The novel ER stress inducer Sec C triggers apoptosis by sulfating ER cysteine residues and degrading YAP via ER stress in pancreatic cancer cells

Pancreatic adenocarcinoma (PAAD) is one of the most lethal malignancies. Although gemcitabine (GEM) is a standard treatment for PAAD, resistance limits its application and therapy. Secoemestrin C (Sec C) is a natural compound from the endophytic fungus Emericella, and its anticancer activity has not been investigated since it was isolated. Our research is the first to indicate that Sec C is a broad-spectrum anticancer agent and could exhibit potently similar anticancer activity both in GEM-resistant and GEM-sensitive PAAD cells. Interestingly, Sec C exerted a rapid growth-inhibiting effect (80% death at 6 h), which might be beneficial for patients who need rapid tumor shrinkage before surgery. Liquid chromatography/mass spectrometry and N-acetyl-l-cysteine (NAC) reverse assays show that Sec C sulfates cysteines to disrupt disulfide-bonds formation in endoplasmic reticulum (ER) proteins to cause protein misfolding, leading to ER stress and disorder of lipid biosynthesis. Microarray data and subsequent assays show that ER stress-mediated ER-associated degradation (ERAD) ubiquitinates and downregulates YAP to enhance ER stress via destruction complex (YAP-Axin-GSK-βTrCP), which also elucidates a unique degrading style for YAP. Potent anticancer activity in GEM-resistant cells and low toxicity make Sec C a promising anti-PAAD candidate.

Sulfur-enriched alkaloids from the root of

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).

Breast reconstruction with pedicled perforator flaps / 中国癌症杂志

Comparing with free perforator flap, pedicled flap is a relatively simpler and safer technique, with lesser donor site morbidity. In recent years, the application of pedicled perforator flaps has emerged as a new option for breast reconstruction. Those pedicled perforator flaps include thoracodorsal artery perforator flap, intercostal artery perforator flap (lateral intercostal artery perforator flap, anterior intercostal perforator flap) etc. Serratus anterior artery perforator flap, superior epigastric artery perforator flap, and lateral thoracic artery perforator flap can also be raised technically. To enhance surgical accuracy, it is necessary to evaluate the location and quality of perforator vessels preoperatively. Proper flap design is of more importance for pedicled flap when compared with it's free flap counterpart. Although free flap approach remains the golden standard in breast reconstruction when considering autologous tissue transplantation, pedicled perforator flap has the apparent merits of minimized surgical trauma, less time-consuming and less stress for reconstructive surgeons.

Aromatic compounds from an aqueous extract of "ban lan gen" and their antiviral activities

A pair of new diphenyl glycerol ether enantiomers (-)-and (+)-and two new methyl benzamidobenzoatesand, named (-)-()- and (+)-()-isatindigotrioic acid [(-)-and (+)-] and isatindigoticamides A () and B (), respectively, were isolated from an aqueous decoction of the roots of(ban lan gen). Their structures were elucidated by spectroscopic data analysis including 2D NMR experiments. The absolute configurations of (-)-and (+)-were assigned based on the CD exciton chirality method. Compoundsandexhibited antiviral activities against HSV-1 with ICvalues of 4.87 and 25.87 μmol/L, respectively. Compoundwas also found active against Coxsackie virus B3 and LPS-induced NO production.

Indole alkaloid sulfonic acids from an aqueous extract ofroots and their antiviral activity

Six new indole alkaloid sulfonic acids (-), together with two analogues (and) that were previously reported as synthetic products, were isolated from an aqueous extract of theroot. Their structures including the absolute configurations were determined by spectroscopic data analysis, combined with enzyme hydrolysis and comparison of experimental circular dichroism and calculated electronic circular dichroism spectra. In the preliminary assay, compoundsandshowed antiviral activity against Coxsackie virus B3 and influenza virus A/Hanfang/359/95 (H3N2), respectively.

Three pairs of alkaloid enantiomers from the root of Isatis indigotica

Three pairs of enantiomerically pure alkaloids with diverse structure features, named isatindigoticoic acid A and epiisatindigoticoic acid A [(-)-1 and (+)-1], phaitanthrin A and epiphaitanthrin A [(-)-2 and (+)-2], and isatindopyrromizol A and epiisatindopyrromizol A [(-)-3 and (+)-3], respectively, were isolated from an aqueous extract of the roots of Isatis indigotica. Racemic and scalemic mixtures of these enantiomers were separated by HPLC on a chiral semi-preparative column. Their structures including absolute configurations were determined by extensive spectroscopic analysis in conjunction with the calculation of electronic circular dichroism (ECD) spectra. The enantiomer pairs possess parent structures of 2-oxo-1,2,3,4-tetrahydroquinoline-4-carboxylic acid, indolo[2,1-b]quinazolinone, and 3-thioxohexahydro-1H-pyrrolo[1,2-c]imidazol-1-one, respectively. Except for phaitanthrin A [(-)-2] which the configuration was previously undetermined, these compounds are new enantiomeric natural products.

