PoSnf1 affects cellulose utilization through interaction with cellobiose transporter in Pleurotus ostreatus.

Pleurotus ostreatus is one of the most cultivated edible fungi worldwide, but its lignocellulose utilization efficiency is relatively low (<50 %), which eventually affects the biological efficiency of P. ostreatus. Improving cellulase production and activity will contribute to enhancing the lignocellulose-degrading capacity of P. ostreatus. AMP-activated/Snf1 protein kinase plays important roles in regulating carbon and energy metabolism. The Snf1 homolog (PoSnf1) in P. ostreatus was obtained and analyzed using bioinformatics. The cellulose response of PoSnf1, the effect of the phosphorylation level of PoSnf1 on the expression of cellulose degradation-related genes, the putative proteins that interact with the phosphorylated PoSnf1 (P-PoSnf1), the cellobiose transport function of two sugar transporters (STP1 and STP2), and the interactions between PoSnf1 and STP1/STP2 were studied in this research. We found that cellulose treatment improved the phosphorylation level of PoSnf1, which further affected cellulase activity and the expression of most cellulose degradation-related genes. A total of 1, 024 proteins putatively interacting with P-PoSnf1 were identified, and they were enriched mainly in the substances transport and metabolism. Most of the putative cellulose degradation-related protein-coding genes could respond to cellulose. Among the P-PoSnf1-interacting proteins, the functions of two sugar transporters (STP1 and STP2) were further studied, and the results showed that both could transport cellobiose and were indirectly regulated by P-PoSnf1, and that STP2 could directly interact with PoSnf1. The results of this study indicated that PoSnf1 plays an important role in regulating the expression of cellulose degradation genes possibly by affecting cellobiose transport.

Anus preservation in low rectal adenocarcinoma based on MMR/MSI status (APRAM): a study protocol for a randomised, controlled, open-label, multicentre phase III trial.

BACKGROUND: Anus preservation has been a challenge in the treatment of patients with low rectal adenocarcinoma (within 5 cm from the anal verge) because it is difficult to spare the anus with its functioning sphincter complex under the safe margin of tumour resection. Patients with dMMR/MSI-H can achieve a favourable complete response (CR) rate by using a single immune checkpoint inhibitor. For patients with pMMR/MSS/MSI-L, intensified neoadjuvant three-drug chemotherapy may be the preferred option for anal preservation. In addition, the watch and wait (W&W) strategy has been proven safe and feasible for patients with rectal cancer who achieve a clinical complete response (cCR). Therefore, we initiated this clinical trial to explore the optimal neoadjuvant treatment pattern for patients with low locally advanced rectal cancer (LARC) with different MMR/MSI statuses, aiming to achieve a higher cCR rate with the W&W strategy and ultimately provide more patients with a chance of anus preservation. METHODS: This is a randomised, controlled, open-label, multicentre phase III trial. Patients with clinical stage T2-4 and/or N + tumours located within 5 cm from the anal verge are considered eligible. Based on the results of pathological biopsy, the patients are divided into two groups: dMMR/MSI-H and pMMR/MSS. Patients in the dMMR/MSI-H group will be randomly allocated in a 1:1 ratio to either arm A (monoimmunotherapy) or arm B (short-course radiotherapy followed by monoimmunotherapy). Patients in the pMMR/MSS group will be initially treated with long-term pelvic radiation with concurrent capecitabine combined with irinotecan. Two weeks after the completion of chemoradiotherapy (CRT), the patients will be randomly allocated in a 1:1 ratio to arm C (XELIRI six cycle regime) or arm D (FOLFIRINOX nine cycle regime). The irinotecan dose will be adjusted according to the UGT1A1-genotype. After treatment, a comprehensive assessment will be performed to determine whether a cCR has been achieved. If achieved, the W&W strategy will be adopted; otherwise, total mesorectal excision (TME) will be performed. The primary endpoint is cCR with the maintenance of 12 months at least, determined using digital rectal examination, endoscopy, and rectal MRI or PET/CT as a supplementary method. DISCUSSION: APRAM will explore the best anus preservation model for low LARC, combining the strategies of consolidation chemotherapy, immunotherapy, and short-course radiotherapy, and aims to preserve the anus of more patients using W&W. Our study provides an accurate individual treatment mode based on the MMR/MSI status for patients with low LARC, and more patients will receive the opportunity for anus preservation under our therapeutic strategy, which would transform into long-term benefits. TRIAL REGISTRATION: Clinicaltrials.gov NCT05669092 (Registered 28th Nov 2022).

