[Effect of P311 microspheres-loaded thermosensitive chitosan hydrogel on the wound healing of full-thickness skin defects in rats].

Objective: To explore the effect of P311 microspheres-loaded thermosensitive chitosan hydrogel on the wound healing of full-thickness skin defects in rats. Methods: The method of experimental study was adopted. The polyvinyl alcohol/sodium alginate microspheres (simple microspheres), P311 microspheres, and bovine serum albumin labeled with fluorescein isothiocyanate (FITC-BSA) microspheres were prepared by water-in-oil emulsification, and then their morphology was observed under a light microscope/inverted fluorescence microscope. Chitosan solution was prepared, chitosan solution and ß-glycerol phosphate disodium hydrate were mixed to prepare simple thermosensitive hydrogels, and thermosensitive hydrogels loaded with simple microspheres or P311 microspheres were prepared by adding corresponding substances in simple thermosensitive hydrogels. The morphological changes of the prepared four liquids in the state of tilt was observed at 37 ℃. After being freeze-dried, the micromorphology of the prepared four liquids was observed under a scanning electron microscope. Eighteen 3-4-week-old male Sprague-Dawley rats were divided into normal group without any treatment, dressing group, chitosan group, hydrogel alone group, simple microspheres-loaded hydrogel group, and P311 microspheres-loaded hydrogel group, which were inflicted with one full-thickness skin defect wound on both sides of the back spine and were dealt correspondingly, with 3 rats in each group. Rats with full-thickness skin defects in the five groups were collected, the wound healing was observed on post injury day (PID) 0 (immediately), 5, 10, and 15, and the wound healing rates on PID 5, 10, and 15 were calculated. The wound and wound margin tissue of rats with full-thickness skin defects in the five groups on PID 15 and normal skin tissue in the same site of rats in normal group were collected, hematoxylin and eosin staining was conducted to observe the histological changes, immunohistochemical staining was performed to observe the expressions of CD31 and vascular endothelial growth factor (VEGF), and Western blotting was conducted to detect the protein expressions of CD31 and VEGF. The number of samples was all three. Data were statistically analyzed with one-way analysis of variance, analysis of variance for repeated measurement, and Bonferroni correction. Results: Simple microspheres were spherical, with loose and porous surface. The surfaces of P311 microspheres and FITC-BSA microspheres were smooth without pores, and the FITC-BSA microspheres emitted uniform green fluorescence. The diameters of the three microspheres were basically consistent, being 33.1 to 37.7 µm. Compared with chitosan solution and simple thermosensitive hydrogel, the structures of the two microspheres-loaded hydrogels were more stable in the state of tilt at 37 ℃. The two microspheres-loaded hydrogels had denser network structures than those of chitosan solution and simple thermosensitive hydrogel, and in the cross section of which microspheres with a diameter of about 30 µm could be seen. Within PID 15, the wounds of rats in the five groups were healed to different degrees, and the wound healing of rats in P311 microspheres-loaded hydrogel group was the best. On PID 5, 10, and 15, the wound healing rates of rats in dressing group and chitosan group were (26.6±2.4)%, (38.5±3.1)%, (50.9±1.5)%, (47.6±2.0)%, (58.5±3.6)%, and (66.7±4.1)%, respectively, which were significantly lower than (59.3±4.8)%, (87.6±3.2)%, (97.2±1.0)% in P311 microspheres-loaded hydrogel group (P<0.05 or P<0.01). The wound healing rates of rats in hydrogel alone group on PID 10 and 15, and in simple microspheres-loaded hydrogel group on PID 15 were (76.0±3.3)%, (84.5±3.6)%, and (88.0±2.6)%, respectively, which were significantly lower than those in P311 microspheres-loaded hydrogel group (P<0.05). The epidermis, hair follicles, and sebaceous glands could be seen in the normal skin of rats in normal group, without positive expressions of CD31 or VEGF. The wounds of rats in P311 microspheres-loaded hydrogel group on PID 15 were almost completely epithelialized, with more blood vessels, hair follicles, sebaceous glands, and positive expressions of CD31 and VEGF in the wounds than those of rats with full-thickness skin defects in the other four groups, and more protein expressions of CD31 and VEGF than those of rats in the other five groups. Conclusions: The P311 microspheres-loaded thermosensitive chitosan hydrogel can release the encapsulated drug slowly, prolong the drug action time, and promote wound healing in rats with full-thickness skin defects by promoting wound angiogenesis and re-epithelialization.

