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.

Polygonati Rhizoma demonstrates significant potential for addressing both chronic and hidden hunger. The supply of high-quality seedlings is a primary factor influencing the development of the Polygonati Rhizoma industry. Warm water soaking is often used in agriculture to promote the rapid germination of seeds, while its application and molecular mechanism in Polygonati Rhizoma have not been reported. To rapidly obtain high-quality seedlings, this study treated Polygonatum kingianum var. grandifolium seeds with sand storage at low temperatures, warm water soaking, and cultivation temperature gradients. The results showed that the culture at 25 ℃ or sand storage at 4 ℃ for 2 months rapidly broke the seed dormancy of P. kingianum var. grandifolium, while the culture at 20 ℃ or sand storage at 4 ℃ for 1 month failed to break the seed dormancy. Soaking seeds in 60 ℃ warm water further increased the germination rate, germination potential, and germination index. Specifically, the seeds soaked at 60 ℃ and cultured at 25 ℃ without sand storage treatment(Aa25) achieved a germination rate of 78. 67%±1. 53% on day 42 and 83. 40%±4. 63% on day 77. The seeds pretreated with sand storage at 4 ℃ for 2 months, soaked in 60 ℃ water, and then cultured at 25 ℃ achieved a germination rate comparable to that of Aa25 on day 77. Transcriptomic analysis indicated that warm water soaking might promote germination by triggering reactive oxygen species( ROS), inducing the expression of heat shock factors( HSFs) and heat shock proteins( HSPs), which accelerated DNA replication, transcript maturation, translation, and processing, thereby facilitating the accumulation and turnover of genetic materials. According to the results of indoor controlled experiments and field practices, maintaining a germination and seedling cultivation environment at approximately 25 ℃ was crucial for the one-year seedling cultivation of P. kingianum var. grandifolium.
Germination ; Seedlings/genetics* ; Water/metabolism* ; Seeds/metabolism* ; Polygonatum/genetics* ; Temperature ; Plant Proteins/genetics* ; Plant Dormancy

In this study, the pharmacodynamic components and potential pharmacological functions of Danzhi Xiaoyao Formula in treating nervous system diseases were investigated by hippocampal component characterization and network pharmacology. After rats were administrated with Danzhi Xiaoyao Formula by gavage, high performance liquid chromatography coupled with quadrupole time-of-flight tandem mass spectrometry(HPLC-Q-TOF-MS/MS) was employed to explore the components in the hippocampus of rats. Fifty-seven components were identified in the hippocampus of rats by comparing the extract of Danzhi Xiaoyao Formula, herbal components in the hippocampus after administration, and blank samples. KEGG and GO analyses predicted 74 core targets including GSK3B, MAPK1, AKT, IL6. These targets were involved in PI3K/Akt, NF-κB, MAPK, JAK/STAT, Wnt, and other signaling pathways. The results indicated that Danzhi Xiaoyao Formula may ameliorate other nervous system diseases enriched in DO, such as neurodegenerative diseases, cerebrovascular diseases, and mental and emotional disorders by mediating target pathways, inhibiting inflammation, reducing neuronal damage, and alleviating hippocampal atrophy. The relevant activities exhibited by this formula in nervous system diseases such as Alzheimer's disease, Parkinson's disease, and diabetic neuropathy have extremely high development value and are worthy of further in-depth research. This study provides a theoretical basis and practical guidance for expanding the application of Danzhi Xiaoyao Formula in the treatment of nervous system diseases.
Drugs, Chinese Herbal/administration & dosage* ; Animals ; Rats ; Hippocampus/metabolism* ; Network Pharmacology ; Chromatography, High Pressure Liquid ; Tandem Mass Spectrometry ; Rats, Sprague-Dawley ; Male ; Nervous System Diseases/genetics* ; Humans ; Signal Transduction/drug effects*