A pyroptosis-related signature in colorectal cancer: exploring its prognostic value and immunological characteristics.

Background: The heterogeneity of colorectal cancer (CRC) is the main cause of the disparity of drug sensitivity and the variability of prognosis. Pyroptosis is closely associated with the development and prognosis of various tumors, including CRC. Dividing CRC into distinct subgroups based on pyroptosis is a worthwhile topic for improving the precision treatment and prognosis prediction of CRC. Methods: We classified patients into two clusters using the consensus clustering based on the pyroptosis-related genes (PRGs). Next, the prognostic signature was developed with LASSO regression analysis using the screened genes from differentially expressed genes (DEGs) by univariate and multivariate Cox analyses. According to the pyroptosis-related score (PR score) calculated with the signature, patients belonged to two groups with distinct prognosis. Moreover, we assessed the immune profile to explore the relationship between the signature and immunological characteristics. Two single cell sequencing databases were adopted for further exploration of tumor immune microenvironment (TME). In addition, we applied our own cohort and Drugbank to explore the correlation of the signature and clinical therapies. We also studied the expression of key genes by immunohistochemistry. Results: The signature performed well in predicting the prognosis of CRC as the high area under curve (AUC) value demonstrated. Patients with a higher PR score had poorer prognosis and higher expression of immune checkpoints but more abundant infiltration of immune cells. Combining with the indicator of therapeutic analysis, they might benefit more from immune checkpoint blockade (ICB) and neo-adjuvant chemoradiotherapy (nCRT). Conclusion: In conclusion, our study is based on genomics and transcriptomics to investigate the role of PRGs in CRC. We have established a prognostic signature and integrated single-cell data to study the relationship between the signature with the TME in CRC. Its clinical application in reliable prediction of prognosis and personalized treatment was validated by public and own sequencing cohort. It provided a new insight for the personalized treatment of CRC.

Clinical efficacy and safety of targeted injection of PRP with skin booster in the treatment of aging face.

Platelet-rich plasma (PRP) with skin booster is a popular treatment for improving skin quality and reducing the signs of aging. However, few studies have evaluated its clinical efficacy in patients with aging face. This study aimed to evaluate the clinical efficacy, adverse reactions, and follow-up results of targeted injection of PRP with skin booster in treating patients with aging face. The study included 80 patients treated with targeted injection of PRP with skin booster from July 2022 to February 2023. The doctors compared the changes of the patients' facial skin indicators, quality of life, and satisfaction with their appearance before and after treatment, and analyzed the clinical efficacy, adverse reactions, and follow-up results of the patients after treatment. After one course of treatment, the patients' facial skin indicators, quality of life, and satisfaction with their appearance improved significantly, with P < 0.05. The total clinical effective rate was 88.75%, and the incidence of adverse reactions was 6.25%. After half a year of follow-up, 48.75% of the patients were willing to receive further treatment, and their facial soft feel, natural expression, and self-feeling comfort had significantly improved. Targeted injection of PRP with skin booster is an effective and safe treatment for improving facial skin symptoms such as coarse pores and wrinkles in patients with aging face. The results of this study provide evidence for the clinical use of PRP with skin booster in aesthetic medicine.

Heat stress and excessive maturity of fruiting bodies suppress GABA accumulation by modulating GABA metabolism in Pleurotus ostreatus (Jacq. ex Fr.) P. Kumm.

