ObjectiveTo explore the effect of Buzhong Yiqitang on exercise-induced fatigue and its potential mechanism. MethodsSixty male SPF-grade C57BL/6J mice were randomized into blank， model， low-， medium-， high-dose （4.1， 8.2， 16.4 g·kg^-1， respectively） Buzhong Yiqitang， and vitamin C （0.04 g·kg^-1） groups. The blank and model groups were administrated with normal saline. Each group was administrated with corresponding agents by gavage at a dose of 0.2 mL once a day. Except the blank group， other groups underwent a 6-weeks exhaustive swimming test under negative gravity. At the end of the experiment， blood was collected， and the thymus， spleen， liver， and kidney weights were measured. Serum levels of lactic acid （LD）， blood urea nitrogen （BUN）， creatine kinase （CK）， and malondialdehyde （MDA） were assessed by kits to evaluate fatigue. Hematoxylin-eosin staining was performed to observe pathological changes in the skeletal muscle. Electron microscopy was used to examine the skeletal muscle cell ultrastructure， with a focus on mitochondrial morphological changes. The adenosine triphosphate （ATP） content and activities of mitochondrial respiratory chain complexes Ⅰ， Ⅱ， and Ⅴ in skeletal muscle were determined by kits. The expression levels of key genes and proteins in the PTEN-induced putative kinase 1 （PINK1）-mediated mitochondrial homeostasis pathways in the skeletal muscle were evaluated via Real-time PCR and Western blot， respectively. ResultsCompared with the blank group， the model group showed reductions in weight gain rate （P<0.01） and thymus index （P<0.01）， rises in serum levels of LD， BUN， MDA， and CK （P<0.01）， disarrangement of skeletal muscle， broken muscle fibers， inflammatory cell infiltration in muscle fiber gaps， abnormal morphological changes （increased vacuolated mitochondria and disappearance of cristae） of mitochondria in skeletal muscle cells， and decreased mitochondria. In addition， the skeletal muscle in the model group showed reduced content of ATP， weakened activities of mitochondrial respiratory chain complexes Ⅰ， Ⅱ， and Ⅴ （P<0.05）， up-regulated mRNA levels of PINK1， E3 ubiquitin-protein ligase （Parkin）， hairy/enhancer-of-split related with YRPW motif 1 （HEY1）， dynamin-related protein 1 （Drp1）， sequestosome 1 （p62）， and hypoxia-inducible factor 1 alpha （HIF-1α） （P<0.05）， and down-regulated protein level of microtubule-associated protein 1-light chain 3B （LC3B） （P<0.01）. Compared with the model group， Buzhong Yiqitang prolonged the swimming exhaustion time （P<0.01）， increased the weight gain rate （P<0.01） and thymus index （P<0.01）， lowered the serum levels of LD， BUN， MDA， and CK （P<0.05， P<0.01）. The skeletal muscle in the Buzhong Yiqitang groups showed neat arrangement， reduced inflammatory cells， intact mitochondria with dense cristae， and increased mitochondria. In addition， the skeletal muscle in the Buzhong Yiqitang groups showcased increased ATP content， enhanced activities of mitochondrial respiratory chain complexes Ⅰ， Ⅱ， and Ⅴ （P<0.05， P<0.01）， up-regulated protein levels of PINK1， Parkin， HEY1， LC3B， and Drp1 and mRNA level of HIF-1α （P<0.05， P<0.01）， and down-regulated expression level of p62 （P<0.05， P<0.01）. ConclusionBuzhong Yiqitang can prevent and treat exercise-induced fatigue by regulating the mitochondrial homeostasis of skeletal muscle via the HIF-1α/PINK1/Parkin and HIF-1α/HEY1/PINK1 signaling pathways.