Fritillariae Cirrhosae Bulbus is the dried bulb of perennial herbaceous plants in the Fritillaria genus(Liliaceae family) and is a representative traditional Chinese medicinal material with distinctive regional characteristics. Clinically, it is widely used in the treatment of dry cough, bronchial asthma, and other respiratory diseases, possessing significant medicinal and economic value and being highly esteemed in TCM. Currently, Fritillariae Cirrhosae Bulbus primarily relies on wild harvesting. However, due to excessive collection, its wild resources have drastically declined, and all source species have been classified as category Ⅱ in the List of National Key Protected Wild Plants, exacerbating the supply-demand imbalance in the market. To mitigate this issue, large-scale cultivation through the domestication of wild Fritillariae Cirrhosae Bulbus has become an inevitable trend. However, its strict environmental requirements, low propagation efficiency, high seedling mortality, and immature cultivation techniques have severely hindered industrialization. This study investigates the domestication process of Fritillariae Cirrhosae Bulbus, focusing on seed propagation, seedling cultivation, and medicinal material production. It also reviews the species and distribution of wild resources, their endangered status, market supply-demand dynamics, and the historical and current development of domestication. The findings indicate that enhancing propagation efficiency, optimizing cultivation models, and distinguishing between seed propagation and medicinal material production are key measures to accelerate the industrialization of domesticated Fritillariae Cirrhosae Bulbus. This research aims to promote the industrialization of Fritillariae Cirrhosae Bulbus domestication and provide a reference model for the conservation and sustainable utilization of rare and endangered medicinal plant resources.
Fritillaria/chemistry* ; Endangered Species ; Plants, Medicinal/growth & development* ; Drugs, Chinese Herbal/economics* ; China

BACKGROUND: Based on the China-VHD database, this study sought to develop and validate a Valvular Heart Disease- specific Age-adjusted Comorbidity Index (VHD-ACI) for predicting mortality risk in patients with VHD. METHODS & RESULTS: The China-VHD study was a nationwide, multi-centre multi-centre cohort study enrolling 13,917 patients with moderate or severe VHD across 46 medical centres in China between April-June 2018. After excluding cases with missing key variables, 11,459 patients were retained for final analysis. The primary endpoint was 2-year all-cause mortality, with 941 deaths (10.0%) observed during follow-up. The VHD-ACI was derived after identifying 13 independent mortality predictors: cardiomyopathy, myocardial infarction, chronic obstructive pulmonary disease, pulmonary artery hypertension, low body weight, anaemia, hypoalbuminaemia, renal insufficiency, moderate/severe hepatic dysfunction, heart failure, cancer, NYHA functional class and age. The index exhibited good discrimination (AUC, 0.79) and calibration (Brier score, 0.062) in the total cohort, outperforming both EuroSCORE II and ACCI (P < 0.001 for comparison). Internal validation through 100 bootstrap iterations yielded a C statistic of 0.694 (95% CI: 0.665-0.723) for 2-year mortality prediction. VHD-ACI scores, as a continuous variable (VHD-ACI score: adjusted HR (95% CI): 1.263 (1.245-1.282), P < 0.001) or categorized using thresholds determined by the Yoden index (VHD-ACI ≥ 9 vs. < 9, adjusted HR (95% CI): 6.216 (5.378-7.184), P < 0.001), were independently associated with mortality. The prognostic performance remained consistent across all VHD subtypes (aortic stenosis, aortic regurgitation, mitral stenosis, mitral regurgitation, tricuspid valve disease, mixed aortic/mitral valve disease and multiple VHD), and clinical subgroups stratified by therapeutic strategy, LVEF status (preserved vs. reduced), disease severity and etiology. CONCLUSION The VHD-ACI is a simple 13-comorbidity algorithm for the prediction of mortality in VHD patients and providing a simple and rapid tool for risk stratification.

Pulpotomy, which belongs to vital pulp therapy, has become a strategy for managing pulpitis in recent decades. This minimally invasive treatment reflects the recognition of preserving healthy dental pulp and optimizing long-term patient-centered outcomes. Pulpotomy is categorized into partial pulpotomy (PP), the removal of a partial segment of the coronal pulp tissue, and full pulpotomy (FP), the removal of whole coronal pulp, which is followed by applying the biomaterials onto the remaining pulp tissue and ultimately restoring the tooth. Procedural decisions for the amount of pulp tissue removal or retention depend on the diagnostic of pulp vitality, the overall treatment plan, the patient's general health status, and pulp inflammation reassessment during operation. This statement represents the consensus of an expert committee convened by the Society of Cariology and Endodontics, Chinese Stomatological Association. It addresses the current evidence to support the application of pulpotomy as a potential alternative to root canal treatment (RCT) on mature permanent teeth with pulpitis from a biological basis, the development of capping biomaterial, and the diagnostic considerations to evidence-based medicine. This expert statement intends to provide a clinical protocol of pulpotomy, which facilitates practitioners in choosing the optimal procedure and increasing their confidence in this rapidly evolving field.
Humans ; Calcium Compounds/therapeutic use* ; Consensus ; Dental Pulp ; Dentition, Permanent ; Oxides/therapeutic use* ; Pulpitis/therapy* ; Pulpotomy/standards*

