ObjectiveThis study aimed to observe the impact of sinomenine hydrochloride on the proliferation of fibroblasts and the mRNA expression of related genes in knee joint adhesion and contracture in rabbits. Additionally, we sought to explore its potential mechanisms in combating knee joint adhesion and contracture. MethodsFibroblasts were cultured in vitro, and experimental groups with varying concentrations of sinomenine hydrochloride were established alongside a control group. Cell proliferation was assessed using the CCK-8 assay. Changes in the mRNA expression of fibroblast-related genes following sinomenine hydrochloride treatment were evaluated using RT-qPCR. The impact of the drug on serum levels of inflammatory cytokines was determined using the ELISA method, and the expression of related proteins was assessed using Western blot. ResultsSinomenine hydrochloride was found to inhibit fibroblast viability, with viability decreasing as the concentration of sinomenine hydrochloride increased. The effects of sinomenine hydrochloride in all experimental groups were highly significant (P<0.05). At the mRNA expression level, compared to the control group, sinomenine hydrochloride led to a significant downregulation of inflammatory cytokines in all groups (P<0.05). Additionally, the expression levels of apoptosis-related proteins significantly increased, while Bcl-2 mRNA expression decreased (P<0.05). The mRNA expression levels of the PI3K/mTOR/AKT3 signaling pathway also decreased (P<0.05). At the protein expression level, in comparison to the control group, the levels of inflammatory cytokines IL-6, IL-8, IL-1β, and TGF-β were significantly downregulated in the middle and high-dose sinomenine hydrochloride groups (P<0.05). The expression levels of cleaved-PARP, cleaved caspase-3/7, and Bax increased and were positively correlated with the dose, while the expression levels of the anti-apoptotic protein Bcl-2 and the PI3K/AKT3/mTOR signaling pathway were negatively correlated with the dose. Sinomenine hydrochloride exhibited a significant inhibitory effect on the viability of rabbit knee joint fibroblasts, which may be associated with the downregulation of inflammatory cytokines IL-6, IL-8, and IL-1β, promotion of apoptosis-related proteins cleaved-PARP, cleaved caspase-3/7, and Bax, suppression of Bcl-2 expression, and inhibition of gene expression in the downstream PI3K/AKT3/mTOR signaling pathway. ConclusionSinomenine hydrochloride can inhibit the inflammatory response of fibroblasts in adhesive knee joints and accelerate fibroblast apoptosis. This mechanism may offer a novel approach to improving and treating knee joint adhesion.

Objective To observe the therapeutic effect and mechanism of Guhuaisi Kangfu Pills on rats with steroid-induced osteonecrosis of the femoral head(SONFH).Methods Sixty rats were randomly divided into blank group,model group,Xianling Gubao Capsules group and Guhuaisi Kangfu Pills low-,medium-and high-dose groups,10 rats in each group.Except for the blank group,the SONFH model was established by lipopolysaccharide combined with Glucocorticoid induction method in all other groups of rats.At the end of the intervention,for the femoral head,blood vessel radiography was performed to observe the microvascular changes in the bone marrow,and hematoxylin-eosin(HE)staining and calculation of the empty bone trap rate,Micro-CT scanning analysis,and compression experiments were carried out,and the real-time quantitative polymerase chain reaction(RT-qPCR)was used to detect the gene expressions of phosphatidylinositol 3-kinase(PI3K),protein kinase B(Akt)1,vascular endothelial growth factor(VEGF)and platelet endothelial cell adhesion molecule 1(CD31)in whole blood.Results Compared with the blank group,the blood supply in the femoral head medullary cavity of the model group was poor,the empty bone lacuna rate was increased(P＜0.05),the bone mineral density and bone volume fraction were significantly decreased(P＜0.05),the maximum load and elastic modulus of the femoral head were decreased(P＜0.05),and the mRNA expression levels of Akt1,PI3K,VEGF and CD31 in whole blood were decreased(P＜0.05).Compared with the model group,the blood supply in the femoral head medullary cavity was relatively good,the empty bone lacuna rate was decreased(P＜0.05),the bone mineral density,bone volume fraction,trabecular number and trabecular thickness were significantly increased(P＜0.05),the trabecular separation was significantly decreased(P＜0.05),the maximum load and elastic modulus of the femoral head were increased(P＜0.05),and the mRNA expression levels of Akt1,PI3K,VEGF and CD31 in the whole blood were increased(P＜0.05)in the high-dose group of Guhuaisi Kangfu Pills and Xianling Gubao Capsules group.There was no significant difference in the above indexes between the high-dose group of Guhuaisi Kangfu Pills and the Xianling Gubao Capsules group(P＞0.05).Conclusion Guhuaisi Kangfu Pills improves SONFH in rats,and its mechanism is related to the promotion of VEGF/PI3K/Akt pathway gene expression,thereby promoting angiogenesis.

