OBJECTIVE To investigate the effect of sodium ferulate (SF) on lipopolysaccharide (LPS)-induced preterm delivery and intra-uterine fetal death (IUFD). METHODS Pregnant Kunming mice were subcutaneously pretreated with SF (25 or 50 mg · kg-1) from gestational day (GD) 10 to GD 15 and with the single injection of LPS (150μg·kg-1, ip) on GD15.5. The incidence of preterm delivery and IUFD was observed. HE staining was used for uterine and placental histological evaluation. The levels of thiobarbituric acid reactive substances (TBARS) and reduced glutathione (GSH) as well as the activities of glutathione S-transferase (GST) and glutathione peroxidase (GSH-Px) were detected in the maternal liver, placenta, and fetal liver using commercial kits. Interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α) levels in amniotic fluid were evaluated by enzyme linked immunosorbent assay. RESULTS For LPS group, the incidence of preterm was 47.8%, delivery time was (17.5 ± 1.3) d, and the pups′survival rate was only 42.6%. Compared with LPS-treated group, SF 50 mg · kg-1 group showed a lower incidence of preterm (14.3%, P<0.01), longer gestational days (18.4 ± 0.5, P<0.05), and a higher pups′survival rate (75.6%, P<0.01). SF 50 mg · kg-1 restored the LPS-induced GSH both in the maternal and fatal liver (a tendency without statistical significance), GST activity〔(163±82) kU·g-1 protein vs (95±90) kU·g-1 protein, P<0.01)〕in the placenta, TBARS content〔(2.5±0.4)μmol·g-1 protein vs (3.1±0.6)μmol·g-1 protein, P<0.01〕in the fetal liver, and TNF-αlevel〔(11±8) ng·L-1 vs (20±8) ng·L-1, P<0.01〕in the amniotic fluid. SF also attenuated LPS-induced placental congestion and neutrophil infiltra?tion in the uterus. CONCLUSION SF may protect against LPS-induced preterm delivery and IUFD, and anti-oxidation as well as anti-inflammation may contribute to these effects.

Objective To explore the CT features of gastrointestinal tract diospyrobezoar and its complications,to improve the recognition. Methods The plain CT scan of 36 patients with gastrointestinal tract diospyrobezoar confirmed by gastroscope and surgery were analyzed retrospectively.Results The number and location of diospyrobezoar showed by CT were consistent with the results of gastroscope and surgery.There were 1 1 cases of stomach diospyrobezoar,1 9 cases of small intestine diospyrobezoar,and 6 cases of stomach and small intestine diospyrobezoar.32 cases were solitary lesion,and 4 cases were multiple lesions.A total of 41 diospyrobezoars were removed, most of which were wel-l defined ovoid mass.3 1 lesions presented mottled internal gas bubbles with high-density encapsulating wall.6 lesions showed mottled gas pattern without encapsulating wall.4 lesions showed uneven high density.Over time,1 lesion moved in the digestive tract and the boundary and density were changed.Complications:gastric and duodenal diospyrobezoar accompanied by gastric retention,which manifested as a significant expansion of the gastric cavity effusion.Small intestine diospyrobezoar was accompanied by small bowel obstruction,which showed that the proximal intestinal tube of the diospyrobezoar was obviously dilated,and the distal intestine was suddenly collapsed.There was a focal transition zone between them.Conclusion Gastrointestinal tract diospyrobezoar has a variety of CT manifestations,of which oval shape,clear boundary,uneven mass composed of gas and soft tissue are common.

Intensive cancer treatment with drug combination is widely exploited in the clinic but suffers from inconsistent pharmacokinetics among different therapeutic agents.To overcome it,the emerging nanomedicine offers an unparalleled opportunity for encapsulating multiple drugs in a nano-carrier.Herein,a two-step super-assembled strategy was performed to unify the pharmacokinetics of a pep-tide and a small molecular compound.In this proof-of-concept study,the bioinformatics analysis firstly revealed the potential synergies towards hepatoma therapy for the associative inhibition of exportin 1(XPO1)and ataxia telangiectasia mutated-Rad3-related(ATR),and then a super-assembled nano-pill(gold nano drug carrier loaded AZD6738 and 97-110 amino acids of apoptin(AP)(AA@G))was con-structed through camouflaging AZD6738(ATR small-molecule inhibitor)-binding human serum albumin onto the AP-Au supramolecular nanoparticle.As expected,both in vitro and in vivo experiment results verified that the AA@G possessed extraordinary biocompatibility and enhanced therapeutic effect through inducing cell cycle arrest,promoting DNA damage and inhibiting DNA repair of hepatoma cell.This work not only provides a co-delivery strategy for intensive liver cancer treatment with the clinical translational potential,but develops a common approach to unify the pharmacokinetics of peptide and small-molecular compounds,thereby extending the scope of drugs for developing the advanced com-bination therapy.

