Features and development trends in international standardization of Chinese materia medica in ISO/TC 249.

Chinese materia medica (CMM) is indispensable component of Traditional Chinese Medicine (TCM) therapy. With the widespread of TCM around the world, the quality control and safe use of CMM become a major concern. This paper introduces the role of ISO standards for industrial development and current development status of CMM standards in ISO/TC 249. Through the comparison of similarities and differences between CMM standards in ISO/TC 249 and pharmacopoeias of main stakeholders, this paper suggests strengthening standard formulation in the following areas to provide more appropriate documents to facilitate the international trade and promote the industrial development of CMM: (1) Develop standards to fill the blanks among the whole industry chain of CMM; (2) Develop standards for new forms of CMM and services; (3) Develop specification and grade standards for CMM with large quantity and high value.

Pharmacokinetics-based identification of pseudoaldosterogenic compounds originating from Glycyrrhiza uralensis roots (Gancao) after dosing LianhuaQingwen capsule.

LianhuaQingwen capsule, prepared from an herbal combination, is officially recommended as treatment for COVID-19 in China. Of the serial pharmacokinetic investigations we designed to facilitate identifying LianhuaQingwen compounds that are likely to be therapeutically important, the current investigation focused on the component Glycyrrhiza uralensis roots (Gancao). Besides its function in COVID-19 treatment, Gancao is able to induce pseudoaldosteronism by inhibiting renal 11ß-HSD2. Systemic and colon-luminal exposure to Gancao compounds were characterized in volunteers receiving LianhuaQingwen and by in vitro metabolism studies. Access of Gancao compounds to 11ß-HSD2 was characterized using human/rat, in vitro transport, and plasma protein binding studies, while 11ß-HSD2 inhibition was assessed using human kidney microsomes. LianhuaQingwen contained a total of 41 Gancao constituents (0.01-8.56 µmol/day). Although glycyrrhizin (1), licorice saponin G2 (2), and liquiritin/liquiritin apioside (21/22) were the major Gancao constituents in LianhuaQingwen, their poor intestinal absorption and access to colonic microbiota resulted in significant levels of their respective deglycosylated metabolites glycyrrhetic acid (8), 24-hydroxyglycyrrhetic acid (M2D; a new Gancao metabolite), and liquiritigenin (27) in human plasma and feces after dosing. These circulating metabolites were glucuronized/sulfated in the liver and then excreted into bile. Hepatic oxidation of 8 also yielded M2D. Circulating 8 and M2D, having good membrane permeability, could access (via passive tubular reabsorption) and inhibit renal 11ß-HSD2. Collectively, 1 and 2 were metabolically activated to the pseudoaldosterogenic compounds 8 and M2D. This investigation, together with such investigations of other components, has implications for precisely defining therapeutic benefit of LianhuaQingwen and conditions for its safe use.

[Pharmacological effects of Huangqin Decoction prepared from roots of multi-originated peony on ulcerative colitis in mice:a comparative study].

Huangqin Decoction(HQD) is a classic prescription for treating dysentery in the Treatise on Cold Damage and now is mainly used for the treatment of ulcerative colitis(UC). Since there are no requirements on specific Paeonia species, both Paeoniae Radix Alba(white peony root, WPR) and Paeoniae Radix Rubra(red peony root, RPR) are clinically used in HQD now. Although the two types of peony roots are close in origin and similar in primary components, the medicinal properties and efficacies are different. Furthermore, the systematic comparative analysis on the efficacy differences in treating UC of HQD with the roots of multi-originated peony has been seldom reported. This study compared and evaluated the pharmacological effects of HQD prepared from the roots of multi-originated peony, including WPR, RPR-l(derived from P. lactiflora), and RPR-v(derived from P. veitchii) based on the mouse model of UC induced by dextran sodium sulfate(DSS) by animal behaviors, pathological section(colon), and cytokine expression(IL-1ß and IL-6), aiming to provide evidence for the identification of the original resource of peony root in HQD. The results indicated that all HQD samples prepared from WPR, RPR-l, and RPR-v could improve the symptoms of UC. Compared with the HQD-WPR, HQD-RPR-l and HQD-RPR-v were significantly different in weight loss, colon length, and disease activity index(DAI) score, but there was no significant difference between HQD-RPR-l and HQD-RPR-v. Moreover, HQD-RPR-v exhibited the most significant improvement in the pathological morphology of colonic tissue and mucosal defects. According to the previous comparative analysis of chemical profiling and content distribution of HQD prepared from the roots of multi-originated peony, RPR-v in HQD was potent in protecting against UC, which was presumedly attributed to a large number of monoterpene glycosides and galloyl glucoses. This study provided a scientific basis for the determination of peony root in HQD and its clinical medication.