GABA is a health-promoting bioactive substance. Here, the GABA biosynthetic pathways were investigated, and then the dynamic quantitative changes in GABA and the expression levels of genes related to GABA metabolism under heat stress or at different developmental stages of fruiting bodies in Pleurotus ostreatus (Jacq. ex Fr.) P. Kumm were determined. We found that the polyamine degradation pathway was the main route of GABA production under growth normal condition. The accumulation of GABA and the expression of most genes related to GABA biosynthesis, including genes encoding glutamate decarboxylase (PoGAD-2), polyamine oxidase (PoPAO-1), diamine oxidase (PoDAO) and aminoaldehyde dehydrogenase (PoAMADH-1 and PoAMADH-2), were significantly suppressed by heat stress and the excessive maturity of fruiting bodies. Finally, the effects of GABA on the mycelial growth, heat tolerance and the morphogenesis and development of fruiting bodies were studied, the results showed that the deficiency of endogenous GABA inhibited the mycelial growth and primordial formation and aggravated heat damage, whereas exogenous application of GABA could improve thermotolerance and promote the development of fruiting bodies.

Lidocaine alleviates inflammation and pruritus in atopic dermatitis by blocking different population of sensory neurons.

BACKGROUND AND PURPOSE: Atopic dermatitis is a common chronic pruritic inflammatory disease of the skin involving neuro-immune communication. Neuronal mechanism-based therapeutic treatments remain lacking. We investigated the efficacy of intravenous lidocaine therapy on atopic dermatitis and the underlying neuro-immune mechanism. EXPERIMENTAL APPROACH: Pharmacological intervention, immunofluorescence, RNA-sequencing, genetic modification and immunoassay were performed to dissect the neuro-immune basis of itch and inflammation in atopic dermatitis-like mouse model and in patients. KEY RESULTS: Lidocaine alleviated skin lesions and itch in both atopic dermatitis patients and calcipotriol (MC903)-induced atopic dermatitis model by blocking subpopulation of sensory neurons. QX-314, a charged NaV blocker that enters through pathologically activated large-pore ion channels and selectivity inhibits a subpopulation of sensory neurons, has the same effects as lidocaine in atopic dermatitis model. Genetic silencing NaV 1.8-expressing sensory neurons was sufficient to restrict cutaneous inflammation and itch in the atopic dermatitis model. However, pharmacological blockade of TRPV1-positive nociceptors only abolished persistent itch but did not affect skin inflammation in the atopic dermatitis model, indicating a difference between sensory neuronal modulation of skin inflammation and itch. Inhibition of activity-dependent release of calcitonin gene-related peptide (CGRP) from sensory neurons by lidocaine largely accounts for the therapeutic effect of lidocaine in the atopic dermatitis model. CONCLUSION AND IMPLICATIONS: NaV 1.8+ sensory neurons play a critical role in pathogenesis of atopic dermatitis and lidocaine is a potential anti-inflammatory and anti-pruritic agent for atopic dermatitis. A dissociable difference for sensory neuronal modulation of skin inflammation and itch contributes to further understanding of pathogenesis in atopic dermatitis.

Efficacy and safety of radiotherapy combined with raltitrexed and irinotecan for treating unresectable recurrent colorectal cancer: a single-arm phase II trial.

Background: Local recurrence of colorectal cancer is associated with poor prognosis and quality of life. For patients not eligible for curative surgery, chemoradiation could be a promising therapeutic option, but there is no consensus yet for the concurrent chemotherapy regimen. This study evaluated the effects and safety of intensity-modulated radiation therapy (IMRT) when administered concurrently with raltitrexed and irinotecan to patients with unresectable recurrent colorectal cancer. Methods: Eligible patients developed unresectable recurrent colorectal cancer, and were refractory to, or intolerant of, chemotherapy with fluoropyrimidine and oxaliplatin. IMRT was delivered (total dose: 50-60 Gy in 25-30 fractions) concurrently with irinotecan and raltitrexed (200 and 3 mg/m2, respectively, on days 1 and 22). After treatment completion, patients underwent surgery or continued the same regimen of chemotherapy and were assessed by a multidisciplinary team. The primary endpoint was the objective response rate, defined as the proportion of patients with a confirmed complete response or partial response, assessed by radiologist and investigator after the completion of radiotherapy and reconfirmed a month later, in accordance with the Response Evaluation Criteria in Solid Tumors version 1.1. Results: All 30 patients enrolled in this study between January 2019 and July 2020 completed radiotherapy and received a median of five chemotherapy cycles (range, 2-10 cycles). Twelve patients (40.0%) experienced an objective response (two complete responses and ten partial responses) and 17 patients exhibited stable disease [disease control rate (DCR): 96.7%]. The median follow-up was 22 months (range, 4-35 months), by the end of follow-up, six (20.0%) patients had local failure in the irradiation field, four (13.3%) had regional progression outside the irradiation field, 13 (43.3%) had distant metastasis or metastatic progression and nine (30.0%) died. The median progression-free survival (PFS) and local PFS (LPFS) were 13.5 and 23 months, respectively. The incidence of grade 3 or 4 adverse events was 26.7%, the most common of which was neutropenia (13.3%). Conclusions: IMRT with concurrent raltitrexed and irinotecan is a feasible treatment for unresectable recurrent colorectal cancer, which allows good tumor response and local control with acceptable toxicity profile.

