Objective: This study aimed to evaluate the prognostic value of [ 18F]ALF-NOTA-FAPI-04 PET/CT-derived parameters, including the maximum standardized uptake value (SUVmax), FAPI-avid tumor volume (FTV), and total lesion FAP expression (TLF), in patients with recurrent gastric cancer undergoing combined chemoimmunotherapy. We sought to establish a noninvasive imaging biomarker framework to optimize patient stratification and therapeutic decision-making. Materials and Methods: This retrospective cohort study analyzed 51 patients with recurrent gastric cancer who received programmed cell death protein 1 (PD-1) inhibitors combined with chemotherapy after gastrectomy. All patients underwent [ 18F]ALF-NOTA-FAPI-04 PET/CT within 14 days of chemoimmunotherapy. Semi-quantitative parameters (SUVmax, FTV, and TLF) were derived using semi-automated tumor segmentation. The primary endpoint of this study was the assessment of the clinical efficacy of chemoimmunotherapy, categorized as a durable or nondurable clinical benefit. The secondary endpoints included progression-free survival (PFS) and overall survival (OS). In a subgroup of 16 patients who underwent sequential [ 18F]FDG PET/CT within seven days of [ 18F]ALF-NOTA-FAPI-04 PET/CT, tracer uptake values were compared between the two PET/CT examinations. Results: 51 patients were included. The median PFS and OS were 7 and 10 months, respectively. Durable clinical benefit (DCB) was observed in 30 patients and showed significantly lower SUVmax, FTV, and TLF values than non-DCB. TLF demonstrated the highest diagnostic accuracy for DCB (area under the receiver operating characteristic curve [AUC] = 0.80). Multivariable analysis identified TLF ≥ 188.88 SUVbw·cm 3 as an independent factor associated with PFS (hazard ratio [HR] = 7.29, P = 0.001) and FTV ≥ 44.17 cm 3 as an independent factor associated with OS (HR = 5.16, P = 0.010). In the subgroup analysis of 16 patients, semi-quantitative analysis demonstrated consistently higher values of [ 18F]ALF-NOTA-FAPI-04-derived parameters than [ 18F]FDG-derived parameters (all P < 0.001). Conclusion [ 18F]ALF-NOTA-FAPI-04 PET/CT may be a useful imaging tool for predicting clinical outcomes in patients with recurrent gastric cancer undergoing treatment with PD-1 inhibitors and chemotherapy.

Body weight abnormalities, including overweight, obesity, and underweight, have become a dual public health challenge in Chinese adults: overweight and obesity lead to a variety of chronic complications, while underweight increases the risks of malnutrition, sarcopenia, and organ dysfunction. To systematically address these issues, multidisciplinary experts in endocrinology, sports science, nutrition, and psychiatry from various regions have held multiple weight management seminars. Based on the latest epidemiological data and clinical evidence, they expanded the guideline to include assessment and intervention strategies for underweight, in addition to the core content of obesity management. This guideline outlines the etiological mechanisms, evaluation methods, and multidimensional management strategies for overweight and obesity, covering key areas such as diagnosis and assessment, medical nutrition therapy, exercise prescription, pharmacological intervention, and psychological support. It is intended to provide a scientific and standardized approach to weight management across the adult population, aiming to curb the rising prevalence of obesity, mitigate complications associated with abnormal body weight, and improve nutritional status and overall quality of life.

