Objective:To investigate the clinical manifestation, diagnosis and treatment of chronic lymphocytic leukemia patients with renal involvement.Methods:The clinical data of a chronic lymphocytic leukemia patient with nephrotic syndrome as the initial manifestation in Fujian Provincial People's Hospital in October 2020 were retrospectively analyzed, and the related literature was reviewed.Results:The patient was a 68-year-old male with recurrent edema and foam urine as the initial manifestations, and he was diagnosed as nephrotic syndrome in the nephrology department. After treatment, the symptoms showed no significant improvement, and the lymphocyte count gradually increased. The patient was diagnosed as chronic lymphocytic leukemia in the hematology department. After ibrutinib monotherapy, the lymphocyte count and urine protein gradually decreased to normal levels, and the clinical efficacy evaluation of the patient was complete remission at the end of follow-up.Conclusions:Chronic lymphocytic leukemia with nephrotic syndrome as the initial manifestation is rare, and the clinical presentations are variable. Early diagnosis is the guarantee of successful treatment. The efficacy and safety of first-line Bruton tyrosine kinase inhibitor monotherapy are good.

Seven indole alkaloid glycosides containing a 1'-(4″-hydroxy-3″,5″-dimethoxyphenyl)ethyl unit (-) were isolated from an aqueous extract of leaves (da qing ye). Their structures were determined by spectroscopic data analysis combined with enzymatic hydrolysis as well as comparison of their experimental CD (circular dichroism) and calculated ECD (electrostatic circular dichroism) spectra. Based on analysis of and/or Cotton effect (CE) data of -, two simple roles to assign location and/or configuration of -glycopyranosyloxy and 1'-(phenyl)ethyl units in the indole alkaloid glycosides are proposed. Stereoselectivity in plausible biosynthetic pathways of - is discussed. Compounds and and their mixture in a 3:2 ratio showed activity against KCNQ2 in CHO cells. The mixture of and (3:2) exhibited antiviral activity against influenza virus H1N1 PR8 with IC 64.7 μmol/L (ribavirin, IC 54.3 μmol/L), however, the individual or was inactive. Preliminary structure-activity relationships were observed.

Five new sulfur-enriched alkaloids isatithioetherins A-E (-), and two pairs of scalemic enantiomers (+)- and (-)-isatithiopyrin B ( and ) and isoepigoitrin and isogoitrin and ), along with the known scalemic enantiomers epigoitrin and goitrin ( and ), were isolated and characterized from an aqueous extract of the roots. Their structures were determined by extensive spectroscopic data analysis, including 2D NMR and theoretical calculations of electronic circular dichroism (ECD) spectra based on the quantum-mechanical time-dependent density functional theory (TDDFT). Compounds - represent a novel group of sulfur-enriched alkaloids, biogenetically originating from stereoselective assemblies of epigoitrin-derived units. Isolation and structure characterization of and support the postulated biosynthetic pathways for the diastereomers and a rare thio-Diels-Alder reaction. Compounds and showed antiviral activity against the influenza virus A/Hanfang/359/95 (H3N2, IC 0.60 and 1.92 μmol/L) and the herpes simplex virus 1 (HSV-1, IC 3.70 and 2.87 μmol/L), and also inhibited Coxsackie virus B3 (IC 0.71 μmol/L).

Eight new C-diterpenoid alkaloid arabinosides, named aconicarmichosides E-L (-), were isolated from an aqueous extract of the lateral roots of (Fu Zi). Their structures were determined by spectroscopic and chemical methods including 2D NMR experiments and acid hydrolysis. Compounds -, together with the previously reported four neoline 14--arabinosides from the same plant, represent the only examples of glycosidic diterpenoid alkaloids so far. At a dose of 1.0 mg/kg (i.p.), as compared with the black control, compounds , , and - exhibited analgesic effects with >65.6% inhibitions against acetic acid-induced writhing of mice. Structure-activity relationship was also discussed.

