The present study aimed to investigate the effects of eccentric treadmill exercise on adaptive hypertrophy of skeletal muscle in rats. Thirty-two 3-month-old Sprague Dawley (SD) rats were selected and randomly assigned to one of the four groups based on their body weights: 2-week quiet control group (2C), 2-week downhill running exercise group (2E), 4-week quiet control group (4C), and 4-week downhill running exercise group (4E). The downhill running protocol for rats in the exercise groups involved slope of -16°, running speed of 16 m/min, training duration of 90 min, and 5 training sessions per week. Twenty-four hours after the final session of training, all the four groups of rats underwent an exhaustion treadmill exercise. After resting for 48 h, all the rats were euthanized and their gastrocnemius muscles were harvested for analysis. HE staining was used to measure the cross-sectional area (CSA) and diameter of muscle fibers. Transmission electron microscope was used to observe the ultrastructural changes in muscle fibers. Purithromycin surface labeling translation method was used to measure protein synthesis rate. Immunofluorescence double labeling was used to detect the colocalization levels of lysosomal-associated membrane protein 2 (Lamp2)-leucyl-tRNA synthetase (LARS) and Lamp2-mammalian target of rapamycin (mTOR). Western blot was used to measure the protein expression levels of myosin heavy chain (MHC) IIb and LARS, as well as the phosphorylation levels of mTOR, p70 ribosomal protein S6 kinase (p70S6K), and eukaryotic translation initiation factor 4E binding protein 1 (4E-BP1). The results showed that, compared with the 2C group rats, the 2E group rats showed significant increases in wet weight of gastrocnemius muscle, wet weight/body weight ratio, running distance, running time, pre- and post-exercise blood lactate levels, myofibrillar protein content, colocalization levels of Lamp2-LARS and Lamp2-mTOR, and LARS protein expression. Besides these above changes, compared with the 4C group, the 4E group further exhibited significantly increased fiber CSA, fiber diameter, protein synthesis rate, and phosphorylation levels of mTOR, p70S6K, and 4E-BP1. Compared with the quiet control groups, the exercise groups exhibited ultrastructural damage of rat gastrocnemius muscle, which was more pronounced in the 4E group. These findings suggest that eccentric treadmill exercise may promote mTOR translocation to lysosomal membrane, activating mTOR signaling via up-regulating LARS expression. This, in turn, increases protein synthesis rate through the mTOR-p70S6K-4E-BP1 signaling pathway, promoting protein deposition and inducing adaptive skeletal muscle hypertrophy. Although the ultrastructural changes of skeletal muscle are more pronounced, the relatively long training cycles during short-term exercise periods have a more significant effect on promoting gastrocnemius muscle protein synthesis and adaptive hypertrophy.
Animals ; Rats, Sprague-Dawley ; Physical Conditioning, Animal/physiology* ; Rats ; Muscle, Skeletal/metabolism* ; TOR Serine-Threonine Kinases/metabolism* ; Male ; Hypertrophy ; Adaptation, Physiological/physiology* ; Adaptor Proteins, Signal Transducing/metabolism* ; Ribosomal Protein S6 Kinases, 70-kDa/metabolism* ; Intracellular Signaling Peptides and Proteins

Traditional Chinese medicine(TCM) is the pillar for the development of motherland medicine, and animal medicine has a long history of application in China, characterized by wide resources, strong activity, definite efficacy, and great benefits. It has significant potential and important status in the consumption market of raw materials of TCM. In the context of global climate change, farming system alterations, and low renewability, the depletion of wild medicinal animal resources has accelerated. Accordingly, the conservation and sustainable utilization of wild resources of animal medicinal materials has become a problem that garners increasing attention and urgently needs to be solved. This paper summarizes the current situation of domestic and foreign medicinal animal breeding and research progress in industrial application in recent years and points out the issues related to standardized breeding, germplasm selection and breeding, and quality evaluation standards for medicinal animals. Furthermore, this paper discusses standardized breeding, quality standards, resource protection and utilization, and the search for alternative resources for rare and endangered medicinal animals. It proposes that researchers should systematically carry out in-depth basic research on animal medicine, improve the breeding scale and level of medicinal animals, employ modern technology to enhance the quality standards of medicinal materials, and strengthen the research and development of alternative resources. This approach aims to effectively address the relationship between protection and utilization and make a significant contribution to the sustainable development of medicinal animal resources and the animal-based Chinese medicinal material industry.
Animals ; Breeding ; China ; Medicine, Chinese Traditional ; Conservation of Natural Resources

