A Predictive Model for the Risk of Postsurgery Pain Recurrence in the V1 Branch of the Trigeminal Nerve.

BACKGROUND: The factors influencing pain recurrence following V1 trigeminal nerve surgery are still unknown. OBJECTIVE: We aimed to analyze the risk factors affecting pain recurrence following surgery in the V1 branch of the trigeminal nerve, construct a nomogram-based therapeutic efficacy prediction model using logistic regression analysis, and validate the model's predictive performance. STUDY DESIGN: A retrospective study. SETTING: This study was performed at the Affiliated Hospital of Jiaxing University, People's Republic of China. METHODS: Data were retrospectively collected from 131 patients with trigeminal neuralgia and V1 branch algesia who underwent either radiofrequency thermocoagulation through the supraorbital foramen or percutaneous balloon compression at the Pain Department of the Affiliated Hospital of Jiaxing University from March 2017 through January 2021. The patients were randomly divided into a training group (n = 92) and a testing group (n = 39) in a 7:3 ratio. A least absolute shrinkage and selection operator (LASSO) regression was used to screen independent predictive factors. The outcome variable was whether the patient experienced pain recurrence within 2 years postsurgery. Those results were used to construct a nomogram-based predictive model, followed by a multivariate logistic regression analysis. The feasibility of the nomogram-based predictive model was evaluated by the validation group. Finally, the predictive model's discrimination ability, accuracy, and clinical usability were evaluated using a receiver operating characteristic curve, calibration curves, and decision curve analysis, respectively. RESULTS: The results indicate that among the total 131 patients, 76 patients did not experience pain recurrence within 2 years postsurgery, while 55 patients suffered a pain recurrence. The results of the LASSO regression, combined with a multivariate logistic regression analysis, showed that age, pre-Numeric Rating Scale score, and surgery type were the influencing factors for patients with V1 branch pain who experienced pain recurrence within 2 years postsurgery (P < 0.05). From this data a nomogram-based predictive model was established. The area under the curve of the nomogram-based predictive model for the training group was found to be 0.890 (95% CI, 0.818 - 0.961); in the test group it was 0.857 (95% CI, 0.748 - 0.965) in the test group. The Hosmer-Lemeshow goodness-of-fit test revealed an excellent fit (P > 0.05), while the decision curve analysis showed that the net benefit of using the nomogram-based predictive model to predict the risk of recurrence after 2 years was higher when the patient's threshold probability was 0 to 0.990. LIMITATIONS: This was a single-center study. CONCLUSION: A high-precision nomogram-based predictive model was successfully established and validated (with predictive variables including age, pre-Numeric Rating Scale score, and surgery type). We envisage this model will help improve the early identification and screening of high-risk patients for postsurgery pain recurrence of the V1 trigeminal nerve branch.

Application of Dexmedetomidine as an Opioid Substitute in Opioid-Free Anesthesia: A Systematic Review and Meta-analysis.

BACKGROUND: Opioid-based general anesthesia was previously used to alleviate perioperative pain; however, several complications associated with using anesthesia have raised several concerns. Various studies have investigated the application prospect of using opioid-free general anesthesia, such as dexmedetomidine, as an opioid substitute. OBJECTIVES: We performed a systematic review and meta-analysis to explore and highlight the safety and effectiveness of dexmedetomidine as an opioid substitute for opioid-free anesthesia. STUDY DESIGN: A systematic review and meta-analysis. SETTING: We screened for suitable clinical trials from electronic databases, including "PubMed," "Cochrane Library," "EMBASE," and "Web of Science." Eligible trials were included in this meta-analysis. METHODS: The quality of the screened randomized controlled trials (RCTs) was determined using the risk of bias assessment criteria by the Cochrane Collaboration tool. We used the "Review Manager 5.3" and "Stata 10.0" software to perform the meta-analysis. We evaluated the quality of evidence using the "Grading of Recommendations Assessment, Development, and Evaluation" approach. RESULTS: For the analysis, we included 32 RCTs encompassing 2,509 patients. In the opioid-free group, the 2-hour postoperative pain score of patients (mean difference = -0.53, 95% CI: -1.00, -0.07; P = 0.02, I2=78%) was significantly lower compared to those in the opioid-based group. In addition, several patients required rescue analgesia (risk ratio = 0.70, 95% CI: 0.58, 0.84, P < 0.05, I2 = 71%) and opioids postsurgery. However, the duration of extubation and postanesthesia care unit, as well as the incidences of bradycardia, were high in patients receiving dexmedetomidine as opioid-free general anesthesia. LIMITATIONS: Subgroup analysis for different anesthesia-maintaining drugs had not been conducted. The heterogeneity did not reduce after subgroup analysis. Different doses of dexmedetomidine had not been evaluated. CONCLUSIONS: These findings indicate that opioid-free general anesthesia based on dexmedetomidine could be effective; however, prolonged extubation time and cardiovascular complications are a few risks associated with dexmedetomidine.

