Synergetic Enzyme-Incorporated Metal-Organic Framework and Polyoxometalate Nanozyme: Achieving Stable Tandem Catalysis for Organic Photoelectrochemical Transistor Bioanalysis.

Organic photoelectrochemical transistor (OPECT) has emerged as a promising technique for biomolecule detection, yet its operational rationale remains limited due to its short development time. This study introduces a stable tandem catalysis protocol by synergizing the enzyme-incorporated metal-organic frameworks (E-MOFs) with polyoxometalate (POM) nanozyme for sensitive OPECT bioanalysis. The zeolitic imidazolate framework-8 (ZIF-8) acts as the skeleton to protect the encapsulated glucose oxidase (GOx), allowing the stable catalytic generation of H2O2. With peroxidase-like activity, a phosphotungstic acid hydrate (PW12) is then able to utilize the H2O2 to induce the biomimetic precipitation on the photogate, ultimately resulting in the altered device characteristics for quantitative detection. This work reveals the potential and versatility of an engineered enzymatic system as a key enabler to achieve novel OPECT bioanalysis, which is believed to offer a feasible framework to explore new operational rationale in optoelectronic and bioelectronic detection.

Polymer solubility mechanism in ionic liquids: 1H-NMR spectra and two-parameter hydrogen bonding analysis.

Understanding the polymer solubility in ionic liquids (ILs) is important for polymer processing or polymeric material preparation. Previously, two-parameter H-bonding analysis has been proposed to clarify that polymer solubility in ILs is dominated by H-bonding interactions (Y. F. Yuan et al., Phys. Chem. Chem. Phys., 2021, 23, 21893-21900). In the present work, 1H-NMR spectra are adopted to characterize the H-bonding interactions between polymers and ILs, which provide a microscopic relation between polymer solubility and two-parameter H-bonding analysis.

[Research progress on anti-tumor effects by traditional Chinese medicine based on "soothing" or "blockage" regulation of tumor vessels].

Regulation of tumor vessels has become one of the most common strategies for clinical anti-tumor therapy. In recent years, studies have found that the anti-tumor effect of limotherapy, which routinely inhibits tumor angiogenesis, is not ideal and may even deteriorate the tumor microenvironment, causing tumor resistance and distal metastasis and increasing the risk of tumor metastasis and recurrence. However, the proper use of anti-angiogenic drugs can promote the normalization of tumor vessels, improve the structure and function of tumor vessels, increase the number of functional vessels in the tumor, and reduce the number of ineffective vessels. It is beneficial to promote the penetration of anti-tumor drugs into the tumor, improve the microenvironment of tumor hypoxia and immunosuppression, and enhance the anti-tumor effect. Traditional Chinese medicine(TCM) has a long history of understanding the etiology and pathogenesis of tumors and has accumulated rich experience in tumor treatment, with significant clinical advantages and broad application prospects. In this study, from the perspective of bidirectional "soothing" or "blockage" regulation of tumor vessels, the commonly used molecular targets were sorted out, and the research status of anti-tumor regulation of tumor vessels by monomer-single herb-compound(herb pair) of TCM in recent years was summarized. The research on the anti-tumor effects of TCM compounds and active ingredients by regulating tumor vessels combined with other therapies was analyzed and sorted out, so as to provide ideas for the clinical application of TCM in regulating functions and anti-tumor effects of tumor vessels.

[Q-marker prediction of resin ethanol extract of Gegen Qinlian Decoction based on characteristic spectrum and network pharmacology].

The resin ethanol extract of Gegen Qinlian Decoction(GGQLD) has been found to significantly alleviate the intestinal toxicity caused by Irinotecan, but further research is needed to establish its overall quality and clinical medication standards. This study aimed to establish an HPLC characteristic fingerprint of the resin ethanol extract of GGQLD, predicted the targets and signaling pathways of its pharmacological effects based on network pharmacology, identified core compounds with pharmacological relevance, and analyzed potential quality markers(Q-markers) of the resin eluate of GGQLD for relieving Irinotecan-induced toxicity. By considering the uniqueness, measurability, and traceability of Q-markers based on the "five principles" of Q-markers and combining them with network pharmacology techniques, the overall efficacy of the resin ethanol extract of GGQLD can be characterized. Preliminary predictions suggested that the four components of puerarin, berberine, baicalin, and baicalein might serve as potential Q-markers for the resin etha-nol extract of GGQLD. This study provides a basis and references for the quality control and clinical mechanism of the resin ethanol extract of GGQLD.

