Four New Species of Strobilomyces (Boletaceae, Boletales) from Hainan Island, Tropical China.

Strobilomyces, one of the most noticeable genera of Boletaceae (Boletales), is both ecologically and economically important. Although many studies have focused on Strobilomyces in China, the diversity still remains incompletely understood. In the present study, several collections of Strobilomyces from Hainan Island, tropical China were studied based on morphology and molecular phylogenetic analyses. Four species are described as new, viz. S. baozhengii, S. conicus, S. hainanensis, and S. pachycystidiatus. Detailed descriptions, color photos of fresh basidiomata, and line drawings of microstructures of the four species are presented.

[Spatiotemporal evolution of habitat quality in three basins of Hainan Island based on InVEST model]. / 基于InVEST模型的海南岛三大流域生境质量时空演变.

Based on land use data of five periods during 1980 to 2020, using the InVEST model and the methods of land use transfer, habitat quality change rate and spatial statistical analysis, we explored the changes of habitat quality and its spatial distribution characteristics in the three major basins of Hainan Island (Nandu River, Changhua River and Wanquan River). The results showed that woodlands were the main land use type in the three basins of Hainan Island, accounting for more than 70% of the total area. From 1980 to 2020, the area of construction land increased the most, reaching up to 169.09 km2, mainly from cultivated land and woodland. The spatial distribution pattern of habitat quality in the study area was higher in the upstream and head water areas and lower in the mid and downstream regions. Overall, habitat quality index increased slightly for a short period and then decreased significantly during the study period. Among the three basins, habitat quality of Wanquan River Basin was the highest, followed by Changhua River Basin, and Nandu River Basin was the lowest. The habitat quality of Nandu River Basin fluctuated greatly and was strongly affected by human disturbance. From 1980 to 2020, the change rate of habitat quality in the three basins generally decreased by 0.5%, which was significantly degraded from 2010 to 2020. From 1980 to 2020, the spatial distribution of habitat quality in the study area displayed strong autocorrelation and significant aggregation. The hot spot area of habitat quality was mainly concentrated near the head water and upstream areas of the three basins, while the cold spot area was mainly distributed in the estuary area of the three basins, along with the mid and downstream areas of the Nandu River. These results would provide scientific reference for biodiversity conservation and ecological restoration efforts in the three basins of Hainan Island.

Gross ecosystem product accounting of national park: Taking Hainan Tropical Rainforest National Park as an example.

Hainan Tropical Rainforest National Park has the most representative and largest contiguous tropical rainforest in China, which has advantages in exploring the realization mechanism of ecological product value in national parks. Based on the basic framework of "The Technical Guideline on Gross Ecosystem Product (GEP)", we constructed a GEP accounting system in line with the characteristics of tropical rain forest national park, and calculated the GEP of Hainan Tropical Rainforest National Park in 2019. The results showed that the GEP of Hainan Tropical Rainforest National Park in 2019 was 204.513 billion yuan, and the GEP per unit area was 0.046 billion yuan·km-2. Among all the service types, the value of material services was 4.850 billion yuan, accounting for 2.4% of the total GEP in the national park. The ecosystem regulation service value was 168.891 billion yuan, accounting for 82.6%. The value of cultural services was 30.772 billion yuan, accounting for 15.0%. Among different ecosystem types, the unit area value of the tropical rain forest ecosystem represented by mountain rain forest, lowland rain forest, deciduous monsoon forest, and tropical cloud forest was much higher than that of plantation or other ecosystems, indicating the dominant role of tropical rain forest ecosystem in providing ecosystem services. In addition, based on the GEP accounting results of the national park, we put forward relevant suggestions for further exploring the realization path and realization mechanism of ecological product value.