Micro/Nanoengineered α-Fe2 O3 Nanoaggregate Conformably Enclosed by Ultrathin N-Doped Carbon Shell for Ultrastable Lithium Storage and Insight into Phase Evolution Mechanism.

The Fe-based transition metal oxides are promising anode candidates for lithium storage considering their high specific capacity, low cost, and environmental compatibility. However, the poor electron/ion conductivity and significant volume stress limit their cycle and rate performances. Furthermore, the phenomena of capacity rise and sudden decay for α-Fe2 O3 have appeared in most reports. Here, a uniform micro/nano α-Fe2 O3 nanoaggregate conformably enclosed in an ultrathin N-doped carbon network (denoted as M/N-α-Fe2 O3 @NC) is designed. The M/N porous balls combine the merits of secondary nanoparticles to shorten the Li+ transportation pathways as well as alleviating volume expansion, and primary microballs to stabilize the electrode/electrolyte interface. Furthermore, the ultrathin carbon shell favors fast electron transfer and protects the electrode from electrolyte corrosion. Therefore, the M/N-α-Fe2 O3 @NC electrode delivers an excellent reversible capacity of 901 mA h g-1 with capacity retention up to 94.0 % after 200 cycles at 0.2 A g-1 . Notably, the capacity rise does not happen during cycling. Moreover, the lithium storage mechanism is elucidated by ex situ XRD and HRTEM experiments. It is verified that the reversible phase transformation of α↔γ occurs during the first cycle, whereas only the α-Fe2 O3 phase is reversibly transformed during subsequent cycles. This study offers a simple and scalable strategy for the practical application of high-performance Fe2 O3 electrodes.

Analysis on the current quality standards of Chinese materia Medica used in COVID-19 prevention and treatment.

PURPOSE: Traditional Chinese medicine (TCM) has fully engaged and played an essential role in the prevention and treatment of Coronavirus Disease 2019 (COVID-19). This study compares relevant standards on high-frequent Chinese Materia Medicia (CMM) used in this pandemic aiming at reaching a global consensus and ensuring the use of Chinese medicines safely. METHODS: 141 representative Chinese formulas and Chinese Patent Medicines from the National Protocol and the most of Provincial Protocols for controlling COVID-19 in China have been collected to statistical analyze the composition and characteristics of CMM. Among them, the domestic and international standards of 47 varieties with the frequency usage over 10 times were selected to compare their quality requirements in the mainstream pharmacopoeias and international standards. RESULTS: The quality requirements of used CMM for fighting COVID-19 on the terms of overall quality control, marker compounds, and safety indicators showed different patterns in these mainstream pharmacopoeias and international standards. The uniformed and scientific quality standards of CMM were urgently needed to promote global acceptation and trade. CONCLUSIONS: These findings will provide evidence for building unified quality and safety standards that can adapt to the characteristics of CMM and promote international trade, and also will be stated that it is of the highest priority for ISO/TC 249 to formulate high-quality standards that consolidate international consensus to ensure quality and safety of the urgently needed CMM.

[Simultaneous determination of four anthraquinones in Polygonum multiflorum by QAMS].

