Based on the "regulating the pivot and unblocking the stomach" theory， this article proposes that the core pathogenesis of bile reflux gastritis （BRG） is disharmony of the three pivots and imbalance between the gallbladder and the stomach. Specifically， the pivot of zang-fu （脏腑） organs （spleen and stomach） exhibits abnormal ascending and descending functions， while the pivot of opening and closing （shaoyang） shows impaired flow， and the pivot of mind （heart and brain） has disordered regulation. These three pivots interact， ultimately leading to bile reflux attacking the stomach， injuring the gastric mucosa， and causing symptoms such as epigastric distension， pain， acid regurgitation， and heartburn. Clinically， the treatment principle is unblocking and regulating the three pivots， harmonizing the gallbladder and descending stomach qi， which closely follows the different pathomechanisms of three-pivot dysregulation， applying treatment according to syndrome differentiation. The regulation of the pivot of zang-fu organs focuses on fortifying the spleen and harmonzing stomach， raising the clear and directing the turbid downward. The regulation of the opening-and-closing pivot emphasizes harmonizing shaoyang， promoting gallbladder function and bowel movement. The regulation of the mind pivot centers on calming the heart and the mind， and harmonizing the stomach to ensure smooth qi flow. "Unblocking and regulating three pivots" method aims to restore the physiological functions of the gallbladder and stomach， providing a conceptual framework for the clinical management of BRG.

Purpose: This Phase II trial was objected to evaluate the efficacy and safety of adding fulvestrant to neoadjuvant chemotherapy in patients with estrogen receptor (ER)+/human epidermal growth factor receptor 2 (HER2)– locally advanced breast cancer (LABC). Additionally, the study aimed to investigate the association of 16α-18F-fluoro-17β-fluoroestradiol (18F-FES) positron emission tomography (PET)–computed tomography (CT) and metabolites with efficacy. Materials and Methods: Fulvestrant and EC-T regimen were given to ER+/HER2– LABC patients before surgery. At baseline, patients received 18F-FES PET-CT scan, and plasma samples were taken for liquid chromatography–mass spectrometry analysis. The primary endpoint was objective response rate (ORR). Secondary endpoints included total pathologic complete response (tpCR) and safety. Results: Among the 36 patients enrolled, the ORR was 86.1%, the tpCR rate was 8.3%. The incidence of grade ≥ 3 treatment-emergent adverse events was 22%. The decrease in ER value in sensitive patients was larger than that in non-sensitive patients, as was Ki-67 (p < 0.05). The maximum standardized uptake value, mean standardized uptake values, total lesion ER expression of 18F-FES PET-CT in sensitive patients were significantly higher than those in non-sensitive patients (p < 0.05). Moreover, these parameters were significantly correlated with Miller and Payne grade and the change in ER expression before and after treatment (p < 0.05). Thirteen differential expressed metabolites were identified, which were markedly enriched in 19 metabolic pathways. Conclusion This regimen demonstrated acceptable toxicity and encouraging antitumor efficacy. 18F-FES PET-CT might serve as a tool to predict the effectiveness of this therapy. Altered metabolites or metabolic pathways might be associated with treatment response.

BACKGROUND: Pancreatic cancer is a lethal malignancy prone to gemcitabine resistance. The single-strand selective monofunctional uracil DNA glycosylase (SMUG1), which is responsible for initiating base excision repair, has been reported to predict the outcomes of different cancer types. However, the function of SMUG1 in pancreatic cancer is still unclear. METHODS: Gene and protein expression of SMUG1 as well as survival outcomes were assessed by bioinformatic analysis and verified in a cohort from Fudan University Shanghai Cancer Center. Subsequently, the effect of SMUG1 on proliferation, cell cycle, and migration abilities of SMUG1 cells were detected in vitro . DNA damage repair, apoptosis, and gemcitabine resistance were also tested. RNA sequencing was performed to determine the differentially expressed genes and signaling pathways, followed by quantitative real-time polymerase chain reaction and Western blotting verification. The cancer-promoting effect of forkhead box Q1 (FOXQ1) and SMUG1 on the ubiquitylation of myelocytomatosis oncogene (c-Myc) was also evaluated. Finally, a xenograft model was established to verify the results. RESULTS: SMUG1 was highly expressed in pancreatic tumor tissues and cells, which also predicted a poor prognosis. Downregulation of SMUG1 inhibited the proliferation, G1 to S transition, migration, and DNA damage repair ability against gemcitabine in pancreatic cancer cells. SMUG1 exerted its function by binding with FOXQ1 to activate the Protein Kinase B (AKT)/p21 and p27 pathway. Moreover, SMUG1 also stabilized the c-Myc protein via AKT signaling in pancreatic cancer cells. CONCLUSIONS SMUG1 promotes proliferation, migration, gemcitabine resistance, and c-Myc protein stability in pancreatic cancer via protein kinase B signaling through binding with FOXQ1. Furthermore, SMUG1 may be a new potential prognostic and gemcitabine resistance predictor in pancreatic ductal adenocarcinoma.
Humans ; Pancreatic Neoplasms/pathology* ; Forkhead Transcription Factors/genetics* ; Signal Transduction/genetics* ; Animals ; Cell Line, Tumor ; Proto-Oncogene Proteins c-akt/metabolism* ; Cell Proliferation/physiology* ; Mice ; Uracil-DNA Glycosidase/genetics* ; Female ; Male ; Gemcitabine ; Mice, Nude ; Apoptosis/physiology* ; Deoxycytidine/analogs & derivatives* ; Cell Movement/genetics*

