ObjectiveTo analyze the characteristic expression patterns of six neurotransmitters including 5-hydroxytryptamine （5-HT）， dopamine （DA）， acetylcholine （ACh）， norepinephrine （NE）， inhibitory neurotransmitter （INH）， and excitatory neurotransmitter （EXC） in the whole brain and different brain regions of depression patients by Search of Encephalo Telex （SET）， providing new ideas for the study of heterogeneous etiology of depression. Methods（1） A retrospective study was conducted on supra-slow signals of EEG fluctuations in 1 028 patients with depression. The SET system was used to obtain the expression information of six neurotransmitters in the whole brain and 12 brain regions： left frontal region （F3）， right frontal region （F4）， left central region （C3）， right central region （C4）， left parietal region （P3）， right parietal region （P4）， left occipital region （O1）， right occipital region （O2）， left anterior temporal region （F7）， right anterior temporal region （F8）， left posterior temporal region （T5）， and right posterior temporal region （T6）. The expression information of each neurotransmitter was compared with the normal model， and it was found that single neurotransmitter was in one of three states： increased， decreased， or normal expression. The simultaneous expression states of six neurotransmitters in the brain space were referred to as the expression pattern of multiple neurotransmitters. （2） A MySQL database was established to analyze the actual expression patterns of different neurotransmitters in the whole brain of patients with depression. （3） Factor analysis was conducted to further analyze the characteristic rules of 78 variables of neurotransmitters in the whole brain and 12 brain regions in depression patients. Results（1） The expression of single neurotransmitters in the whole brain and different brain regions of the total depression population showed one of three expression states （increased/decreased/normal）， being normal in the majority. The decreased and increased expression of 5-HT， ACh， DA， INH， EXC， and NE in the whole brain occurred in 6% and 25%， 31% and 17%， 36% and 9%， 15% and 31%， 32% and 14%， and 22% and 22%， respectively. （2） The antagonizing pairs of neurotransmitters （EXC/INH， DA/5-HT， and ACh/NE） showed significant antagonistic relationships in the whole brain and different brain regions， with a strong negative correlation between EXC and INH （P<0.01， |r| values ranging from 0.69 to 0.76）， a strong negative correlation between DA and 5-HT （P<0.01， |r| values ranging from 0.83 to 0.90）， and a moderate negative correlation between ACh and NE （P<0.01， with |r| values ranging from 0.56 to 0.66）. Meanwhile， non-antagonizing pairs of neurotransmitters in the whole brain and different brain regions also showed correlations， with DA/NE （P<0.01， |r| values ranging from 0.38 to 0.46） and NE/EXC （P<0.01， |r| values ranging from 0.56 to 0.61） showing weak and moderate negative correlations， respectively， and DA/EXC showing a weak positive correlation （P<0.01， |r| values ranging from 0.38 to 0.47）. （3） The six neurotransmitters in the 1 028 patients with depression presented a total of 170 expression patterns in the whole brain. The top 30 expression patterns were reported in this paper， with a cumulative rate of 60.60%， including patterns ① INH+/5-HT-/ACh+/DA+/NE-/EXC- （9.05%）， ② INH+/5-HT-/ACh↓/DA+/NE-/EXC- （4.57%）， and ③ INH+/5-HT-/ACh+/DA+/NE↓/EXC- （3.31%）. That is， the proportion of depression patients with normal levels of all the six neurotransmitters was 9.05%， and the patients with at least one neurotransmitter abnormality accounted for 91.95%. （4） The factor analysis extracted 22 common factors from 78 variables in the whole brain and different brain regions. These common factors showed the absolute values of loadings ranging from 0.32 to 0.86 and the eigenvalues （F） ranging from 1.03 to 13.43， with a cumulative contribution rate of 76.82%. The characteristic expression patterns included ① ACh_P3↓/ACh_W↓/ACh_C3↓/ACh_F3↓/ACh_O1↓/ACh_T5↓/ACh_F7↓/NE_P3↑/NE_W↑/NE_C3↑/NE_F3↑/NE_O1↑/NE_T5↑/NE_F7↑ （F=13.43， whole brain）， ② 5-HT_O2↑/DA_O2↓/5-HT_P4↑/DA_P4↓/5-HT_W↑/DA_W↓/5-HT_C4↑/DA_C4↓ （F=5.94）， and ③ EXC_F4↓/DA_F4↓/NE_F4↑/INH_F4↑/5-HT_F4↑/ACh_F4↓ （F=5.33）. ConclusionThe actual 170 expression patterns of 6 neurotransmitters in the whole brain of 1 028 depression patients indicate that depression is a heterogeneous disease with individualized characteristics. The 22 characteristic expression patterns in the whole brain and 12 brain regions verify the pathogenesis hypothesis of multi-neurotransmitters oscillation imbalance in brains of depression patients. In summary， this study provides new guidance for the etiology， diagnosis， and treatment of depression and establishes a methodological foundation for the effectiveness evaluation of individualized treatment of depression by traditional Chinese medicine based on the objective biological markers.

