As the number of patients with compromised immune function increases and fungal resistance develops, so does the risk of contracting deadly fungi in humans. Both fungi and humans are eukaryotes, so identifying unique targets for antifungal drug development is difficult. In addition, the existing antifungal drugs are limited by toxicity, drug interaction and drug resistance in practical application, which leads to the increasing incidence and fatal rate of fungal infections. Therefore, it is urgent to develop new antifungal drugs. The semi-synthetic technology using microbial fermentation products from natural sources as lead compounds has become the most used method in structural modification of antifungal drugs due to its advantages of few reaction steps and easy operation. This paper will introduce the current status of natural antifungal drugs in clinical use, as well as the latest progress in the research and development of new semi-synthetic antifungal drugs, and summarize their mechanism of action, structural modifications, advantages and disadvantages, so as to provide reference for the subsequent development of new antifungal drugs.

This article proposes the "Efficacy Theory" hypothesis of the traditional Chinese medicines (TCMs): TCMs take effects and weaken toxicities through the additive effects of numerous effective forms (including their constituents or/and metabolites) on a same target, the synergistic effects based on the overall action of the additive effects on individual targets and their toxicities scattering effects. A TCM may include approximately 1000 constituents and each constituent may produce about 100 metabolites in vivo after oral administration. Numerous effective forms of incalculable constituents and their metabolites could work like a "army group" together. When the quantity of a specific target molecule is larger than the pharmaceutical molecules, the molecules of different kinds of effective forms could combine with the target molecules successively, to exert the additive effects. When the target molecules are mostly occupied ("target most spaces occupied"), this TCM begins to work. The additive effects maybe exert not only in concentration but also in a time order way, which gives a sustained efficacy of TCM. The additive effects and the toxicities scattering effects are resulted from the same effective groups and not identical toxic groups among different effective form molecules. The "toxicities scattering effect" can be used to explain the non-toxic TCMs, but not fit for toxic TCMs. The efficacy theory showed that the variety of constituents and metabolites may participate in the process of pharmacodynamic actions, including the additive effects, synergy effects and toxicities scattering effects, which may be useful for explaining and developing the characteristic advantage of the TCMs. The questions we need to study or confirm are as follows: What are the TCMs' pharmacodynamic substance basis and mechanism made up of Why are toxicities of most TCMs' smaller How is the TCMs' "Efficacy Theory" which reflects characteristic advantage of TCMs applied in the research and development of new drugs.
Animals ; Drug Therapy ; Drugs, Chinese Herbal ; chemistry ; pharmacology ; Humans ; Medicine, Chinese Traditional ; Pharmaceutical Preparations ; chemistry

Background Studies showed that macophenolic acid (MPA)down-regulates and inhibits the expression and secretion of tissue growth factor and inflammatory factor,and further impacts the proliferation and inflammation process.Pterygium is an inflammatory and proliferative lesion.Whether MPA has an inhibitory effect on pterygium is unclear.Objective This study was to investigate the antifibrotic effects of macophenolic acid on pterygium fibroblasts(PFBs) in vitro and discuss its mechanism.Methods Pterygium tissue was obtained from pterygium patient during the surgery.PFBs were cultured using explants and identified with vimentin immunohistochemisty.0,0.125,0.250,0.500,1.000 μmol/L MPA were added into the culture medium,respectively,and the cells were cultured in the medium without MPA as the control group.MTT colorimetry was used to find the optimization effective concentration of MPA and evaluate their inhibitory effect on PFBs,and BrdU fluorescence staining was used to assess the growth statue of PFBs.Expressions of nuclear factor-κB(NF-κB),p65 and inhibitor of NF-κB-α(IκB-α) in the cells were detected by Western blot.Results The cells was spindle in shape 3 days after cultured and showed the vortex and radial arrangement with the positive response to vimentin.With the increase of MPA,the proliferative value of PFBs (A560)showed gradually decline,with a significant difference among the five groups (F =42.874,P＜0.01).In addition,the proliferative value of PFBs (A560) significantly lowed as the prolong of MPA active time(F=26.038,P＜0.01).BrdU fluorescence staining showed a significant decrease of DNA synthesis of PFBs with the elevation of MPA dose among the five groups(F=175.279,P＜0.05),and the A560of PFBs DNA synthesis in different concentrations of MPA groups was lower than that of the control group (all at P＜0.05).No apoptotic and necrotic cell was found after MPA action by DAPI staining.The expression level of p65 in the PFBs was 0.886±0.072 and 1.542±0.124 in the MPA group and the control group,indicating a declined value in the MPA group(P＜0.05).However,the expression value of IκB-α in the cytoplasm PFBs was significantly higher in the MPA group compared with the control group(2.141 ±0.305 vs.1.559±0.267) (P＜0.05).Conclusions MPA has an inhibitory effect on the growth of PFBs,which probably is related to the arresting of NF-κB pathway.

