ObjectiveTo assess the availability of bronchodilators for treatment of chronic obstructive pulmonary disease (COPD) in community health service centers (CHCs) in Shanghai. MethodsOn the basis of previous research, the questionnaire was updated, and surveys were conducted from April to May 2023 in CHCs in Shanghai, with a focus on the availability of medications for COPD treatment. According to the National Basic Medical Insurance, Work Injury Insurance, and Maternity Insurance Drug List (2023 Edition), a total of 24 types of bronchodilators for COPD treatment were identified. The availability rates were used to assess the accessibility of specific drugs in CHCs, and the dispensing rates were used to evaluate the variety of these medications in CHCs. ResultsA total of 248 CHCs responded, with a response rate of 100.0%. Among them, a total of 232 CHCs (93.5%) were equipped with bronchodilators. In terms of availability rates, the availability rates for β₂ adrenoreceptor agonists, muscarinic antagonists, combination drugs, and xanthines drugs were 86.3%, 52.0%, 52.4%, and 85.1%, respectively. Regional differences were observed, in that salbutamol/levalbuterol and budesonide-formoterol were less available in suburban CHCs, ipratropium bromide had lower availability in urban CHCs, and aminophylline was more available in suburban CHCs. Regarding the dispensing rates of the 24 types of bronchodilators for COPD treatment, the median of types equipped by CHCs was 5, with a total of 200 CHCs (80.6%) equipped with fewer than 7 types of bronchodilator drugs. ConclusionThe proportion of CHCs in Shanghai equipped with bronchodilators for COPD is relatively high. However, there exist problems such as limited variety of stocked medications, significant differences in the availability of different drugs, and regional imbalances in drug stocking. To improve the standardized diagnosis, treatment, and management of COPD patients, it is recommended to enhance the availability of COPD treatment medications in CHCs.

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

Emodin is a hydroxyanthraquinone compound that is widely distributed and has multiple pharmacological activities, including anti-diarrheal, anti-inflammatory, and liver-protective effects. Research indicates that emodin may be one of the main components responsible for inducing hepatotoxicity. However, studies on the mechanisms of liver injury are relatively limited, particularly those related to bile acids(BAs) metabolism. This study aims to systematically investigate the effects of different dosages of emodin on BAs metabolism, providing a basis for the safe clinical use of traditional Chinese medicine(TCM)containing emodin. First, this study evaluated the safety of repeated administration of different dosages of emodin over a 5-week period, with a particular focus on its impact on the liver. Next, the composition and content of BAs in serum and liver were analyzed. Subsequently, qRT-PCR was used to detect the mRNA expression of nuclear receptors and transporters related to BAs metabolism. The results showed that 1 g·kg~(-1) emodin induced hepatic damage, with bile duct hyperplasia as the primary pathological manifestation. It significantly increased the levels of various BAs in the serum and primary BAs(including taurine-conjugated and free BAs) in the liver. Additionally, it downregulated the mRNA expression of farnesoid X receptor(FXR), retinoid X receptor(RXR), and sodium taurocholate cotransporting polypeptide(NTCP), and upregulated the mRNA expression of cholesterol 7α-hydroxylase(CYP7A1) in the liver. Although 0.01 g·kg~(-1) and 0.03 g·kg~(-1) emodin did not induce obvious liver injury, they significantly increased the level of taurine-conjugated BAs in the liver, suggesting a potential interference with BAs homeostasis. In conclusion, 1 g·kg~(-1) emodin may promote the production of primary BAs in the liver by affecting the FXR-RXR-CYP7A1 pathway, inhibit NTCP expression, and reduce BA reabsorption in the liver, resulting in BA accumulation in the peripheral blood. This disruption of BA homeostasis leads to liver injury. Even doses of emodin close to the clinical dose can also have a certain effect on the homeostasis of BAs. Therefore, when using traditional Chinese medicine or formulas containing emodin in clinical practice, it is necessary to regularly monitor liver function indicators and closely monitor the risk of drug-induced liver injury.
Emodin/administration & dosage* ; Bile Acids and Salts/metabolism* ; Animals ; Male ; Liver/injuries* ; Chemical and Drug Induced Liver Injury/genetics* ; Drugs, Chinese Herbal/adverse effects* ; Humans ; Rats, Sprague-Dawley ; Mice ; Rats