PURPOSE: To compare the efficacy of continuous renal replacement therapy (CRRT) using either oXiris or conventional hemopurification filters in the treatment of intra-abdominal sepsis. METHODS: We conducted a retrospective analysis of septic patients with severe intra-abdominal infections admitted to our hospital from October 2019 to August 2023. Patients who meet the criteria for intra-abdominal sepsis based on medical history, symptoms, physical examination, and laboratory/imaging findings were included. EXCLUSION CRITERIA: pregnancy, terminal malignancy, prior CRRT before intensive care unit admission, pre-existing liver or renal failure. Heart rate (HR), mean arterial pressure, oxygenation index, lactic acid level (Lac), platelet count (PLT), neutrophil percentage, serum levels of procalcitonin, C-reactive protein, interleukin (IL)-6, norepinephrine dosage, acute physiology and chronic health evaluation II (APACHE II), and sequential organ failure assessment (SOFA) scores before and after 24 h and 72 h of treatment, as well as ventilator use time, hemopurification treatment time, intensive care unit and hospital lengths of stay, and 14-day and 28-day mortality were compared between patients receiving CRRT using either oXiris or conventional hemofiltration. Statistical analysis was performed using SPSS Statistics 26.0 software, including the construction of predictive models via logistic regression equations and repeated measures ANOVA. RESULTS: Baseline values including time to antibiotic administration, time to source control, and time to initiation of CRRT were similar between the 2 groups (all p>0.05). Patients receiving conventional CRRT exhibited significant changes in HR but of none of the other indexes at the 24 h and 72 h time points (p=0.041, p=0.026, respectively). The oXiris group showed significant improvements in HR, Lac, IL-6, and APACHE II score 24 h after treatment (p<0.05); after 72 h, all indexes were improved except PLT (all p<0.05). Intergroup comparison disclosed significant differences in HR, Lac, norepinephrine dose, APACHE II, SOFA, neutrophil percentage, and IL-6 after 24 h of treatment (p<0.05). Mean arterial pressure, serum levels of procalcitonin, C-reactive protein, SOFA score, and norepinephrine dosage were similar between the 2 groups at 24 h (p>0.05). Except for HR, oxygenation index, and PLT, post-treatment change rates of △ (%) were significantly greater in the oXiris group (p < 0.05). Duration of ventilator use, CRRT time, and intensive care unit and hospital lengths of stay were similar between the 2 groups (p>0.05). The 14-day mortality rates of the 2 groups were similar (p=0.091). After excluding patients whose CRRT was interrupted, 28-day mortality was significantly lower in the oXiris than in the conventional group (25.0% vs. 54.2%; p=0.050). The 28-day mortality rate increased by 9.6% for each additional hour required for source control and by 21.3% for each 1-point increase in APACHE II score. CONCLUSIONS In severe abdominal infections, the oXiris filter may have advantages over conventional CRRT, which may provide an alternative to clinical treatment. Meanwhile, early active infection source control may reduce the case mortality rate of patients with severe abdominal infections.
Humans ; Retrospective Studies ; Female ; Male ; Middle Aged ; Sepsis/mortality* ; Aged ; Adult ; Continuous Renal Replacement Therapy/methods* ; Intraabdominal Infections/mortality* ; APACHE ; Organ Dysfunction Scores ; Intensive Care Units ; Treatment Outcome

Periodontitis is a common oral disease characterized by progressive alveolar bone resorption and inflammation of the periodontal tissues. Dimethyl fumarate (DMF) has been used in the treatment of various immune-inflammatory diseases due to its excellent anti-inflammatory and antioxidant functions. Here, we investigated for the first time the therapeutic effect of DMF on periodontitis. In vivo studies showed that DMF significantly inhibited periodontal destruction, enhanced mitophagy, and decreased the M1/M2 macrophage ratio. In vitro studies showed that DMF inhibited macrophage polarization toward M1 macrophages and promoted polarization toward M2 macrophages, with improved mitochondrial function, inhibited oxidative stress, and increased mitophagy in RAW 264.7 cells. Furthermore, DMF increased intracellular mitochondrial Tu translation elongation factor (TUFM) levels to maintain mitochondrial homeostasis, promoted mitophagy, and modulated macrophage polarization, whereas TUFM knockdown decreased the protective effect of DMF. Finally, mechanistic studies showed that DMF increased intracellular TUFM levels by protecting TUFM from degradation via the ubiquitin-proteasomal degradation pathway. Our results demonstrate for the first time that DMF protects mitochondrial function and inhibits oxidative stress through TUFM-mediated mitophagy in macrophages, resulting in a shift in the balance of macrophage polarization, thereby attenuating periodontitis. Importantly, this study provides new insights into the prevention of periodontitis.
Dimethyl Fumarate/pharmacology* ; Mitophagy/drug effects* ; Animals ; Mice ; Macrophages/metabolism* ; Periodontitis/prevention & control* ; RAW 264.7 Cells ; Oxidative Stress/drug effects* ; Peptide Elongation Factor Tu/metabolism* ; Mice, Inbred C57BL ; Male ; Mitochondria/drug effects*

Cemental tear is a rare and indetectable condition unless obvious clinical signs present with the involvement of surrounding periodontal and periapical tissues. Due to its clinical manifestations similar to common dental issues, such as vertical root fracture, primary endodontic diseases, and periodontal diseases, as well as the low awareness of cemental tear for clinicians, misdiagnosis often occurs. The critical principle for cemental tear treatment is to remove torn fragments, and overlooking fragments leads to futile therapy, which could deteriorate the conditions of the affected teeth. Therefore, accurate diagnosis and subsequent appropriate interventions are vital for managing cemental tear. Novel diagnostic tools, including cone-beam computed tomography (CBCT), microscopes, and enamel matrix derivatives, have improved early detection and management, enhancing tooth retention. The implementation of standardized diagnostic criteria and treatment protocols, combined with improved clinical awareness among dental professionals, serves to mitigate risks of diagnostic errors and suboptimal therapeutic interventions. This expert consensus reviewed the epidemiology, pathogenesis, potential predisposing factors, clinical manifestations, diagnosis, differential diagnosis, treatment, and prognosis of cemental tear, aiming to provide a clinical guideline and facilitate clinicians to have a better understanding of cemental tear.
Humans ; Dental Cementum/injuries* ; Consensus ; Diagnosis, Differential ; Cone-Beam Computed Tomography ; Tooth Fractures/therapy*