Based on the plasma activation and the sensing ability of cataluminescence, a low temperature plasma-assisted cataluminescence sensor was developed for ethylene detection using the low-cost and abundant alkaline-earth oxides of MgO nanomaterials as the sensing materials.Taking advantage of the high activity of the plasma, the working temperature of this method was greatly decreased than that of traditional detection method (300-500℃), and the sensing of ethylene was realized at room temperature without any heating device.This ethylene cataluminescence sensor gave a linear range of 112-4997 ng/mL (90-3998 ppm, R=0.97669) with a detection limit of 37 ng/mL (30 ppm).Besides, the sensor showed good selectivity and stability in ethylene detection.Due to the absence of the heating element, the present sensor was simple, rapid, low-cost, low energy-consumption and stable for ethylene sensing.This study improved the applicability of cataluminescence sensors and might promote the development of cataluminescence sensors.

BCG Purified Protein Derivative (BCG-PPD)was isolated and purified from BCG Culture filtrate by trichloroacetic acid and ammonium sulfate methods. The purity of BCG-PPD was Similar to PPD-S(international standard) and PPD-C(China), but more than that of PPD-CT68 (Canada)and PPD-RT23(Danish). The Delayed-Type Hyperseusitivity(DTH) to BCG-PPD was more sensitivity than other PPD on BCG vaccinated guinea pigs, but less sensitivity than other PPD on Mycobacterium tuberculosis infected guinea pigs. The conversion rate and induration diameter to BCG-PPD was higher than PPD in 333 of 12 weeks after BCG vaccination newborns, but lower than that of other PPD in 97 tuberculosis patients. It was shown that DTH reaction to PPD was more sensitivity in Mycobacteria homogeneous strain vaccinated individual than Mycobacteria heterogeneous strain vaccinated individual. It was demonstrated that BCG-PPD was better than other PPD on observation conversion rates and induration diameter of BCG vaccinated individual. It maybe help to identification BCG vaccinated or tuberculosis infected with DTH of BCG-PPD and PPD in same individual.

Objective To evaluate the development of extravascular leakage of 6％ hydroxyethyl starch (HES) 130/0.4 when used for acute hemodilution in the pediatric patients undergoing open heart surgery.Methods Forty-eight American Society of Anesthesiologists physical status Ⅰ or Ⅱ pediatric patients,aged 2-12 yr,weighing 12-53 kg,scheduled for elective surgical repair of ventricular or atrial septal defect,were divided into 2 groups (n =24 each) according to age:preschool group (2 yr ≤ age ≤ 6 yr) and school-age group (6 yr＜age ≤ 12yr).After anesthesia induction and endotracheal intubation,a volume of 6％ HES 130/0.4 equivalent to 10％ of the blood volume was infused via the central veins at 0.5 ml · kg-1 · min-1 in two groups.Immediately before infusion of HES (T0) and at 15 and 30 min after the end of infusion (T1,2),blood samples were collected fron the central vein for determination of plasma colloid osmotic pressure (COP) and hemnoglobin (Hb) concentrations.The concentrations of 6％ HES 130/ 0.4 in plasma at T1 and T2 and in urine at T2 were measured by the anthranone colorimetric method.Results Compared with the baseline value at T0,the concentrations of Hh in plasma were significantly decreased at T1,2 in preschool group,and the concentrations of Hb in plasma were significantly decreased and plasma COP was increased at T1,2 in school-age group (P＜0.05).There were no significant differences in plasma Hb concentrations or COP at each time point between two groups (P＞0.05).The plasma 6％ HES 130/0.4 concentrations were significantly lower at T2 than at T1 in two groups (P＞0.05).Compared with school-age group,the plasma 6％ HES 130/0.4 concentrations were significantly decreased at T1,2 in preschool group (P＜0.05).There was no significant difference in 6％ HES 130/0.4 concentrations in urine between the two groups (P＞0.05).Conclusion When 6％ HES 130/0.4 is used for acute hemodilution,extravascular leakage happens after acute hemodilution and is more obvious in the preschool pediatric patients undergoing open heart surgery.