Effects of Heat Stress and Exogenous Salicylic Acid on Secondary Metabolites Biosynthesis in Pleurotus ostreatus (Jacq.) P. Kumm.

Pleurotus ostreatus (Jacq.) P. Kumm has high medicinal value, but few studies exist on regulating secondary metabolite biosynthesis. Environmental factors play a substantial role in the accumulation of microbial secondary metabolites. In this study, the effects of heat stress (24 h) and salicylic acid (0.05 mmol/L) treatment on the secondary metabolism of P. ostreatus were analyzed by metabolome, transcriptome, and gene differential expression analysis. Metabolome and transcriptome analyses showed that salicylic acid significantly increased the accumulation of antibiotics and polyketones, while heat stress increased the accumulation of flavonoids, polyketones, terpenoids, and polysaccharides. The content and the biosynthetic genes expression of heparin were markedly increased by heat stress, and the former was increased by 4565.54-fold. This study provides a reference for future studies on secondary metabolite accumulation in edible fungi.

Salicylic Acid Enhances Heat Stress Resistance of Pleurotus ostreatus (Jacq.) P. Kumm through Metabolic Rearrangement.

Pleurotus ostreatus (Jacq.) P. Kumm is cultivated worldwide, and its growth is seriously threatened by heat stress. Here, we performed a comprehensive analysis to investigate the influence of the phytohormone salicylic acid (SA) in P. ostreatus under HS. The results showed that the hyphal growth recovery rate and the antioxidant capacity of P. ostreatus increased with exogenous SA application (0.01 mmol/L and 0.05 mmol/L) after HS treatment. Metabolomic and transcriptomic analyses showed that SA application (0.05 mmol/L) weakened central carbon metabolism to allow cells to survive HS efficiently. In addition, SA shifted glycolysis to one-carbon metabolism to produce ROS scavengers (GSH and NADPH) and reduced ROS production by altering mitochondrial metabolism. SA also maintained nucleotide homeostasis, led to membrane lipid remodeling, activated the MAPK pathway, and promoted the synthesis of cell-wall components. This study provides a reference for further study of SA in microorganisms.

Comparison of the efficacy and safety between a low-fluence 1064-nm Q-switched neodymium-doped yttrium aluminum garnet laser and a conventional Q-switched 532-nm laser for the treatment of cafe-au-lait macules in 40 Chinese children: a prospective, randomized, parallel-controlled, evaluator-blinded trial.

Cafe-au-lait macules (CALMs) affect the appearance of patients and can result in serious psychological problems. Successful treatments without adverse effects remain challenging. We designed a prospective, randomized, controlled, evaluator-blinded trial on 40 pediatric patients to compare the efficacy between a low-fluence 1064-nm Q-switched Nd:YAG laser and a Q-switched Nd:YAG 532-nm laser for the treatment of solitary CALMs in children. We randomly assigned participants into 2 groups. We treated those in the first group with 3 sessions of 532-nm QS laser at 1-month intervals, and those in the second group with 6 sessions of 1064-nm LFQS laser at 2-week intervals. We found no significant differences in treatment efficacy (p = 0.14). The 1064-nm laser group referred significantly less pain than the 532-nm laser group (p = 0.0001). Side effects were detected in 5 patients in the 532-nm laser group. The difference of the side effects was statistically significant (p = 0.04). Two patients in 532-nm laser group were recurred and none in 1064-nm laser group. On a univariate logistic regression analysis, lesions with brown color, small size, and irregular edges were significantly associated with better outcomes (> 50% clearance). Multivariate logistic regression analysis found that brown lesions and lesions with irregular edges had higher odds of getting > 50% clearance (p < 0.05). In conclusion, the 1064-nm LFQS laser produced fewer side effects, less pain, and shorter recovery time than the 532-nm laser. Irregular-bordered, smaller, brown lesions improved better than smooth-bordered, larger, light brown lesions. Moreover, the 1064-nm laser may be a better choice for treating large size CALMs. However, no significant differences were found in terms of the treatment efficacy and recurrence.

