Myocardial fibrosis is a serious cause of heart failure and even sudden cardiac death. However, the mechanisms underlying myocardial ischemia-induced cardiac fibrosis remain unclear. Here, we identified that the expression of sterile alpha and TIR motif containing 1 (SARM1), was increased significantly in the ischemic cardiomyopathy patients, dilated cardiomyopathy patients (GSE116250) and fibrotic heart tissues of mice. Additionally, inhibition or knockdown of SARM1 can improve myocardial fibrosis and cardiac function of myocardial infarction (MI) mice. Moreover, SARM1 fibroblasts-specific knock-in mice had increased deposition of extracellular matrix and impaired cardiac function. Mechanically, elevated expression of SARM1 promotes the deposition of extracellular matrix by directly modulating P4HA1. Notably, by using the Click-iT reaction, we identified that the increased expression of ZDHHC17 promotes the palmitoylation levels of SARM1, thereby accelerating the fibrosis process. Based on the fibrosis-promoting effect of SARM1, we screened several drugs with anti-myocardial fibrosis activity. In conclusion, we have unveiled that palmitoylated SARM1 targeting P4HA1 promotes collagen deposition and myocardial fibrosis. Inhibition of SARM1 is a potential strategy for the treatment of myocardial fibrosis. The sites where SARM1 interacts with P4HA1 and the palmitoylation modification sites of SARM1 may be the active targets for anti-fibrosis drugs.

OBJECTIVE: To describe survival trends and global patterns of esophageal cancer (EC) using survival data from population-based cancer registries. METHODS: We systematically searched PubMed, EMBASE, Web of Science, SEER, and SinoMed databases for articles published up to 31 December 2023. Eligible EC survival estimates were evaluated according to country or region, period, sex, age group, pathology, and disease stage. RESULTS: After 2010, Jordan exhibited the highest age-standardized 5-year relative survival rates (RSRs)/net survival rates (NSRs) at 41.1% between 2010 and 2014, while India had the lowest, at 4.1%. Survival rates generally improved with diagnostic age across most countries, with significant increases in South Korea and China, of 12.7% and 10.5% between 2000 and 2017, respectively. Survival was higher among women compared to men, ranging from 0.4%-10.9%. Survival rates for adenocarcinoma and squamous cell carcinoma were similar, differing by about 4%. In China, the highest age-standardized RSRs/NSRs was 33.4% between 2015 and 2017. Meanwhile, the lowest was 5.3%, in Qidong (Jiangsu province) between 1992-1996. CONCLUSION Global EC survival rates have improved significantly in recent decades, but substantial geographical, sex, and age disparities still exist. In Asia, squamous cell carcinoma demonstrated superior survival rates compared to adenocarcinoma, while the opposite trend was observed in Western countries. Future research should clarify the prognostic factors influencing EC survival and tailor prevention and screening strategies to the changing EC survival patterns.
Humans ; Esophageal Neoplasms/mortality* ; Registries ; Male ; Female ; Survival Analysis ; Middle Aged ; Survival Rate ; Aged ; Global Health

Gadopiclenol was used in adults and pediatric patients 2 years of age and older during magnetic resonance imaging(MRI)to detect and view lesions of the central nervous system(brain,spine,and associated tissues)and body(head and neck,chest,abdomen,pelvis,and musculoskeletal system)with abnormal vascular properties.Gadopiclenol is a new type of macrocyclic gadolinium-based contrast agent(GBCA).In this article,the molecular structure,principle of action,pharmacodynamics,pharmacokinetics,clinical studies,safety and other aspects of Gadopiclenol were reviewed,in order to introduce the current research status and existing achievements of Gadopiclenol.

On May 27,2021,the U.S.Food and Drug Administration(FDA)officially approved Lantheus'PYLARIFY?(Piflufolastat F 18,18 F-labeled imaging agent),which can be used for positron emission computed tomography(PET)of prostate-specific membrane antigen(PSMA)-positive lesions in prostate cancer patients to accurately identify prostate cancer with suspected metastasis or recurrence.Piflufolastat F 18 is approved by FDA for two indications.The first is the initial staging for suspected metastatic lesions in men with newly diagnosed prostate cancer.The second is restaging,with the goal of identifying lesions in the setting of biochem ical recurrence.

