework.

The training and test cohorts were gathered from The Cancer Genome Atlas and Genome Expression Omnibus databases, respectively. The cohorts were divided into low-GREM1 and high-GREM1 groups. Differentially expressed gene analysis, weighted gene co-expression network analysis, and Mfuzz clustering were implemented in the training cohort to screen genes with GREM1. The genes were subjected to machine learning-based integration for selecting key genes with GREM1. Together with the Bayesian network inference and Kyoto Encyclopedia of Genes and Genome enrichment analysis on key genes and GREM1, the potential pathway of GREM1 in endometrial cancer was illustrated. Leveraging the CIBERSORT analysis tool and single sample gene set enrichment analysis, the immune landscape of endometrial cancer was investigated to identify the immune cells with GREM1 and key genes.

A set of 10 key genes (FAP, THBS1, POSTN, INHBA, ASPN, COL3A1, IGFBP5, COL8A1, FN1, and COL5A2) highly linked to GREM1 were obtained. Moreover, GREM1 may regulate extracellular matrix-related pathways in endometrial cancer, affecting extracellular matrix degradation involving collagen-related key genes. Finally, we found increased infiltration of mast cells in the high-GREM1 group, accompanied by their positive correlations.

GREM1 regulated extracellular matrix modulation in endometrial cancer by interacting with key genes, with mast cells serving as a signature.

Human papillomavirus (HPV) has been clearly linked to the occurrence of some cancers such as cervical cancer, anogenital cancer, and head and neck cancer. However, studies suggest that the virus can also be the reason for other forms of malignant diseases. Traditionally, countries in the Middle East, including Iran, were thought to be less exposed to HPV infections due to conservative sexual customs. Moreover, owing to the lack of a proper vaccination program in adolescence, malignancies caused by the HPV virus are increasing and are of concern. Additionally, in the absence of a well-established vaccination schedule, changes in sexual behavior have resulted in an increasing number of young individuals engaging in premarital intercourse. In this article, we provide an overview of the current prevalence of common cancers in Iran closely associated with HPV, the status of vaccination programs aimed at preventing malignancies, and early detection strategies to halt cancer progression

The study aimed to analyze the prevalence, trends, and outcomes of twin pregnancies in Ile-Ife, Nigeria, over two distinct periods.

This research, based on a 14-year retrospective cohort study, scrutinized twin births occurring in two-time frames: recent years (2012–2018; Period II) and the recent past (2005–2011; Period I) at a University Teaching Hospital in Ile-Ife, Nigeria. The inclusion criteria were limited to twin births, excluding singleton and higher-order gestations. Outcomes were evaluated based on several parameters, including mode of delivery, birth weights, fetal gender combinations, APGAR scores, perinatal mortality, and maternal complications. Data analysis was conducted using the 26th version of Statistical Package for the Social Science, with a significance threshold of p < 0.05.

The study documented a stable prevalence of twin gestations, registering at 20.7 per 1,000 births without a significant discrepancy between the two time periods (21.7‰ versus 19.7‰; p = 0.699). Individuals from the Yoruba tribe predominantly featured in both cohorts, showing no considerable variation between the two time periods [83 (95.4) vs. 120 (99.2); p-value = 0.116]). The data exhibited recurrent instances of caesarean delivery (65.6% vs. 50.2%, p = 0.119), vertex-vertex presentation (38.0% vs. 44.7%, p = 0.352), and differing sex combinations (33.3% vs. 38.0%, p = 0.722) across both time frames. Twin II neonates born through Caesarean section were more frequently admitted to neonatal intensive care units than Twin I (5.1% versus 4.6%; p = 0.001). The recent years witnessed a surge in preterm labor complications, notably higher than the earlier period (17.1% versus 7.8%; p = 0.008).

The prevalence of twin births in Ile-Ife, Nigeria, demonstrates a fluctuating decline. To comprehensively understand the dynamics of twin births in the region, there is a pressing need for expansive, community-centric research in southwest Nigeria.