[Equivalence of combined decoction and mixed single decoctions of Gegen Qinlian Decoction in alleviating chemotherapy-associated diarrhea].

This study compared the chemical profiles, component content, dry paste yield, and pharmacological effects of samples obtained from the mixed single decoctions and the combined decoction of Gegen Qinlian Decoction(GQD), aiming to provide an experimental foundation for evaluating the equivalence of the two decocting methods and the suitability of TCM formula granules in clinical application. The same decoction process was used to prepare the combined decoction and mixed single decoctions of GQD. Ultra-performance liquid chromatography coupled with Q-Exactive Orbitrap mass spectrometry(UPLC-Q-Exactive Orbitrap MS) was employed to compare the chemical profiles between the two groups. High-performance liquid chromatography(HPLC) was used to compare the content of nine characteristic components between the two groups. Then, a delayed diarrhea mouse model induced by irinotecan was established to compare the pharmacological effects of the two groups on chemotherapy-induced diarrhea. The UPLC-Q-Exactive Orbitrap MS in ESI~+ and ESI~- modes identified 59 chemical components in the compound decoction and mixed single decoctions, which showed no obvious differences in component species. The content of baicalin and wogonoside was higher in the compound decoction, while that of puerarin, daidzein-8-C-apiosylglucoside, berberine, epiberberine, wogonin, glycyrrhizic acid, and daidzein was higher in the mixed single decoctions. Further statistical analysis revealed no significant difference in the content of the nine characteristic components between the compound decoction and the mixed single decoctions. The dry paste yield had no significant difference between the two groups. Compared with the model group, both compound decoction and mixed single decoctions alleviated the weight loss and reduced diarrhea index in mice. Both of them lowered the levels of tumor necrosis factor-α(TNF-α), interleukin-1ß(IL-1ß), cyclooxygenase-2(COX-2), intercellular adhesion molecule-1(ICAM-1), interleukin-10(IL-10), malondialdehyde(MDA), and nitric oxide(NO) in the colon tissue. Furthermore, they significantly increased the levels of glutathione peroxidase(GSH-Px) and superoxide dismutase(SOD). Hematoxylin-eosin(HE) staining showed that colon tissue cells were tightly arranged with clear nuclei in both groups without obvious difference. The compound decoction and mixed single decoctions showed no significant differences in chemical component species, content of nine characteristic components, dry paste yield, or the pharmacological effects on alleviating chemotherapy-induced diarrhea. The findings provide a reference for evaluating the flexibility and superiority of combined or single decocting method in the preparation of TCM decoctions or formula granules.

The efficacy of platelet rich plasma on anterior cruciate ligament reconstruction: a systematic review and meta-analysis.

Anterior cruciate ligament (ACL) rupture is a common musculoskeletal injury, most frequently affecting young and physically active patients. Platelet-rich plasma (PRP) has been widely used in ACL reconstruction to augment the graft healing. However, high-level studies addressing its clinical efficacy could not reach a consensus. In this study, we assess the efficacy of PRP on pain relief, functional improvement along with radiological changes in patients who underwent ACL reconstruction. We performed comprehensive literature search and included 17 RCTs containing 970 participants who underwent ACL reconstruction. The combined data showed significant difference between PRP and control with regard to VAS score (MD: -1.12, 95% CI -1.92, -0.31; P = .007), subjective IKDC score (MD: 6.08, 95% CI 4.39, 7.77; P < .00001) and Lysholm score (MD: 8.49, 95% CI 1.63, 15.36; P = .02) by postoperative 6 months, but only pain reduction was deemed clinically important. At the end of one year's follow-up, no clinically meaningful improvement in VAS (MD: -0.47, P = .04), subjective IKDC score (MD: 3.99, P = .03), Lysholm score (MD: 2.30, P = .32), objective IKDC score (RR: 1.03, P = .09) and knee joint laxity (MD: 0.17, P = .28) was seen. In terms of radiological findings, about one-third of the studies favored PRP to facilitate the graft healing, improve the harvest site morbidity and prevent tunnel widening. In summary, moderate quality of evidence suggested that PRP could provide short-term but not long-term clinically important pain reduction.

