As an important part of Chinese traditional culture， the processing technology of traditional Chinese medicine（TCM） carries the wisdom of TCM for thousands of years， and its process is complex and rigorous. With the popularization of modern production technology， traditional processing techiques are facing the dual pressures from technological innovation and production standardization under the perspective of intangible cultural heritage. The modernization of TCM processing technology is an inevitable trend for industrial upgrading， but it cannot be separated from the foundation of traditional skills and ignore the core concepts and cultural values it embodies. Therefore， by analyzing the core characteristics of TCM processing technology and its differences with modern production， this paper discusses the establishment of a synergistic innovation mechanism between traditional techniques and modern technologies， the promotion of joint research and development between scientific research institutes and the industry， the strengthening of standardization of processing techniques， and the enhancement of social education and industry training to improve the recognition and inheritance of processing techniques in order to achieve the goal of innovation and protection of TCM processing technologies in the context of modernization， and to promote the high-quality development of the TCM processing industry.

Guided by the concept of quality by design(QbD), this study optimizes the calcination and quenching process of calcined Magnetitum and establishes the XRD characteristic spectra of calcined Magnetitum, providing a scientific basis for the formulation of quality standards. Based on the processing methods and quality requirements of Magnetitum in the Chinese Pharmacopoeia, the critical process parameters(CPPs) identified were calcination temperature, calcination time, particle size, laying thickness, and the number of vinegar quenching cycles. The critical quality attributes(CQAs) included Fe mass fraction, Fe~(2+) dissolution, and surface color. The weight coefficients were determined by combining Analytic Hierarchy Process(AHP) and the criteria importance though intercrieria correlation(CRITIC) method, and the calcination process was optimized using orthogonal experimentation. Surface color was selected as a CQA, and based on the principle of color value, the surface color of calcined Magnetitum was objectively quantified. The vinegar quenching process was then optimized to determine the best processing conditions. X-ray diffraction(XRD) was used to establish the characteristic spectra of calcined Magnetitum, and methods such as similarity evaluation, cluster analysis, and orthogonal partial least squares-discriminant analysis(OPLS-DA) were used to evaluate the quality of the spectra. The optimized calcined Magnetitum preparation process was found to be calcination at 750 ℃ for 1 h, with a laying thickness of 4 cm, a particle size of 0.4-0.8 cm, and one vinegar quenching cycle(Magnetitum-vinegar ratio 10∶3), which was stable and feasible. The XRD characteristic spectra analysis method, featuring 9 common peaks as fingerprint information, was established. The average correlation coefficient ranged from 0.839 5-0.988 1, and the average angle cosine ranged from 0.914 4 to 0.995 6, indicating good similarity. Cluster analysis results showed that Magnetitum and calcined Magnetitum could be grouped together, with similar compositions. OPLS-DA discriminant analysis identified three key characteristic peaks, with Fe_2O_3 being the distinguishing component between the two. The final optimized processing method is stable and feasible, and the XRD characteristic spectra of calcined Magnetitum was initially established, providing a reference for subsequent quality control and the formulation of quality standards for calcined Magnetitum.
X-Ray Diffraction/methods* ; Drugs, Chinese Herbal/chemistry* ; Quality Control ; Particle Size