ObjectiveTo explore the effect of Buzhong Yiqitang on exercise-induced fatigue and its potential mechanism. MethodsSixty male SPF-grade C57BL/6J mice were randomized into blank， model， low-， medium-， high-dose （4.1， 8.2， 16.4 g·kg^-1， respectively） Buzhong Yiqitang， and vitamin C （0.04 g·kg^-1） groups. The blank and model groups were administrated with normal saline. Each group was administrated with corresponding agents by gavage at a dose of 0.2 mL once a day. Except the blank group， other groups underwent a 6-weeks exhaustive swimming test under negative gravity. At the end of the experiment， blood was collected， and the thymus， spleen， liver， and kidney weights were measured. Serum levels of lactic acid （LD）， blood urea nitrogen （BUN）， creatine kinase （CK）， and malondialdehyde （MDA） were assessed by kits to evaluate fatigue. Hematoxylin-eosin staining was performed to observe pathological changes in the skeletal muscle. Electron microscopy was used to examine the skeletal muscle cell ultrastructure， with a focus on mitochondrial morphological changes. The adenosine triphosphate （ATP） content and activities of mitochondrial respiratory chain complexes Ⅰ， Ⅱ， and Ⅴ in skeletal muscle were determined by kits. The expression levels of key genes and proteins in the PTEN-induced putative kinase 1 （PINK1）-mediated mitochondrial homeostasis pathways in the skeletal muscle were evaluated via Real-time PCR and Western blot， respectively. ResultsCompared with the blank group， the model group showed reductions in weight gain rate （P<0.01） and thymus index （P<0.01）， rises in serum levels of LD， BUN， MDA， and CK （P<0.01）， disarrangement of skeletal muscle， broken muscle fibers， inflammatory cell infiltration in muscle fiber gaps， abnormal morphological changes （increased vacuolated mitochondria and disappearance of cristae） of mitochondria in skeletal muscle cells， and decreased mitochondria. In addition， the skeletal muscle in the model group showed reduced content of ATP， weakened activities of mitochondrial respiratory chain complexes Ⅰ， Ⅱ， and Ⅴ （P<0.05）， up-regulated mRNA levels of PINK1， E3 ubiquitin-protein ligase （Parkin）， hairy/enhancer-of-split related with YRPW motif 1 （HEY1）， dynamin-related protein 1 （Drp1）， sequestosome 1 （p62）， and hypoxia-inducible factor 1 alpha （HIF-1α） （P<0.05）， and down-regulated protein level of microtubule-associated protein 1-light chain 3B （LC3B） （P<0.01）. Compared with the model group， Buzhong Yiqitang prolonged the swimming exhaustion time （P<0.01）， increased the weight gain rate （P<0.01） and thymus index （P<0.01）， lowered the serum levels of LD， BUN， MDA， and CK （P<0.05， P<0.01）. The skeletal muscle in the Buzhong Yiqitang groups showed neat arrangement， reduced inflammatory cells， intact mitochondria with dense cristae， and increased mitochondria. In addition， the skeletal muscle in the Buzhong Yiqitang groups showcased increased ATP content， enhanced activities of mitochondrial respiratory chain complexes Ⅰ， Ⅱ， and Ⅴ （P<0.05， P<0.01）， up-regulated protein levels of PINK1， Parkin， HEY1， LC3B， and Drp1 and mRNA level of HIF-1α （P<0.05， P<0.01）， and down-regulated expression level of p62 （P<0.05， P<0.01）. ConclusionBuzhong Yiqitang can prevent and treat exercise-induced fatigue by regulating the mitochondrial homeostasis of skeletal muscle via the HIF-1α/PINK1/Parkin and HIF-1α/HEY1/PINK1 signaling pathways.

Cinnabar(HgS) was widely used in ancient times for medicinal purposes, religious rituals, and pigments. A group of bright red powdery clumps was excavated from Mawangdui Tomb No.3 of the Han Dynasty. Early studies considered the clumps as evidence of cinnabar's medicinal use during the Qin-Han period. This study employed a range of archaeometric techniques, including extended-depth-of-field stereo imaging, micro-CT, scanning electron microscopy-energy dispersive spectroscopy, Raman spectroscopy, and Fourier transform infrared spectrometry FTIR, to systematically analyze the material composition and structural characteristics of these remains. The results revealed that the cinnabar particles were granular, finely ground, and tightly bound to silk matrix, with no detectable excipients typically associated with medicinal formulations. Micro-CT imaging indicated a well-preserved textile structure, with clear signs of sedimentary accumulation and mechanical damage. Based on historical and archaeological studies, this study suggested that these remains were more likely degraded accumulations of cinnabar-colored silk textiles rather than medicinal cinnabar. By clarifying the diversity of ancient cinnabar applications and preservation states, this study provides new insights for the archaeological identification of mineral medicinal materials and contributes to the standardized study of Chinese medicinal materials and understanding of the historical use of cinnabar.
History, Ancient ; China ; Humans ; Medicine, Chinese Traditional/history* ; Archaeology ; Drugs, Chinese Herbal/history* ; Spectroscopy, Fourier Transform Infrared ; Spectrum Analysis, Raman ; Mercury Compounds

