Research Progress in Treatment of Chemical Liver Injury with Chinese Medicine Based on Metabolomics / 中国实验方剂学杂志

Liver， as a critical organ of metabolism and detoxification， can be damaged by viral infection， drug abuse， and heavy drinking. Liver diseases pose a serious threat to people's health and life in China.At present， drug therapy has been primarily adopted clinically in the treatment of the liver injury.In-depth investigation of the mechanism of liver-protective drugs is of great significance to the prevention and treatment of clinical liver diseases.In recent years， with the development of the medical industry in China， an increasing number of studies have focused on the treatment of liver injury with Chinese medicine.Compared with western medicine， Chinese medicine is advantageous in few side effects and overall regulation， which plays a pivotal role in liver protection.However， its underlying mechanism in liver protection still needs to be further studied due to its complex compositions and diverse targets.Metabolomics， a new approach to studying the metabolic pathway of biological systems， provides integral and systematic views in the investigation of liver protection with Chinese medicine. By virtue of metabolomics， the mechanism of Chinese medicine in multi-target and multi-pathway liver protection can be analyzed comprehensively， and the corresponding biomarkers can also be screened out. The authors analyzed the studies of the treatment of chemical liver injury models induced by carbon tetrachloride （CCl4）， dimethylnitrosamine （DMN）， α-naphthyl isothiocyanate （ANIT）， and alcohol by Chinese medicinal compounds， single herbal medicines， and monomers of Chinese medicine based on metabolomics， and summarized the biomarkers and related metabolic pathways of Chinese medicine in the intervention of each type of liver injury， aiming at providing a reference for the further research and clinical application in the treatment of different types of liver injuries by Chinese medicine.

Artificial Dermis Composite Tissue Flaps versus Traditional Prefabricated Flaps.

OBJECTIVE: We compared the application of artificial dermis composite tissue flaps and traditional prefabricated flaps in a rat model of exposed bone and tendon injury. METHODS: Sprague Dawley rats were randomly divided into two groups (n = 40 per group). Group A rats received artificial dermis composite tissue flaps and group B rats received traditional prefabricated flaps. Flap appearance, range of motion, degree of swelling, tissue histologic results, and imaging findings were compared between groups at 7, 14, 21, and 28 days. RESULTS: There was no difference in flap appearance, range of motion, or degree of swelling between groups. However, blood perfusion of the artificial dermis composite tissue flap was better than that of the traditional prefabricated flap; the artificial dermis was also found to be thicker than the traditional prefabricated flap. CONCLUSIONS: The artificial dermis composite tissue flap is an ideal method for repairing exposed bone and tendon, and it displays repair effects comparable with those of the traditional prefabricated flap and may be a better alternative.

Critical role for non­GAP function of Gαs in RGS1­mediated promotion of melanoma progression through AKT and ERK phosphorylation.

Regulator of G­protein signaling 1 (RGS1) has been found to be a critical factor in melanoma and other malignancies. However, the mechanism involved in the RGS1­mediated promotion of melanoma progression is not clear. We based our study on samples collected from pathological specimens of melanoma patients. We found by immunohistochemistry that RGS1 expression was significantly higher in melanoma than that noted in nevus tissue (P<0.05). Kaplan­Meier analysis demonstrated a significant correlation between increased RGS1 expression and reduced disease­specific survival (P<0.05). RGS1 expression was also found to be related to the proliferation and migration of melanoma cells. RGS1 was able to bind to the Gαs in immunoprecipitation, but this interaction did not accelerate GTP hydrolysis in our experiment. Furthermore, we found that RGS1 may promote melanoma progression through the downstream effects of Gαs signaling, such as the increased phosphorylation of AKT and ERK by western blotting. Our results demonstrated that RGS1 promotes melanoma progression through regulation of Gαs­mediated inactivation of AKT and ERK. Therefore, RGS1 is a novel therapeutic target for melanoma treatment.

Reconstruction of auricular conchal defects with local flaps.

Reconstruction of the auricular conchal cavity is relatively difficult because of its unique structure, shape, and location. We compared different methods of repair of the auricular concha to determine the method that would cause the least injury to the donor site.The method selected was based on the location and size of the defect. If the defect was located in the upper part of the concha, or if the defect was >15 mm in diameter, we used a post-auricular subcutaneous pedicle island flap that was pulled through a post-auricular sulcus tunnel to cover the wound. If the defect was located in the lower part of the concha and was <15 mm in diameter, we used a pre-auricular translocation flap that was passed through the intertragic notch to cover the wound. The donor site was closed primarily. All flaps survived well and any scars associated with the surgery were unnoticeable. No tumor relapse or metastasis was observed over a mean follow-up period of 35 months. All patients were satisfied with the outcome.The periauricular flap technique chosen for reconstruction of skin defects in the auricular concha depends on the size and location of the defect. With appropriate flap selection, excellent functional, and aesthetic outcomes are achieved.

