Lactylation: the novel histone modification influence on gene expression, protein function, and disease.

Lactic acid, traditionally considered as a metabolic waste product arising from glycolysis, has undergone a resurgence in scientific interest since the discovery of the Warburg effect in tumor cells. Numerous studies have proved that lactic acid could promote angiogenesis and impair the function of immune cells within tumor microenvironments. Nevertheless, the precise molecular mechanisms governing these biological functions remain inadequately understood. Recently, lactic acid has been found to induce a posttranslational modification, lactylation, that may offer insight into lactic acid's non-metabolic functions. Notably, the posttranslational modification of proteins by lactylation has emerged as a crucial mechanism by which lactate regulates cellular processes. This article provides an overview of the discovery of lactate acidification, outlines the potential "writers" and "erasers" responsible for protein lactylation, presents an overview of protein lactylation patterns across different organisms, and discusses the diverse physiological roles of lactylation. Besides, the article highlights the latest research progress concerning the regulatory functions of protein lactylation in pathological processes and underscores its scientific significance for future investigations.

A novel long non-coding RNA SLNCR1 promotes proliferation, migration, and invasion of melanoma via transcriptionally regulating SOX5.

Steroid receptor RNA activator (SRA)-like non-coding RNA (SLNCR1) has been implicated in various tumorigenic processes, but the precise regulatory role in melanoma progression remains uncertain. We performed a comprehensive analysis to investigate the prognostic value of SLNCR1 expression in patients with melanoma by TCGA database and melanoma tissue samples via the Kaplan-Meier method. Subsequently, we conducted qRT-PCR and Fluorescence in Situ Hybridization (FISH) assays to identify SLNCR1 expression levels and localization in tissues and cells, respectively. Loss-of-function assays utilizing shRNAs vectors were used to investigate the potential impact of SLNCR1. Our data showed that SLNCR1 is significantly up-regulated in human malignant melanoma tissues and cell lines and functions as an oncogene. Silencing of SLNCR1 suppressed melanoma cell proliferation, migration, invasion, and inhibited tumorigenesis in a mouse xenograft model. Additionally, we employed bioinformatic predictive analysis, combined with dual-luciferase reporter analysis and functional rescue assays, to elucidate the mechanistic target of the SLNCR1/SOX5 axis in melanoma. Mechanistically, we discovered that SLNCR1 promotes EMT of human melanoma by targeting SOX5, as downregulation of SLNCR1 expression leads to a decrease in SOX5 protein levels and inhibits melanoma tumorigenesis. Our research offers promising insights for more precise diagnosis and treatment of human melanoma.

Arginine methylation-dependent cGAS stability promotes non-small cell lung cancer cell proliferation.

Cyclic GMP-AMP synthase (cGAS), promotes non-small cell lung cancer (NSCLC) cell proliferation. However, the specific mechanisms of cGAS-mediated NSCLC cell proliferation are largely unknown. In this study, we found asymmetric dimethylation by protein arginine methyltransferase 1 (PRMT1) at R127 of cGAS. This facilitated the binding of deubiquitinase USP7 and contributed to deubiquitination and stabilization of cGAS. PRMT1-and USP7-dependent cGAS stability, which also played a pivotal role in accelerating NSCLC cell proliferation through activating AKT pathway. We validated that the expression of cGAS and PRMT1 were positive correlated in human non-small cell lung cancer samples. Our study demonstrates a unique mechanism for managing cGAS stability by arginine methylation and indicates that PRMT1-cGAS-USP7 axis is a potential therapeutic target for NSCLC.

Association between NTCP hepatic expression and inflammation/fibrosis as well as gender-specific differences in chronic HBV-infected patients.