Triterpenoid saponins from Ilex cornuta protect H9c2 cardiomyocytes against H2O2-induced apoptosis by modulating Ezh2 phosphorylation.

ETHNOPHARMACOLOGICAL RELEVANCE: Ilex cornuta Lindl. et Paxt. (Aquifoliaceae family) belongs to the Ilex genus. The leaves of this plant are used for the popular herbal tea "Ku-Ding-Cha" in China due to their health benefits for sore throat, obesity and hypertension. Our previous studies have shown that the extract of Ilex cornuta root exerts cardioprotective effects in rat models of myocardial ischaemic injury, and several new kinds of triterpenoid saponins from Ilex cornuta (TSIC) have protective effects against hydrogen peroxide (H2O2)-induced cardiomyocyte injury. AIM OF THE STUDY: The aim of this study was to clarify the underlying mechanisms by which TSIC protect against H2O2-induced cardiomyocyte injury. MATERIALS AND METHODS: An H2O2-treated H9c2 cardiomyocyte line was used as an in vitro model of oxidation-damaged cardiomyocytes to evaluate the effects of TSIC. Apoptosis was detected with CCK-8 and annexin V assays and via analysis of the levels of apoptosis-associated proteins or genes. The underlying mechanisms related to Akt signalling, Ezh2 expression and activity, and ROS were clarified by Western blotting, quantitative PCR, flow cytometry and rescue experiments. RESULTS: TSIC protected H9c2 cells from H2O2-induced apoptosis. This effect of TSIC was attributable to inhibition of Ezh2 activity, as exhibited by attenuation of H2O2-induced Akt signalling-dependent phosphorylation of Ezh2 at serine 21 (pEzh2S21) upon TSIC pretreatment. In addition, feedback pathway between Akt-dependent Ezh2 phosphorylation and ROS was involved in TSIC-mediated protection of H9c2 cells from apoptosis. CONCLUSIONS: Our findings indicate a pivotal role of the pEzh2S21 network in TSIC-mediated protection against cardiomyocyte apoptosis, potentially providing evidence of the mechanism of TSIC in the treatment and prevention of cardiovascular diseases.

Luteolin inhibits proliferation and induces apoptosis of human melanoma cells in vivo and in vitro by suppressing MMP-2 and MMP-9 through the PI3K/AKT pathway.

Since the incidence rate of malignant melanoma is increasing annually, development of drugs against melanoma cell metastasis has become more urgent. Luteolin, a naturally occurring flavonoid, is abundant in our daily dietary intake and exhibits a wide spectrum of pharmacological properties. However, the potential anti-cancer role of luteolin in melanoma cells has not been fully investigated. In this study, we have explored whether luteolin inhibits the migration and invasion of A375 human melanoma cells and further elucidated the underlying anti-cancer molecular mechanism of luteolin in melanoma cells. A proliferation assay, flow cytometry and an apoptosis assay were applied to detect the effect of luteolin on the growth and apoptosis of A375 cells. Wound healing assay and transwell invasion assay were used to explore the impact of luteolin on the migration and invasion of A375 cells. Real-time quantitative PCR, western blot and immunofluorescence analysis were used to investigate the effects of luteolin on the expressions of MMP-2, MMP-9 and PI3K/AKT1 in A375 cells. A xenograft tumor animal model was used to investigate the anti-cancer effect of luteolin on the growth of the A375 cells in vivo. Our data indicated that luteolin significantly inhibited the proliferation, migration and invasion of A375 cells and induced the apoptosis of A375 cells in a concentration-dependent manner. Moreover, luteolin reduced the expressions of MMP-2 and MMP-9 and increased the expression of TIMP-1 and TIMP-2. Furthermore, luteolin significantly inhibited the tumor growth of A375 cells in a xenograft mouse model. The immunofluorescence and immunoblotting assays indicated that luteolin inhibited the phosphorylation of AKT1 and PI3K. In conclusion, both in vivo and in vitro studies showed that luteolin inhibited the proliferation and induced the apoptosis of A375 human melanoma cells by reducing the expressions of MMP-2 and MMP-9 through the PI3K/AKT pathway. Overall, luteolin can be considered as a promising anti-cancer agent for the treatment of human melanoma.