Recent technical advances in liver imaging and surveillance for patients at high risk for developing hepatocellular carcinoma (HCC) have led to an increase in the detection of borderline hepatic nodules in the gray area of multistep carcinogenesis, particularly in those that are hypointense at the hepatobiliary phase (HBP) and do not show arterial phase hyperenhancement. Given their potential to transform and advance into hypervascular HCC, these nodules have progressively attracted the interest of the scientific community. To date, however, no shared guidelines have been established for the decision management of these borderline hepatic nodules. It is therefore extremely important to identify features that indicate the malignant potential of these nodules and the likelihood of vascularization. In fact, a more complete knowledge of their history and evolution would allow outlining shared guidelines for their clinical-surgical management, to implement early treatment programs and decide between a preventive curative treatment or a watchful follow-up. This review aims to summarize the current knowledge on hepatic borderline nodules, particularly focusing on those imaging features which are hypothetically correlated with their malignant evolution, and to discuss current guidelines and ongoing management in clinical practice.

Nonalcoholic fatty liver disease (NAFLD) is commonly associated with obesity but can develop in normal-weight people (lean NAFLD). We compared outcomes in lean, overweight, and obese NAFLD.

This retrospective chart review included patients at Stanford University Medical Center with NAFLD confirmed by imaging between March 1995 and December 2021. Lean, overweight, and obese patients had body mass index of <25.0, >25.0 and <29.9, and ≥30.0 kg/m2 for non-Asian and >23.0 and ≥27.5 for overweight and obese Asian patients.

A total of 9061 lean (10.2%), overweight (31.7%), and obese (58.1%) patients were included. Lean patients were 5 years older than obese patients (53±17.4 vs. 48.7±15.1 years), more were female (59.6% vs. 55.2%), white (49.1% vs. 46.5%), had NASH (29.2% vs. 22.5%), cirrhosis (25.3% vs.19.2%), or nonliver cancer (25.3% vs. 18.3%). Fewer had diabetes (21.7% vs. 35.8%) or metabolic comorbidities (all p<0.0001). Lean NAFLD patients had liver-related mortality similar to other groups but higher overall (p=0.01) and nonliver-related (p=0.02) mortality. After multivariable model adjustment for covariates, differences between lean and obese NAFLD in liver-related, nonliver-related, and overall mortality (adjusted hazard ratios of 1.34, 1.00, and 1.32; p=0.66, 0.99, and 0.20, respectively) were not significant.

Lean NAFLD had fewer metabolic comorbidities but similar adverse or worse outcomes, suggesting that it is not benign. Healthcare providers should provide the same level of care and intervention as for overweight and obese NAFLD.

Gastric cancer (GC) is a preventable disease, and Helicobacter pylori infection is the most important controllable risk factor. Despite numerous studies confirming that eradicating H. pylori can reduce the risk of GC, there remains a significant gap between the fundamental and clinical knowledge and public health interventions. This article provides a review of the progress made in the last decade by gastroenterologists in understanding the carcinogenic effects of H. pylori. The authors also summarize the evidence demonstrating the beneficial effects of eradication of H. pylori on gastric precancerous lesions and GC, and outline current strategies for H. pylori management. Notably, a family-based approach to H. pylori management represents a novel strategy for future GC prevention and control, boasting numerous advantages and having the potential to play a crucial role in future policymaking.

Exosomes are 60–120 nm diameter double-membrane lipid organelles discharged by cells. Various studies have shown that exosomes exert multiple functions in both physical and diseased processes, such as intercellular information exchange, immune response, and disease progression. Repeated chronic injury to the liver often leads to inflammation and liver fibrosis (LF), a disorder that, if unchecked, may progress to cirrhosis, liver failure, portal hypertension, and even hepatocellular carcinoma. As an essential component of host innate immunity against pathogen invasion, macrophages play an important role in modulating inflammation homeostasis by finely tuning the polarization process of macrophages into either M1 or M2 subtypes in response to different microenvironments. As a critical contributor to the inflammation process, macrophages also play a complex and instrumental function in the progression of LF. This review focuses on recent advancements in the role of macrophage-associated exosomes implicated in LF, including macrophage-released exosomes and macrophage-targeted exosomes. In addition, the progress made in exosome-based antifibrotic therapy by in vivo and in vitro studies is also highlighted.

