A Rare Hemoglobin Variant Detected in a Pregnant Chinese Woman.

BACKGROUND: Hemoglobin Variant (HBB:c.155 C>A) is a rare mutation caused by ß-globin gene mutation called Hemoglobin North Manchester. So far, its existence has no adverse effect on human body, and it is a rare benign hemoglobin variant. METHODS: We reported a 32-year-old pregnant woman with discordant HbA1c and glucose measurements. In 75 g oral glucose tolerance test (OGTT), the pregnant woman got hyperglycemia at 1h-OGTT and 2h-OGTT. However, the pregnant woman had a low HbA1c of 3.9%. Subsequently, gene sequencing identified a rare mutation in the gene (HBB:c.155 C>A). RESULTS: We report for the first time that a case of North Manchester mutation in a Chinese female patient. In this case, it was found that the North Manchester variant could affect the examination of HbA1c when measured by ion-exchange high-performance liquid chromatography (HPLC), causing in falsely low HbA1c. CONCLUSIONS: Hemoglobin variants may lead to false HbA1c measurement. Clinicians should consider hemoglobin variants when HbA1c results are inconsistent with other laboratory tests.

Activation of CB1R alleviates central sensitization by regulating HCN2-pNR2B signaling in a chronic migraine rat model.

BACKGROUND: Central sensitization has been widely accepted as an underlying pathophysiological mechanism of chronic migraine (CM), activation of cannabinoid type-1 receptor (CB1R) exerts antinociceptive effects by relieving central sensitization in many pain models. However, the role of CB1R in the central sensitization of CM is still unclear. METHODS: A CM model was established by infusing inflammatory soup (IS) into the dura of male Wistar rats for 7 days, and hyperalgesia was assessed by the mechanical and thermal thresholds. In the periaqueductal gray (PAG), the mRNA and protein levels of CB1R and hyperpolarization-activated cyclic nucleotide-gated cation channel 2 (HCN2) were measured by qRT-PCR and western blotting. After intraventricular injection of Noladin ether (NE) (a CB1R agonist), ZD 7288 (an HCN2 blocker), and AM 251 (a CB1R antagonist), the expression of tyrosine phosphorylation of N-methyl-D-aspartate receptor subtype 2B (pNR2B), calcium-calmodulin-dependent kinase II (CaMKII), and phosphorylated cAMP-responsive element binding protein (pCREB) was detected, and central sensitization was evaluated by the expression of calcitonin gene-related peptide (CGRP), c-Fos, and substance P (SP). Synaptic-associated protein (postsynaptic density protein 95 (PSD95) and synaptophysin (Syp)) and synaptic ultrastructure were detected to explore synaptic plasticity in central sensitization. RESULTS: We observed that the mRNA and protein levels of CB1R and HCN2 were both significantly increased in the PAG of CM rats. The application of NE or ZD 7288 ameliorated IS-induced hyperalgesia; repressed the pNR2B/CaMKII/pCREB pathway; reduced CGRP, c-Fos, SP, PSD95, and Syp expression; and inhibited synaptic transmission. Strikingly, the application of ZD 7288 relieved AM 251-evoked elevation of pNR2B, CGRP, and c-Fos expression. CONCLUSIONS: These data reveal that activation of CB1R alleviates central sensitization by regulating HCN2-pNR2B signaling in CM rats. The activation of CB1R might have a positive influence on the prevention of CM by mitigating central sensitization.

Molecular mechanisms of platinum­based chemotherapy resistance in ovarian cancer (Review).

Cisplatin is one of the most effective chemotherapy drugs for ovarian cancer, but resistance is common. The initial response to platinum­based chemotherapy is as high as 80%, but in most advanced patients, final relapse and death are caused by acquired drug resistance. The development of resistance to therapy in ovarian cancer is a significant hindrance to therapeutic efficacy. The resistance of ovarian cancer cells to chemotherapeutic mechanisms is rather complex and includes multidrug resistance, DNA damage repair, cell metabolism, oxidative stress, cell cycle regulation, cancer stem cells, immunity, apoptotic pathways, autophagy and abnormal signaling pathways. The present review provided an update of recent developments in our understanding of the mechanisms of ovarian cancer platinum­based chemotherapy resistance, discussed current and emerging approaches for targeting these patients and presented challenges associated with these approaches, with a focus on development and overcoming resistance.

Establishment of trimester-specific reference intervals for thyroid stimulating hormone and free thyroxine during pregnancy in southwest China by indirect method.

