Background: Surgeons face challenges in selecting cost-effective and biologically active agents for rotator cuff healing, given the numerous commercial products available, such as polydeoxyribonucleotide (PDRN) and atelocollagen (ATC). However, the precise efficacy of PDRN and ATC in rotator cuff healing remains debatable, and there is currently a lack of studies directly comparing the effects of the 2 agents on repaired cuff tendons. Therefore, the purpose of this study was to compare the efficacy of PDRN and ATC on bone-to-tendon interface (BTI) healing using a chronic rotator cuff tear (RCT) model in rabbits. Methods: Forty-eight rabbits were randomly divided into 3 groups. To create chronic RCT models, transected tendons were left untreated for 6 weeks, and then were repaired in a transosseous manner with PDRN and ATC injection into the repair site according to group allocation (group A: saline, group B: PDRN, group C: ATC; n = 16 per group). Genetic and immunofluorescence analyses were performed at 4 weeks after surgery. Furthermore, genetic, histologic, and biomechanical analyses were performed at 12 weeks after surgery. Results: At 4 weeks after surgery, ATC-injected shoulders showed the highest mRNA expression levels of collagen type I alpha 1 and aggrecan compared to the other 2 groups (p < 0.001 and p = 0.002, respectively). Meanwhile, there was more preliminary fibrocartilaginous matrix formation in the ATC-injected group. At 12 weeks after surgery, ATC-injected shoulders demonstrated better collagen fiber continuity and orientation, denser collagen fibers, a more mature bone-to-tendon junction, and greater fibrocartilage layer formation compared to the other 2 groups (all p < 0.001). Furthermore, ATC-injected shoulders also demonstrated a significantly higher load-to-failure value (40.4 ± 4.5 N/kg) than the remaining groups (group A, 26.7 ± 3.0 N/kg; group B, 32.8 ± 4.2 N/kg; p < 0.001). Conclusions ATC demonstrated superior efficacy in promoting BTI healing following surgical repair in a chronic RCT model of rabbits.

ObjectiveOxygen partial pressure (pO₂) is a critical indicator of the tumor microenvironment and plays an essential role in regulating tumor progression and therapeutic response, particularly for oxygen-dependent treatments such as photodynamic therapy (PDT). Although photoacoustic imaging (PAI) has shown great potential for functional and molecular imaging, conventional oxygenation imaging approaches based on hemoglobin absorption mainly provide relative oxygen saturation information and cannot directly quantify tissue oxygen partial pressure. Therefore, this study aimed to develop a fast laser sequence-based pump-probe photoacoustic tomography (PP-PAT) system for quantitative, non-invasive, and dynamic monitoring of oxygen partial pressure in tumor tissues. MethodsThe proposed PP-PAT system was developed based on the oxygen-sensitive triplet-state lifetime characteristics of methylene blue (MB). Upon optical excitation, MB molecules undergo transitions from the ground state to an excited state and subsequently form metastable triplet states through intersystem crossing. The lifetime of the triplet state is strongly affected by surrounding oxygen concentration due to dynamic oxygen quenching, providing a direct correlation between triplet-state kinetics and local oxygen partial pressure. A dual-wavelength pump-probe excitation scheme was implemented to selectively interrogate MB triplet-state dynamics. The pump pulse was used to initiate the triplet-state population, while the delayed probe pulse was applied to detect the transient triplet-state response. By optimizing the temporal interval between the pump and probe pulses, transient triplet-state differential (TTD) signals were extracted to enhance the specificity of oxygen-dependent molecular information and suppress background interference from conventional photoacoustic signals. The performance of the PP-PAT system was systematically evaluated through phantom and in vivo experiments. First, a single-tube phantom containing MB solution was used to investigate signal stability, reproducibility, and the influence of signal averaging on imaging quality. Subsequently, a dual-tube phantom model was established to simulate oxygen consumption during PDT, where one MB-containing tube was exposed to laser irradiation and the other served as a control. Finally, in vivo experiments were performed using a subcutaneous tumor model in nude mice. MB was locally injected into the tumor region before imaging to evaluate the feasibility of tumor oxygen partial pressure mapping using the proposed PP-PAT system. ResultsPhantom experiments demonstrated that the extracted TTD signals exhibited high stability and effectively reflected MB triplet-state dynamics while reducing non-specific background contributions. Signal averaging significantly improved the signal-to-noise ratio, and 50 repeated acquisitions provided an optimal compromise between image quality and acquisition efficiency. In the dual-tube phantom experiments, continuous PDT irradiation induced progressive oxygen depletion in the treated sample. The corresponding TTD decay rate gradually decreased, accompanied by an increase in the calculated triplet-state lifetime, indicating reduced oxygen quenching and decreased oxygen partial pressure. In contrast, the control sample showed relatively stable TTD kinetics and oxygenation levels during the same period. These results demonstrated that PP-PAT could quantitatively characterize oxygen consumption dynamics associated with photochemical reactions. In vivo experiments further demonstrated the capability of PP-PAT for spatially resolved oxygen partial pressure imaging in MB-injected tumor tissues. The reconstructed pO₂ maps revealed heterogeneous oxygen distributions within tumors, showing relatively hypoxic regions in the tumor core and higher oxygenation levels near the tumor boundary. This spatial oxygen distribution pattern was consistent with the typical physiological characteristics of solid tumors, where abnormal vascular structures and limited oxygen diffusion result in intratumoral oxygen gradients. ConclusionThis study presents a fast laser sequence-based PP-PAT system capable of quantitative and non-invasive imaging of tissue oxygen partial pressure. By utilizing the oxygen-dependent triplet-state lifetime of MB and extracting TTD signals, the proposed method provides molecularly specific information related to oxygen dynamics beyond conventional photoacoustic oxygenation imaging. The system enables dynamic monitoring of oxygen consumption during PDT and reveals spatial oxygen heterogeneity within tumors. This technique provides a promising imaging approach for tumor hypoxia characterization, evaluation of oxygen-dependent therapeutic responses, and precision-guided cancer treatment.