BRCC36 promotes intestinal mucosal barrier injury caused by BMP2 after ischemia reperfusion via inhibiting PPARγ signaling.

As one of the most common pathological changes in trauma and surgery practice, intestinal ischemia-reperfusion (I/R) injury is regarded as a major precipitating factor in the occurrence and development of fatal diseases. BRCA1-BRCA2-containing complex subunit 36 (BRCC36), a deubiquitinase, has been proved important in a variety of pathophysiological processes such as DNA repair, cell cycle regulation, tumorigenesis, and inflammatory response. However, the effect of BRCC36 on intestinal mucosal barrier injury after I/R has not been fully elucidated. Our research found that BRCC36 aggravated intestinal mucosal barrier injury caused by bone morphogenetic protein 2 after I/R by downregulating peroxisome proliferator-activated receptor-γ (PPARγ) signaling. These results suggested that BRCC36/PPARγ axis might serve as a potential therapeutic target for preventing intestinal mucosal barrier injury after I/R.

[UPLC fingerprint and determination of five components of substance benchmark of classical prescription Shentong Zhuyu Decoction].

Fingerprints of 18 batches of substance benchmark of Shentong Zhuyu Decoction(SZD) were established by UPLC under the following conditions: Waters Sun Fire C_(18) column(3.0 mm×150 mm, 3.5 µm), column temperature of 35 ℃, gradient elution with mobile phase of acetonitrile(A)-0.1% phosphoric acid aqueous solution(B) at the flow rate of 0.4 mL·min~(-1), and detection by wavelength switching. A total of 16 common peaks were identified. The similarities among the fingerprints were calculated by Similarity Evaluation System for Chromatographic Fingerprint of Traditional Chinese Medicine(2012 Edition) and the result showed they were in the range of 0.911-0.988. Based on the 16 common peaks, cluster analysis(CA), principal component analysis(PCA), and partial least square discriminant analysis(PLS-DA) all categorized the 18 batches of samples into two groups(S1, S2, S5-S8, S14, and S17 in one group, and S1, S2, S5-S8, S14, and S17 in another), and 11 most influential components were screened. Five known components with great difference among samples(hydroxysafflor yellow A, ferulic acid, benzoic acid, ecdysone, and ammonium glycyrrhizinate) were determined. The combination of multi-component content determination and fingerprints can reflect the overall cha-racteristics of the primary standards of SZD, which is simple, feasible, reproducible, and stable. This study can serve as a reference for the quality control of the primary standards of SZD.

EBV-specific cytotoxic T lymphocytes for refractory EBV-associated post-transplant lymphoproliferative disorder in solid organ transplant recipients: a systematic review.

The use of Epstein-Barr virus-specific cytotoxic T lymphocytes (EBV-CTLs) in adoptive immunotherapy in hematopoietic stem cell transplantation (HSCT) patients with post-transplantation lymphoproliferative disorder (PTLD) has demonstrated safety and effectiveness. EBV-CTLs might also be the effective treatment of refractory PTLD of solid organ transplantation (SOT) recipients. Two independent assessors searched Pubmed, Embase, Cochrane Library, and Web of Science from their inception to November 2020. Eleven studies with 76 patients (42, 55% male) were included. We extracted the data and completed the quality assessments. Most of the studies were from Europe and the USA. Liver and kidney transplantation accounted for most of the transplant types. Thirty-five (46.1%) patients were diagnosed with monomorphic PTLD, and B lymphocyte type was the most common. All the patients received primary treatment for PTLD while it was ineffective. CTLs included autologous EBV-CTLs (15/76, 22%) and HLA-matched third-party EBV-CTLs (61/76, 78%). The response rate for EBV-CTL treatment of refractory PTLD was 66%. Of 50 patients, 36 achieved complete remission and 14 achieved partial remission. EBV-DNA level decreased in 39 patients. Adverse reactions were rare and mild. We conclude that adoptive therapy with EBV-specific CTLs is safe, well-tolerated, and effective in PTLD.

