Occlusive portal vein thrombosis (PVT) often causes portal hypertension-related complications in cirrhotic patients. Transjugular intrahepatic portosystemic shunt (TIPS) is an effective treatment for this difficult problem. However, the factors influencing TIPS success and overall survival in patients with occlusive PVT are unknown. This study investigated the factors influencing TIPS success and overall survival in cirrhotic patients with occlusive PVT.

Cirrhotic patients with occlusive PVT were selected from a prospective database of consecutive patients treated with TIPS in Xijing Hospital between January 2015 and May 2021. Baseline characteristics, TIPS success rate, complications, and survival were collected, and the factors associated with the TIPS success rate and transplant-free survival were analyzed.

A total of 155 cirrhotic patients with occlusive PVT were enrolled. TIPS succeeded in 126 (81.29%) cases. The 1-year survival rate was 74%. Compared with those without, patients with portal fibrotic cord had a lower TIPS success rate (39.02% vs. 96.49%, p<0.001), shorter median overall survival (300 vs. 1,730 days, p<0.001) and more operation-related complications (12.20% vs. 1.75%, p<0.01). Logistic regression analysis found that portal fibrotic cord (odds ratio 0.024) was a risk factor for TIPS failure. Univariate and multivariate analysis showed that portal fibrotic cord was an independent predictor of death (hazard ratio 2.111; 95% CI: 1.094–4.071, p=0.026).

Portal fibrotic cord increased the TIPS failure rate and is a risk factor for poor prognosis in cirrhotic patients.

The pathogenesis of portal hypertension remains unclear, and is believed to involve dysfunction of liver sinusoidal endothelial cells (LSEC), activation of hepatic stellate cells (HSC), dysregulation of endogenous hydrogen sulfide (H2S) synthesis, and hypoxia-induced angiogenic responses. H2S, a novel gas transmitter, plays an important role in various pathophysiological processes, especially in hepatic angiogenesis. Inhibition of endogenous H2S synthase by pharmaceutical agents or gene silencing may enhance the angiogenic response of endothelial cells. Hypoxia-inducible factor-1 (HIF-1) is the main transcription factor of hypoxia, which induces hepatic angiogenesis through up-regulation of vascular endothelial growth factor (VEGF) in HSC and LSEC. H2S has also been shown to be involved in the regulation of VEGF-mediated angiogenesis. Therefore, H2S and HIF-1 may be potential therapeutic targets for portal hypertension. The effects of H2S donors or prodrugs on the hemodynamics of portal hypertension and the mechanism of H2S-induced angiogenesis are promising areas for future research.

Essential oils (EOs) are natural products with bioactive functions that are obtained from various plant species, including Lavandula angustifolia and plant parts, through extraction methods, such as hydro-distillation, steam distillation and cold pressing, which can be dated back to ancient Egyptian and Greek times. Although various EOs are effective for disease treatment, such as human infectious diseases and mental disorders, the specific pharmacological mechanisms remain unclear due to its complex composition. Previous studies have attempted to recruit pharmaceutical analysis techniques, such as HPLC and MALDI-TOF, in order to elucidate the compositions of EOs. However, these have provided limited information on the mechanism of the bioactive functions of EOs. In recent years, network pharmacology has emerged as a convenient and appropriate approach to study the molecular mechanism of traditional medicines. To date, there is a lack of updated reviews on the recent progress of network pharmacology in the field of interactions between EOs and human diseases. Therefore, the present study scrutinized recent and important literatures in the field of network pharmacology and EOs, aiming to provide a timely yet brief overview of EOs as a potential treatment for diseases via network pharmacology, and facilitating the application of EOs as a complementary medicine and therapy for human diseases.

Alzheimer’s disease (AD) is a common geriatric disease with a complex pathogenesis and challenging treatment options. Wuling capsule is a single herbal formula mainly composed of Xylaria nigripes powder, which has sedative and neuroprotective effects on the central nervous system. This study aimed to explore various potential pathways and targets of Wuling capsules for the treatment of AD.