ObjectiveTo analyze the characteristic expression patterns of six neurotransmitters including 5-hydroxytryptamine （5-HT）， dopamine （DA）， acetylcholine （ACh）， norepinephrine （NE）， inhibitory neurotransmitter （INH）， and excitatory neurotransmitter （EXC） in the whole brain and different brain regions of depression patients by Search of Encephalo Telex （SET）， providing new ideas for the study of heterogeneous etiology of depression. Methods（1） A retrospective study was conducted on supra-slow signals of EEG fluctuations in 1 028 patients with depression. The SET system was used to obtain the expression information of six neurotransmitters in the whole brain and 12 brain regions： left frontal region （F3）， right frontal region （F4）， left central region （C3）， right central region （C4）， left parietal region （P3）， right parietal region （P4）， left occipital region （O1）， right occipital region （O2）， left anterior temporal region （F7）， right anterior temporal region （F8）， left posterior temporal region （T5）， and right posterior temporal region （T6）. The expression information of each neurotransmitter was compared with the normal model， and it was found that single neurotransmitter was in one of three states： increased， decreased， or normal expression. The simultaneous expression states of six neurotransmitters in the brain space were referred to as the expression pattern of multiple neurotransmitters. （2） A MySQL database was established to analyze the actual expression patterns of different neurotransmitters in the whole brain of patients with depression. （3） Factor analysis was conducted to further analyze the characteristic rules of 78 variables of neurotransmitters in the whole brain and 12 brain regions in depression patients. Results（1） The expression of single neurotransmitters in the whole brain and different brain regions of the total depression population showed one of three expression states （increased/decreased/normal）， being normal in the majority. The decreased and increased expression of 5-HT， ACh， DA， INH， EXC， and NE in the whole brain occurred in 6% and 25%， 31% and 17%， 36% and 9%， 15% and 31%， 32% and 14%， and 22% and 22%， respectively. （2） The antagonizing pairs of neurotransmitters （EXC/INH， DA/5-HT， and ACh/NE） showed significant antagonistic relationships in the whole brain and different brain regions， with a strong negative correlation between EXC and INH （P<0.01， |r| values ranging from 0.69 to 0.76）， a strong negative correlation between DA and 5-HT （P<0.01， |r| values ranging from 0.83 to 0.90）， and a moderate negative correlation between ACh and NE （P<0.01， with |r| values ranging from 0.56 to 0.66）. Meanwhile， non-antagonizing pairs of neurotransmitters in the whole brain and different brain regions also showed correlations， with DA/NE （P<0.01， |r| values ranging from 0.38 to 0.46） and NE/EXC （P<0.01， |r| values ranging from 0.56 to 0.61） showing weak and moderate negative correlations， respectively， and DA/EXC showing a weak positive correlation （P<0.01， |r| values ranging from 0.38 to 0.47）. （3） The six neurotransmitters in the 1 028 patients with depression presented a total of 170 expression patterns in the whole brain. The top 30 expression patterns were reported in this paper， with a cumulative rate of 60.60%， including patterns ① INH+/5-HT-/ACh+/DA+/NE-/EXC- （9.05%）， ② INH+/5-HT-/ACh↓/DA+/NE-/EXC- （4.57%）， and ③ INH+/5-HT-/ACh+/DA+/NE↓/EXC- （3.31%）. That is， the proportion of depression patients with normal levels of all the six neurotransmitters was 9.05%， and the patients with at least one neurotransmitter abnormality accounted for 91.95%. （4） The factor analysis extracted 22 common factors