Early detection of oral cancer is crucial for improving prognosis, increasing survival rates, and reducing treatment-related morbidity, considering the high mortality rate associated with this condition. However, the conventional approach within communities has led to a growing exploration of different screening methods to detect potentially malignant oral disorders, with particular emphasis on imaging and artificial intelligence and their integration with conventional approaches. The article reviewed literature on oral neoplasms and early cancer detection from databases like Medline, Google Scholar, and Web of Science, mainly from 2001 to 2023. This review aims to shed light on the potential of these technologies, new ideas, and methods in improving the accuracy and effectiveness of oral cancer screening, ultimately leading to earlier detection and more successful prevention strategies, which are unmet needs, especially in underdeveloped and developing nations.

Molecular testing has emerged as a valuable tool for stratifying cytologically indeterminate thyroid nodules (ITNs), with Harvey rat sarcoma viral oncogene homolog/neuroblastoma RAS viral oncogene homolog (HRAS/NRAS) mutations being among the most prevalent molecular alterations. The study aimed to evaluate the malignancy risk of ITNs with these mutations.

We conducted a retrospective study involving ITNs (Bethesda category III and IV) that underwent ThyroSeq testing between February 2016 and January 2022. A smaller subset of ITNs also underwent Afirma testing. We specifically identified nodules with HRAS/NRAS mutations and collected radiological, clinical, histological, and follow-up data.

Our analysis identified 45 ITNs with NRAS (29 cases) and HRAS (15 cases) mutations. Of the 29 nodules with NRAS mutations, 25 underwent surgical treatment (14 total thyroidectomies and 11 hemithyroidectomies), resulting in a surgical resection rate of approximately 86%. Among the resected nodules, six were malignant, yielding a calculated risk of malignancy (ROM) ranging from 20.6% to 25%. Three of these malignant nodules were managed with total thyroidectomy, while the other three underwent hemithyroidectomy. During a follow-up period of 43.8 months for total thyroidectomy and 32.9 months for hemithyroidectomy, no recurrence or metastasis was detected among the patients. Among the four nodules treated conservatively, three remained stable, with an average follow-up duration of 34.7 months, while one patient was lost to follow-up. Regarding HRAS mutations, 15 nodules were identified, with 12 of them undergoing surgical treatment (six total thyroidectomies and 6 hemithyroidectomies), resulting in an 80% surgical resection rate. Two of the resected nodules were malignant, with a calculated ROM of 13.3% to 16.7%. Both malignant nodules were managed with total thyroidectomy, and during a follow-up period of 37.9 months, no recurrence or metastasis occurred. Of the three nodules managed conservatively, all remained stable, with an average follow-up duration of 31.1 months.

The ROM for nodules with NRAS (20.6–25%) or HRAS (13.3–16.7%) mutations was found to be low. Therefore, before opting for total thyroidectomy, conservative management, including limited resection, should be considered as a viable alternative.

Despite efforts, tumor recurrence is diagnosed in 35–40% of patients with stage III squamous cell lung carcinoma (SCLC) during the first year after treatment. The purpose of the present investigation was to determine the levels of cytokeratin-fragment 19 (CYFRA 21-1) in blood serum, the percentages of lymphocytes containing chemokine receptor 1 (CXCR1, %, lymphocytes), and the percentages of monocytes containing chemokine receptor 2 (CXCR2, %, monocytes), as well as their combined model before and after treatment for the early detection of recurrence.

Forty-eight patients (29 men and 19 women) with newly diagnosed stage III SCLC were examined. Serum levels of CYFRA 21-1, CXCR1, %, lymphocytes, and CXCR2, %, monocytes in peripheral blood were measured before treatment and at three weeks, three months, and six months after treatment using a chemiluminescence immunoassay analyzer and a flow cytometer, respectively.

The levels of all determined indicators, which were elevated before treatment, decreased sharply three weeks after treatment. Subsequently, three months and six months after treatment, the levels steadily increased in patients with diagnosed tumor recurrence. The differences in these indicators in three weeks to three months, three months to six months, and three weeks to six months after treatment, when included in a regression equation, corresponded to the presence of recurrence with accuracies of 83.3%, 91.7%, and 95.8%, respectively.