BACKGROUND: Early control of low-density lipoprotein cholesterol (LDL-C) is crucial for reducing the progress of cardiovascular disease. However, its additional role to the risk of primary osteoporosis in men with coronary heart disease was inconclusive. Our study aims to determine the association of LDL-C and its trajectories for osteoporosis risk in the middle-aged and aged men of China. METHODS: The retrospective cohort study of 1546 men aged 69.74 ± 11.30 years conducted in Beijing, China from 2015 to 2022. And the incidence of primary osteoporosis was annually recorded. LDL-C trajectories were further identified by latent class growth model using repeated measurements of LDL-C. The association of baseline LDL-C for osteoporosis was estimated using hazard ratio (HR) with 95% CI in Cox proportional hazard model, while mean level and trajectories of LDL-C for osteoporosis were evaluated using odds ratio (OR) with 95% CI in logistic regression model. RESULTS: During the median 6.2-year follow-up period, 70 men developed primary osteoporosis. The higher level of baseline LDL-C (HR = 1.539, 95% CI: 1.012-2.342) and mean LDL-C (OR = 2.190, 95% CI: 1.443-3.324) were associated with higher risk of osteoporosis in men with coronary heart disease after adjusted for covariates. Compared with those in the LDL-C trajectory of low-stable decrease, participants with medium-fluctuant trajectory, whose longitudinal LDL-C started with a medium LDL-C level and appeared an increase and then decrease, were negatively associated with osteoporosis risk (OR = 2.451, 95% CI: 1.152-5.216). And participants with initially high LDL-C level and then a rapid decrease demonstrated a tendency towards reduced risk (OR = 0.718, 95% CI: 0.212-2.437). CONCLUSIONS Elevated LDL-C level and its long-term fluctuation may increase the risk of primary osteoporosis in men. Early controlling a stable level of LDL-C is also essential for bone health.

Radiopharmaceuticals operate by combining radionuclides with carriers. The radiation energy emitted by radionuclides is utilized to selectively irradiate diseased tissues while minimizing damage to healthy tissues. In comparison to external beam radiation therapy, radionuclide drugs demonstrate research potential due to their biological targeting capabilities and reduced normal tissue toxicity. This article reviews the applications and research progress of radiopharmaceuticals in cancer treatment. Several key radionuclides are examined, including ²²³Ra, ⁹⁰Y, Lutetium-177 (¹⁷⁷Lu), ²¹²Pb, and Actinium-225 (²²⁵Ac). It also explores the current development trends of radiopharmaceuticals, encompassing the introduction of novel radionuclides, advancements in imaging technologies, integrated diagnosis and treatment approaches, and equipment-medication combinations. We review the progress in the development of new treatments, such as neutron capture therapy, proton therapy, and heavy ion therapy. Furthermore, we examine the challenges and breakthroughs associated with the clinical translation of radiopharmaceuticals and provide recommendations for the research and development of novel radionuclide drugs.
Humans ; Radiopharmaceuticals/therapeutic use* ; Neoplasms/radiotherapy* ; Radioisotopes/therapeutic use* ; Animals

Objective: To evaluate the effect of exercise prescription intervention among patients with type 2 diabetes mellitus (T2DM), so as to provide the evidence for guiding appropriate physical activity and glycemic control in this population. Methods: In July 2023, T2DM patients managed by two community health service centers in Qingjiangpu District, Huai'an City, Jiangsu Province, were selected as the study participants and randomly assigned divided into a control group and an intervention group. The control group received routine chronic disease management under the basic public health services, while the intervention group, in addition to receiving the same routine chronic disease management, was provided with exercise prescription to guide their physical activity at baseline (T0), after 3 months of intervention (T1), and after 6 months of intervention (T2). Data on weight-related indicators, glycated hemoglobin (HbA1c), and blood lipid were collected through physical examinations and laboratory tests at T0 and after 12 months of intervention (T3). The differences in indicators between the two groups before and after the intervention were analyzed using generalized estimating equations. Results: The intervention group consisted of 197 patients, including 99 males, accounting for 50.25%. The median disease duration was 7.10 (interquartile range, 7.80) years, and 113 patients had suboptimal HbA1c levels, accounting for 57.36%. The control group included 196 patients, including 99 females, accounting for 50.51%. The median disease duration was 6.10 (interquartile range, 7.00) years, and 100 patients had suboptimal HbA1c levels, accounting for 51.02%. Before the intervention, no statistically significant differences were observed between the two groups in gender, educational level, disease duration, pharmacological treatment, smoking, alcohol consumption, and HbA1c levels (all P>0.05). In the intervention group, the proportion of participants engaging in aerobic exercise and strength training increased from 78.17% and 8.12% at T0 to 85.79% and 16.24% at T3, respectively (both P<0.05). The results of the generalized estimating equations revealed significant interactions between group and time for waist-to-hip ratio, total cholesterol (TC), and low-density lipoprotein cholesterol (LDL-C) following the intervention (all P<0.05). A statistically significant difference in waist-to-hip ratio was found between the two groups (P<0.05), with a greater reduction observed in the intervention group compared to the control group. Significant differences in TC and LDL-C levels were noted across different intervention time points (both P<0.05). Specifically, the intervention group demonstrated reductions of 0.35 mmol/L in TC and 0.42 mmol/L in LDL-C from baseline to follow-up (both P<0.05). Conclusion The 12-month exercise prescription intervention can effectively enhance exercise participation and reduce waist-to-hip ratio, TC, and LDL-C levels among patients with T2DM.

