Objective: To investigate the protective effects of morusin on lipopolysaccharide (LPS)-induced acute liver injury in mice and its underlying mechanisms. Methods: Thirty-two male specific pathogen-free (SPF) C57BL/6J mice were randomly divided into four groups (n = 8 per group): control, LPS, low-dose morusin (morusin-L, 10 mg/kg), and high-dose morusin (morusin-H, 20 mg/kg) groups. The mice in each group were administered the corresponding drugs or normal saline via continuous gavage daily for 16 consecutive days. Except for control group, which received an equal volume of normal saline, other groups were intraperitoneally injected with LPS (5 mg/kg) 2 h after the last gavage to establish the acute liver injury model. Serum and liver tissues were collected for subsequent analysis 6 h after LPS injection. The activities of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) in serum were detected with biochemical methods. The levels of tumor necrosis factor (TNF)-α, interleukin (IL)-6, and IL-1β in serum were measured by enzyme-linked immunosorbent assay (ELISA). Hepatic pathological changes were evaluated by hematoxylin-eosin (HE) staining. The 16S ribosomal RNA (16S rRNA) sequencing was performed to assess the composition of intestinal flora, linear discriminant analysis effect size (LEfSe) was applied for multi-level species discrimination, and Spearman’s correlation analysis was performed. The liver tissues of mice with acute liver injury were analyzed by RNA sequencing (RNA-seq) technology to identify differentially expressed genes (DEGs), and then enrichment analysis of the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway was conducted. The expression levels of selected genes was validated by quantitative reverse transcription polymerase chain reaction (qRT-PCR), while immunohistochemistry (IHC) was performed to examine the expression levels of IL-6, myeloid differentiation primary response 88 (MYD88), and toll-like receptor 2 (TLR2). Results: Morusin significantly reduced the serum levels of ALT, AST, and inflammatory factors (TNF-α, IL-6, and IL-1β) (P < 0.05, P < 0.01, or P < 0.001), while alleviating the hepatic pathological damage in mice. Based on efficacy comparisons, morusin-H group was selected for subsequent microbiome and transcriptome analyses. Microbiome analysis revealed that morusin-H effectively mitigated LPS-induced gut dysbiosis and restored the Firmicutes/Bacteroidota balance (P < 0.01). At the genus level, morusin-H significantly reduced the abundances of norank_f_Muribaculaceae, Desulfovibrio, Parabacteroides, and Muribaculum (P < 0.05, P < 0.01, or P < 0.001). At the phylum, family, and genus levels, our findings indicated that morusin-H treatment caused a significant decrease in the abundance of Desulfobacterota, Desulfovibrionaceae, and Desulfovibrio (P < 0.01). Importantly, the abundance of Desulfovibrio was positively correlated with the levels of ALT, AST, TNF-α, IL-1β, and IL-6. Transcriptomic and molecular analyses showed that the therapeutic mechanism of morusin-H involved suppression of the IL-17/TNF signaling pathways and downregulating the mRNA levels of Tlr2, Tlr3, Myd88, Il6, and Cxcl10 (P < 0.05 or P < 0.001), as well as the protein levels of key inflammatory mediators (IL-6, MYD88, and TLR2) (P < 0.001). Conclusion Morusin demonstrates protective effects against LPS-induced acute liver injury, likely through modulation of gut microbiota and suppression of pro-inflammatory factor expression. These findings indicate that morusin exerts its effects through the "microbiota-inflammation-liver" axis, providing a theoretical basis for its use as a multi-target plant-based drug in the treatment of metabolic inflammation-related liver diseases.