Determining the combination of CYFRA 21-1 levels, CXCR1, %, lymphocytes, and CXCR2, %, monocytes in the blood of patients with stage III SCLC is important for assessing the probability of recurrence after treatment.

Inflammatory bowel diseases (IBD), which include Crohn’s disease and ulcerative colitis, are chronic inflammatory disorders of the GI tract. The etiology is unclear, and most clinical symptoms are nonspecific, making the diagnosis and prognosis of IBD challenging as there is no gold-standard diagnostic test. Both endoscopy and imaging are essential diagnostic tools for determining disease state, location, and severity. However, the high cost and invasive nature of these tests make them unrealistic for frequent assessment. Given these limitations, laboratory testing of blood and feces has proven to be a viable alternative for routine disease monitoring. To integrate more efficient and personalized treatment strategies, new studies are consistently emerging to develop minimally invasive testing that can predict disease severity and response to available treatments. The goal is to develop better predictors of disease course, response to therapy, and therapy-related adverse events, thereby establishing a more efficient and personalized treatment strategy. This review aimed to delve into existing literature to assemble a collection of currently used biomarkers that aid in monitoring treatment response, as well as highlight select novel and combined biomarkers that hold promise for future management of IBD.

Nodular lymphocyte predominant Hodgkin lymphoma was termed “nodular lymphocyte predominant B-cell lymphoma” in the International Consensus Classification (ICC), to emphasize clinical and biological differences from classic Hodgkin lymphoma (CHL). The abbreviation “NLP” represents both terms in the ICC and World Health Organization classifications. Variations in the growth pattern, originally reported as Fan patterns A-F, are designated as either grade 1 or grade 2 in the ICC. NLP is uncommon, and in some cases an accurate diagnosis is challenging. The objectives of this article were to review the histopathologic features of NLP and the differential diagnosis from other key entities including de novo T-cell/histiocyte-rich large B-cell lymphoma (THRLBL) and lymphocyte-rich classic Hodgkin lymphoma (LRCHL). Histologically, NLP Fan pattern E (THRLBL-like) can be indistinguishable from de novo THRLBL. However, focal nodular areas, clustering of tumor cells, presence of few admixed small B-cells or FDC meshworks, and T-cell rosettes favor NLP Fan pattern E and argue against de novo THRLBL. NLP may also be confused with LRCHL. Patients with NLP are younger than those with LRCHL, and LRCHL may show mediastinal involvement. In LRCHL, the nodular pattern often contains eccentrically located small regressed germinal centers and intact small dense FDC meshworks, in contrast to the expanded, and fragmented FDC meshworks in NLP. Neoplastic cells that are positive for CD30 and CD15 but negative for CD20 and CD79a are characteristic of LRCHL. Additionally, Fascin and Gata3 are commonly positive in LRCHL but usually negative in NLP.

As practice patterns and hepatitis C virus (HCV) genotypes (GT) vary geographically, a global real-world study from both East and West covering all GTs can help inform practice policy toward the 2030 HCV elimination goal. This study aimed to assess the effectiveness and tolerability of DAA treatment in routine clinical practice in a multinational cohort for patients infected with all HCV GTs, focusing on GT3 and GT6.

We analyzed the sustained virological response (SVR12) of 15,849 chronic hepatitis C patients from 39 Real-World Evidence from the Asia Liver Consortium for HCV clinical sites in Asia Pacific, North America, and Europe between 07/01/2014–07/01/2021.

The mean age was 62±13 years, with 49.6% male. The demographic breakdown was 91.1% Asian (52.9% Japanese, 25.7% Chinese/Taiwanese, 5.4% Korean, 3.3% Malaysian, and 2.9% Vietnamese), 6.4% White, 1.3% Hispanic/Latino, and 1% Black/African-American. Additionally, 34.8% had cirrhosis, 8.6% had hepatocellular carcinoma (HCC), and 24.9% were treatment-experienced (20.7% with interferon, 4.3% with direct-acting antivirals). The largest group was GT1 (10,246 [64.6%]), followed by GT2 (3,686 [23.2%]), GT3 (1,151 [7.2%]), GT6 (457 [2.8%]), GT4 (47 [0.3%]), GT5 (1 [0.006%]), and untyped GTs (261 [1.6%]). The overall SVR12 was 96.9%, with rates over 95% for GT1/2/3/6 but 91.5% for GT4. SVR12 for GT3 was 95.1% overall, 98.2% for GT3a, and 94.0% for GT3b. SVR12 was 98.3% overall for GT6, lower for patients with cirrhosis and treatment-experienced (TE) (93.8%) but ≥97.5% for treatment-naive patients regardless of cirrhosis status. On multivariable analysis, advanced age, prior treatment failure, cirrhosis, active HCC, and GT3/4 were independent predictors of lower SVR12, while being Asian was a significant predictor of achieving SVR12.

