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Celastrol ( 1 ), obtained from the roots of Tripterygium wilfordii Hook F., is most likely to become an antitumor drug, but with severe cytotoxicity. Due to the lack of modifiable sites in the structure of celastrol, the structural diversity of the modified products obtained by synthesis in the previous studies is insufficient, which hinders the pace of its patent medicine. This study describes a method of microbial transformation to increase the modification site of celastrol and reduce its toxicity. The screening of endophytes from native plants was introduced in this context, which led to two novel stereoselective oxidation products such as S -16-hydroxyl celastrol ( 2 ) and A-ring aromatized S -16-hydroxyl celastrol ( 3 ), along with a rare 7,9-octadecadienoic acid ester of celastrol ( 4 ). Their structures were determined by extensive spectroscopic data analysis, especially 1D and 2D NMR. Compared with 1 , compounds 3 and 4 exhibited similar antitumor activity in U251, A549, KG-1, and B16 cell lines. Compound 2 had slightly decreased antitumor activity when compared with compound 1 . Furthermore, compound 2 - 4 showed lower cytotoxicity against BV-2 (about 21-fold lower, 2 : 92.82 μM, 3 : 34.25 μM, and 4 : 74.75 μM vs. celastrol: 4.35 μM), and also identical trends against H9c2 and PC12 cell lines., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Ma, Geng, Ji, Yue, Liu, Wang, Jiang, Chen and Wu.)

An ultra-high performance liquid chromatography-tandem mass spectrometry(UHPLC-MS/MS) method was established to investigate the pharmacokinetic behaviors of psoralenoside, isopsoralenoside, calycosin-7-glucoside, ononin, psoralen, isopsoralen, methylnissolin, and neobavaisoflavone in rat plasma after oral administration of Bufei Huoxue Capsules. After SD rats were administered with Bufei Huoxue Capsules suspension by gavage, blood samples were collected from the inner canthus at different time points. After protein precipitation, plasma samples were separated on ACQUITY UPLC BEH C_(18) column(2.1 mm×100 mm, 1.7 μm). The mobile phase consisted of acetonitrile(A) and water(B) containing 0.1% formic acid in gradient elution. The positive and negative ions were measured simultaneously in the multi-reaction monitoring(MRM) mode. The pharmacokinetic parameters were calculated and fitted by DAS 3.2.8. Psoralenoside, isopsoralenoside, calycosin-7-glucoside, ononin, psoralen, isopsoralen, methylnissolin, and neobavaisoflavone were detected in the rat plasma after drug administration, with AUC_(0-t) of(3 357±1 348),(3 555±1 696),(3.03±0.88),(2.21±0.33),(1 787±522),(2 295±539),(5.69±1.41) and(3.40±0.75) μg·L~(-1)·h, and T_(max) of(1.56±0.62),(1.40±0.70),(0.21±0.05),(0.25±0.12),(0.26±0.11),(0.34±0.29),(0.74±0.59), and 0.25 h. The method is proved specific and repeatable and is suitable for the determination of psoralenoside, isopsoralenoside, calycosin-7-glucoside, ononin, pso-ralen, isopsoralen, methylnissolin, and neobavaisoflavone in the rat plasma, which can be applied to pharmacokinetic study.

Objective: To determinate the range of quantitative myocardial perfusion parameters (MBF, MBV) in subjects without coronary artery lesions by dynamic computed tomography myocardial perfusion imaging (CTP). Methods: Subjects with occasional chest tightness or family history of coronary artery disease coming to Fuwai Hospital underwent coronary computed tomography angiography (CCTA) were prospectively enrolled. A total of 34 subjects [mean age (50±7) years, range from 33 to 65 years; 15 male and 19 female] were enrolled. Coronary lesions were not confirmed in any subjects using CCTA and volunteered for stress and rest dynamic CTP examination. MBF and MBV values were calculated in each myocardial segment using a 17-segment model. The global ranges of MBF and MBV were analyzed, and the gender variability and regional variability were compared. Results: The mean global MBF and MBV at rest and under stress were (115.5±27.4) ml·100 g -1 ·min -1 , (212.8±40.8) ml·100 g -1 ·min -1 and (17.6±4.0) ml/100 g, (25.8±4.6) ml/100 g, respectively. The absolute and resolute reserves of MBF and MBV [(102.8±41.5) ml·100 g -1 ·min -1 , 107.7%±52.5%; (9.3±5.2) ml/100 g, 62.1%±47.4%] were highest in the right coronary artery territory, but without any significant differences. The stress MBF and absolute reserve of MBF in females were higher than those of males [(228.6±39.9) ml·100 g -1 ·min -1 , (113.3±46.2) ml·100 g -1 ·min -1 ; (192.8±33.4) ml·100 g -1 ·min -1 , (77.0±41.2) ml·100 g -1 ·min -1 ] (both P< 0.05). The MBF resolute reserve, rest MBV, stress MBV and MBV absolute and resolute reserves were higher in females, but without significant differences (all P> 0.05). Conclusion: The mean global MBF and MBV at rest and under stress were (115.5±27.4) ml·100 g -1 ·min -1 , (212.8±40.8) ml·100 g -1 ·min -1 and (17.6±4.0) ml/100 g, (25.8±4.6) ml/100 g. The MBF under stress perfusion and MBF absolute reserve of females are higher than those of males.

