Animals ; Cell Differentiation ; drug effects ; Cell Transplantation ; Cells, Cultured ; Disease Models, Animal ; Drug Evaluation, Preclinical ; Embryonic Stem Cells ; cytology ; Humans ; Regeneration ; drug effects

OBJECTIVETo evaluate the antitumor activity of a novel class of 4, 8-Disubstituted-8, 9-dihydropyrazine[2, 3-g]quinazoline-7(6H)-ketones in vitro, and to screen potential anticancer compounds for further study.

METHODSSeventeen compounds of 4, 8-Disubstituted-8, 9-dihydropyrazine[2, 3-g]quinazoline-7(6H)-ketones were synthesized with solid-phase method for biological evaluation of EGFR tyrosine kinase. MTT method was used to evaluate the cytotoxic activity in vitro against three human cancer cell lines (human lung carcinoma cell line A549, human leukemia cell lines K562 and human gastric carcinoma cell line SGC7901).

RESULTSCompound 7-13 and 7-14 showed potent antitumor activities against A549 cells, with IC(50) values of 8.10 and 8.12 mol/L, respectively. Eight compounds showed proliferative inhibition effect on K562 cells, especially 7-2, 7-13 and 7-17, with IC(50) values of 2.22,0.57 and 7.20 mol/L,respectively.And compound 7-13 and 7-3 showed potent antitumor activity against SGC7901 cells, with IC(50) values of 4.20 and 9.71 mol/L, respectively.

CONCLUSIONThe synthesized compounds 4, 8-Disubstituted-8, 9-dihydropyrazine[2, 3-g] quinazoline-7(6H)-ketones show inhibition effects on human cancer cell lines in vitro. Compound 7-13 has anticancer activity in all three cancer cell lines, which might be used as a potential antitumor drug for further study.

Antineoplastic Agents ; chemical synthesis ; chemistry ; pharmacology ; Cell Line, Tumor ; Drug Screening Assays, Antitumor ; Humans ; K562 Cells ; Lung Neoplasms ; pathology ; Molecular Structure ; Pyrazines ; chemical synthesis ; chemistry ; pharmacology ; Quinazolines ; chemical synthesis ; chemistry ; pharmacology ; Receptor, Epidermal Growth Factor ; antagonists & inhibitors ; Stomach Neoplasms ; pathology ; Structure-Activity Relationship

OBJECTIVETo investigate the effect of Rongshi granule on osteopontin(OPN) expression.

METHODThe urlisthiasis rats were induced by ethylene glycol (EG) and ammonium chloride, the control group rats were non-treated, and the Rongshi granule groups (low-dose group, middle-dose group and high-dose group) were administered Rongshi granule in addition to EG and ammonium chloride in 21 days. Pooled 24 h urine samples from each group were collected weekly with the use of metabolic cages, the concentration of uric calcium and oxalic acid were respectively measured by EDTA and photoelectric colorimetric method. Eight animals from each group were killed at 0, 7, 14, and 21 days, kidneys were histologic examinaed and immunohistochemical staining.

RESULTThe expression of kidney osteopontin in model group was obviously higher than that of control group (P <0.01), and was up to the highest at 21 days with 1.4 times (0.281 3/0.201 8) of the control group. The expression of kidney osteopontin in all of the Rongshi granule groups were lower than those of model group (P < 0.05), with an obvious dose-dependent manner. The degree of the kidney calcium oxalate crystal of the rats in all the Rongshi granule groups was much lower than that of model group, and the uric calcium and oxalic acid were much lower than those of model group (P < 0.01).

CONCLUSIONThe Rongshi granule could inhibit the expression of osteopontin in rat urolithiasis model.

Ammonium Chloride ; Animals ; Calcium ; urine ; Calcium Oxalate ; metabolism ; Dose-Response Relationship, Drug ; Drug Combinations ; Drugs, Chinese Herbal ; administration & dosage ; isolation & purification ; pharmacology ; Ethylene Glycol ; Female ; Kidney ; metabolism ; Kidney Calculi ; chemically induced ; metabolism ; Male ; Osteopontin ; metabolism ; Oxalic Acid ; urine ; Plants, Medicinal ; chemistry ; Random Allocation ; Rats ; Rats, Sprague-Dawley

OBJECTIVETo investigate the expression of Junctophilin 1 (JP1) in cardiogenesis of mammalian.