Objective:To design and evaluate the application value of intracavitary-interstitial brachytherapy (IC-ISBT) applicator template for locally advanced cervical cancer.Methods:MRI data of 100 patients with ⅡB-ⅣA stage cervical cancer (International Federation of Gynecology and Obstetrics 2018 staging system) before and after external beam radiation therapy (EBRT) admitted to Sun Yat-sen University Cancer Center from March 2019 to September 2020 were collected. The range of primary cervical lesions was retrospectively analyzed and compared. Based on the residual mass of patients, the corresponding high-risk clinical target volume (HR-CTV) was delineated, and the IC-ISBT applicator template was designed and initially applied to cervical cancer patients. Dosimetry analysis and efficacy evaluation were compared between the applicator template-guided ( n=37) and free-hand implantation groups ( n=63). Chi-square test or Fisher exact test was performed for categorical variables, and t-test or U-test for continuous variables. Results:The median distance between the residual tumor margin (clockwise 3, 6, 9, 12 o'clock) and the center of 100 patients with ⅡB-ⅣA stage cervical cancer after EBRT was 16.5, 14.0, 17.0 and 13.0 mm, respectively. The corresponding HR-CTV was superimposed to reconstruct the three-dimensional diagram, and the cylindrical IC-ISBT applicator template with mushroom-like head was designed and manufactured: the longest and shortest diameter of the head was 35 and 20 mm, respectively; the central channel was adapted to the uterine tube, the C1-C12 channels was arranged in inner circle, and the peripheral B1-B5 and A1-A4 pin channels were expanded bilaterally. In terms of dose coverage, there was no significant difference between the HR-CTV D 90% [(635.12±22.65) vs. (635.80±25.84) cGy], bladder D 2 cm3 [(473.79±44.78) vs. (463.55±66.43) cGy)], rectum D 2 cm3 [(396.99±73.54) vs. (408.00±73.94) cGy] and sigmoid colon D 2 cm3 [(293.07±152.72) vs. (311.31±135.77) cGy] between the template-guided and free-hand implantation groups (all P>0.05), but the HR-CTV D 98% was significantly higher [(544.78±32.07) vs. (536.78±32.04) cGy, P=0.007] and the rectum D 1 cm3 and D 0.1 cm3 were significantly lower [(438.62±69.65) vs. (453.97±67.89) cGy, P=0.016; (519.46±70.67) vs. (543.82±81.24) cGy, P=0.001] in the template-guided implantation group. In addition, there was no significant difference in the complete response rate between two groups (86% vs. 83%, P>0.05). Conclusions:This IC-ISBT applicator template is reasonably designed, and the therapeutic efficacy of the template-guided implantation is equivalent to that of free-hand implantation. The dose coverage of the target area meets the clinical demand with a better protection of the organs at risk. The applicator template has the potential to be widely used as a conventional template in clinical practice as the applicator-guided implantation is convenient to operate and repeat.

OBJECTIVE To investigate the improvement effect and mechanism of different extracts from Tylophora yunnanensis on non-alcoholic steatohepatitis （NASH）. METHODS Normal human liver LO2 cells were induced to steatosis by free fatty acid， then were divided into normal group， model group， silybin group （100 μmol/mL）， T. yunnanensis ethanol extracts （TYS） group （50 μg/mL）， T. yunnanensis ethyl acetate extracts （TYSA） group （50 μg/mL）， and T. yunnanensis n-butanol extracts （TYSB） group （50 μg/mL）. After 24 hours of drug intervention， the deposition of lipid droplets was observed in LO2 cells in each group. The contents of total cholesterol （TC）， triacylglycerol （TG）， malondialdehyde （MDA） and glutathione （GSH）， the activities of aspartate transaminase （AST）， alanine transaminase （ALT） and superoxide dismutase （SOD）， the mRNA expressions of Kelch-like ECH-associated protein 1（ Keap1）， nuclear factor E2-related factor 2（ Nrf2） and heme oxygenase 1（ HO- 1） were detected. NASH rat model was induced by a high-fat diet， and then divided into normal group， model group， silybin group （12.6 mg/kg）， TYS group （80 mg/kg）， TYSA group （80 mg/kg） and TYSB group （80 mg/kg）， with six rats in each group. The liver indexes of rats in each group were calculated after 6 weeks of drug intervention. The liver histopathological changes were observed， and the contents of TC， TG， HDL-C and LDL-C， AST and ALT activities in serum， the contents of MDA and GSH， SOD activities in liver tissue were detected. RESULTS Compared with model group， TYS， TYSA and TYSB could reduce lipid droplet deposition， intracellular TC， TG and MDA contents， AST and ALT activities， and increase SOD activity， GSH content， and Keap1， Nrf2， HO-1 mRNA expression levels in LO2 cells after steatosis to varying degrees， with some differences being statistically significant （P＜0.05）. They also significantly improved liver injury in NASH model rats， reduced their liver indexes， TC， TG， LDL-C and MDA contents， AST and ALT 1-042） activities， and increased HDL-C （except for TYS and TYSB）， GSH contents and SOD activity， with TYSA having the most significant effect （P＜0.05）. CONCLUSIONS TYS， TYSA and TYSB have a certain improvement effect on NASH， among which TYSA has the most obvious effect. Its mechanism of action may be related to upregulating the Keap1/Nrf2/HO-1 signaling pathway and inhibiting oxidative stress

