Objective To investigated the efficacy and toxic effects of combined chemotherapy of vinorelbine plus cisplatin or carboplatin in patients aged ≥ 70 years and with non-small cell lung cancer (NSCLC).Methods One hundred patients with lung cancer aged ≥70 years were enrolled in the study.Fifty patients in chemotherapy group were assigned to receive vinorelbine 25 mg/m2 at the first day and the fifth day plus cisplatin 60-70 mg/m2 or carboplatin 250 mg/m2 at the second day.All treatments were repeated every 3 or 4 weeks.Another fifty patients aged ≥ 70 years were taken as control group, not receiving treatment.The primary endpoint was survival.Results Forty-five patients were evaluable for response and the partial remission rate was 35.6% (16/45).One year survival rate was 37.8% and median survival time was 9.75 months in chemotherapy group.The median survival time was 4.0 months for patients in control group.All 50 patients in chemotherapy group were evaluable for toxic side effects.WHO grade Ⅲ incidences of leucopoenia, neutropenia and anemia were 38.0%, 52.0% and 2.2%, respectively.Grade IV incidence of neutropenia was 35.5%.WHO grade Ⅲ incidences of fatigue, constipation and vomit were 22.0%, 8.0% and 14.8%,respectively.Five patients failed to complete the treatment due to side effects.Conclusions Combined chemotherapy of vinorelbine plus platinum drugs is effective and tolerated in patients aged over 70 years with advanced NSCLC.Even patients with stable clinical effects shows benefit of survival time.

Bone formation on hydroxyapatite (HA) coating in the presence of gaps is important for clinical application. Pure Ti and hydroxyapatite coated by plasma sprayed samples were implanted in dog respectively. The implants were surrounded by gaps of 2 mm, and the follow-up period was 12 weeks. Histological examination and histomorphometry revealed that gaps could be bridged by bone provided the hydroxyapatite coating was applied, and that pure Ti implants were surrounded by fibrous tissue with no bone contact at all.
Animals ; Bone Substitutes ; Coated Materials, Biocompatible ; pharmacology ; Dogs ; Femur ; injuries ; surgery ; Hydroxyapatites ; pharmacology ; Implants, Experimental ; Male ; Osseointegration ; Osteogenesis ; drug effects ; Titanium

BACKGROUNDTo evaluate the activity and toxicity of paclitaxel as second-line treatment for advanced non-small cell lung cancer (NSCLC).

METHODSForty patients with recurrent advanced NSCLC were enrolled. Thirty-six patients were managed with regular regimen. Paclitaxel 135 mg/m², 3 h, on day 1; DDP 75 mg/m² or carboplatin 300-350 mg/m² on day 2. Four patients were managed with weekly regimen. Paclitaxel 60 mg/m²,3 h, on days 1,8,15; DDP 75 mg/m² on day 2. It was repeated every three or four weeks, up to two to four cycles.

RESULTSThirty-six cases were evaluated for response and 27 for survival. The objective response rate was 13.9% (5/36). At least one tumor-related symptom relief was observed in 21 patients (58.3%). The median survival duration was 26.4 weeks and 1-year survival rate was 8% (4/36). The main toxicities included myelosuppression, fatigue and myalgia-arthralgia neuropathy.

CONCLUSIONSPaclitaxel has advantage to be well-tolerated and improve tumor-related symptom. Further studies with standardization of dose and regimen will be needed to clarify its role in the second-line treatment.

OBJECTIVETo investigate the expression of TMEMl6A in the colon of intractable functional constipation patients and its clinical implications.

METHODSA total of 30 patients with intractable chronic functional constipation were selected as trial group (full thickness tissue of sigmoid colon), 30 patients with colon cancer as control group (distant tissues at least 5 cm away from cancer). Tissues from two groups were collected in our hospital from February 2012 to June 2014 and confirmed by pathological diagnosis. Immunofluorescence staining, RT-PCR and Western blot were performed to detect the mRNA and protein expression of TMEM16A and c-kit in colon.

RESULTSTMEM16A and c-kit protein expressions were observed in similar sites of colon tissues in two groups. Expressions of TMEM16A and C-kit in colon tissues detected by immunofluorescence, RT-PCR, and Western blotting were significantly lower in trial group than those in control group (TMEM16A: mean A 1.84±0.25 vs. 3.65±0.32, P<0.05, gray intensity ratio 0.66±0.07 vs. 1.04±0.17, P<0.05, relative mRNA 0.41±0.05 vs. 1.00, P<0.05; c-kit: mean A 3.38±0.24 vs. 5.06±0.31, gray intensity ratio 0.64±0.06 vs. 0.98±0.09, relative mRNA 0.18±0.08 vs. 1.00, all P<0.05).