A simple, specific and selective quantitative analysis of multi-components by single marker(QAMS) method for simultaneous determination of anthraquinones and anthraquinone glycosides in Polygonum multiflorum was developed. Four main anthraquinones and its glycosides, emodin, emodin-8-O-ß-D-glucoside, physcion and physcion-8-O-ß-D-glucoside were selected as analytes to evaluate the quality of P. multiflorum. Emodin was used as the internal standard, and the relative correction factors(RCFs) between emodin and the other three anthraquinones were calculated. Comparison of the contents of the four components in 30 batches of P. multiflorum from different regions and 12 batches decoction pieces from different manufacturers by QAMS and external standard method(ESM) showed that there was no significant difference between QAMS and ESM for quantification of the four main components by using relative error results, and the QAMS method was accurate and reliable, and had a good repeatability. In addition, compared with the results calculated by the difference method between total anthraquinone and free anthraquinone in the content determination of P. multiflorum in Chinese Pharmacopoeia, the results of direct determination combined anthraquinone by QAMS were very close to that by measured the external standard method. Therefore, simultaneous quantification of four main anthraquinones by using QAMS is suitable to evaluate the quality of P. multiflorum. Then the optimized assay method of the combined anthraquinone contents showed simple and feasible, which could be replaced and improved the quantification method of the combined anthraquinone in the current Chinese Pharmacopeia.

3 D Porous CoS2 Hexadecahedron Derived from MOC toward Ultrafast and Long-Lifespan Lithium Storage.

A new hexadecahedron assembled by core-shell CoS2 particles@N-doped carbon (CoS2 @NCH) is prepared successfully through the self-templating method. The CoS2 @NCH hybrid electrode delivers a high lithium-storage capacity of 778 mA h g-1 after 1000 cycles at a high current density of 1 A g-1 , which is the longest cycle lifespan among the reported CoS2 anode materials in lithium-ion batteries. Furthermore, the CoS2 @NCH hybrid electrode shows excellent rate capability with a discharge capacity of 220 mA h g-1 at an extremely high current density of 20 A g-1 , and a charge capacity of 649 mA h g-1 is restored upon returning the current density back to 2 A g-1 . The superior performance is attributed to the unique construction of CoS2 @NCH. The N-doped interconnected porous carbon shells form highly conductive skeletons for quick electron transfer and prevent the electrode from collapsing. Moreover, the porous characteristic of the materials plays a key role: as some effective channels, the mesopores on the porous carbon shells provide greater access for lithium, and the mesopores derived from the particle interspace enables the complete immersion of the electrodes in electrolyte, which alleviates the volume expansion and ensures the integrity of the electrode. In addition, the nanosized CoS2 particles, which shorten the ion-transport path and provide extra electroactive sites, also improve the reaction kinetics.

Abietane Diterpenoids from the Roots of Clerodendrum trichotomum and Their Nitric Oxide Inhibitory Activities.

Twelve new abietane diterpenoids (1-12) and 31 known analogues (13-43) were isolated from a medicinal Chinese herb, Clerodendrum trichotomum Thunberg. The absolute configurations of 1-3 were established on the basis of ECD and X-ray crystallography data, whereas that of 4 was elucidated by comparison of experimental and calculated ECD data. Eight diterpenoids, 15,16-dehydroteuvincenone G (1), trichotomin A (4), 2α-hydrocaryopincaolide F (7), villosin C (20), 15-dehydro-17-hydroxycyrtophyllone A (22), demethylcryptojaponol (38), 6ß-hydroxydemethylcryptojaponol (39), and trichotomone (43), exerted inhibitory effects against NO production with IC50 values of 5.6-16.1 µM. The structure-activity relationships of the isolated diterpenoids are also estimated.

Dissipation and Migration of Pyrethroids in Auricularia polytricha Mont. from Cultivation to Postharvest Processing and Dietary Risk.