This study aims to investigate the effect of Chaijin Jieyu Anshen Formula on the neuroinflammation of rats with insomnia complicated with depression through the regulation of triggering receptor expressed on myeloid cells 2(TREM2)/complement protein C1q signaling pathway. Rats were randomly divided into a normal group, a model group, a positive drug group, as well as a high, medium, and low-dose groups of Chaijin Jieyu Anshen Formula, with 10 rats in each group. Except for the normal group, the other groups were injected with p-chlorophenylalanine and exposed to chronic unpredictable mild stress to establish the rat model of insomnia complicated with depression. The sucrose preference experiment, open field experiment, and water maze test were performed to evaluate the depression in rats. Enzyme-linked immunosorbent assay was employed to detect serum 5-hydroxytryptamine(5-HT), dopamine(DA), and norepinephrine(NE) levels. Hematoxylin and eosin staining and Nissl staining were used to observe the damage in nucleus accumbens neurons. Western blot and immunofluorescence were performed to detect TREM2, C1q, postsynaptic density 95(PSD-95), and synaptophysin 1(SYN1) expressions in rat nucleus accumbens, respectively. Golgi-Cox staining was utilized to observe the synaptic spine density of nucleus accumbens neurons. The results show that, compared with the model group, Chaijin Jieyu Anshen Formula can significantly increase the sucrose preference as well as the distance and number of voluntary activities, shorten the immobility time in forced swimming test and the successful incubation period of positioning navigation, and prolong the stay time of space exploration in the target quadrant test. The serum 5-HT, DA, and NE contents in the model group are significantly lower than those in the normal group, with the above contents significantly increased after the intervention of Chaijin Jieyu Anshen Formula. In addition, Chaijin Jieyu Anshen Formula can alleviate pathological damages such as swelling and loose arrangement of tissue cells in the nucleus accumbens, while increasing the Nissl body numbers. Chaijin Jieyu Anshen Formula can improve synaptic damage in the nucleus accumbens and increase the synaptic spine density. Compared to the normal group, the expression of C1q protein was significantly higher in the model group, while the expression of TREM2 protein was significantly lower. Compared to the model group, the intervention with Chaijin Jieyu Anshen Formula significantly downregulated the expression of C1q protein and significantly upregulated the expression of TREM2. Compared with the model group, the PSD-95 and SYN1 fluorescence intensity is significantly increased in the groups receiving different doses of Chaijin Jieyu Anshen Formula. In summary, Chaijin Jieyu Anshen Formula can reduce the C1q protein expression, relieve the TREM2 inhibition, and promote the synapse-related proteins PSD-95 and SNY1 expression. Chaijin Jieyu Anshen Formula improves synaptic injury of the nucleus accumbens neurons, thereby treating insomnia complicated with depression.
Animals ; Male ; Rats ; Nucleus Accumbens/metabolism* ; Drugs, Chinese Herbal/administration & dosage* ; Depression/complications* ; Membrane Glycoproteins/genetics* ; Rats, Sprague-Dawley ; Sleep Initiation and Maintenance Disorders/complications* ; Neurons/metabolism* ; Receptors, Immunologic/genetics* ; Signal Transduction/drug effects* ; Synapses/metabolism*