Triple-negative breast cancer (TNBC) represents an aggressive breast cancer subtype with poor prognosis and limited targeted treatment options. This investigation examined the anti-cancer potential of Caerulomycin A (Cae A), a natural compound derived from marine actinomycetes, against TNBC. Cae A demonstrated selective inhibition of viability and proliferation in TNBC cell lines, including 4T1, MDA-MB-231, and MDA-MB-468, through apoptosis induction. Mechanistic analyses revealed that the compound induced sustained endoplasmic reticulum (ER) stress and subsequent upregulation of C/EBP homologous protein (CHOP) expression, resulting in mitochondrial damage-mediated apoptosis. Inhibition of ER stress or CHOP expression knockdown reversed mitochondrial damage and apoptosis, highlighting the essential role of ER stress and CHOP in Cae A's anti-tumor mechanism. Both oxygen consumption rate (OCR) and extracellular acidification rate (ECAR) decreased in TNBC cells following Cae A treatment, indicating reduced mitochondrial respiratory and glycolytic capacities. This diminished energy metabolism potentially triggers ER stress and subsequent apoptosis. Furthermore, Cae A exhibited significant anti-tumor effects in the 4T1 tumor model in vivo without apparent toxicity. The compound also effectively inhibited human TNBC organoid growth. These results indicate that Cae A may serve as a potential therapeutic agent for TNBC, with its efficacy likely mediated through the disruption of glucose metabolism and the induction of ER stress-associated apoptosis.
Humans ; Endoplasmic Reticulum Stress/drug effects* ; Triple Negative Breast Neoplasms/genetics* ; Apoptosis/drug effects* ; Cell Line, Tumor ; Female ; Animals ; Glucose/metabolism* ; Mice ; Cell Proliferation/drug effects* ; Transcription Factor CHOP/genetics* ; Antineoplastic Agents/pharmacology* ; Mitochondria/metabolism* ; Mice, Inbred BALB C

Objective: To investigate the awareness of knowledge about hepatitis C prevention and control among outpatients in Ningbo City, Zhejiang Province, and its influencing factors, so as to provide the evidence for strengthening health education on hepatitis C prevention and control. Methods: Based on sentinel surveillance of hepatitis C, the outpatients aged 15 to 65 years at seven hospitals in Yinzhou District, Cixi City and Xiangshan County of Ningbo City were selected using the convenient sampling method from April to June during 2020 and 2022. Demographic information, knowledge and behaviors related to hepatitis C prevention and control were collected through questionnaire surveys. The influencing factors for knowledge about hepatitis C prevention and control were analyzed using a multivariable logistic regression model. Results: A total of 2 792 participants were surveyed, including 1 157 males (41.44%) and 1 635 females (58.56%). The awareness rate of knowledge about hepatitis C prevention and control was 56.23%, and was lower in knowledge about hepatitis C vaccine and treatment. The awareness rates of knowledge about hepatitis C prevention and control among outpatients from 2020 to 2022 were 47.11%, 53.22% and 70.65%, respectively, showing an upward trend (P<0.05). Multivariable logistic regression analysis showed that participants aged 25 to <50 years (OR=1.358, 95%CI: 1.073-1.719), with an educational level of high school or junior college (OR=1.431, 95%CI: 1.134-1.806) or above junior college (OR=3.728, 95%CI: 2.958-4.699), with household monthly income per capita of 3 000 to <5 000 yuan (OR=1.828, 95%CI: 1.344-2.486) or ≥5 000 yuan (OR=1.858, 95%CI: 1.366-2.526), without a history of invasive treatments such as pedicure in public places (OR=1.287, 95%CI: 1.024-1.618), without a history of contact with family members' blood-contaminated items (OR=2.050, 95%CI: 1.552-2.707), and always using condoms during sexual contacts (OR=1.740, 95%CI: 1.273-2.378) had higher awareness of knowledge about hepatitis C prevention and control. Conclusions The awareness of knowledge about hepatitis C vaccine and treatment among outpatients in Ningbo City needs to be improved. Age, educational level, household monthly income per capita, history of invasive treatments such as pedicure in public places, history of contact with family members' blood-contaminated items and frequency of condom use during sexual contacts are associated with outpatients' awareness of knowledge about hepatitis C prevention and control.