In order to ensure raw consumption safety the dissipation behavior, migration, postharvest processing, and dietary risk assessment of five pyrethroids in mushroom (Auricularia polytricha Mont.) cultivated under Chinese greenhouse-field conditions. Half-lives (t1/2) of pyrethroids in fruiting body and substrate samples were 3.10-5.26 and 17.46-40.06 d, respectively. Fenpropathrin dissipated rapidly in fruiting bodies (t1/2 3.10 d); bifenthrin had the longest t1/2. At harvest, pyrethroid residues in A. polytricha (except fenpropathrin) were above the respective maximum residue limits (MRLs). Some migration of lambda-cyhalothrin was observed in the substrate-fruit body system. In postharvest-processing, sun-drying and soaking reduced pyrethroid residues by 25-83%. We therefore recommend that consumers soak these mushrooms in 0.5% NaHCO3 at 50 °C for 90 min. Pyrethroids exhibit a particularly low PF value of 0.08-0.13%, resulting in a negligible exposure risk upon mushroom consumption. This study provides guidance for the safe application of pyrethroids to edible fungi, and for the establishment of MRLs in mushrooms to reduce pesticide exposure in humans.

[Chemical constituents from hypoglycemic active part of Plantaginis Semen].

The chemical constituents of Plantaginis Semen with hypoglycemic effect was investigated in this paper. The previous results of the in vivo hypoglycemic effect showed that 60% ethanol extract of Plantaginis Semen decreased the levels of FBG and improved the glucose tolerance in high fat diet(HFD)-induced diabetic C57BL/6 mice. Then, in the present study, the above potential bioactive extract was separated and purified by silica gel, ODS, Sephadex LH-20 column chromatography, medium pressure liquid chromatography(MPLC)and preparative HPLC. The structures of isolated compounds were identified by physicochemical properties and spectral analyses. Eight compounds were obtained and identified as 4, 4a, 5, 7a-tetrahydro-7-(hydroxymethyl)cyclopenta[c]pyran-3(1H)-one(1), iridolactone(2), pedicularislacton(3), rehmaglutin C(4), geniposidic acid(5), p-hydroxylphenylglycerol(6), 1, 2-benzenediol-4-(2-hydroxyethyl)(7), and 3-buten-2-one-4-[3-(ß-D-glucopyranosyloxy)-4-hydroxyphenyl](8). Among them, compounds 1-5 were iridoids, and 6-8 were phenolic acids. Compound 1 was a new natural product, and compounds 2-4, 6 and 8 were isolated from the Plantaginaceae family for the first time.

Multi-Residue Analysis of Pesticide Residues in Crude Pollens by UPLC-MS/MS.

A multi-residue method for the determination of 54 pesticide residues in pollens has been developed and validated. The proposed method was applied to the analysis of 48 crude pollen samples collected from eight provinces of China. The recovery of analytes ranged from 60% to 136% with relative standard deviations (RSDs) below 30%. Of the 54 targeted compounds, 19 pesticides were detected. The major detection rates of each compound were 77.1% for carbendazim, 58.3% for fenpropathrin, 56.3% for chlorpyrifos, 50.0% for fluvalinate, 31.3% for chlorbenzuron, and 29.2% for triadimefon in crude pollen samples. The maximum values of each pesticide were 4516 ng/g for carbendazim, 162.8 ng/g for fenpropathrin, 176.6 ng/g for chlorpyrifos, 316.2 ng/g for fluvalinate, 437.2 ng/g for chlorbenzuron, 79.00 ng/g for triadimefon, and so on. This study provides basis for the research on the risks to honeybee health.

Clinical and Imaging Features of Pulmonary Nodular Lymphoid Hyperplasia.

PURPOSE: To investigate the clinical and radiographic features of PNLH and the relationship with pathologic features. MATERIALS AND METHODS: A total of 11 patients in whom PNLH was confirmed in our department were retrospectively studied. The clinical and radiographic features were extracted and analyzed, and we also discussed the relationship between radiologic and pathologic features. RESULTS: Of the 11 patients with PNLH, 5 were discovered incidentally, while 4 presented with chest symptoms. Laboratory tests showed no specificity and the lesions were located under the pleura with an adjacent pleural indentation. Most lesions were solid, with some showing signs of spiculation or spiculate protuberance. In some cases, hypodense areas and vocules were visible. The enhanced scan showed marked enhancement, but most had no lymph node enlargement, and there was no pleural effusion. CONCLUSIONS: The clinical manifestations of PNLH are nonspecific and the imaging features overlap with those of malignant lung tumors, and the diagnosis depends on pathologic examination.