Mixed phenotype acute leukemia (MPAL) is an uncommon acute leukemia, representing only 2–5% of acute leukemia cases. Extramedullary disease (EMD) is typically seen during a relapse or with disease progression. When EMD occurs in acute myeloid leukemia, it is called myeloid sarcoma. However, to the best of our knowledge, there are no reports of EMD in MPAL patients at the initial diagnosis. We provide the first case, which shows EMD associated with bone marrow necrosis of MPAL with minor BCR/ABL (BCR::ABL1 fusion gene) at disease onset. A 50-year-old Japanese man presented to a hematologist with a month-long history of immobility due to severe lumbar pain. Bone marrow aspirations were unsuccessful. Computed tomography revealed a mass in the left iliopsoas muscle and hepatosplenomegaly. He was diagnosed with MPAL associated with minor BCR/ABL, and EMD was confirmed by the analysis of blast phenotype in peripheral blood and necrotic bone marrow, as well as the biopsied mass in the iliopsoas muscle. He was first treated with cytarabine, then treatment was switched to a combination of steroids and dasatinib after the final diagnosis. The blast in peripheral blood disappeared, and the mass in the left iliopsoas shrunk one month after dasatinib treatment. Later bone marrow biopsy findings confirmed initial bone marrow necrosis. Although EMD associated with bone marrow necrosis at disease onset of MPAL with minor BCR/ABL is rare, our case underscores that no type of leukemia should be excluded from the differential diagnosis of bone marrow necrosis and EMD.

Coronary stenosis is responsible for angina attacks in coronary heart disease (CHD). A prospective pilot study was conducted to investigate the effects of combining remote ischemic preconditioning (RIPC) with Radix salviae decoction (RSD).

A total of 60 patients diagnosed with CHD were enrolled and divided into the control group and the RIPC-RSD treatment group. The primary outcome was the frequency of angina attacks, while the secondary outcomes included Canadian Cardiovascular Society levels, emergency medications, and prognosis indicators.

A total of 57 patients were included in the final analysis. Demographic characteristics and vessel stenosis comparisons showed similar results (p > 0.05). There was no significant difference in the frequency of angina attacks before (χ2 = 2.170, p = 0.404) or after (χ2 = 1.509, p = 0.662) treatment. Similarly, there was no significant difference in CCS levels of angina attacks between the two groups before (χ2 = 1.504, p = 0.681) or after (χ2 = 1.392, p = 0.707) treatment. Although there was no significant difference in the use of emergency medications for angina attacks before (χ2 = 1.321, p = 0.517) or after (χ2 = 2.457, p = 0.356) treatment, a significant decrease in the frequency of emergency medications was observed (Z = −2.188, p = 0.029). However, the RIPC-RSD treatment did not have a significant impact on the prognosis (cardiac death, χ2 = 1.831, p = 0.176; target vessel revascularization, χ2 = 1.111, p = 0.292; rehospitalization, χ2 = 0.495, p = 0.482) of coronary stenosis in CHD patients.

Due to the limitations of a relatively small sample size, this prospective pilot study did not observe a significant effect of RIPC-RSD on angina attacks and prognosis in CHD patients, but it implied potential efficacy in reducing the frequency of emergency medications.

Various risk engines exist for predicting future cardiovascular disease. We developed a noninvasive cardiovascular disease risk app which appeared to work well for us without need for invasive tests. This is an attempt to compare its predictive accuracy with an already existing widely used risk engine.

