The incidence of autoimmune liver diseases (ALDs) and research on their pathogenesis are increasing annually. However, except for autoimmune hepatitis, which responds well to immunosuppression, primary biliary cholangitis and primary sclerosing cholangitis are insensitive to immunosuppressive therapy. Besides the known effects of the environment, genetics, and immunity on ALDs, the heterogeneity of target cells provides new insights into their pathogenesis. This review started by exploring the heterogeneity in the development, structures, and functions of hepatocytes and epithelial cells of the small and large bile ducts. For example, cytokeratin (CK) 8 and CK18 are primarily expressed in hepatocytes, while CK7 and CK19 are primarily expressed in intrahepatic cholangiocytes. Additionally, emerging technologies of single-cell RNA sequencing and spatial transcriptomic are being applied to study ALDs. This review offered a new perspective on understanding the pathogenic mechanisms and potential treatment strategies for ALDs.

Acute-on-chronic liver failure (ACLF) is a distinct condition characterized by the abrupt exacerbation of pre-existing chronic liver disease, often leading to multi-organ failures and significant short-term mortalities. Bacterial infection is one of the most frequent triggers for ACLF and a common complication following its onset. The impact of bacterial infections on the clinical course and outcome of ACLF underscores their critical role in the pathogenesis of systemic inflammation and organ failures. In addition, the evolving epidemiology and increasing prevalence of multidrug-resistant bacteria in cirrhosis and ACLF highlight the importance of appropriate empirical antibiotic use, as well as accurate and prompt microbiological diagnosis. This review provided an update on recent advances in the epidemiology, diagnosis, pathogenesis, and management of bacterial infections in ACLF.

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.

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.

Cholestatic liver disease is a group of diseases in which bile acid accumulates in the liver for various reasons, resulting in abnormal liver biochemical indicators and histological damage. Cholestasis can be divided into intrahepatic cholestasis and extrahepatic cholestasis, which will contribute to liver damage and progress to liver fibrosis and cirrhosis. Primary biliary cholangitis (PBC) and primary sclerosing cholangitis are the two most typical cholestatic liver diseases. Ursodeoxycholic acid is currently the first-line treatment for PBC, while obeticholic acid, budesonide and fibrates have also shown good potential in the treatment of PBC. There are currently no official drugs approved to treat primary sclerosing cholangitis, and the use of ursodeoxycholic acid may have certain clinical benefits. At present, progress has been made in new treatment directions for cholestatic liver disease, including fibroblast growth factor 19, cholestyramine, S-adenosyl-L-methionine, steroid drugs, farnesoid X receptor agonists, and more. Considerable progress has been made in the management of cholestatic liver disease but there are still many opportunities and challenges. In this review, we summarized the recommended guidelines for the management of cholestatic disease and the progress of new drug research and development, in order to provide an important reference for the clinical practice of cholestatic liver disease.

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.

Malaria can be fatal during pregnancy, posing a serious risk to both mothers and fetuses, especially in sub-Saharan Africa. Primigravidae are particularly susceptible to placental malaria in areas with high rates of transmission due to insufficient immunity. This study aimed to determine the prevalence of placental malaria infection, risk factors, types of Plasmodium causing malaria during pregnancy, and its relationship with neonatal birth weight among primigravidae.

This was an analytical cross-sectional study involving 357 primigravidae who delivered at Abubakar Tafawa Balewa University Teaching Hospital, Bauchi, Nigeria. Placental blocks were taken from the pericentric area of the maternal surface of the placenta, and the birth weights of the neonates were recorded. The samples were fixed in 10% neutral-buffered formalin, and histopathological analysis was performed. The primary outcome measure was to determine the relationship between placental malaria and neonatal birth weight. Demographics and outcomes were analyzed using standard statistical tests. Multivariable regression models accounting for potential confounders were created for the primary and secondary outcomes with adjusted odds ratios as the measures of effect.

The prevalence of placental malaria was 38.4%. Among the participants with positive placenta malaria parasitemia, 49.6%, 36.5%, and 13.9% had chronic, acute, and past placental malaria infections, respectively. Only Plasmodium falciparum was found in the placenta. According to the bivariate analysis, unbooked status (p = 0.001), non-use of intermittent preventive therapy for malaria (p < 0.001), and village dwelling (p = 0.020) were significantly associated with placental malaria. However, on multivariable logistic regression, only non-uptake of intermittent preventive therapy for malaria was independently associated with placental malaria (adjusted odds ratio, 2.2, 95% confidence interval: 1.20, 4.1, p = 0.011). There was a significant difference in the mean birth weight between those with placental malaria and those without placental malaria (2.8 ± 0.5 kg vs. 3.2 ± 0.4 kg, p = 0.001). Additionally, placental malaria was significantly associated with low birth weight among the primigravidae (p < 0.001).

In Nigeria, there is a strong correlation between low birth weight and placental malaria in Primidravidae. Placental malaria was found to be independently correlated with non-uptake of intermittent preventive therapy for malaria.

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.

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.

This review highlighted the significant changes in the 2022 WHO classification of kidney epithelial tumors and the rationale behind these revisions. The updates included modifications to the classification of renal epithelial tumors, a greater emphasis on histopathological criteria, a structural reorganization of renal tumor categories, changes to established renal tumors, the creation of a new category for molecularly defined renal tumors, the introduction of an “other renal tumors” category, and the identification of novel, emerging, or provisional tumors and categories. These advancements reflect substantial progress in the diagnosis, classification, and prognostication of genitourinary system tumors, driven by key contributions from molecular studies and immunohistochemistry markers.