Objective:To investigate the effect of diallyl trisulfide (DATS) on the expression of folate receptor α (FRα) in human gastric cancer cells and the related regulatory mechanism.Methods:Human gastric cancer cell lines BGC823 and AGS were selected, BGC823 cells were treated with 10, 20, 40, 80 μmol/L DATS for 48 hours, and AGS cells were treated with 5, 10, 20, 40 μmol/L DATS for 48 hours. Cells treated with 6 μmol/L histone deacetylase (HDAC) inhibitor trichostatin A (TSA) were used as positive control for epigenetic study, and cells untreated with DATS were used as negative control. The apoptosis of gastric cancer cells induced by DATS was detected by flow cytometry. After BGC823 and AGS cells were treated by DATS for 48 hours, they were replaced with DATS-free cell culture medium and cultured for different time to detect the changes in FRα protein expression. BGC823 and AGS cells were treated with 6 μmol/L TSA or 40 μmol/L DATS. The protein expression levels of FRα, HDAC1 and HDAC2, and histone H3 lysine 9 acetylation (H3K9ac) and histone H4 lysine 5 acetylation (H4K5ac) were detected by Western blot. BGC823 cells were inoculated into BALB/c nude mice to establish tumor bearing model. The nude mice in DATS group were injected intraperitoneally with 10 mg/kg DATS for 16 days, and then the protein in tumor-bearing tissues was extracted to detect the expression of target protein, while the control group was injected with equal dose of 0.9% NaCl solution.Results:The expressions of FRα protein in BGC823 and AGS cells were up-regulated in a dose-dependent way after gradient concentrations of DATS treatment ( F = 65.68, P < 0.01; F = 26.65, P < 0.01). After changing the cell culture medium without DATS, the expressions of FRα protein in BGC823 and AGS cells gradually decreased and returned to the initial levels ( F = 74.57, P < 0.01; F = 30.92, P < 0.01). With the increase of DATS concentration, the apoptosis rates of BGC823 and AGS cells increased ( F = 32.95, P < 0.01; F = 38.97, P < 0.01). After TSA treatment, FRα protein expressions in BGC823 and AGS cells were up-regulated by 4.5 times ( t = -12.62, P < 0.01) and 3.6 times ( t = -10.00, P < 0.01). After 40 μmol/L and 20 μmol/L DATS treatment, the expression level of FRα protein in BGC823 and AGS cells was up-regulated (both P < 0.01), the expressions of HDAC1 and HDAC2 were inhibited (all P < 0.01), and the levels of H3K9ac and H4K5ac acetylation modification increased (all P < 0.01). The results of tumor-bearing nude mice experiment showed that the volume of transplanted tumor in DATS group was smaller than that in the control group [(214±39) mm 3 vs. (577±98) mm 3], and the difference was statistically significant ( t = 4.86, P < 0.01). Compared with the control group, FRα protein expression in the transplanted tumor tissues of DATS group was up-regulated about 2 times ( t = -5.29, P < 0.01), and the expression levels of HDAC1 and HDAC2 proteins were down-regulated ( t = 9.36, P < 0.01; t = 9.88, P < 0.01). Conclusions:DATS up-regulates the expression of FRα protein in human gastric cancer BGC823 and AGS cells in a dose-dependent and reversible manner. The mechanism may be related to the effect of DATS on histone acetylation modification in tumor cells.

Jinlingzi San is a formula frequently used in treating pain syndrome， first recorded in the Collection of Writings on the Mechanism of Disease， Suitability of Qi， and the Safeguarding of Life as Discussed in the 'Basic Questions' written by LIU Wansu in the Jin Dynasty. Jinlingzi San is composed of 2 Chinese medicinals Toosendan Fructus and Corydalis Rhizoma with a concise composition and exact clinical efficacy， having been included in the Catalogue of Ancient Classical Formulas （Second Batch： Han Chinese Medicine）. The formula name， historic evolution， medicine origins， composition， dosage， decocting methods， and ancient and modern clinical application were sorted out and analyzed with the bibliometric method. A total of 209 pieces of information were collected from ancient books and literature. After screening， 49 pieces of effective data involving 45 ancient books were included. Results showed that the name of Jinlingzi San was first recorded in Secret Formulas of the Yang Family written by Yang Tan in the Southern Song Dynasty and developed into 3 other versions of the decoction. The Jinlingzi San included in the Collection of Writings on the Mechanism of Disease， Suitability of Qi， and the Safeguarding of Life as Discussed in the 'Basic Questions' written by LIU Wansu invariably plays a dominant role. As for the 3 other versions， although they have the same name of Jinlingzi San， their composition and indications are different from those of the original formula， which were therefore viewed as prescriptions based on Jinlingzi San and also included in the research. The medicine origins and processing of Jinlingzi San are suggested： Toosendan Fructus is the dry mature fruit of Melia toosendan of Meliaceae， and the crude is used after cleansing without putamen. Corydalis Rhizoma is the dry tuber of Corydalis yanhusuo of Papaveraceae， which is used after impurity removal， cleaning， and drying. Depending on the conversion from the measurement system in the Jin Dynasty to modern measurement， it is suggested that Toosendan Fructus and Corydalis Rhizoma （41.3 g each） are ground into fine powder， and one dose includes 12.39 g of the powder， which should be taken with an appropriate amount of wine. If wine is not suitable for the patient， the decoction can also be taken with warm water. Jinlingzi San has the effects of soothing the liver， discharging heat， and activating blood to stop pain. As recorded in ancient books， Jinlingzi San is specialized in treating heart pain caused by reversal heat， chest and abdominal pain， hypochondriac pain， jaundice， hernia， and other diseases. Modern studies have shown that modified Jinlingzi San can be used in treating diseases involving the digestive system， the integumentary system， the gynecological system， the reproductive system， and other systems and has wide clinical application in treating epigastric pain， herpes zoster， dysmenorrhea， and other diseases. This study has made clear the key information of Jinlingzi San by textual research of ancient books and literature in the hope of providing a theoretical reference for the clinical application， set prescriptions， and new drug development.