Objective:To systematically evaluate the efficacy and safety of neoadjuvant chemoradiotherapy (NCRT) plus surgery versus neoadjuvant chemotherapy (NCT) plus surgery in the treatment of advanced esophageal squamous cell carcinoma.Methods:Clinical controlled trials of comparing the treatment of NCRT plus surgery with NCT plus surgery for esophageal squamous cell carcinoma were electronically searched from the databases including PubMed, The Cochrane Library, EMbase, CBM, CNKI, WanFang and VIP from the inception of databases to January, 2019. Two reviewers independently screened the literatures, extracted data and assessed the risk of bias of the included studies. And then, a meta-analysis was performed by using RevMan 5.3 software.Results:A total of 8 clinical control studies were included, including 995 patients with esophageal squamous cell carcinoma. Meta-analysis results showed that compared with the NCT group, the R 0 resection rate was significantly higher ( OR=2.14, 95% CI: 1.03-4.45, P=0.040) and the pathological complete response (pCR) rate was significantly higher ( OR=4.19, 95% CI: 1.71-10.28, P=0.002) in the NCRT group. The incidence of postoperative complications ( OR=1.37, 95% CI: 0.76-2.48, P=0.300) and the risk of perioperative death ( OR=1.28, 95% CI: 0.58-2.83, P=0.54) were not significantly different between two groups. The long-term survival of patients with esophageal squamous cell carcinoma in the NCRT group was significantly better compared with that in the NCT group ( HR=0.77, 95% CI: 0.64-0.92, P=0.005). Conclusions:Compared with NCT plus surgery for advanced esophageal squamous cell carcinoma, NCRT plus surgery has higher R 0 resection rate and pCR rate, does not significantly increase the risk of perioperative complications or perioperative death, and significantly improves the long-term survival of esophageal squamous cell carcinoma patients.

OBJECTIVETo investigate the effects of saikosaponin-d (SSd) on glomerular mesangial cells (MCs) proliferation and hyperplastic extracellular matrix (ECM) induced by lipopolysaccharide (LPS) to provide experimental proof for its use in prevention and treatment of glomerulosclerosis.

METHODSRat's MCs were cultivated and identified. The cultured MCs were stimulated by LPS and incubated with different concentrations of SSd. Cell proliferation was determined by MTT assay, LDH assay and flow cytometry, respectively. Type IV collagen (Col IV), fibronectin (FN) and transforming growth factor beta1 (TGF-beta1) in the conditioned medium were measured by ELISA. The expressions of cyclin-dependent kinase 4 (CDK4), c-Jun and c-Fos were detected by immunohistochemistry.

RESULTSAfter treated by SSd, MC proliferation was inhibited, cells in G0/G1 phase increased, and apoptosis induced. Moreover, secretion of Col IV, FN and TGF-beta1 and the expressions of CDK4, c-Jun and c-Fos in MC were inhibited.

CONCLUSIONThe inhibitory action of SSd on glomerulosclerosis was realized through inhibiting the expressions of CDK4, c-J un and c-Fos.

Animals ; Apoptosis ; drug effects ; Cell Cycle ; drug effects ; Cell Proliferation ; drug effects ; Cell Survival ; drug effects ; Cells, Cultured ; Collagen Type IV ; analysis ; Cyclin-Dependent Kinase 4 ; metabolism ; Enzyme-Linked Immunosorbent Assay ; Extracellular Matrix ; drug effects ; pathology ; Flow Cytometry ; Hyperplasia ; Immunohistochemistry ; Immunosuppressive Agents ; pharmacology ; Lipopolysaccharides ; Male ; Mesangial Cells ; cytology ; drug effects ; metabolism ; Oleanolic Acid ; analogs & derivatives ; pharmacology ; Rats ; Rats, Sprague-Dawley ; Saponins ; pharmacology ; Transforming Growth Factor beta1 ; analysis