Glutamine provides carbon and nitrogen to support the proliferation of cancer cells. However, the precise reason why cancer cells are particularly dependent on glutamine remains unclear. In this study, we report that glutamine modulates the tumor suppressor F-box and WD repeat domain-containing 7 (FBW7) to promote cancer cell proliferation and survival. Specifically, lysine 604 (K604) in the sixth of the 7 substrate-recruiting WD repeats of FBW7 undergoes glutaminylation (Gln-K604) by glutaminyl tRNA synthetase. Gln-K604 inhibits SCFFBW7-mediated degradation of c-Myc and Mcl-1, enhances glutamine utilization, and stimulates nucleotide and DNA biosynthesis through the activation of c-Myc. Additionally, Gln-K604 promotes resistance to apoptosis by activating Mcl-1. In contrast, SIRT1 deglutaminylates Gln-K604, thereby reversing its effects. Cancer cells lacking Gln-K604 exhibit overexpression of c-Myc and Mcl-1 and display resistance to chemotherapy-induced apoptosis. Silencing both c-MYC and MCL-1 in these cells sensitizes them to chemotherapy. These findings indicate that the glutamine-mediated signal via Gln-K604 is a key driver of cancer progression and suggest potential strategies for targeted cancer therapies based on varying Gln-K604 status.
Glutamine/metabolism* ; Myeloid Cell Leukemia Sequence 1 Protein/genetics* ; Humans ; Proto-Oncogene Proteins c-myc/genetics* ; Cell Proliferation ; Signal Transduction ; Neoplasms/pathology* ; F-Box-WD Repeat-Containing Protein 7/genetics* ; Cell Survival ; Cell Line, Tumor ; Apoptosis

177Lu-prostate specific membrane antigen(PSMA)radio-ligand therapy has been approved abroad for advanced prostate cancer and has been in several clinical trials in China.Based on domestic clinical practice and experimental data and referred to international experience and viewpoints,the expert group forms a consensus on the clinical application of 177Lu-PSMA radio-ligand therapy in prostate cancer to guide clinical practice.

Objective To understand the prevalence characteristics of influenza and changes of influenza virus strains,and provide reference for the prevention and control of influenza in the province.Methods Surveillance da-ta about influenza in Hunan Province from 2014 to 2023 were exported from China Influenza Surveillance Informa-tion System.Differences in the percentage of influenza-like illness(ILI)cases(percentage of influenza-like cases[ILI％]in outpatient and emergency department visits)among different years and different populations,as well as the positive rate of influenza virus in ILI specimens were compared.Results From 2014 to 2023,over 2.65 million cases of ILI were reported,with an ILI％of 4.70％.ILI％among different years presented statistically significant differences(P＜0.001).People aged 0-14 years old were the main population with ILI,accounting for 82.90％.The positive rate of influenza virus in ILI specimens was 14.14％,the positive rate of influenza virus among diffe-rent years and age groups were both significantly different(both P＜0.001).The main prevalent influenza strains from 2014 to 2023 included types A(H1N1),A(H3N2),B(Victoria),and B(Yamagata),alternating among di-fferent years.However,type B(Yamagata)strains were not detected from 2020 to 2023.There were basically two influenza prevalence seasons every year,namely winter-spring and summer.Conclusion People＜15 years old are the main population of influenza,and the prevalence peaks are in winter-spring and summer.From 2021 to 2023,the prevalence alternates mainly among 3 types:A(H1N1),A(H3N2),and B(Victoria).