Assessment of efficacy of narrow-band ultraviolet B for the treatment of early-stage mycosis fungoides / 中华皮肤科杂志

Objective To evaluate the efficacy of narrow-band ultraviolet B (NB-UVB) for the treatment of early-stage mycosis fungoides (MF).Methods A retrospective study was performed on 98 patients with early-stage MF treated with NB-UVB from January 2003 to December 2013.The rate of and time to recurrence of MF were assessed,and long-term side effects were evaluated in these patients.Results Among 52 patients achieving complete remission,the median number of sessions of NB-UVB radiation was 30 (range,18-87),the median cumulative radiation dose was 24.16 J/cm2 (range,9.11-108.86 J/cm2),and the median follow-up duration was 41 months (range,11-90 months).Relapse occurred in 14 (26.9％) patients with the median time to recurrence being 8.2 months (range,3-60 months).The patients suffering from relapse achieved complete remission after treatment with NB-UVB again.Adverse reactions mainly included skin erythema and itching at the early stage of radiation,as well as temporary pigmentation after radiation.Cutaneous carcinoma occurred in none of these patients during 11-90 months of follow-up.Conclusions NB-UVB phototherapy appeared to be effective for the treatment of early-stage MF,and no cutaneous carcinoma occurred in these patients during the follow-up.Although MF may relapse in some cases,repeated NB-UVB phototherapy is still effective.

4-Hydroxybenzyl-substituted amino acid derivatives from Gastrodia elata

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.

Chemical constituents from aqueous extract of Gastrodia elata / 中国中药杂志

Two new compounds (1 and 2), together with twenty-one known compounds (3-23), were isolated by a combination of various chromatographic techniques including column chromatography over macroporous resin, MCI gel, silica gel, and Sephadex LH-20 and reversed-phase HPLC. Their structures were identified by spectroscopic data analysis as 4-hydroxy-3-(4-hydroxybenzyl) benzyl methyl ether (1), 4-( methoxymethyl) phenyl-1-O-beta-D-glucopyranoside (2), hibicutaiwanin (3), 4-(4-hydroxybenzyl)-2-methoxyphenol (4), 4,4'-methylenebis(2-methoxyphenol) (5), L-phenyllactic acid (6) ,4-hydroxy-3-methoxybenzyl ethol ether (7), p-hydroxylbenzyl alcohol (8), p-hydroxylbenzyl methyl ether (9), p-hydroxylbenzyl ethyl ether (10), p-hydroxybenzaldehyde (11), p-hydroxybenzoic acid (12), p-hydroxybenzoic acid (13), gastrodin (14), 4-(ethoxymethyl) phenyl-1-O-beta-D-glucopyranoside (15), 4-(beta-D-glucopyranosyloxy) benzaldehyde (16), p-methylphenyl-1-O-beta-D-glucopyranoside (17 ), methyl-O-beta-D-glucopyranoside (18), 5-hydroxymethl-furan aldehyde (19), parishin (20), parishin B (21), parishin C (22), and diosgenin (23). The 13C-NMR data of compound 4 was first reported.

Lignans from Sinocalamus affinis / 中国中药杂志

Fifteen compounds were isolated from the stem (with skin removed) of Sinocalamus affinis by a combination of various chromatographic techniques including silica gel, macroporous adsorbent resin, Sephadex LH-20, and preparative HPLC. Their structures were elucidated by spectroscopic data as ( + )-(1S, 2R)-1, 2-bis (4-hydroxy- 3-methoxyphenyl)-1, 3-propanediol (1), threo-guaiacylglycerol-beta-O-4'-coniferyl ether(2), erythro-guaiacylglycerol-beta-O-4'-coniferyl ether(3), ( + )-(7S, 8R, 8'R)-5'-methoxylariciresinol(4), ( + )-(7S, 8R, 8'R)-5, 5'-dimethoxylariciresinol (5), ( +/- )-glaberide I (6), ( - )-syringaresinol (7), ( - )-medioresinol(8), ( - )-(8R, 8R')-4, 4'-dihydroxy-3, 3', 5, 5'-tetramethoxyligna-9, 9'-diol(9), ( - )-secoisolariciresinol-9, 9'-acetonide (10), and ( + )-lyoniresinol (11); a new natural product 2, 6-dimethoxypyran4-one (12), and beta-sitosterol, 4-hydroxycinnamic acid, and 2, 6-dimethoxy-p-benzoquinone. These compounds were isolated from the genus Sinocalamus for the first time, compound 10 should be an artifact.