Chemotherapy remains one of the major tools, along with surgery, radiotherapy, and more recently targeted therapy, in the war against cancer. There have appeared a plethora of highly potent cytotoxic drugs but the poor discriminability between cancerous and healthy cells of these agents limits their broader application in clinical settings. Therapeutic antibodies have emerged as an important class of biological anticancer agents, thanks to their ability in specific binding to tumor-associated antigens. While this important class of biologics can be used as single agents for the treatment of cancer through antibody-dependent cell cytotoxicity (ADCC), their therapeutical efficacy is often limited. Antitumor antibody drug conjugates (ADCs) combine the target-specificity of monoclonal antibody (mAb) and the highly active cell-killing drugs, taking advantages of the best characteristics out of both components. Thus, insufficiency of most naked mAbs in cancer therapy has been circumvented by arming the immunoglobulin with cytotoxic drugs. Here mAbs are used as vehicles to transport potent payloads to tumor cells. ADCs contain three main components: antibody, linker and cytotoxics (also frequently referred as payload). Antibodies can recognize and specifically bind to the tumor-specific antigens, leading to an antibody-assisted internalization, and payload release. While ADC has demonstrated tremendous success, a number of practical challenges limit the broader applications of this new class of anticancer therapy, including inefficient cellular uptake, low cytotoxicity, and off-target effects. This review article aims to cover recent advances in optimizing linkers with increased stability in circulation while allowing efficient payload release within tumor cells. We also attempt to provide some practical strategies in resolving the current challenges in this attractive research area, particularly to those new to the field.
Aminobenzoates ; pharmacology ; therapeutic use ; Animals ; Antibodies, Monoclonal ; pharmacology ; therapeutic use ; Antineoplastic Agents ; pharmacology ; therapeutic use ; Cell Survival ; drug effects ; Cytotoxins ; pharmacology ; therapeutic use ; Drug Design ; Humans ; Immunoconjugates ; chemistry ; pharmacology ; therapeutic use ; Maytansine ; pharmacology ; therapeutic use ; Neoplasms ; drug therapy ; pathology ; Oligopeptides ; pharmacology ; therapeutic use

Objective Prospective comparison was done on concurrent chemo-radiotherapy and se- quential chemo-radiotherapy for unresectable stageⅢnon-small cell lung cancer(NSCLC) and to evaluate three different regimens of concurrent chemo-radiotherapy.Methods Ninety-six such patients were ran- domized into four groups:1.sequential chemo-radiotherapy group received two cycles of induction chemother- apy with 40 mg/m~2 of cisplatin on D 1-3,29-31 and 100 mg/m~2 of etoposide on D 1-3,29-31 before conven- tional radiotherapy,2.concurrent chemo-radiotherapy group 1 received 100 mg/m~2 etoposide on D 1-3 and DDP 40 mg/m~2 on D 1-3,D 29-31,iv.drip,3.concurrent chemo-radiotherapy group 2 received concurrent chemotherapy with 40 mg/m~2 of paclitaxel every Monday during conventional radiotherapy,4.concurrent chemo-radiotherapy group 3 received concurrent chemotherapy with 40 mg/m~2 of paclitaxel every Monday during three-dimensional conformal radiotherapy.All patients were irradiated with 2.0 Gy/fraction,5 frac- tions/week,to a total dose of 60-64 Gy.They all received two cycles of consolidation themotherapy with 40 mg/m~2 of cisplatin on D 1-3 and 100 mg/m~2 of etoposide on D 1-3.Results The overa/1 response rate was 67%,71%,71% and 79% for sequential ehemo-radiotherapy group,concurrent chemo-radiotherapy group 1,2 and 3,respectively.There was a significant difference between the concurrent chemo-radiotherapy and sequential chemo-radiotherapy(P＜0.05).The 1-,3-and 5-year overall survival rate(OS) was 54%,8% and 4%;71%,17% and 8%;79%,17% and 8%;83%,46% and 13%,respectively for the four groups. The difference among all these groups(P=0.017) was significant.It was also significant between the con- current chemo-radiotherapy group 1 and 3 (P=0.046).The difference of distant metastasis rate among all the groups was statistically insignificant (P＞0.05) also was the difference of toxicity (P＞0.05),but the severe toxicity of concurrent chemo-radiotherapy groups 1 and 2 were higher than the sequential chemo-radio- therapy group and concurrent chemo-radiotherapy group 3.Conclusions Better locoregional progression- free survival and overall survival of unresectable stageⅢnon-small cell lung cancer could be achieved by concurrent chemo-radiotherapy as compared with sequential chemo-radiotherapy though at the expense of in- crease in toxicity.With the combination of concurrent chemo-radiotherapy and conforrnal radiotherapy,the o- verall survival rate could be much improved with miider toxicity.