Management of concealed penis with modified penoplasty.

INTRODUCTION: To investigate the effect of penile degloving in combination with penoscrotal angle reconstruction for the correction of concealed penis. TECHNICAL CONSIDERATIONS: A foreskin circumcision incision was made along the coronal sulcus. After a sharp dissection under the superficial layer of tunica albuginea, the penile shaft was degloved to release the fibrous bands of the tunica dartos. Through a longitudinal incision or Z-plasty at the penoscrotal junction, securing of the tunica albuginea to the proximal tunica dartos was performed. The penoscrotal angle was reconstructed. This procedure effectively corrected the concealed penis, while correcting other problems such as phimosis. From August 2008 to August 2013, we performed 41 procedures for concealed penis. Correction was successful in all patients with an improved median length of 2.1 cm in the flaccid state. Follow-up ranged from 6 months to 2 years, and satisfactory cosmetic outcomes were obtained without scars or erectile discomfort. CONCLUSION: Our technique includes degloving and penoscrotal angle reconstruction, which provides proper visualization for fixation of the penile base. The longitudinal or Z-plasty incision also opened the degloving dead cavity, which was good for drainage. The procedure is straight forward with good functional and cosmetic outcomes and is thus ideal for correction of the concealed penis.

Prognostic role of microRNA-205 in multiple human malignant neoplasms: a meta-analysis of 17 studies.

OBJECTIVE: MicroRNA-205 (miRNA-205) was revealed as an attractive prognostic tumour biomarker in recent studies. However, the results of different studies have been inconsistent. We conducted a meta-analysis to elucidate the precise predictive value of miRNA-205 in various human malignant neoplasms. DESIGN: Meta-analysis. DATA SOURCES: Qualified studies were identified up to 5 June 2014 by performing online searches in PubMed, EMBASE and Web of Science, and additional quality evaluations. PARTICIPANTS: Seventeen eligible studies with 4827 patients were ultimately enrolled in this meta-analysis. OUTCOME MEASURES: The heterogeneity between studies was assessed using I(2) statistics. Pooled HRs with 95% CIs for patient survival and disease recurrence were calculated to investigate the correlation between miRNA-205 expression and cancer prognosis. RESULTS: Our results indicate that elevated miRNA-205 was significantly associated with enhanced overall survival in the breast cancer subgroup (HR=0.78, 95% CI 0.67 to 0.91) and superior disease-free survival/recurrence-free survival in the adenocarcinoma subgroup (HR=0.68, 95% CI 0.49 to 0.94). CONCLUSIONS: miRNA-205 is a promising biomarker for predicting the recurrence and progression of patients with adenocarcinomas or breast cancer. Owing to its complex roles, further relevant studies are warranted.

[The application of pedicle orbital fat flap for the correction of lacrimal groove and palpebromalar groove deformity in the middle-aged and old people].

OBJECTIVE: To explore the effective techniques for correction of lacrimal groove and palpebromalar groove deformity in the middle-aged and old people. METHOD: The lacrimal groove and palpebromalar groove deformity was corrected by the techniques of transcutaneous orbital fat releasing and pedicle orbital fat flap filling. From 1996 to 2011, 426 patients, aged from 35 to 72 (average, 48), were treated by the techniques. Among them, 54 patients had underwent the surgical treatment before this operation. 362 patients were followed up for 3-24 months. RESULTS: Completely correction was achieved in 283 patients, obvious improvement in 79 patients. The result was not satisfied in 2 patients with severe deformity who had surgical treatment before. CONCLUSION: The lacrimal groove and palpebromalar groove deformity can be effectively corrected by transcutaneous orbital fat releasing and pedicle orbital fat flap in the middle-aged and old people.

Involvement of melanocortin-1 receptor in the hyperpigmentation of human skin autografts.