AIM: To observe the clinical effects of intravitreal injection of triamcinolone acetonide ( TA ) before vitrectomy for retinal detachment associated with choroidal detachment. · METHODS: Totally 23 cases ( 23 eyes ) of retinal detachment associated with choroidal detachment in our hospital were treated by intravitreal injection of TA 4-5d before 23-Gauge micro-invasive vitrectomy combined with silicone oil injection. All the cases were followed up between 6 to 9mo. The anatomic retinal reattachment, visual acuity, intraocular pressure and postoperative complications were observed and analyzed. ·RESULTS: After the surgery, the visual acuity of all patients were improved, with 9 eyes better than 0. 3 (39%), and 18 eyes better than 0. 05 (78%). The BCVA at 1wk, 1 and 3mo and last follow up were different compared with before operations (P<0. 05). The mean intraocular pressure was 4. 02±1. 47mmHg before injection, 13.69±4. 68mmHg before operation (P<0. 05), and17.72±5.87 mmHg after operation (P<0.05). The retina of all patients treated were reattached 2wk post-operatively. The retinal reattachment rate after the primary surgery and the secondary surgery was 87% and 100%, respectively. Post-operative complications included 7 eyes of transient high intraocular pressure, occurred during 12-14d after operations and returned to normal after less glucocorticoid eye drops and giving IOP lowering drugs. There were no intraocular hemorrhage, iatrogenic retinal breaks, infections, or lens injuries. · CONCLUSION: Intravitreal injection of TA before vitrectomy for retinal detachment associated with choroidal could improve the clinical effects, and decrease the difficulty of surgery while the injection itself is pretty safe.

AIM:To observe the efficacy and safety of 1g/L bromfenac sodium hydrate ophthalmic solution in the partial substitution of glucocorticoid after laser subepithelial keratomileusis (LASEK).METHODS: Totally 104 cases (208 eyes) were received LASEK, which were selected and divided into study group and control group.The study group were adopted 1g/L bromfenac sodium hydrate ophthalmic solution combined with tobramycin dexamethasone eye drops and fluorometholone eye drops, the control group were adopted tobramycin dexamethasone eye drops and fluorometholone eye drops.The changes of visual acuity and intraocular pressure of two groups were recorded before and after surgery, and the score of painness and the occurrence of haze were observed after surgery.RESULTS: At postoperative 1, 2, 3d, respectively, the pain score of the study group were 1.70±0.35, 1.25±0.34, 0.82±0.32, the pain score of the control group were 2.30±0.43, 1.68±0.44, 1.12±0.33, the differences were significant (P<0.05).Before and at 2wk, 1, 3mo after surgery, respectively, uncorrected visual acuity of study group were 0.035±0.02, 0.71±0.13, 0.89±0.17, 0.88±0.18, while which of control group were 0.037±0.015, 0.73±0.15, 0.87±0.14, 0.86±0.15 (P>0.05), and the differences were not significant(P>0.05).At preoperative and postoperative 1, 2wk, 1 and 3mo of surgery, respectively, the intraocular pressure of study group were 17.33±1.58, 7.54±1.28, 7.23±1.58, 7.26±1.47, and 7.30±1.36 mmHg;the intraocular pressure of control group were 17.53±1.43,7.57±1.32,7.73±1.55,7.80±1.38,7.86±1.43 mmHg,the differences were not significant between before and at 2wk after surgery(P>0.05), the differences were significant between the two groups at 2wk, 1mo and 3mo (P<0.05).At postoperative 1, 3mo of surgery, the score of haze level of the study group were 91.7% and 93.3%, respectively and which in control group were 92.0% and 92.9%, respectively, and the differences were not significant between the two groups at every time point(P>0.05).CONCLUSION: It is safe and effective that 1g/L bromfenac sodium hydrate ophthalmic solution in the partial substitution of glucocorticoid after laser subepithelial keratomileusis.The patient has a lower intraocular pressure, has similar therapeutic effect as glucocorticoid in vision and antiinflammatory.