The anti-AD mechanism of Wuling capsule was systematically analyzed by integrating multiple databases and using network pharmacology. The active ingredients of Wuling capsules were screened through the Pubchem website, the SwissADME database, and a literature search. The related targets of AD were then screened in the GeneCards database. Using Cytoscape software and STRING, the disease-drug-target interaction network and the protein-protein interaction network were visualized, and topological analysis revealed the differences in the effects of different types of compounds.

Fifty-four compounds and 284 targets were screened by network pharmacology. The main active ingredients included quercetin, xylaric acid A-D, lysine, gamma-aminobutyric acid, glutamic acid, other amino acids, trace elements, guanosine, adenosine, etc. The targets in the network cover inflammation, oxidative stress, modulation of chemical synaptic transmission, and other related proteins, including protein kinase B, tumor necrosis factor-alpha, and tumor suppressor p53. The enrichment analysis results showed that these pathways include the phosphoinositide-3-kinase/protein kinase B, mitogen-activated protein kinase, and tumor necrosis factor-alpha signaling pathways. We also explored five potential protein functional modules.

This study revealed the multi-target and multi-pathway effects of the drug-ingredient-target-disease network through network pharmacology. This systematic screening strategy provides a new concept and theoretical basis for the treatment of AD with Wuling capsules.

The quantity of Gleason pattern (GP) 4 in Grade Group 2 prostate cancer (PCa) is an important prognostic factor and may influence treatment decisions. To be impactful for patient prognosis and management, GP4 quantification must be done in a uniform and reproducible way. This study aimed to investigate the interobserver reproducibility of GP4 quantification, and whether it may be affected by any histological features, including GP4 sub-patterns and tumor size.

Glass slides containing 55 biopsy cores of various amounts of GP4 were distributed to 12 pathologists who quantified GP4 and determined the most common GP4 sub-patterns (poorly formed glands [P], fused glands [F], cribriform [C], and glomeruloid [G]) in each core.

The interobserver reproducibility for 12 pathologists to quantify GP4 in 55 biopsy cores was moderate (κ = 0.57). The κ values for cores with a PCa length ≤2 mm, 2.1–5 mm, and >5 mm were 0.51, 0.50, and 0.66, respectively. The κ values for cores with the most common sub-pattern (P, F, [C and G], no consensus) were 0.43. 0.57, 0.74, and 0.57, respectively. When the consensus of the percentages of GP4 were 41–50% and 51–60%, 35% and 41.7% of the individual measurements, respectively, were significantly different from the consensus values.

The reproducibility of quantifying GP4 PCa is moderate and significantly lower for small-sized cancer with a predominant P pattern. There is significant variability in quantifying GP4 when it is 40–60%. These findings highlight the significant limitations of GP4 quantification that pathologists and clinicians must be aware of, and argue for more training for pathologists and standardization of methodology to improve the GP4 quantification.

Nonalcoholic fatty liver disease (NAFLD) is the most common liver disease worldwide, with an estimated prevalence of 25% globally. NAFLD is closely associated with metabolic syndrome, which are both becoming increasingly more common with increasing rates of insulin resistance, dyslipidemia, and hypertension. Although NAFLD is strongly associated with obesity, lean or nonobese NAFLD is a relatively new phenotype and occurs in patients without increased waist circumference and with or without visceral fat. Currently, there is limited literature comparing and illustrating the differences between lean/nonobese and obese NAFLD patients with regard to risk factors, pathophysiology, and clinical outcomes. In this review, we aim to define and further delineate different phenotypes of NAFLD and present a comprehensive review on the prevalence, incidence, risk factors, genetic predisposition, and pathophysiology. Furthermore, we discuss and compare the clinical outcomes, such as insulin resistance, dyslipidemia, hypertension, coronary artery disease, mortality, and progression to nonalcoholic steatohepatitis, among lean/nonobese and obese NAFLD patients. Finally, we summarize the most up to date current management of NAFLD, including lifestyle interventions, pharmacologic therapies, and surgical options.

