Objective: To identify the spatio-temporal clustering analysis of mumps in Wenzhou City, Zhejiang Province from 2010 to 2023, so as to provide the basis for improving mumps prevention and control strategies. Methods: Data of mumps cases in Wenzhou City from 2010 to 2023 were collected from the Monitoring and Reporting Management System of Chinese Disease Prevention and Control Information System. The spatio-temporal clustering characteristics of mumps incidence were identified using spatial autocorrelation analysis and spatio-temporal scan analysis. Results: A total of 20 455 mumps cases were reported in Wenzhou City from 2010 to 2023, with an average annual incidence of 17.54/105. There were 12 919 male and 7 536 female cases, with a male-to-female ratio of 1.71∶1. The children aged 5-<10 years had the highest incidence of mumps at 135.29/105. The incidence of mumps showed a downward trend from 46.82/105 in 2010 to 3.59/105 in 2023 (P<0.05). The incidence of mumps peaked from May to July and from November to January during 2010 and 2012, the winter peak became less evident after 2013, and no seasonal trends were observed after 2020. Spatial autocorrelation analysis showed there was a positive spatial correlation of mumps of other years, with the exception of 2018 (all Moran's I >0, all P<0.05). Lucheng District, Longwan District, Ouhai District, Cangnan County and Rui'an City were high-high clustering sites. Spatio-temporal scan analysis showed that the primary clustering area was centered in Nanbaixiang Street, Ouhai District, covering 50 towns (streets), with the clustering time from April 2010 to August 2013; the secondary clustering area was centered in Zaoxi Town, Cangnan County, covering 24 towns (streets), with the clustering time from January 2010 to June 2013. Conclusions The incidence of mumps in Wenzhou City from 2010 to 2023 showed a downward trend. The urban areas, Cangnan County and Rui'an City were the clustering areas.

Dopamine, as a catecholamine neurotransmitter widely distributed in the central nervous system, is involved in physiological functions such as motivation, arousal, reinforcement, and movement through various dopamine signaling pathways. The hippocampus receives dopaminergic neuron projections from regions such as the ventral tegmental area, locus coeruleus, and substantia nigra. Through D1-like and D2-like receptors, dopamine exerts significant regulatory effects such as spatial navigation, episodic memory, fear, anxiety, and reward. This review mainly summarizes the research progress on the functions of dopamine in the hippocampus from aspects including the sources of dopamine, receptor distribution and function, and the association of hippocampal dopamine system dysregulation with neurodegenerative diseases. The aim is to provide insights into the involvement of the dopamine system in hippocampal functions and the diagnosis and treatment of related diseases.
Hippocampus/physiology* ; Dopamine/physiology* ; Humans ; Animals ; Receptors, Dopamine D2/physiology* ; Memory/physiology* ; Signal Transduction/physiology* ; Neurodegenerative Diseases/physiopathology*

Gambogic acid(GA), a caged xanthone derivative isolated from Garcinia Hanburyi, exhibits significant antitumor activity and has advanced to phase Ⅱ clinical trials for lung cancer treatment in China. However, the clinical application of GA is severely hindered by its inherent limitations, including poor water solubility, a lack of targeting specificity, and significant side effects. Novel drug delivery systems not only overcome these pharmacological deficiencies but also integrate multiple therapeutic modalities, transcending the limitations of monotherapeutic approaches. In this study, we designed a multifunctional nanodelivery platform(PDA-PEG-Fe(Ⅲ)-GOx-GA) using polydopamine(PDA) as the core material. After the modification of PDA with polyethylene glycol(PEG), Fe(Ⅲ) ions, glucose oxidase(GOx), and GA were sequentially loaded via coordination interactions, electrostatic adsorption, and hydrophobic interactions, respectively. This system demonstrated excellent physiological stability, hemocompatibility, and photothermal conversion efficiency. Notably, under dual stimuli of pH and near-infrared(NIR) irradiation, PDA-PEG-Fe(Ⅲ)-GOx-GA achieved controlled GA release, with a cumulative release rate of 58.3% at 12 h, 3.6-fold higher than that under non-stimulated conditions. Under NIR irradiation, the synergistic effects of PDA-mediated photothermal therapy, Fe(Ⅲ)-induced chemodynamic therapy, GOx-generated starvation therapy, and GA-mediated chemotherapy resulted in effective inhibition of tumor cell proliferation(91.5% inhibition rate) and induction of apoptosis(83.3% apoptosis rate). This multi-modal approach realized a comprehensive treatment strategy for lung cancer, integrating various therapeutic pathways.
Xanthones/pharmacology* ; Humans ; Polymers/chemistry* ; Glucose Oxidase/pharmacology* ; Indoles/chemistry* ; Drug Delivery Systems ; Drug Carriers/chemistry* ; Nanoparticles/chemistry* ; Cell Line, Tumor