OBJECTIVE: A series of physiological changes in thyroid function occur during pregnancy and differ from those non-pregnant women. This study aimed to establish the pregnancy-specific reference intervals of TSH and FT4 using an indirect method based on the healthy pregnant women from southwest China population. METHODS: Thyroid function test results which available on the Laboratory Information System (LIS) were collected from the pregnancies who visited the Obstetric Clinic or the Department of Gynecology between 1 January 2015, and 30 December 2020. We grouped the data by trimesters to establish the reference intervals (RIs) based on the clinical consensus of different levels of TSH and FT4 at different weeks of gestation. All arrangements were referenced to the document CLSI EP28-A3C. RESULTS: A total of 33,040 thyroid function test results of pregnant women, aged 31 (28,33) years were statistical analyzed. Estimated RIs for TSH and FT4 in the first, second and third trimesters corresponding to the 2.5th and 97.5th percentiles in TPOAb negative were 0.02-5.23, 0.03-5.24, 0.37-5.68 mIU/L, 11.66-20.69, 10.1-18.59, 9.85-16.86pmol/L, respectively. CONCLUSION: This study provides trimester-specific RIs for TSH and FT4 among healthy pregnant women in southwest China which guides clinicians to diagnosis and screen for thyroid disorders in this region.

Comparison of prognosis predictive value of 4 disease severity scoring systems in patients with acute respiratory failure in intensive care unit: A STROBE report.

ABSTRACT: Various disease severity scoring systems were currently used in critically ill patients with acute respiratory failure, while their performances were not well investigated.The study aimed to investigate the difference in prognosis predictive value of 4 different disease severity scoring systems in patients with acute respiratory failure.With a retrospective cohort study design, adult patients admitted to intensive care unit (ICU) with acute respiratory failure were screened and relevant data were extracted from an open-access American intensive care database to calculate the following disease severity scores on ICU admission: acute physiology score (APS) III, Sequential Organ Failure Assessment score (SOFA), quick SOFA (qSOFA), and Oxford Acute Severity of Illness Score (OASIS). Hospital mortality was chosen as the primary outcome. Multivariable logistic regression analyses were performed to analyze the association of each scoring system with the outcome. Receiver operating characteristic curve analyses were conducted to evaluate the prognosis predictive performance of each scoring system.A total of 4828 patients with acute respiratory failure were enrolled with a hospital mortality rate of 16.78%. APS III (odds ratio [OR] 1.03, 95% confidence interval [CI] 1.02-1.03), SOFA (OR 1.15, 95% CI 1.12-1.18), qSOFA (OR 1.26, 95% CI 1.11-1.42), and OASIS (OR 1.06, 95% CI 1.05-1.08) were all significantly associated with hospital mortality after adjustment for age and comorbidities. Receiver operating characteristic analyses showed that APS III had the highest area under the curve (AUC) (0.703, 95% CI 0.683-0.722), and SOFA and OASIS shared similar predictive performance (area under the curve 0.653 [95% CI 0.631-0.675] and 0.664 [95% CI 0.644-0.685], respectively), while qSOFA had the worst predictive performance for predicting hospital mortality (0.553, 95% CI 0.535-0.572).These results suggested the prognosis predictive value varied among the 4 different disease severity scores for patients admitted to ICU with acute respiratory failure.

CNT/Sericin Conductive Nerve Guidance Conduit Promotes Functional Recovery of Transected Peripheral Nerve Injury in a Rat Model.

Peripheral nerve injury usually leads to poor outcomes such as painful neuropathies and disabilities. Autogenous nerve grafting is the current gold standard; however, the limited source of a donor nerve remains a problem. Numerous tissue engineering nerve guidance conduits have been developed as substitutes for autografts. However, a few conduits can achieve the reparative effect equivalent to autografts. Here, we report for the development and application of a carbon nanotube (CNT)/sericin nerve conduit with electrical conductivity and suitable mechanical properties for nerve repair. This CNT/sericin conduit possesses favorable properties including biocompatibility, biodegradability, porous microarchitecture, and suitable swelling property. We thus applied this conduit for bridging a 10 mm gap defect of a transected sciatic nerve combined with electrical stimulation (ES) in a rat injury model. By the end of 12 weeks, we observed that the CNT/sericin conduit combined with electrical stimulation could effectively promote both structural repair and functional recovery comparable to those of the autografts, evidenced by the morphological and histological analyses, electrophysiological responses, functional studies, and target muscle reinnervation evaluations. These findings suggest that this electric conductive CNT/sericin conduit combined with electrical stimulation may have the potential to serve as a new alternative for the repair of transected peripheral nerves.