The skin is a physical barrier that protects our body against various environmental, chemical and physical agents, and is the main organ that is easily visible as time progresses. Aging is a dynamic, progressive and undesirable biological process that unfortunately cannot be stopped, according to present knowledge. Intrinsic aging (chronological, spontaneous and biological aging) is a programmed natural process, while extrinsic aging (environmental aging and photoaging) is associated with sun exposure, smoking and malnutrition, which weakens the skin structure and functions. Over time, aging skin starts to lose elastin fibers, collagen and other proteins, which are the basic constituents that make skin healthy, bright, fit and elastic. There has been increasing interest in studies on various molecular and hormonal mechanisms, such as hormone dysfunction, changes in signaling pathways, the downregulation of mitochondrial function with cytokine increase, and mitochondrial DNA mutation. Antiaging treatment strategies can be divided into two parts: primary (basic) preventive antiaging approaches and secondary antiaging approaches after the phenotypic features of aging are revealed. The present study aims to review the literature information on the underlying causes of skin aging, healthy skin aging, and basic protective antiaging approaches. Understanding the extrinsic and intrinsic pathophysiological processes of aging would increase the effectiveness of future treatment-finding efforts.

Age-related macular degeneration (AMD) is difficult to treat and causes visual impairment worldwide, especially for dry AMD. The aging phenomenon can affect macular function, manifesting as blurred central vision. There are two types of AMD: dry and wet. By 2040, some variants of AMD are estimated to affect 288 million people globally. Although wet (exudative) AMD accounts for 10% of all AMD cases, it also contributes to 90% of the cases of patients with vision loss. Therapeutic options for wet age-related macular degeneration have expanded during the last few years. The therapeutic strategies mainly rely on anti-vascular endothelial growth factor (anti-VEGF) drugs and photodynamic therapy (PDT), though the treatment approaches for dry AMD are limited to dietary supplementation to delay progression. Moreover, clinical trials with potential candidate molecules for wet AMD exceed those for dry AMD. Although the disease is not rare, there are few therapeutic targets in the pipeline for dry AMD, and these targets may serve as promising pharmacotherapeutic options in the future. The current review sheds light on successes and failures of the existing novel drug molecules and potential targets for treating dry AMD in clinical trials registered at the Clinical Trials.gov registry run by the United States Food and Drug Administration (U.S. FDA) and published in relevant journals.

Primary biliary cholangitis (PBC) has been shown to occur more often in the West than in the East. The reason for this geographical disparity remains to be determined. Some researchers have considered that this was merely due to the lack of awareness on PBC in the East. Thus, the reported case and epidemiological studies on this disease remain scarce in the East. Other studies have suggested genetic predisposition and environmental factors proven to play important roles in the disease pathogenesis. In addition, these might also cause the disease to be more susceptible in some populations. The findings reported by multiple genome-wide association studies (GWAS) in recent years have not yet identified the specific genes responsible for the development of PBC, with different susceptible genes identified on each study in different regions. The present review describes some factors that might be associated with this geographical disparity.

Primary biliary cholangitis (PBC) is an organ-specific chronic autoimmune disease characterized by T-lymphocyte mediated destruction of intrahepatic biliary epithelial cells due to a combination of genetic and possible environmental factors. PBC progresses to hepatic fibrosis and cirrhosis, with the potential of developing hepatocellular carcinoma (HCC) if left untreated. PBC is more common in middle-aged women. It is diagnosed in patients with elevated liver enzymes and the serological hallmark of antimitochondrial antibody (AMA). Early diagnosis and treatment are crucial in improving survival and preventing long-term complications of liver disease. Ursodeoxycholic acid (UDCA) is first-line treatment for PBC. Obeticholic acid (OCA) and fibrates, in combination with UDCA or as monotherapy, may be given to PBC patients with partial or no UDCA response. Liver transplantation has thus been indicated in patients with decompensated cirrhosis or unresectable HCC.

