3CL protease (3CLpro) of SARS-CoV-2 is a pivotal enzyme required in coronavirus replication and transcription. Its highly conserved structure and the absence of homologous proteins in the host make it an ideal target for broad-spectrum anti-coronavirus drug development. In this work, we systematically investigated and compared the binding modes and dynamic properties of the four stereoisomers of a pyridyl-urea diyne ester (PyDU) molecule with two chiral centers within the 3CLpro active site. Through molecular docking, MD simulations, MM/GBSA binding free-energy calculations, and DCCM analysis, all four stereoisomers were stabilized primarily by hydrophobic packing. Among them, the (R,S) isomer exhibited the best overall performance, including docking score, binding free-energy components, and key residue interactions. The (R,S) and (S,R) isomers also enhanced the cooperative motions around the binding pocket, while the (R,S) isomer further modulated the flexibility of domain III, which may influence 3CLpro dimerization. Conversely, the (S,S) isomer exhibited the weakest affinity due to insufficient hydrophobic contact. By innovatively integrating chirality, binding energy and protein dynamical features, we revealed the dual role of chirality in modulating affinity and dynamic responses, which provides a theoretical basis for the chiral-guided design of coronavirus inhibitors.

Cardiotoxicity induced by antineoplastic agents is an important factor affecting the prognosis of cancer patients. This article systematically summarizes the clinical manifestations of cardiotoxicity caused by chemotherapeutic drugs, molecular targeted cancer therapies, and immunotherapeutic drugs, and identifies the core injury mechanisms, including cardiomyocyte apoptosis, oxidative stress, and mitochondrial dysfunction. In Traditional Chinese Medicine (TCM) theory, anticancer drug-induced cardiotoxicity falls under the category of “heat toxins” characterized by dual deficiency of qi and blood, upward flaming of heart heat, stagnation of the heart vessels, and meridian obstruction induced by phlegm-dampness. Therefore, by reviewing the preventive and therapeutic effects and the underlying mechanisms of tonic medicines, interior heat-clearing medicines, blood-circulating and stasis-resolving medicines, phlegm-transforming, cough-suppressing and panting-relieving medicines, and interior-warming medicines, this paper concludes that TCM prevention and treatment of this condition adheres to the formulation principle of “reinforcing healthy qi, removing toxins, and resolving blood stasis”. Its mechanisms of action—including antioxidation effects, regulation of autophagic balance, antagonism of inflammatory responses, and improvement of microcirculation—are highly consistent with modern medical treatment strategies (e.g., dexrazoxane for inhibiting iron-dependent oxidative stress, statins for anti-inflammatory effects). This study provides theoretical support and practical guidance for the collaborative and precise prevention and treatment of anticancer drug-induced cardiotoxicity through the integration of traditional Chinese and Western medicine.

The sixth edition of the Korean Medication Algorithm Project for Depressive Disorder (KMAP-DD) was published in 2025. This review compared KMAP-DD 2025 with four major international clinical practice guidelines: Canadian Network for Mood and Anxiety Treatments Clinical Guidelines for the Management of Major Depressive Disorders, National Institute for Health and Care Excellence Depression Guideline, Royal Australian and New Zealand College of Psychiatrists Clinical Practice Guidelines for Mood Disorders, and British Association for Psychopharmacology Guideline. While KMAP-DD is based on expert consensus, and others on evidence-based methods, overall treatment strategies for depressive episodes were fairly consistent. Especially, KMAP-DD 2025 offers more structured recommendations in areas lacking strong evidence, such as premenstrual dysphoric disorder, perinatal depression, and depression with medical comorbidities. KMAP-DD 2025 also reflected Korean clinical practice patterns emphasizing rapid symptom relief and early use of combination strategies. Despite limitations as a consensus-based guideline, KMAP-DD 2025 complements evidence-based approaches and provides practical, situation-specific guidance for real-world clinical decision-making in Korea.