In this diverse multinational real-world cohort of patients with various GTs, the overall cure rate was 96.9%, despite large numbers of patients with cirrhosis, HCC, TE, and GT3/6. SVR12 for GT3/6 with cirrhosis and TE was lower but still excellent (>91%).

The role of platelet autophagy in cirrhotic thrombocytopenia (CTP) remains unclear. This study aimed to investigate the impact of platelet autophagy in CTP and elucidate the regulatory mechanism of hydrogen sulfide (H2S) on platelet autophagy.

Platelets from 56 cirrhotic patients and 56 healthy individuals were isolated for in vitro analyses. Autophagy markers (ATG7, BECN1, LC3, and SQSTM1) were quantified using enzyme-linked immunosorbent assay, while autophagosomes were visualized through electron microscopy. Western blotting was used to assess the autophagy-related proteins and the PDGFR/PI3K/Akt/mTOR pathway following treatment with NaHS (an H2S donor), hydroxocobalamin (an H2S scavenger), or AG 1295 (a selective PDGFR-α inhibitor). A carbon tetrachloride-induced cirrhotic BALB/c mouse model was established. Cirrhotic mice with thrombocytopenia were randomly treated with normal saline, NaHS, or hydroxocobalamin for 15 days. Changes in platelet count and aggregation rate were observed every three days.

Cirrhotic patients with thrombocytopenia exhibited significantly decreased platelet autophagy markers and endogenous H2S levels, alongside increased platelet aggregation, compared to healthy controls. In vitro, NaHS treatment of platelets from severe CTP patients elevated LC3-II levels, reduced SQSTM1 levels, and decreased platelet aggregation in a dose-dependent manner. H2S treatment inhibited PDGFR, PI3K, Akt, and mTOR phosphorylation. In vivo, NaHS significantly increased LC3-II and decreased SQSTM1 expressions in platelets of cirrhotic mice, reducing platelet aggregation without affecting the platelet count.

Diminished platelet autophagy potentially contributes to thrombocytopenia in cirrhotic patients. H2S modulates platelet autophagy and functions possibly via the PDGFR-α/PI3K/Akt/mTOR signaling pathway.

The genome editing technology based on clustered regularly interspaced short palindromic repeats/CRISPR-associated protein-9 (CRISPR/Cas9), is revolutionizing research, particularly in the context of human neurodegenerative disorders. This review examines recent advancements in CRISPR/Cas9 and its potential to address the protein misfolding mechanisms underlying these diseases. Proteins, the fundamental units of life, can misfold due to various changes, resulting in aggregation and contributing to devastating illnesses such as Alzheimer’s disease, Parkinson’s disease, Amyotrophic lateral sclerosis, and Huntington’s disease. Understanding the pathology of these disorders and the methods used for their detection is vital for developing effective treatments. CRISPR/Cas9 offers a powerful tool for combating neurodegenerative disorders at the molecular level. Its groundbreaking gene-editing capabilities are advancing preclinical and animal studies, paving the way for potential human trials and innovative therapeutic strategies. This review explores the complex challenge of protein misfolding and highlights how CRISPR technology could provide a crucial breakthrough in the fight against neurodegenerative disorders. It offers a synthesis of CRISPR advancements for neurodegenerative disorders. However, it is essential to be aware of the review’s limitations, including potential selection bias, the risk of oversimplification, and possible obsolescence in rapidly changing research fields. Despite these considerations, the transformative promise of CRISPR in understanding and potentially treating neurodegenerative diseases warrants continued research and thorough analysis.