The chemical constituents from leaves of Cyclocarya paliurus were isolated and purified by chromatography on silica gel, C_(18) reverse-phase silica gel, and Sephadex LH-20 gel, as well as semi-preparative high-performance liquid chromatography. Six compounds were identified by UV, IR, NMR, MS, calculated ECD, and comparison with literature data as cyclopaloside D(1), boscialin(2),(5R,6S)-6-hydroxy-6-[(E)-3-hydroxybut-1-enyl]-1,1,5-trimethylcyclohexanone(3), 3S,5R-dihydroxy-6R,7-megastigmadien-9-one(4), 3S,5R-dihydroxy-6S,7-megastigmadien-9-one(5), and gingerglycolipid A(6), respectively. Among them, compound 1 was identified as a new tetralone glycoside, and compounds 2-6 were isolated from leaves of C. paliurus for the first time. Furthermore, compound 1 exhibited strong antioxidant activity, with the IC_(50) of(454.20±31.81)μmol·L~(-1) and(881.82±42.31)μmol·L~(-1) in scavenging DPPH and ABTS free radicals, respectively.
Plant Leaves/chemistry* ; Glycosides/isolation & purification* ; Juglandaceae/chemistry* ; Tetralones/isolation & purification* ; Drugs, Chinese Herbal/isolation & purification*

Diterpenoid ferruginol is a key intermediate in biosynthesis of active ingredients such as tanshinone and carnosic acid.However, the traditional process of obtaining ferruginol from plants is often cumbersome and inefficient. In recent years, the increasingly developing gene editing technology has been gradually applied to the heterologous production of natural products, but the production of ferruginol in microbe is still very low, which has become an obstacle to the efficient biosynthesis of downstream chemicals, such as tanshinone. In this study, miltiradiene was produced by integrating the shortened diterpene synthase fusion protein,and the key genes in the MVA pathway were overexpressed to improve the yield of miltiradiene. Under the shake flask fermentation condition, the yield of miltiradiene reached about(113. 12±17. 4)mg·L~(-1). Subsequently, this study integrated the ferruginol synthase Sm CYP76AH1 and Sm CPR1 to reconstruct the ferruginol pathway and thereby realized the heterologous synthesis of ferruginol in Saccharomyces cerevisiae. The study selected the best ferruginol synthase(Il CYP76AH46) from different plants and optimized the expression of pathway genes through redox partner engineering to increase the yield of ferruginol. By increasing the copy number of diterpene synthase, CYP450, and CPR, the yield of ferruginol reached(370. 39± 21. 65) mg·L~(-1) in the shake flask, which was increased by 21. 57-fold compared with that when the initial ferruginol strain JMLT05 was used. Finally, 1 083. 51 mg·L~(-1) ferruginol was obtained by fed-batch fermentation, which is the highest yield of ferruginol from biosynthesis so far. This study provides not only research ideas for other metabolic engineering but also a platform for the construction of cell factories for downstream products.
Saccharomyces cerevisiae/genetics* ; Diterpenes/metabolism* ; Metabolic Engineering ; Fermentation ; Abietanes

Medical institutions, with their clinical practice foundation and abundant human use experience data, have become important carriers for the inheritance and innovation of traditional Chinese medicine(TCM) and the "cradles" of the preparation of new TCM. To effectively promote the transformation of new TCM originating from the TCM clinical practice in medical institutions and establish an effective evaluation index system for the transformation of new TCM conforming to the characteristics of TCM, consensus experts adopted the literature research, questionnaire survey, Delphi method, etc. By focusing on the policy and technical evaluation of new TCM originating from the TCM clinical practice in medical institutions, a comprehensive evaluation from the dimensions of drug safety, efficacy, feasibility, and characteristic advantages was conducted, thus forming a comprehensive evaluation system with four primary indicators and 37 secondary indicators. The expert consensus reached aims to encourage medical institutions at all levels to continuously improve the high-quality research and development and transformation of new TCM originating from the TCM clinical practice in medical institutions and targeted at clinical needs, so as to provide a decision-making basis for the preparation, selection, cultivation, and transformation of new TCM for medical institutions, improve the development efficiency of new TCM, and precisely respond to the public medication needs.
Medicine, Chinese Traditional/standards* ; Humans ; Consensus ; Drugs, Chinese Herbal/therapeutic use* ; Surveys and Questionnaires