ObjectiveTo compare female C57BL/6J and BALB/c mice models of ulcerative colitis (UC) induced by dextran sulfate sodium salt (DSS), providing a reference for selecting female animal models in studies of innovative drugs for UC treatment. MethodsA total of 48 female mice aged 6–8 weeks, including 24 C57BL/6J and 24 BALB/c mice, were divided into four groups: control group, UC-3d group (2.5% DSS drinking for 3 days), UC-7d group (2.5% DSS drinking for 7 days), and UC-withdrawal group (2.5% DSS drinking for 7 days followed by 3 days of pure water replacement), with 6 mice in each group. Body weight, fecal occult blood, and stool characteristics were recorded daily, and disease activity index (DAI) scores were calculated. At the end of DSS induction, mice were gavaged with fluorescein isothiocyanate (FITC)-labeled dextran solution before tissue collection. Four hours later, under deep anesthesia induced by inhalation of 4% isoflurane, blood samples were collected from the retro-orbital venous plexus, and euthanasia was performed by cervical dislocation. The colon was then separated immediately, and its length from the anus to the ileocecal junction was measured. Colon tissues were fixed, embedded, and sectioned, and they were evaluated using hematoxylin-eosin (HE) staining and alcian blue-periodic acid-Schiff (AB-PAS) staining to comprehensively assess the degree of colonic inflammation. The spleen was also collected and weighed, and the spleen coefficient was calculated. Serum FITC fluorescence intensity and D-lactic acid concentration were measured to evaluate intestinal permeability and barrier injury. The grooming duration, the number of buried marbles, the time spent in the center of the open field, and the total distance traveled were measured to evaluate anxiety/depression-like behaviors in mice. ResultsFecal occult blood appeared in both C57BL/6J and BALB/c mice after 3 days of ad libitum access to DSS. Compared with the control group, there was no significant change in the weight loss rate of female BALB/c mice in the UC-7d and UC-withdrawal groups (P > 0.05), but the DAI score increased (P < 0.01). Conversely, both the weight loss rate and DAI score increased for female C57BL/6J mice in the UC-7d and UC-withdrawal groups (P < 0.01). In female C57BL/6J mice, both the UC-7d and UC-withdrawal groups had higher spleen coefficients than the control group (P < 0.05). Additionally, in these groups, colon length was significantly reduced (P < 0.01), FITC fluorescence intensity in serum was markedly increased (P < 0.01), obvious inflammatory reaction areas appeared in the colon, and the goblet cells and acidic mucus layer were damaged. In contrast, in female BALB/c mice, no significant differences were observed in colon length, serum FITC fluorescence intensity, or D-lactic acid concentration between the UC-7d and UC-withdrawal groups compared with the control group (P > 0.05). Only a few inflammatory cells and damaged goblet cells were observed in the colonic mucosal layer, and no other obvious pathological changes were detected. In addition, female C57BL/6J mice in the UC-7d group showed a significantly reduced total distance in the open field and fewer buried marbles (P < 0.05), indicating depression-like behavior, as well as prolonged grooming duration (P < 0.05), indicating anxiety-like behavior. ConclusionFemale BALB/c mice are not sensitive to 2.5% DSS and do not show typical colonic pathological changes of UC. In contrast, ad libitum access to 2.5% DSS for 7 days successfully induces typical UC pathological symptoms and colonic pathological changes in female C57BL/6J mice. These changes persist for 3 days after DSS withdrawal, and the mice also exhibit symptoms of anxiety/depression. The results suggest that this model can be used for research on the pathogenesis and therapeutic drugs of UC.

