Platelet-rich plasma regulating the repair of ultraviolet B-induced acute tissue inflammation: adjusting macrophage polarization through the activin receptor-follistatin system.

Ultraviolet B (UVB) is one of the most common exogenous factors in skin aging, especially photoaging. Once a large amount of UVB accumulates within a short period of time, skin tissue can become inflamed. It has also been found in clinics that platelet-rich plasma (PRP) can promote wound repair; therefore, the aim of this study was to identify the mechanism by which PRP repairs UVB-induced skin photodamage. We used PRP of Sprague-Dawley rats with the two-spin technique in the established acute UVB radiation photodamage model and harvested the corresponding skin after 1, 7, and 28 d. Hematoxylin and eosin staining was used to observe tissue inflammation. We found that PRP reduces inflammation in the early stages of UVB-induced acute skin damage, and then promotes the proliferation of collagen in the middle and late stages. Moreover, PRP can stimulate Act A and M1 polarization in the early stage, while inhibiting activin A (Act A) and inducing M2 polarization in the middle and late stages. In conclusion, this study demonstrates that PRP plays an important regulatory role in helping reduce UVB-induced acute skin tissue inflammation by adjusting macrophage polarization, which alleviates skin inflammation and stimulates collagen regeneration.

Corrigendum to "Protective Effects of Soy Oligopeptides in Ultraviolet B-Induced Acute Photodamage of Human Skin".

[This corrects the article DOI: 10.1155/2016/5846865.].

Famitinib versus placebo in the treatment of refractory metastatic colorectal cancer: a multicenter, randomized, double-blinded, placebo-controlled, phase II clinical trial.

BACKGROUND: Metastatic colorectal cancer (mCRC) patients with progressive disease after all available standard therapies need new medication for further treatment. Famitinib is a small-molecule multikinase inhibitor, with promising anticancer activities. This multicenter, randomized, double-blinded, placebo-controlled, phase II clinical trial was designed to evaluate the safety and efficacy of famitinib in mCRC. METHODS: Famitinib or placebo was administered orally once daily. The primary endpoint was progression-free survival (PFS). Secondary endpoints included objective response rate (ORR), disease control rate (DCR), overall survival (OS), quality-of-life (QoL), and safety. RESULTS: Between July 18, 2012 and Jan 22, 2014, a total of 167 patients were screened, and 154 patients were randomized in a 2:1 ratio to receive either famitinib (n = 99) or placebo (n = 55). The median PFS was 2.8 and 1.5 months in the famitinib and placebo groups (hazard ratio = 0.60, 95% confidence interval = 0.41-0.86, P = 0.004). The DCR was 59.8% and 31.4% (P = 0.002) and the ORR was 2.2% and 0.0% (P = 0.540) in the famitinib and placebo groups, respectively. The most frequent grade 3-4 adverse events were hypertension (11.1%), hand-foot syndrome (10.1%), thrombocytopenia (10.1%), and neutropenia (9.1%). Serious adverse events occurred in 11 (11.1%) patients in the famitinib group and 5 (9.1%) in the placebo group (P = 0.788). The median OS of the famitinib and placebo groups was 7.4 and 7.2 months (P = 0.657). CONCLUSION: Famitinib prolonged PFS in refractory mCRC patients with acceptable tolerability. Trial registration This study was registered on ClinicalTrials.gov (NCT01762293) and was orally presented in the 2015 ASCO-Gastrointestinal Symposium.

Protective Effects of Soy Oligopeptides in Ultraviolet B-Induced Acute Photodamage of Human Skin.

Aim. We explored the effects of soy oligopeptides (SOP) in ultraviolet B- (UVB-) induced acute photodamage of human skin in vivo and foreskin ex vivo. Methods. We irradiated the forearm with 1.5 minimal erythemal dose (MED) of UVB for 3 consecutive days, establishing acute photodamage of skin, and topically applied SOP. Erythema index (EI), melanin index, stratum corneum hydration, and transepidermal water loss were measured by using Multiprobe Adapter 9 device. We irradiated foreskin ex vivo with the same dose of UVB (180 mJ/cm(2)) for 3 consecutive days and topically applied SOP. Sunburn cells were detected by using hematoxylin and eosin staining. Apoptotic cells were detected by using terminal deoxynucleotidyl transferase dUTP nick end labeling assay. Cyclobutane pyrimidine dimers (CPDs), p53 protein, Bax protein, and Bcl-2 protein were detected by using immunohistochemical staining. Results. Compared with UVB group, UVB-irradiated skin with topically applied SOP showed significantly decreased EI. Compared with UVB group, topical SOP significantly increased Bcl-2 protein expression and decreased CPDs-positive cells, sunburn cells, apoptotic cells, p53 protein expression, and Bax protein expressions in the epidermis of UVB-irradiated foreskin. Conclusion. Our study demonstrated that topical SOP can protect human skin against UVB-induced photodamage.