Objective To reveal the chromosome abnormalities and their relationship with the clinical phenotype of neonates with congenital malformation.Methods Karyotype analysis of peripheral blood lymphocytes was performed on 396 newborns with congenital malformation,who were recruited at the Children's Hospital Affiliated to Soochow University from Jan.2006 to May 2012,chromosome karyotypes were prepared with neonatal peripheral lymphocytes by conventional G-banding technique.Results 1.Of 396 newborns,159 (40.2％) cases were detected to have chromosomal abnormalities,including karyotype first reported domestically and internationally in 3 cases.2.Trisomy-21 (Down's syndrome),which was the most common abnormal karyotype,was seen in 130 cases,accounting for 81.8％,of whom 119 cases show the standard type,10 cases accompanied by the Robertsonian translocation involving group D or group G,and 1 case accompanied by sexual chromosomal abnormality:inv(Y) (p1 1 q 1 1),+ 21.3.Other common karyotype abnormalities were as follows:del (5) (p 1 2-14) (cats cry syndrome) in 4 cases,trisomy-18 (Edwards syndrome)in 4 cases,45,XO (Turner' s syndrome) in 4 cases,inv (9) (p1 1 q1 2-21) in 4 cases,trisomy-X (super female syndrome) in 1 case,rob(13;14) in 1 case,trisomy-8 in 1 case and del(18) (q22) in 1 case.4.Special faces were seen in 147 cases (92.5 ％),congenital heart disease in 97 cases (61.0％),low birth weight in 72 cases (45.3 ％),congenital anal atresia in 13 cases(8.1％),multiple malformations in 11 cases (6.8％),intestinal malformations in 10 cases (6.2％),extrinsic genital abnormalities in 9 cases(5.7％),meow-like cry in 4 cases(2.5％),limb edema in 4 cases (2.5％),fingers and toe abnormalities in 6 cases(3.6％),congenital brain dysplasia in 6 cases (3.6％),webbed neck in 5 cases(3.1％) and cleft lip and palate in 3 cases(1.8％).Conclusions Chromosomal abnormality is an important factor leading to neonatal birth defects,of which special face,congenital heart disease,low birth weight,and multiple malformations are the main clinical manifestations of chromosomal diseases.

Objective To report two childhood acute myeloid leukemia (AML) patients with t(8;20)(q22;q13) and t(1;8;21)(q32;q22;q22) respectively,as variant t(8；21).Methods Chromosome preparation of bone marrow cells were made using short-term culture and karyotypic analysis was carried out using R and G-banding techniques.Interphase-fluorescence in situ hybridization (I-FISH) and metaphase-FISH (M-FISH) were performed using dual color,dual fusion AML1-ETO probe to detect the AML1-ETO fusion gene.Multiplex RT-PCR was used to demonstrate the expression of AML1-ETO fusion transcript.Results The karyotype of bone marrow cells for these two childhood AML patients were 45,X,-Y,t(8;20)(q22;q13)[12]/46,XY[3](case 1) and 46,XX,t(1;8;21)(q32；q22;q22)[18]/46,XX[2](case 2),respectively.I-FISH and M-FISH confirmed that they all had the AML1-ETO fusion gene and variant t(8;21).The AML1-ETO fusion transcript in both patients was detected by RT-PCR.Conclusion t (8;20)(q22;q13) and t (1;8;21)(q32;q22;q22) are variant t (8;21) in nature.It is important to combine the conventional karyotypic analysis with D-FISH and multiplex RT-PCR to determine the nature and prognosis of AML patients with variant t(8;21).