Efficacy of Getong Tongluo Capsule () for Convalescent-Phase of Ischemic Stroke and Primary Hypertension: A Multicenter, Randomized, Double-Blind, Controlled Trial / 中国结合医学杂志

OBJECTIVE@#To evaluate whether the efficacy of Getong Tongluo Capsule (, GTC, consisted of total flavone of Radix Puerariae) on improving patients' quality of life and lowering blood pressure are superior to the extract of Ginkgo biloba (EGB) for patients with convalescent-phase ischemic stroke and primary hypertension.@*METHODS@#This randomized, positive-drug- and placebo-controlled, double-blind trial was conducted from September 2015 to October 2017. Totally 477 eligible patients from 18 hospitals in China were randomly assigned in a 2:1:1 ratio to the following interventions, twice a day for 12 weeks: (1) GTC 250 mg plus EGB-matching placebo 40 mg (237 cases, GTC group), (2) EGB 40 mg plus GTC-matching placebo 250 mg (120 cases, EGB group) or (3) GTC-matching placebo 250 mg plus EGB-matching placebo 40 mg (120 cases, placebo group). Moreover, all patients were orally administered aspirin enteric-coated tablets 100 mg, once a day for 12 weeks. The primary outcome was the Barthel Index (BI). The secondary outcomes included the control rate of blood pressure and National Institutes of Health Stroke Scale (NIHSS) scores. The incidence and severity of adverse events (AEs) were calculated and assessed.@*RESULTS@#The BI relative independence rates, the clinical recovery rates of NIHSS, and the total effective rates of NIHSS in the GTC and EGB groups were significantly higher than the placebo group at 12 weeks after treatment (P0.05). The control rate of blood pressure in the GTC group was significantly higher than the EGB and placebo groups at 12, 18 and 24 weeks after treatment (P0.05).@*CONCLUSION@#GTC exhibited significant efficacy in improving patients' quality of life as well as neurological function and controlling hypertension. (Registration No. ChiCTR1800016667).

Observations on the Efficacy of Electrothermal Acupuncture plus Joint Mobilization in Treating Knee Osteoarthritis / 上海针灸杂志

Objective To investigate the clinical efficacy of electrothermal acupuncture plus joint mobilization in treating knee osteoarthritis.Methods One hundred patients with knee osteoarthritis were randomized to treatment and control groups, 50 cases each. The control group received Maitland's technique and the treatment group, electrothermal acupuncture in addition. The Osteoarthritis Index score was recorded and cytokines (IL-1, IL-6 and TNF-α) contents were measured in the two groups before and after four weeks of treatment. The clinical therapeutic effects were compared between the two groups.Results The total efficacy rate was 91.5％ in the treatment group and 80.0％ in the control group; there was a statistically significant difference between the two groups (P<0.05). There were statistically significant pre-/post-treatment differences in the WOMAC score and cytokines in the two groups (P<0.01,P<0.05). There were statistically significant post-treatment differences in the WOMAC score and cytokines between the treatment and control groups (P<0.05).Conclusion Electrothermal acupuncture plus joint mobilization is an effective way to treat knee osteoarthritis.

Formulation and in vivo human bioavailability of dissolving tablets containing a self-nanoemulsifying itraconazole solid dispersion without precipitation in simulated gastrointestinal fluid.

To investigate the performance of a solid-state self-nanoemulsifying system with no precipitation in gastric and intestinal fluid, itraconazole (ITZ) was selected as a model drug because of its practically insoluble nature in intestinal fluid. A self-nanoemulsifying ITZ solid dispersion (SNESD) system was prepared as follows: (1) establishment of self-nanoemulsifying composition via the hot melting method, (2) solidification with fumed silicon dioxide (Aerosil 300) via adsorption to prepare SNESD and (3) preparation of a directly compressible tablet containing SNESD. This SNESD was easily formulated in the form of a dissolving tablet and provided a favourable nanoemulsifying microenvironment with no precipitation in the testing media. The SNESD and SNESD-loaded tablet displayed highly enhanced dissolution via nanomisation (266.8 nm and 258.3 nm at 60 min and 120 min, respectively), whereas the drug alone or a reference ITZ Sporanox® capsule displayed very low dissolution and precipitated immediately in intestinal fluid. Drug precipitation in intestinal fluid may affect the in vivo performance of poorly soluble weakly basic drugs and was estimated according to the crystal growth theory. The superdisintegrant and surfactant in the formulation of the tablet were very crucial to the dissolution of the SNESD-loaded tablet. The drug contents and dissolution rates of the SNESD-loaded tablets were also stable during storage in terms of dissolution and drug content. The SNESD-loaded tablet displayed significantly increased oral bioavailability in healthy human volunteers compared with the reference Sporanox® capsule. The current solid-state SNESD-loaded tablet could provide an alternative to liquid-based emulsifying preparations for various poorly water-soluble drugs without precipitation in testing media.

