Pyrrolizidine alkaloids (PAs), widely distributed in plants, are known to induce liver failure. Hepatic platelet accumulation has been reported during the progression of PA-induced liver injury (PA-ILI). This study aimed to investigate the mechanisms underlying platelet accumulation in PA-ILI.

Cases of PA-ILI, non-PA-ILI, and control subjects were collected from patients hospitalized at Zhongshan Hospital, Fudan University (Shanghai, China) between 2012 and 2019. A mouse model of PA-ILI was established using monocrotaline administration. Liver RNA sequencing was performed, and gene interactions were analyzed using the Search Tool for the Retrieval of Interacting Genes/Proteins online database. Low-molecular-weight heparin and recombinant a disintegrin and metalloproteinase with a thrombospondin type I motif member 13 (ADAMTS13) were applied. The necrotic liver area, hepatic platelet accumulation, and von Willebrand factor (VWF) deposition were examined using hematoxylin and eosin staining and immunofluorescence assay.

Hepatic platelet accumulation, necrotic area expansion, and increased VWF expression were observed in both PA-ILI patients and mice. The Search Tool for the Retrieval of Interacting Genes/Proteins database indicated that ADAMTS13 regulates VWF expression and was differentially expressed in the livers of PA-ILI mice. Plasma and hepatic ADAMTS13 levels were significantly downregulated in both PA-ILI patients and mice. Systemic administration of recombinant ADAMTS13 decreased hepatic platelet accumulation, downregulated VWF expression, and mitigated mouse hepatic necrosis.

Hepatic platelet accumulation in PA-ILI was confirmed in both patients and mice. Deficiency of ADAMTS13 plays a critical role in platelet accumulation in PA-ILI, suggesting that ADAMTS13 could be a potential therapeutic target for this condition.

The polymer’s slow hydrolysis facilitates the sustained release of the immunogen, stabilizing the antigen encapsulated within the microspheres. As a result, microspheres ranging from 40 µm to 70 µm in diameter can be formed. This innovative microsphere formulation allows for efficient uptake by macrophages and other antigen-presenting cells. This study aimed to use biocompatible polymethyl methacrylate microspheres for the controlled delivery of antigens.

The potency of various formulations containing encapsulated tetanus toxoid (TT) with polymethyl methacrylate polymer microspheres was assessed using the toxin neutralization and challenge methods. The neutralization test was conducted on pooled sera two weeks after the initial immunization and weekly for four weeks following the booster dose administration. Scanning electron micrographs of the microspheres revealed drug leaching from spherical granular matrices.

The injection site showed a higher distribution of smaller microparticles, resulting in depot release. The polymer coating’s thickness was significantly lower compared to the 25% polymer microspheres. Concentrations ranging from 0.00024 mL to 0.00030 mL caused significant tetanic paralysis. Two weeks after the initial immunization, the antigenic activity of TT was below the minimum threshold, possibly due to insufficient levels of antigenic TT within the system within seven days post-immunization. The polymethacrylate microsphere elicited a notable immune response, but only the polymer concentration of 25% w/v met the I.P. requirements; lower polymer concentrations were ineffective.

The polymer’s slow hydrolysis facilitates the sustained release of the immunogen, stabilizing the antigen encapsulated within microspheres. Consequently, microspheres ranging from 40 µm to 70 µm in diameter can be assembled. This innovative microsphere formulation allows for efficient uptake by macrophages and other antigen-presenting cells.

T lymphocytes play a pivotal role in resolving hepatitis B virus infection. This study aimed to investigate the dynamics of peripheral blood T lymphocyte subsets during peginterferon alpha (peg-IFN-α) therapy and their association with hepatitis B surface antigen (HBsAg) clearance in inactive HBsAg carriers (IHCs).

This prospective observational study enrolled 197 IHCs treated with peg-IFNα-2a/2b for 48 weeks and followed for 24 weeks (treatment group), and 221 IHCs who were regularly monitored for 72 weeks without treatment (IHC control group). Peripheral blood T lymphocyte subsets were evaluated using flow cytometry at baseline, and at 12, 24, 48, and 72 weeks in both groups. At 72 weeks, IHCs in the treatment group were categorized into an HBsAg clearance group and an HBsAg persistence group. Differences in T lymphocyte subsets among these groups were compared, and correlations between T lymphocyte subsets and HBsAg clearance were analyzed.