Protective effect of Ginkgo biloba leaves extract, EGb761, on myocardium injury in ischemia reperfusion rats via regulation of TLR-4/NF-κB signaling pathway.

Beneficial actions of EGb 761 against ischemia/reperfusion (I/R) injury in lung, brain and renal ischemia have been described. However, the relationship between EGb 761 and signal molecules in myocardial ischemia reperfusion has not been well elucidated. In this study, we investigated the effects and mechanism of EGb 761 preconditioning on anti-myocardial I/R injuries in vivo. Meanwhile, their potential anti-oxidative stress and anti-inflammation effect were assessed. Hemodynamic parameters were monitored as left ventricular systolic pressure, LV end-diastolic pressure and maximal rate of increase and decrease of left ventricular pressure (dP/dtmax). The oxidative stress indicators and inflammatory factors were also evaluated. Western blot method was used for analysis of toll-like receptor 4 (TLR4), p-TLR4, nuclear factor-κB (NF-κB), p-NF-κB p65, Bax and Bcl-2 protein expressions. EGb 761 significantly improved cardiac function, decreased levels of creatine kinase, aspartate aminotransferase and lactate dehydrogenase. EGb 761 also restrained the oxidative stress related to myocardial ischemia injury as evidenced by decreased malondialdehyde, superoxide dismutase, catalase, glutathione-peroxidase, glutathione reductase activity. Meanwhile, the inflammatory cascade was inhibited as evidenced by decreased cytokines such as tumor necrosis factor-α, interleukin-6 and interleukin-1ß. Our results still showed that EGb 761 pretreatment significantly decrease the level of cleaved Bax, and increase the level of Bcl-2 in rats subjected to I/R injury. Simultaneously, the expressions of myocardial TLR4 and NF-κB were significantly decreased. It can be concluded that EGb 761 pretreatment was protected against myocardium I/R injury by decreasing oxidative stress, repressing inflammatory cascade in vivo and inhibiting TLR4/NF-κB pathway.

Protective effect of naringenin against lipopolysaccharide-induced injury in normal human bronchial epithelium via suppression of MAPK signaling.

The present study aimed to evaluate the effect of naringenin on protection in lipopolysaccharide (LPS)-induced injury in normal human bronchial epithelium (NHBE) and to provide insights into the possible underlying mechanisms. NHBE were stimulated by LPS in the presence or absence of the narigenin. In vitro treatment with naringenin led to a significant attenuation in the LPS-induced NHBE secretion of tumor necrosis factor alpha (TNF-α), interleukin-6 (IL-6), superoxidase dismutase (SOD), nitricoxide synthase (NOS), myeloperoxidase (MPO), and nitric oxide (NO). RT-qPCR demonstrated that naringenin significantly reduced the LPS-induced upregulation of TNF-α, IL-6, and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) p65 mRNA expression in a dose-dependent manner. Additionally, Western blot analysis revealed that naringenin effectively suppressed NF-κB activation by inhibiting the degradation of IκB-α and the translocation of p65. Naringenin also attenuated mitogen-activated protein kinase (MAPK) activation by inhibiting the phosphorylation of ERK1/2, c-Jun NH(2)-terminal kinase (JNK), and p38 MAPK. Taken together, these demonstrate that naringenin reduces TNF-α and IL-6 secretion and mRNA expression, possibly by blocking the activation of the NF-κB and MAPK signaling pathways in LPS-treated NHBE. These results indicated that naringenin had a protective effect on LPS-induced injury in NHBE.