Objective To develop effective measures to reduce antibiotic use duration in very low birth weight(VLBW)preterm infants in the neonatal intensive care unit through quality improvement methods.Methods The study population consisted of hospitalized VLBW preterm infants,with the percentage of hospitalization time during which antibiotics were used from November 2020 to June 2021 serving as the baseline.The specific quality improvement goal was to reduce the duration of antibiotic use.Factors affecting antibiotic use duration in preterm infants were analyzed using Pareto charts.Key drivers were identified,and specific interventions were formulated based on the stages of antibiotic use.Changes in the percentage of antibiotic use duration were monitored with run charts until the quality improvement target was achieved.Results From November 2020 to June 2021,the baseline antibiotic use duration percentage was 49%,with a quality improvement target to reduce this by 10%within 12 months.The Pareto analysis indicated that major factors influencing antibiotic duration included non-standard antibiotic use;delayed cessation of antibiotics when no infection evidence was present;prolonged central venous catheter placement;insufficient application of kangaroo care;and delayed progress in enteral nutrition.The interventions implemented included:(1)establishing sepsis evaluation and management standards;(2)educating medical staff on the rational use of antibiotics for preterm infants;(3)supervising the enforcement of antibiotic use standards during ward rounds;(4)for those without clear signs of infection and with negative blood cultures,discontinued the use of antibiotics 36 hours after initiation;(5)reducing the duration of central venous catheterization and parenteral nutrition to lower the risk of infection in preterm infants.The control chart showed that with continuous implementation of interventions,the percentage of antibiotic use duration was reduced from 49%to 32%,a statistically significant decrease.Conclusions The application of quality improvement tools based on statistical principles and process control may significantly reduce the antibiotic use duration in VLBW preterm infants.

Currently,the research or publications related to the clinical comprehensive evaluation of Chinese patent medicine are increasing,which attracts the broad attention of all circles. According to the completed clinical evaluation report on Chinese patent medicine,there are still practical problems and technical difficulties such as unclear responsibility of the evaluation organization,unclear evaluation subject,miscellaneous evaluation objects,and incomplete and nonstandard evaluation process. In terms of evaluation standards and specifications,there are different types of specifications or guidelines with different emphases issued by different academic groups or relevant institutions. The professional guideline is required to guide the standardized and efficient clinical comprehensive evaluation of Chinese patent medicine and further improve the authority and quality of evaluation. In combination with the characteristics of Chinese patent medicine and the latest research achievement at home and abroad,the detailed specifications were formulated from six aspects including design,theme selection,content and index,outcome,application and appraisal,and quality control. The guideline was developed based on the guideline development requirements of China Assoication of Chinese medicine. After several rounds of expert consensus and public consultation,the current version of the guideline has been developed.
Medicine, Chinese Traditional ; Nonprescription Drugs ; Consensus ; China ; Reference Standards ; Drugs, Chinese Herbal

The poor solubility of insoluble components of traditional Chinese medicine(TCM) is an important factor restricting the development of its preparations. Natural polysaccharides of TCM can be used as functional components to increase the solubility of insoluble components. Epimedium flavonoid secondary glycoside components(EFSGC) have been shown to have positive effects on the prevention and treatment of osteoporosis, but they exhibit poor solubility. Therefore, the strategy of solubilizing EFSGC with TCM polysaccharides was adopted, and its effect on the permeability and stability of EFSGC was evaluated in this study. Based on the equilibrium solubility experiment of EFSGC, it was found that Panax notoginseng crude polysaccharide(PNCP) had the best solubilization effect on EFSGC among the ten kinds of TCM polysaccharides, which increased the solubility of EFSGC from 0.8 mg·mL~(-1) to 13.3 mg·mL~(-1). It should be noted that after the solubilization of EFSGC by preparation technology, the effects on permeability and stability should be considered. Therefore, this study also investigated these two properties. The results showed that PNCP increased the effective transmittance of EFSGC from 50.5% to 71.1%, which could increase the permeability of EFSGC significantly. At the same time, it could improve the stability of EFSGC in the simulated gastric juice environment. In order to explain the solubilization mechanism of PNCP on EGSGC, critical micelle concentration, particle size, potential, differential scanning calorimetry, and infrared spectroscopy were analyzed. It was preliminarily inferred that the mechanism was as follows: PNCP and EFSGC could self-assemble into aggregates for solubilization by intermolecular hydrogen bonding interaction in water. In summary, PNCP can not only improve the solubility of EFSGC but also improve its permeability and stability. This study lays the foundation for the application of TCM polysaccharides as a functional component to solubilize insoluble components.
Medicine, Chinese Traditional ; Flavonoids/chemistry* ; Glycosides ; Epimedium/chemistry* ; Solubility ; Cardiac Glycosides ; Polysaccharides/chemistry*