Chronic cholestasis due to heritable causes is usually diagnosed in childhood. However, many cases can present and survive into adulthood. The time course varies considerably depending on the underlying etiology. Laboratory data usually reveal elevated conjugated hyperbilirubinemia, alkaline phosphatase, and gamma-glutamyl transpeptidase. Patients may be asymptomatic; however, when present, the typical symptoms are pruritus, jaundice, fatigue, and alcoholic stools. The diagnostic methods and management required depend on the underlying etiology. The development of genome-wide associated studies has allowed the identification of specific genetic mutations related to the pathophysiology of cholestatic liver diseases. The aim of this review was to highlight the genetics, clinical pathophysiology, presentation, diagnosis, and treatment of heritable etiologies of chronic cholestatic liver disease.

HLA-G gene harbors certain polymorphic variations that can potentially impact its biological activity, and therefore, may confer a risk for recurrent pregnancy loss (RPL). This study aimed to analyze whether HLA-G polymorphic variations (G*0103, G*0104, and G0105N) are related to the risk of RPL in women from Kashmir, North India.

A total of 200 women who suffered ≥2 RPLs and 240 healthy controls were recruited from the same geographical region. Additionally, 100 spouses of RPL affected women and 60 products of conception were evaluated. HLA-G genotyping was performed using the polymerase chain reaction-restriction fragment length polymorphism method.

The variant genotype 0103:0103 in exon 2 of HLA-G was not detected. The genotype 0104/0105 was detected in 100% of RPL patients, spouses, and controls. Exon 2 and variant genotypes G*0103 in exon 2 and G*0105 in exon 3 of HLA-G were absent in our population and thus did not contribute to the etiopathogenesis of RPL. In contrast, the exon 3 HLA-G variant G*0104N was significantly more frequent in RPL patients and their spouses compared to the control group (p<0.05). The presence of the HLA-G variant genotype G*0104N (exon 3) was detected in 13% of RPL patients and 7% of their male partners, indicating a significantly higher frequency than in controls and suggesting a substantial risk for RPL (p<0.05).

This study revealed that the higher frequency of the HLA-G*0104 allele in both partners strongly predicted a substantial risk for RPL in our population.

Tissue inhibitor of metalloproteinase-1 (TIMP-1) plays a role in the excessive generation of extracellular matrix in liver fibrosis. This study aimed to explore the pathways through which TIMP-1 controls monocyte chemoattractant protein-1 (MCP-1) expression and promotes hepatic macrophage recruitment.

Liver fibrosis was triggered through carbon tetrachloride, and an adeno-associated virus containing small interfering RNA targeting TIMP-1 (siRNA-TIMP-1) was administered to both rats and mice. We assessed the extent of fibrosis and macrophage recruitment. The molecular mechanisms regulating macrophage recruitment by TIMP-1 were investigated through transwell migration assays, luciferase reporter assays, the use of pharmacological modulators, and an analysis of extracellular vesicles (EVs).

siRNA-TIMP-1 alleviated carbon tetrachloride-induced liver fibrosis, reducing macrophage migration and MCP-1 expression. Co-culturing macrophages with hepatic stellate cells (HSCs) post-TIMP-1 downregulation inhibited macrophage migration. In siRNA-TIMP-1-treated HSCs, microRNA-145 (miRNA-145) expression increased, while the expression of Friend leukemia virus integration-1 (Fli-1) and MCP-1 was inhibited. Downregulation of Fli-1 led to decreased MCP-1 expression, whereas Fli-1 overexpression increased MCP-1 expression within HSCs. Transfection with miRNA-145 mimics reduced the expression of both Fli-1 and MCP-1, while miRNA-145 inhibitors elevated the expression of both Fli-1 and MCP-1 in HSCs. miRNA-145 bound directly to the 3′-UTR of Fli-1, and miRNA-145-enriched EVs secreted by HSCs after TIMP-1 downregulation influenced macrophage recruitment.

TIMP-1 induces Fli-1 expression through miRNA-145, subsequently increasing MCP-1 expression and macrophage recruitment. MiRNA-145-enriched EVs from HSCs can transmit biological information and magnify the function of TIMP-1.