In vitro inhalation bioaccessibility and health risk assessment of difenoconazole in the atmosphere.

BACKGROUND: Assessment of the risk of pesticide inhalation in populations around farmland is necessary because inhalation is one of the ways in which pesticides can risk human health. This study aimed to identify the inhalation risk of difenoconazole on humans by using dose-response and exposure assessments. RESULTS: In the field simulation application, respiratory exposure in populations around farmland ranged from 71 to 430 ng/m3 . Using response surface methodology, the maximum bioaccessibility of difenoconazole in three simulated lung fluids was 35.33% in Gamble's solution (GS), 34.12% in artificial lysosomal fluid (ALF), and 42.06% in simulated interstitial lung fluid (SLF). Taking the proliferation activity of the A549 cell model as the endpoint, the benchmark dose limit and benchmark dose of difenoconazole on A549 cells were 16.36 and 5.60 mg/kg, respectively. The margin of exposure to difenoconazole in GS, ALF and SLF were, respectively, 8.66 × 105 to 5.28 × 106 , 8.97 × 105 to 5.47 × 106 and 7.28 × 105 to 4.44 × 106 . CONCLUSION: The risk assessment results indicate that under all circumstances, applying difenoconazole is safe for populations around farmland. However, a fan-shaped nozzle, suspension concentrate and greater inhalation height increase the risk of inhalation. © 2023 Society of Chemical Industry.

[Evaluation of the expression and significance of Claudin-5 and CD99 in solid-pseudopapillary neoplasms and neuroendocrine tumors of pancreas].

OBJECTIVE: To investigate the expression of endothelium tight junction protein Claudin-5 and intercellular adhesion molecule CD99 in solid-pseudopapillary neoplasms (SPN) and neuroendocrine tumors of pancreas (P-NET), and their significance in the differential diagnoses. METHODS: Immunohistochemical staining of Claudin-5 and CD99 was performed in 37 cases SPN and 21 cases of P-NET. RESULTS: Membranous Claudin-5 expression was observed in all cases of SPN but was absent in all cases of P-NET. The difference was significant (P < 0.01). In SPN, 91.9% (34/37) of the cases displayed paranuclear dot-like immunoreactivity for CD99; in contrast, 61.9% (13/21) of the cases of P-NET displayed membranous staining (P < 0.01). There was a positive association between the expression of Claudin-5 and CD99 in SPN (r = 0.421,P = 0.001). CONCLUSIONS: Although the macroscopic and microscopic features of SPN are quite characteristic, they may not allow confident differentiation from P-NET in all cases, especially when these characteristics are not classical. If necessary, immunostaining for Claudin-5 and CD99 can help to differentiate between these entities.

Characterization and Comparison Analysis of WHO Monographs on Selected Medicinal Plants and ISO Standards of Chinese Materia Medica.

Medicinal plants or Chinese materia medica (CMM) are now attracting worldwide attention as they have increasingly prominent advantages over chemical drugs in disease treatment and healthcare. Since the 1990s, World Health Organization (WHO) and International Organization for Standardization established the Technical Committee of Traditional Chinese Medicine (ISO/TC 249) have carried out the development of quality standards on medicinal plants or CMMs respectively, and a considerable number of monographs and international standards have been published. Since the two international organizations adhere to different principles, the standards they develop naturally have different emphasis. Driven by market demand and international trade, ISO mainly takes quality, efficacy and safety into consideration when developing standards, while WHO pays more attention to clinical practice, quality control and medication guidance. Up to now, there is a lack of comparative analysis on the records, background, principles, basic content, and main requirements of quality standards on medicinal plants or CMMs respectively published by WHO and ISO. Therefore, based on international standards of CMM developed by ISO/TC 249 platform and WHO Monographs on Selected Medicinal Plants, this paper systematically compares the purposes, selected principles, standard-developing process, basic content, and main quality requirements to summarize their similarities and differences, and find their merits, aiming to serve as a reference to the development of international standards for CMMs that helps them go global.