[Comparison of long-term outcomes between endoscopic submucosal dissection and surgical resection for early gastric cancer with undifferentiated histology].

Objective: Endoscopic submucosal dissection (ESD) of undifferentiated early gastric cancer (UD-EGC) remains controversial due to high positive rate of horizontal and vertical resection margins and the risk of lymph node metastasis. The purpose of this study was to compare long-term outcomes of patients with UD-EGC undergoing ESD versus surgery. Methods: This study was a retrospective cohort study. Inclusion criteria: (1) patients with early gastric cancer undergoing ESD or surgical resection; (2) histological types included poorly differentiated adenocarcinoma, poorly differentiated adenocarcima with signet ring cell carcinoma, and signet ring cell carcinoma; (3) no lymph node metastasis or distant metastasis was confirmed by preoperative CT and endoscopic ultrasonography. Exclusion criteria: (1) previous surgical treatment for gastric cancer; (2) synchronous tumors; (3) death with unknown cause; (4) additional surgical treatment was performed within 1 month after ESD. According to the above criteria, clinical data of patients with UD-EGC who received ESD or surgery treatment in Cancer Hospital of Chinese Academy of Medical Sciences from January 2009 to December 2016 were collected. After further comparing the clinical outcomes between the two groups by 1:1 propensity score matching, 61 patients in the ESD group and 61 patients in the surgery group were finally included in this study. The disease-free and overall survivals were analyzed by Kaplan-Meier method. Results: All patients in the two groups completed operations successfully. In the ESD group, the median operation time was 46.3 (26.5, 102.3) minutes, 61 cases (100%) were en-bloc resection, and 57 cases (93.4%) were complete resection. Positive margin was found in 4 (6.6%) patients, of whom 2 were positive in horizontal margin and 2 were positive both in horizontal and vertical margins. In the surgery group, only 1 case had positive horizontal margin and no positive vertical margin was observed. There was no significant difference in the positive rate of margin between the two groups (P>0.05). Median follow-up time was 59.8 (3.0, 131.5) months. The follow-up rate of ESD group and surgery group was 82.0% (50/61) and 95.1% (58/61), respectively. The 5-year disease-free survival rate in ESD group and surgery group was 98.2% and 96.7%, respectively (P=0.641), and the 5-year overall survival rate was 98.2% and 96.6%, respectively (P=0.680). In the ESD group, 1 patient (1.6%) had lymph node recurrence, without local recurrence or distant metastasis. In the surgery group, 1 case (1.6%) had anastomotic recurrence and 1 (1.6%) had distant metastasis. Conclusion: ESD has a sinilar long-term efficacy to surgery in the treatment of UD-EGC.

[Clinical outcomes of endoscopic piecemeal mucosal resection for superficial esophageal carcinoma and precancerous lesions].

Objective: To explore the short and long-term outcomes of endoscopic piecemeal mucosal resection including endoscopic mucosal resection (EMR) and multiband mucosectomy (MBM) for superficial esophageal carcinoma and precancerous lesions, and analyze the risk factors for prognosis. Methods: From March 1 2001 to May 31 2017, 371 patients with 416 lesions who were diagnosed as superficial esophageal carcinoma or high-grade intraepithelial neoplasm and underwent EMR or MBM were retrospectively enrolled in this study. Long-term recurrence free survival (RFS) rate and the risk factors, including submucosal invasion, poorly differentiation, vascular invasion and positive vertical margin, for the long-term outcome were also analyzed. Results: The incidence of complication was 17.1% in the EMR group and 17.4% in the MBM group, without significant difference (P=1.000). The median follow-up period was 70.6 months. The 5-years RFS was 93.9% and 10-years RFS was 87.8%, respectively. Local recurrence was found in 2 cases in each group and they were curatively treated by endoscopic submucosal dissection. Heterogeneous multiple primary esophageal cancer was diagnosed in 5 and 3 cases for the EMR and MBM group, of whom 5 cases were curatively treated with endoscopic resection. Other 3 cases were diagnosed with advanced esophageal cancer, of whom 2 patients died. Lymph node metastasis (LNM) was found in 5 cases in the EMR group and 4 cases in the MBM group, of whom 6 patients died. Distant metastasis was found in 5 cases in the EMR group and 3 cases in the MBM group, of whom 5 patients died. There were 83 patients combined with risk factors including submucosal invasion, poorly differentiation, vascular invasion and positive vertical margin, of whom 8 patients were diagnosed as LNM and 8 patients as distant metastasis. The 5-years RFS of patients with 1, 2, and 3 risk factors were 93.6%, 82.2%, and 25.0%, and the difference was statistically significant (P<0.001). Conclusions: EMR and MBM are both safe and feasible procedures for superficial esophageal carcinoma and precancerous lesions. Additional treatments should be selected according to the variety of risk factors to acquire better long-term outcome and life quality.