Objective:To analyze the epidemiological, etiological and genetic characteristics of influenza virus in Shandong Province during 2023-2024.Methods:The surveillance data of influenza-like illness (ILI) in sentinel hospitals in Shandong from 2023 to 2024 were collected and analyzed. The isolated influenza strains with hemagglutination titers ≥8 were selected for antigenicity analysis, drug susceptibility test, gene sequencing and evolutionary analysis.Results:From 2023 to 2024, the positive rate of influenza virus in Shandong was 8.51% (23 663/277 995), the highest positive rate was in the age group of 5-14 years (15.78%, 6 073/38 478), and the highest positive rate was in the 49 th week (35.86%, 2 264/6 313). Both antigenicity analysis and evolutionary analysis showed that the A(H1N1)pdm09 subtype and B(Victoria) strain had good matching effect and close evolutionary distance with the 2023-2024 surveillance year vaccine strain. The A(H3N2) subtype strain did not have a high matching effect with the 2023-2024 vaccine strain and had a long evolutionary distance, but had a close evolutionary distance with the 2024-2025 vaccine strain. Drug susceptibility test showed that oseltamivir sensitivity of influenza A(H1N1)pdm09 strain decreased greatly, and the amino acid site mutation of neuraminidase was H275Y. Conclusions:In the 2023-2024 surveillance year, the peak of influenza virus epidemic in Shandong was mainly occurred in winter and spring, and the age group of 5-14 years was the focus of prevention and control. The dominant strain was subtype A(H3N2), which had poor matching effect with the vaccine strain in the 2023-2024 surveillance year. One A(H1N1)pdm09 resistant strain was found in the drug resistance monitoring work. Follow-up prevention and control work should be strengthen the surveillance for the epidemiological characteristics, genetic variation and drug resistance of influenza viruses, timely understand the epidemic trend and mutation of influenza viruses, timely discover drug-resistant strains of influenza viruses, promote influenza vaccination, and improve of influenza prevention and control.

Objective:To analyze the respiratory virus infection status and epidemiological characteristics of influenza-like illness (ILI) cases in Shandong Province during the 2020 -2021 influenza surveillance year. Methods:According to the National Influenza Surveillance Plan (2017 version), throat swab samples of ILI cases were collected from 14 surveillance sentinel hospitals in Shandong Province. Nucleic acid was extracted from all samples. Real-time fluorescence quantitative PCR (RT-PCR) was utilized to detect six common viruses, including human metapneumovirus (HMPV), human parainfluenza virus (HPIV) types 1, 2 and 3, respiratory syncytial virus (RSV), and adenovirus (ADV). Subsequently, the obtained detection results were analyzed.Results:A total of 2 386 specimens were collected, with a detection rate of 24.22% (578). Six viruses were detected, with detection rates of 6.75% (162 cases) for HMPV, 5.87% (140 cases) for RSV, 3.56% (85 cases) for HPIV3, 3.14% (75 cases) for HPIV2, 2.98% (71 cases) for HPIV1, and 2.77% (66 cases) for ADV. There was no significant difference in detection rates between genders, but a notable variation among different age groups ( P<0.001). The highest detection rate was observed in individuals aged 0-4 years (31.94%), followed by those aged≥60 years (26.06%). The prevalence of six viruses showed a monthly variation, with the detection rate of HMPV being higher in December and HPIV1 being higher in February. HPIV2, HPIV3, RSV, and ADV had higher detection rates in November. The co-detection rate of multiple viruses was 0.80%, with RSV being the most common pathogen involved in co-detection, primarily in individuals aged 0-4 years. Conclusion:The detection of six multiple pathogens in ILI cases in Shandong Province is dominated by HMPV, RSV and HPIV3. The prevalence of respiratory viruses varies by age and time.