Impact of Vitamin D and Vitamin D Receptor on Risk of Cardiovascular Diseases in Children and Adolescents with Obesity in Sichuan, China: A Cross-Sectional Study.

BACKGROUND: Previous studies have demonstrated the close relationship between vitamin D, vitamin D receptor (VDR), and obesity. Nevertheless, few studies have reported wherther the relationship among these is associated with the risk of cardiovascular diseases (CVDs) in Chinese children and adolescents. OBJECTIVE: The present study aimed to reveal the effects of obesity, serum vitamin D levels, and VDR FokI genotype on the risk of CVDs in children and adolescents in Sichuan, China. METHODS: Children and adolescents were recruited into a cross-sectional study. Serum vitamin D levels, serum lipid levels, and VDR FokI gene polymorphisms were measured in the laboratory. The selected lipid factors were used as biomarkers of CVD risk. The impact of obesity, vitamin D levels and VDR FokI genotype on CVD risk factors were investigated. RESULTS: Higher lipid levels were observed in children and adolescents in the obese group, when compared to the nonobese group. In the obese group, the C allele carriers had significantly lower concentrations of lipids, when compared to the TT genotype. C allele carriers who were vitamin D deficient had lower levels of total cholesterol (TC), triglycerides (TG), apolipoprotein B (Apo-B), total cholesterol/high-density lipoprotein cholesterol (TC/HDL-C), low-density lipoprotein cholesterol/high-density lipoprotein cholesterol (LDL-C/HDL-C), and triglycerides/high-density lipoprotein cholesterol (TG/HDL-C), when compared to those with the TT genotype in obese children and adolescents. For vitamin D-insufficient obese children and adolescents, the TC, Apo-B, and TC/HDL-C in the C allele carriers were significantly lower, when compared to those in the TT genotype in obese children and adolescents. CONCLUSION: Obese children with low vitamin D levels, who are carriers of the C allele of the FokI gene, have lower levels of several biochemical markers of CVD risk, when compared to those who were TT homozygous. Obese children and adolescents may benefit from vitamin D supplementation, terms of lowering their CVD risk, particularly when they are carriers of the C allele of the FokI gene.

Long non­coding RNA CASC2 enhances berberine­induced cytotoxicity in colorectal cancer cells by silencing BCL2.

Berberine, a natural isoquinoline alkaloid derived from Berberis species, has been reported to have anticancer effects. However, the mechanisms of action in human colorectal cancer (CRC) are not well established to date. In the present study, the cell cytotoxicity effect of berberine on human CRC cells, as well as the possible mechanisms involved, was investigated. The results of the cell viability and apoptosis assay revealed that treatment of CRC cells with berberine resulted in inhibition of cell viability and activation of cell apoptosis in a concentration­dependent manner. To reveal the underlying mechanism of berberine­induced anti­tumor activity and cell apoptosis, RNA­sequencing followed by reverse­transcription quantitative PCR were performed. In addition, RNA immunoprecipitation, chromatin immunoprecipitation and western blot analysis were used to identify the functional regulation of CASC2/EZH2/BCL2 axis in berberine­induced CRC cell apoptosis. The data revealed that lncRNA CASC2 was upregulated by berberine treatment. Gain­ or loss­of­function assays suggested that lncRNA CASC2 was required for the berberine­induced inhibition of cell viability and activation of cell apoptosis. Subsequently, the downstream antiapoptotic gene BCL2 was identified as a functional target of the berberine/CASC2 mechanism, as BCL2 reversed the berberine/CASC2­induced cell cytotoxicity. lncRNA CASC2 silenced BCL2 expression by binding to the promoter region of BCL2 in an EZH2­dependent manner. In summary, berberine may be a novel therapeutic agent for CRC and lncRNA CASC2 may serve as an important therapeutic target to improve the anticancer effect of berberine.

Berberine Promotes Apoptosis of Colorectal Cancer via Regulation of the Long Non-Coding RNA (lncRNA) Cancer Susceptibility Candidate 2 (CASC2)/AU-Binding Factor 1 (AUF1)/B-Cell CLL/Lymphoma 2 (Bcl-2) Axis.