METHODSCardiac differentiation of embryonic stem cells (ESCs) was generated by hanging drop method. Fetal heart was obtained from the rats aged d 14-20 of gestation. The expression of JP1 and JP2 during cardiogenesis of ESCs and rat embryos was analyzed by RT-PCR or Western blotting. Immunofluorescence staining was employed to reveal the distribution of JP1 and JP2 in embryoid body (EB), probing for merging of JP1 and JP2 and cardiac sarcomeric α-Actinin or Troponin-T. Percentage of JP1 and JP2-positive staining cells was analyzed quantitatively by FCS on d17.

RESULTSJP1 mRNA was up-regulated at the early stage (d 5-11) and then decreased. The expression of JP1 protein was up-regulated at the early stage (d 7-9), then decreased gradually and disappeared after d 15. While JP2 gene and protein expression increased in a time-dependent manner during cardiogenesis of rat embryos. The results of immunofluorescence staining showed that there was a parallel co-localization of JP2 with Troponin-T or α-Actinin on d17, while JP1 failed to express in the sarcomeric positive area at the same time point. Furthermore, FCS analysis showed that about 16.59% of cells were JP2-positive, while no cells were stained positively for JP1 in d17 EBs.

CONCLUSIONJP1 gene is expressed during the whole process of cardiogenesis, while JP1 protein only appears on the early stage. The expression of JP1 in cardiogenesis of ESCs is consistent with that of rat embryos.

Actinin ; genetics ; metabolism ; Animals ; Cell Differentiation ; Cell Line ; Embryonic Stem Cells ; cytology ; metabolism ; Heart ; embryology ; Membrane Proteins ; genetics ; metabolism ; Mice ; Mice, Inbred ICR ; Myocytes, Cardiac ; cytology ; metabolism ; RNA, Messenger ; genetics ; Rats ; Troponin T ; genetics ; metabolism

Objective To investigate the outcomes of patients with diabetic retinopathy (DR) in Shanghai communities and the influencing factors.Methods From October 2015 to April 2016,533 type 2 diabetic patients with DR were selected by target sampling and cluster random sampling method from six community health service centers in Shanghai.Patients were followed up for 1 year.The demographic information,physical examination,laboratory tests and eye fundus exam results were documented and the DR was graded.The factors associated with the regression of DR were analyzed.Results Total 478 patients,including 280 females (58.6％) and 198 males (41.4％),were followed up for 1 year.The mean age of patients was (64±7) years and the mean disease duration was (8.85±4.20) years.The original DR lesion was remitted in 35 patients with an improvement rate of 7.3％;while the original DR lesion was aggravated in 29 patients with a progression rate of 6.1％.Ordinal logistic regression analysis revealed that age (OR=0.197,95％CI:0.056-0.699),body mass index (BMI) (OR=0.383,95％CI:0.171-0.856),glycosylated hemoglobin (HbAlc) (OR=0.287,95％CI:0.102-0.803),triglycerides (TG) (OR=0.541,95％CI:0.295-0.991),urinary albumin to creatinine ratio (ACR)(OR=0.218,95％CI:0.066-0.720) were associated with DR in type 2 diabetic patients.Conclusion The regression of DR is closely related to age,BMI,glucose,serum lipids and renal function,so it is suggested that lowering BMI,controlling glucose and serum lipids and maintaining normal kidney function are necessary for preventing the progression and promoting the improvement of DR in diabetic patients.