We used data partly generated in our earlier study on resistant hypertension. Between May and October 2021, those who were still attending care had abdominal height, blood pressure, weight, and height measured. Body surface index was derived from height and weight. Information on sex, family history of cardiovascular disease, alcohol use, physical inactivity, smoking, and diabetes history, total, and high-density lipoprotein cholesterol was extracted from the records. Data as appropriate were imputed into our new app and the atherosclerotic cardiovascular disease risk estimator app of the American Heart Association. The results were compared.

Fifty-two patients with complete data were studied. Both methods strongly correlated positively (R = 0.805, p = 0.000), showing equivalence. Risk levels determined by both methods agreed on high cardiovascular disease risk in 21(40.30%) and intermediate risk in 22 (42.31%) patients. Four patients were classified as high risk and as medium risk by the established American Heart Association app. Five were at intermediate risk with our app and at low risk with the American Heart Association app.

In 43 cases (82.69%), both tools agreed on cardiovascular disease risk prediction. In nine there was a tendency for the American Heart Association app to put patients in a lower risk category. This tends to delay the initiation of appropriate preventive or curative measures. Given the total dependence on anthropometric and historical indices, it is felt that our new method is cheaper and should be more widely deployed in preventive cardiology.

There has been a recent increase in the incidence of allergies and the severity of allergic reactions worldwide. Most allergy treatments, such as antihistamines, only treat the symptoms of the allergy. In contrast, allergen-specific immunotherapy (ASIT) refers to a pathogenetic treatment that prevents the progression of allergies. ASIT can also reduce the risk of mild reactions, such as allergic rhinitis, worsening into more serious conditions, such as allergic bronchial asthma. ASIT is performed by administration of an allergen, usually either subcutaneously or sublingually. Sublingual administration is regarded as safer than subcutaneous administration because of a reduction in the risks associated with systemic effects. The uptake of allergens by the mucous membranes in sublingual administration can be improved using delivery agents, such as liposomes, dendrimers, and nanoparticles. Glycyrrhizic acid can self-associate to form micelles and thus, form complexes to enable the delivery of poorly soluble drugs. In addition, glycyrrhizic acid has been shown to have anti-inflammatory effects and is itself a potential treatment for allergic diseases such as allergic rhinitis and asthma. Thus, the development of an ASIT using glycyrrhizic acid is of interest. Herein, we review allergic bronchial asthma and allergic rhinitis and the use of ASIT in the treatment of these conditions. We then discuss glycyrrhizic acid and the potential development of delivery agents using glycyrrhizic acid for use in ASIT.

Ophiocordyceps sinensis is widely used in traditional Asian medicine and grows at high altitudes (3,000–4,000 meters) on the Qinghai-Tibet Plateau. This fungus is an expensive and rare species that is difficult to cultivate. Increasing global demand, limited commercial trade, and precious resources drive an urgent need for the development of artificial cultivation techniques to produce bioactive compounds. This paper reviews the genome biology, culture systems, solid-state and submerged fermentation processes used to produce bioactive compounds in O. sinensis. It also elucidates its biological properties at the genome level for the development of synthetic media. We performed a bibliometric analysis, retrieving information on various aspects of this fungus from NCBI PubMed. A total of 135 research articles on O. sinensis were collected, of which 104 focused on the production of bioactive compounds and 26 focused on ‘x-omics’ studies. Next-generation sequencing data provides a genetic basis for fungal biology and host specificity. Recent developmental transcriptomic studies described mechanisms underlying the transcriptional regulation of fruiting body development and cold adaptation. Metabolic data indicate that many bioactive compounds are produced by cultured mycelia or fruiting bodies. The biological properties of this fungus can be used to design and develop synthetic media for fruiting body development and enhance the production of bioactive compounds. Several bioactive compounds and their pharmacological properties have been studied in the mycelia and culture supernatants. Since cultured O. sinensis is an alternative to natural and cultured C. militaris strains, research on the design and formulation of solid media for the production of fruiting bodies and bioactive compounds is currently attracting attention.