In-stent restenosis (ISR) is a common complication after percutaneous coronary intervention. This study aimed to investigate the mechanisms of Radix Salviae in preventing ISR based on network pharmacology.

The bioactive compounds were searched from natural product databases. The related targets were collected from the databases and screened. The drug-compound-target-disease network was then constructed by Venny and Cytoscape software, and the intersection targets were further investigated in the STRING database. Functional enrichment analysis was performed in the DAVID database by conducting gene ontology and Kyoto Encyclopaedia of Genes and Genomes analyses. The software AutoDock Vina was used to conduct the molecular docking simulation.

A total of 33 bioactive compounds, including Luteolin, Tanshinone iia, and Dihydrotanshinlactone of Radix Salviae, were predicted with 53 targets as the compound-related targets in the ISR disease. Then the protein-protein interaction analysis discovered three key nodes, i.e., STAT3, JUN, and TP53. Moreover, functional enrichment of the gene ontology analysis demonstrated that the main biological processes included the response to the drug and regulation of the transcription from the RNA polymerase II promoter. The main molecular functions included protein binding, etc. The Kyoto Encyclopaedia of Genes and Genomes analysis revealed that the signaling pathways were mainly related to the PI3K-Akt signaling pathway, lipid-atherosclerosis signaling pathway, etc. Further investigation by molecular docking simulation between the ligands of the Radix Salviae compounds and target proteins revealed great probability binding activities between Luteolin-STAT3 (−7.4 kcal/mol), Tanshinone iia-TP53 (−7.2 kcal/mol), and Luteolin-TP53 (−6.2 kcal/mol).

This study indicated that the bioactive compounds like Tanshinone in Radix Salviae could modulate ISR via PI3K-Akt and lipid-atherosclerosis pathways, and the targets probably included STAT3, JUN, and TP53.

Congenital absence of the anterior cruciate ligament (ACL) is an extremely rare condition associated with a wide spectrum of malformation. Here we describe a rare complication in a patient with congenital absence of the ACL after ACL reconstruction using a bioabsorbable screw. A 35- year-old woman presented a right knee mass that had been slowly growing for several months. Five years previously, she experienced acute right knee pain, locking, and instability after hiking. Images and diagnostic arthroscopy at that time revealed an absence of the anterior cruciate ligament, a hypoplastic lateral distal femoral condyle, a stenotic intercondylar notch, and hypoplastic posterior cruciate ligament along with a bucket handle tear of the medial meniscus. A right anterior cruciate ligament reconstruction was performed, and she did well for the next five years without knee joint instability until she presented a mildly painful subcutaneous pretibial soft tissue mass. Imaging studies demonstrated a 2.4 cm subcutaneous lobulated soft tissue mass protruding from the expanded tibial tunnel. The mass was excised, and the histology showed a solid and cystic lesion composed of a histiocytic and foreign body giant cell reaction to the degraded polymer along with spheres of calcium phosphate particles. At a two-year follow-up after debridement, the patient reported an overall improvement without any knee instability or local recurrence. To the best of our knowledge, this is the first report of a pseudotumor developed after ACL reconstruction in a patient with a congenital absence of the ACL.

Despite its short length, the anal canal is an anatomically and histologically complex organ that can harbor many benign and malignant conditions. The trend for anal cancer has been on the rise, affecting predominantly women. In recent years, new concepts have emerged regarding anal tumor origin, pathogenesis, classification, and molecular characterization. Particularly, the role of human papillomavirus (HPV) has been increasingly recognized for its important role in anal carcinogenesis, not just for squamous lesions, but also for non-squamous neoplasia. Understanding different mechanisms of tumorigenesis are essential for proper tumor classification, which will allow more accurate diagnosis, proper clinical management, and optimal patient outcomes. This review aims to provide an overview of the normal anatomy, histogenesis, and pathogenesis of the anal canal, as well as to update on current knowledge of epithelial tumors associated with HPV.