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

In this study, lipopolysaccharide(LPS), ovalbumin(OVA), and compound 48/80(C48/80) were administered to establish non-infectious pneumonia models under simulated clinical conditions, and the correlation between their pathological characteristics and traditional Chinese medicine(TCM) syndromes was compared, providing the basis for the selection of appropriate animal models for TCM efficacy evaluation. An acute pneumonia model was established by nasal instillation of LPS combined with intraperitoneal injection for intensive stimulation. Three doses of OVA mixed with aluminum hydroxide adjuvant were injected intraperitoneally on days one, three, and five and OVA was administered via endotracheal drip for excitation on days 14-18 to establish an OVA-induced allergic pneumonia model. A single intravenous injection of three doses of C48/80 was adopted to establish a C48/80-induced pneumonia model. By detecting the changes in peripheral blood leukocyte classification, lung tissue and plasma cytokines, immunoglobulins(Ig), histamine levels, and arachidonic acid metabolites, the multi-dimensional analysis was carried out based on pathological evaluation. The results showed that the three models could cause pulmonary edema, increased wet weight in the lung, and obvious exudative inflammation in lung tissue pathology, especially for LPS. A number of pyrogenic cytokines, inclading interleukin(IL)-6, interferon(IFN)-γ, IL-1β, and IL-4 were significantly elevated in the LPS pneumonia model. Significantly increased levels of prostacyclin analogs such as prostaglandin E2(PGE2) and PGD2, which cause increased vascular permeability, and neutrophils in peripheral blood were significantly elevated. The model could partly reflect the clinical characteristics of phlegm heat accumulating in the lung or dampness toxin obstructing the lung. The OVA model showed that the sensitization mediators IgE and leukotriene E4(LTE4) were increased, and the anti-inflammatory prostacyclin 6-keto-PGF2α was decreased. Immune cells(lymphocytes and monocytes) were decreased, and inflammatory cells(neutrophils and basophils) were increased, reflecting the characteristics of "deficiency", "phlegm", or "dampness". Lymphocytes, monocytes, and basophils were significantly increased in the C48/80 model. The phenotype of the model was that the content of histamine, a large number of prostacyclins(6-keto-PGE1, PGF2α, 15-keto-PGF2α, 6-keto-PGF1α, 13,14-D-15-keto-PGE2, PGD2, PGE2, and PGH2), LTE4, and 5-hydroxyeicosatetraenoic acid(5S-HETE) was significantly increased, and these indicators were associated with vascular expansion and increased vascular permeability. The pyrogenic inflammatory cytokines were not increased. The C48/80 model reflected the characteristics of cold and damp accumulation. In the study, three non-infectious pneumonia models were constructed. The LPS model exhibited neutrophil infiltration and elevated inflammatory factors, which was suitable for the efficacy study of TCM for clearing heat, detoxifying, removing dampness, and eliminating phlegm. The OVA model, which took allergic inflammation as an index, was suitable for the efficacy study of Yiqi Gubiao formulas. The C48/80 model exhibited increased vasoactive substances(histamine, PGs, and LTE4), which was suitable for the efficacy study and evaluation of TCM for warming the lung, dispersing cold, drying dampness, and resolving phlegm. The study provides a theoretical basis for model selection for the efficacy evaluation of TCM in the treatment of pneumonia.
Animals ; Disease Models, Animal ; Mice ; Pneumonia/genetics* ; Medicine, Chinese Traditional ; Male ; Humans ; Cytokines/immunology* ; Female ; Lipopolysaccharides/adverse effects* ; Lung/drug effects* ; Drugs, Chinese Herbal ; Ovalbumin ; Mice, Inbred BALB C