Background: Previous studies have shown that patients with long-term diabetes require more opioids after surgery than patients without diabetes. Gestational diabetes mellitus (GDM) normally only lasts for a brief period; nevertheless, its effect on sufentanil consumption after cesarean section is unknown., Methods: This prospective cohort study included two groups: a GDM group (n = 32) and a matched non-GDM (NGDM) group (n = 32). All patients underwent routine combined spinal-epidural anesthesia for cesarean delivery. Sufentanil consumption through an intravenous patient-controlled analgesia (PCA) pump, the frequency of PCA requests, and visual analog scale (VAS) scores 6 and 24 h after surgery were compared between groups., Results: Sufentanil consumption (μg) 6 h after surgery was higher in the GDM group than in the NGDM group (24.0 ± 6.6 vs 20.1 ± 5.7, P = 0.023). PCA was used more frequently 6 and 24 h after surgery by the GDM group than by the NGDM group (1[0-2] vs 0[0-1], P = 0.001; 6 [1-5] vs 3 [1, 2, 6-8], P = 0.001, respectively). The VAS score during activity 24 h after surgery was higher in the GDM group than in the NGDM group (5 [2, 3] vs 5 [1, 2], respectively, P = 0.03)., Conclusion: Pregnant women with GDM require more opioids during the immediate postoperative period after cesarean section than those without GDM., Clinical Trials Registration: No. ChiCTR1800016014, ChenYang, May 6th 2018.

Aims: The aim of this study was to evaluate the safety and efficacy of percutaneous closure in patients with a ruptured sinus of Valsalva aneurysm (RSVA)., Methods and Results: A total of 29 patients with RSVA were retrospectively enrolled in our study. All patients were successfully treated by percutaneous closure and had a complete closure at discharge; however, two patients had a trivial procedure-related aortic regurgitation (AR) after the procedure. On a mean follow-up of 29.7±23.8 months (range 1-83 months), the two procedure-related AR disappeared three months and two years after the procedure, respectively. Trivial residual shunt was found in one patient, sinus of Valsalva aneurysm ruptured again in one patient and trivial to moderate AR was found in two patients during the follow-up., Conclusions: In appropriately selected patients with RSVA, percutaneous closure is an attractive alternative to surgery with high technical success and good short-term and midterm outcomes; however, long-term follow-up is mandatory.

Objective: To evaluate the safety, efficacy, predictability, stability and complications of femtosecond laser corneal small incision lenticule extraction (SMILE) procedure for the correction of myopia and myopic astigmatism., Methods: In this prospective study, 50 patients (88 eyes) with myopia and myopic astigmatism were chosen to be performed SMILE procedure randomly. These patients were followed up at 1 day, 1 week, 1 month and 3 months postoperatively and were examined for uncorrected visual acuity (UCVA), best corrected visual acuity (BCVA), manifest refraction, intraocular pressure (IOP) and corneal topography. The results were analyzed with paired-t test, independent-samples t test and regression analysis., Results: SMILE procedure was performed well in all patients, only 3 cases (3 eyes, 3.4%) suffered from the suction loss, 14 cases (26 eyes, 29.5%) developed opaque bubble layer. All patients gained perfect UCVA (20/20), no eye had decrease of BCVA. The residual spherical equivalent was (-0.11 ± 0.29) D, the astigmatism was (0.01 ± 0.33) D 3 months postoperatively. The incidence of diffuse lamellar keratitis and haze was low, and no other complications were observed. The IOP was decreased slightly after 1 month(t = 6.238, P < 0.05), but no changes after 3 months (t = 0.053, P < 0.05)., Conclusion: The SMILE procedure is good at the safety, efficacy, predictability and stability for the correction of myopia and myopic astigmatism.