CONCLUSIONSTMEM16A expression in colon tissues of intractable functional constipation patients is significantly lower and may adjust the movement of colonic smooth muscle by regulating the c-kit expression. TMEMl6A may be used as a new candidate target for diagnosis and treatment of intractable functional constipation.

Anoctamin-1 ; Blotting, Western ; Chloride Channels ; Colon, Sigmoid ; Colonic Neoplasms ; Constipation ; Humans ; Muscle, Smooth ; Neoplasm Proteins ; Proteomics ; Proto-Oncogene Proteins c-kit ; RNA, Messenger

OBJECTIVETo establish an innovative rat model of slow transit constipation by selective chemical ablation of the colon enteric plexus.

METHODSSprague Dawley rats, 5-6 weeks old, were randomly divided into normal control group, sham operation group, treatment group I, II, III, IIII. The normal control group did not receive treatment. Rats in the sham operation group and the treatment groups received abdominal operation under anesthesia, and the gauze containing 0.9% normal saline, 0.05%, 0.1%, 0.25%, 0.5% benzalkonium chloride (BAC) was applied into colon for 30 minutes. Two weeks after operation, the number of feces, fecal dry weight in 24 h and gastrointestinal transit time were recorded, then hematoxylin-eosin (HE) staining, immunohistochemistry, ELISA were used for the evaluation of colonic pathology, enteric plexus, Interstitial cells of Cajal and neurotransmitters 5-hydroxytryptamine(5-HT).

RESULTSCompared to the normal control group and the sham operation group, the gastrointestinal transit time was significantly prolonged and fecal dry weight was lower in the treatment group II, III (all P<0.05). HE and immunohistochemical staining showed varying degrees of pathological changes in the treatment groups and in line with the pathological changes of slow transit constipation. 5-HT concentration reduced significantly in treatment group III compared to other groups (P<0.01).

CONCLUSIONThe animal model of STC is successfully established by applying 0.25% BAC selective chemical ablation of the colon enteric plexus. This model is simple, stable, and is more in line with pathological changes of slow transit constipation.

Animals ; Autonomic Pathways ; Constipation ; Disease Models, Animal ; Gastrointestinal Transit ; Immunohistochemistry ; Interstitial Cells of Cajal ; Rats ; Rats, Sprague-Dawley

OBJECTIVETo investigate the safety, efficacy and long-term outcomes of Jinling procedure in the treatment of adult Hirschsprung disease.

METHODSClinical and follow-up data of 125 patients with adult Hirschsprung disease undergoing Jinling procedure at the Department of General Surgery between January 2000 and January 2013 were summarized. All the patients were diagnosed by CT, barium enema, anorectal pressure detection and pathology examination. Abdominal symptoms, gastrointestinal quality of life index(GIQLI, the lower score, the worse quality of life), Wexner constipation score (higher score indicated worse symptom), defecography (evaluation included rectocele, mucosal prolapse, intramucosal intussusception, perineal prolapse) and other operative complications were compared before and after operation.

RESULTSAmong 125 patients, 69 were male and 56 were female with median age of (41.2±15.5) (18 to 75) years. The follow-up rates were 94.4%(118/125), 92.0%(115/125), 89.6%(112/125) and 88.0%(110/125) at postoperative months 1, 3, 6, and 12. Incidences of abdominal distension and abdominal pain were 100% and 82.4%(103/125) before operation, and were 7.3%(8/110) and 20.9%(23/110) at 12 months after surgery. Wexner score was significantly lower at postoperative months 1(8.7±2.9), 3 (7.2±2.8), 6(6.7±2.2) and 12(6.3±1.7) than that before operation (21.4±7.2) (P<0.01). GIQLI score was 51.6±11.9 before operation, though it decreased at 1 month (47.3±5.5)(P<0.05) after surgery, but increased significantly at postoperative months 3, 6, 12(68.9±8.0, 96.5±8.2, 103.2±8.6)(P<0.01). Abnormal rate of defecography was 70.4%(81/115), 48.2%(54/112) and 27.3%(30/110) at postoperative months 3, 6, 12, which was significantly lower than 91.2%(114/125) before operation (P<0.01). Morbidity of postoperative complication was 29.6%(37/125), including 5 cases of surgical site infection (4.0%), 2 of anastomotic bleeding (1.6%), 8 of anastomotic leakage (6.4%, one died of severe abdominal infection), 4 of urinary retention (3.2%), 3 of recurrent constipation (2.4%, without megacolon relapse), 11 of bowel obstruction (8.8%), 2 of anastomotic stricture(1.6%) and 2 of refractory staphylococcus aureus enteritis (1.6%, diagnosed by stool smear and culture, and both died finally).

CONCLUSIONJinling procedure is a safe and effective surgical procedure for adult Hirschsprung's disease.