[Study thought of pharmaceutical preparations quality standards by dynamic quality control technology].

Pharmaceutical preparations, particularly as a "secret recipe" of traditional Chinese medicine in medical institutions, are the product of China's medical and health industry, and they are also an important means of competing of different medical institutions. Although pharmaceutical preparations have advantages and characteristics than institutes for drug and pharmaceutical companies, the quality standards of pharmaceutical preparations in medical institutions has not reached the desired level over the years. As we all know, the quality of pharmaceutical preparations is important to ensure the efficacy, especially under the environment of people pay more sttention on drug safety and effectiveness and contry increase emphasis on the stste of pharmaceutical preparations. In view of this, we will improve the grade, stability, and clinical efficacy of pharmaceutical preparations by the advanced equipment, testing instruments and the process dynamic quality control technology. Finally, we hope we can provide new ideas for the quality control of pharmaceutical preparations.

[Study on preparation of salvianolic acid phospholipid compound].

To prepare salvianolic acid phospholipid compound. With the compound of salvianolic acids and soybean phospholipid as the index, mono-factor experiment and orthogonal design experiment were conducted to screen its technical parameters. According to the results, the optimal preparation conditions of salvianolic acid phospholipid compound were that THF were taken as the reaction solvent, the concentration time was 3 h, the reactant concentration was 5 g x L(-1), the mass ratio of salvianolic acids and phospholipid was 1: 1.5, and the reaction temperature was 40 degrees C. The oil/water partition coefficient of the prepared salvianolic acid phospholipid compound significant increased in water and buffers with different pH values. The results of phase analysis such as DSC, XRD and FTIR indicated that salvianolic acids existed in phospholipid in an amorphous state.

[Construction of analytical method for similarity of traditional Chinese medicine components on the basis of biopharmaceutic properties].

Traditional Chinese medicine components are a complex multi-component system. How to characterize and evaluate their diverse properties have long been key scientific problems in the modernization process of traditional Chinese medicines. According to the relevant regulations for biopharmaceutical properties, we made the criteria for evaluating similarity of Chinese medicine components, while establish an analytical method based on cosine and Grubbs to evaluate the dispersion degree of properties of representative components, so as to provide ideas and methods for classifying traditional Chinese medicine sub-components and evaluating the integrity of component properties.

[Study on pharmaceutical screening of representative components of Salvia miltiorrhiza diterpene quinones].

OBJECTIVE: To screen out the main components with no significant difference with Salvia miltiorrhiza diterpene quinones pharmacological action, in order to determine the compatible form of representative components that can describe the overall property of S. miltiorrhiza diterpene quinones. METHOD: According to the results of the in vitro pharmacological experiment, the myocardial ischemia model of rats was induced through intraperitoneal injection of isoproterenol. The pharmacologic effects of S. miltiorrhiza diterpene quinones, combination with principal component A and combination with principal component B were compared in electrocardiogram (changes in J point), enzymology indicators (SOD, MDA, CK, LDH) and pathology (myocardial histological changes), so as to screen out the compatible form of representative components that can describe the overall property of S. miltiorrhiza diterpene quinones. RESULT: The S. miltiorrhiza diterpenoid quinone high-dose group and the B high-dose group were similar in all pharmacological effects, with equal efficacy but no significant difference. CONCLUSION: The S. miltiorrhiza diterpenoid quinone high-dose group and the B high-dose group showed a certain therapeutic effect on ISO-induced myocardial ischemia. Therefore, the four components in the B high-dose group can be used as representative components of S. miltiorrhiza diterpene quinones.

[Investigation on equilibrium solubility and apparent oil/water partition coefficient of diterpenoid tanshinone component by similarity analysis methods].