This study aims to explore the scientific connotation of sinking Rehmanniae Radix has the best quality and compare the quality between floating and sinking fresh Rehmanniae Radix samples. Ultra-performance liquid chromatography tandem quadrupole electrostatic field Orbitrap high-resolution mass spectrometry(UHPLC-Q-Orbitrap HRMS) was employed to detect the chemical components in floating and sinking fresh Rehmanniae Radix samples. The fingerprint of fresh Rehmanniae Radix was established by high performance liquid chromatography(HPLC), and four index components were determined simultaneously. The cluster analysis, principal component analysis(PCA), and orthogonal partial least squares-discriminant analysis(OPLS-DA) were conducted to compare the quality of floating and sinking fresh Rehmanniae Radix samples. An evaporative light-scattering detector was used to compare the content of five sugars. The extract yield and drying rate were determined, and the quality connotation of sinking Rehmanniae Radix has the best quality was explained by multiple indicators. A total of 41 components were preliminarily identified from fresh Rehmanniae Radix by UHPLC-Q-Orbitrap HRMS, including 7 iridoid glycosides, 9 phenylethanol glycosides, 6 amino acids, 4 sugars, 3 phenolic acids, 5 nucleosides, 3 organic acids, 1 ionone, 1 furan, 1 coumarin, and 1 phenylpropanoid. The results showed that the main chemical components were consistent between floating and sinking fresh Rehmanniae Radix. Nine common peaks were identified in the fingerprints of 15 batches of floating and sinking fresh Rehmanniae Radix samples, and the similarity of fingerprints was greater than 0.9. The cluster analysis, PCA, and OPLS-DA classified floating and sinking fresh Rehmanniae Radix sasmples into two categories, indicating differences in the quality between them. The total content of catalpol, rehmannioside D, ajugol, and verbascoside in sinking fresh Rehmanniae Radix samples was higher than that in floating samples of the same batch and specification, and the main differential component was catalpol. The total content of fructose, glucose, sucrose, raffinose, and stachyose in sinking fresh Rehmanniae Radix samples was higher than that in floating samples of the same batch and specification, and the main differential component was stachyose. The extract yield and drying rate of the sinking samples were higher than those of floating samples. This study preliminarily showed that floating and sinking fresh Rehmanniae Radix samples had the same components but great differences in the content of medicinal substance basis. The total content of four glycosides and five sugars, extract yield, and drying rate of sinking fresh Rehmanniae Radix samples is higher than that of floating samples of the same batch and specification. These findings, to a certain extent, explains the scientificity of sinking Rehmanniae Radix has the best quality recorded in ancient books and provide a reference for the quality control and clinical application of fresh Rehmanniae Radix.
Chromatography, High Pressure Liquid/methods* ; Drugs, Chinese Herbal/chemistry* ; Rehmannia/chemistry* ; Chemometrics ; Mass Spectrometry/methods* ; Quality Control ; Principal Component Analysis ; Plant Extracts