Changes in cerebral glucose metabolism induced by postoperative delirium in elderly patients and the effects of dexmedetomidine on it / 中华麻醉学杂志

Objective To investigate the changes in cerebral glucose metabolism induced by postoperative delirium in the elderly patients and the effects of dexmedetomidine on it.Methods Forty-two patients of both sexes aged 65-85 yr with a body mass index of 19-25 kg/m2 undergoing abdominal surgery under general anesthesia were enrolled in this study.Delirium occurred during the first 2 days after operation in 39 out of the 42 patients (29/42).The 29 patients were randomly divided into 2 groups:group delirium without any treatment (group D,n =13) and group delirium + dexmedetomidine (group Dex,n =16).The remaining 13 patients did not develop delirium after operation and served as control group (group C).In group Dex a loading dose of dexmedetomidine 1 μg/kg was administered iv over 10 min after occurrence of delirium followed by continuous infusion at 0.2-0.7μg· kg-1 · h-1.PET scan was performed within the time period in which delirium occurred.18 Fluorine-deoxyglucose was injected for observation of imaging of glucose metabolism.The standard uptake value of glucose of bilateral parietal,temporal and frontal lobes was calculated.Results Delirium was controlled within 30 min after adminnistration of dexmedetomidine.Delirium significantly reduced cerebral glucose metabolism in the bilateral parietal,temporal and frontal lobes in group D as compared with group C (P ＜ 0.05).Dexmedetomidine significantly attenuated the delirium-induced decrease in cerebral glucose metabolic rate of the 3 lobes in group Dex as compared with group D (P ＜ 0.05).Conclusion Postoperative delirium reduces cerebral glucose metabolism and dexmedetomidine can significantly control pastoperative delirium in the elderly patients.

Effects of dexmedetomidine on postoperative cognitive function and monocytes Toll-like receptor 2 and Tolllike receptor 4 expression in elderly patients / 中华麻醉学杂志

ObjectiveTo investigate the effects of dexmedetomidine on postoperative cognitive function and monocytes Toll-like receptor 2 (TLR2)and TLR 4 expression in elderly patients.MethodsForty-five ASA Ⅰ or Ⅱ elderly patients aged ≥65 yr weighing 53-72 kg were randomly divided into 3 groups: control group (group Ⅰ ) and different doses of dexmedetomidine groups(groups Ⅱ and Ⅲ ).Dexmedetomidine 1.0 μg/kg was injected iv over 15 min after anesthesia induction,and then was infused at a rate of 0.5 μg·kg-1 ·h-1 (group Ⅱ ) or 1.0 μg· kg-1 ·h-1 (group Ⅲ ) untile the end of operation.Group Ⅰ received equal volume of normal saline.Blood samples were taken before anesthesia induction,at 1.5 h after the beginning of operation,at the end of operation and at 24 h after operation(T,-T5 ) for determination of monocytes TLR2 and TLR4 expression by flow cytometrybased method.Postoperative cognitive function was evaluated at 1 d before and 7 d after operation with Mini-mental state examination and Wechsler memory scale and Wechsler adult intelligence scale,and the postoperative cognitive dysfunction was recorded.ResultsThe incidence of postoperative cognitive dysfunction and monocytes TLR2 and TLR4 expression were significantly lower in groups Ⅱ and Ⅲ than in group Ⅰ,and in group Ⅲ than in group Ⅱ (P ＜ 0.05).ConclusionDexmedetomidine can prevent postoperative cognitive dysfunction in elderly patients,and the mechanism may be related to down-regulation of monocytes TLR2 and TLR4 expression.

Accuracy of hippocampal formation measurement by MRI in predicting postoperative cognitive dysfunction in elderly patients / 中华麻醉学杂志