A primary hallmark of pathological cardiac hypertrophy is excess protein synthesis due to enhanced translational activity. However, regulatory mechanisms at the translational level under cardiac stress remain poorly understood. Here we examined the translational regulations in a mouse cardiac hypertrophy model induced by transaortic constriction (TAC) and explored the conservative networks versus the translatome pattern in human dilated cardiomyopathy (DCM). The results showed that the heart weight to body weight ratio was significantly elevated, and the ejection fraction and fractional shortening significantly decreased 8 weeks after TAC. Puromycin incorporation assay showed that TAC significantly increased protein synthesis rate in the left ventricle. RNA-seq revealed 1,632 differentially expressed genes showing functional enrichment in pathways including extracellular matrix remodeling, metabolic processes, and signaling cascades associated with pathological cardiomyocyte growth. When combined with ribosome profiling analysis, we revealed that translation efficiency (TE) of 1,495 genes was enhanced, while the TE of 933 genes was inhibited following TAC. In DCM patients, 1,354 genes were upregulated versus 1,213 genes were downregulated at the translation level. Although the majority of the genes were not shared between mouse and human, we identified 93 genes, including Nos3, Kcnj8, Adcy4, Itpr1, Fasn, Scd1, etc., with highly conserved translational regulations. These genes were remarkably associated with myocardial function, signal transduction, and energy metabolism, particularly related to cGMP-PKG signaling and fatty acid metabolism. Motif analysis revealed enriched regulatory elements in the 5' untranslated regions (5'UTRs) of transcripts with differential TE, which exhibited strong cross-species sequence conservation. Our study revealed novel regulatory mechanisms at the translational level in cardiac hypertrophy and identified conserved translation-sensitive targets with potential applications to treat cardiac hypertrophy and heart failure in the clinic.
Animals ; Humans ; Cardiomegaly/physiopathology* ; Ribosomes/physiology* ; Protein Biosynthesis/physiology* ; Mice ; Cardiomyopathy, Dilated/genetics* ; Ribosome Profiling