Objective: To evaluate and compare the recovery of central and peripheral corneal sensitivity in the early period after small incision lenticule extraction (SMILE) and femtosecond lenticule extraction (FLEx)., Methods: In this study, 47 cases (87 eyes) which underwent SMILE and FLEx were included. Central, superior, inferior, nasal and temporal corneal sensitivity was measured using a Cochet-Bonnet esthesiometer (Luneau Ophthalmologic) before and 1 week, 1 month, and 3 months after SMILE and FLEx. The results were analyzed with Mann-Whitney test by SPSS13.0 software., Results: There were statistical differences between SMILE and FLEx group in the central, inferior, nasal and temporal corneal sensitivity at 1 week, 1 month and 3 months postoperatively (Z = -5.219, -7.120, -6.735, -7.139, -5.945, -6.644, -7.006, -7.121, -5.262, -3.086, -4.140, -3.523. P < 0.01). However, the superior corneal sensitivity in the SMILE group did not show significant difference (Z = -1.807, P = 0.071) as compared to FLEx group (with exception of 1 week postoperatively). At 1 month and 3 months postoperatively, corneal sensitivity in the superior quadrant were (5.23 ± 0.62) and (5.57 ± 0.57) cm in the SMILE group, and were (4.43 ± 1.20) and (4.85 ± 1.11) cm in the FLEx group. There were statistical differences between these two groups (Z = -2.935, -2.678. P = 0.003, 0.007). In the SMILE group, corneal sensitivity in the central, superior, inferior, nasal and temporal quadrants at 3 months postoperatively was (5.74 ± 0.51), (5.57 ± 0.57), (5.70 ± 0.55), (5.83 ± 0.37), (5.84 ± 0.30) cm respectively, there were no significant differences as compared with preoperative data (Z = -1.255, -0.893, -0.570, -0.630, -0.935. P = 0.209, 0.440, 0.569, 0.529, 0.350). In the FLEx group, corneal sensitivity in the superior at 3 months postoperatively was 4.85 ± 1.11, there was not significant difference compared with preoperative data (Z = -1.095, P = 0.272). There were no correlations between the changes of central corneal sensitivity and central corneal ablation depth, central corneal thickness and preoperative spherical equivalent (SMILE group: r = 0.159, -0.202, 0.106, 0.060. P > 0.05. FLEx group: r = -0.156, -0.059, 0.058, -0.005. P > 0.05) after SMILE and FLEx surgery., Conclusions: Corneal sensitivity decreases after SMILE and FLEx, and then returns to its original state over time. The decrease of corneal sensitivity after the SMILE was fewer and the recovery was faster as compared with FLEx.

Herbarone (1), a novel heptaketide with a tetrahydro-5,9-methanobenzo[8]annulen-10(5H)-one skeleton, together with the new ent-astropaquinones B (2) and C (3) and four known pyranonaphthoquinones (4-7), was isolated from the sea hare associated fungus Torula herbarum. The structures of the new compounds were elucidated by detailed spectroscopic analysis, and the absolute configurations were determined by solution TDDFT/ECD calculations. Absolute configurations of the known compounds were studied by ECD measurements and calculations. The isolation of heptaketide 1 suggests that an intramolecular aldol reaction takes place to form the tricyclic scaffold.