Polymer solubility in ionic liquids: dominated by hydrogen bonding.

Polymer solubility in ionic liquids (ILs) cannot be predicted by the solubility parameter approach based on the "like dissolves like" principle. According to the Kamlet-Abraham-Taft (KAT) multi-parameter polarity scale, ILs can be categorized on the basis of hydrogen-bond acidity or basicity ones. The experimental observations, that acidic ILs easily dissolve basic polymers and basic ILs dissolve acidic polymers, reflect the complementary nature of hydrogen-bonding interactions. A quantitative hydrogen-bonding analysis is proposed for predicting the solubility by taking the product of ΔαΔß as an indicator of the competition between cross-association and self-association hydrogen bonding (H-bonding), where Δα is the difference of acidity parameters between the polymer and IL, and Δß is the difference of basicity. This solubility criterion has been validated by the solubility data of 19 polymers (11 acidic and 8 basic) in 11 ILs (7 acidic and 4 basic). These principles based on KAT parameters can be applied to other systems dominated by hydrogen bonding.

[Mechanisms and application of triptolide against breast cancer].

Overtaking lung cancer,breast cancer is now the most commonly diagnosed cancer seriously threatening people's health and life. As the main effective component of Tripterygium wilfordii,triptolide( TP) has attracted increasing attention due to its multitarget and multi-pathway anti-tumor activity. Recent studies have revealed that breast cancer-sensitive TP enables the inactivation of breast cancer cells by inducing tumor cell apoptosis and autophagy,interfering in tumor cell metastasis,resisting drug resistance,arresting tumor cell cycle,and influencing tumor microenvironment. It has been recognized as a promising clinical antitumor agent by virtue of its widely accepted therapeutic efficacy. This paper reviewed the anti-breast cancer action and its molecular mechanisms of TP on the basis of the relevant literature in the past ten years,and proposed application strategies in view of the inadequacy of TP to provide a reference for further research on the application of TP in the treatment of breast cancer.

[Research progress on triptolide functionalized nanoparticulate drug delivery systems for tumor treatment].

Nowadays,the advantages of traditional Chinese medicine(TCM) for treatment of tumors are increasingly prominent.Triptolide shows wide-spectrum and highly effective anti-tumor activity. Moreover,nano-carrier-based triptolide drug delivery system is more powerful in improving water solubility and pharmacokinetic behavior of the drug,but it is easy to cause toxic and side effects that should not be neglected on human body. Because of tumor vascular heterogeneity and PEGylation dilemma,nanoparticulate drug delivery systems need to overcome multiple physiological and pathological barriers from drug administration to functioning. It is difficult for traditional triptolide nanoparticulate drug delivery systems to achieve active accumulation of nano-drug in tumor tissues and specific drug release in tumor target site solely relying on enhanced permeability and retention effect of solid tumor,limiting their application and clinical transformation in treatment of tumors. Based on the traditional nano-preparation system,the new functionalized nano-drug delivery system further enhances the nano-drug enrichment,penetration and controlled release at the tumor sites,which is of great significance in improving bioavailability,anti-tumor efficacy and reducing the side effects of drugs. In this paper,we summarized and analyzed the researches on new triptolide functionalized nano-drug delivery system from four perspectives,including tumor active targeting,tumor microenvironment response,polymer-drug conjugates,and multidrug co-delivery for tumor treatment,expecting to provide ideas for in-depth research and clinical application of triptolide and some other active anti-tumor TCM ingredients.

