Oral lichen planus (OLP) is a chronic inflammatory disease associated with oral microbiome imbalance and immune dysregulation. To evaluate the effects of CPC mouthwash combined with triamcinolone acetonide on oral microbiota and Th17/Treg balance in erosive OLP patients. This study involved 80 patients with erosive OLP from January 2023 to January 2025. They were divided into: A control group treated with triamcinolone acetonide and a combination group treated with triamcinolone acetonide plus cetylpyridinium chloride mouthwash. After 4 weeks, primary outcomes included clinical efficacy, visual analog scale (VAS) pain scores, changes in signs and erosive area, oral salivary bacteria detection rate, Th17/Treg ratio, serum adipokine chemerin and cytokine levels (IL-17, TNF-α, IL-10) and OHIP-14 scores. Secondary outcomes were adverse reaction incidence and recurrence rates during follow-up. The combination group showed better outcomes after 4 weeks of treatment. The total effective rate was 95%, higher than the control group's 80% (P=0.022). The combination group had superior pain relief (P=0.024), better mucosal repair (P=0.002) and a significant decrease in erosive area (P=0.021). It also had lower oral detection rates of Staphylococcus and Candida albicans (P<0.05). Immunologically, the combination therapy significantly reduced serum levels of chemerin, Th17 cells, Th17/Treg ratio, IL-17 and TNF-α (P<0.001), while increasing Treg cells and IL-10 levels (P=0.003), indicating stronger anti-inflammatory and immune-balancing effects. The combination group showed a greater reduction in the OHIP-14 score (P < 0.001), indicating improved oral health-related quality of life. No significant difference in adverse reactions was observed (P>0.05) and all were mild. The combination group had a lower recurrence rate within 3 months post-treatment, although the difference was not statistically significant (P=0.521). The combination of cetylpyridinium chloride mouthwash with triamcinolone acetonide effectively regulates the oral microbiota structure and restores the Th17/Treg immune balance in OLP patients.

Depression is a common mental disorder. Patients with treatment-resistant depression (TRD) often experience sleep disorders (SD), which interact with each other and aggravate the deterioration of the disease. In this study, we analyzed the effect of paroxetine combined with low-dose quetiapine on patients with treatment-resistant depression complicated by sleep disorders. We divided treatment-resistant depression + sleep disorders 120 patients into a control group treated with paroxetine and a research group treated with paroxetine + low-dose-quetiapine. Hamilton Depression Scale (HAMD-17), Self-rating Anxiety and Depression Scale (SAS/SDS), Pittsburgh Sleep Quality Index (PSQI) and serum indexes (cortisol, epinephrine, thyroid hormone, etc.) were used to analyze the data. In terms of clinical efficacy, the research group demonstrated superior efficacy. Besides, the research group showed lower self-rating anxiety/depression scale scores than the control group after treatment (P<0.05). In terms of sleep quality, the Pittsburgh Sleep Quality Index of the research group also decreased more significantly compared with the control group (P<0.05). Moreover, better stress injury alleviation and endocrine function improvement were determined in the research group (P<0.05). The two groups were not statistically different in treatment compliance and adverse reactions (P>0.05). Paroxetine combined with a low dose of quetiapine is a clinically effective approach for treatment-resistant depression with sleep disorders and is recommended for clinical use.