Objectives: To investigated the safety and efficacy of treating patients with acute non-ST-segment elevation myocardial infarction (NSTEMI) and elevated levels of N-terminal pro-hormone B-type natriuretic peptide (NT-proBNP) with levosimendan within 24 hours of first medical contact (FMC). Methods: This multicenter, open-label, block-randomized controlled trial (NCT03189901) investigated the safety and efficacy of levosimendan as an early management strategy of acute heart failure (EMS-AHF) for patients with NSTEMI and high NT-proBNP levels. This study included 255 patients with NSTEMI and elevated NT-proBNP levels, including 142 males and 113 females with a median age of 65 (58-70) years, and were admitted in the emergency or outpatient departments at 14 medical centers in China between October 2017 and October 2021. The patients were randomly divided into a levosimendan group (n=129) and a control group (n=126). The primary outcome measure was NT-proBNP levels on day 3 of treatment and changes in the NT-proBNP levels from baseline on day 5 after randomization. The secondary outcome measures included the proportion of patients with more than 30% reduction in NT-proBNP levels from baseline, major adverse cardiovascular events (MACE) during hospitalization and at 6 months after hospitalization, safety during the treatment, and health economics indices. The measurement data parameters between groups were compared using the t-test or the non-parametric test. The count data parameters were compared between groups using the χ² test. Results: On day 3, the NT-proBNP levels in the levosimendan group were lower than the control group but were statistically insignificant [866 (455, 1 960) vs. 1 118 (459, 2 417) ng/L, Z=-1.25,P=0.21]. However, on day 5, changes in the NT-proBNP levels from baseline in the levosimendan group were significantly higher than the control group [67.6% (33.8%,82.5%)vs.54.8% (7.3%,77.9%), Z=-2.14, P=0.03]. There were no significant differences in the proportion of patients with more than 30% reduction in the NT-proBNP levels on day 5 between the levosimendan and the control groups [77.5% (100/129) vs. 69.0% (87/126), χ²=2.34, P=0.13]. Furthermore, incidences of MACE did not show any significant differences between the two groups during hospitalization [4.7% (6/129) vs. 7.1% (9/126), χ²=0.72, P=0.40] and at 6 months [14.7% (19/129) vs. 12.7% (16/126), χ²=0.22, P=0.64]. Four cardiac deaths were reported in the control group during hospitalization [0 (0/129) vs. 3.2% (4/126), P=0.06]. However, 6-month survival rates were comparable between the two groups (log-rank test, P=0.18). Moreover, adverse events or serious adverse events such as shock, ventricular fibrillation, and ventricular tachycardia were not reported in both the groups during levosimendan treatment (days 0-1). The total cost of hospitalization [34 591.00(15 527.46,59 324.80) vs. 37 144.65(16 066.90,63 919.00)yuan, Z=-0.26, P=0.80] and the total length of hospitalization [9 (8, 12) vs. 10 (7, 13) days, Z=0.72, P=0.72] were lower for patients in the levosimendan group compared to those in the control group, but did not show statistically significant differences. Conclusions: Early administration of levosimendan reduced NT-proBNP levels in NSTEMI patients with elevated NT-proBNP and did not increase the total cost and length of hospitalization, but did not significantly improve MACE during hospitalization or at 6 months.
Male ; Female ; Humans ; Aged ; Natriuretic Peptide, Brain ; Simendan/therapeutic use* ; Non-ST Elevated Myocardial Infarction ; Heart Failure/drug therapy* ; Peptide Fragments ; Arrhythmias, Cardiac ; Biomarkers ; Prognosis

The research on the processing mechanism of Chinese medicine is the key and core foundation to improve processing technologies of Chinese medicine, formulate the quality standards of Chinese medicinal pieces, enhance the clinical efficacy of Chinese medicine, enrich Chinese medicine processing theories, and promote the development of Chinese medicine processing. Many researc-hers have conducted in-depth exploration on the processing mechanism of Chinese medicine in the 20 years in the 21 st century. Significant progress has been made in the transformation of chemical components during the processing, the change of active components in the body, the law of toxicity attenuation in the processing of toxic Chinese medicine, the mechanism of efficacy enhancement and toxicity attenuation of processing with auxiliary materials, and the application of new biomedical technologies. At present, the processing mechanism of multiple Chinese medicines has been preliminarily clarified, which has greatly promoted the development of Chinese me-dicine processing. The development of the processing mechanism of Chinese medicine reveals that the in vitro transformation of chemical components is combined with the in vivo absorption, transport, and metabolism, and the macroscopic biological effects of the organism are combined with the cells, molecules, targets, and pathways in the study of the processing mechanism of Chinese medicine. More attention has been paid to exploring the processing mechanism from the overall level, and a modern systematic research system on the processing mechanism of Chinese medicine has been initially formed. To further promote the scientific development of Chinese me-dicine processing, the present study proposed that the research on the processing mechanism of Chinese medicine should take Chinese medicine properties into account, focus on the influence of disease condition on the mode of action and effect strength of the drugs, comply with the characteristics of clinical compound compatibility of Chinese medicine, use the holistic view research strategies of systems bio-logy, and deeply explore the processing mechanism of Chinese medicine from traditional Chinese medicine theories and the characteristics of clinical medication of Chinese medicine.
Drugs, Chinese Herbal/pharmacology* ; Medicine, Chinese Traditional ; Reference Standards ; Research Design ; Technology