Germplasm degeneration occurs during the long-term cultivation of root-and rhizome-derived traditional Chinese medicine(RR-TCM), which seriously restricts the high-quality development of their industry. Therefore, it is urgent to solve the problem of germplasm degeneration through variety breeding. In this paper, based on previously published research articles, monographs, and news reports, the research progresses on the number and origins, breeding methods, and selection of new varieties of RR-TCM listed in the Chinese Pharmacopoeia(Edition 2020) were summarized and analyzed. The results show that there are 169 kinds of RR-TCM listed in the Chinese Pharmacopoeia(Edition 2020), originated from 223 origins with three breeding methods(i.e., seed propagation, vegetative reproduction, and tissue culture), and there are 215 species derived from seed propagation, 177 species derived from vegetative reproduction, and 164 species derived from tissue culture. To date, there are 62 origins breeding new varieties through conventional breeding, cross breeding, mutation breeding, ploidy breeding, or modern biotechnology breeding methods, including 57 origins breeding 145 new varieties through conventional breeding, 10 origins breeding 43 new varieties through mutation breeding, and seven origins breeding 12 new varieties through cross breeding method. They are used mainly to improve yield, disease resistance, and active ingredient content, but only a few new varieties have been widely used. This review will provide useful references in variety breeding, quality breeding, and standardized planting of RR-TCM.
Plant Breeding/methods* ; Plant Roots/growth & development* ; Rhizome/growth & development* ; Drugs, Chinese Herbal ; Plants, Medicinal/classification* ; Medicine, Chinese Traditional

A high performance liquid chromatography-tandem mass spectrometry(HPLC-MS/MS) method was established for simultaneous determination of seven characteristic components from the active fraction of Alpiniae Officinarum Rhizoma in rat plasma, including galangin, kaempferol, kaempferide, pinocembrin, 1,7-diphenyl-4-en-3-heptanone, 5-hydroxy-7-(4-hydroxy-3-methoxyphenyl)-1-phenyl-3-heptanone(DHPA), and 7-(4-hydroxy-3-methoxyphenyl)-1-phenyl-4-en-3-heptanone(DPHB). The new developed HPLC-MS/MS method was applied to study the pharmacokinetics of the 7 characteristic components in rats with Helicobacter pylori gastritis. A Waters Sunfire C_(18) column(2.1 mm×150 mm, 3.5 μm) was used. The acetonitrile-aqueous solution(containing 0.1% formic acid) was adopted as the mobile phase for gradient elution. Seven components and internal standard(chlorogenic acid) were separated within 12 min. Mass spectrometric detection was performed in multiple reaction monitoring(MRM) mode using electrospray ionization(ESI) source with fast switching between positive and negative ions. The method was verified by specificity, linearity, precision, accuracy, recovery, matrix effect, and stability and met the requirements of pharmacokinetic study on the 7 components in rat plasma. Pharmacokinetic results showed that the average peak time(T_(max)) of the 7 components was 0.31-2.19 h, their elimination half-life(t_(1/2)) was 5.26-16.65 h, and the average residence time(MRT) was 6.29-31.03 h after the oral administration of the active fraction of Alpiniae Officinarum Rhizoma to rats with H. pylori gastritis. The plasma exposure levels of galangin and DHPA were higher than those of the other components. The concentration-time curves of four detected flavonoids showed obvious double peaks. This study elucidated the pharmacokinetic characteristics of 7 characteristic components from the active fraction of Alpiniae Officinarum Rhizoma in rats with H. pylori gastritis, providing a scientific basis for the identification of the pharmacodynamic substances of Alpiniae Officinarum Rhizoma for treatment of H. pylori gastritis and the clinical application of Alpiniae Officinarum Rhizoma in the prevention and treatment of H. pylori gastritis.
Animals ; Rats ; Chromatography, High Pressure Liquid/methods* ; Tandem Mass Spectrometry/methods* ; Drugs, Chinese Herbal/administration & dosage* ; Male ; Helicobacter pylori/drug effects* ; Alpinia/chemistry* ; Rats, Sprague-Dawley ; Gastritis/metabolism* ; Helicobacter Infections/metabolism* ; Flavonoids/blood* ; Rhizome/chemistry* ; Liquid Chromatography-Mass Spectrometry