ObjectiveTo investigate the value of liver stiffness measurement （LSM） and spleen stiffness measurement （SSM） measured by two-dimensional shear wave elastography （2D-SWE） in the diagnosis of severe portal hypertension （SPH） and high-risk varices （HRV）， and to provide a basis for noninvasive assessment of portal hypertension. MethodsA prospective study was conducted among 78 patients with cirrhotic portal hypertension who were treated in Liver Research Center of Beijing Friendship Hospital， Capital Medical University， from December 2019 to April 2023. According to hepatic venous pressure gradient （HVPG）， the patients were divided into 6 mmHg≤HVPG<12 mmHg group， 12 mmHg≤HVPG<20 mmHg group， and HVPG ≥20 mmHg group. All patients underwent gastroscopy and 2D-SWE within 1 week after HVPG measurement， and SWE-LSM and SWE-SSM measured by 2D-SWE were recorded. A one-way analysis of variance or the Kruskal-Wallis H test was used for comparison of continuous data between multiple groups， and the chi-square test or the Fisher’s exact test was used for comparison of categorical data between groups. With HVPG and gastroscopy findings as the gold standard， the receiver operating characteristic （ROC） curve was plotted and the area under the ROC curve （AUC） was calculated to evaluate diagnostic performance， while the DeLong test was used for comparison of AUC. The Pearson or Spearman correlation analysis was used to investigate the correlation between variables， and the linear regression analysis and the Logistic regression analysis were used to investigate the influencing factors for HVPG and HRV. ResultsThe mean HVPG was 18.1±6.4 mmHg for the patients enrolled in this study， and HRV was observed in 62 patients （79.5%）. Both SWE-LSM and SWE-SSM were significantly positively correlated with HVPG （r=0.413 and 0.633， both P<0.001）， with an AUC of 0.812 and 0.902， respectively， in the diagnosis of HVPG≥12 mmHg and an AUC of 0.804 and 0.789， respectively， in the diagnosis of HVPG≥20 mmHg （all P>0.05）. The multivariate linear regression analysis showed that SWE-SSM was an independent influencing factor for HVPG （β=0.17， P<0.001）. In the diagnosis of HRV， only SWE-SSM showed a significant positive correlation with HRV （r=0.432， P<0.001）， with a better diagnostic performance than SWE-LSM in terms of AUC （0.808 vs 0.642， Z=2.775， P=0.006）. The multivariate Logistic regression analysis showed that platelet count was an independent influencing factor for HRV （odds ratio=0.97， P=0.014）. ConclusionSWE-SSM is closely correlated with both HVPG and HRV， showing a good performance in the diagnosis of SPH and HRV， and therefore， it is expected to become an effective noninvasive tool for assessing portal hypertension.

This article reports a rare case of autoinflammatory disease presenting initially with skin induration and swelling after trauma as the initial manifestation, followed by progressive limb weakness. The patient was a middle-aged female who developed skin induration and swelling after trauma, which gradually progressed to limb weakness, dysarthria and bilateral facial paralysis, accompanied by livedo reticularis of the lower extremities, diffuse skin induration of the limbs, and beaded subcutaneous nodules in the right upper limb. The patient had a susceptibility to infection since childhood and a history of chronic livedo reticularis. Skin pathological examination revealed panniculitis. A comprehensive etiological screening for special infections and autoimmune diseases was completed with an unremarkable results, and whole-exome sequencing showed no abnormal findings. Following a multidisciplinary discussion combined with RNA sequencing results, the patient was diagnosed with an autoinflammatory disease, with a suspected type Ⅰ interferonopathy. Treatment with tofacitinib resulted in gradual improvement of clinical symptoms. This case highlights the importance of detailed medical history collection, systematic physical examination and multidisciplinary collaborative diagnosis and treatment, and underscores the pivotal role of molecular diagnosis in the confirmation of rare diseases. It can provide a reference for the clinical diagnosis and management of similar rare cases.