Age-related sarcopenia is a degenerative disease characterized by the decline in skeletal muscle mass and function during the aging process. Anabolic resistance, which refers to the diminished response of skeletal muscle to anabolic stimulation from leucine and other nutrients, is a significant contributing factor to its development. Recent studies have suggested that large neutral amino acid-transporter 1 (LAT1/SLC7A5) may play an important role in enhancing leucine's effects on protein synthesis in aging skeletal muscle. In this paper, the structure and function of LAT1 and its key molecules regulating aging skeletal muscle protein synthesis were reviewed, and the potential relationship between LAT1, as a transmembrane transporter of leucine, and protein synthesis in aging skeletal muscle was analyzed. The aim is to explore new mechanisms and insights for prevention and treatment of age-related sarcopenia, and provide reference for the application of relevant targets in clinical translational medicine.
Humans ; Leucine/metabolism* ; Muscle, Skeletal/metabolism* ; Aging/metabolism* ; Large Neutral Amino Acid-Transporter 1/metabolism* ; Protein Biosynthesis ; Sarcopenia/metabolism* ; Animals ; Muscle Proteins/biosynthesis*

Shaoyao Gancao Decoction(SGD) is a classic formula used in the clinical treatment of joint diseases, such as rheumatoid arthritis(RA), though its mechanism of action remains unclear. This study aimed to explore the mechanism of SGD in treating RA through chemical and network pharmacology analyses, combined with cellular experiments. UPLC-Orbitrap-MS~2 was used to qualitatively analyze SGD and drug-containing serum of rats after oral administration of SGD, thereby identifying the chemical composition and plasma components of SGD. Potential targets for the plasma components in treating RA were identified using the SwissTargetPrediction, PharmMapper, GeneCards, and DrugBank databases, and a protein-protein interaction(PPI) network was constructed using the STRING data platform. GO functional enrichment and KEGG pathway enrichment analyses were conducted using the Metascape database. Molecular docking and lipopolysaccharide(LPS)-induced RAW264.7 cell experiments were utilized for in vitro validation. The results identified 95 compounds in SGD, including 15 prototypical absorbed components, i.e., 7 flavonoids, 5 terpenoids, 2 phenolic compounds, and 1 other compound. Network pharmacology analysis revealed that licoisoflavanone, liquiritin apioside, 5-hydroxyferulic acid, albiflorin, hederagenin, and paeoniflorin were the pharmacodynamic components of SGD for treating RA. The core targets of SGD for RA treatment were identified as SRC, MAPK, EGFR, HSP90AA1, and STAT3, with regulation of the NF-κB, PI3K-Akt, and MAPK signaling pathways identified as key mechanisms for anti-RA effects of SGD. Molecular docking results showed that the six core components exhibited high affinity with the key targets SRC, MAPK, and NF-κB. In vitro cellular experiments demonstrated that SGD down-regulated the expression of inflammatory factors, including interleukin-1β(IL-1β), cyclooxygenase-2(COX-2), and tumor necrosis factor-α(TNF-α), in LPS-induced RAW264.7 cells. Western blot analysis revealed that SGD significantly reduced the phosphorylation levels of NF-κB p65 and p38 MAPK proteins. This study provides a scientific basis for further research into the active components and mechanisms of action of SGD in treating RA.
Animals ; Drugs, Chinese Herbal/chemistry* ; Arthritis, Rheumatoid/metabolism* ; Mice ; Network Pharmacology ; RAW 264.7 Cells ; Rats ; Chromatography, High Pressure Liquid/methods* ; Molecular Docking Simulation ; Male ; Rats, Sprague-Dawley ; Humans ; Signal Transduction/drug effects* ; NF-kappa B/genetics* ; Protein Interaction Maps/drug effects*