Feedback loops or compensatory mechanisms are present in a wide range of biological systems and processes. Here, we hypothesize that endogenous opioid peptides, such as endorphins and enkephalins, can be broken down and enzymatically converted to catecholamines (dopamine, norepinephrine, epinephrine) locally. Particularly, this proposed local production of norepinephrine may modulate analgesia through feedback mechanisms. A similar arrangement may occur for corticotropin-releasing factor and adrenocorticotropic hormone (hypothalamic-pituitary-adrenal axis mediation), insulin (blood glucose regulation), and angiotensin II (cardiovascular regulation). Endorphins, enkephalins, and dynorphins have an initial amino acid sequence of Tyr-Gly-Gly-Phe, where tyrosine (and possibly phenylalanine) could be enzymatically clipped from the peptide and converted to catecholamines locally, through the canonical biosynthetic molecular pathway for catecholamines. Spatially and possibly temporally precise conversion of these terminal amino acids to catecholamines may allow them to be produced “on demand” in specific regions of the brain, spinal cord, or periphery. This hypothesis is readily testable by infusing stable isotopically labeled opioids into the brain or periphery of model organisms, and observing through liquid chromatography-mass spectrometry whether the terminal amino acids of these opioids are converted to catecholamines.

Sarcopenia is associated with the prognosis of patients with liver cirrhosis and hepatocellular carcinoma (HCC). Given their diverse physiological activities, we hypothesized that plasma fatty acids might influence the progression of sarcopenia. This study aimed to clarify the association between fatty acids and sarcopenia in cirrhotic patients with HCC.

In this single-center retrospective study, we registered 516 cases and analyzed 414 cases of liver cirrhosis and HCC. The skeletal muscle mass index was measured using a transverse computed tomography scan image at the third lumbar vertebra. The cutoff value for sarcopenia followed the criteria set by the Japan Society of Hepatology. Fatty acid concentrations were measured by gas chromatography.

Fatty acid levels, particularly omega-3 (n-3) polyunsaturated fatty acid (PUFA), were lower in patients with poor liver function (Child-Pugh grade B/C) and were negatively correlated with the albumin-bilirubin score (p<0.0001). The prognosis of HCC patients with low PUFA levels was significantly worse. Among the different fatty acid fractions, only n-3 PUFAs significantly correlated with skeletal muscle mass index (p=0.0026). In the multivariate analysis, the n-3 PUFA level was an independent variable associated with sarcopenia (p=0.0006).

A low level of n-3 PUFAs was associated with sarcopenia in patients with liver cirrhosis and HCC.

Alcoholic liver disease (ALD) encompasses liver damage caused by chronic, excessive alcohol consumption. It manifests initially as marked hepatocellular steatosis and can progress to steatohepatitis, liver fibrosis, and cirrhosis. With China’s rapid economic growth, coupled with a complex social background and the influence of a deleterious wine culture, the number of patients with ALD in China has increased significantly; the disease has become a social and health problem that cannot be ignored. In this review, we briefly described the social factors affecting ALD in China and elaborated on differences between alcoholic and other liver diseases in terms of complications (e.g., cirrhosis, upper gastrointestinal bleeding, hepatic encephalopathy, hepatocellular carcinoma, addiction, and other extrahepatic diseases). We also emphasized that ALD was more dangerous and difficult to treat than other liver diseases due to its complications, and that precise and effective treatment measures were lacking. In addition, we considered new ideas and treatment methods that may be generated in the future.

Harm caused by crude oil spillage and its associated environmental toxicants manifests slowly. This study examined the impact of crude oil environmental toxicants on neonates’ thyroid and cognitive functions in crude oil-producing communities.

The case-control study comprised 55 crude oil-exposed expectant mothers and 33 non-crude oil-exposed expectant mothers as controls. Serum Benzo Pyrene Dihydrodiol Epoxide (BPDE), triiodothyronine (T3), thyroxine (T4), and thyroid stimulating hormone (TSH) were assayed in expectant mothers and neonates. Intelligence quotient and APGAR scores were determined in the children using Fagan’s test of infant intelligence.

Serum TSH (p < 0.05) and BPDE (p < 0.001) were higher, while T3 and T3/T4 ratio were significantly lower (p < 0.001) in exposed pregnant women compared to the control. Cord blood TSH and T3/T4 ratio were lower (p < 0.001) while T4 and BDPE were higher (p < 0.001) in prenatally exposed neonates than prenatally non-exposed infants. Serum TSH correlated with BDPE (R2 = 0.080, p < 0.036) and APGAR score (R2 = 0.341, p < 0.012), while T3 and T4 were not associated with BDPE and APGAR score. TSH correlated with T3 (R2 = 0.0.082, p < 0.05), T3 correlated with T4 (R2 = 0.111, p < 0.013) and TSH (R2 = 0.082, p < 0.05). Exactly 54.5% (30/55) of prenatally exposed neonates had a low intelligence quotient compared to 36.4% (12/33) in prenatally non-exposed neonates.