Standardization of Panax ginseng: Current Status of Global Trade, Demands, and Development.

Panax ginseng, as a kind of rare and valuable Chinese materia medica with the largest global trade volume, has been widely applied in many fields, such as medicine, food, health care, and production of daily chemical products. It is widely used in Asia, Europe, and America. However, its global trade and standardization present different features and an uneven development in different countries or regions. As the main country for its production and consumption, Panax ginseng in China is characterized by its large cultivation area and high total yield and is mainly sold as a raw material or primary processed product. By contrast, Panax ginseng produced in South Korea is mainly sold in manufactured products. Besides, European countries, as another consumption market of Panax ginseng, pay more attention to the research and development of its products. Although Panax ginseng has been widely recorded in various national pharmacopoeias and regional standards, the current standards of Panax ginseng differ in quantity, composition, and distribution, and the existing standards cannot be enough to meet the demands of its global trade. Based on the above issues, we systemically summarized and analyzed the status and features of Panax ginseng standardization and put forward suggestions on the development needs of international standardization of Panax ginseng to guarantee its quality and safety, regulate the order of its global trade, and resolve trade disputes, thereby promoting the high-quality development of the Panax ginseng industry.

Radix Paeoniae Rubra and Radix Paeoniae Alba Attenuate CCl4-induced acute liver injury: an ultra-performance liquid chromatography-mass spectrometry (UPLC-MS) based metabolomic approach for the pharmacodynamic study of Traditional Chinese Medicines (TCMs).

Metabolomics has been frequently used in pharmacodynamic studies, especially those on traditional Chinese medicine (TCM). Radix Paeoniae Alba and Radix Paeoniae Rubra are popularly used in TCM, and both have hepatoprotective effects. In this study, a CCl(4)-induced acute liver injury rat model was established and confirmed by the observed serum aminotransferase activities. The metabolomics approach was applied to study the influence of Radix Paeoniae Alba and Radix Paeoniae Rubra on the metabolic changes in rats with acute liver injury. The partial least-squares-discriminant analysis (PLS-DA) of rat serum and their ultra-performance liquid chromatography-mass spectrometry (UPLC-MS) fingerprints allowed discrimination of controlled, acute liver injury-model rats after administration of the two types of TCMs. The time-dependent PLS-DA plots showed that the changes in the metabolic patterns of the rats, which were administered with the TCMs, had stabilized within 2 h after they received the intraperitoneal CCl(4) injection. The results indicated the protective effect of TCMs against liver injury. Several potential biomarkers were detected and identified, which included creatine, deoxycholic acid, choline, 5-methylenetetrahydrofolate, folic acid, and glycocholic acid. The physiological significance of these metabolic changes was discussed.

Quantitative and chemical fingerprint analysis for the quality evaluation of Isatis indigotica based on ultra-performance liquid chromatography with photodiode array detector combined with chemometric methods.

A simple and reliable method of ultra-performance liquid chromatography with photodiode array detector (UPLC-PDA) was developed to control the quality of Radix Isatidis (dried root of Isatis indigotica) for chemical fingerprint analysis and quantitative analysis of eight bioactive constituents, including R,S-goitrin, progoitrin, epiprogoitrin, gluconapin, adenosine, uridine, guanosine, and hypoxanthine. In quantitative analysis, the eight components showed good regression (R > 0.9997) within test ranges, and the recovery method ranged from 99.5% to 103.0%. The UPLC fingerprints of the Radix Isatidis samples were compared by performing chemometric procedures, including similarity analysis, hierarchical clustering analysis, and principal component analysis. The chemometric procedures classified Radix Isatidis and its finished products such that all samples could be successfully grouped according to crude herbs, prepared slices, and adulterant Baphicacanthis cusiae Rhizoma et Radix. The combination of quantitative and chromatographic fingerprint analysis can be used for the quality assessment of Radix Isatidis and its finished products.