Objective: This study’s objective is to assess the efficacy and safety of Pulsed Magnetic Therapy System (PMTS) in improving insomnia disorder. Methods: Participants with insomnia disorder were randomly assigned to receive either PMTS or sham treatment for four weeks (n= 153; PMTS: 76, sham: 77). Primary outcomes are the Insomnia Severity Index (ISI) scores at week 0 (baseline), 1, 2, 3, 4 (treatment), and 5 (follow-up). Secondary outcomes are the Pittsburgh Sleep Quality Index at baseline and week 4, and weekly sleep diary-derived values for sleep latency, sleep efficiency, real sleep time, waking after sleep onset, and sleep duration. Results: The ISI scores of the PMTS group and the sham group were 7.13±0.50, 11.07±0.51 at week 4, respectively. There was a significant group×time interaction for ISI (F3.214, 485.271=24.25, p<0.001, ηp 2=0.138). Only the PMTS group experienced continuous improvement throughout the study; in contrast, the sham group only experienced a modest improvement after the first week of therapy. At the end of the treatment and one week after it, the response of the PMTS group were 69.7% (95% confidence interval [CI]: 58.6%–79.0%), 75.0% (95% CI: 64.1%–83.4%), respectively, which were higher than the response of the sham group (p<0.001). For each of the secondary outcomes, similar group×time interactions were discovered. The effects of the treatment persisted for at least a week. Conclusion PMTS is safe and effective in improving insomnia disorders.

Objective:To investigate the safety and efficacy of FOLFOX (5-fluorouracil + calcium folinate + oxaliplatin) hepatic arterial infusion chemotherapy (FOLFOX-HAIC) combined with immune and targeted therapy as triple combination therapy for patients with single China Liver Cancer Staging (CNLC) Ⅰb hepatocellular carcinoma.Methods:A total of 20 patients with single CNLC Ⅰb hepatocellular carcinoma who received FOLFOX-HAIC combined with immune and targeted therapy as triple combination therapy in the First Affiliated Hospital of Guangxi Medical University from October 2021 to August 2022 were included. The clinical data of all patients was retrospectively analyzed. There were 18 males and 2 females, with the age of (55.1±9.9) years. Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 and Modified Response Evaluation Criteria in Solid Tumors (mRECIST) were used to evaluate the efficacy of FOLFOX-HAIC combined with immune and targeted therapy, and the clinical safety of triple combination therapy was evaluated by common terminology criteria for adverse events 4.0.Results:According to RECIST 1.1, objective response rate of 20 patients was 70.0% (14/20) and disease control rate was 100.0% (20/20) after 2 cycles of treatment (one cycle of FOLFOX-HAIC plus programmed death-1 antibody). According to mRECIST, objective response rate was 90.0% (18/20) and the disease control rate was 100.0% (20/20) after 2 cycles of treatment. Following the treatment, 12 patients (60.0%) received liver tumor resection, and all of them achieved R 0 resection, 2 patients (10.0%) received radiotherapy, 3 patients (15.0%) stopped drug treatment for surgery, 2 patients (10.0%) refused surgery, and 1 patient (5.0%) died of multiple organ failure caused by immune hepatitis. According to pathological results, 3 patients (25.0%, 3/12) achieved pathological complete response, and 4 patients (33.3%, 4/12) achieved major pathological response. In the safety evaluation, the overall incidence of adverse events was 100.0% (20/20). Seven patients (35.0%) had grade 3 adverse events and 1 patient (5.0%) died of multiple organ failure due to immune hepatitis (grade 5). Grade 1-3 adverse events could be relieved after symptomatic treatment. Conclusion:The triple combination therapy of FOLFOX-HAIC combined with immune and targeted therapy is safe and has high objective response rate and disease control rate, which could be a new strategy for the neoadjuvant treatment of hepatocellular carcinoma.

The American College of Rheumatology (ACR) and the American Association of Hip and Knee Surgeons (AAHKS) convened a writing group to develop a consensus report on the management of anti-rheumatic medication in patients with rheumatic diseases undergoing elective total hip or total knee arthroplasty in June 2022. In particular, the consensus provides significant updates on target synthetic disease modifying anti-rheumatic drugs and perioperative medication management in patients with systemic lupus erythematosus, as well as the addition of newly approved antirheumatic medications for administration. This article will interpret the consensus and provide a reference for the perioperative management of antirheumatic medications for hip and knee arthroplasty in patients with rheumatic diseases in China.