Adjuvant SOX chemotherapy versus concurrent chemoradiotherapy after D2 radical resection of locally advanced esophagogastric junction (EGJ) adenocarcinoma: study protocol for a randomized phase III trial (ARTEG).

BACKGROUND: Survival benefit of adjuvant radiotherapy for locally advanced gastric cancer following gastrectomy plus D2 lymphadenectomy has always been controversial. Esophagogastric junction (EGJ) adenocarcinoma, which is usually classified as gastric cancer in East Asia, often has a higher locoregional recurrence rate after operation because of its special anatomical characteristics. The aim of this study is to determine whether adjuvant radiotherapy can improve survival of locally advanced EGJ adenocarcinoma after D2 radical resection. METHODS: In this phase III, randomized, open label, controlled trial, we plan to recruit 378 patients with Siewert type II and III adenocarcinoma of EGJ, who had undergone transabdominal radical surgery and D2 lymphadenectomy, and were divided into pathological stage IIB to IIIC. All patients will be randomized 1:1 to receive either adjuvant chemotherapy alone (control group) or adjuvant chemotherapy plus chemoradiotherapy (experimental group). Patients allocated to control group will receive eight cycles of S-1 plus oxaliplatin (SOX), while the experimental group will receive two cycles of SOX followed by 45-Gy RT combined with S-1 and four additional cycles of SOX. The primary endpoint is 3-year disease-free survival rate (DFS). The secondary endpoints are 3-year overall survival rate (OS), 3-year locoregional recurrence-free survival rate (LRFS), 3-year distant metastasis-free survival rate (DMFS), and quality of life (QoL). DISCUSSION: In the past, the adjuvant treatment of EGJ adenocarcinoma needs to draw on the experience of esophageal adenocarcinoma or gastric adenocarcinoma. In this study, EGJ adenocarcinoma is considered as an independent disease, and the conclusion will provide evidence for optimal adjuvant therapy of locally advanced EGJ adenocarcinoma after D2 radical resection. TRIAL REGISTRATION: ClinicalTrials.gov NCT03973008 . Registered on 1 June 2019 (retrospectively registered), URL: https://clinicaltrials.gov/ct2/show/NCT03973008?term=NCT03973008&draw=2&rank=1.

Effects of exogenous ascorbic acid on the mycelia growth and primordia formation of Pleurotus ostreatus.

Primordia formation is the first and most critical step in the development of fruiting bodies of edible fungi. In this study, the effects of exogenous ascorbic acid (ASA) on the Pleurotus ostreatus mycelia growth and primordia formation were researched and the results showed that the growth rate of P. ostreatus mycelia was accelerated and the time of primordia formation was advanced. The protein content and ascorbate oxidase (AAO) activity analysis showed that with the increase of ASA concentration, the protein content of mycelia first decreased and then increased, and in a certain concentration range, exogenous ASA could significantly promote the activity of AAO. Further expression analysis of the development regulating genes (Pofst3 and Pofst4) as well as blue light receptor coding genes (PoWC-1 and PoWC-2) showed the expression levels of those four genes all changed after the exogenous ASA addition, which indicated that the expression changes of PoWC-1 and PoWC-2, two key genes in the light morphogenesis, might affect the expression levels of development regulating genes Pofst3 and Pofst4, so as to lead to the formation of primordia in advance.

Expanding mutational spectrum of HRAS by a patient with Schimmelpenning-Feuerstein-Mims syndrome.