from 78 variables in the whole brain and different brain regions. These common factors showed the absolute values of loadings ranging from 0.32 to 0.86 and the eigenvalues （F） ranging from 1.03 to 13.43， with a cumulative contribution rate of 76.82%. The characteristic expression patterns included ① ACh_P3↓/ACh_W↓/ACh_C3↓/ACh_F3↓/ACh_O1↓/ACh_T5↓/ACh_F7↓/NE_P3↑/NE_W↑/NE_C3↑/NE_F3↑/NE_O1↑/NE_T5↑/NE_F7↑ （F=13.43， whole brain）， ② 5-HT_O2↑/DA_O2↓/5-HT_P4↑/DA_P4↓/5-HT_W↑/DA_W↓/5-HT_C4↑/DA_C4↓ （F=5.94）， and ③ EXC_F4↓/DA_F4↓/NE_F4↑/INH_F4↑/5-HT_F4↑/ACh_F4↓ （F=5.33）. ConclusionThe actual 170 expression patterns of 6 neurotransmitters in the whole brain of 1 028 depression patients indicate that depression is a heterogeneous disease with individualized characteristics. The 22 characteristic expression patterns in the whole brain and 12 brain regions verify the pathogenesis hypothesis of multi-neurotransmitters oscillation imbalance in brains of depression patients. In summary， this study provides new guidance for the etiology， diagnosis， and treatment of depression and establishes a methodological foundation for the effectiveness evaluation of individualized treatment of depression by traditional Chinese medicine based on the objective biological markers.

Objective: To investigate the current status of knowledge, attitudes and practices regarding drinking water among primary school students in rural areas of China, so as to provide scientific basis for implementing health interventions related to drinking water. Methods: From November to December 2023, a stratified cluster random sampling method was employed to select 6 354 fourth to sixth grade primary school students in Shanxi, Zhejiang, Jiangxi, Guangxi and Gansu for a questionnaire survey. A uniformly designed questionnaire (including basic information, drinking water-related knowledge, attitudes and practices indicators) was distributed and completed by the students themselves. The χ 2 test was used to analyze the differences in drinking water-related indicators among students of different gender and boarder, and Logistic regression was used to analyze the influencing factors of drinking water practices among students. Results: Among the indicators of drinking water knowledge, the awareness rate of appropriate daily water intake for respective student age groups was the lowest (27.90%). The awareness rate among nonresident students was significantly higher than that among boarding students (31.29%, 15.49%, χ 2=132.75, P <0.01). Regarding attitudes toward drinking water, 13.33% of the students believed that well water or tap water could be drunk directly, and 9.58% believed that going to the toilet at school was troublesome. Regarding practices, the self-reported water intake among students was 1 000 (600, 1 200) mL. The results of multifactorial Logistic regression showed that higher grades ( OR=1.60, 95%CI =1.34-1.92), nonresident students ( OR=1.32, 95%CI = 1.15 -1.52), northern region ( OR=1.43, 95%CI =1.27-1.61), knowledge of appropriate daily water intake ( OR=1.41, 95%CI =1.24-1.60), drinking temperature ( OR=1.43, 95%CI =1.28-1.60), scientific hydration methods ( OR=1.25, 95%CI =1.08- 1.44 ), and adopting scientific hydration methods regularly ( OR=1.75, 95%CI =1.50-2.04) were the independent influences on daily water intake attainment ( P <0.05). Conclusions Rural primary school students lack knowledge about healthy drinking water, have cognitive biases about safe drinking water and exhibit unhealthy drinking behavior. It is suggested that health education be carried out in combination with the characteristics of students to enhance their drinking water literacy.