In April 2011, a survey of diseases was conducted on strawberry plants grown in greenhouses in the town of Xingshou, Changping District, Beijing, China. A tan-brown leaf spot with the presence of pink spore masses was observed on older leaves of strawberry plants. In general, the leaf spots began as small, round, water-soaked lesions in the middle or on the margin of leaves, which enlarged gradually up to 1 to 3 cm in diameter and were circular or irregular and brown to dark brown. Occasionally, the center of some spots cracked in the middle lesion under dry conditions. Eventually, black sporodochia were produced on the upper surface of spots and exuded pink conidial masses under humid conditions. Fungal structures were taken directly from the diseased leaves and examined microscopically for morphological characteristics. Sporodochia, 172 to 451 × 138 to 343 μm, were dark and suborbicular. Conidiophores, 8.4 to 48.3 × 0.8 to 2.1 μm, were hyaline, unicellular, and cylindrical. Conidia, 3.1 to 10.2 × 1.5 to 3.0 μm, were hyaline, aseptate, and canoe-shaped to allantoid, forming singly. For further study, the fungus was isolated in pure culture on potato dextrose agar (PDA) medium from symptomatic leaf tissue. In culture, the mycelium was white at first and then changed to brownish. The sporodochia were light colored at first and turned brownish or almost black in older cultures. To identify the fungus, the ITS1-5.8S-ITS2 rDNA region of the isolate was amplified by PCR with primers ITS1 (5'-TCCGTAGGTGAACCTGCGG-3') and ITS4 (5'-TCCTCCGCTTATTGATATGC-3') and sequenced. The 462-nt sequence (GenBank Accession No. JQ995228) was identical to that of Pilidium concavum (1). To validate Koch's postulates, pathogenicity was tested by inoculating 20 leaves on 10 healthy strawberry plants with a mycelial plug from a 15-day-old colony (0.5 cm in diameter). Controls were treated with plugs of PDA medium. The inoculated and control plants were then maintained in growth chambers at 25°C (12 h of light per day, 80% humidity). After 12 days, 100% of the inoculated leaves showed symptoms identical to those observed on leaves in the field while the control leaves remained healthy. The original fungus was reisolated from inoculated leaves showing the symptoms. Thus, it was concluded that the fungus was the causal organism of the leaf spot. On the basis of morphological characteristics, molecular features, and pathogenicity tests, the pathogen of tan-brown leaf spot on strawberry was identified as P. concavum. To our knowledge, this is the first report of P. concavum causing tan-brown leaf spot on strawberry in China. This fungus was reported to cause leaf spot on Paeonia suffruticosa in China (2). It also caused tan-brown rot on strawberry fruit in our pathogenicity test. References: (1) L. Cardin et al. Plant Dis. 93:548, 2009. (2) Y. B. Duan et al. Plant Dis. 94:271, 2010.

Objective: To investigate changes of visual performance and effects of higher order aberration on visual performance after Epi-LASIK for myopia., Method: In this prospective study, 102 patients were included. The trial group had 52 patients with Epi-LASIK, and 50 cases with LASIK as the control group. Ocular higher order aberrations were measured with the Hartman-shack wavefront analyzer, and high (100%), moderate (25%), low contrast (10%) and very low contrast (5%) visual acuity with and without glare were measured with Multi-Function Visual Acuity Tester under mesopic condition preoperatively and 4 - 6 months after surgery. 35 subjects in Epi-LASIK and 33 cases in LASIK were followed up 4 - 6 months later. Paired t test were used to analyze different contrast visual acuity before and after Epi-LASIK. Multiple linear regression analysis was performed to find the explanatory aberrations which contributed to the visual acuity. The Pearson correlation was used to explore the correlation between high- and low-contrast visual acuity and the explanatory higher order aberrations. The independent t test was used to analyze the difference of refraction power and visual acuity between Epi-LASIK and LASIK., Results: There were significantly statistical differences at 5% and 10% contrast level compared to preoperation with glare and with no glare. With no glare, the mean logMAR visual acuity at 5% and 10% contrast level were 0.32 + or - 0.14 and 0.21 + or - 0.12 preoperatively, and 0.47 + or - 0.15 and 0.33 + or - 0.16 postoperatively (t = -4.863, 3.950; P = 0.000, 0.000). With glare, the mean logMAR visual acuity were 0.37 + or - 0.20 and 0.22 + or - 0.13 preoperatively, and 0.46 + or - 0.18 and 0.30 + or - 0.17 postoperatively (t = -1.949, -2.283; P = 0.047, 0.029). Using stepwise multiple linear regressions to evaluate which higher order aberration was significantly associated with each contrast VA. For each order RMS, S(4) was positive correlated with 5% contrast visual acuity (r(2) = 0.282;P = 0.025); S(4) was positive and S(5) was negative correlated with 10% contrast visual acuity (r(2) = 0.192;P = 0.033). None of the higher order RMS can significantly affect the 25% and 100% contrast visual acuity. For each Zernike coefficients, C(4)(0) and C(6)(4) were positive correlated with 5% contrast visual acuity (r(2) = 0.233; P = 0.024); C(4)(-4) was negative, C(4)(0) and C(5)(-5) were positive correlated with 10% contrast visual acuity (r(2) = 0.289; P = 0.013); None of Zernike coefficients had a significant correlation with 25% and 100% contrast visual acuity. The Pearson correlated coefficients between S(4), C(4)(0) and each contrast visual acuity increased as the contrast level decreased. S(4) and C(4)(0) were associated significantly with 5% contrast visual acuity, the correlation coefficients were 0.378 and 0.390 (P = 0.025 and 0.021). The visual acuity under 100% contrast with no glare was a little poorer than in LASIK., Conclusions: At the early stage after Epi-LASIK, the visual acuity for lower contrast level was worse compared to preoperative with glare and with no glare. Spherical aberration and the spherical-like aberration may contribute to this.