At 72 weeks, intention-to-treat analysis showed significantly higher HBsAg clearance (46.7%) and seroconversion rates (34.5%) in the treatment group compared to the IHC control group (HBsAg clearance rate of 1.4%, seroconversion rate of 0.9%; both p < 0.001). The median absolute counts of CD3+, CD4+, and CD8+ cells significantly decreased at 12, 24, and 48 weeks in both the HBsAg clearance and persistence groups, returning to baseline at 72 weeks (all p < 0.001). IHCs with HBsAg clearance had higher median percentages of CD3+ CD8+ cells and lower median percentages of CD3+ CD4+ cells and CD4+/CD8+ ratios at 12, 24, and 48 weeks compared to the HBsAg persistence and IHC control groups (all p < 0.001). Baseline HBsAg levels (below 2.0 log10 IU/mL) and hepatitis B virus DNA levels (below 20 IU/mL), alanine aminotransferase elevation at 12 weeks (greater than 2×upper limit of normal), and CD4+/CD8+ ratios (less than 1.5 at 12 weeks and below 1.4 at 24 weeks) were predictive of HBsAg clearance.

Peripheral blood CD4+/CD8+ ratios at 12 and 24 weeks may serve as predictive markers for HBsAg clearance in IHCs treated with peg-IFN-α.

The performance of neurodegenerative biomarkers—neurofilament light chain (NfL), glial fibrillary acidic protein (GFAP), tau, and ubiquitin carboxy-terminal hydrolase L1 (UCHL1)—in diagnosing minimal hepatic encephalopathy (MHE) has not been systematically evaluated, simultaneously, nor have their associations with the development of overt hepatic encephalopathy (OHE). This study aimed to evaluate the performance of plasma NfL, GFAP, tau, and UCHL1 in diagnosing MHE and predicting the development of OHE in Chinese patients with hepatic cirrhosis.

In this prospective study, 124 patients with hepatic cirrhosis were recruited. The Psychometric Hepatic Encephalopathy Score was used to diagnose MHE, and OHE development was observed during a 30-day follow-up period. Plasma levels of NfL, GFAP, tau, and UCHL1 were measured using the highly sensitive single-molecule array when MHE was diagnosed. Additionally, serum interleukin-6 (IL-6) levels and the model for end-stage liver disease (MELD) and MELD-Na scores were also measured.

MHE was diagnosed in 57 (46.0%) patients. Patients with MHE had significantly higher plasma levels of NfL and GFAP (34.2 vs. 22.4 pg/mL and 173 vs. 97.6 pg/mL, respectively; both p < 0.001) and lower tau levels (8.4 vs. 11.6 pg/mL, p = 0.048) compared to those without MHE. Plasma NfL (odds ratios = 1.027, 95% confidence interval [CI]: 1.006–1.048; p = 0.013) and serum ammonia levels (odds ratios = 1.021, 95% CI: 1.006–1.036; p = 0.007) were independently associated with MHE occurrence. A combination of NfL, GFAP, tau, and UCHL1 was effective in diagnosing MHE in all cirrhotic patients (area under the receiver operating characteristic curve [hereinafter referred to as AUROC]: 0.748, 95% CI: 0.662–0.821), with an accuracy, sensitivity, and specificity of 71.0%, 71.9%, and 71.6%, respectively. In patients without previous OHE, the combination had an AUROC of 0.764 (95% CI: 0.673–0.840), with an accuracy, sensitivity, and specificity of 72.5%, 71.7%, and 73.0%, respectively. Furthermore, GFAP (hazard ratio (HR) = 1.003, 95% CI: 1.000–1.005; p = 0.044), IL-6 (HR = 1.003, 95% CI: 1.001–1.004; p < 0.001), and MELD score (HR = 1.139, 95% CI: 1.072–1.210; p < 0.001)—but not NfL, tau, and UCHL1—were identified as risk factors for 30-day OHE development.

The combination of plasma levels of NfL, GFAP, tau, and UCHL1 performs well in diagnosing MHE. Additionally, MELD score, IL-6, and GFAP appear to be significant predictors of OHE development in patients with hepatic cirrhosis.

Breast cancer is one of the leading causes of mortality among women worldwide. Tumor necrosis factor α-induced protein 3-interacting protein 1 (TNIP1) is a ubiquitin-binding protein that is widely expressed, but its function in breast cancer cells remains unknown. This study aimed to elucidate the molecular mechanism of TNIP1 regulation in the proliferation and apoptosis of breast cancer cells.