OBJECTIVE To explore the molecular mechanism of Xijiao Dihuang Decoction(XJDHT)in inhibiting inflammatory response in sepsis based on network pharmacology,molecular docking and in vitro and in vivo experiments.METHODS Active com-ponents of XJDHT were screened using the TCMSP and HERB databases.Sepsis-related targets and histone H3K36 trimethylation(H3K36me3)-associated targets were retrieved from GeneCard,OMIM,and DisGeNet databases.A protein-protein interaction(PPI)network was constructed using the STRING database,and core targets were identified via Cytoscape 3.9.1.Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analyses were performed to predict potential mechanisms.Mo-lecular docking validated ligand-receptor binding affinity.A cecal ligation and puncture(CLP)model was established in mice to evalu-ate 24-hour sepsis scores(MSS)and survival rates.Blood routine parameters were analyzed using an automated hematology analyzer.Serum IL-1β and TNF-α levels were measured by ELISA.Liver histopathology was assessed via HE staining,and H3K36me3 expression in Kupffer cells was detected by immunofluorescence.In vitro,LPS-induced THP-1 cells were used as an in-flammatory model.ChIP-qPCR evaluated H3K36me3 enrichment at IL-1β and TNF-α gene loci.Western blot analyzed HIF-1α,EGFR,and AKT1 pathway proteins.RESULTS A total of 28 active components of XJDHT were identified,corresponding to 987 gene targets,with 189 overlapping sepsis-related targets.Core targets included TNF,IL1B,and GAPDH.Enriched pathways includ-ed EGFR tyrosine kinase inhibitor resistance.Molecular docking confirmed strong binding between core components and key targets.In vivo,compared to the sham group,the CLP group exhibited significantly reduced 24-hour survival(P<0.01),elevated MSS(P<0.01),immune imbalance,and increased serum IL-1β and TNF-α levels(P<0.01).High-and low-dose XJDHT intervention im-proved survival(P<0.01),reduced MSS(P<0.01),restored immune homeostasis,and dose-dependently suppressed IL-1β and TNF-α(P<0.01).CLP mice showed elevated H3K36me3 in Kupffer cells and severe hepatic inflammation,while XJDHT dose-de-pendently reduced H3K36me3(P<0.05)and attenuated liver injury.In peritoneal macrophages,CLP upregulated H3K36me3,IL-1β,TNF-α,HIF-1α,p-AKT1/AKT1,and EGFR(P<0.01),which were reversed by XJDHT(P<0.05,P<0.01).In vitro,LPS increased H3K36me3 and IL-1β and TNF-α expression(P<0.01),with ChIP-qPCR confirming H3K36me3 enrichment at IL-1β lo-ci(P<0.01).Treatment with 15%XJDHT-containing serum for 24 h reduced H3K36me3(P<0.01),diminished its recruitment to IL-1β loci(P<0.01),and inhibited LPS-induced activation of EGFR,HIF-1α,and p-AKT1/AKT1(P<0.05,P<0.01).HIF-1α agonist Dimethyloxallyl Glycine(DMOG)further validated that XJDHT suppressed H3K36me3-mediated epigenetic remodeling via HIF-1α-related pathways.CONCLUSION XJDHT inhibits inflammatory responses,regulates immune homeostasis,and improves sepsis prognosis,potentially by modulating H3K36me3 epigenetic modifications at IL-1β loci.