Collagen is a major structural protein in the matrix of animal cells and the most widely distributed and abundant functional protein in mammals. Collagen’s good biocompatibility, biodegradability and biological activity make it a very valuable biomaterial. According to the source of collagen, it can be broadly categorized into two types: one is animal collagen; the other is recombinant collagen. Animal collagen is mainly extracted and purified from animal connective tissues by chemical methods, such as acid, alkali and enzyme methods, etc. Recombinant collagen refers to collagen produced by gene splicing technology, where the amino acid sequence is first designed and improved according to one’s own needs, and the gene sequence of improved recombinant collagen is highly consistent with that of human beings, and then the designed gene sequence is cloned into the appropriate vector, and then transferred to the appropriate expression vector. The designed gene sequence is cloned into a suitable vector, and then transferred to a suitable expression system for full expression, and finally the target protein is obtained by extraction and purification technology. Recombinant collagen has excellent histocompatibility and water solubility, can be directly absorbed by the human body and participate in the construction of collagen, remodeling of the extracellular matrix, cell growth, wound healing and site filling, etc., which has demonstrated significant effects, and has become the focus of the development of modern biomedical materials. This paper firstly elaborates the structure, type, and tissue distribution of human collagen, as well as the associated genetic diseases of different types of collagen, then introduces the specific process of producing animal source collagen and recombinant collagen, explains the advantages of recombinant collagen production method, and then introduces the various systems of expressing recombinant collagen, as well as their advantages and disadvantages, and finally briefly introduces the application of animal collagen, focusing on the use of animal collagen in the development of biopharmaceutical materials. In terms of application, it focuses on the use of animal disease models exploring the application effects of recombinant collagen in wound hemostasis, wound repair, corneal therapy, female pelvic floor dysfunction (FPFD), vaginal atrophy (VA) and vaginal dryness, thin endometritis (TE), chronic endometritis (CE), bone tissue regeneration in vivo, cardiovascular diseases, breast cancer (BC) and anti-aging. The mechanism of action of recombinant collagen in the treatment of FPFD and CE was introduced, and the clinical application and curative effect of recombinant collagen in skin burn, skin wound, dermatitis, acne and menopausal urogenital syndrome (GSM) were summarized. From the exploratory studies and clinical applications, it is evident that recombinant collagen has demonstrated surprising effects in the treatment of all types of diseases, such as reducing inflammation, promoting cell proliferation, migration and adhesion, increasing collagen deposition, and remodeling the extracellular matrix. At the end of the review, the challenges faced by recombinant collagen are summarized: to develop new recombinant collagen types and dosage forms, to explore the mechanism of action of recombinant collagen, and to provide an outlook for the future development and application of recombinant collagen.

Electromagnetic fields can regulate the fundamental biological processes involved in bone remodeling. As a non-invasive physical therapy, electromagnetic fields with specific parameters have demonstrated therapeutic effects on bone remodeling diseases, such as fractures and osteoporosis. Electromagnetic fields can be generated by the movement of charged particles or induced by varying currents. Based on whether the strength and direction of the electric field change over time, electromagnetic fields can be classified into static and time-varying fields. The treatment of bone remodeling diseases with static magnetic fields primarily focuses on fractures, often using magnetic splints to immobilize the fracture site while studying the effects of static magnetic fields on bone healing. However, there has been relatively little research on the prevention and treatment of osteoporosis using static magnetic fields. Pulsed electromagnetic fields, a type of time-varying field, have been widely used in clinical studies for treating fractures, osteoporosis, and non-union. However, current clinical applications are limited to low-frequency, and research on the relationship between frequency and biological effects remains insufficient. We believe that different types of electromagnetic fields acting on bone can induce various “secondary physical quantities”, such as magnetism, force, electricity, acoustics, and thermal energy, which can stimulate bone cells either individually or simultaneously. Bone cells possess specific electromagnetic properties, and in a static magnetic field, the presence of a magnetic field gradient can exert a certain magnetism on the bone tissue, leading to observable effects. In a time-varying magnetic field, the charged particles within the bone experience varying Lorentz forces, causing vibrations and generating acoustic effects. Additionally, as the frequency of the time-varying field increases, induced currents or potentials can be generated within the bone, leading to electrical effects. When the frequency and power exceed a certain threshold, electromagnetic energy can be converted into thermal energy, producing thermal effects. In summary, external electromagnetic fields with different characteristics can generate multiple physical quantities within biological tissues, such as magnetic, electric, mechanical, acoustic, and thermal effects. These physical quantities may also interact and couple with each other, stimulating the biological tissues in a combined or composite manner, thereby producing biological effects. This understanding is key to elucidating the electromagnetic mechanisms of how electromagnetic fields influence biological tissues. In the study of electromagnetic fields for bone remodeling diseases, attention should be paid to the biological effects of bone remodeling under different electromagnetic wave characteristics. This includes exploring innovative electromagnetic source technologies applicable to bone remodeling, identifying safe and effective electromagnetic field parameters, and combining basic research with technological invention to develop scientifically grounded, advanced key technologies for innovative electromagnetic treatment devices targeting bone remodeling diseases. In conclusion, electromagnetic fields and multiple physical factors have the potential to prevent and treat bone remodeling diseases, and have significant application prospects.