Pelvic organ prolapse (POP), whose etiology is influenced by genetic and clinical risk factors, considerably impacts women's quality of life. However, the genetic underpinnings in non-European populations and comprehensive risk models integrating genetic and clinical factors remain underexplored. This study constructed the first polygenic risk score (PRS) for POP in the Chinese population by utilizing 20 disease-associated variants from the largest existing genome-wide association study. We analyzed a discovery cohort of 576 cases and 623 controls and a validation cohort of 264 cases and 200 controls. Results showed that the case group exhibited a significantly higher PRS than the control group. Moreover, the odds ratio of the top 10% risk group was 2.6 times higher than that of the bottom 10%. A high PRS was significantly correlated with POP occurrence in women older than 50 years old and in those with one or no childbirths. As far as we know, the integrated prediction model, which combined PRS and clinical risk factors, demonstrated better predictive accuracy than other existing PRS models. This combined risk assessment model serves as a robust tool for POP risk prediction and stratification, thereby offering insights into individualized preventive measures and treatment strategies in future clinical practice.
Humans ; Female ; Pelvic Organ Prolapse/epidemiology* ; Middle Aged ; Risk Assessment/methods* ; China/epidemiology* ; Multifactorial Inheritance ; Aged ; Risk Factors ; Genome-Wide Association Study ; Genetic Predisposition to Disease ; Case-Control Studies ; Adult ; Polymorphism, Single Nucleotide ; Genetic Risk Score ; East Asian People

Aging is characterized by a gradual deterioration of the physiological integrity of cells,tissues,and or-gans,resulting in a decrease in the body's physiological functions and an acceleration of the onset of age-related diseases,ultimately leading to death.The aging of the liver,which is a critical metabolic organ,is closely linked to various chronic liver diseases,such as hepatitis,liver fibrosis,and cirrhosis,and it ex-acerbates their prognosis and is a primary risk factor for their development at all stages.Therefore,a comprehensive understanding of the causes,mechanisms,and potential therapeutic targets associated with liver aging holds significant clinical importance for delaying or potentially reversing liver aging and for treating chronic liver diseases.Stem cells,which are potential anti-aging agents,present a promising and effective alternative for managing liver aging.In this review,we systematically assess the driving factors,characteristics,and underlying mechanisms of liver aging.We then discuss the current status of the use of stem cells to mitigate liver senescence and address related liver diseases.The review reveals that a stem cell-based approach represents a promising therapeutic strategy for combating liver aging and associated diseases.

Aim To explore the protective effect of icariin on the damage of tight junctional function of Sertoli cells in naturally aging mice and the related mechanism.Methods 15-month-old C57BL/6J male mice were randomly divided into three groups:aging model group,low-dose and high-dose icariin treatment group(5 and 20 mg·kg-1).Another 1-month-old C57BL/6J male mice were considered as adult control group(n=10).The mice in adult control group and aging model group were given the vehicle(0.5％sodi-um carboxymethyl cellulose solution)by intragastric administration,while the mice in icariin-treated groups were given different concentrations of icariin,respec-tively.After continuous administration of icariin for three months,the testes and epididymis were immedi-ately removed,weighed,and the organ index was calcu-lated.Sperm viability and sperm concentration in epi-didymis were measured.The morphological changes of testes were observed by HE staining.The ultrastructur-al changes of tight junctions of Sertoli cells were ob-served by transmission electron microscopy.The ex-pression levels of tight junction-related proteins ZO-1,Occludin,and Claudin11 of testicular Sertoli cells were detected by Western blot.The expression and localiza-tion of ZO-1,Occludin,Raptor,Rictor,p-70S6K,and p-rps6 were detected by immunofluorescence.Results Compared with the aging model group,icariin signifi-cantly increased testicular weight and its index,and ep-ididymal index,improved sperm viability and increased sperm concentration in naturally aging mice.In addi-tion,icariin improved the degeneration of testicular morphology and the damage of ultrastructure of Sertoli cell tight junction with aging.Furthermore,Western blot results showed that icariin up-regulated the expres-sion of ZO-1 and Occludin,but had no significant effect on the expression of Claudin 11.Immunofluorescence assay showed that icariin up-regulated the expression of Rictor,and down-regulated the expression of p-70S6K,p-rps6 and Raptor.Conclusions Icariin improves the tight junction damage of Sertoli cells in naturally aging mice,and its mechanism may be related to restoring the balance between mTORC1 and mTORC2.