Objective To study the optimum technological conditions of macroporous resin separation and purification of polyphenol composition. Methods Fingerprint of Ilex paraguariensis was established by HPLC method. The best resin, loading conditions and elution requirements were screened with chlorogenic acid and elution rate of total active constituents served as the index. Results The optimum technological conditions were as follows:the separation carrier was D101 macroporous resin,the concentration of the sample liquid was 0.10 g?mL-1 ,the resin adsorption quantity of crude drugs was 1.5 g?g-1 ,the impurity was removed by four times of amount of water at first,and then eluted with four times the amount of 70％ ethanol in a gradient manner.After purification,the elution rate of chlorogenic acid was up to 82.83％,and the elution rate of total effective component was about 72. 48％. The resemblance of HPLC fingerprint was over 0. 98, and the components were balancedly recoveried. Conclusion The purification process of total polyphenols in Ilex paraguariensis by D101 macroporous resin was simple,reliable,and can be used for large-scale production.

OBJECTIVETo study the promoter methylation status of SFRP genes and the effect of 5- aza- 2'- deoxycytidine (5- Aza- CdR)induced apoptosis via Wnt/β- catenin pathway by demethylation in Jurkat cells.

METHODSJurkat cells were treated with different concentrations of 5- Aza- CdR. The cell proliferation level of Jurkat cells was detected by MTT assay. Apoptosis was evaluated by flow cytometry. Methylation- spcific PCR (MSP) was used to determine the methylation status of SFRP genes. The expressions of SFRP genes were detected by real time fluorescence quantitative PCR. The mRNA expression levels of survivin, c- myc and cyclin- D1 were analyzed by RT- PCR. Western blot was used to detect the levels of β-catenin protein.

RESULTSCompared with control group, the different concentrations of 5-Aza-CdR could significantly inhibit the proliferation of Jurkat cells in a time-dose dependent manner (P<0.05). After being treated by 5- Aza- CdR for 48 hours, the cell early apoptosis rate in experiment group was significantly higher than that in control group (P<0.05). The promoters of SFRP1, SFRP2, SFRP4, SFRP5 genes were hypermethylation state in the control group, after being treated by 5-Aza-CdR for 72 hours, the brightness of SFRP1, SFRP2, SFRP4, SFRP5 genes' methylation strips weakened in a dose- dependent manner. SFRP mRNA expression increased (P<0.05) when 5- Aza- CdR concentration increased, and the level of β- catenin protein was dampened in a dose- dependent manner (P<0.05). As compared to the control group, the mRNA expressions of associated apoptosis genes survivin, c-myc and cyclin- D1, respectively were obviously down- regulated in a dose- dependent manner (P<0.05).

CONCLUSIONThe effect of demethylation could up- regulate SFRP genes expressions by reversing its hypermethylation and induced apoptosis by down-regulation of β-catenin and associated apoptosis genes.

Apoptosis ; Azacitidine ; analogs & derivatives ; pharmacology ; Cell Proliferation ; DNA Methylation ; Down-Regulation ; Gene Expression ; Humans ; Intercellular Signaling Peptides and Proteins ; genetics ; Jurkat Cells ; Membrane Proteins ; genetics ; Promoter Regions, Genetic ; Wnt Signaling Pathway ; beta Catenin ; metabolism

Three new sesquiterpene glycosides, named codonopsesquilosides A-C (1-3), were isolated from an aqueous extract of the dried roots of Codonopsis pilosula. Their structures including absolute configurations were determined by spectroscopic and chemical methods. These glycosides are categorized as C15 carotenoid (1), gymnomitrane (2), and eudesmane (3) types of sesquiterpenoids, respectively. Compound 1 is the first diglycoside of C15 carotenoids to be reported. Compound 2 represents the second reported example of gymnomitrane-type sesquiterpenoids from higher plants. The absolute configurations were supported by comparison of the experimental circular dichroism (CD) spectra with the calculated electronic CD (ECD) spectra of 1-3, their aglycones, and model compounds based on quantum-mechanical time-dependent density functional theory. The influences of the glycosyls on the calculated ECD spectra of the glycosidic sesquiterpenoids, as well as some nomenclature and descriptive problems with gymnomitrane-type sesquiterpenoids are discussed.