OBJECTIVE: To investigate the expression levels of EZH2 and KMT2D in patients with diffuse large B-cell lymphoma (DLBCL) and their relationship with pathological features. METHODS: 84 patients with DLBCL treated in our hospital from January 2021 to June 2022 were selected as the study subjects, and clinical characteristics such as sex, age and pathological classification of the patients were collected. Immunohistochemistry was used to detecet the expression of KMT2D and EZH2 proteins in tumor tissue cells of the DLBCL patients. The differential expression of KMT2D and EZH2 in subgroups of different sexes, ages, primary sites, clinical stages, Hans subtypes, etc. were compared. The correlation between the expression of KMT2D and EZH2 protein and BCL-6, CD79A was analyzed and validated through the interaction of protein molecular structures. We followed up and recorded the survival status of the patients for 12 months, and analyzed the factors that affect the mortality of DLBCL patients. RESULTS: The positive rate of KMT2D and EZH2 was high (over 95%) in DLBCL patients. There was no significant difference in the expression of EZH2 and KMT2D among subgroups of different sexes, ages and stages (P >0.05). However, patients with different levels of BCL-6 and CD79A expression showed differences in EZH2 and KMT2D expression (P < 0.05). EZH2 and KMT2D were positively correlated with BCL-6 (r =0.391, r =0.332) and CD79A (r =0.309, r =0.258), respectively, and there were interactions in the protein molecular structures. The risk factors for mortality in DLBCL patients include male sex (OR =1.106, 95%CI : 1.082-1.130, P < 0.001), stage II (OR =1.778, 95%CI : 1.567-2.016, P < 0.001), stage IV (OR =2.233, 95%CI : 2.021-2.467, P < 0.001), EZH2 positive (OR =2.762, 95%CI : 1.304-5.850, P =0.008), BCL-6 positive (OR =7.309, 95%CI : 1.340-39.859, P =0.022), age≥74 years (OR =3.080, 95%CI : 1.658-5.723, P < 0.001), and 63-73 years old (OR =2.400, 95%CI : 1.564-3.682, P < 0.001), while KMT2D positive (OR =0.180, 95%CI : 0.054-0.608, P =0.006) and 41-51 years old (OR =0.406, 95%CI : 0.274-0.603, P < 0.001) were factors which could reduce the risk of mortality. CONCLUSION EZH2 and KMT2D are highly expressed in patients with DLBCL, and they are positively correlated with BCL-6 and CD79A, and affect the prognosis of DLBCL patients.
Humans ; Enhancer of Zeste Homolog 2 Protein/metabolism* ; Lymphoma, Large B-Cell, Diffuse/metabolism* ; DNA-Binding Proteins/metabolism* ; Female ; Male ; Middle Aged ; Adult ; Neoplasm Proteins/metabolism* ; Aged ; Immunohistochemistry ; Proto-Oncogene Proteins c-bcl-6/metabolism* ; Prognosis

Attempts have been made to modulate motor sequence learning (MSL) through repetitive transcranial magnetic stimulation, targeting different sites within the sensorimotor network. However, the target with the optimum modulatory effect on neural plasticity associated with MSL remains unclarified. This study was therefore designed to compare the role of the left primary motor cortex and the left supplementary motor area proper (SMAp) in modulating MSL across different complexity levels and for both hands, as well as the associated neuroplasticity by applying intermittent theta burst stimulation together with the electroencephalogram and concurrent transcranial magnetic stimulation. Our data demonstrated the role of SMAp stimulation in modulating neural communication to support MSL, which is achieved by facilitating regional activation and orchestrating neural coupling across distributed brain regions, particularly in interhemispheric connections. These findings may have important clinical implications, particularly for motor rehabilitation in populations such as post-stroke patients.
Humans ; Transcranial Magnetic Stimulation ; Motor Cortex/physiology* ; Male ; Electroencephalography ; Neuronal Plasticity/physiology* ; Female ; Adult ; Evoked Potentials, Motor/physiology* ; Young Adult ; Learning/physiology*

Loss of protein homeostasis is a hallmark of cellular senescence, and ribosome pausing plays a crucial role in the collapse of proteostasis. However, our understanding of ribosome pausing in senescent cells remains limited. In this study, we utilized ribosome profiling and G-quadruplex RNA immunoprecipitation sequencing techniques to explore the impact of RNA G-quadruplex (rG4) on the translation efficiency in senescent cells. Our results revealed a reduction in the translation efficiency of rG4-rich genes in senescent cells and demonstrated that rG4 structures within coding sequence can impede translation both in vivo and in vitro. Moreover, we observed a significant increase in the abundance of rG4 structures in senescent cells, and the stabilization of the rG4 structures further exacerbated cellular senescence. Mechanistically, the RNA helicase DHX9 functions as a key regulator of rG4 abundance, and its reduced expression in senescent cells contributing to increased ribosome pausing. Additionally, we also observed an increased abundance of rG4, an imbalance in protein homeostasis, and reduced DHX9 expression in aged mice. In summary, our findings reveal a novel biological role for rG4 and DHX9 in the regulation of translation and proteostasis, which may have implications for delaying cellular senescence and the aging process.
G-Quadruplexes ; Cellular Senescence ; Ribosomes/genetics* ; Humans ; Animals ; Mice ; DEAD-box RNA Helicases/genetics* ; Protein Biosynthesis ; RNA/chemistry* ; Neoplasm Proteins