OBJECTIVE: To study the equilibrium solubility and apparent oil/water partition coefficient of diterpenoid tanshinone component by similarity analysis methods, so as to lay the foundation for Salvia diterpenoid quinone component of the overall solubility characterization. METHOD: Taking Salvia diterpenoid quinone component as model drug, determined the equilibrium solubility and partition coefficients of the components in different buffer, evaluated the degree of similarity of each component based on the cosine and Grubbs. RESULT: The representative composition of Salvia diterpenoid quinone component, namely dihydrotanshinone I, tanshinone I, cryptotanshinone and tanshinone II(A) had similar properties of equilibrium solubility and partition coefficients in different pH buffer. This similarity was not only manifested in the trends, but also reflected the value. CONCLUSION: This similarity assessment reflected the degree of deviation and dispersion of components, which was applicable to the study of the components; the similarity assessment could increase the science and rationality of component evaluation, and at the same time could optimize the structure of the component.

[Establishment of modern multi-component sustained-release preparations of oral traditional Chinese medicines].

Traditional Chinese medicines have a long history, with a large quantity of efficient traditional Chinese medicines and prescriptions. However, the vast majority of pharmaceutical dose forms remain common preparations, with very few efficient, long-lasting and low-dose preparations. The sustain-release preparation allows sustained drug release in a longer period of time, maintains blood drug concentration, reduces the toxic effect and medication frequency, and improves medication compliance. Unlike monomer drugs, the material base of traditional Chinese medicine and compounds is multi-component, instead of single or several active monomers. Therefore, under the guidance of the Chinese medicine theories, modern multi-component sustained-release preparations were developed for oral traditional Chinese medicines, with the aim of finally improving the clinical efficacy of traditional Chinese medicines.

[Drug releasing characteristics evaluation to multi-drug delivery system of tongmai pellets].

OBJECTIVE: To establish the drug release method of multi-drug delivery system of tongmai pellets. METHOD: The drug releasing characteristics were researched by HPLC and UV spectrophotometric method. The drug releasing characteristics of the multi-drug delivery system of tongmai pellets between single unit and multiple drug delivery system were evaluated by HPLC. RESULT: The four pellets release unit isoflavones pellets, tanshinone pellets, Sal pellets, chuanxiong acid by ultraviolet spectrophotometry and HPLC method of dissolution obtained similar curves, and the similarity factor f2 were 63.31, 81.59, 70.93, 68.08. The release unit after the formation of multiple drug delivery system had no influence on single unit. CONCLUSION: Initial construction of multiple drug delivery system tongmai pellets improved the dissolution of insoluble components, the overall performance of the combination of rapid release and sustained release characteristics, in line with the design requirements.

[Design technology of traditional Chinese medicine component and formulation].

The development of traditional Chinese medicine lies in its significant clinical efficacy which is closely related to the bioavailability of drugs. The nature of the material foundation of compounds of traditional Chinese medicine is reflected in multi-component. As for the nature of components themselves, the level of their bioavailability depends on the biopharmaceutical properties, namely solubility and permeability, to a great extent. Therefore, under the guidance of the theory of traditional Chinese medicine and in the combination with modern preparation techniques, this essay reveals key techniques capable of improving the biopharmaceutical properties of components, in the hope of enhancing the clinical efficacy of components of traditional Chinese medicine.

[Traditional Chinese medicine components and construction of components biopharmaceutical classification system].

Traditional Chinese medicine compound of material base is multi-components. It should be divided into groups to study traditional Chinese medicine biopharmaceutical properties. To study traditional Chinese medicine multi-component biopharmaceutical, this paper puts forward the scientific representative Chinese medicine integrated nature of the components of the composition, choose ideas. Secondly, this paper introduces the concept of "discrete degree" to examine difference about representative nature of each component. It should he more comprehensive evaluation of traditional Chinese medicine scientific nature of the components. With the comprehensive property value final components and discrete degrees, setting up a part of traditional Chinese medicine biopharmaceutical classification system, traditional Chinese medicine for the multi-composition biopharmaceutical nature study puts forward a new way and method.

[Construction of evaluation systems for traditional Chinese medicine multiple drug delivery system on basis of component level].