As one of the epidermal nevus syndromes, Schimmelpenning-Feuerstein-Mims (SFM) is characterized by craniofacial nevus sebaceous (NS) and extracutaneous abnormalities (e.g., brain, eyes, and bone). Here, we report a case of a 4-year-old boy who presented with significant skin abnormalities (NS in the scalp, extensive epidermal nevus along Blaschko's lines), ocular abnormalities (strabismus), central nervous system abnormalities (seizure and mental retardation), lymphatic dysplasia (chylous pleural and pericardial effusion), cardiac abnormalities (patent foramen ovale), urogenital system abnormalities (cryptorchidism, hypospadias), and a tumor predisposition (embryonal rhabdomyosarcoma). DNA samples from NS, rhabdomyosarcoma, and peripheral blood leukocytes were analyzed by next-generation sequencing. A novel mutation in the HRAS gene (c.38G>T; p.Gly13Val) was detected in a mosaic state in NS, rhabdomyosarcoma, and peripheral blood leukocytes, with different ratio of heterozygous mutation (HRAS c.38G>T) of 39.90% (9412/23 588 reads), 73.03% (205 562/281 468 reads), and 14.16% (15 837/111 842 reads), respectively. By predicting the impact of the mutation on the biological function of protein, we found that the novel HRAS mutation (c.38G>T; p.Gly13Val) had the highest damaging scores among other HRAS mutations reported so far. This is the first reported SFM syndrome patient with novel mosaic HRAS mutation, which may help to expand the mutational spectrum of HRAS and better understand the role of HRAS in the disease.

miR­576­5p promotes epithelial­to­mesenchymal transition in colorectal cancer by targeting the Wnt5a­mediated Wnt/ß­catenin signaling pathway.

Colorectal cancer (CRC) is one of the most common types of malignancy and the third most commonly diagnosed form of cancer worldwide, ranking as the fourth leading cause of cancer­associated mortality. MicroRNA (miR)­576­5p has been reported to be highly expressed in patients with CRC; however, its biological role remains unclear. The present study aimed therefore to investigate the biological role and underlying mechanism of miR­576­5p in CRC cell line SW480. The viability of SW480 cells following transfection with miR­576­5p mimic or inhibitor was analyzed using MTT assay. Wound healing and Transwell assays were performed to determine the cell migratory and invasive abilities, respectively. A dual luciferase reporter assay was used to verify the predicted binding site between miR­576­5p and Wnt5a. Reverse transcription­quantitative PCR and western blotting were used to analyze the expression levels of miR­576­5p, E­cadherin, N­cadherin, vimentin, Snail1, Wnt5a, ß­catenin, c­myc, cyclin D1 and p/t­c­Jun. Using bioinformatics analysis, high expression of miR­576­5p was found not only in tumor tissues, compared with the normal tissue, but also in CRC cells, compared with NCM460 cells. Furthermore, the inhibition of miR­576­5p expression significantly decreased the cell viability and the migratory and invasive abilities of SW480 cells, and suppressed the epithelial­to­mesenchymal transition (EMT). In addition, miR­576­5p could interact with Wnt5a and regulate the expression level of Wnt5a in order to influence the activity of Wnt/ß­catenin signaling. The results from rescue experiments further demonstrated that the effect of miR­576­5p overexpression on cell metastasis and EMT was reversed by Wnt5a overexpression or treatment with XAV­939, which is an inhibitor of the Wnt/ß­catenin signaling pathway. In conclusion, the findings from the present study suggested that inhibition of miR­576­5p may suppress SW480 cell metastasis and EMT by targeting Wnt5a and regulating the Wnt5a­mediated Wnt/ß­catenin signaling pathway, providing a potential therapeutic target for the treatment of CRC.

The 256 kb mitochondrial genome of Clavaria fumosa is the largest among phylum Basidiomycota and is rich in introns and intronic ORFs.