Age-related macular degeneration (AMD) represents a predominant cause of blindness among older adults, with limited therapeutic options currently available. Oxidative stress, inflammation, and retinal pigment epithelium injury are recognized as key contributors to the pathogenesis of AMD. Regulated cell death plays a pivotal role in mediating cellular responses to stress, maintaining tissue homeostasis, and contributing to disease progression. Recent research has elucidated several regulated cell death pathways-such as apoptosis, ferroptosis, pyroptosis, necroptosis, and autophagy-that may contribute to the progression of AMD owing to cell death in the retinal pigment epithelium. These discoveries open new avenues for therapeutic interventions in patients with AMD. In this review, we provide a comprehensive summary and analysis of the latest advancements regarding the relationship between regulated cell death and AMD. Moreover, we examined the therapeutic potential of targeting regulated cell death pathways for the treatment and prevention of AMD, highlighting their roles as promising targets for future therapeutic strategies.

Bone grafting is a primary method for treating bone defects. Among various graft materials, xenogeneic bone substitutes are widely used in clinical practice due to their abundant sources, convenient processing and storage, and avoidance of secondary surgeries. With the advancement of domestic production and the limitations of imported products, an increasing number of bone filling or grafting substitute materials isentering clinical trials. Relevant experts have drafted this consensus to enhance the management of medical device clinical trials, protect the rights of participants, and ensure the scientific and effective execution of trials. It summarizes clinical experience in aspects, such as design principles, participant inclusion/exclusion criteria, observation periods, efficacy evaluation metrics, safety assessment indicators, and quality control, to provide guidance for professionals in the field.
Humans ; Bone Substitutes/therapeutic use* ; Randomized Controlled Trials as Topic/methods* ; Consensus ; Bone Transplantation ; Research Design

Objective To explore the dynamic changes and mechanisms of neurological and cognitive functions in mice with traumatic brain injury (TBI). Methods Totally 60 12⁃month⁃old Balb/ c mice were divided into control group (10 in group) and TBI group (50 in group). TBT model mice were divided into 5 subgroups according to the time of model construction, including model 1 day, model 1 day, model 3 day, model 7 day, model 14 days and model 28 days group with 10 in each group. At the 29th day of the experiment, neurological scores and step down tests were carried out. After the test, the mice were sacrificed for brains which were detected by immunohistochemistry staining, inflammatory cytokine tests and Western blotting. Results Compared with the control group, the neurological scores of mice in TBI group increased, and then decreased after the 7th day when the scores reached the peak. However, the latency of step down errors was lower than control group, and the number of step down errors was higher than control group which had no changes. Compared with the control group, the expression of lonized calcium⁃binding adapter molecule 1(IBA1), chemokine C⁃X3⁃C⁃motif ligand1 (CX3CL1), C⁃X3⁃C chemokine receptor 1(CX3CR1), NOD⁃like receptor thermal protein domain associated protein 3 (NLRP3), and phosphorylation nuclear factor(p⁃NF)⁃κB in TBI group increased and reached to the peak at the 7th day, and then started to decrease. At the same time, the levels of inflammatory cytokines interleukin⁃6(IL⁃6) and tumor necrosis factor⁃α(TNF⁃α) first increased to the peak, and then began to decrease. However, compared with the control group, the expression of amyloid β(Aβ) protein and p⁃Tau protein in the model group continued to increase at all time. Conclusion The TBI model caused continuous activation of microglia along with inflammatory response, which first increased and then decreased, resultsing in neurological scores changes. In addition, the inflammatory response may act as a promoter of Aβ protein deposition and Tau protein phosphorylation, leading to cognitive impairment in mice.