This study established the HPLC fingerprints, characteristic chromatograms, and a multi-component content determination method for Bidens bipinnata and B. biternata. The chemical pattern recognition analysis was then employed to clarify the characteristic indexes of quality differences between the two original plants of Bidentis Herba, providing a reference for establishing the quality standards of Bidentis Herba. HPLC was launched on an Agilent Poroshell 120 EC-C_(18) chromatographic column(4.6 mm×250 mm, 4 μm) by gradient elution with a mobile phase of 0.1% aqueous phosphoric acid-acetonitrile at a flow rate of 0.7 mL·min~(-1), detection wavelength of 270 nm, column temperature of 25 ℃, and an injection volume of 5 μL. The similarity between the fingerprints of 18 batches of Bidentis Herba samples and the common pattern(R) ranged from 0.572 to 0.933. A total of 23 chromatographic peaks were calibrated. Through comparison with the reference substances, six components(neochlorogenic acid, chlorogenic acid, isochlorogenic acid A, isochlorogenic acid B, rutin, and hyperoside) were identified and subjected to quantitative analysis. The characteristic fingerprints of B. bipinnata and B. biternata were calibrated with 20 and 17 characteristic peaks, respectively. Among them, peaks 8, 9, 22, and 23 were the characteristic peaks of B. bipinnata, and peak 7 was the characteristic peak of B. biternata, which can be used to distinguish the two original plants of Bidentis Herba. The relative standard deviation of the content of the above-mentioned six components ranged from 36% to 123%. The cluster analysis, principal component analysis, and orthogonal partial least squares-discriminant analysis(OPLS-DA) classified the 18 batches of Bidentis Herba samples into two categories. Additionally, through the analysis of variable importance in projection(VIP) under OPLS-DA, three characteristic indexes, rutin, isochlorogenic acid A, and isochlorogenic acid B, were identified. The analytical method established in this study can comprehensively evaluate the consistency of Bidentis Herba samples derived from different original plants, specifically identify the differential components between them, and effectively distinguish the two original plants of Bidentis Herba, providing a basis for the differentiation between different original plants and the quality control of Bidentis Herba.
Chromatography, High Pressure Liquid/methods* ; Drugs, Chinese Herbal/chemistry* ; Quality Control ; Bidens/chemistry*

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*

BACKGROUND:Osteoblasts are the main cell types responsible for bone formation and remodeling,and the normal performance of their function is precisely regulated by various signaling pathways.Among them,the bone morphogenetic protein and Wnt signaling pathways play a key role in osteogenesis. OBJECTIVE:To review the role of bone morphogenetic protein/Wnt signaling pathway in the regulation of osteoblast function and analyze its changes in different physiological and pathological conditions in order to further reveal the molecular mechanism of bone formation and remodeling. METHODS:The Chinese and English search terms"BMP signaling pathway,Wnt signaling pathway,and osteogenesis"were searched in CNKI,Wanfang,and PubMed databases for original researches published from the inception to June 2023.Totally 61 articles were finally selected for analysis and summary.Using the method of the literature review,the studies of the bone morphogenetic protein/Wnt signaling pathway in regulating osteogenesis were sorted out and analyzed. RESULTS AND CONCLUSION:(1)Bone morphogenetic protein and Wnt signaling pathways play important roles in the differentiation,proliferation,and maturation of osteoblasts.Bone morphogenetic protein signaling pathway mainly regulates the expression of osteogenesis-related genes through the activation of Smad protein.Smad protein enters the nucleus and regulates the expression of genes related to osteogenesis.Different Wnt signaling pathway from bone morphogenetic protein mainly depends on the activation of β-catenin to exert its biological effects.(2)The regulatory effect of bone morphogenetic protein/Wnt signaling pathway will be affected by many factors in different physiological and pathological states.Growth factors,hormones,and mechanical stress can affect the activity of bone morphogenetic protein/Wnt signaling pathway to some extent.(3)Bone morphogenetic protein/Wnt signaling pathway interacts with other signaling pathways in the regulation of osteogenesis,and they together constitute a complex regulatory network.(4)Chinese medicine and natural compounds can promote bone health by regulating signaling pathways,providing new possibilities for treating bone diseases.(5)Future studies can further explore the interaction of bone morphogenetic protein/Wnt signaling pathway and other signaling pathways and its changes in different physiological and pathological conditions,resolve the key nodes and regulation mechanism in the complex network,to provide more precise targets for the treatment of bone-related diseases,and also provide new ideas to reveal the molecular mechanism of bone formation and remodeling.