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

OBJECTIVES: To identify risk factors contributing to prolonged postoperative length of stay (LOS) in very elderly patients following hip fracture surgery, with a focus on postoperative complications and the impact of different anesthesia approaches. METHODS: This retrospective single-center cohort study enrolled patients aged 90 years or older who underwent hip fracture surgery at Peking Union Medical College Hospital between January 31, 2013 and December 31, 2023. Relevant perioperative data were collected. The primary outcome was postoperative LOS, and the study cohort was divided into two groups: postoperative LOS ≤ 7 days and LOS > 7 days. Logistic regression was performed to identify factors related to prolonged postoperative LOS. RESULTS: A total of 155 patients were included. The average age was 92.7 ± 2.6 years. There were 73 (47%) patients with postoperative LOS > 7 days. Postoperative pneumonia was the only factor associated with a prolonged postoperative LOS (OR = 2.12, 95% CI [1.09, 4.16], P = 0.028). Neither the type of anesthesia (regional vs. general anesthesia, OR = 1.00, 95% CI [0.53, 1.90], P = 0.993) nor the method of airway management (laryngeal mask ventilation vs. spontaneous breathing, OR = 1.46, 95% CI [0.58, 3.76], P = 0.424; endotracheal intubation vs. spontaneous breathing, OR = 0.82, 95% CI [0.39, 1.69], P = 0.592) showed a significant association with a prolonged postoperative LOS. Preoperative chronic obstructive pulmonary disease (OR = 2.78, 95% CI [1.05, 7.65], P = 0.040) and preoperative neutrophil count (OR = 1.13, 95% CI [1.01, 1.26], P = 0.029) were both significantly associated with the occurrence of postoperative pneumonia, while anesthesia type and airway management method were not. CONCLUSIONS Postoperative pneumonia was associated with prolonged postoperative LOS in very elderly patients undergoing hip fracture surgery, whereas anesthesia types and airway management methods show no association with prolonged postoperative LOS or postoperative pneumonia. Preoperative comorbidities, especially respiratory conditions and systemic inflammation, potentially play a substantial role in postoperative recovery.
Humans ; Hip Fractures/surgery* ; Aged, 80 and over ; Risk Factors ; Length of Stay ; Female ; Male ; Retrospective Studies ; Postoperative Complications/etiology*

PURPOSE: The secondary damage of spinal cord injury (SCI) starts from the collapse of the blood spinal cord barrier (BSCB) to chronic and devastating neurological deficits. Thereby, the retention of the integrity and permeability of BSCB is well-recognized as one of the major therapies to promote functional recovery after SCI. Previous studies have demonstrated that activation of hypoxia inducible factor-1α (HIF-1α) provides anti-apoptosis and neuroprotection in SCI. Endogenous HIF-1α, rapidly degraded by prolylhydroxylase, is insufficient for promoting functional recovery. Dimethyloxalylglycine (DMOG), a highly selective inhibitor of prolylhydroxylase, has been reported to have a positive effect on axon regeneration. However, the roles and underlying mechanisms of DMOG in BSCB restoration remain unclear. Herein, we aim to investigate pathological changes of BSCB restoration in rats with SCI treated by DOMG and evaluate the therapeutic effects of DMOG. METHODS: The work was performed from 2022 to 2023. In this study, Allen's impact model and human umbilical vein endothelial cells were employed to explore the mechanism of DMOG. In the phenotypic validation experiment, the rats were randomly divided into 3 groups: sham group, SCI group, and SCI + DMOG group (10 rats for each). Histological analysis via Nissl staining, Basso-Beattie-Bresnahan scale, and footprint analysis was used to evaluate the functional recovery after SCI. Western blotting, TUNEL assay, and immunofluorescence staining were employed to exhibit levels of tight junction and adhesion junction of BSCB, HIF-1α, cell apoptosis, and endoplasmic reticulum (ER) stress. The one-way ANOVA test was used for statistical analysis. The difference was considered statistically significant at p < 0.05. RESULTS: In this study, we observed the expression of HIF-1α reduced in the SCI model. DMOG treatment remarkably augmented HIF-1α level, alleviated endothelial cells apoptosis and disruption of BSCB, and enhanced functional recovery post-SCI. Besides, the administration of DMOG offset the activation of ER stress induced by SCI, but this phenomenon was blocked by tunicamycin (an ER stress activator). Finally, we disclosed that DMOG maintained the integrity and permeability of BSCB by inhibiting ER stress, and inhibition of HIF-1α erased the protection from DMOG. CONCLUSIONS Our findings illustrate that the administration of DMOG alleviates the devastation of BSCB and HIF-1α-induced inhibition of ER stress.
Spinal Cord Injuries/pathology* ; Animals ; Apoptosis/drug effects* ; Amino Acids, Dicarboxylic/therapeutic use* ; Recovery of Function/drug effects* ; Rats ; Rats, Sprague-Dawley ; Hypoxia-Inducible Factor 1, alpha Subunit/metabolism* ; Male ; Spinal Cord/blood supply*