Objective:To investigate the clinical efficacy and major complications (postoperative hemorrhage and cerebral edema) of 3 surgical methods in spontaneous supratentorial intracerebral hemorrhage (SSICH).Methods:A retrospective analysis was performed; 294 patients with SSICH admitted to Department of Neurosurgery, Renmin Hospital of Wuhan University from December 2018 to October 2021 were selected. According to different surgical methods, these patients were divided into neuroendoscopic hematoma removal group ( n=126), stereotactic drilling and drainage group ( n=98), and craniotomy hematoma removal group ( n=70). The surgical efficacy and complications in the 3 groups were analyzed, and the postoperative residual hematoma and edema volumes were quantitatively calculated based on 3D Slicer software. Results:The hematoma evacuation rate in the neuroendoscopic hematoma removal group, stereotactic drilling and drainage group, and craniotomy hematoma removal group was 86.25%±2.27%, 44.45%±3.61%, and 75.45%±2.89%, respectively; Glasgow coma Scale scores at discharge were 13.51±1.28, 11.24±2.17 and 10.25±2.56, respectively; postoperative hemorrhage incidence was 16.1%, 26.0% and 22.9%, respectively; postoperative residual hematoma volume was (18.90±12.33) mL, (25.75±11.43) mL and (22.91±7.93) mL, and postoperative peak edema volume was (37.43±11.07) mL, (39.54±9.43) mL, and (42.26±10.94) mL, respectively; percentage of patients with peak edema on 3-5 days after surgery was 31.0%, 65.3% and 68.6%; the diameter of edema zone was (20.04±2.98) mm, (24.12±5.85) mm and (23.59±3.81) mm, respectively, on 7 days after surgery; percentage of patients with edema resolution was 45.2%, 24.5%, 42.9% and 76.2%, 57.1%, 62.9%, respectively, on 9-11 days and 12-14 days after surgery; these indexes in the neuroendoscopic hematoma removal group were significantly different compared with those in the other two groups ( P<0.05). Conclusion:Compared with stereotactic drilling and drainage or craniotomy hematoma removal, neuroendoscopic surgery can effectively remove the hematoma and reduce the occurrences of postoperative hemorrhage and brain edema.

OBJECTIVE To explore the molecular mechanism of Xijiao Dihuang Decoction(XJDHT)in inhibiting inflammatory response in sepsis based on network pharmacology,molecular docking and in vitro and in vivo experiments.METHODS Active com-ponents of XJDHT were screened using the TCMSP and HERB databases.Sepsis-related targets and histone H3K36 trimethylation(H3K36me3)-associated targets were retrieved from GeneCard,OMIM,and DisGeNet databases.A protein-protein interaction(PPI)network was constructed using the STRING database,and core targets were identified via Cytoscape 3.9.1.Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analyses were performed to predict potential mechanisms.Mo-lecular docking validated ligand-receptor binding affinity.A cecal ligation and puncture(CLP)model was established in mice to evalu-ate 24-hour sepsis scores(MSS)and survival rates.Blood routine parameters were analyzed using an automated hematology analyzer.Serum IL-1β and TNF-α levels were measured by ELISA.Liver histopathology was assessed via HE staining,and H3K36me3 expression in Kupffer cells was detected by immunofluorescence.In vitro,LPS-induced THP-1 cells were used as an in-flammatory model.ChIP-qPCR evaluated H3K36me3 enrichment at IL-1β and TNF-α gene loci.Western blot analyzed HIF-1α,EGFR,and AKT1 pathway proteins.RESULTS A total of 28 active components of XJDHT were identified,corresponding to 987 gene targets,with 189 overlapping sepsis-related targets.Core targets included TNF,IL1B,and GAPDH.Enriched pathways includ-ed EGFR tyrosine kinase inhibitor resistance.Molecular docking confirmed strong binding between core components and key targets.In vivo,compared to the sham group,the CLP group exhibited significantly reduced 24-hour survival(P<0.01),elevated MSS(P<0.01),immune imbalance,and increased serum IL-1β and TNF-α levels(P<0.01).High-and low-dose XJDHT intervention im-proved survival(P<0.01),reduced MSS(P<0.01),restored immune homeostasis,and dose-dependently suppressed IL-1β and TNF-α(P<0.01).CLP mice showed elevated H3K36me3 in Kupffer cells and severe hepatic inflammation,while XJDHT dose-de-pendently reduced H3K36me3(P<0.05)and attenuated liver injury.In peritoneal macrophages,CLP upregulated H3K36me3,IL-1β,TNF-α,HIF-1α,p-AKT1/AKT1,and EGFR(P<0.01),which were reversed by XJDHT(P<0.05,P<0.01).In vitro,LPS increased H3K36me3 and IL-1β and TNF-α expression(P<0.01),with ChIP-qPCR confirming H3K36me3 enrichment at IL-1β lo-ci(P<0.01).Treatment with 15%XJDHT-containing serum for 24 h reduced H3K36me3(P<0.01),diminished its recruitment to IL-1β loci(P<0.01),and inhibited LPS-induced activation of EGFR,HIF-1α,and p-AKT1/AKT1(P<0.05,P<0.01).HIF-1α agonist Dimethyloxallyl Glycine(DMOG)further validated that XJDHT suppressed H3K36me3-mediated epigenetic remodeling via HIF-1α-related pathways.CONCLUSION XJDHT inhibits inflammatory responses,regulates immune homeostasis,and improves sepsis prognosis,potentially by modulating H3K36me3 epigenetic modifications at IL-1β loci.