Hypercholesterolemia is a major modifiable risk factor for cardiovascular disease, largely driven by excessive activity of 3-hydroxy-3-methylglutaryl-CoA reductase (Hmgcr), the rate-limiting enzyme in cholesterol biosynthesis. Although statins are effective inhibitors of this enzyme, their long-term use is often limited by their adverse effects. This has encouraged the search for safer, plant-derived alternatives. Withania coagulans, a medicinal plant rich in withanolides, has demonstrated lipid-lowering potential; however, its molecular interactions with Hmgcr remain insufficiently explored. This study aimed to identify and characterize bioactive compounds from Withania coagulans as potential natural inhibitors of Hmgcr in Mus musculus, using an integrated in silico strategy. A validated three-dimensional model of Mus musculus Hmgcr was generated using homology modeling. Twenty bioactive compounds from Withania coagulans, along with standard statins, were screened using molecular docking and ADMET profiling, following Lipinski's rule of five. High-ranking complexes were further explored using MM/PBSA and MM/GBSA binding-free energy calculations. Molecular dynamics simulations (100 ns) were performed for top-ranked selected ligand-protein complexes to assess their structural stability and interaction persistence under physiologically relevant conditions. Several Withania coagulans compounds demonstrated strong binding affinities toward the Hmgcr active site, in some cases comparable to or exceeding those of standard statins. The key interactions involved conserved catalytic residues, such as Tyr516, Met533, Ile535, Ile761, Pro812 and Gln813. Molecular dynamics analyses revealed stable complexes with low RMSD fluctuations and minimal active site flexibility, confirming sustained ligand binding. ADMET predictions suggested favorable oral absorption and acceptable drug-like properties for the leading compounds. This study highlights Withania coagulans as a promising source of natural Hmgcr inhibitors. The identified compounds exhibited stable binding, favorable pharmacokinetic profiles, and mechanistic similarity to established statins, supporting their potential for further experimental validation as cholesterol-lowering agents.

Fufang Banmao Capsule (FBC) is clinically applied in the treatment of non-small cell lung cancer (NSCLC), yet its underlying pharmacological mechanism remains to be fully elucidated. This study aimed to systematically elucidate the pharmacological actions of FBC against NSCLC by integrating network pharmacology and Mendelian randomization approaches. Active components and potential targets of FBC were retrieved from the BATMAN-TCM database, while NSCLC-related therapeutic targets were collected from OMIM, TTD, and DisGeNet. Enrichment analysis and a "Herbs-Ingredients-Targets-Pathways" network were constructed. Core targets were further identified through protein-protein interaction and Mendelian randomization analyses, followed by colocaliza tion tests and molecular docking validation. A total of 152 potential FBC targets for NSCLC were identified, with seven candidates shortlisted. Among these, TNF and PIK3CA emerged as key protective targets (P<0.0025, OR<1). Colocalization analysis suggested possible shared genetic causality of TNF and PIK3CA single nucleotide polymorphisms with increased NSCLC risk. Molecular docking confirmed strong binding interactions between these targets and active FBC compounds such as resveratrol. The findings provide a theoretical foundation and new research directions for further investigation into the anti-NSCLC mechanism of FBC, supporting future innovation in therapeutic strategies.

Early identification of high-risk individuals is essential to guide infection-prevention strategies and optimize antibiotic stewardship in this vulnerable population. To identify independent risk factors associated with hospital-acquired infections in elderly ICU patients following antibiotic use and to develop and internally validate a clinical risk prediction model for early infection detection. A retrospective cohort study was conducted in the ICU of Nanjing First Hospital, Nanjing Medical University. A total of 120 patients aged ≥65 years, with ICU stay >48 hours, no documented infection at ICU admission and antibiotic exposure within 48 hours before or at ICU admission were included. Demographic data, comorbidities, Sequential Organ Failure Assessment (SOFA) scores, antibiotic exposure characteristics, invasive device use and nutritional support were collected from electronic health records. Hospital-acquired infections occurred in 46 patients (38.3%). Independent predictors included advanced age (odds ratio [OR] 1.08 per year), higher SOFA score (OR 1.25 per point), diabetes mellitus (OR 1.45), chronic kidney disease (OR 1.65), use of central venous catheters (OR 1.75), mechanical ventilation (OR 1.85), Foley catheterization (OR 1.55), broad-spectrum antibiotic use (OR 1.50), longer antibiotic duration (OR 1.20 per day) and prolonged ICU stay (all p<0.05). The prediction model demonstrated good discrimination (AUC-ROC = 0.82), which improved slightly after variable refinement (AUC-ROC = 0.83). Cross-validated performance remained robust (AUC = 0.80). A multivariable risk prediction model using routinely available clinical parameters demonstrated good internal validity and may assist clinicians in early identification of high-risk patients, enabling targeted infection prevention and improved antibiotic stewardship.