Hyperpigmentation frequently occurs in human skin autografts resulting in an unsatisfactory appearance. This study aimed to elucidate the role of melanocortin-1 receptor in the hyperpigmentation process of skin autografts by analyzing the expression of melanocortin-1 receptor. The data were correlated with the amount of melanin in autografted human skin and normal skin determined in a previous study. Immunohistochemistry, western blotting and quantitative real-time polymerase chain reaction were carried out to detect the expression and distribution of melanocortin-1 receptor in skin autografts including full-thickness skin autografts, split-thickness skin autografts and normal full-thickness skin. Fontana-Masson stain was used to detect melanin in all types of skin specimens. The expression level of melanocortin-1 receptor in autografted skin was much higher than that in control normal skin, and thinner split-thickness skin autografts had higher levels of expression of melanocortin-1 receptor than thicker grafts. The amount of melanin in skin autografts was significantly increased compared with normal skin. The expression of melanocortin-1 receptor correlated well with the amount of melanin in the epidermis of skin autografts. These results indicate that melanogenesis is dramatically enhanced in skin autografts by the melanocortin-1 receptor, and suggest that overexpression of melanocortin-1 receptor may play an important role in the hyperpigmented process of skin autografts. This study provides a novel mechanism for hyperpigmentation in skin autografts.

Reconstruction of lower eyelid retraction or ectropion using a paranasal flap.

BACKGROUND: This report aims to describe a paranasal flap technique for reconstruction of lower eyelid retraction and ectropion. METHODS: After the contracture of the lower eyelid skin or conjunctiva had been thoroughly released, the ipsilateral upper pedicle paranasal flap was designed according to the size of the lower eyelid skin wound. After dissection of the flap, the subcutaneous tissue of the flap was trimmed according to the depth of the wound, the flap was rotated to cover the defect, and an anchor was fixed to the distal aspect of the outer canthus. The secondary defect of the donor area was sutured directly. RESULTS: In this study, 67 patients with lower eyelid defects resulting from correction of eyelid retraction and ectropion were reconstructed using paranasal flaps between April 2004 and October 2009. The sizes of the paranasal flaps ranged from 0.6×2.2 to 1.5×3.5 cm. At the follow-up assessment, the patients could close their eyes easily and completely without lagophthalmos, and neither the upper lips or the nasal ala showed any anatomic deformities. The features of the paranasal flaps, such as skin color, texture, and contour of the repaired tissue, were a good match with the surrounding skin. The suture lines of the donor areas were sheltered well. CONCLUSIONS: Paranasal flaps were used for effective reconstruction of lower eyelid retraction or ectropion, with achievement of good eyelid function and a good color, contour, and texture match with the surrounding skin. Overall, the functional and cosmetic results were satisfactory. LEVEL OF EVIDENCE V: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors at www.springer.com/00266.

Combined flaps for reconstructing wide-range facial defects.

BACKGROUND: This report aims to describe the technique of using combined flaps for reconstruction of wide-range facial defects. METHODS: Two or more flaps were combined to repair wide-range facial wounds, complying with the principle of facial aesthetic subunits to maintain the inherent structural characteristics of the face, to design incision lines conforming to the natural facial contour lines (e.g., nasolabial fold, sulcus alaris, nasomaxillary suture, palpebral margin, vermilion border, hairline) or wrinkles, and to leave hidden incision lines if possible. There were 18 cases with excessively large facial defects requiring the use of a graft with local flaps. RESULTS: From April 1996 to May 2008, 124 patients had their wide-range facial defects repaired by combined flaps. The size of the defects ranged in size from 2.5 × 4 to 9 × 10 cm. The healing for all the patients was uneventful, and the flap survived completely without complications. After an average of 6 months (range, 1-48 months), 87 of the patients were available for follow-up evaluation. There was no recurrence of tumor. The repaired tissues were well matched with surrounding tissue in color, texture, and contour. Incision lines were sheltered, and there were no anatomic deformities of the eyelid, upper lip, or nasal ala. CONCLUSIONS: Based on the facial aesthetic subregion principle, combined flaps were used to reconstruct wide-range facial defects effectively, obtaining good color, contour, and texture match with the surrounding skin. All in all, the cosmetic results were satisfactory.

[The treatment of lower eyelid retraction at the different degree].