Objective:To investigate the clinical characteristics of patients with rheumatic diseases and abnormal liver function, as well as determine the proportion and severity of liver function abnormalities.Methods:Cross-sectional study. Data were collected from patients registered in the Chinese Rheumatism Date Center from 2011 to 2021. The rheumatic diseases analyzed in this study were rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), Sjogren syndrome (SS), ankylosing spondylitis (AS), and gout. Patient data, including demographic characteristics [ such as age, sex, body mass index,(BMI), and smoking history], liver function test results [including alanine aminotransferase (ALT), aspartate aminotransferase, alkaline phosphatase(ALP), and total bilirubin], and use of anti-rheumatic immune drugs and liver-protective drugs, were collected and compared between groups with normal and abnormal liver functions. In addition, the proportions of abnormal liver function were compared between sex and age groups.Results:A total of 116 308 patients were included in this study, including 49 659 with RA, 17 597 with SLE, 9 039 with SS, 11 321 with AS, and 28 692 with gout. The lowest proportion of liver function abnormalities was observed in patients with RA[11.02% (5 470/49 659)], followed by those with SS[17.97% (1 624/9 039)] and AS [18.22% (2 063/11 321) ], whereas patients with SLE [21.14% (3 720/17 597) ] and gout [28.73% (8 242/28 692)] exhibited the highest proportion of these abnormalities. Elevated ALT, mostly classified as grade 1, was the most commonly noted liver function abnormality, whereas elevated ALP was the least common. Some patients who took liver-protective drugs had normal liver function, with the lowest percentage observed in patients with gout [7.45% (36/483) ] and ranging from 21.7% to 30.34% in patients with RA, SLE, SS, and AS. The proportion of liver function abnormalities was higher in males than in females for all disease types [RA: 13.8%(1 368/9 906) vs. 10.3%(4 102/39 753); SLE: 33.6% (479/1 424) vs. 20.0% (3 241/16 173); SS: 25.4%(111/437) vs. 17.6%(1 513/8 602); AS: 20.1%(1 629/8 119) vs. 13.6% (434/3 202); and gout: 29.3% (8 033/27 394) vs. 16.1% (209/1 298)]. In RA, SLE, and AS, the proportions of liver function abnormalities were similar across all age groups. In SS, the proportion of liver function abnormalities increased with age [<40 years: 14.9%(294/1 979); 40-59 years: 18.1%(858/4 741); ≥60 years: 20.4%(472/2 319)], whereas a reversal of this trend was observed in gout [<40 years: 34.9%(4 294/12 320); 40-59 years: 25.5%(2 905/11 398);≥60 years: 21.0%(1 042/4 971)].Conclusions:The proportions of combined liver function abnormalities in patients with rheumatologic diseases were high, and the utilization rates of liver-protective drugs were low. It is necessary to pay more attention to monitoring patients′ liver function, timely administer liver-protective drugs, and optimize liver-protective regimens during the treatment of rheumatic diseases.

Tooth transposition is a challenge for orthodontists, especially in correcting the order of teeth. At present, the literature on transposition canines mainly focuses on epidemiological studies and case reports, and no systematic treatment guidance has been formed. In this article, the definition and classification, epidemiology and etiology, imaging diagnosis, treatment and risk control of transposed canines are systematically described in order to provide reference for clinical practice.

Objective:To discuss the essentials of anesthesia management and treatment strategies for emergency transcatheter aortic valve replacement (TAVR), and to provide standardized recommendations for the development of emergency TAVR technology in China.Methods:This study retrospectively analyzed the relevant data of patients undergoing emergency TAVR surgery in the Second Affiliated Hospital of Zhejiang University School of Medicine from March 2019 to February 2021, including baseline patient characteristics, perioperative echocardiography data, prognosis and 30-day follow-up. Post-operative data were compared with pre-operative data using paired-sample test.Results:Thirteen patients, aged (75.62±9.63) years, underwent emergency TAVR surgery, and 6 of them were male. Eleven patients were New York Heart Association class Ⅳ. The preoperative Society of Thoracic Surgeons score was (20.31±15.15)%. The trans-aortic valve differential pressure was significantly reduced after surgery [(68.92±30.66)mmHg vs. (2.70±2.36)mmHg, P<0.01]. Two patients died within 30 days after surgery, one patient developed a new third degree atrioventricular block, one patient had a stroke, and 4 patients developed pulmonary infection. Conclusions:Emergency TAVR surgery is a feasible and effective rescue strategy for patients with aortic stenosis in critical condition. The establishment of anesthesia standard operation procedure process for TAVR surgery helps ensure homogenized medical behavior and good teamwork.

Tumor-targeted immunotherapy is a remarkable breakthrough, offering the inimitable advantage of specific tumoricidal effects with reduced immune-associated cytotoxicity. However, existing platforms suffer from low efficacy, inability to induce strong immunogenic cell death (ICD), and restrained capacity of transforming immune-deserted tumors into immune-cultivated ones. Here, an innovative platform, perfluorooctyl bromide (PFOB) nanoemulsions holding MnO₂ nanoparticles (MBP), was developed to orchestrate cancer immunotherapy, serving as a theranostic nanoagent for MRI/CT dual-modality imaging and advanced ICD. By simultaneously depleting the GSH and eliciting the ICD effect via high-intensity focused ultrasound (HIFU) therapy, the MBP nanomedicine can regulate the tumor immune microenvironment by inducing maturation of dendritic cells (DCs) and facilitating the activation of CD8⁺ and CD4⁺ T cells. The synergistic GSH depletion and HIFU ablation also amplify the inhibition of tumor growth and lung metastasis. Together, these findings inaugurate a new strategy of tumor-targeted immunotherapy, realizing a novel therapeutics paradigm with great clinical significance.