Crude oil and associated environmental pollutants might significantly affect the thyroid function. Environmental surveillance, biomonitoring and environmental cleanup are emphasized. Future research on the mechanisms of the observed toxicological effects on thyroid hormones and targeted protection of pregnant women and their offspring is suggested.

Following complete peripheral nerve injury, collateral sprouting (CS) by adjacent nerves causes concentric shrinkage of the insensate area. Such take-over of insensate territory is unknown in proximal lesions such as stroke, spinal cord injury, and cauda equina syndrome, as peripheral nerves supplying insensate territories still maintain continuity from the cell body in the dorsal root ganglion (DRG) to the skin innervation territory. This preserved distal continuity opposes territory take-over by the expansion of adjacent sensate territories; sectioning peripheral nerves in insensate territories distal to DRGs disconnects nerve cell bodies from their skin territory, thus facilitating sensate territory expansion of adjacent nerves. Similar motor system applications in paralyzed territories include lower motor neurone lesioning and fasciectomies, facilitating motor territory expansion of adjacent nerves through CS. A search for evidence of previous conception of these hypotheses was conducted in the literature, using a combination of relevant terms from three categories (proximal neuraxial lesions, nerve-muscle interventions, collateral sprouting); however, this yielded no pertinent results, suggesting that these concepts are novel. Observations from the literature on peripheral nerve injury indicate a sound scientific basis for these hypotheses. Therefore, the suggested “weeding” interventions are likely to succeed in minimizing neurological deficits and improving patients’ quality of life. Various interventions to expand sensory/motor territories are considered; these include nerve lesioning distal to DRGs and removing fascial barriers between innervated and paralyzed muscles. Experience from such interventions will help expand our understanding of the speed and extent of CS-mediated neurological recovery as well as brain’s plastic abilities in reorienting after such procedures.

Metabolic-associated fatty liver disease (MAFLD) may increase the risk of cardiovascular events. In this study, we assessed the predictive value of pentraxin 3 (PTX3) for severe fibrosis and carotid intima-media thickness (CIMT) in patients with MAFLD.

188 patients (114 with MAFLD, 74 with dual etiology MAFLD and chronic hepatitis C) were included. All participants underwent clinical history and examination, metabolic parameter assessment, serum level evaluation of PTX3, Fibrosis-4 index and nafld fibrosis score scores, abdominal ultrasound, and CIMT assessment.

The serum PTX3 was significantly elevated in patients with advanced fibrosis compared to those with mild/moderate fibrosis (1.8 vs 1.4, p = 0.006). The PTX3 level was independently associated with advanced fibrosis (odds ratio = 1.26, 95% confidence interval 1.008–1.040). In MAFLD patients, the PTX3 levels in patients with low fibrosis compared to those with advanced fibrosis were 1.4 (1–2.1) and 1.9 (1.3–3.8), respectively (p = 0.027). A significantly greater CIMT was noted in patients with elevated PTX3 levels (3.85 (3.42–4) vs 4.05 (3.7–4.67), p = 0.0001) compared to those with low PTX3 levels.

Serum PTX3 levels can accurately predict advanced fibrosis and CIMT in MAFLD patients. Thus, it could be useful for management and risk stratification.

Prostate cancer is virtually the most common type of cancer, leading to multiple complications within the male gender worldwide. However, prostatic complications have been increasing recently due to probable changes in lifestyles. Affected patients try every treatment technique to confront their cancer. Thus, radiation therapy has been demonstrated to be one of the most efficient lanes of long-term survivorship in men with malignant prostatic cancer. Although radiotherapy has the potential to seem irritating, due to the studies, metastasis-free survival, biochemical recurrence-free survival, and prostate cancer-specific survival have experienced a major increase in various cases of the disease. Subsequently, still, radiation therapy has revealed the superlative approach to avoiding the risk of cancer relapse and case mortalities. This manuscript would radically discuss novel approaches that could probably increase the lifespan and survivorship of patients owning to previous examinations.