A colony formation assay was conducted on MCF-7 and T47D cells stably transfected with TNIP1/cyclin G1 (CCNG1) short hairpin RNAs. Quantitative polymerase chain reaction was performed to assess the relative abundances of TNIP1, CCNG1, and cyclin D1 (CCND1) messenger RNAs. Immunoprecipitation and immunoblotting were used to detect the expression of TNIP1, CCNG1, CCND1, and related proteins. A dual-luciferase reporter assay was employed to explore the molecular mechanism of TNIP1 in signal transduction. Caspase activity in MCF-7 and T47D cells transfected with TNIP1 short hairpin RNAs was measured using the Caspase-Glo 3/7 assay.

Ablation of TNIP1 induced growth arrest in breast cancer cells. TNIP1 directly interacted with CCNG1, and TNIP1 knockdown increased the ubiquitination of CCNG1. CCNG1 knockdown also induced growth arrest in MCF-7 and T47D cells. Furthermore, TNIP1 knockdown activated the NF-κB pathway and induced apoptosis in these cells.

TNIP1 regulates the proliferation and apoptosis of breast cancer cells, suggesting that TNIP1 may serve as a potential biomarker for breast cancer.

Atypical trigeminal neuralgia (ATN) is a chronic pain condition characterized by persistent facial pain that does not respond well to conventional medical treatments, often leading to significant impairment in quality of life. This study examined the clinical characteristics and surgical outcomes of microvascular decompression combined with nerve combing in patients with ATN.

We conducted a retrospective analysis of surgical techniques, clinical data, and treatment outcomes in 40 patients from January 2009 to January 2018. Pain levels and patient prognoses were assessed using the Visual Analog Scale and the Barrow Neurological Institute (BNI) pain score. Dynamic monitoring of arterial blood pressure was performed, and levels of total adrenaline, norepinephrine, and dopamine were measured before and during the nerve combing procedure.

During surgery, veins combined with arachnoid adhesions and arachnoid adhesions alone were observed compressing the trigeminal nerve in seven patients (17.50%) and 33 patients (82.50%), respectively. Immediate postoperative BNI scores indicated excellent outcomes (P = 2) in 30 patients (75.00%) and good outcomes (P = 3) in four patients (10.00%). Long-term postoperative BNI scores showed excellent outcomes (P = 2) in 25 patients (62.50%) and good outcomes (P = 3) in seven patients (17.50%). All patients experienced an increase in arterial blood pressure during nerve combing, and the mean levels of adrenaline and norepinephrine before combing showed significant improvement (P < 0.05).

Microvascular decompression combined with nerve combing achieves favorable results in treating ATN. Long-term trigeminal nerve compression and central sensitization may contribute to the etiology in these patients.

Gastrointestinal dysmotility commonly follows thermal injuries, such as burns. This study aimed to investigate the effects and mechanisms of electroacupuncture (EA) on burn-induced gastric dysmotility in rats.

Sprague-Dawley rats were divided into sham and thermal injury groups subjected to a 60% scald burn. Antagonists, including β-blockade (propranolol), α-blockade (phentolamine), or a selective cyclooxygenase (COX)-2 inhibitor (nimsulide), were administered to verify the pathways involved. Six hours after the burn, the animals were evaluated for gastric emptying and heart rate variability. Blood and gastric tissues were collected for assays of cytokines, hormones, and COX-2 levels. EA was performed at bilateral ST36 (Zusanli) acupoints for 45 m.

Burn injury delayed gastric emptying by 61% (P < 0.01), which was normalized by nimsulide or propranolol but not by phentolamine. EA improved gastric emptying by 87% (P = 0.03) in burned rats. Heart rate variability and plasma hormone (noradrenaline and pancreatic polypeptide) analyses indicated sympathetic hyperactivity in burned rats; EA improved burn-induced sympathovagal imbalance by enhancing vagal activity. Protein and mRNA expressions of COX-2 in the gastric fundus and antrum increased with burn but were normalized by propranolol. EA reduced the burn-induced increase in COX-2 expression in the gastric fundus but not in the antrum. EA also decreased burn-induced elevations in plasma interleukin (IL)-6 and IL-10. Negative correlations were found between gastric emptying and plasma IL-6 levels, as well as between gastric emptying and COX-2 mRNA levels.

These findings suggest that burn-induced gastric dysmotility is mediated via autonomic-COX-2 pathways. EA at acupoint ST36 improves burn-induced delays in gastric emptying by down-regulating COX-2 and pro-inflammatory cytokines through the autonomic nervous pathway.