Traditional Chinese medicine （TCM） thinking serves as a comprehensive cognitive approach of TCM in recognizing and solving problem. It encompasses specific techniques （methods）and particular structures （patterns） in application. Its essential characteristics include the holistic view of "harmony between humanity and nature"， the dialectical perspective of "differences and similarities in disease treatment"， and the practical outlook of "unity of knowledge and action". The methods of TCM thinking emphasizes the integration of multiple cognitive approaches， forming various modes of thinking such as TCM holistic thinking， TCM four-dimensional thinking， TCM Xiang （象） and numerical thinking， and TCM clinical thinking. Currently， TCM faces both opportunities and challenges. TCM thinking plays a crucial role in the inheritance and innovation pathways of TCM， such as "cultivating medicine through culture"， "leading medicine through pharmaceutical practices"， "boosting industries with pharmaceuticals"， and "benefiting the people through industry". At the same time， integrating TCM and modern technology not only enriches the connotation of TCM thinking， but also advances the innovation of TCM theories， addressing challenges in complex disease treatment， health management， and preventive healthcare. This integration promotes the continued prosperity of the TCM and accelerates its internationalization.

Objective By combining biological detection and imaging evaluation, a clinical prediction model is constructed based on a large cohort to improve the accuracy of distinguishing between benign and malignant pulmonary nodules. Methods A retrospective analysis was conducted on the clinical data of the 32 627 patients with pulmonary nodules who underwent chest CT and testing for 7 types of lung cancer-related serum autoantibodies (7-AABs) at our hospital from January 2020 to April 2024. The univariate and multivariate logistic regression models were performed to screen independent risk factors for benign and malignant pulmonary nodules, based on which a nomogram model was established. The performance of the model was evaluated using receiver operating characteristic (ROC) curves, calibration curves, and decision curve analysis (DCA). Results A total of 1 017 patients with pulmonary nodules were included in the study. The training set consisted of 712 patients, including 291 males and 421 females, with a mean age of (58±12) years. The validation set included 305 patients, comprising 129 males and 176 females, with a mean age of (58±13) years. Univariate ROC curve analysis indicated that the combination of CT and 7-AABs testing achieved the highest area under the curve (AUC) value (0.794), surpassing the diagnostic efficacy of CT alone (AUC=0.667) or 7-AABs alone (AUC=0.514). Multivariate logistic regression analysis showed that radiological nodule diameter, nodule nature, and CT combined with 7-AABs detection were independent predictors, which were used to construct a nomogram prediction model. The AUC values for this model were 0.826 and 0.862 in the training and validation sets, respectively, demonstrating excellent performance in DCA. Conclusion The combination of 7-AABs with CT significantly enhances the accuracy of distinguishing between benign and malignant pulmonary nodules. The developed predictive model provides strong support for clinical decision-making and contributes to achieving precise diagnosis and treatment of pulmonary nodules.