Stevens-Johnson Syndrome and toxic epidermal necrolysis: a multi-aspect comparative 7-year study from the People's Republic of China.

BACKGROUND: Stevens-Johnson Syndrome (SJS) and toxic epidermal necrolysis (TEN) are rare but severe cutaneous drug reactions. They are differentiated based on the fraction of the body surface area affected. Optimal therapy for SJS and TEN is a controversial issue. OBJECTIVE: We compared the treatments given to and the clinical outcomes of 39 cases of SJS and 48 cases of TEN seen at a single institution between January 2007 and December 2013 for better understanding of the clinical characteristics and development of the two conditions. METHODS: Demographic data, clinical characteristics, treatments given, and therapeutic responses observed were retrospectively collected. RESULTS: The incidence rates of hypoproteinemia and secondary infections are significantly higher in TEN than in SJS (P=0.001 and P=0.002, respectively). The corticosteroid dose did not influence the time from the initiation of therapy to control of the lesions in SJS, but increasing the dosage of corticosteroids progressively decreased the time from the initiation of therapy to control of the lesions in TEN. With increases in the utilization ratio of intravenous immunoglobulin (IVIG), the length of the hospital stay became shorter, whereas the time from the initiation of therapy to control of the lesions remained the same in SJS. However, for TEN, both the length of the hospital stay and the time from the initiation of therapy to control of the lesions became shorter with increases in the utilization ratio of IVIG. CONCLUSION: SJS and TEN are two variants of the same spectrum, and they differ from each other not only in the severity of epidermal detachment but also in other clinical parameters and their distinct clinical courses. Thus, differential treatment of both conditions may have benefits for their prognosis.

The protective effect of baicalin against UVB irradiation induced photoaging: an in vitro and in vivo study.

OBJECTIVE: This study was aimed to evaluate the anti-photoaging effects of baicalin on Ultraviolet B (UVB)-induced photoaging in the dorsal skin of hairless mice and premature senescence in human dermal fibroblasts. METHODS: We established in vivo and in vitro photoaging models by repeated exposures to UVB irradiation. By HE staining, masson staining, immunohistostaing and real-time RT-PCR, we analyzed epidermal thickness, collagen expression and the mRNA and protein levels of type I collagen, type III collagen, interstitial collagenase (MMP-1 and MMP-3) in UVB exposed dorsal mice skin. The aging condition in human dermal fibroblasts was determined by senescence-associated ß-galactosidase (SA-ß-gal) staining. Cell viability was determined using the Cell Counting Kit-8 (CCK-8). The G1 phase cell growth arrest was analyzed by flow cytometry. The senescence-related protein levels of p16INK-4a, p21WAF-1, and p53 and protein levels of phosphorylated histone H2AX were estimated by Western blotting. RESULTS: Topically application of baicalin treatment reduced UVB-induced epidermal thickening of mouse skin and also result in an increase in the production of collagen I and III, and a decrease in the expression of MMP-1 and MMP-3. Compared with the UVB-irradiated group, we found that the irradiated fibroblasts additionally treated with baicalin demonstrated a decrease in the expression of SA-ß-gal, a increase in the cell viability, a decrease in the G1 phase cell proportion, a downregulation in the level of senescence-associated and γ-H2AX proteins. However, Baicalin had no difference in the normal fibroblasts without UVB irradiation and long-term Baicalin incubation of UVB-SIPS fibroblasts gave no effects on the cell proliferation. CONCLUSIONS: Taken together, these results suggest that baicalin significantly antagonizes photoaging induced by UVB in vivo and in vitro, indicating the potential of baicalin application for anti-photoaging treatment.

Clinical observation of peripheral nerve injury in 2 patients with cancer after radiotherapy.