Objective: To investigate the influence of light and heavy bite force on the mandibular movement trajectories, and the influence of bite force on virtual occlusal pre-adjustment of digital full crown. Methods: From October 2021 to March 2022, 10 postgraduate volunteers (3 males and 7 females, aged 22-26 years) were recruited from Peking University School and Hospital of Stomatology. Maxillary and mandibular digital models of the participants were obtained by intraoral scanning. Jaw relations were digitally transferred under heavy bite force and mandibular movement trajectories under light and heavy bite force were recorded by jaw motion analyser. Three mandibular markers were chosen, namely the mesial proximal contact point of the central incisor (incisal point) and the mesial buccal cusp tips of the bilateral first molars. The three-dimensional displacements of the markers under two kinds of bite force in the intercuspal position (ICP), the sagittal projection of the three-dimensional displacements in the protrusive edge-to-edge position, and the coronal projection of the three-dimensional displacements in the lateral edge-to-edge position of upper and lower posterior teeth were measured. Single-sample t-test was used to compare the three-dimensional displacements and the corresponding sagittal projection and coronal projection with 0, respectively. The left maxillary central incisor and left mandibular first molar were virtually prepared by the reverse engineering software. Then dental design software was used to design digital full crown using the copy method. The mandibular movement trajectories under light and heavy bite force were separately used to guide virtual occlusal pre-adjustment. The three-dimensional deviations (mean deviations and root mean square) between the lingual surface of the left maxillary central incisor or the occlusal surface of the left mandibular first molar and that of the natural tooth before preparation were calculated (light bite force group and heavy bite force group), and the differences between the two groups were compared by the paired t-test. Results: Under the two kinds of bite force, the three-dimensional displacements of the markers in the ICP were (0.217±0.135), (0.210±0.133) and (0.237±0.101) mm, respectively; the sagittal projection of the three-dimensional displacements of the markers in the protrusive edge-to-edge position were (0.204±0.133), (0.288±0.148) and (0.292±0.136) mm, respectively; the coronal projection of the three-dimensional displacements of the mesial buccal cusp tips of the bilateral first molars in the lateral edge-to-edge position were (0.254±0.140) and (0.295±0.190) mm, respectively. The differences between the above displacements and 0 were statistically significant (P<0.05). The results of occlusal pre-adjustment showed that the mean deviations of the lingual surface of the left maxillary central incisor in the light and heavy bite force groups were (0.215±0.036) and (0.195±0.041) mm (t=3.95, P=0.004), respectively. The mean deviations of the occlusal surface of the left mandibular first molar were (0.144±0.084) and (0.100±0.096) mm (t=0.84, P=0.036), respectively. Conclusions: Both the light and heavy bite force have an influence on the mandibular movement trajectories. Virtual occlusal pre-adjustment of prostheses with mandibular movement trajectories under heavy bite force can obtain morphology of lingual or occlusal surfaces closer to the natural teeth before preparation.
Male ; Female ; Humans ; Bite Force ; Tooth ; Mandible ; Molar ; Occlusal Adjustment

This study constructed a nano-drug delivery system, A3@GMH, by co-delivering the stapled anoplin peptide(Ano-3, A3) with the light-harvesting material graphene oxide(GO), and evaluated its oncolytic immunotherapy effect on triple-negative breast cancer(TNBC). A3@GMH was prepared using an emulsion template method and its physicochemical properties were characterized. The in vivo and in vitro photothermal conversion abilities of A3@GMH were investigated using an infrared thermal imager. The oncoly-tic activity of A3@GMH against TNBC 4T1 cells was evaluated through cell counting kit-8(CCK-8), lactate dehydrogenase(LDH) release, live/dead cell staining, and super-resolution microscopy. The targeting properties of A3@GMH on 4T1 cells were assessed using a high-content imaging system and flow cytometry. In vitro and in vivo studies were conducted to investigate the antitumor mechanism of A3@GMH in combination with photothermal therapy(PTT) through inducing immunogenic cell death(ICD) in 4T1 cells. The results showed that the prepared A3@GMH exhibited distinct mesoporous and coated structures with an average particle size of(308.9±7.5) nm and a surface potential of(-6.79±0.58) mV. The encapsulation efficiency and drug loading of A3 were 23.9%±0.6% and 20.5%±0.5%, respectively. A3@GMH demonstrated excellent photothermal conversion ability and biological safety. A3@GMH actively mediated oncolytic features such as 4T1 cell lysis and LDH release, as well as ICD effects, and showed enhanced in vitro antitumor activity when combined with PTT. In vivo, A3@GMH efficiently induced ICD effects with two rounds of PTT, activated the host's antitumor immune response, and effectively suppressed tumor growth in 4T1 tumor-bearing mice, achieving an 88.9% tumor inhibition rate with no apparent toxic side effects. This study suggests that the combination of stapled anoplin peptide and PTT significantly enhances the oncolytic immunotherapy for TNBC and provides a basis for the innovative application of anti-tumor peptides derived from TCM in TNBC treatment.
Humans ; Animals ; Mice ; Photothermal Therapy ; Triple Negative Breast Neoplasms/pathology* ; Antimicrobial Cationic Peptides ; Immunotherapy/methods* ; Cell Line, Tumor ; Phototherapy/methods* ; Nanoparticles/chemistry*