ObjectiveThe nucleolar protein PES1 (Pescadillo homolog 1) plays critical roles in ribosome biogenesis and cell cycle regulation, yet its involvement in cellular senescence remains poorly understood. This study aimed to comprehensively investigate the functional consequences of PES1 suppression in cellular senescence and elucidate the molecular mechanisms underlying its regulatory role. MethodsInitially, we assessed PES1 expression patterns in two distinct senescence models: replicative senescent mouse embryonic fibroblasts (MEFs) and doxorubicin-induced senescent human hepatocellular carcinoma HepG2 cells. Subsequently, PES1 expression was specifically downregulated using siRNA-mediated knockdown in these cell lines as well as additional relevant cell types. Cellular proliferation and senescence were assessed by EdU incorporation and SA-β-gal staining assays, respectively. The expression of senescence-associated proteins (p53, p21, and Rb) and SASP factors (IL-6, IL-1β, and IL-8) were analyzed by Western blot or qPCR. Furthermore, Northern blot and immunofluorescence were employed to evaluate pre-rRNA processing and nucleolar morphology. ResultsPES1 expression was significantly downregulated in senescent MEFs and HepG2 cells. PES1 knockdown resulted in decreased EdU-positive cells and increased SA‑β‑gal-positive cells, indicating proliferation inhibition and senescence induction. Mechanistically, PES1 suppression activated the p53-p21 pathway without affecting Rb expression, while upregulating IL-6, IL-1β, and IL-8 production. Notably, PES1 depletion impaired pre-rRNA maturation and induced nucleolar stress, as evidenced by aberrant nucleolar morphology. ConclusionOur findings demonstrate that PES1 deficiency triggers nucleolar stress and promotes p53-dependent (but Rb-independent) cellular senescence, highlighting its crucial role in maintaining nucleolar homeostasis and regulating senescence-associated pathways.

Aim To explore the mechanism of Yanghe decoction-containing serum on the migration and inva-sion of MCF-7 breast cancer cells in a co-culture sys-tem with M2 tumor-associated macrophages(TAMs)based on the paracrine epidermal growth factor(EGF)/epidermal growth factor receptor(EGFR)sig-naling pathway.Methods The M2-type TAMs model was induced from THP-1 monocytic cell line through in vitro treatment with phorbol 12-myristate 13-acetate(PMA)and recombinant human macrophage colony-stimulating factor(M-CSF).The MCF-7 cells were co-cultured with M2-type TAMs using a Transwell non-contact co-culture system to evaluate their effects on migration and invasion.Subsequently,the cells were intervened with serum containing Yanghe decoction,and the proliferation of MCF-7 cells was detected using the CCK-8 assay,while their lateral migration ability was assessed through scratch assays.The invasion and vertical migration abilities of the cells were evaluated separately using Transwell assays,and the concentra-tion of EGF was measured using ELISA.Finally,the expression of EGFR,MCP-1,and MMP9 proteins was detected using Western blot.Results Compared to the control group,Yanghe decoction-containing serum in-hibited the proliferation of MCF-7 cells before and after co-culture.The serum reduced the scratch healing a-bility before and after co-culture and decreased their migration and invasion abilities.Additionally,Yanghe decoction-containing serum reduced the levels of EGF before and after co-culture and decreased the expres-sion of EGFR,MCP-1,and MMP9 proteins before and after+co-culture.Conclusion Yanghe decoction-containing serum can inhibit the migration and invasion of breast cancer MCF-7 cells before and after co-cul-ture with M2 TAMs.This effect may be related to the inhibition of the EGF-EGFR signaling pathway.

Objective:To determine the relative correction factor of pre-vitamin D and simplify the calculation method of vitamin D assay.Methods:By studying the calculation method of vitamin D content in drug standards of various countries,HPLC was used to determine the relative correction factor of pre-vitamin D,and the influencing factors of determination were investigated.Results:The relative correction factors of pre-vitamin D at 254 nm and 265nm wavelength were determined by statistical analysis of 7 laboratories in China.Conclusion:Using the pre-vi-tamin D relative correction factor method to calculate the total amount of vitamin D simplified the experimental steps can be simplified by the pre-vitamin D relative correction factor method to calculate the total amount of vitamin D and the random operating errors can be avoided.The method is rapid and accurate,and lay a solid foundation for further improving the standard of vitamin D preparations.