Yinyang Gongji Pills have the effects of strengthening the body resistance to eliminate pathogenic factors, removing stasis, and reducing swelling, which is a commonly used traditional Chinese medicine(TCM) formula for treating intestinal accumulation. A real-world, registered, and single-arm clinical trial was conducted to observe the clinical efficacy and safety of Yinyang Gongji Pills combined with capecitabine in the treatment of advanced colorectal cancer and analyze the clinical characteristics of the patients. A total of 60 patients with advanced colorectal cancer who refused or could not tolerate standard treatment of western medicine were included in the study. They were treated with Yinyang Gongji Pills combined with capecitabine until disease progression or intolerable adverse events occurred. The main observation indicators were progression-free survival(PFS) and safety. The treatment effects of the patients under different baseline characteristics were analyzed. The clinical trial has found that the median PFS of all enrolled patients was 7.3 months, with 30.1% of patients having a PFS exceeding 12.0 months. Layered analysis showed that the median PFS of patients with the onset site being the colon and rectum were respectively 8.4 and 4.7 months. The median PFS of patients with high, medium, and low tumor burden were respectively 7.0, 4.7, and 10.8 months. The median PFS of patients with wild-type and mutant-type RAS/BRAF were respectively 7.9 and 6.9 months. The median PFS of patients with KPS scores ≥80 and ≤70 were respectively 7.9 and 6.5 months. The median PFS of patients treated with Yinyang Gongji Pills for ≥6, 3-6, and ≤3 months were respectively 8.0, 5.2, and 4.2 months. The median PFS of patients with spleen, kidney, liver, and lung syndrome differentiation in TCM were respectively 8.3, 6.7, 7.3, and 5.6 months. The median PFS of patients with TCM pathological factors including phlegm, dampness, and blood stasis were respectively 7.0, 7.3, and 6.5 months. Common adverse reactions include anemia, decreased white blood cells, decreased appetite, fatigue, and hand foot syndrome, with incidence rates being respectively 44.2%, 34.6%, 42.3%, 32.7%, and 17.3%. The results showed that the combination of Yinyang Gongji Pills and capecitabine demonstrated potential clinical efficacy and good safety in this study. The patients have clinical characteristics such as low tumor burden, onset site at the colon, KPS scores ≥ 80, long duration of oral TCM, and TCM syndrome differentiation including spleen or liver.
Humans ; Capecitabine/adverse effects* ; Colorectal Neoplasms/mortality* ; Drugs, Chinese Herbal/adverse effects* ; Male ; Middle Aged ; Female ; Aged ; Adult ; Treatment Outcome

Through consulting herbal medicine， medical books， and local chronicles from past dynasties to modern times， this paper systematically researched Spatholobi Caulis from name， origin， producing areas， harvesting， processing， usage， quality evaluation， functions and indications， providing a reference for the development and utilization of famous classical formulas containing Spatholobi Caulis. According to the research， Spatholobi Caulis was first recorded in the Annals of Shunning Prefecture from the Qing dynasty. It was originally a medicinal herb commonly used in Shunning， Yunnan， and was named from the red juice resembling chicken blood that flowed out after the vein was cut off. The mainstream original plants of each dynasty were Kadsura heteroclita and Spatholobus suberectus. Among them， K. heteroclita mainly focused on dispersing blood stasis and unblocking meridians， mainly treating rheumatic pain and injuries caused by falls or blows， and it is mostly used as the raw material of Jixueteng ointments. S. suberectus was commonly used as decoction pieces in decoction， which had the functions of promoting blood circulation and replenishing blood， activating meridians and collaterals， and mainly used for treating anemia， irregular menstruation， and rheumatic bone pain. The production area of Spatholobi Caulis recorded in the Qing dynasty was Yunnan. Currently， the main production area of S. suberectus is Guangxi， while the main production area of K. interior is Yunnan. In the Qing dynasty， the usage of Spatholobi Caulis was an individual prescription with other herbs before making ointments， which was usually composed of the juice of it， safflower， angelica， and glutinous rice. But in modern times， Spatholobi Caulis is mostly sliced and dried for use. The quality of Spatholobi Caulis is often determined by the number of reddish-brown concentric circles on the cut surface， with a higher number indicating better quality. Additionally， the presence of resinous secretions is also considered desirable. Based on the research findings， it is suggested that when developing famous classical formulas containing Spatholobi Caulis， the choice of the primary source should be S. suberectus or K. heteroclita， taking into consideration the therapeutic effects of the formula. It is also recommended that the latest plant classification be referenced in the next edition of Chinese Pharmacopoeia， adjusting the primary source of Kadsurae Caulis to K. heteroclita to avoid confusion caused by inconsistent original names， and the functions adjust to promote Qi circulation and relieve pain， disperse blood stasis and unblock collaterals， treating injuries caused by falls and bruises.