[Therapeutic effect of endoscopic submucosal dissection on the treatment of early gastric cancer].

Objective: To analyze the long-term therapeutic effect of endoscopic submucosal dissection (ESD) on the treatment of early gastric cancer (EGC). Methods: We retrospectively reviewed EGC patients who underwent ESD at Cancer Hospital, Chinese Academy of Medical Sciences (CAMS), from January 2009 to December 2016. The incidence rates of local recurrence, synchronous cancer and heterogeneous cancer were analyzed. Kaplan-Meier method was used to analyze 5-years recurrence free survival (RFS) and 5-years disease special survival (DSS) of all patients. Results: A total of 255 EGC patients were enrolled in this study, included 175 differentiated early gastric cancer (D-EGC) patients and 80 undifferentiated early gastric cancer (UD-EGC) patients. Among them, 171 patients within the extended indication of ESD while 84 patients beyond the extended indication of ESD. Among the 225 patients, the incidence rates of local recurrence, synchronous cancer and heterogeneous cancer were 2.0%, 2.0% and 2.4%, respectively. The local recurrence rates of D-EGC group and UD-EGC group was 1.7% and 2.5%, respectively, without significant difference (χ(2)=0.176, P=0.675). The incidence rates of synchronous and heterogenous cancer in the D-EGC group were 2.3% and 3.4%, higher than 1.2% and 0 of UD-EGC group, although there was no significant difference (χ(2)=0.306, P=0.580 vs χ(2)=2.809, P=0.094). There were no significant differences in 5-years RFS (91.3% vs 95.9%, P=0.236) and 5-years DSS (100% vs 98.6%, P=0.156) between D-EGC group and UD-EGC group. Conclusions: The long-term outcome of ESD in the treatment of EGS is good. More attention should be paid to the occurrence of local recurrence and heterogeneous cancer in EGC patients undergo ESD. These patients still have a good long-tern outcome even undergoing ESD for more than once.

[Long-term outcome after endoscopic resection for early colorectal carcinoma].

Objective: To analysis the clinical and follow-up data of the early colorectal carcinoma (ECC) after endoscopic resection, and explore the long-term outcome of patients who underwent the endoscopic resection. Methods: During June 2008 to June 2016, data of endoscopic resection for 550 cases of ECC were collected, including general information and follow-up data. The influence factors of disease-free survival rate of ECC after endoscopic resection were analyzed and the risk factors on long-term outcomes such as submucosa invasion depth, poorly differentiated adenocarcinoma, vascular invasion and positive vertical margin were investigated. Results: The mean follow-up time of 550 patients treated with endoscopy was (60.7±36.8) months. Among them, 433 cases were high-level intra-mucosal neoplasia, 117 cases were submucosa invasion carcinoma (the invasion depth <1 000 µm were 33 cases, ≥1 000 µm were 84 cases), 461 cases were curative resection, while 89 cases were non-curative resection. During the follow-up, 6 patients occurred recurrence or metastasis, including 2 patients with local recurrence (1 patient accompanied by lymph node metastasis) and 4 patients with lymph node metastasis (2 patients accompanied by distant metastasis). The overall 5-years disease-free survival rate was 98.8%, the 5-years disease-free survival rate was 100.0% for patients with curative resection and 93.3% for patients with non-curative resection. A total of 89 cases underwent non-curative resection were accompanied with invasion depth ≥1 000 µm, vascular invasion, poorly differentiated adenocarcinoma and positive vertical margin. Among them, 62 cases were accompanied with 1 risk factor, 23 cases with 2 risk factors and 4 cases with 3 risk factors. The risks of lymph nodes and distant metastasis raised with the increase of risk factors. Conclusions: The incidence of lymph node metastasis in ECC is extremely low. Endoscopic treatment can achieve a good long-term outcome. Close follow-up should be conducted after endoscopic treatment, and additional treatment should be selected reasonably for the early colorectal carcinoma after endoscopic non-curative resection to improve the therapeutic efficacy of endoscopic resection.