Objective: To establish a method for increasing T regulatory cells (Treg) in the graft by using in vivo treatment with dexamethasone (Dex) plus IL-2 and observe its suppressing effect on graft-versus-host-disease (GVHD) in mice., Methods: After treatment of male C57BL/6N mice (donor) with Dex (5 mgxkg(-1)xd(-1)) combined with IL-2 (300 000 IUxmouse(-1)xday(-1)) for three days, spleen mononuclear cells were isolated for flow cytometry analysis of CD4(+)CD25(+) POXP3(+) Treg cells. The allogeneic lymphocytes were transplanted from male C57BL/6N mice to female BALB/c mice aged 8-12 weeks. GVHD and survival time were investigated after transplantation. Donor-derived hematopoiesis reconstituted in recipient mice was detected by Y-chromosome-specific PCR and H-2K(b) by flow cytometry., Results: Administration of Dex and IL-2 markedly expanded functional CD4(+)CD25(+)FOXP3(+) Treg cells in murine spleen, the number of which in treated group was (24.2 +/- 7.6)% while in control group was (4.0 +/- 0.8)% (P = 0.01). The ratio of Treg to effector T cells (Teff) increased obviously in the treated group (0.43 +/- 0.15 vs 0.14 +/- 0.01, P = 0.01). In a murine allogeneic lymphocyte transplantation model, the grafts from donor with combined treatment of Dex and IL-2 led to a longer survival time than that from the control group (median survival time > 60 d vs 12 d, P = 0.0045), while the mortality rate was decreased (29.4% vs 71.4%, P < 0.05)., Conclusion: Costimulation with Dex and IL-2 can selectively expand the functional CD4(+)CD25(+)FOXP3(+) Treg in vivo, which can suppress acute GVHD.

Objective: To assess the effects of 20% ethanol used in LASEK on corneal wound healing., Methods: Forty-eight eyes from 24 rabbits were deepithelialized by two techniques. The epithelium were detached with either 20% ethanol (applied for 30 seconds) or mechanical scraping, then ablated was performed. The number of superficial stromal keratocytes was counted and the morphologic changes were observed. Expression of TGF-beta1 and bFGF mRNAs was detected and analyzed by reverse transcription-polymerase chain reaction and immunocytochemical methods at 1, 7, 30 and 90 days after the surgery., Results: One day after the surgery, the expression of TGF-beta1 and bFGF in the keratocytes in both treated groups was lower than that of the normal controls. Seven days after the surgery, the expression of TGF-beta1 and bFGF in both treated groups was greater than that of the normal controls (P < 0.01). The expression in the alcohol-treated group was greater than that of the surgical-treated group (P < 0.01). The expression of TGF-beta1 and bFGF reached the peak 30 days after the surgery, no significant difference was detected between the alcohol-treated and surgical-treated groups. There was no significant difference in expression level between the alcohol-treated and surgical-treated groups 3 months after the surgery; as well as between treated groups and normal group. The amount of TGF-beta1 and bFGF mRNA was positively correlated with the number of keratocytes. The correlation coefficient between TGF-beta1 and bFGF mRNA and the number of the keratocytes was 0.744 (P < 0.01) and 0.738 (P < 0.01) in the alcohol-treated group; and was 0.664 (P < 0.01) and 0.785 (P < 0.01) in the surgical-treated group, respectively., Conclusions: The expression of TGF-beta1 and bFGF mRNA undergo a dynamic process of "decrease-increase-normal". Although ethanol has a slight toxic effect on rabbit epithelial cells, but the effects do not persist over time, therefore, it is relatively safe to use the alcohol treatment in the LASEK.