Physical properties and in vivo bioavailability in human volunteers of isradipine using controlled release matrix tablet containing self-emulsifying solid dispersion.

Poorly water-soluble drug with a short half-life such as isradipine (IDP) offer challenges in the controlled release formulation because of low dissolution rate and poor bioavailability. Self-emulsifying solid dispersions (SESD) of IDP consisted of surfactant and fatty acid in poloxamer 407 (POX 407) as a carrier and were manufactured by the melting method. Then, controlled release HPMC matrix tablet containing SESD were prepared via direct compression. The dissolution behaviors and in vivo bioavailability of controlled release matrix tablet in healthy human volunteers were investigated. The physical properties of solid dispersion were also examined using differential scanning calorimetry (DSC), powder X-ray diffraction (PXRD) and scanning electron microscopy (SEM). It was shown that structure of IDP was amorphous in the solid dispersion. The dissolution rate of IDP from SESD was markedly enhanced because of increased solubility and wetting effect. Controlled release HPMC matrix tablets containing SESD released drug in a controlled manner and were stable during storage over 3 months at 40 °C/75% RH. Furthermore, the tablet containing 5mg IDP SESD showed significantly increased oral bioavailability and extended plasma concentration compared with the marketed 5 mg Dynacirc(®) capsule. A combined method of solid dispersion and controlled release technology could provide versatile dosage formulations containing IDP with poor water solubility and short half-life.

Electroacupuncture for post-stroke urinary incontinence: a multi-center randomized controlled study / 中国针灸

<p><b>OBJECTIVE</b>To evaluate the clinical efficacy of electroacupuncture(EA) for apoplectic urinary incontinence.</p><p><b>METHODS</b>Two hundred and four cases of apoplectic urinary incontinence were randomized into an EA group (136 cases) and an indwelling catheter group (68 cases). The EA was applied at Qugu (CV 2), Zhongji (CV 3), Shuidao (ST 28), Qihai (CV 6) and Guanyuan (CV 4), etc. in the EA group,5 times a week. Indwelling catheter was applied in the indwelling catheter group at intervals of 2-4 hours, and periodic bladder irrigation along with bladder rehabilitation training were also given. The efficacies were evaluated after 4 weeks of treatment. Before and after treatment, the urination diary (including the interval of urination, nocturia frequency, urination difficulty, urinary incontinence severity), bladder capacity, patients' satisfaction of the two groups were observed and the efficacy was evaluated.</p><p><b>RESULTS</b>The total effective rate was 96.2% (125/130) in the EA group, which was apparently superior to 87.5% (56/64) in the indwelling catheter group (P < 0.05); except for nocturia frequency in the indwelling catheter group, the total score and the subitem score in the urination diary were all improved significantly after treatment in both groups (all P < 0.001), which were more obvious in the EA group (P < 0.001, P < 0.05); the patients' satisfaction and bladder capacity were all improved significantly after treatment in both groups (all P < 0.001), which were more obvious in the EA group (both P < 0.001).</p><p><b>CONCLUSION</b>The EA has an obvious effect for apoplectic urinary incontinence in urinary incontinence alleviation and bladder capacity increase, which has better efficacy than indwelling catheter therapy.</p>

Enhanced bioavailability and retinal accumulation of lutein from self-emulsifying phospholipid suspension (SEPS).