The fundamental principle of traditional Chinese medicine(TCM) is holism, and it is crucial for TCM to address the key issue of the "holistic view" of Chinese herbal medicine. While the overall regulatory effects of Chinese herbal medicine have been widely recognized, the holistic internal logic of individual ingredients of Chinese herbal medicines require further clarification. In order to comprehensively understand the mechanism of action of Chinese herbal medicine, this paper combined the holistic view of Chinese herbal medicine with differentiation thinking to explore the intrinsic logical relationships within Chinese herbal medicine. Starting from the perspective of the coexistence of multiple components in Chinese herbal medicine, this paper systematically examined the "self-consistent" phenomenon within single Chinese herbal medicine. This phenomenon refers to the consistent or opposing actions of various components in terms of their physical and chemical properties, pharmacokinetic effects, biological effects, flavors and properties, and TCM efficacy. The paper summarized various logical relationships of syndrome differentiation exhibited by the same Chinese herbal medicine, analyzed the underlying reasons, and focused on analyzing external factors affecting the "self-consistent" phenomenon in the efficacy of Chinese herbal medicine, aiming to better elucidate the theoretical basis of the pharmacological effects of Chinese herbal medicine, further enrich the scientific connotation of the holistic view of Chinese herbal medicine, and provide theoretical guidance for the preparation process, compatibility patterns, and formulation design of Chinese herbal medicine.
Medicine, Chinese Traditional ; Drugs, Chinese Herbal/therapeutic use*

Humans ; Stroke, Lacunar ; Mendelian Randomization Analysis ; Leukocytes ; Telomere/genetics* ; Genome-Wide Association Study ; Polymorphism, Single Nucleotide

Objective To investigate whether the semen quality of men undergoing conventional semen analysis from this center has changed over time in 10 years.Methods The data of 231 519 semen samples provided by males undergoing conventional seminal anal-ysis in outpatient department of Reproductive Medicine Affiliated to Shandong University from January 2013 to December 2022 were ret-rospectively analyzed.The sperm concentration,motility,percentage of progressively motile sperm and percentage of normal morphology sperm were analyzed according to the World Health Organization(WHO)Laboratory Manual for the Examination and Treatment of Hu-man Semen(5th edition)and the changes of these parameters in 10 years were compared.Results From 2013 to 2022,there were no significant changes in the proportions of men with different sperm concentration,motility,percentage of progressively motile sperm in reproductive clinics.Approximately 27％of infertile male patients had low sperm concentration each year,approximately 34％of infer-tile male patients had low sperm motility each year,approximately 10％of infertile male patients was not found sperm in semen samples each year,and the percentages of normal morphology sperm of approximately 57％of infertile male patients were lower than the refer-ence value.The semen routine analysis results of approximately 50％of infertile male patients were in the normal range.The proportion of normal semen population did not change significantly.Conclusion The semen quality of infertile men does not change significantly in recent 10 years.

Astragali Radix, a medicinal herb for invigorating Qi, has anti-aging, anti-tumor, immunoregulatory, blood sugar-and lipid-lowering, anti-fibrosis, anti-radiation and other pharmacological effects. This article reviewed the studies about the chemical components and pharmacological effects of Astragali Radix. According to the theory of quality markers(Q-markers) of Chinese medicinal materials, we predicted the Q-markers of Astragali Radix from traditional efficacy, chemical component validity, measurability, plant phylogeny, and pharmacokinetis. The results showed that total polysaccharides, flavonoids(e.g., calycosin-7-O-β-D-glucoside, formononetin, calycosin, quercetin, and ononin), and saponins(e.g., astragalosides Ⅱ, Ⅲ, and Ⅳ) can be taken as the main Q-markers. This review lays a foundation for regulating the quality research and standard establishment of Astragali Radix, and benefits the control and quality supervision of the production process of Astragali Radix and its related products.
Astragalus Plant ; Chromatography, High Pressure Liquid/methods* ; Drugs, Chinese Herbal/pharmacology* ; Flavonoids ; Plant Roots