Purpose: This Phase II trial was objected to evaluate the efficacy and safety of adding fulvestrant to neoadjuvant chemotherapy in patients with estrogen receptor (ER)+/human epidermal growth factor receptor 2 (HER2)– locally advanced breast cancer (LABC). Additionally, the study aimed to investigate the association of 16α-18F-fluoro-17β-fluoroestradiol (18F-FES) positron emission tomography (PET)–computed tomography (CT) and metabolites with efficacy. Materials and Methods: Fulvestrant and EC-T regimen were given to ER+/HER2– LABC patients before surgery. At baseline, patients received 18F-FES PET-CT scan, and plasma samples were taken for liquid chromatography–mass spectrometry analysis. The primary endpoint was objective response rate (ORR). Secondary endpoints included total pathologic complete response (tpCR) and safety. Results: Among the 36 patients enrolled, the ORR was 86.1%, the tpCR rate was 8.3%. The incidence of grade ≥ 3 treatment-emergent adverse events was 22%. The decrease in ER value in sensitive patients was larger than that in non-sensitive patients, as was Ki-67 (p < 0.05). The maximum standardized uptake value, mean standardized uptake values, total lesion ER expression of 18F-FES PET-CT in sensitive patients were significantly higher than those in non-sensitive patients (p < 0.05). Moreover, these parameters were significantly correlated with Miller and Payne grade and the change in ER expression before and after treatment (p < 0.05). Thirteen differential expressed metabolites were identified, which were markedly enriched in 19 metabolic pathways. Conclusion This regimen demonstrated acceptable toxicity and encouraging antitumor efficacy. 18F-FES PET-CT might serve as a tool to predict the effectiveness of this therapy. Altered metabolites or metabolic pathways might be associated with treatment response.

Pancreatic cancer is a highly malignant tumor,and its incidence rate has been slowly increasing since 2000.Although the improvement of diagnosis and treatment has led to an increase in the five-year survival rate of pancreatic cancer compared to 50 years ago,it remains one of the discouraging tumor diseases regarding its prognosis.In 2024,many achievements were made in the research of early screening,disease mechanism,clinical diagnosis and treatment of pancreatic cancer,showing a good prospect for clinical application.In early screening,artificial intelligence(AI)technology has empowered early diagnosis and screening of pancreatic cancer,pushing clinical diagnosis and treatment to a new level.Additionally,improvements in the accuracy of technologies such as liquid biopsy have provided new directions for early screening of pancreatic cancer.In terms of research on disease pathogenesis,3D genome mapping technology has revealed the polyclonal origin and genetic heterogeneity of pancreatic intraepithelial neoplasm(PanIN).In basic research,a branched organ simulation system that mimics the unique structural characteristics of pancreatic cancer provides a new model for in vitro studies of pancreatic cancer.Lactate,an important tumor metabolite,links the metabolic microenvironment of pancreatic cancer with epigenetic changes,revealing potential therapeutic targets.Defects in the histone H3K36 trimethyltransferase SETD2 contribute to endogenous epigenetic dysregulation in pancreatic cancer and promote mitochondrial oxidative phosphorylation(OXPHOS)and tumor progression.The platelet-derived growth factor receptor(PDGFR)axis,which facilitates communication between stromal cells and cancer cells,forms a bidirectional secretory circuit and may become a new therapeutic target.Chimeric antigen receptor macrophage(CAR-M)therapy targeting the tyrosine kinase receptor c-MET demonstrates potential for synergistic enhancement with chemotherapy drugs.Macrophages in the pancreatic cancer microenvironment promote the development of pancreatic cancer cachexia through the CCL5/TRAF6/nuclear factor-κB(NF-κB)pathway,suggesting that macrophages could be an effective target for predicting and intervening in the development of pancreatic cancer cachexia.In terms of advancements in diagnosis and treatment,surgery following neoadjuvant chemotherapy can improve overall survival(OS)in resectable and borderline resectable patients,but further optimization of neoadjuvant chemotherapy protocols is needed.The first clinically effective KRASG12D-targeted drug has been reported,and research on inhibitors of a wide range of KRAS mutants is continually emerging.Patient stratification based on glycolysis-related scores(GRS)can further guide the selection of treatment protocols."Intelligent exosomes"(ExoSmart)enhance cellular uptake capacity to assist in improving chemotherapy efficacy.The implementation of clinical trials combining immunotherapy with chemotherapy is expected to synergistically improve the efficacy of pancreatic cancer treatment.Pembrolizumab and anlotinib combined with albumin-bound paclitaxel/gemcitabine(PAAG)have shown great efficacy and safety in first-line treatment of metastatic pancreatic cancer(mPC)patients.The cancer vaccine ELI-002 2P,which targets KRAS mutation-encoded neoantigens,can induce an antitumor immune response.Oncolytic adenovirus therapy can synergistically improve the efficacy of treatment in advanced pancreatic ductal adenocarcinoma patients when combined with chemotherapy.This article reviewed the latest major progress in the field of basic research and diagnosis and treatment of pancreatic cancer in 2024.