Ability of any formulation to keep the drug in solubilized form in vivo is essential for bioavailability (BA) enhancement rather than the solubility of drug in the formulation vehicle/matrix itself. Besides, utilization of an excess amount of surfactants/co-surfactants to solubilize the drug in the lipid formulation poses potential pharmaceutical as well as health problems. To address this problem, self-emulsifying phospholipid suspension (SEPS) consisting of high amount of phospholipid (an endogenous lipid with efficient in vivo emulsification capability) and relatively low amount of surfactant/co-surfactant has been proposed to enhance the bioavailability (BA) of lutein. In this study, the ability of SEPS formulation to enhance the BA of lutein was assessed from three SEPS formulations with various amounts of phospholipid (SEPS-0, SEPS-I, and SEPS-II with 0mg, 250 mg, and 500 mg of Phosal 53 MCT, respectively) in beagle dogs following a single oral administration of lutein equivalent to 100mg, and were compared with commercial formulation (CF). In addition, the retinal accumulation of lutein in Sprague Dawley (SD) rats' eyes from SEPS-II formulation (lutein dose of 100mg/kg/day) was investigated following single daily oral administration for a period of 14 days. CF and placebo (vegetable oil without lutein) were also administered for the same period of time and were compared with the SEPS-II formulation. In the relative BA study in beagle dogs, no significant differences were observed between the pharmacokinetic (PK) parameters of formulation SEPS-O and CF. However, the C(max) in comparison to CF was 3.70 folds and 11.76 folds higher for SEPS-I and SEPS-II, respectively. Relative BA compared to CF was 178.88% and 473.13% for SEPS-I and SEPS-II, respectively. The retinal lutein accumulation was 0.91 ± 0.31 ng/g, 3.45 ± 1.63 ng/g, and 14.72 ± 2.02 ng/g for placebo, CF, and SEPS-II, respectively. This enhancement was about 16.1 folds and 4.27 folds compared to placebo and CF, respectively. The relative BA study in dogs and retinal accumulation study in rats demonstrated the excellent ability of SEPS to enhance the BA of lutein. For this reason, SEPS containing lutein could be a promising lipid based delivery system for the prevention of ocular diseases.

Comparison of release-controlling efficiency of polymeric coating materials using matrix-type casted films and diffusion-controlled coated tablet.

Polymeric coating materials have been widely used to modify release rate of drug. We compared physical properties and release-controlling efficiency of polymeric coating materials using matrix-type casted film and diffusion-controlled coated tablet. Hydroxypropylmethyl cellulose (HPMC) with low or high viscosity grade, ethylcellulose (EC) and Eudragit(R) RS100 as pH-independent polymers and Eudragit S100 for enteric coatings were chosen to prepare the casted film and coated tablet. Tensile strength and contact angle of matrix-type casted film were invariably in the decreasing order: EC> Eudragit S100> HPMC 100000> Eudragit RS100>HPMC 4000. There was a strong linear correlation between tensile strength and contact angle of the casted films. In contrast, weight loss (film solubility) of the matrix-type casted films in three release media (gastric, intestinal fluid and water) was invariably in the increasing order: EC < HPMC 100000 < Eudragit RS100 < HPMC 4000 with an exception of Eudragit S100. The order of release rate of matrix-type casted films was EC > HPMC 100000 > Eudragit RS100 > HPMC 4000 > Eudragit S100. Interestingly, diffusion-controlled coated tablet also followed this rank order except Eudragit S100 although release profiles and lag time were highly dependent on the coating levels and type of polymeric coating materials. EC and Eudragit RS100 produced sustained release while HPMC and Eudragit S100 produced pulsed release. No molecular interactions occurred between drug and coating materials using (1)H-NMR analysis. The current information on release-controlling power of five different coating materials as matrix carrier or diffusion-controlled film could be applicable in designing oral sustained drug delivery.

Improved analytical validation and pharmacokinetics of valsartan using HPLC with UV detection.

The primary objective of the study was to validate a simple and sensitive method of determining valsartan concentration in human plasma samples using high performance liquid chromatography (HPLC) combined with ultraviolet (UV) detection. Methanol appeared to be the best with a high recovery efficiency compared to other solvents such as acetonitrile, ethylacetate and methyl-tert-butyl ether. After a simple protein precipitation using methanol, the analytes were separated on a Phenomenex Luna C(18) column using 42% acetonitrile with 15 mM potassium dihydrogenphosphate in water (pH 2.0; adjusted with phosphoric acid) as the mobile phase at a flow rate of 1.2 mL/min. The standard calibration curve constructed in the concentration range of 50-2000 ng/mL showed good linearity (r(2)>0.9997). Spironolactone was used as an internal standard (IS). Valsartan and IS eluted at 10.25 and 12.17 min, respectively. The intra-day and inter-day precision and accuracy were satisfactory with relative standard deviations of less than 15%. No interference peaks or matrix effects were observed in human plasma. Valsartan concentration in human plasma was well established following a single 80 mg oral dose (Diovan capsule) to eight healthy volunteers. The current determination of valsartan concentration by protein precipitation using methanol followed by analysis using HPLC with UV detection was rapid and sensitive, and provide an alternative to the analysis of valsartan by studying its clinical applications.