Objective To evaluate the accuracy of endoscopic titanium clip localization combined with CT three?dimensional reconstruction for the control of incision margin in early gastric cancer under laparoscopy. Methods A prospective analysis was made for gastric cancer whose lesions were located in the middle of the stomach and T stage was 1 to 2 from October 2017 to January 2019 at Department of Gastrointestinal and Pancreatic Surgery, Zhejiang Provincial People′s Hospital. Totally 25 patients were eventually enrolled in the study. There were 17 males and 8 females aging of (63.6± 7.2) years (range: 48 to 77 years). All cases were treated with titanium clip localization under endoscope combined with CT three?dimensional(3D) reconstruction to construct a virtual panorama of gastric cavity and lesions, and to design surgical margins. Laparoscopic surgical resection was performed according to the surgical margins designed before operation. The distance from the gastric angle to the origin of the minor curvature of the incisional margin, the distance from the gastric angle to the the center of lesion and the distance of the upper incision margin were measured under three?dimensional CT reconstruction and under actual specimen. Paired t test was used to compare the three distances measured by two methods. Results The measured distances from the gastric angle to the center of the lesion and the proximal incisional margin under 3D reconstruction CT were according to the measured values of actual specimens ((2.67±1.38) cm vs. (2.83±1.56) cm, t=1.51, P=0.14; (5.23±0.60) cm vs. 5 cm, t=1.93, P=0.07); the measured distances from the gastric angle to the origin of the minor curvature of the incisional margin under CT 3D reconstruction were different with the measured values of solid specimens ((5.94±0.94) cm vs. (6.37±0.90) cm, t=3.52, P=0.00). Conclusion The method of titanium clip localization combined with CT 3D reconstruction can provide a feasible laparoscopic localization method and incision edge solution for T1 to T2 gastric central cancer.

Objective To evaluate the accuracy of endoscopic titanium clip localization combined with CT three?dimensional reconstruction for the control of incision margin in early gastric cancer under laparoscopy. Methods A prospective analysis was made for gastric cancer whose lesions were located in the middle of the stomach and T stage was 1 to 2 from October 2017 to January 2019 at Department of Gastrointestinal and Pancreatic Surgery, Zhejiang Provincial People′s Hospital. Totally 25 patients were eventually enrolled in the study. There were 17 males and 8 females aging of (63.6± 7.2) years (range: 48 to 77 years). All cases were treated with titanium clip localization under endoscope combined with CT three?dimensional(3D) reconstruction to construct a virtual panorama of gastric cavity and lesions, and to design surgical margins. Laparoscopic surgical resection was performed according to the surgical margins designed before operation. The distance from the gastric angle to the origin of the minor curvature of the incisional margin, the distance from the gastric angle to the the center of lesion and the distance of the upper incision margin were measured under three?dimensional CT reconstruction and under actual specimen. Paired t test was used to compare the three distances measured by two methods. Results The measured distances from the gastric angle to the center of the lesion and the proximal incisional margin under 3D reconstruction CT were according to the measured values of actual specimens ((2.67±1.38) cm vs. (2.83±1.56) cm, t=1.51, P=0.14; (5.23±0.60) cm vs. 5 cm, t=1.93, P=0.07); the measured distances from the gastric angle to the origin of the minor curvature of the incisional margin under CT 3D reconstruction were different with the measured values of solid specimens ((5.94±0.94) cm vs. (6.37±0.90) cm, t=3.52, P=0.00). Conclusion The method of titanium clip localization combined with CT 3D reconstruction can provide a feasible laparoscopic localization method and incision edge solution for T1 to T2 gastric central cancer.

Objective To investigate the characteristics of fertility-sparing surgery for non-invasive low-grade serous carcinoma ( LGSC) of the ovary .Methods All the histologically diagnosed patients of non-inva-sive LGSC who admitted to Peking Union Medical College Hospital and received fertility -sparing surgeries between January 2015 and June 2015 were reviewed and their clinicopathological characteristics , surgical procedures , and follow-up results were retrospectively analyzed .Results Totally five cases of non-invasive LGSC receiving fertili-ty-sparing surgeries were reviewed .Their median age was 29 years (range, 24-34 years).One case received laparotomy and four received laparoscopies; four cases received ovarian cystectomy and one received emergency unilateral adnexectomy for the affected and necrotic ovary because of acute torsion .One case was diagnosed at In-ternational Federation of Gynecology and Obstetrics ( FIGO) stage IB, and the other four were at stage IA .All the five cases received no further therapy after the surgery .The median follow-up period was 7 months ( range , 6-12 months ) .No case relapsed so far .One case conceived naturally and both the mother and the fetus were in good condition .Conclusions For non-invasive LGSC patients , there are many unresolved issues in aspects of spare of fertility , conception after fertility-sparing surgeries , recurrence , and follow-up.Although the possibility to spare the ovary is supported by this study for young non-invasive LGSC patients , long-term prognosis ( inclu-ding fertility and survival ) needs to be observed in further follow-up.