Patients with congenital unilateral absence of the vas deferens (CUAVD) manifest diverse symptoms from normospermia to azoospermia. Treatment for CUAVD patients with obstructive azoospermia (OA) is complicated, and there is a lack of relevant reports. In this study, we describe the clinical features and evaluate the treatments and outcomes of CUAVD patients with OA. From December 2015 to December 2020, 33 patients were diagnosed as CUAVD with OA in Shanghai General Hospital (Shanghai, China). Patient information, ultrasound findings, semen analysis, hormone profiles, and treatment information were collected, and the clinical outcomes were evaluated. Of 33 patients, 29 patients were retrospectively analyzed. Vasoepididymostomy (VE) or cross VE was performed in 12 patients, the patency rate was 41.7% (5/12), and natural pregnancy was achieved in one of the patients. The other 17 patients underwent testicular sperm extraction as the distal vas deferens (contralateral side) was obstructed. These findings showed that VE or cross VE remains an alternative treatment for CUAVD patients with OA, even with a relatively low rate of patency and natural pregnancy.
Pregnancy ; Female ; Humans ; Male ; Vas Deferens/abnormalities* ; Azoospermia/surgery* ; Epididymis/surgery* ; Retrospective Studies ; Tertiary Care Centers ; China ; Semen

AIM: To investigate the changes in retinal and choroidal blood flow after pars plana vitrectomy(PPV)for proliferative diabetic retinopathy(PDR).METHODS: A cross-sectional study was conducted on 35 patients(35 eyes)who were diagnosed as monocular PDR and received 23GPPV in ophthalmology department of the Second People's Hospital of Hefei between September 2020 and July 2022. All eyes underwent swept-source optical coherence tomography angiography(SS-OCTA)examination. Retinal and choroidal vascular parameters within 3mm×3mm of macular zone were measured by built-in analyzer, and its correlation with postoperative best corrected visual acuity(BCVA)was analyzed.RESULTS: The follow-up was 1～22(average 9.72±6.67)mo. At the last follow-up, flow area(FA)of intermediate capillary plexus(ICP)layer in paranasal foveal region was significantly reduced in PPV eyes(0.31±0.06mm2)compared with contralateral eyes(0.38±0.05mm2), and FA of deep capillary plexus(DCP)in temporal foveal region was significantly lower in PPV eyes(0.19±0.08mm2)than contralateral eyes(0.27±0.07mm2; all P<0.05). Choroidal vascularity index(CVI)were lower in PPV eyes than contralateral eyes in parafoveal subregions except temporal region(P<0.05). After PPV, BCVA had a certain correlation with the density and FA of middle and deep retinal vessels.CONCLUSIONS: Eyes with severe PDR may be prone to having a decrease in the DCP and parafoveal choroidal perfusion in the parafoveal regions after PPV than contralateral eyes.

Purpose: This study aimed to evaluate the diagnostic value of combined fine-needle aspiration (FNA) with core needle biopsy (CNB) in thyroid nodules. Methods: FNA and CNB were performed simultaneously on 703 nodules. We compared the proportions of inconclusive results and the diagnostic performance for malignancy among FNA, CNB, and combined FNA/CNB for different nodule sizes. Results: Combined FNA/CNB showed lower proportions of inconclusive results than CNB for all nodules (2.8% vs. 5.7%, P<0.001), nodules ≤1.0 cm (4.9% vs. 7.3%, P=0.063), nodules >1.0 cm (2.0% vs. 5.0 %, P<0.001), nodules ≤1.5 cm (3.8% vs. 7.9 %, P<0.001), and nodules >1.5 cm (2.1% vs. 3.9 %, P=0.016). The sensitivity of combined FNA/CNB in predicting malignancy was significantly higher than that of CNB (89.0% vs. 80.0%, P<0.001) and FNA (89.0% vs. 58.1%, P<0.001) for all nodules. Within American College of Radiology Thyroid and Imaging Reporting and Data System grades 4-5, in the subgroup of nodules ≤1.5 cm, combined FNA/ CNB showed the best sensitivity in predicting malignancy (91.4%), significantly higher than that of CNB (81.0%, P<0.001) and FNA (57.8%, P<0.001). However, in the subgroup of nodules >1.5 cm, the difference between combined FNA/CNB and CNB was not significant (84.2% vs. 78.9%, P=0.500). Conclusion Regardless of nodule size, combined FNA/CNB tended to yield lower proportions of inconclusive results than CNB or FNA alone and exhibited higher performance in diagnosing malignancy. The combined FNA/CNB technique may be a more valuable diagnostic method for nodules ≤1.5 cm and nodules with a risk of malignancy than CNB and FNA alone.