Colonic release and reduced intestinal tissue damage of coated tablets containing naproxen inclusion complex.

A colonic-release delivery system containing naproxen inclusion complex with 2-hydroxypropyl-beta-cyclodextrin (2-HPbetaCD) was originally proposed. The core tablets consisting of the naproxen inclusion complex and disintegrants (Ac-Di-Sol), Primojel), Avicel) or Polyplasdone) were formed by direct compression, and then coated with the polymers, either pH-dependent Eudragit S100 and/or pH-independent Eudragit RS100 with plasticizers like dibutyl sebacate (DBS) and aluminum tristearate (AT). The in vitro release characteristics were evaluated in simulated gastric fluid for 2h and then subsequently in simulated intestinal fluid for 12h. The potential histological changes were also evaluated after direct dosing of suspensions of naproxen alone and powdered mixtures of inclusion complex-loaded tablet into rat intestinal segments. No distinct colonic release was observed when disintegrants were excluded in the single-layered coated tablets regardless of coated structures, giving a zero-order fashion over 12h. The coated tablet with double-layered structures of Eudragit S100 and Eudragit RS100 was not also applicable. In contrast, colonic release was achieved when the core tablet containing inclusion complex and disintegrant was coated with only Eudragit S100 in a single-layered structure. The colonic-release tablet was resistant in gastric fluid for 2h and for 2-4h in intestinal fluid, followed by rapid release of the drug after a total of 4-6h of lag time depending on the type of disintegrants. The lag time was advanced in case of DBS while delayed in case of AT. On histological examination, the inclusion complex-loaded suspension caused less intestinal tissue damage than naproxen alone. Based on these findings, the colonic-release tablet with enteric coatings which contains inclusion complex and disintegrants could be useful to deliver drugs like naproxen to the lower small intestine and upper colon with increased dissolution and reduced intestinal tissue damage.

Effect of solubilizing and microemulsifying excipients in polyethylene glycol 6000 solid dispersion on enhanced dissolution and bioavailability of ketoconazole.

Polyethylene glycol (PEG) 6000-based solid dispersions (SDs), by incorporating various pharmaceutical excipients or microemulsion systems, were prepared using a fusion method, to compare the dissolution rates and bioavailabilities in rats. The amorphous structure of the drug in SDs was also characterized by powder X-ray diffractometry (XRD) and differential scanning calorimetry (DSC). The ketoconazole (KT), as an antifungal agent, was selected as a model drug. The dissolution rate of KT increased when solubilizing excipients were incorporated into the PEG-based SDs. When hydrophilic and lipophilic excipients were combined and incorporated into PEG-based SDs, a remarkable enhancement of the dissolution rate was observed. The PEG-based SDs, incorporating a self microemulsifying drug delivery system (SMEDDS) or microemulsion (ME), were also useful at improving the dissolution rate by forming a microemulsion or dispersible particles within the aqueous medium. However, due to the limited solubilization capacity, these PEG-based SDs showed dissolution rates, below 50% in this study, under sink conditions. The PEG-based SD, with no pharmaceutical excipients incorporated, increased the maximum plasma concentration (Cmax) and area under the plasma concentration curve (AUC(0-6h)) two-fold compared to the drug only. The bioavailability was more pronounced in the cases of solubilizing and microemulsifying PEG-based SDs. The thermograms of the PEG-based SDs showed the characteristic peak of the carrier matrix around 60 degrees C, without a drug peak, indicating that the drug had changed into an amorphous structure. The diffraction pattern of the pure drug showed the drug to be highly crystalline in nature, as indicated by numerous distinctive peaks. The lack of the numerous distinctive peaks of the drug in the PEG-based SDs demonstrated that a high concentration of the drug molecules was dissolved in the solid-state carrier matrix of the amorphous structure. The utilization of oils, fatty acid and surfactant, or their mixtures, in PEG-based SD could be a useful tool to enhance the dissolution and bioavailability of poorly water-soluble drugs by forming solubilizing and microemulsifying systems when exposed to gastrointestinal fluid.