Seven new 4-hydroxybenzyl-substituted amino acid derivatives (1-7), together with 11 known compounds, were isolated from an aqueous extract of the rhizomes of Gastrodia elata Blume. Their structures were determined by spectroscopic and chemical methods. Compounds 1-3 are pyroglutamate derivatives containing 4-hydroxybenzyl units at the N atom and 4-7 are the first examples of natural products with the 4-hydroxybenzyl unit linked via a thioether bond to 2-hydroxy-3-mercaptopropanoic acid (4-6) and 2-hydroxy-4-mercaptobutanoic acid (7), which would be biogenetically derived from cysteine and homocysteine, respectively. The structures of 1 and 2 were verified by synthesis, while the absolute configurations of 4, 5 and 7 were assigned using Mosher's method based on the MPA determination rule of Δδ RS values. The known compound 4-(hydroxymethyl)-5-nitrobenzene-1,2-diol (8) exhibited activity against Fe(2+)-cysteine induced rat liver microsomal lipid peroxidation with IC50 values of 9.99×10(-6) mol/L.

Four new acetylenes (1-4) and one new unsaturated ω-hydroxy fatty acid (5), together with 5 known analogues, were isolated from an aqueous extract of Codonopsis pilosula roots. Their structures were determined by spectroscopic and chemical methods. The new acetylenes are categorized as an unusual cyclotetradecatrienynone (1), tetradecenynetriol (2), and rare octenynoic acids (3 and 4), respectively, and 3 and 4 are possibly derived from oxidative metabolic degradation of 1 and/or 2. The absolute configuration of 1 was assigned by comparison of the experimental circular dichroism (CD) spectrum with the calculated electronic circular dichroism (ECD) spectra of stereoisomers based on the quantum-mechanical time-dependent density functional theory, while the configuration of 2 was assigned by using modified Mosher׳s method based on the MPA determination rule of Δδ RS values for diols.

Objective To investigate the intensity modulated radiation therapy (IMRT) planning optimization method to reduce the additional dose resulting from megavoltage cone-beam CT (MVCBCT) imaging for nasopharyngeal carcinoma IMRT treatment. Methods MVCBCT images collection process was simulated using XiO treatment planning system. The mean doses of MVCBCT ( DMVCBCT ) were calculated in gross tumor volume ( GTV), clinical target volume ( CTV ) and risk at organ or tissue using 27. 4 cm× 27.4 cm portal radiation 8 MU,5 MU (A,C) and 27.4 cm× 15.0 cm portal radiation 8 MU,5 MU (B,D). The dose correct factor of MVCBCT (CFMVCBCT) according to IMRT TPS and DMVCBCT ,but CFMVCBCT plus MVCBCT imaging process for radiotherapy planning optimization. The paired t-test was play for A∶ B,C∶ D,A∶ C,B∶ D of DMVCBCT. Results The DMVCBCT and CFMVCBCT of A, B, C, D were 7. 78,5. 78,4. 88,3.55 cGy ( A∶ C, t =24.41,P＜0.01) and 0.993 -0.997 in GTV,with 7.88,6.95,4.88,4.38 cGy (A∶ B,A∶ C,B∶ C,t=3. 85, -31.82, -8.52, all P＜0. 01) and 0.992 -0.996 in CTV1 ,with 8.28,6.67,5. 17,4. 17 cGy (A ∶B,A∶C,B∶C,B∶D,t=6.41 -18.24,all P＜0. 01) and 0.991 -0.996 in CTV2;with 6.88,5.00,4.28,3. 50 cGy ( A∶ B, A∶ C,t = 2. 83,11.03, all P ＜ 0. 05 ) and 0. 989 - 0. 995 in spinal cord, with 7.88,7. 38,4. 95,4. 62 cGy and 0. 984 -0. 990 in left parotid, with 8. 67,0. 28,5. 33,0. 28 cGy and 0. 963 -0. 999 in left optic nerve,with 9. 17,0.22,5.72,0. 17 cGy and 0.821 -0.997 in left eye lens,with 6.95,2. 17,4. 38,1.38 cGy and 0. 987 -0. 997 in brain stem, with 7.78,0.45,4. 95,0. 28 cGy and 0. 978 -0. 999 ( A ∶ B,A∶ C,B∶ C,B∶ D for five organ or tissue,t =5. 06 -335. 16 ,all P ＜0. 01 ) in optic chiasm. Conclusions The MVCBCT imaging process resulted in radiation doses to patient. The impact of MVCBCT image acquired dose on IMRT treatment plan for NPC was eliminated by a compensation method.