Objective To explore the protective effect and mechanism of Jinyinqingre oral liquid on acute lung injury in-duced by lipopolysaccharide(LPS)in mice.Methods C57BL/6J mice were randomly divided into six groups according to the random number table method:blank control group,model control group,Jinyinqingre oral liquid low-dose group,Jinyinqingre oral liquid medium-dose group,Jinyinqingre oral liquid high-dose group,and dexamethasone group.Except for the blank control group,the other groups were injected with lipopolysac charide(LPS)(5 mg·kg-1)into the trachea to establish the acute lung injury model of mice,and the Jinyinqingre oral liquid low,medium,and high groups were continuously administered the drug by gavage for three days.After 24 h,lung tissue and bronchoalveolar lavage fluid(BALF)were collected from the six groups for follow-up detection.The pathological injury of lung tissue in each group was observed by HE staining.The total number of cells in BALF was detected.The to-tal protein content of BALF was detected by the BCA method.The contents of inflammatory cytokines TNF-α,IL-1β,IL-6,and IgM in BALF were detected by ELISA.The expression of NF-κB and NLRP3 proteins in lung tissues was detected by immunohistochemistry and Western blotting.Results Compared with model control group,Jinyinqingre oral liquid alleviated the pathological injury of lung tissue(P＜0.05),decreased the total cell count,total protein content and IgM expression in BALF(P＜0.01),and the expres-sion of inflammatory cytokines TNF-α,IL-6 and IL-1β in BALF was dreased(P＜0.05),the protein expressions of NF-κB and NL-RP3 in lung tissues was dreased(P＜0.05).Conclusion Jinyinqingre oral liquid attenuated the pathological injury,inflammatory exudation,and expression of inflammatory cytokines in LPS-induced lung injury in mice,and its mechanism may be through the reg-ulation of NF-κB/NLRP3 signaling pathway,providing a theoretical basis for its clinical application.

Objective To explore the mechanism of hydroxyl safflower flavin A(HSYA)in the treatment of sepsis-induced liver injury by using metabolomics and network pharmacology.Methods A total of 50 male C57BL/6 mice were randomly divided into sham-operation group(10 mice),sepsis group(20 mice)and HSYA group(20 mice).Cecal ligation and puncture was conducted to establish the sepsis-induced liver injury mouse model.The mice in HSYA group were subcutaneously injected with HSYA after 2 hours of modeling.The content of serum inflammatory factors and liver function were detected,and the pathological changes of liver tissue were observed with HE staining,UPLC-Q-TOF-MS metabolomics was used to analyze liver tissue,screening for differential metabolites using multivariate statistical methods,network pharmacology was used to predict potential targets for HSYA treatment of sepsis-induced liver injury,and conduct GO and KEGG pathway enrichment analysis on potential targets,Metabo Analyst 5.0 database was used to match differential metabolites and potential targets between the model group and HSYA group,a targets metabolite-metabolism pathway network was constructed.AutoDock Vina software was used to perform molecular docking between HSYA and core genes,and finally RT-qPCR was used to verify the expression of core genes.Results HSYA can reduce the contents of IL-6,IL-1β and TNF-α in serum,restore liver function,and alleviate the morphological alternation in liver induced by sepsis.A total of 26 differential metabolites identified by metabolomics were screened out,including flufenamic acid,cryptolepine,opthalmic acid,fenpropathrin etc.,which were mainly involved in 5 metabolic pathways such as biosynthesis of unsaturated fatty acids and alpha-linolenic acid metabolism.Network pharmacology identified 81 potential targets,2 735 items enriched in GO and 124 signaling pathways enriched in KEGG;a total of 5 differential metabolites were matched for joint analysis,corresponding to 14 targets including IL1B,STAT3,PTGS2,TP53,etc.,involved in the regulation of metabolic disorders in sepsis-induced liver injury by HSYA.Molecular docking results showed that HSYA had good binding activity to IL1B,STAT3,PTGS2 and TP53 targets.RT-qPCR results showed that HSYA could inhibit the expressions of IL1B,STAT3 and PTGS2 in liver tissue.Conclusions HSYA may inhibit the release of inflammatory cytokines,maintain metabolic homeostasis,and alleviate sepsis-induced liver injury through modulating the expressions of IL1B,STAT3,and PTGS2.