Impact of acute rejection episodes on long-term renal allograft survival / 中华医学杂志(英文版)

<p><b>OBJECTIVE</b>To assess the impact of the number, and time of acute rejection (AR) and outcome of anti-rejection therapy on the long-term survival of renal allografts and the relative risk factors.</p><p><b>METHODS</b>The Kaplan-Meier analysis and log-rank test were used to calculate the survival rates of patients and grafts in no acute rejection group (NAR, 895 patients), 1 rejection episode group (1AR, 183), 2 and more than 2 rejection episodes group (2AR, 17), acute rejection group [AR (1AR + 2AR), 200], early acute rejection group (within 90 days after transplantation, EAR, 125), late acute rejection group (91 days later, LAR, 58), completely AR reversed group (CAR, 105), and incompletely AR reversed group (IAR, 68). The relative risk factors were analyzed by the Cox proportional hazards regression.</p><p><b>RESULTS</b>The 5- and 10-year survival rates of renal allografts were 75.4% and 17.1% in AR and 93.2% and 86.5% in the NAR group (P < 0.0001). The long-term graft survival was much lower in the 2AR group than in the NAR or 1AR groups (P < 0.0001 and P = 0.002, respectively). It was similar in either the NAR or CAR groups (P = 0.31), but it was significantly lower (P < 0.0001) in the IAR group. Multivariate Cox regression analysis revealed that the outcome of anti-rejection therapy is an important risk factor affecting the long-term survival of allografts.</p><p><b>CONCLUSIONS</b>AR is significantly associated with poor long-term survival of renal allografts. But the long-term graft survival of patients with one acute rejection but completely reversed is not significantly different from that of patients without acute rejection.</p>

Effect of Jie-jing Mixture on spasticity of apoplectic hemiparalysis / 中国康复理论与实践

@#ObjectiveTo observe the clinical effect of Jie-jing Mixture in treating spasticity of apoplectic hemiparalysis.Methods60 cases with spasticity of apoplectie hemipuralysis were divided into 2 groups.30 case for treatment group (routine treatment added by Jie-jing Mixture ) and 30 case for control (only receiving routine treatment ).ResultsThe effective rates was 86.7% (treatment group )and 33.3%(control group )with statistical significance ( P<0.01).Conclusions The Jie-jing Mixture has better effect in treating spastisticity of apoplectic hemiparalysis than that of the conventional therapy.

Effect of Boschniakia rossica on expression of GST-P, p53 and p21(ras)proteins in early stage of chemical hepatocarcinogenesis and its anti-inflammatory activities in rats.

AIM:To investigate the effect of Boschniakia rossica (BR) extract on expression of GST-P, p53 and p21(ras) proteins in early stage of chemical hepatocarcinogenesis in rats and its anti-inflammatory activities.METHODS:The expression of tumor marker-placental form glutathione S-transferase (GST-P), p53 and p21(ras) proteins were investigated by immunohisto-chemical techniques and ABC method. Anti-inflammatory activities of BR were studied by xylene and croton oil-induced mouse ear edema, carrageenin, histamine and hot scald-induced rat pow edema, adjuvant-induced rat arthritis and cotton pellet induced mouse granuloma formation methods.RESULTS:The 500mg/kg of BR-H2O extract frac-tionated from BR-Methanol extract had inhibitory effect on the formation of DEN-induced GST-P-positive foci in rat liver (GST-P staining was 78% positive in DEN+AAF group vs 20% positive in DEN+AAF+BR group, P<0.05) and the expression of mutant p53 and p21(ras) protein was lower than that of hepatic preneoplastic lesions (33% and 22% positive respectively in DEN+AAF group vs negative in DEN+AAF+BR group). Both CH(2)Cl(2) and H(2)O extracts from BR had anti-inflamatory effect in xylene and crotonoil induced mouse ear edema (inhibitory rates were 26%-29% and 35%-59%, respectively). BR H(2)O extract exhibited inhibitory effect in carrageenin, histamine and hot scald-induced hind paw edema and adjuvant-induced arthritis in rats and cotton pellet-induced granuloma formation in mice.CONCLUSION:BR extract exhibited inhibitory effect on formation of preneoplastic hepatic foci in early stage of rat chemical hepato-carcinogenesis.Both CH(2)Cl(2) and H(2)O extracts from BR exerted anti-inflammatory effect in rats and mice.