Tryptophan 2,3-dioxygenase (TDO) is a haem-containing enzyme of the kynurenine pathway, which is imperative for tryptophan metabolism. Primarily found in the liver, TDO facilitates the breakdown of TRP into N-formyl kynurenine. TDO is regarded as a promising target for antidepressant therapies. As an enzyme responsible for tryptophan degradation, its inhibition may enhance serotonin availability, which plays a key role in mood regulation. This study identifies TDO as a potential target for central nervous system drugs (acamprosate, roxindole, and L-ascorbic acid) that may alter brain activity and potentially impact mood and behavior. The study involved male Albino Wistar rats, each weighing between 150 and 200 grams. The rats were decapitated, the livers were promptly excised within 10 seconds, and perfused in situ with ice-cold saline. The perfused livers were then immediately frozen at -80°C for subsequent analysis. In vitro TDO enzyme activity was assessed in frozen liver homogenates. Enzymatic activity was measured for both the holoenzyme and total enzyme spectrophotometrically. Molecular docking of the selected compounds with TDO was conducted using AutoDock Vina. The crystal structure of TDO was retrieved from the Protein Data Bank (PDB), while ligand structures were obtained from PubChem. In vitro experiments revealed that these drugs inhibited apoenzyme activity by 68-85%, while total enzyme activity was reduced by 34%, 38% and 37% for acamprosate, roxindole, and L-ascorbic acid, respectively. Further validation through molecular docking analysis confirmed their strong binding affinity to the TDO active site, with l-ascorbic acid showing the highest binding energy (-7.2 kcal/mol), followed by acamprosate (-6.7 kcal/mol) and roxindole (-6.4 kcal/mol). These findings suggest that acamprosate, roxindole, and L-ascorbic acid act as competitive TDO inhibitors, potentially enhancing serotonin synthesis and mitigating depressive symptoms.

Solanum americanum, or American black nightshade, is a common weed in Pakistan with a rich history of medicinal applications. Traditionally, its leaves and fruits have been employed to treat various conditions, including skin problems, inflammation, and menstrual irregularities. The plant's therapeutic potential is attributed to its diverse phytochemical composition, encompassing alkaloids, glycosides, and flavonoids. Its traditional use highlights the reliance on folk knowledge for treating liver disease. This study aimed to investigate the pharmacognostic features and evaluate the hepatoprotective activity of the crude fruit extract of S. americanum against ethanol-induced liver toxicity in rats. An aqueous ethanolic extract of S. americanum fruit was administered to rats with ethanol-induced liver toxicity. Silymarin was used as a reference drug for comparison. Hepatoprotective activity was assessed through biochemical analysis of aspartate transaminase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), total bilirubin, and total protein levels. Histopathological examination of liver tissues was also conducted. The ethanol-treated group exhibited intense hepatocellular injuries and necrosis in liver tissues. Treatment with the aqueous ethanolic extract of S. americanum and silymarin resulted in near-normal lobular architecture, with only slight centrilobular degeneration of hepatocytes and minimal necrotic changes. The S. americanum extract demonstrated hepatoprotective activity, as evidenced by the partial normalization of liver biomarkers. However, its effect was less pronounced than that of silymarin. The aqueous ethanolic fruit extract of S. americanum possesses hepatoprotective properties against ethanol-induced liver toxicity in rats. S. americanum mitigates ethanol-induced liver toxicity in rats, partially normalizing liver biomarkers, likely through its antioxidant and nutritional properties, supporting its traditional use in liver disease management.