Traditional Chinese medicine (TCM) is a multi-component complex system and its research must consider its components characteristics of multi-component, multi-target and multi-effect. According to the whole concept of Chinese medicine, also combining with the status quo of Chinese drugs pharmaceutics and setting the material basis component as the premise, this study will develope TCM multiple drug delivery evaluation system, respectively from three aspects, namely in vitro release, in vivo bioavailability and PK-PD. At the same time, we will try to offer the new thoughts of the programly release, so as to provide new strategies and methods for the development of modern Chinese drug delivery systems.

[Construction of multiple drug release system based on components of traditional Chinese medicine].

With the development of the modernization drive of traditional Chinese medicine (TCM) preparations, new-type TCM dosage forms research have become a hot spot in the field. Because of complexity of TCM components as well as uncertainty of material base, there is still not a scientific system for modern TCM dosage forms so far. Modern TCM preparations inevitably take the nature of the multi-component and the general function characteristics of multi-link and multi-target into account. The author suggests building a multiple drug release system for TCM using diverse preparation techniques and drug release methods at levels on the basis the nature and function characteristics of TCM components. This essay expounds elaborates the ideas to build the multiple traditional Chinese medicine release system, theoretical basis, preparation techniques and assessment system, current problems and solutions, in order to build a multiple TCM release system with a view of enhancing the bioavailability of TCM components and provide a new form for TCM preparations.

[Response surface method optimize of nano-silica solid dispersion technology assistant enzymatic hydrolysis preparation genistein].

This article reports that nano-silica solid dispersion technology was used to raise genistein efficiency through increasing the enzymatic hydrolysis rate. Firstly, genistin-nano-silica solid dispersion was prepared by solvent method. And differential scanning calorimetry (DSC) and transmission electron microscopy (TEM) were used to verify the formation of solid dispersion, then enzymatic hydrolysis of solid dispersion was done by snailase to get genistein. With the conversion of genistein as criteria, single factor experiments were used to study the different factors affecting enzymatic hydrolysis of genistin and its solid dispersion. And then, response surface method was used to optimize of nano-silica solid dispersion technology assistant enzymatic hydrolysis. The optimum condition to get genistein through enzymatic hydrolysis of genistin-nano-silica solid dispersion was pH 7.1, temperature 52.2 degrees C, enzyme concentration 5.0 mg x mL(-1) and reaction time 7 h. Under this condition, the conversion of genistein was (93.47 +/- 2.40)%. Comparing with that without forming the genistin-nano-silica solid dispersion, the conversion increased 2.62 fold. At the same time, the product of hydrolysis was purified to get pure genistein. The method of enzymatic hydrolysis of genistin-nano-silica solid dispersion by snailase to obtain genistein is simple, efficiency and suitable for the modern scale production.

[New idea of traditional Chinese medicine quality control based on "composition structure" theory].

On the road of the modern Chinese medicine developing internationally, there is a key issues that setting up a reasonable, accurate and be quantified quality evaluation system which is comply with the basic theory of Chinese medicine. Based on the overall understanding of the role of traditional Chinese medicine components, author suggested that the idea of "structural components" theory should be embedded into the system and thought the Chinese medicine play a multi-target, multi-channel pharmacodynamic effects founded on the specific microcosmic structural relationship between the components and the components within the group. At present, the way of Chinese pharmacopoeia checking the quality of Chinese medicine is mainly depends on controlling the single or multiple targets of ingredients. In fact, this way is out of the overall effectiveness of the Chinese medicine, so we can not thoroughly controlling the quality of Chinese medicine from the essence of the Chinese medicine. Secondly, it's only macro-structural quantity that the Chinese pharmacopoeia just controlling the less effective ingredients, this is not enough to reflect the internal microstructure of the integrity and systematic. In other words, this cannot reflect the structural components of the Chinese medicine (the essence of traditional Chinese medicine). In view of above mentioned reasons, the author propose the new idea on the quality control in the medicine that quantify the ratio structural relationship in component and the ingredients of the components, set the optimal controlling proportion between the components and ingredients. At the same time, author thought we should conduct the depth study in the micro-quantified the multi-component and multi-ingredient, in the process of studying the material basis of Chinese medicine. Therefore, it could establish a more rational basis for the Chinese medicine quality controlling system.