Against the backdrop of "Internet+" and Made in China 2025, Chinese medicinal processing equipment embraces various opportunities and develops to an unprecedented level. In the 20 years of the new century, the processing equipment has gradually developed in the direction of high efficiency, energy saving, environmental protection, integration, and automation, and this field has tended to highlight the establishment and application of the linkage production line for the processing of Chinese medicinal decoction pieces. Integrating automation control technology, online detection technique, and the internet of things technology, the online detection system of Chinese medicinal processing equipment and the computer information management system of Chinese medicinal proces-sing are the mainstream development trends of Chinese medicinal processing equipment. Standard Chinese medicine processing equipment is the prerequisite for the standardization of processing parameters. A standard system for processing equipment and processing parameters is the key to the modernization of Chinese medicinal decoction pieces. This paper summarized the research and application of Chinese medicinal processing equipment in the 20 years of the 21 st century and predicted the development trend, which is expected to serve as a reference for the technological innovation and development of the processing equipment.
Automation ; Drugs, Chinese Herbal ; Medicine, Chinese Traditional ; Quality Control ; Reference Standards

The study aims to explore the intervention mechanism of Tingli Dazao Xiefei Decoction on asthma from the perspective of immune inflammation and intestinal flora, providing a theoretical basis for guiding clinical medication. The ovalbumin (OVA) asthmatic rat model was established by intraperitoneal injection of OVA sensitization solution and aerosol challenge, and divided into control (CON), model (M), dexamethasone group (DEX, 0.075 mg·kg^-1) and Tingli Dazao Xiefei Decoction (TLDZ, 3.5 g·kg^-1). Firstly, the effects of Tingli Dazao Xiefei Decoction on asthma symptoms of rats, lung and trachea pathological changes of asthmatic rats were observed by inducing cough and asthma experiment, phenol red excretion, hematoxylin-eosin staining (H&E), Masson and periodic acid Schiff (PAS) staining; the levels of transforming growth factor β1 (TGF-β1), interleukin (IL) 6 and IL-10 in rat serum and the levels of interferon γ (IFN-γ), immunoglobulin E (IgE), IL-4, IL-17A and tumor necrosis factor α (TNF-α) in bronchoalveolar lavage fluid (BALF) were detected by ELISA; the mRNA levels of IL-5, IL-13 and IL-33 in the lung were determined by qRT-PCR; the levels of macrophages and neutrophils in the spleen and the levels of natural killer cell (NK), helper T cell (Thc), dendritic cell (DC), regulatory T cell (Treg) and T helper cell 17 (Th17) in the peripheral blood were measured by flow cytometry combined with immunohistochemistry; the intestinal flora of asthmatic rats were analyzed by 16S rDNA high-throughput sequencing. Pathology and inflammatory results showed that Tingli Dazao Xiefei Decoction could effectively alleviate the asthma symptoms in rats, improve the pathological changes of lung tissue, reduce the production of goblet cells and collagen fibers, and reduce the inflammatory response in asthmatic rats; the results of immune cells showed that Tingli Dazao Xiefei Decoction could effectively increase the levels of NK, Thc, DC and Treg cells and reduce the levels of macrophages, neutrophils and Th17 cells in asthmatic rats; the results of intestinal flora showed that Tingli Dazao Xiefei Decoction could increase the levels of Lactobacillus, Ruminococcus, Christensenellaceae, Bifidobacterium and Eubacterium]_xylanophilum-group, and decrease the levels of Firmicutes, Desulfovibrio, Mucispirillum and Romboutsia in asthmatic rats. Therefore, it is speculated that Tingli Dazao Xiefei Decoction can improve the symptom of asthmatic rats by regulating the immune inflammation and intestinal flora in the asthmatic rats. All animal experiments in this article were approved by the Ethics Committee of Henan University of Chinese Medicine.