BACKGROUND Berberine, a natural isoquinoline alkaloid derived from Berberis genus plants, has been reported to have anti-cancer effects. While cell behavior can be modulated by long non-coding RNAs (lncRNAs), the contributions of lncRNAs in progression and berberine effects on colorectal cancer are largely unknown. Therefore, the present study investigated the involvement and regulatory function of lncRNA cancer susceptibility candidate 2 (CASC2) during the treatment of human colorectal cancer using berberine. MATERIAL AND METHODS Reverse transcription-quantitative PCR (RT-qPCR) was performed to detect the expression levels of lncRNA CASC2 and Bcl-2 mRNA in colorectal cancer cells. MTT assay was performed to evaluate cell viability. Flow cytometry and TUNEL assay were used to analyze the apoptosis of cancer cells. RNA immunoprecipitation (RIP) assay was done to verify the interaction between lncRNA CASC2 and (AU-binding factor 1) AUF1, or AUF1 and B-cell CLL/lymphoma 2 (Bcl-2). RESULTS Treatment with berberine suppressed cell viability of colorectal cancer by promoting apoptosis level. LncRNA CASC2 was upregulated in cells treated with berberine, and knockdown of lncRNA CASC2 reversed the berberine-induced apoptosis. In addition, anti-apoptotic gene Bcl-2 was suppressed by berberine treatment and lncRNA CASC2, inducing the pro-apoptotic effects. Moreover, lncRNA CASC2 binds to AUF1, which sequestered AUF1 from binding to Bcl-2 mRNA, thus inducing the inactivation of Bcl-2 translation. CONCLUSIONS Our study reveals that lncRNA CASC2 mediates the berberine-induced pro-apoptotic effect via inhibition of Bcl-2 expression at the post-transcriptional level.

Sericin Nerve Guidance Conduit Delivering Therapeutically Repurposed Clobetasol for Functional and Structural Regeneration of Transected Peripheral Nerves.

Peripheral nerve injury often causes significant function loss. Autologous nerve grafting as a gold-standard repair strategy for treating such an injury is limited by donor nerve supply. Tissue-engineered nerve guidance conduits (TENGCs) as a promising alternative for autografting are challenged by large nerve gaps. Herein, we fabricate a glutaraldehyde-cross-linked sericin nerve guidance conduit (GSC) incorporated with clobetasol, a glucocorticoid receptor agonist, for repairing a 10 mm long sciatic nerve gap in a rat model. The GSC exhibits biocompatibility and regeneration-favorable physicochemical properties. GSC's degradation products promote the secretion of neurotrophic factors in Schwann cells. By repurposing clobetasol for peripheral nerve regeneration, our work uncovers clobetasol's previously unknown functions in promoting Schwann cell proliferation and upregulating the expression of myelin-related genes. Importantly, the implantation of this clobetasol-loaded GSC in vivo leads to successful regeneration of the transected sciatic nerve. Strikingly, the regeneration outcome is functionally comparable to that of autologous nerve grafting (evidenced by three parameters). Specifically, the static sciatic index (SSI), relative reaction time (RRT) and nerve conduction velocity (NCV) in Clobetasol/GSC group are -74.55, 1.30, and 46.4 mm/s at Week 12, respectively, while these parameters are -64.53, 1.23, and 49.8 mm/s in Autograft group. Thus, this work represents the first report unveiling clobetasol's potential in peripheral nerve regeneration, reveals the feasibility of applying a sericin conduit for repairing a large nerve defect, and demonstrates the effectiveness of the clobetasol-loaded-GSC based strategy in transected nerves' regeneration.

miR-34a regulates HDAC1 expression to affect the proliferation and apoptosis of hepatocellular carcinoma.

miR-34a is an important molecule that can inhibit the tumor growth. This study aimed to investigate the functional role of miR-34a in hepatocellular carcinoma (HCC) and explore the interaction between miR-34a and histone deacetylase 1 (HDAC1). RT-qPCR was employed to detect the mRNA expression of miR-34a and HDAC1 in 60 HCC tissues. Results showed miR-34a expression in HCC tissues was significantly lower than in normal tissues (P<0.05), but HDAC1 expression in HCC tissues was markedly higher than in normal tissues (P<0.05). In addition, miR-34a expression was negatively related to HDAC1 expression. miR-34a mimic was transfected into HCC cell lines (HepB3 and HepG2). CCK8 assay, colony formation assay and flow cytometry showed miR-34a over-expression could inhibit the proliferation of HCC cells and induce their apoptosis. Western blotting indicated miR-34a over-expression down-regulated the expression of Bcl-2, procaspase-3, procaspase-9 and c-Myc, but up-regulate p21 expression. Bioinformatics analysis indicated HDAC1 was a target gene of miR-34a. Dual Luciferase Reporter Gene Assay and retrieval assay showed miR-34a could act at the 3'UTR of HDAC1 gene to regulate its expression. Thus, miR-34a may inhibit the proliferation of HCC cells and induce their apoptosis via regulating HDAC1 expression. Our findings provide evidence for the diagnosis and therapeutic target of HCC.