AIM OF THE STUDY: This study aims to analyze the clinical manifestations and sequelae of peripheral nerve radiation damage of two cases of cancer patients after radiotherapy at the corresponding sites in clinical practice and to summarize experiences and lesions in order to provide a reference for future tumor radiotherapy. MATERIAL AND METHODS: Some data of two cases of patients, such as doses of radiotherapy, clinical manifestations and damage occurrence time, were collected and examinations were conducted to define diagnosis. Afterwards, therapies and follow-up were conducted. RESULTS: Case 1 (rectal cancer) was diagnosed as mild left lower extremity nerve damage. After the symptomatic treatment, the disease condition was improved, and there was no tumor recurrence sign. Case 2 (breast cancer) was diagnosed as left brachial plexus damage, and left upper extremity movement function was lost completely. While the analgesic treatment was conducted, anti-tumor relevant treatments were being carried out. CONCLUSIONS: Radiotherapy can cause different extents of radioactive nerve damage. In practice, it is necessary to constantly improve the radiotherapy technology level and actively prevent the occurrence of complications. Once symptoms appear, the diagnosis and treatment should be conducted as early as possible in order to avoid aggravating damage to cause dysfunction and cause lifetime pain to patients.

Cytogenetic analysis in 16-year follow-up study of a mother and fetus exposed in a radiation accident in Xinzhou, China.

In November 1992, a radiation accident occurred in Xinzhou, due to the collection by a farmer of an unused (60)Co source; 37 individuals were exposed to ionizing radiation. Three individuals died and the farmer's 19-weeks-pregnant wife suffered acute radiation symptoms. Conventional chromosome analysis, cytokinesis-block micronuclei (CBMN) assay and fluorescence in situ hybridization (FISH) painting with three pairs of whole chromosome probes were used to analyze chromosomal aberrations for the pregnant female and her baby during the 16 years following the accident. The yields of dicentrics and rings (dic+r) continually declined between 41 days and 16 years after the accident. The frequency of binucleated MN also decreased over time for both mother and daughter. Sixteen years after exposure, the yields of dic+r and binucleated MN decreased to normal levels, but the reciprocal translocation frequencies remained elevated, for both mother and daughter. FISH results showed a decreasing yield of translocations with time. Based on the changes in maternal translocation frequency, the daughter's dose at the time of exposure was estimated as 1.82 (1.35-2.54)Gy. This was consistent with the clinical manifestations of severe mental retardation and low IQ score. FISH-based translocation analysis can be used for follow-up studies on accidental exposure and, after correction, for retrospective dose estimation for individuals prenatally exposed to radiation.

[Long-term outcome and analysis of prognostic factors in 114 cases of postoperative stage III gastric cancer].

OBJECTIVE: To analyze the results of long-term follow up of patients with postoperative stage III gastric cancer and the prognostic factors. METHODS: We retrospectively analyzed the clinicopathological data of 114 patients with stage III gastric cancer treated in our hospital from April 1998 to January 2006. Kaplan-Meier univariate analysis and Cox regression analysis were performed to evaluate the candidate prognostic factors, such as gender, age, pathological stage, histological differentiation, lymphovascular tumor thrombus, tumor residual and postoperative chemotherapy. RESULTS: In the 114 cases, the 5-year overall survival rate was 28.6% and 10-year survival rate was 22.6%. The 5-year survival rates of stage IIIA, IIIB and IIIC patients were 38.3%, 33.8% and 19.5%, respectively, and 10-year survival rates were 33.5%, 29.6% and 11.1%, respectively. Univariate analysis showed that pathological stage, tumor residual and postoperative chemotherapy were significantly correlated with prognosis (P < 0.05). Multivariate analysis showed that pathological stage, tumor residual and postoperative chemotherapy were independent prognostic factors of stage III gastric cancer patients (P < 0.05 for all). CONCLUSIONS: The long-term survival of stage III gastric cancer patients remains poor. Pathological stage, tumor residual and postoperative chemotherapy are the most significant factors influencing prognosis of stage III gastric cancer after radical resection. Postoperative chemotherapy can improve their survival.

A prospective, multicenter, controlled, observational study to evaluate the efficacy of a patient support program in improving patients' persistence to adjuvant aromatase inhibitor medication for postmenopausal, early stage breast cancer.