Acute pancreatitis (AP) is a common gastrointestinal emergency characterized by unpredictable severity. Early identification of patients at risk for severe disease is essential for timely intervention and improved outcomes, yet reliable prognostic markers remain limited, particularly in Central Asian clinical settings. To identify early clinical, laboratory, and demographic predictors of acute pancreatitis (AP) severity using statistical and machine learning approaches, to improve early risk stratification and guide prompt clinical management. This retrospective case series analysed 40 patients diagnosed with AP between 2022 and 2024 at tertiary hospitals in Bishkek, Kyrgyzstan. Admission data, including demographic characteristics, clinical symptoms, and laboratory values, were collected and evaluated using the revised Atlanta criteria. Statistical analyses included correlation testing, subgroup comparisons, and logistic regression, while a machine-learning-based feature importance analysis was used to identify key predictors of severe AP. Several variables were significantly associated with severe AP. Serum amylase >500 U/L (OR = 5.2, p 7lt; 0.001), WBC count >15×109/L (OR = 4.7, p <0.001), and BMI ≥30 (OR = 3.4, p = 0.003) emerged as strong predictors of severity. A strong correlation was observed between total bilirubin and jaundice (r = 0.62, p < 0.001). Obese patients had longer hospital stays compared with non-obese patients (median 12 vs. 7 days; p = 0.021). Machine learning analysis confirmed serum amylase, WBC count, and BMI as the most influential predictors. Serum amylase, WBC count and BMI are practical, easily accessible markers that can support early prediction of AP severity. Incorporating these indicators into initial assessment protocols may enhance risk stratification and optimize clinical decision-making. Prospective multicentre studies are needed to validate these findings and refine AP severity prediction models.

Elderly patients with severe pneumonia face elevated mortality from complex, often resistant, polymicrobial infections. This investigation aimed at assessing the efficacy and determinants of PTZ plus moxifloxacin for severe elderly pneumonia. Retrospectively, this study evaluated 120 elderly severe pneumonia patients (2021-2024), grouped by treatment: Control (n=60): IV piperacillin-tazobactam (PTZ), 4.5g q6h; observation (n=60): PTZ + daily moxifloxacin 400mg. Primary outcomes pathogen resistance/clearance; secondary: 30-day mortality, readmission, CURB-65, ventilation duration, serum biomarkers. Logistic regression identified mortality factors; adverse events were recorded. Baseline characteristics were comparable between groups (P>0.05). The observation group demonstrated superior primary outcomes (P<0.001) and pathogen clearance (P=0.013). No significant intergroup differences were found in secondary outcomes, including mortality, readmission, PLT and adverse events. Post-treatment CURB-65≥3, PCT and CRP significantly correlated with 30-day mortality (all P<0.001). The moxifloxacin-PTZ regimen enhanced microbial clearance without affecting survival, readmission, or adverse event rates, supporting its targeted clinical use.

Neuropathic pain (NP) is a debilitating condition with limited treatment options. The ethanolic extract of Bauhinia brachycarpa Benth (EEBb) has demonstrated antinociceptive effects in NP, but its active components and underlying mechanisms of action remain largely unexplored. Bauhinia brachycarpa Benth (BBB), an ethnic medicine in China, has antinociceptive effect on neuropathic pain (NP). In this study, an effective portion from BBB was screened and its antinociceptive mechanism was investigated. After the preparation of ethanolic extract from BBB (EEBb) and different soluble portion from EEBb (peEEBb, eaEEBb, nbEEBb), the total content of flavonoids and phenolic acids were measured. A partial sciatic nerve ligation (PSNL) model in vivo was applied to evaluate the antinociceptive effect and the influence on microglia function of these samples. The possible acting target of BBB was predicted by network pharmacology. And the mechanism of nbEEBb, the most effective antinociceptive portion, were studied by PSNL model in vivo and ATP-induced activation of BV2 model in vitro. nbEEBb had the strongest ability of alleviating NP as well as the obvious effect on microglia polarization. The action of nbEEBb was positively correlated to the total content of flavonoids or phenolic acids. nbEEBb inhibited the protein and gene expressions of most key components in P2X4-BDNF-TrkB signaling pathway. nbEEBb is the most effective portion from BBB on NP, and its mechanism refers to the inhibition of P2X4-BDNF-TrkB signaling pathway, which involved in neuron-microglia interaction.