Adolescent ; Adult ; Aged ; Anastomosis, Surgical ; Colectomy ; Constipation ; Defecography ; Digestive System Surgical Procedures ; Female ; Hirschsprung Disease ; surgery ; Humans ; Intestinal Obstruction ; Intussusception ; Male ; Middle Aged ; Perineum ; Postoperative Complications ; Postoperative Period ; Quality of Life ; Rectocele ; Staphylococcus aureus ; Treatment Outcome ; Young Adult

BACKGROUNDTo evaluate the efficacy, side-effects, median survival duration and survival rate of vinorelbine (NVB) combined with cisplatin (DDP) in the treatment of non-small cell lung cancer (NSCLC).

METHODSA total of 220 patients with inoperable NSCLC received NVB and DDP combined chemotherapy: NVB 25-30 mg/(m²*d) on days 1 and 5 (or 8), DDP 60-80 mg/(m²*d) on day 2. The schedule was repeated every 28 days. The efficacy and side-effects were analysed and followed-up after at least two cycles of chemotherapy.

RESULTSThe overall response rate (CR+PR) was 30.9% (68/220). The response rate was 31.3% (51/163) in initial treatment group, and 29.8% (17/57) in retreatment group. The median survival duration was 8.3 months. The 1-, 2- and 3-year survival rates were 39.23%, 19.31% and 6.32%, respectively. The main side-effects were myelosuppression and digestive tract reactions.

CONCLUSIONSVinorelbine plus cisplatin is an effective and well-tolerated regimen for non small cell lung cancer and myelosuppression is its dose-limiting toxicity.

BACKGROUNDUroacitides is a group of cell differentiation inducers, which is purified from fresh human urine. Preclinical studies of Uroacitides have showed that cancer cells could be induced to differentiate, and the growth of cancer cells could be inhibited by Uroacitides. The aim of this study is to compare the efficacy and toxicity between Uroacitides combined with NP regimen and NP alone in treatment of advanced non-small cell lung cancer (NSCLC).

METHODSForty-two cases of advanced NSCLC were randomized into Uroacitides+NP and NP groups. NP group: NVB 25mg/m² on days 1 and 8, DDP 75mg/m² on day 1. Uroacitides combined with NP group: Uroacitides of 300mL was given through subclavian catheter daily for 7 days prior to the NP chemotherapy, then concurrently with NP regimen for 2 cycles, except the days of administration of chemotherapy.

RESULTSIn the Uroacitides+NP group, the overall response rate was 44.4%, and 20.0% in the NP group (P > 0.05). The median survival time was 9 months in the Uroacitides+NP group and 6 months in the NP group (P=0.0287). The main toxicities were myelosuppression, gastrointestinal reaction and alopecia, and there was no significant difference in incidences of toxicities between the two groups (P > 0.05).

CONCLUSIONSUroacitides combined with NP regimen shows a good curative effect and low toxicity, and may significantly prolong the median survival time for advanced NSCLC.

Cytomegalovirus (CMV) is distinct among members of the Herpesviridae family for having the largest dsDNA genome (230 kb). Packaging of large dsDNA genome is known to give rise to a highly pressurized viral capsid, but molecular interactions conducive to the formation of CMV capsid resistant to pressurization have not been described. Here, we report a cryo electron microscopy (cryoEM) structure of the murine cytomegalovirus (MCMV) capsid at a 9.1 Å resolution and describe the molecular interactions among the ∼3000 protein molecules in the MCMV capsid at the secondary structure level. Secondary structural elements are resolved to provide landmarks for correlating with results from sequence-based prediction and for structure-based homology modeling. The major capsid protein (MCP) upper domain (MCPud) contains α-helices and β-sheets conserved with those in MCPud of herpes simplex virus type 1 (HSV-1), with the largest differences identified as a "saddle loop" region, located at the tip of MCPud and involved in interaction with the smallest capsid protein (SCP). Interactions among the bacteriophage HK97-like floor domain of MCP, the middle domain of MCP, the hook and clamp domains of the triplex proteins (hoop and clamp domains of TRI-1 and clamp domain of TRI-2) contribute to the formation of a mature capsid. These results offer a framework for understanding how cytomegalovirus uses various secondary structural elements of its capsid proteins to build a robust capsid for packaging its large dsDNA genome inside and for attaching unique functional tegument proteins outside.
Amino Acid Sequence ; Capsid Proteins ; chemistry ; metabolism ; ultrastructure ; Cryoelectron Microscopy ; Models, Molecular ; Molecular Sequence Data ; Muromegalovirus ; chemistry ; ultrastructure ; Protein Binding ; Protein Multimerization ; Protein Structure, Quaternary ; Protein Structure, Tertiary