Celastrol and wilforlide A are the main active triterpenoids of the traditional Chinese medicine Lei Gong Teng, which have anti-tumour, anti-inflammatory and immunosuppressive activities, and are the material basis for the clinical efficacy of Lei Gong Teng-related Chinese medicinal preparations. By analysing the biosynthetic pathway of active ingredients, optimizing genetic elements and utilizing "cell factory" to produce triterpenoids heterologously will be an effective way to obtain from Tripterygium wilfordii in the future in a "low-cost and high-efficient" manner. CYP712Ks are the first cytochrome P450s involved in the skeleton modification of friedelane-type and oleanane-type triterpenoids in T. wilfordii, and they can catalyse the generation of polpunonic acid from friedelin and 3-epi-katonic acid from β-amyrin by carboxylation at C-29 position. In this study, four multifunctional TwCYP712K1/2/3/5 were used to clarify the catalytic function and substrate selection preference using in vivo functional characterization in Saccharomyces cerevisiae. The spatial structure of the protein-substrate binding was clarified through homology modeling and molecular docking, and then the differential amino acids in the active pocket of the protein were mutated to clarify the crucial amino acids determining the catalytic function and the selection of substrate structure. A total of 63 mutant elements were constructed, and the amino acid sites affecting the carboxylation function of TwCYP712Ks were analyzed. In particular, the key amino acids affecting the substrate selectivity of TwCYP712K2 towards oleanane-type and friedelane-type triterpenoids were revealed and the TwCYP712K2^F127I and TwCYP712K2^A227T mutants would result in a reversal of the product ratio. In conclusion, four proteins of TwCYP712Ks were semi-rationally designed by homologous protein alignment and mutual mutation to elucidate multiple amino acid sites determining the catalytic function of the proteins, and a series of activity-enhancing or altering mutants were obtained, which provide abundant catalytic elements for the biosynthesis of active triterpenoids from T. wilfordii, and the mechanism of carboxylation in the C-29 position was initially elucidated.

The objective of this study was to observe the effect of Astragalus membranaceus on high sugar-induced Caenorhabditis elegans, and to explore its mechanism of action. UPLC-MS method was used to identify the components of Astragalus membranaceus. A high glucose model was established by using Caenorhabditis elegans as a model organism, and the effects of Astragalus membranaceus on body length, body bending, swallowing frequency, and reactive oxygen species (ROS) of the nematode were determined; the effects of Astragalus membranaceus on the expression of mRNA of genes related to the protein skinhead-1 (SKN-1) signaling pathway were examined by using the real-time fluorescence quantitative polymerase chain reaction (PCR). The results showed that compared with the normal group, the nematode body length, body bending, and swallowing frequency expression were significantly reduced and the ROS content in the body was significantly increased in the high glucose state; after the administration of Astragalus membranaceus, the body length, body bending, and swallowing frequency expression were significantly increased, and the ROS content was significantly reduced (P < 0.01). Compared with the normal group, SKN-1, superoxide dismutas-3 (SOD-3), glutathione S-transferase 4 (GST-4), and glutathione S-transferase 7 (GST-7) expression were significantly decreased in Caenorhabditis elegans in the high glucose condition; SKN-1, SOD-3, GST-4, and GST-7 expression were significantly increased after administration of Astragalus membranaceus (P < 0.01). In the present study, we demonstrated that Astragalus membranaceus has an effect on high glucose-induced Caenorhabditis elegans nematodes, and its mechanism of action may be through the modulation of the SKN-1 signaling pathwaym in order to ameliorate the oxidative stress response induced by high glucose.