In the present study, the complete mitogenome of Clavaria fumosa, was sequenced, assembled, and compared. The complete mitogenome of C. fumosa is 256,807 bp in length and is the largest mitogenomes among all Basidiomycota mitogenomes reported. Comparative mitogenomic analysis indicated that the C. fumosa mitogenome contained the most introns and intronic ORFs among all fungal mitogenomes. Large intergenic regions, intronic regions, accumulation of repeat sequences and plasmid-derived genes together promoted the size expansion of the C. fumosa mitogenome. In addition, the rps3 gene was found subjected to positive selection between some Agaricales species. We found frequent intron gain/loss events in Agaricales mitogenomes, and four novel intron classes were detected in the C. fumosa mitogenome. Large-scale gene rearrangements were found occurred in Agaricales species and the C. fumosa mitogenome had a unique gene arrangement which differed from other Agaricales species. Phylogenetic analysis for 76 Basidiomycetes based on combined mitochondrial gene sets indicated that mitochondrial genes could be used as effective molecular markers for reconstructing evolution of Basidiomycota. The study served as the first report on the mitogenomes of the family Clavariaceae, which will promote the understanding of the genetics, evolution and taxonomy of C. fumosa and related species.

Clinical Outcomes and Safety of Different Treatment Modes for Local Recurrence of Rectal Cancer.

OBJECTIVE: Optimal approaches to patients with local recurrence of rectal cancer are unclear in China. This study aimed to evaluaty -30te the clinical outcomes and toxicity associated with different treatment regimens for patients with local recurrence of rectal cancer. METHODS: A retrospective chart review of patients with local recurrence of rectal cancer and previous radical surgical treatment between March 2010 and December 2017 with curative intent was performed. Disease-related endpoints included treatment progression-free survival (PFS) and overall survival (OS) using the Kaplan-Meier method. Toxicities were assessed using Common Terminology Criteria for Adverse Events, version 5.0, and complications were scored according to the Clavien-Dindo classification. RESULTS: A total of 71 patients met the inclusion criteria in this study. The recurrence sites were mainly local recurrence in the pelvic cavity and regional lymph node metastasis. Twenty patients received chemoradiotherapy combined with surgery, 10 underwent surgery alone, and others received chemoradiotherapy-alone (n = 27) and chemotherapy-alone (n = 14) treatment. A clear difference was found in PFS between surgery/chemoradiotherapy with surgery and chemoradiotherapy/chemotherapy groups (26.6 months vs 14.1 months, P = 0.033). The PFS of patients in the surgery combined with chemoradiotherapy, surgery alone, and chemotherapy/chemoradiotherapy groups was 65.2 months, 20.2 months, and 14.2 months, respectively (P = 0.042). The multivariate analysis of PFS demonstrated that surgery was an independent factor. The proportion of patients with distant metastases after chemoradiotherapy/chemotherapy was higher than that of patients undergoing surgery (36.6% vs 21.4%, P = 0.179). The OS of patients in the surgery combined with chemoradiotherapy, surgery alone, and chemotherapy/chemoradiotherapy groups was 89.4 months, 66.0 months, and 62.8 months, respectively (P = 0.189). Radiation treatment and surgery did not increase extra severe toxicities. CONCLUSION: Surgery combined with chemoradiotherapy was a beneficial treatment mode for managing patients with locally recurrent, nonmetastatic rectal cancer. It was associated with better local disease control, no increase in toxicity, and prolonged survival among patients with locally recurrent rectal cancer.

Next-generation sequencing through multigene panel testing for the diagnosis of hereditary epidermolysis bullosa in Chinese population.

Epidermolysis bullosa (EB) is a heritable blistering disorder. We performed a next-generation sequencing-based multigene panel test and successfully predicted 100% of the EB types, including, 36 EB simplex (EBS), 13 junctional EB (JEB), 86 dystrophic EB (DEB), and 3 Kindler EB. Chinese JEB and recessive DEB (RDEB) patients have relatively mild phenotypes; for severe type separately accounts for 45.5% and 23.8%, respectively. We identified 96 novel and 49 recurrent pathogenic variants in 11 genes, although we failed to detect the second mutation in one JEB and five RDEB patients. We identified one novel p.E475K mosaic mutation in the clinically normal mother of one out of 13 EBS patients with KRT5 mutations, one recurrent p.G2034R mosaic mutation, and one novel p.G2043R mosaic mutation in the clinically normal relatives of two out of 19 dominant DEB patients. This study shows that next-generation technology could be an effective tool in diagnosing EB.