[Evaluation of chemical quality profile of Polygoni Multiflori Radix at different processing degrees based on its classic processing method "nine-steaming and nine-sun-curing"].

Based on the ancient method of nine-steaming and nine-sun-curing,the chemical composition changes and quality profiles in different processes of Polygoni Multiflori Radix were studied. Their contents of stilbene glycoside,anthraquinones and polysaccharides were determined by nine-steaming and nine-sun-curing with black bean juice and pharmacopoeia method. HPLC chemical fingerprints were established,and orthogonal partial least squares-discriminant analysis( OPLS-DA) was performed on different processed products using SIMCA 14. 1 software to evaluate the quality difference between samples. The results of content determination show that,with the increase of the number of processing and steaming times,the stilbene glycoside and the combined anthraquinone showed a decreasing trend,and the free anthraquinone,total anthraquinone and polysaccharide showed an upward trend in the different preparations of Polygoni Multiflori Radix and Pharmacopoeia. Six-steamed and six-sun-cured products can be used as the finishing point for the classic steaming. Fingerprint results showed that there were significant differences in chemical composition in Polygoni Multiflori Radix at different processing processes. It can be identified stilbene glycoside( peak 13),emodin( peak 21),and physcion( peak 24). By comparing the relative peak areas of the 26 chromatographic peaks in the sample after normalization( the reference is peak 7),it was found that the relative peak areas of 12 peaks in the processed products were higher than the raw products,13 peaks were reduced; according to statistical analysis of OPLS-DA,Polygoni Multiflori Radix at different processing degrees was further divided into three categories,sample S1 was class I,S2-S5 were class Ⅱ,and S6-S11 were class Ⅲ． And 8 peaks with the VIP value higher than 1. 0 were peak 13,21,4,3,11,14,5,and 24 in order. The eight chemical components were the main components to distinguish the difference between Polygoni Multiflori Radix in the process of nine-steaming and nine-sun-curing,suggesting that it was rational to use stilbene glycoside,emodin and emodin methyl ether as quality control indicators of Polygoni Multiflori Radix. The method established in this experiment conformed to the methodological verification requirements,established a method of multi-component content determination combined with fingerprint,and clarified that six-steaming and six-sun-curing was used as an improved classical processing technology,and more clearly defined the whole dynamic change of chemical composition in Polygoni Multiflori Radix by nine-steaming and ninesun-curing process. It provides a basis for the chemical quality evaluation model about different processed products of Polygoni Multiflori Radix.

[Research progress on anti-tumor effects and mechanisms of triptolide and its combined application].

Tumors are major chronic diseases and seriously threaten human health all over the world. How to effectively control and cure tumors is one of the most pivotal problems in the medical field. At present,surgery,radiotherapy and chemotherapy are still the main treatment methods. However,the side effects of radiotherapy and chemotherapy cannot be underestimated. Therefore,it is of great practical significance to find new anti-cancer drugs with low toxicity,high efficiency and targeting to cancer cells. With the increasing incidence of tumor,the anti-tumor effect of traditional Chinese medicine has increasingly become a research hotspot. Triptolide,which is a natural diterpenoid active ingredient derived from of Tripterygium wilfordii,as one of the highly active components,has anti-inflammatory,immunosuppressive,anti-tumor and other multiple effects. A large number of studies have confirmed that it has good anti-tumor activity against various tumors in vivo and in vitro. It can play an anti-tumor role by inhibiting the proliferation of cancer cells,inducing apoptosis of cancer cells,inducing autophagy of cancer cells,blocking the cell cycle,inhibiting the migration,invasion and metastasis of cancer cells,reversing multidrug resistance,mediating tumor immunity and inhibiting angiogenesis. On the basis of literatures,this paper reviews the anti-tumor effect and mechanism of triptolide,and analyzes the current situation of triptolide combined with other chemotherapy drugs,in order to promote deep research and better clinical application about triptolide.

A comparative study of surgical outcomes using a Colorado microdissection needle versus standard-size needle electrocautery in one-stage hypospadias repair using a transverse preputial island flap.