Objective To assess the accuracy of MRI measurement of hippocampal formation in predicting postoperative cognitive dysfunction (POCD) in elderly patients.Methods Forty-one ASA Ⅱor Ⅲ patients aged≥65 yr undergoing gastrointestinal tract surgery were enrolled in this study.MRI was performed to measure the volume of hippocampal formation before surgery and the results were standardized according to the individual intracranial volume.All patients underwent a battery of neuropsychological tests including sensitive tests on the Wechsler adult memory scale and Wechsler adult intelligence scale,trail making test and the grooved pegboard test.We used the Z score to identify POCD as recommended by Moiler.All patients were then divided into POCD group and non-POCD group according to the results of the neuropsychological tests.The results of the tests were correlated with the volume of hippocampal formation measured by MRI.The value of MPI measurement of hippocampal volume in predicting POCD was analyzed.Results Thirty-six patients completed the whole battery of neuropsychological tests after surgery.Thirteen of the 36 patients were found to have COPD (36%) on the 4th postoperative day.The hippocampal volume was significandy smaller in POCD group (4.75±0.23) than in non-POCD group(5.06±0.31).Hippocampal volume was found to be effective in predicting POCD.The overall accuracy of prediction was 77.8%(28/36 patients) with 92.3% sensitivity (12/13 patients),70.0% specificity (16/23 patients) and 0.623 Youden index.Conclusion The MRI measurement of hippocampal volume is valuable as a predictor of POCD in the elderly.

Association between HLA-B51 alleles and Behcet's disease in Chinese Han nationality / 中华皮肤科杂志

Objective To investigate the possible association between HLA-B51 alleles and Behcet's disease (BD). Methods Totally, 61 Chinese patients of Han nationality, who were diagnosed with BD according to the International Study Group (ISG) criteria, were recruited. The control cohort consisted of 100 healthy individuals. Blood samples were obtained from all the subjects. PCR-sequenee specific primers (SSPs) were used to for the genotyping of HLA-B51 alleles (HLA-B5101-HLA-B5109). Results Com- pared with the control group (11 positive, 11% ), the frequency of HLA-B51 (18 positive, 29.5% ) was sig- nificantly increased in BD patients (χ2=8.79, P<0.01, RR=3.39). The HLA-B51-positive patients and controls consistently carried HLA-B5101 allele with no other alleles observed. There were 15 males and 3 females in HLA-B51 positive patients, 22 males and 21 females in HLA-B51-negative patients, and signifi- cant differences in gender distribution was observed between HLA-B51-positive and negative patients (P<0.05 ). Moreover, the average age of onset in HLA-B51-positive patients significantly differed from that in HLA-B51-negative patients (28.4±10 years vs 37.3±12 years, P<0.05). However, no significant differ- ences were noticed in the clinical types, course, skin lesions, prevalence of genital ulcer, eye damage, joint involvement, or pathergy reaction between HLA-B51-positive and -negative patients (P0.05). Conclu- sions This study supports that HLA-B5101 allele is associated not only with the development of BD, but also with the gender and onset age of patients with BD of Chinese Han nationality.

A case of Langerhans cell histiocytosis and Sj(o)gren's syndrome / 中华皮肤科杂志

The patient was a 38-year woman.Six years prior to presentation,she developed erythema and papules with occasional pruritus in both labium majora,which gradually confluenced into plaques with the formation of superficial erosion and ulcer;extension into the vulva and crissum occurred later.Half a year prior to presentation,a subcutaneous firm nodule measuring about 1.5cm in diameter with intact epidermis,developed on the right submaxilla,associated with mild swelling in the area;the nodule enlarged gradually.A subcutaneous induration measuring 0.5 cm in diameter was observed in the left chin 2 months later.She also reported a 20-year history of dry eye and dry mouth.The patient tested postive for antinuclear antibody cally,there was a focal infiltration of lymphocytes in tissue of minor salivary glands.The pathology of lesions on the right labium majus showed a dense dermal infiltration with S100-and CD1a-positive,irregulady-shaped histiocyte-like cells with abundant eosinophilic cytoplasm and few mitotic figures.Needle biopsy of the right submaxilla area showed tumor cells.A diagnosis of Langerhans cell histiocytosis and Sj(o)gren syndrome was made based on clinical manifestation,laboratory findings and histopathological features.Combination chemotherapy with cyclophosphamide,vincristine,corticosteroids and etoposide resulted in clinical improvement.

The promoter effects of sodium butyrate on the malignant transformation of the immortalized esophageal epithelium induced by human papillomavirus / 中华病理学杂志