Since the rate of persistence to adjuvant endocrine therapy such as 5-year aromatase inhibitors (AI) would decrease over time in patients with hormone-sensitive breast cancer, it is necessary to investigate if a patient support program could modify patients' beliefs and improve their persistence to AI treatment. This was a prospective, multicenter, controlled, observational study to evaluate the efficacy of a patient support program in improving postmenopausal patients' persistence to adjuvant AI medication for early stage breast cancer (NCT00769080). The primary objective was to compare the rates of 1-year persistence to upfront adjuvant AI for patients in the two observational arms (standard treatment group and standard treatment plus patient support program group). In this study, 262 patients were enrolled in the standard treatment group and 241 patients in the standard treatment plus patient support program group. The mean 1-year persistence rates were 95.9 and 95.8% for the standard treatment group and the standard treatment plus patient support program group, respectively (P=0.95). The mean times to treatment discontinuation were 231.2 days in the standard treatment group and 227.8 days in the standard treatment plus patient support program group, with no statistically significant difference between the two groups (P=0.96). There was also no statistically significant difference in the reason for treatment discontinuation (P=0.32). There was a significant relationship between the patient centered care questionnaire and poor persistence (odds ratio=3.9; 95% CI, 1.1-13.7; P=0.035), suggesting that the persistence rate of patients with whom the doctor always or usually spends time is greater than that of patients with whom the doctor sometimes or never spends time. Patients' persistence to adjuvant AI medication for postmenopausal, early stage breast cancer is relatively high in the first year and is not significantly increased by adding a patient support program to standard treatment.

[A clinical study on multi-disciplinary team and surgery for resectable colorectal cancer with liver metastases].

OBJECTIVES: To analyze the survival outcomes of the surgery for colorectal cancer with liver metastases (CRCLM), and study the mode of multi-disciplinary team (MDT) for CRCLM. METHODS: The retrospective analysis was conducted for 38 patients with CRCLM received MDT management and surgical treatment from January 2009 to August 2011. The peri-operative and survival outcomes of MDT and surgery were evaluated. RESULTS: All the cases met the present criteria of resetability for CRCLM, but only 4 cases (10.5%) met the previous one. Coloproctectomy and hepatectomy were performed in all cases, with 39 colorectal neoplasms and 155 liver lesions removed. One case died of postoperative septic shock. Colorectal and hepatic specific complications were absent in the others patients except one case of biliary leak which was treated with conservative management. Neoadjuvant chemotherapy was arranged in 13 cases. Adjuvant chemotherapy was administered for every patient. After a mean follow-up of (22 ± 10) months according to the finding time of liver metastases, recurrence and metastases were observed in 16 cases and 6 cases died of late-stage cachexia. The 1-, 2- and 3-overall survival rate were 94.4%, 85.3% and 75.8% respectively, and the 1-, 2- and 3-disease-free survival rate were 70.1%, 54.2% and 54.2% respectively. CONCLUSIONS: MDT mode for resectable CRCLM is recommendable. Surgical resection of CRCLM is feasible and safe, which seems to achieve favourable short-middle oncologic outcomes. And long-term survival is expected.

Follow-up study of a pregnant woman 16 years after exposure in the Xinzhou radiation accident.

To investigate the late effects of radiation on child-bearing women, a follow-up study was performed on a 39-year-old survivor 16 years after a (60)Co radiation accident. The woman, Fang, was 19 weeks pregnant at the time of exposure. Physical examinations, a full range of clinical laboratory and imaging tests, as well as cytogenetic analyses were conducted to evaluate Fang's current health conditions. Fang shows the appearance of premature ageing and has a decreased menstrual period. Laboratory studies and imaging tests suggest nodular goitre disease and osteoporosis. Otherwise, no apparent abnormalities were found in the major organs. No malignant tumours were detected by either tumour markers or imaging tests. However, the existence of chromosome aberrations warrants long-term follow-up for tumour incidence in the future. Fang became pregnant 8 years after the accident, but suffered a miscarriage due to the death of the foetus at 6 months into the pregnancy. In conclusion, our findings suggest that the intrauterine death of the foetus might be associated with the previous exposure. There is no evidence of malignant tumours as of the date of the follow-up study. Non-cancerous diseases, i.e. thyroid disease and osteoporosis, which may be related to radiation exposure, are the major manifestations of the long-term effects of the accident.

Clinical observation of a 16-year-old female exposed to radiation in utero: follow-up after the Shanxi Xinzhou radiation accident.