OBJECTIVE: To explore the effective methods for the correction of lower eyelid retraction at different degree. METHODS: 258 patients with lower eyelid retraction were treated in our department since 1999. The lower eyelid retraction could be divided into mild, moderate and severe degree. The lateral canthal anchoring (n = 150), Hamra's lower eyelid blepharoplasty (n = 80) and translid cheek lifting (n = 28) were adopted according to the severity. The therapeutic effect for different degree of lower eyelid retraction was compared. RESULTS: 98 patients were followed up for 3-12 months, including 51 patients of mild degree, 29 patients of moderate degree, and 18 patients of severe degree. The retraction were corrected completely in 91 patients. The lower eyelid was repositioned to the level of inferior limbus without inferior scleral show when eyes opened. The palpebral fissure could close completely. The blunt lateral canthus turned to be acute and the scar was inconspicious. The retraction was improved, but not corrected completely in 3 patients of moderate degree and 4 patients of severe degree. The complications included petechiae, chemosis, and so on. CONCLUSIONS: The lower eyelid retraction can be corrected effectively if the appropriate techniques are performed according to the degree of retraction.

The involvement of alpha-melanocyte-stimulating hormone in the hyperpigmentation of human skin autografts.

UNLABELLED: Hyperpigmentation occurs frequently in human skin autografts, resulting in an unsatisfactory appearance. OBJECTIVE: This study aims to elucidate the role of alpha-melanocyte-stimulating hormone (alpha-MSH) in the hyperpigmentation process of skin autografts by analysing the expression of alpha-MSH and the amount of melanin in human autografted skin and normal skin. METHODS: Immunohistochemistry and reverse transcription-polymerase chain reaction methods were carried out to detect the expression and distribution of alpha-MSH and pro-opiomelanocortin (POMC) in skin autografts, including full-thickness skin autografts, split-thickness skin autografts and normal skin. The Fontana-Masson stain was used to detect the amount of melanin in all the skin specimens. RESULTS: The level of alpha-MSH and POMC expression in autografted skin was much higher than that of control normal skin, and thinner split-thickness skin autografts expressed higher levels of POMC mRNA and alpha-MSH protein. The amount of melanin in skin autografts was significantly higher compared with normal skin. The expression of alpha-MSH correlated well with the amount of melanin in skin autograft epidermis. CONCLUSIONS: These results indicate that the function of melanogenesis, transfer of melanin in melanocytes, was dramatically enhanced in skin autografts by alpha-MSH. The over-expression of alpha-MSH may play an important role in the hyperpigmentation process of skin autografts and provide a novel mechanism of this process.

[Immediate reconstruction of tissue defects on eyelid caused by tumor excision].

OBJECTIVE: To introduce the methods for immediate reconstruction of tissue defects on eyelid caused by tumor excision. METHODS: Single or combined local skin flaps were used to repair tissue defects on eyelids after tumor excision. RESULTS: Since 1994, 216 patients (224 sides) were treated. All flaps survived with primary healing. 149 patients were followed up for 3 months to 10 years with satisfactory results. 2 patients with squamous cell carcinoma recurred and reoperated with local skin flap again. CONCLUSIONS: It is a simple, safe, flexible and reliable method to immediately repair the tissue defects with local flaps on eyelid caused by tumor excision.

The bilobed flap for reconstruction of distal nasal defect in Asians.

BACKGROUND: The aim of this study was to overcome nasal alar retraction that occurs with the use of the standard Zitelli's bilobed flap for reconstruction of a distal nasal defect. Zitelli's bilobed flap offers the ability to aesthetically reconstruct difficult defects in the distal nasal area. However, the standard Zitelli bilobed flap may sometimes result in nasal alar retraction which is likely to the result of excessive tension upon closure of the primary lobe and primary defect. METHODS: We modified the bilobed flap based on the design of the standard Zitelli bilobed flap. The modification of the bilobed flap was designed to have a primary lobe that was 10% longer than the length of the distal defect edge from the flap's pivot point, and the width of the primary lobe was equal to the width of the defect. The length of the secondary lobe was 130% of the length of the distal defect edge to the flap's pivot point, and the width of the secondary lobe was two-thirds the width of the primary lobe. To make a slight downward displacement of the ipsilateral alar margin, the primary lobe was transposed to fill the primary defects. RESULTS: The results of the reconstruction were satisfactory: there was good nasal contour and appropriate symmetry of the nasal tip and no alar retraction. CONCLUSION: The modification of Zitelli's bilobed flap to have a longer primary lobe, which slightly displaced downward the ipsilateral alar margin intraoperatively, can prevent nasal alar retraction in the reconstruction of distal nasal defects in Asians.

The island myocutaneous flap reconstruction in electrical burn injuries of severely traumatized cervical region.