OBJECTIVE: To evaluate the safety and effectiveness of eyelid margin cleaning using Deep Cleaning Device for the treatment of meibomian gland dysfunction-associated dry eye. METHODS: This was a prospective, randomized, open-label, investigator-masked, and self-controlled study. We randomly assigned one eye of patients with meibomian gland dysfunction-associated dry eye to the treatment group, and the other eye to the control group. Both groups received artificial tears and lid warming; the treatment group received an additional one-time in-office eyelid margin cleaning using Deep Cleaning Device. Non-invasive tear break-up time (NITBUT) and tear meniscus height (TMH) of each eye, and Standard Patient Evaluation for Eye Dryness II (SPEED II) score of each patient were evaluated before and at one week after treatment. RESULTS: Thirty eyes of 15 patients were enrolled. No adverse effects occurred during the treatment. Compared with the baseline values, the SPEED score decreased significantly at one week after treatment (mean±95% confidence interval, 11.00±0.99 vs. 5.67±1.67, P<0.0001), the NITBUT-first in the treatment group increased significantly at one week after treatment ((4.74±1.27) s vs. (7.49±2.22) s, P=0.01). The NITBUT-first was significantly longer in the treatment group ((7.49±2.22) s) than in the control group ((5.17±0.91) s) at one week after treatment (P=0.042). No significant differences were found in other tear film parameters between the two groups. CONCLUSIONS Eyelid margin cleaning using the novel Deep Cleaning Device is a convenient, effective, and safe treatment for patients with meibomian gland dysfunction-associated dry eye.
Adult ; Aged ; Dry Eye Syndromes/therapy* ; Eyelids/physiopathology* ; Female ; Humans ; Hyperthermia, Induced ; Male ; Meibomian Gland Dysfunction/therapy* ; Middle Aged ; Prospective Studies ; Tears

The recycling of traditional Chinese medicine （TCM） wastes is an important research topic to be solved urgently in the industrialization of TCM resources. Rhei Radix et Rhizoma is a bulk Chinese herb mainly derived from Rheum palmatum，R. tanguticum，and R. officinale. At present，these three medicinal plants have been cultivated on a large scale and widely used in the fields of medicine，health care，food，cosmetics，and veterinary medicine，with an annual demand of more than 5 500 tons（1 ton=1 000 kg）. However，a large number of wastes such as non-medicinal parts and residues produced in the production and deep processing are discarded because there is no effective way of utilization，resulting in serious waste of resources and environmental pollution. The non-medicinal parts contain not only the chemical components and pharmacological effects similar to those of roots and rhizomes but also a variety of amino acids，mineral elements，and conventional nutrients. They have a long history of use，and the content of some resource components is higher than that in roots and rhizomes. In particular，their stems and leaves exhibit great potential to be consumed as food and medicine due to high safety. Besides，the content of anthraquinones in Rhei Radix et Rhizoma residue is high and it possesses good antibacterial activity. It can be seen that the waste from the industrialization of Rhei Radix et Rhizoma has high utilization value. Hence，based on the relevant literature and investigation on the application of producing areas in China and abroad，the paper summarized the utilization status of their medicinal and non-medicinal parts，the waste production in the industrialization，as well as the active substances and utilization ways and put forward the multi-level and multi-path utilization strategy of Rhei Radix et Rhizoma wastes，in order to provide reference for the rational development and application of Rhei Radix et Rhizoma resources and promote the effective utilization and green development of the corresponding wastes.