ObjectiveHepatocellular carcinoma (HCC) represents 90% of all primary liver cancers. The main risk factors associated with HCC include viral hepatitis (B and/or C), alcohol abuse, and metabolic dysfunction-associated steatotic liver disease (MASLD), which progressively advance to liver fibrosis, cirrhosis, and ultimately evolve into HCC. Surgical resection represents the most effective treatment for HCC, while recent advances in immunotherapy, including immune checkpoint inhibitors and adoptive cell therapies, have provided improved treatment prospects for patients with unresectable HCC. However, the complex metabolic heterogeneity of HCC limits the therapeutic efficacy. Metabolic intermediates acyl-CoA not only provide energy and substrates for numerous biochemical reactions but also serve as donors for protein lysine acylation, a major class of post-translational modification (PTM). Therefore, a deeper understanding of the molecular mechanisms underlying protein lysine acylation and hepatocarcinogenesis is urgently needed. MethodsThe levels of protein lysine acylation and silence information regulator 5 (SIRT5) expression levels in clinical HCC samples were analyzed by Western blot. Quantitative malonylome and succinylome of HCC samples were analyzed by antibody-based affinity enrichment coupled with tandem mass spectrometry. The proliferation of HCC cells was analyzed with Cell Counting Kit-8 (CCK-8) assays, the apoptosis was quantified by Annexin V-FITC/propidium iodide (PI) staining coupled with flow cytometry, and the ability of cells to migrate was assayed by Transwell assays. The enzymatic activity of glutathione S-transferase Mu 1 (GSTM1) was quantified. Transgenic mice with hepatic overexpression of SIRT5 were constructed using CRISPR-Cas9, and primary hepatocarcinogenesis was induced by administration of diethylnitrosamine. ResultsWestern blot analysis indicated that the expression level of SIRT5 was elevated in clinical samples from HCC patients, and the levels of lysine malonylation, glutarylation, and succinylation were significantly reduced in HCC tissues. Knockout of SIRT5 in MHCC-97H and MHCC-97L hepatoma cells suppressed cell proliferation, and increased the percentage of apoptotic cells significantly. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses of the differentially malonylome and succinylome of HCC samples revealed significant enrichment in two major classes of biological processes: core energy metabolism (e.g., glycolysis/gluconeogenesis, tricarboxylic acid metabolic process, fatty acid beta oxidation) and detoxification and oxidative stress response (e.g., response to toxic substance, chemical carcinogenesis, reactive oxygen species (ROS)). SIRT5 removes malonylation from lysine residues in GSTM1 and restores its detoxification activity, which is crucial for the survival of hepatocytes under stressed conditions. More importantly, in vivo experiment indicated that hepatic-specific overexpression of SIRT5 in mice accelerated diethylnitrosamine-induced liver fibrosis and hepatocarcinogenesis, indicating the critical role of SIRT5 in HCC progression. ConclusionThis study highlights the previously unrecognized SIRT5-GSTM1 axis as a key regulator in hepatocarcinogenesis, and suggests a potential target for the treatment of patients with HCC.

Triclosan (TCS) and triclocarban (TCC) are widely used synthetic broad-spectrum antibacterial agents that can enter the human body through the skin, gastrointestinal tract, and other pathways. More and more studies have found that exposure to TCS and TCC can affect human health, but currently, review reports on the health effects of human exposure to TCS and TCC are limited. Therefore, this study reviewed population studies on the relationship between TCS and TCC exposure and health effects by searching the PubMed database, summarized the associated health outcomes, and elucidated the biological mechanisms. A total of 56 studies were retrieved, among which cross-sectional studies (25 studies, 44.64%) and cohort studies (25 studies, 44.64%) accounted for a relatively large proportion, while case-control studies (6 studies, 10.72%) were relatively few. Studies on TCS exposure (48 studies, 85.71%) were far more prevalent than those on TCC exposure (2 studies, 3.57%). The remaining 6 studies involved both TCS and TCC exposure. The research results revealed that TCS exposure was associated with male and female abnormal reproductive functions, fetal growth restriction, abnormal behavior development in children, obesity, gestational diabetes mellitus (GDM), and immune-related diseases. Although the results of different studies show significant differences, they have indicated that exposure to TCS is a potential risk factor for these health problems. Due to the limited number of studies, the evidence for the relationship between TCC exposure and most of the aforementioned health effects is insufficient. Population studies and in vitro and in vivo studies have shown that exposure to TCS and TCC can interfere with the microbial homeostasis, the endocrine system, oxidative stress and immune function of the body, which are potential mechanisms causing adverse health effects. In the future, large-scale prospective cohort studies, as well as in vivo and in vitro studies, are still needed to further clarify the associations between TCS and TCC exposure and health effects, and to deeply explore its mechanism of action. These efforts will provide references for clarifying the human health hazards of TCS and TCC exposure and formulating targeted prevention and control strategies.