Sustained Local Release of NGF from a Chitosan-Sericin Composite Scaffold for Treating Chronic Nerve Compression.

Chronic nerve compression (CNC), a common form of peripheral nerve injury, always leads to chronic peripheral nerve pain and dysfunction. Current available treatments for CNC are ineffective as they usually aim to alleviate symptoms at the acute phase with limited capability toward restoring injured nerve function. New approaches for effective recovery of CNC injury are highly desired. Here we report for the first time a tissue-engineered approach for the repair of CNC. A genipin cross-linked chitosan-sericin 3D scaffold for delivering nerve growth factor (NGF) was designed and fabricated. This scaffold combines the advantages of both chitosan and sericin, such as high porosity, adjustable mechanical properties and swelling ratios, the ability of supporting Schwann cells growth, and improving nerve regeneration. The degradation products of the composite scaffold upregulate the mRNA levels of the genes important for facilitating nerve function recovery, including glial-derived neurotrophic factor (GDNF), early growth response 2 (EGR2), and neural cell adhesion molecule (NCAM) in Schwann cells, while down-regulating two inflammatory genes' mRNA levels in macrophages, tumor necrosis factor alpha (TNF-α), and interleukin-1 beta (IL-1ß). Importantly, our tissue-engineered strategy achieves significant nerve functional recovery in a preclinical CNC animal model by decreasing neuralgia, improving nerve conduction velocity (NCV), accelerating microstructure restoration, and attenuating gastrocnemius muscles dystrophy. Together, this work suggests a promising clinical alternative for treating chronic peripheral nerve compression injury.

miR-26a inhibits the proliferation of ovarian cancer cells via regulating CDC6 expression.

MicroRNAs (miRNA) play important regulatory roles in the occurrence and development of cancers. This study aimed to investigate the effects of miR-26a on the proliferation and apoptosis of ovarian cancer cells and explore the potential mechanism. qRT-PCR was performed to measure the miR-26a expression in 46 ovarian cancer tissues, and results showed miR-26a expression reduced significantly when compared with normal ovarian tissues (P<0.05). Moreover, miR-26a expression was related to the extent of cell differentiation and clinical stage of ovarian cancer (P<0.05). miR-26a mimic was transfected into SKOV3 cells and ES2 cells, and CCK8 assay, colony formation assay and flow cytometry showed miR-26a over-expression could significantly inhibit the proliferation of ovarian cancer cells and induce their apoptosis. Bioinformatics analysis revealed Cdc6 was a target gene of miR-26a. dual-luciferase assay and validation assay showed miR-26a could act on the 3'UTR of Cdc6 to regulate Cdc6 expression. These findings suggest that miR-26a may act on the 3'UTR of Cdc6 to regulate Cdc6 expression, which then inhibit the proliferation of ovarian cancer cells and induce their apoptosis. Our findings provide a new target for the diagnosis and therapy of ovarian cancer.

Sericin/Dextran Injectable Hydrogel as an Optically Trackable Drug Delivery System for Malignant Melanoma Treatment.

Severe side effects of cancer chemotherapy prompt developing better drug delivery systems. Injectable hydrogels are an effective site-target system. For most of injectable hydrogels, once delivered in vivo, some properties including drug release and degradation, which are critical to chemotherapeutic effects and safety, are challenging to monitor. Developing a drug delivery system for effective cancer therapy with in vivo real-time noninvasive trackability is highly desired. Although fluorescence dyes are used for imaging hydrogels, the cytotoxicity limits their applications. By using sericin, a natural photoluminescent protein from silk, we successfully synthesized a hydrazone cross-linked sericin/dextran injectable hydrogel. This hydrogel is biodegradable and biocompatible. It achieves efficient drug loading and controlled release of both macromolecular and small molecular drugs. Notably, sericin's photoluminescence from this hydrogel is directly and stably correlated with its degradation, enabling long-term in vivo imaging and real-time monitoring of the remaining drug. The hydrogel loaded with Doxorubicin significantly suppresses tumor growth. Together, the work demonstrates the efficacy of this drug delivery system, and the in vivo effectiveness of this sericin-based optical monitoring strategy, providing a potential approach for improving hydrogel design toward optimal efficiency and safety of chemotherapies, which may be widely applicable to other drug delivery systems.