BACKGROUND: The purpose of this study was to compare the surgical outcomes of a Colorado microdissection needle (CMN) with that of a standard-size electrocautery needle in one-stage hypospadias repair using a transverse preputial island flap (TPIF). METHODS: The records of patients who received hypospadias repair from September 2012 to October 2013 were retrospectively reviewed. Patients were divided into a group that received repair using a CMN and those in which a standard-size electrocautery needle was used. Data collected and compared included age, types of hypospadias, duration of surgery, intraoperative blood loss, and postoperative edema and complications. RESULTS: There were 51 patients in the CMN group and 44 in the standard needle group, and the groups were similar with respect to age and type of hypospadias. The median surgery time for the CMN group was significantly shorter than that of the standard group (15.7 minutes vs. 20.6 minutes, respectively, P<0.001). At postoperative day 7 and day 30, the CMN group had significantly less patients with edema than the standard needle group (31.4% vs. 65.9%, P<0.01; and 37.3% vs. 79.5%, P<0.001, respectively). The overall complication rate has no significant difference between two groups. CONCLUSIONS: The use of CMN for tissue dissection and separation in hypospadias repair can facilitate foreskin degloving, shape the flap in a more efficient way, and help maintain adequate blood supply for the new urethra and its skin coverage.

[Dissolution behavior of Fuzi Lizhong pill based on simultaneous determination of two components in Glycyrrhizae Radix et Rhizoma].

To preliminarily investigate the dissolution behavior of Fuzi Lizhong pill, provide the basis for its quality control and lay foundation for in vivo dissolution behavior by determining the dissolution rate of liquiritin and glycyrrhizic acid. High-performance liquid chromatography (HPLC) method for simultaneous content determination of the two active ingredients of liquiritin and glycyrrhizic acid in Fuzi Lizhong pill was established; The dissolution amount of these two active ingredients in fifteen batches of Fuzi Lizhong pill from five manufacturers was obtained at different time points, and then the cumulative dissolution rate was calculated and cumulative dissolution curve was drawn. The similarity of cumulative dissolution curve of different batches was evaluated based on the same factory, and the similarity of cumulative dissolution curve of different factories was evaluated based on the same active ingredients. The dissolution model of Fuzi Lizhong pill based on two kinds of active ingredients was established by fitting with the dissolution data. The best dissolution medium was 0.25% sodium lauryl sulfate. The dissolution behavior of liquiritin and glycyrrhizic acid in Fuzi Lizhong pill was basically the same and sustained release in 48 h. Three batches of the factories (factory 2, factory 3, factory 4 and factory 5) appeared to be similar in dissolution behavior, indicating similarity in dissolution behavior in most factories. Two of the three batches from factory 1 appeared to be not similar in dissolution behavior of liquiritin and glycyrrhizic acid. The dissolution data of the effective ingredients from different factories were same in fitting, and Weibull model was the best model in these batches. Fuzi Lizhong pill in 15 batches from 5 factories showed sustained release in 48 h, proving obviously slow releasing characteristics "pill is lenitive and keeps a long-time efficacy". The generally good dissolution behavior also suggested that quality of different batches from most factories was stable. The dissolution behavior of liquiritin and glycyrrhizic acid in different factories was different, suggesting that the source of medicinal materials and preparation technology parameters in five factories were different.

Reversal of paclitaxel resistance in human ovarian cancer cells with redox-responsive micelles consisting of α-tocopheryl succinate-based polyphosphoester copolymers.