Aim To elucidate the underlying mecha-nism by which total triterpenoids extracted from Hove-nia dulcis(H-TP)enhance the sensitivity of A549/DDP cells to cisplatin.Methods The ARE-Nrf2 lu-ciferase reporter assay was applied to investigate the impact of H-TP on Nrf2 expression.Western blot was used to detect the protein levels of Keap-1/Nrf2/HO-1,Nrf2-GPX4 signaling pathway,apoptosis-related proteins of Bcl-2 and Bax.Further validation of its effects on Nrf2 was conducted by using Nrf2 activator/inhibitor.Results H-TP could enhance the sensitivi-ty of A549/DDP cells to cisplatin by modulating the expression of apoptosis-related proteins Bax and Bcl-2,inhibiting the Keap-1/Nrf2/HO-1/GPX4 signating pathway in A549/DDP cells,and inducing ferroptosis.Conclusion H-TP enhances the sensitivity of A549/DDP cells to cisplatin by inducing the Nrf2-mediated ferroptosis pathway.

The epidemiological and spatiotemporal clustering characteristics of dengue fever in Fujian Province were ana-lyzed,to provide a scientific basis for dengue fever prevention and control.Descriptive epidemiology,spatial autocorrelation a-nalysis,and spatiotemporal scanning were used to analyze dengue fever cases in Fujian Province from 2011 to 2023.In this peri-od,a total of 3 586 cases of dengue fever were reported in Fujian Province,including 2 360 local cases,1 134 imported cases from abroad,and 92 imported cases from China.Cases were reported in ten prefectures and cities of the province,and 81 out of 88 counties reported cases.Imported cases were reported throughout the year in Fujian Province,but the occurrence of local ca-ses showed clear seasonality.Local cases and domestic imports were concentrated in August to October,whereas overseas im-ports occurred primarily from June to October.The imported cases were mainly from Southeast Asian countries,but a trend of spreading from Southeast Asian countries to South Asia,Africa,the Americas,and other regions,was observed.Spatio-tem-poral clustering of dengue fever was found in Fujian Province(Moran's I value 0.14-0.66,P＜0.05),and the high-high ag-gregation areas were distributed primarily in Fuzhou,Quanzhou,and Putian.Spatio-temporal scanning detected three aggrega-tion areas:one main and two secondary.The aggregation time was from the end of July to October,and the distribution was primarily in Fuzhou,Quanzhou,Putian,Zhangzhou,and Xiamen.The distribution of dengue fever in Fujian Province showed clear spatial and temporal clustering from the end of July to October,and the distribution was primarily in Fuzhou,Quanzhou,Putian,Zhangzhou,and Xiamen.For high concentration areas,national health campaigns,mosquito prevention and control,epidemic surveillance,medical personnel training,and other relevant measures could be carried out in advance before local cases appear every year.Reduce local transmission of dengue fever due to importation.

Oropharyngeal squamous cell carcinoma(OPSCC)is a malignant tumor originating from the squamous epithelium of the oro-pharyngeal mucosa,accounting for more than 90％of oropharyngeal malignancies.In recent years,human papillomavirus(HPV)infec-tion has become one of the primary etiological factors of oropharyngeal squamous carcinoma.The incidence of HPV-associated oropharyn-geal squamous carcinoma has been rising annually,with a noticeable trend toward younger populations,posing a significant threat to hu-man health.Due to the distinct biological behavior and clinical characteristics of HPV-associated oropharyngeal squamous carcinoma com-pared to its non-HPV-related counterpart,the diagnostic and treatment strategies for oropharyngeal squamous carcinoma have undergone substantial changes.Prevention and screening for oropharyngeal squamous carcinoma are of critical importance.The diagnostic and treat-ment process involves multi-disciplinary collaboration,including oral and maxillofacial surgery,otolaryngology,head and neck surgery,oncology,radiology and pathology.Based on evidence from clinical practice,a comprehensive,integrated diagnostic and therapeutic ap-proach has been established,centered around the concept of"prevention,screening,diagnosis,treatment,and rehabilitation",covering the entire patient lifecycle and providing a valuable reference for clinical practice.