Association of xeroderma pigmentosum group D (Asp312Asn, Lys751Gln) and cytidine deaminase (Lys27Gln, Ala70Thr) polymorphisms with outcome in Chinese non-small cell lung cancer patients treated with cisplatin-gemcitabine.

Xeroderma pigmentosum group D (XPD) plays a key role in the repair of DNA and platinum resistance lesions. Cytidine deaminase (CDA) genes determine the velocity of gemcitabine catalysis. This study aimed to investigate the relationship between XPD and CDA genotypes and outcome in non-small lung cancer (NSCLC) patients. We used polymerase chain reaction-restriction fragment length polymorphism to evaluate genetic polymorphisms of XPD (Asp312Asn and Lys751Gln) and CDA (Lys27Gln and Ala70Thr) in 93 NSCLC patients treated with a cisplatin-gemcitabine regimen. There were no significant correlations between the XPD polymorphisms Asp312Asn and Lys751Gln with clinical benefits (P>0.05). Time to progression (TTP) did not differ between patients with wild type genotypes and those heterozygous for the single nucleotide polymorphism loci of XPD. However, a significant difference was observed in overall survival (OS) between XPD Asp312Asp and XPD Asp312Asn individuals (20.0 vs 12.4 months, P=0.04). Furthermore, the OS of patients with wild type genotypes was longer (20.5 months) than that of patients carrying the XPD 751Lys/Gln polymorphism (11.5 months). No significant differences in TTP or OS were observed in patients carrying different genotypes of CDA Lys27Gln, and no mutations were observed at the CDA Ala70Thr site. These results provide suggestive evidence of a favorable effect for the XPD 312Asp/Asp and XPD 751Lys/Lys genotypes with respect to overall survival rates in platinum-treated NSCLC patients. However, the CDA 27 polymorphism does not appear to affect the efficacy of gemcitabine.

[Clinical study on treatment of early glottic carcinoma with different cordectomy].

OBJECTIVE: To explore the advantage of KTP laser cordectomy in the treatment of early glottic carcinoma. METHOD: Follow-up observation on 30 patients who had KTP laser cordectomy and 18 patients who had laryneal split cordectomy was applied, then their postoperative laryngeal structure's change, the quality of voice and the quality of life (QOL) were compared and analyzed. RESULT: The patient group treated by KTP laser grew out a piece of new cord just at the place where it was excised after half a year, and the quality of voice was obviously improved near to norm, and they had higher QOL. On the contrary, the other group had no newly grown cord, their quality of voice was better in the first half year but was worse last out. Their QOL was lower than the laser group before decannulation and the same as the laser group after the decannulation. There are 2 cases recurrented in the laser group and 1 case recurrented in the laryneal split group, the two groups all had no metastasis and death in laryneal carcinoma by 2-4 years follow up postoperation. CONCLUSION: On the basis of effecting radical cure, the early glottic carcinoma treated with non-contact KTP laser with suspension laryngoscope can result in good recuperating in laryngeal structure, less injury and high QOL. So it makes micro-injury treatment in laryngeal carcinoma come true and better than the laryngeal split cordectomy.

[Light and electron microscopic studies on lichen sclerosus et atrophicus of the vulva before and after treatment].

Light and electron microscopic studies were carried out on 17 cases of lichen sclerosis et atrophicus of the vulva before treatment and on 8 after treatment. For comparison, normal vulval skin was obtained for examination from 3 cases undergoing plastic surgery. The affected skin, prior to therapy, showed various degrees of atrophic and degenerative changes with widening of intercellular spaces and a diminished number of desmosomes. Increased epithelial keratosis was noted and melanotic granules decreased or totally disappeared. Collagenolysis with broken fibers and degenerative changes of arteriolar walls with scarcity of nerve fibers were noticed in the dermal layer. Round cell infiltration was rather marked. Following therapy, the different layers of the involved skin showed signs of returning to normal. Pathogenesis of the disease was briefly discussed.