P-glycoprotein (P-gp)-mediated multidrug resistance (MDR) is a major obstacle in achieving the therapeutic benefits of paclitaxel (PTX) in the treatment of human ovarian carcinoma. This study is aimed to develop an efficient PTX drug delivery approach to overcome MDR. Redox-responsive micelles consisting of amphiphilic polymers containing disulfide linkages, ie, poly (phosphate ester)-SS-D-α-tocopheryl succinate (POPEA-SS-TOS, PSST) were prepared. PTX-loaded PSST micelles (PTX/PSST-M) designed to display synergistic functions, including reversible inhibition of P-gp, intracellular redox-sensitive release and potent anticancer activities. The average size of PTX/PSST-M was 68.1±4.9 nm. The encapsulated PTX was released quickly through redox-triggered dissociation of micelles. The inhibition of P-gp activity and enhanced cellular accumulation of the PSST micelles were validated. PTX/PSST-M showed significantly increased cytotoxicity against PTX-resistant human ovarian cancer A2780/PTX cells: when the cells were treated with PTX/PSST-M for 48 h, the equivalent IC50 value of PTX was reduced from 61.51 to 0.49 µmol/L. The enhanced cytotoxic effects of PTX/PSST-M against A2780/PTX cells were attributed to their synergistic effects on reducing the mitochondrial transmembrane potential, ATP depletion, ROS production, and activation of apoptotic pathways. Furthermore, PTX/PSST-M significantly increased cell apoptosis/necrosis and cell cycle arrest at the G2/M phase in A2780/PTX cells. These results demonstrate that the redox-responsive PSST micelles inhibit P-gp activity and have a good potential to effectively reverse PTX resistance in human ovarian carcinoma cells by activating intrinsic apoptotic pathways.

[Analysis on dosage form theory and current application situation of traditional Chinese medicine pill].

Traditional Chinese medicine(TCM) pill, the most representative and successive dosage form, is called as one of the four classical TCM dosage forms. "Pills could keep the lasting and lenitive therapeutic efficacy for a long period" is the most classical dosage form theory, showing a guidance significance in making recipe, preparations and clinic application. In this article, we would elucidate the inheritance and development significance of TCM pills in three key points, including dosage form theory, pharmaceutical preparation technology and clinic usage based on the pharmaceutics connotation of this theory. From this, it can provide the basis for researches on pills mechanism, material basis and mode of action in clinical application.

[Comprehensive analysis on "toxicity and effect" of Chinese pharmaceutical preparations].

The manufacturing process of Chinese medicines is the significant link to achieve "effect-enhancing and toxicity-reducing", including an interaction between "toxicity and effect". This paper would elucidate the effects of Chinese herbal compound decoction, preparation, dosage forms, route of administration and quality of pharmaceutical excipients on "toxicity-effect" theory from the formulation approaches. The article pointed out that the comprehensive analysis on "toxicity-effect" theory should be strengthened from the aspects of overall manufacturing, fundamental research and modern Chinese preparation, to explore the mechanism of "effect-enhancing and toxicity-reducing" in the manufacturing process, clarify the core status of Chinese preparation in "toxicity-effect" theory, and ensure the security and effectiveness in traditional Chinese medicine clinical application.

Low- and high-frequency transcutaneous electrical acupoint stimulation induces different effects on cerebral µ-opioid receptor availability in rhesus monkeys.

Although systematic studies have demonstrated that acupuncture or electroacupuncture (EA) analgesia is based on their accelerating endogenous opioid release to activate opioid receptors and that EA of different frequencies is mediated by different opioid receptors in specific areas of the central nervous system, there is little direct, real-time evidence to confirm this in vivo. The present study was designed to investigate the effects of transcutaneous electrical acupoint stimulation (TEAS), an analogue of EA, at low and high frequencies on µ-opioid receptor (MOR) availability in the brain of rhesus monkeys. Monkeys underwent 95-min positron emission tomography (PET) with (11) C-carfentanil three times randomly while receiving 0, 2, or 100 Hz TEAS, respectively. Each TEAS was administered in the middle 30 min during the 95-min PET scan, and each session of PET and TEAS was separated by at least 2 weeks. The results revealed that 2 Hz but not 100 Hz TEAS evoked a significant increase in MOR binding potential in the anterior cingulate cortex, the caudate nucleus, the putamen, the temporal lobe, the somatosensory cortex, and the amygdala compared with 0 Hz TEAS. The effect remained after the end of TEAS in the anterior cingulate cortex and the temporal lobe. The selective increase in MOR availability in multiple brain regions related to pain and sensory processes may play a role in mediating low-frequency TEAS efficacy.