Purpose: This Phase II trial was objected to evaluate the efficacy and safety of adding fulvestrant to neoadjuvant chemotherapy in patients with estrogen receptor (ER)+/human epidermal growth factor receptor 2 (HER2)– locally advanced breast cancer (LABC). Additionally, the study aimed to investigate the association of 16α-18F-fluoro-17β-fluoroestradiol (18F-FES) positron emission tomography (PET)–computed tomography (CT) and metabolites with efficacy. Materials and Methods: Fulvestrant and EC-T regimen were given to ER+/HER2– LABC patients before surgery. At baseline, patients received 18F-FES PET-CT scan, and plasma samples were taken for liquid chromatography–mass spectrometry analysis. The primary endpoint was objective response rate (ORR). Secondary endpoints included total pathologic complete response (tpCR) and safety. Results: Among the 36 patients enrolled, the ORR was 86.1%, the tpCR rate was 8.3%. The incidence of grade ≥ 3 treatment-emergent adverse events was 22%. The decrease in ER value in sensitive patients was larger than that in non-sensitive patients, as was Ki-67 (p < 0.05). The maximum standardized uptake value, mean standardized uptake values, total lesion ER expression of 18F-FES PET-CT in sensitive patients were significantly higher than those in non-sensitive patients (p < 0.05). Moreover, these parameters were significantly correlated with Miller and Payne grade and the change in ER expression before and after treatment (p < 0.05). Thirteen differential expressed metabolites were identified, which were markedly enriched in 19 metabolic pathways. Conclusion This regimen demonstrated acceptable toxicity and encouraging antitumor efficacy. 18F-FES PET-CT might serve as a tool to predict the effectiveness of this therapy. Altered metabolites or metabolic pathways might be associated with treatment response.

Osteoarticular diseases,common chronic degenerative disorders in the elderly,involve the gradual deterioration and degeneration of bones or joints.The metabolic capacity declines with age.Impaired bone metabolism dis-rupts homeostasis,leading to osteoarticular dysfunctions.Cuprotosis,a novel form of programmed cell death mediated by ferredoxin 1,matters for the pathologic process in osteoarticular diseases.Cuprotosis influences the levels of intercellular signal transduction to induce oxidative stress,inflammation,pyroptosis,and ferroptosis in joints.Those cell death and mi-tochondrial dysfunction ultimately exacerbate the progression of osteoarticular diseases.Therefore,this review summarizes the mechanism of copper homeostasis-cuprotosis in osteoarticular diseases and the potential applications targeting copper homeostasis-cuprotosis.

The sustainable utilization and development of marine Chinese medicine are of great significance for protecting marine ecosystems,inheriting traditional Chinese medicine(TCM)culture,and promoting high-quality development of the TCM industry.Through generations of efforts,China has established a solid foundation in marine traditional Chinese medicine(MTCM)research,including the accumulation of traditional application experience,construction of research platforms,professional talent cultivation,establishment of high-level academic exchange platforms,policy support,and industrial environment optimization,with a series of breakthrough achievements.However,challenges persist in sustainable utilization and industrial development,such as unclear dynamic status of marine biological resources(some even depleted),disconnection between research and conservation due to weak awareness,insufficient R&D investment hindering landmark achievements,lack of national-level research platforms,and low industrial scale/intensification.To address these issues,strategic measures should be implemented,including strengthening dynamic monitoring and management of marine Chinese medicine resources,advancing artificial breeding and aquaculture technologies,establishing a national technology innovation center,increasing R&D investment through special funds,innovating research approaches,developing high-value products,and promote the integrated development of the entire industry chain of marine traditional Chinese medicine.Additionally,interdisciplinary collaboration,international cooperation,and public education should be enhanced to achieve effective resource conservation and rational utilization,form a marine traditional Chinese medicine industry cluster with a complete industrial chain,significant driving effect,and concentrated brand effect,ultimately contributing to human health and China's maritime power strategy.