Trauma patients with high-energy injuries often present with severe tissue damage that extends beyond the immediate zone of injury and require recruitment of vascularized and massive tissues. The objective of this study was to evaluate the utility of the island myocutaneous flap for the reconstruction of the electrical burn injuries on the cervical region. We conducted a retrospective chart review on all trauma patients treated by the Department of Plastic Surgery at Changhai Hospital, Second Military Medical University who required a large amount of vascularized tissue for the reconstruction of the electrical burn injuries on the cervical region from July 1994 to June 2006. Of them, 23 patients underwent reconstruction of severe traumatic deformities and disfunction on the cervical region with 23 island myocutaneous flaps from adjacent regions. Of the 23 patients, 17 were male and 6 were female, with an average age of 38 years. Conservative surgery method for debriding necrotic tissues and three different types of island myocutaneous flaps, including pectoralis major island myocutaneous flap, latissimus dorsi island myocutaneous flap and trapezius island myocutaneous flap were used. The defect area ranged from 6 cm x 4 cm to 20 cm x 15 cm. The sizes of the dissected myocutaneous flap ranged from 8 cm x 6 cm to 35 cm x 15 cm. All the 23 cases acquired complete recovery. The secondary defect of donor areas had primary closure after being directly sutured or covered with skin grafts. Island myocutaneous flaps have distinctive advantages in treatment of electrical burn injuries on cervical region and it can obtain satisfactory functional and cosmetic outcomes.

[Local flap for reconstruction of nasal tip defect: functional and aesthetic evaluations].

OBJECTIVE: To introduce the experience of reconstruction of nasal tip defect, which could obtain good functional and aesthetic results. METHODS: Based on the aesthetic subunit principle, according to the size, shape, depth of nasal tip defect, and the conditions of surrounding skin, homologous local flap (include: frontonasal flap, bilobed flap, nasolabial flap, reforming rhomboid flap and forehead flap, etc.) was designed to cover the defect wound. The secondary defect of donor area was directly sutured. RESULTS: A total of 83 patients with nasal tip defect were treated by local flap transfers. The area of the defect ranged between 0.6 x 0.6 cm and 2.5 cm x 2.5 cm. The nasal tip defect was successfully closed in all patients, and all flaps survived well without obvious complications. 76 out of these 83 patients were available for follow-up from 1 to 36 months. The repaired tissue was in good match with surrounding tissue, with nice nasal contour, and cosmetic results were satisfactory. No tumor recurrence occurred. CONCLUSIONS: Based on the nasal aesthetic subunit principle, local flap could be used to reconstruct the nasal tip defect below 2.5 cm x 2.5 cm, and obtain good color, contour and texture in match with the surrounding skin. Cosmetic results were satisfactory.

[Discoidin domain receptors (DDRs) expression in pathological scar fibroblast formation].

OBJECTIVE: To explore the role of discoidin domain receptors (DDRs) in the formation of the keloid. METHODS: The real-time quantitative PCR was used to compare the DDRs expression in the keloids and normal fibroblasts. RESULTS: The level of DDR1 expression was significantly higher in keloid than in normal fibroblast (20.98 vs 4.2, P <0.01; 7.9 vs 4.23, P <0.05). The level of DDR1 expression in keloid was also higher significantly than that in hypertropic scar (20.98 vs 7.9, P < 0.01). However, the level of DDR2 expression was somewhat higher in keloid than in normal fibroblasts, the difference seemed not to be significantly in probability (358, 332 vs 278, P > 0.05). CONCLUSIONS: DDRs may exert effect on keloid cell behaviours.

[Expression of alpha-melanocyte-stimulating hormone in human split-thickness skin graft].

OBJECTIVE: To investigate the expression of alpha-melanocyte-stimulating hormone (alpha-MSH) in human split-thickness skin autograft and the role of alpha-MSH in hyperpigmented process of the grafted skin. METHODS: Immunohistochemical technique was used to detect the expression and distribution of alpha-MSH in the split-thickness grafted skin and normal skin separately. RESULTS: The expression of alpha-MSH in most of the split-thickness grafted skin was much stronger than the control skin. The positive ratio of alpha-MSH expression was 61.1% in the split-thickness grafted skin, 11.1% in the normal skin of the donor area and 16.7% in the normal skin around the recipient area. The expression of alpha-MSH in the split-thickness grafted skin was significant high, compared with the normal skins (P < 0.01). The expression of alpha-MSH in the normal skin of the donor area was no statistic remarkably differences compared to the normal skin around the recipient area. CONCLUSION: The results indicate that the expression of alpha-MSH may markedly increase in the split-thickness grafted skin and correlate with its pigmentation after the skin graft. Overexpression of alpha-MSH may play an important role in hyperpigmented process of the skin graft.