<p><b>OBJECTIVE</b>Study on the promoter effects of sodium butyrate in high or low dosages on carcinogenesis process, based on the immortalization of human fetal esophageal epithelium induced by human papillomavirus (HPV) 18E(6)E(7) genes.</p><p><b>METHODS</b>The immortalized esophageal epithelium SHEE was treated with high concentration of the sodium butyrate (80 mmol/L) and then with low concentration (5 mmol/L) for 8 weeks respectively. The cells were cultured continuously without sodium butyrate for 14 weeks. The morphology, proliferation and apoptosis of the cells were studied by phase contrast microscopy, immunohistochemistry and flow cytometry. The dead and the viable cells were assayed by fluorescent microscopy with Hoechst 33342 and Propidium iodide staining. Tumorigenesis of the cells was assessed by soft agar colony formation and by transplantation of cells into nude mice and SCID mice.</p><p><b>RESULTS</b>When cells were exposed to high concentration of sodium butyrate, cell death was increased leaving few live cells. When cells were cultured in the medium with low concentration of sodium butyrate, the first proliferative stage appeared. Removal of the butyrate caused the cell to enter a crisis stage with a long doubling time resembling senescent cells. After the crisis stage, the cells progressed to the second proliferation stage with continuous replication and atypical hyperplasia. At the end of the second proliferative stage, carcinogenesis of the cells appeared with large colonies in soft-agar and tumor formation in transplanted SCID mice and nude mice.</p><p><b>CONCLUSIONS</b>The malignant change of the immortalized epithelium by the effects of sodium butyrate is the consequence of a two-stage mortality mechanism: cells death by butyrate cytotoxicity and cell crisis by abrogation of sodium butyrate. These data reveal that in high dosage, sodium butyrate induces cell death and in low dosage, it induces cell proliferation, which emphasizes the importance of butyrate as a promotor of carcinogenesis.</p>

Discussion on Sun Simiao's Healthy Ethics Thought / 中国医学伦理学

Sun Simiao expounded much profound healthy ethics thought in his《Qian Jin Fang》.He inherited and developed the harmonious viewpoint of health,and emphasized health based on the morality and advocated launching health education to the masses.Now these ideas also have important actual significance.

Cutaneous Type Adult T-cell Leukemia/Lymphoma: The First Case Report in China / 中华皮肤科杂志

Objective To report the first case of cutaneous type adult T-cell leukemia/lymphoma(cATLL) in China. Methods The skin lesion was examined by histopathology and direct immunofluorescence (DIF), and the immunophenotype was also studied. ELISA and Western blot were used to test the serum antibodies to HTLV-Ⅰ, and HTLV-Ⅰproviral DNA of lymphoid cells was detected by PCR. Results The patient had polymorphic skin lesions including papules, plaques, and bullae with tense or flaccid walls. Histopathogical examination showed subepidermal bullae, and there were small-to-medium-sized atypical lymphoid cell infiltrations in the dermal papilla in the bottom, and border of the bulla. CD45+ and CD45RO+ staining, and negative DIF were observed in the atypical lymphoid cells. The serum antibodies to HTLV-Ⅰ, and proviral DNA of HTLV-Ⅰin the blood lymphoid cells were detected. The patient died with a disease course of one year and ten months. Conclusion ATLL is not extremely rare in China, and cATLL may also exist.

The Effects of Arsenite Trioxide on the Transplanted Hepatic Carcinoma in Mice / 中国肿瘤生物治疗杂志

Objective: To investigate the antitumor effects of arsenic trioxide (As 2 O 3 ) on solid tumor in vivo , the transplanted hepatic carcinoma of mice were treated with various dosages of As 2 O 3 . Methods: After 50 mice were injected intraperitoneally with 0,2, 4, 6, 8 ?mol/g As 2 O 3 respectively for observation of acute toxicity, 1, 2, 3 ?mol/g were selected for this experiment. Eighty mice were transplanted with hepatic carcinoma cells (1.5?10 6 cells/each side) into both subaxillae. As 2 O 3 in 0, 1, 2 and 3 ?mol/g were injected into right subaxilla respectively once every day for 10 days. At the 30th day after transplanted hepatic carcinoma cell, mice were killed and the size of solid tumors was measured. The chronic cytotoxicity of As 2 O 3 was observed in these mice.Results: In right subaxillae tumors, which were injected directly with As 2 O 3 , were apparent smaller than that in the left ( P

A Case Report of Lymphomatoid Papulosis Followed By Mycosis Fungoides:Derived from a Com-mon T Cell Clone / 中华皮肤科杂志

Objective To report a case of lymphomatoid papulosis(LyP)followed by mycosis fun-goides(MF)during his27years course and determine whether these diseases are clonally related.Methods Characteristics of clinicopathology and immunophenotype of skin tissues of different phases of the patients were compared.Simultaneously,clonal T-cell receptor gene rearrangement of skin lesion tissues and blood specimens were detected by means of polymerase chain reaction and Southern blot analysis.Results A dis-tinct clinical and pathological feature was shown in this case of LyP followed by MF.The proliferating lym-phocytes in LyP and MF were mature T helper lymphocytes,and with same T-cell clone.Conclusion LyP followed by MF displays a same T-cell clone.The clonal T-cell is irrelevant to the biological behavior of these diseases.