OBJECTIVETo evaluate the efficacy of Kirschner wires and tension-band fixation through posterolateral minimal incision for the treatment of displaced supracondylar humeral fractures in children.

METHODSFrom January 2005 to December 2010, there were 62 children (38 males and 24 females, ranging in age from 2 to 14 years, averaged 6.8 years) with Gartland type III supracondylar humeral fractures. All the injuries were caused by falling, and all the fractures were fresh injuries. The duration from injury to surgery ranged from 5 to 20 hours. All the children were treated with open reduction through a posterolateral minimal approach, Kirschnere wires and tension-band fixation were fixed with plaster at 90 degrees of elbow flexion, forearm supination, and palms facing upwards. The kirschner pins and wires were removed after fractures healing. The Flynn's criterion was used to evaluate therapeutic effects.

RESULTSThe operation time ranged from 30 to 50 min (averaged 45 min). All the patients achieved solid union. Sixty patients were followed up, and the mean follow-up time was 15 months (ranged from 6 to 24 months). At the 6th month after operation, 48 patients got an excellent result, 9 good, 3 bad (light cubitus varus with varus angle about 6 degree, without infection on function) according to Flynn's criteria. There were no complications such as procedure-related pin tract infection, iatrogenic nerve and vascular injuries and myositis ossificans.

CONCLUSIONThe Kirschner wires and tension-band fixation through posterolateral minimal incision approach can obtain clearer surgical field, simple in operation, and few wound complications. Therefore, this modified treatment is an effective and reliable method for pediatric displaced Gartland type III supracondylar humeral fractures.

Adolescent ; Bone Wires ; Casts, Surgical ; Child ; Child, Preschool ; Female ; Fracture Fixation, Internal ; methods ; Humans ; Humeral Fractures ; surgery ; Male ; Supine Position

On account of the dense cuticles of the fresh stem and the light, hard and pliable texture of the dried stem, Dendrobii Caulis is difficult to dry or pulverize. So, it is very important to the ancient doctors that Dendrobii Caulis should be properly treated and applied to keep or evoke its medicinal effects. The current textual research results about the preliminary processing, processing and usage methods of Dendrobii Caulis showed that: (1) In history the clinical use of fresh or processed Dendrobii Caulis as teas and tinctures were very common. (2) Its roots and rhizomes would be removed before using. (3) Some ancillary approaches were applied to shorten drying times, such as rinsing with boiling mulberry-ash soup, washing or soaking with liquor, mixing with rice pulp and then basking, etc. (4) According to the ancients knowledge, the sufficient pulverization, by means of slicing, rasping, hitting or pestling techniques, was necessary for Dendrobii Caulis to take its effects. (5) The heat processing methods for Dendrobii Caulis included stir-baking, stir-frying, steaming, decocting and stewing techniques, usually with liquor as an auxiliary material. Among above mentioned, steaming by pretreating with liquor was most commonly used, and this scheme was colorfully drawn in Bu Yi Lei Gong Pao Zhi Bian Lan (Ming Dynasty, 1591 CE) ; moreover, decocting in advance or long-time simmering so as to prepare paste products were recommended in the Qing Dynasty. (6) Some different processing programs involving stir-baking with grit, air-tightly baking with ondol (Kangs), fumigating with sulfur, which appeared in modern times and brought attractive outward appearance of the drug, went against ancients original intentions of ensuring drug efficacy.
Dendrobium ; History, Ancient ; Medicine, Chinese Traditional ; history ; Technology, Pharmaceutical ; history

Objective To investigate and compare the pharmacokinetics of midazolam in Chinese Korean and Han healthy volunteers after oral administration.Methods Nine healthy Chinese Korean volunteers and ten healthy Han volunteers were given 15 mg midazolam tablets.The concentration of midazolam in plasma was determined by HPLC method and the pharmacokinetic parameters were calculated by DAS 2.0.1 software.Results The pharmacokinetic parameters of midazolam in Chinese Korean and Han were as follow:t_(max) were(0.63±0.72)and(1.52±0.74)h,C_(max) were(189.03 4±82.05) and (103.11±26.37)μg·L~(-1),t_(1/2) were (3.82±2.33) and (2.96±0.77)h,AUC_(0-12) were (369.75±85.47) and (368.95±103.63)μg·h·L~(-1),AUC_(0-∞) were (403.29±124.28) and (397.29±124.06)μg·h·L~(-1),respectively. Conclusion There is large interindividual variabilities in pharmacokinetic parameters of Chinese Korean and Han healthy volunteers,after administration.There were double peaks in plasma concentration-time profile after oral administration.There is significant difference in the t_(max) and C_(max) between Chinese Korean and Han healthy volunteers.