OBJECTIVE To construct a dual-verification system integrating image pre-screening and Raman spectroscopy for inpatient pharmacy unit-dose dispensing in response to the issue of recognition blind spots for drugs of “same appearance but different spectrum” by drug inspection machines. METHODS An image feature and Raman spectroscopy database， covering 296 oral medications， were established. Spectral matching was performed using a cosine similarity algorithm （decision threshold 0.95）. A dual-verification system of “image pre-screening and Raman spectroscopy confirmation” was designed， and a self-controlled before-and-after study was conducted across 5 clinical wards. RESULTS The system achieved a mean recognition accuracy of 99.2% for all medications in the database， with 100% accurate identification of representative “same-appearance but different-spectrum” drugs. The average verification time per-unit in the experimental group （image recognition+Raman spectroscopy confirmation and verification） was reduced by 31.5%-43.3%， compared with the control group （image recognition+manual visual comparison with actual objects）（ P ＜0.001）. Nurses’ satisfaction scores in the dimensions of operational convenience， identification efficiency， verification confidence， and psychological stress relief in the experimental group were all significantly superior to those of the control group （ P ＜0.01）. CONCLUSIONS The dual-verification system of “image pre-screening and Raman spectroscopy confirmation” effectively overcomes the technical limitations of conventional machine vision. It enhances work efficiency and staff satisfaction while ensuring medication safety.

ObjectiveTo investigate the effects of salidroside （SAL） on the impaired bioactivity of endothelial progenitor cells （EPCs） in atherosclerotic （As） mice and the potential mechanisms regarding AMP-activated protein kinase （AMPK）. MethodsAtherosclerosis was induced in 8-week-old male ApoE^-/- mice with high-fat diet. Intragastric administration of SAL was given to one mice group to investigate the effects of SAL on aortic plaque burden， plasma NO level， the migration and angiogenic capabilities of bone marrow-derived EPCs （BM-EPCs）. The proliferation， migration and vasculogenic properties of EPCs isolated from As mice were investigated in vitro. AMPK-sh-RNA or the AMPK inhibitor Compound C was used to investigate the role of AMPK/Akt/eNOS pathway in the regulatory effects of SAL. ResultsCompared with As group， NO level was significantly elevated in SAL group. The sizes of atherosclerotic plaques at the aortic root were reduced with smaller lipid cores in SAL group compared with As group. Moreover， the migration and angiogenesis capacity of EPCs markedly decreased in As mice， while SAL treatment reversed these impairments. Incubation with SAL at concentrations of 20， 40， and 80 μmol/L for 48 hours significantly promoted the proliferation， migration， and angiogenesis of EPCs. AMPK-sh-RNA transfection abrogated the 20 μmol/L SAL improvement in EPC biological activities. Western blot analysis further demonstrated that treatment with Compound C blocked the activation of AMPK/Akt/eNOS signaling pathway induced by SAL. ConclusionSAL upregulates the biological functions of EPCs through activating the AMPK/Akt/eNOS signaling pathway， thereby ameliorating EPC dysfunction during the pathological progression of atherosclerosis.