Occupational health technical service (OHTS) is one of the core contents in the technical support system of occupational disease prevention and control, and efficient management of OHTS institutions is necessary for improving the service ability. At present, OHTS institutions in China face several issues, such as uneven distribution in terms of quantity, function, unclear area coverage and roles and overlapping responsibilities among different types of institutions, and insufficient service capabilities with inconsistent service levels in some institutions. With the implementation of the national reform like the “separating permits from business license” and “delegate power, streamline administration and optimize government services"”policies, the management mode and operational approach of OHTS institutions have been profoundly changed. In light of this, five key recommendations are proposed to improve the management of OHTS institutions and enhance their management effectiveness, ensuring the sustainable development of national OHTS services. Firstly, it is necessary to clarify the relationship between national and provincial administrative levels in managing OHTS institutions to ensure their healthy and orderly development. Secondly, multiple measurements are taken to strengthen OHTS institutional capacity building to address regional disparities in technical capabilities and service quality. Thirdly, both technical capabilities and service quality should be focused on strengthening the supervision and management of OHTS institutions, preventing the decline of key conditions such as staffing, laboratories, equipment, and quality management after obtaining qualifications. Fourthly, “dual randomized- inspections and one open” and “internet+supervision” methods are used as basic tools for managing OHTS institutions operating across multiple provincial regions and enforcing cross-regional law. Fifthly, professional integrity of radiological health service institutions should be restored to effectively apply their technical advantages in their specialized fields.

Objective To design and synthesize novel Hsp90 inhibitors with dual functions of synergistically enhancing the antifungal activity of fluconazole （FLC） against drug-resistant fungi and anti-tumor activity based on the Hsp90 inhibitor Ganetespib. Methods The previous research found that Ganetespib had a good synergistic anti-resistant fungal activity with FLC, with a fractional inhibitory concentration index （FICI） of 0.023 to 0.039. In this study, structural modifications were made to Ganetespib by replacing its indole ring with a phenyl ring containing different substituents to design and synthesize a series of new compounds. The in vitro synergistic anti-resistant fungal activity against C. albicans 0304103 in combination with FLC, anti-tumor activity （against HEL, HL60 and A549 cells）, and Hsp90α inhibition activity were determined to explore their structure-activity relationship and mechanism of action. Results The chemical structures of 19 new compounds were confirmed by ¹H NMR, ¹³C NMR and HRMS. Most of the compounds exhibited strong Hsp90α inhibitory activity, good synergistic activity against drug-resistant fungi in combination with FLC and anti-tumor activity. The substitution of electron-donating groups on the benzene ring was beneficial to enhancing the synergistic activity against drug-resistant fungi in combination with FLC. Among them, compounds F3 and F5 showed excellent synergistic activity against drug-resistant fungi in combination with FLC （FICI were both 0.047） and anti-tumor activity （IC₅₀ were 0.025 to 0.15 μmol/L and 0.021 to 0.23 μmol/L respectively）, and could down-regulate the expression levels of drug resistance genes and efflux pump genes in fungi, inhibit the formation of fungal biofilms, and arrest the cell cycle of HEL cells at G0/G1 phase. Conclusion The novel Hsp90 inhibitors such as F3 and F5 could both effectively exert the dual activities of synergizing with FLC to combat drug-resistant fungi and fight against tumors, which provided a new idea for the development of new drugs with dual functions of synergizing with FLC to combat drug-resistant fungi and fight against tumors.