OBJECTIVETo explore the effect of 18-β glycyrrhetinic acid (GA) on the endoplasmic reticulum of nasal epithelial cells in allergic rhinitis (AR) model rats.

METHODSTotally 96 Wistar rats were randomly divided into the blank group, the AR model group, the loratadine group, the GA group, 24 in each group. AR models were established by peritoneally injecting ovalbumin (OVA). Morphological scoring was performed. GA at 21. 6 mg/kg was intragastrically administered to rats in the GA group. Nasal mucosal tissues were taken for electron microscopic examinations at the second, fourth, sixth, and tenth week after drug intervention.

RESULTSThe overlapping score was 2.10 ± 0.45 in the blank group, 5.10 ± 0.56 in the loratadine group, 5.10 ± 0.56 in the AR model group, 5.20 ± 0.78 in the GA group, showing statistical difference when compared with the blank group (P < 0.01). Results under transmission electron microscope showed that the number of the endoplasmic reticulum increased in the AR model group, with obvious cystic dilatation, a lot of vacuole formation, and degranulation. A large number of free ribosomes could be seen in cytoplasm. With persistent allergen exposure, changes mentioned above was progressively aggravated in the endoplasmic reticulum of nasal mucosal epithelium in the AR model group. But the dilation of endoplasmic reticulum, vacuole formation, and degranulation were relieved in the GA group, and got close to those of the blank group.

CONCLUSION18-β GA could improve the expansion, vacuolization, and degranulation of the endoplasmic reticulum of nasal epithelial cells in AR model rats.

Animals ; Anti-Inflammatory Agents ; pharmacology ; therapeutic use ; Endoplasmic Reticulum ; Epithelial Cells ; drug effects ; Glycyrrhetinic Acid ; pharmacology ; therapeutic use ; Nasal Mucosa ; drug effects ; Rats ; Rats, Wistar ; Rhinitis, Allergic ; drug therapy

Objective To explore the imaging characteristics of hemiplegic patients with intractable epilepsy before and after modified hemispherectomy and their clinical significances.Methods The clinical data of 29 patients,admitted to and underwent hemispherectomy in our hospital from 1996 to 2010,were retrospectively analyzed.The characteristics ofpre-and post-surgical imaging of these patients were analyzed.Results Pre-surgical imaging showed that the crus cerebri of healthy lateral was enlarged for compensation and another lateral was atrophy with illed hemisphere.Hemispherectomy succeed in all the patients on the illed hemisphere; post-surgical imaging showed that operative cavity was reduced through healthy hemisphere shiftting to operative lateral,frontal sinus enlarging and skull becoming thickness.Follow-up was performed for 2-15 years; the disturbance of the nervous function was not worsened and there was no late complication in all the patients; Engel grading showed grade Ⅰ and Ⅱin 93.1％ patients and grade Ⅲ in 6.9％.Conclusion The CT/MR imaging is more valuable in localizing of the lesions as compared with EEG; the imaging changes before and after hemispherectomy can explain the shrunk cacity and few late complications.

OBJECTIVETo observe the effect of an external film of hyaluronic acid (HA) on the rats wound healing.

METHODSForty-eight SD rats were randomly separated into eight groups of 6 rats each. Bilateral dorsal cuts were performed on each rat, left wound was used as the experiment with HA external film and right wound was used as the control only with normal saline. The process of healing was observed histologically following 1st, 3rd, 5th, 7th, 9th, 14th, 21st, and 28th days postoperatively.

RESULTSInflammation was lighter and epidermal healing was faster in the experimental group than those in the control. The fibroblasts degenerated and the collagen fiber changed to slim and loose bunches in the experimental group.

CONCLUSIONThe results indicated that HA external film could have powerful infiltrating activity at the early stage of wound healing, it could accelerate the healing of epidermis and delay the formation of keratinization layer.

Animals ; Collagen ; metabolism ; Drug Administration Routes ; Fibroblasts ; drug effects ; metabolism ; Hyaluronic Acid ; administration & dosage ; pharmacology ; Male ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Treatment Outcome ; Wound Healing ; drug effects