A follow-up study of the late effects of intrauterine exposure to irradiation has been made on a 16-year-old girl whose mother was exposed to external (60)Co irradiation during the Xinzhou radiation accident 16 years previously. The outcomes of the general medical examinations, conventional chromosome aberration analyses and fluorescence in situ hybridisation (FISH) are presented and the China-revised Wechsler Intelligence Scale for Children (C_WISC) was used to identify her IQ level, which was well below normal for her age. The biological dose of the radiation to which she was exposed when she was in her mother's uterus was inferred to be 1.85 Gy. Although there is no evidence of any other developmental changes or tumour induction at this stage in her life, the child's total intelligence level does appear to have been affected.

[Observation and clinical significance of adjuvant chemotherapy-induced amenorrhea in premenopausal breast cancer patients].

OBJECTIVE: A retrospective analysis of 160 pre-menopausal breast cancer patients was carried out to elucidate the the menstrual outcome in those cases who had undergone adjuvant chemotherapy after surgery, and evaluate the relationship between chemotherapy-induced amenorrhea (CIA) and recurrence of the disease. METHODS: 160 pre-menopausal breast cancer patients were collected, 62/159 (39.0%) of them were node positive, 91/158 (57.6%) were ER positive, and 95/155 (61.3%) were PR positive. 111 cases had infiltrative ductal carcinoma, 26 cases had infiltrative lobular carcinoma, and 22 cases with others. In 152 cases data were collected by face-to-face interview and 8 cases by phone conversation. Types and cycles of chemotherapy regimen as well as menstrual abnormalities were recorded before, during, and after chemotherapy completion. Follow up duration was 12-72 months after chemotherapy completion for all patients. RESULTS: 107 (66.9%) developed CIA, 24 cases returned to normal menses (22.4%), 83 cases continued CIA during more than 12-month follow up (77.6%). The rate of CIA increased with age (P < 0.01). During the follow up, disease free survival (DFS) rate was 85.9% in CIA group and 79.2% in non-CIA group, with no statistically significant difference. But in hormonal receptor positive patients, DFS was 80.0% in non-CIA and 90.1% in CIA, respectively (P = 0.04), showing a significant difference. Because of the small number of died cases, no analysis of the overall outcome was carried out. CONCLUSION: Adjuvant chemotherapy causes ovarian function suppression, and may further leading to amenorrhoea. Women who experienced amenorrhoea after chemotherapy had a significantly better disease-free survival (DFS) rate showed by univariate analysis than women who continued normal menstruation. Chemotherapy is insufficient therapy for very young patients who are in high risk with hormone responsive disease, particularly when chemotherapy fails to induce amenorrhea. Further research is needed to evaluate interventional chemotherapy to improve the quality of life in women with early stage breast cancer who experienced ovarian toxicity. The post-chemotherapy menstruation status is a clinically valuable, objective and salient marker for sufficient endocrine effect of chemotherapy in ER/PR-positive premenopausal patients.

[Adjuvant chemotherapy after orthotopic liver transplantation for advanced hepatocellular carcinoma].

OBJECTIVE: To investigate the feasibility, reliability and therapeutic effectiveness of adjuvant chemotherapy for advanced hepatocellular carcinoma (HCC) after orthotopic liver transplantation (OLT). METHODS: The clinical data of adjuvant chemotherapy after OLT in 10 advanced HCC patients were studied retrospectively. FAP chemotherapy regimen was adopted calcium folinate (CF) 200 mg/m(2) and 5-Fluorouracil 500 mg/m(2) iv on D1 to D5, and doxorubicin 40 mg/m(2), cisplatin 30 mg/m(2) iv on D1, with 28 days as a cycle. The opportune time of chemotherapy, chemotherapy regimen, synergistic action between cytotoxic agent and immunosuppressive agent on liver and kidney and side-effects were preliminarily evaluated. RESULTS: 7/10 patients are surviving, with the longest survival of 32 months, and the shortest 9 months. Three patients died after operation, two at 13 months, one at 20 months after OLT, all died of metastasis. The incidence of one year survival was 9/9. During the period of chemotherapy, the side-effects of adjuvant chemotherapy were moderate. CONCLUSION: Chemotherapy which is able to prolong the life-span of patients with advanced HCC after orthotopic liver transplantation is feasible and effective, the side-effects were mild. The choice of opportune time of chemotherapy might influence the outcome.