Expression of FOXC2 in renal cell carcinoma and its relationship to clinical pathological features.

OBJECTIVE: This study aimed to investigate expression level of FOXC2 and its relationship to clinical pathological features of renal cell carcinoma (RCC). METHODS: The expression levels of FOXC2 in RCC tissues and normal renal tissues (62 samples, respectively) were detected by immunohistochemistry and PCR Array. Statistics analyses were done with SPSS to compare the differences between RCC tissues and normal renal tissue, and to explore the relationship between the expression level of FOXC2 and the clinical pathological features of RCC. RESULTS: Expression level of FOXC2 in RCC tissues was significantly higher than in normal renal tissues, and other related cancer genes also highly expressed in RCC tissues. FOXC2 expression was positively associated with clinical stage and pathological grade (P < 0.05), but not significantly related to the gender and age (P > 0.05). CONCLUSION: The expression of FOXC2 in renal cell carcinoma was significantly higher than that in normal renal tissues. It is suggested that FOXC2 might play a crucial role in the occurrence and development of RCC and could be an important prognostic indicator for clinical therapy.

A Neuroprotective Sericin Hydrogel As an Effective Neuronal Cell Carrier for the Repair of Ischemic Stroke.

Ischemic stroke causes extensive cellular loss that impairs brain functions, resulting in severe disabilities. No effective treatments are currently available for brain tissue regeneration. The need to develop effective therapeutic approaches for treating stroke is compelling. A tissue engineering approach employing a hydrogel carrying both cells and neurotrophic cytokines to damaged regions is an encouraging alternative for neuronal repair. However, this approach is often challenged by low in vivo cell survival rate, and low encapsulation efficiency and loss of cytokines. To address these limitations, we propose to develop a biomaterial that can form a matrix capable of improving in vivo survival of transplanted cells and reducing in vivo loss of cytokines. Here, we report that using sericin, a natural protein from silk, we have fabricated a genipin-cross-linked sericin hydrogel (GSH) with porous structure and mild swelling ratio. The GSH supports the effective attachment and growth of neurons in vitro. Strikingly, our data reveal that sericin protein is intrinsically neurotrophic and neuroprotective, promoting axon extension and branching as well as preventing primary neurons from hypoxia-induced cell death. Notably, these functions are inherited by the GSH's degradation products, which might spare a need of incorporating costly cytokines. We further demonstrate that this neurotrophic effect is dependent on the Lkb1-Nuak1 pathway, while the neuroprotective effect is realized through regulating the Bcl-2/Bax protein ratio. Importantly, when transplanted in vivo, the GSH gives a high cell survival rate and allows the cells to continuously proliferate. Together, this work unmasks the neurotrophic and neuroprotective functions for sericin and provides strong evidence justifying the GSH's suitability as a potential neuronal cell delivery vehicle for ischemic stroke repair.

A silk sericin/silicone nerve guidance conduit promotes regeneration of a transected sciatic nerve.

Peripheral nerve gap defects lead to significant loss of sensory or motor function. Tissue engineering has become an important alternative to nerve repair. Sericin, a major component of silk, is a natural protein whose value in tissue engineering has just begun to be explored. Here, the first time use of sericin in vivo is reported as a long-term implant for peripheral nerve regeneration. A sericin nerve guidance conduit is designed and fabricated. This conduit is highly porous with mechanical strength matching peripheral nerve tissue. It supports Schwann cell proliferation and is capable of up-regulating the transcription of glial cell derived neurotrophic factor and nerve growth factor in Schwann cells. The sericin conduit wrapped with a silicone conduit (sericin/silicone double conduits) is used for bridging repair of a 5 mm gap in a rat sciatic nerve transection model. The sericin/silicone double conduits achieve functional recovery comparable to that of autologous nerve grafting as evidenced by drastically improved nerve function and morphology. Importantly, this improvement is mainly attributed to the sericin conduit as the silicone conduit alone only produces marginal functional recovery. This sericin/silicone-double-conduit strategy offers an efficient and valuable alternative to autologous nerve grafting for repairing damaged peripheral nerve.