[Primary safety evaluation of sulfated paeoniae radix alba].

The paper is to report the development of a method of quantitative analysis of multi-components by high performance liquid chromatography (HPLC) for simultaneously determining paeoniflorin sulfonate (PS), paeoniflorin (PF) and albiflorin (AF) in sulfated Paeoniae Radix Alba. Moreover, the cytotoxicity of paeoniflorin sulfonate by MTT-assay and the acute toxicity of mice by administration of paeoniflorin sulfonate were evaluated. Chromatographic separation of paeoniflorin sulfonate, PF and AF were performed on a SHISEIDO CAPCELL PAK C18 column (250 mm x 4.6 mm, 5 microm) for HPLC and a mixture of acetonitrile and 0.02% phosphoric acid solution (15 : 85) as the mobile phase. As detector a spectrophotometer set at 230 nm; column temperature 30 degrees C; flow rate 1.0 mL x min(-1). The toxicity of paeoniflorin sulfonate was evaluated by in vitro cytotoxicity carried out on mouse and human primary hepatocytes, and by acute oral toxicity test carried out on mice. The calibration curve of paeoniflorin sulfonate, PF and AF revealed linearity in the range of 0.041 8 - 1.045 0, 0.023 5 - 0.587 5, and 0.039 8 - 0.995 0 mg x mL(-1), respectively (r > 0.999 8). The average recovery was ranged from 99.11% to 101.71%, RSD < 2%. Paeoniflorin sulfonate does not have any cytotoxicity to cells at all the tested concentrations (< or = 300 micromol x L(-1)) in the in vitro cytotoxicity assay. The maximum tolerance dose of paeoniflorin sulfonate solution and extraction of Paeoniae Radix Alba to mouse is 5 g x kg(-1) and 80 g x kg(-1) respectively. The contents of these three components in the samples were determined with the developed method. It is a rapid, convenient and accurate method to determine multi-components. The content of PF in sulfated Paeoniae Radix Alba is significantly lower, and there is negative correlationship between the content of paeoniflorin sulfonate and PF. The in vitro cytotoxicity assay and in vivo mouse acute toxicity test showed that there is no obvious toxicity of paeoniflorin sulfonate and water-soluble extract of sulfated Paeoniae Radix Alba.

Risk factors for the long-term prognosis and recurrence of HIV-negative cytomegalovirus retinitis in North China.

AIM: To demonstrate the clinical features, the risk factors, the visual prognosis and the recurrence of cytomegalovirus (CMV) retinitis (CMVR) in HIV-negative patients. METHODS: HIV-negative patients with CMVR were involved in this study. Best corrected visual acuity (BCVA), intraocular pressure (IOP), CMV-DNA load in aqueous and/or serum samples, treatment, follow-up time, recurrence and complications were recorded. Ocular characteristics were evaluated by fundus photographs. Association between ocular factors and visual prognosis were analyzed by regression analysis. RESULTS: Twenty-five eyes of 16 patients were included. All 25 eyes underwent intravitreal injections of anti-viral agents. The mean logMAR BCVA improved from 0.94±0.98 (0.98-0.78) initially to 0.77±0.73 (0.82-0.68) at last visit, but not significantly. After antiviral treatment, the aqueous CMV DNA load significantly reduced to (3.42±1.47)×102 copies/mL (P=0.001), compared with (2.51±3.11)×105 copies/mL at baseline. Macular involvement (R 2=0.475, P=0.049) and initial visual acuity (R 2=0.475, P=0.017) were significantly associated with the poor visual prognosis (BCVA<20/400). The extent of retinal lesions (R 2=0.064, P=0.04) was significant associated with the risk of recurrence of CMVR. CONCLUSION: Intravitreal injection of anti-viral agents offers a safe and effective treatment for CMVR. Macular involvement and initial visual acuity significantly associate with visual prognosis. The extent of retinal lesions is significantly associated with the recurrence of CMVR. These ocular factors can be used as predictive risk factors for long term visual prognosis in HIV-negative CMVR patients.