To investigate the relationship between the expression of hepatitis B virus (HBV) functional receptor sodium taurocholate cotransporting polypeptide (NTCP) with disease progression and gender-specific differences in chronic HBV-infected patients. Liver samples were collected from chronic HBV-infected patients who underwent percutaneous liver biopsy or liver surgery. HBV DNA levels and the mRNA and protein expression levels of NTCP in liver tissues were determined. The relationship between NTCP expression and HBV DNA levels, inflammatory activity, fibrosis, and gender-specific differences were analyzed. A total of 94 chronic HBV-infected patients were included. Compared with patients with a METAVIR score of A0-1 or F0-1, patients with score of A2 or F2/F3 had a relatively higher level of NTCP expression. NTCP levels were positively correlated with HBV DNA levels. The inflammatory activity scores and fibrosis scores of women <50 years were significantly lower than those of women ≥50 years and age-matched males. In patients with score A0-2 or F0-3, women <50 years have lower NTCP expression level compared to women ≥50 years and age-matched males. NTCP can promote the disease progression by affecting the viral load of HBV. The NTCP expression difference may be why male and postmenopausal women are more prone to disease progression than reproductive women.

Taxifolin inhibits melanoma proliferation/migration impeding USP18/Rac1/JNK/ß-catenin oncogenic signaling.

BACKGROUND: Metastatic melanoma is a fatal cancer. Despite the advances in targeted therapy and immunotherapy for patients with melanoma, drug resistance and low response rates pose a considerable challenge. Taxifolin is a multifunctional natural compound with emerging antitumor potentials. However, its utility in melanoma treatment remains unclear. PURPOSE: The study aimed to investigate the effect of purified Taxifolin from Larix olgensis roots (Changbai Mountain, China) on melanoma and explore the underlying mechanism. METHODS: Purified Taxifolin from Larix olgensis roots was evaluated for its antimelanoma effects in vitro and in vivo settings. RNA-seq analysis was performed to explore the underlying mechanism. RESULTS: Purified Taxifolin (> 99 %) from Larix olgensis roots inhibited the proliferation and migration of B16F10 melanoma cells at 200 and 400 µM, and of A375 cells at 100 and 200 µM. Taxifolin administered at 60 mg/kg suppressed tumor growth and metastasis in mouse models without causing significant toxicity. Taxifolin modulated USP18/Rac1/JNK/ß-catenin axis to exert its antitumor effect. CONCLUSION: These findings indicate that Taxifolin derived from Larix olgensis roots may be a promising antimelanoma therapy.

PEN-coated superparamagnetic iron-mediated delivery of siSnail2 to inhibit metastasis and promote ferroptosis in the treatment of cancer.

Cancer represents a significant global public health challenge, and conventional cancer therapies such as surgery and chemoradiotherapy are not enough due to the increased complexity of cancer. Nanotechnology has the potential to revolutionize tumor treatments by integrating gene therapy, tumor targeting, and drug delivery. In this study, we demonstrated that Snail2 plays a crucial role in the migration and invasion of lung and liver carcinoma. We proposed a novel approach to synergize the aminated crosslinking dextran coat of superparamagnetic iron oxide nano worms (CLIO-NH2, CN) with small interfering Snail2 RNA (siSnail2). The efficiency of siSnail2 delivery was significantly improved by coating CN with N-Isopropylacrylamide-modified polyethylenimine (CNP). In vitro, experiments revealed that CNP@siSnail2 effectively inhibited cancer cell EMT, migration, and invasion. Moreover, CNP@ siSnail2 promoted cancer cell death through various mechanisms, including apoptosis and ferroptosis. The combination of CNP@ siSnail2 and cisplatin significantly improved the anti-tumor effect of the treatment. Animal models demonstrated that the combined treatment of CNP@ siSnail2 and cisplatin resulted in excellent tumor inhibition effects. Our findings provide a potential combined treatment strategy for cancer therapy.

The mechanism and application of traditional Chinese medicine extracts in the treatment of lung cancer and other lung-related diseases.

Lung cancer stands as one of the most prevalent malignancies worldwide, bearing the highest morbidity and mortality rates among all malignant tumors. The treatment of lung cancer primarily encompasses surgical procedures, radiotherapy, and chemotherapy, which are fraught with significant side effects, unfavorable prognoses, and a heightened risk of metastasis and relapse. Although targeted therapy and immunotherapy have gradually gained prominence in lung cancer treatment, diversifying the array of available methods, the overall recovery and survival rates for lung cancer patients remain suboptimal. Presently, with a holistic approach and a focus on syndrome differentiation and treatment, Traditional Chinese Medicine (TCM) has emerged as a pivotal player in the prognosis of cancer patients. TCM possesses characteristics such as targeting multiple aspects, addressing a wide range of concerns, and minimizing toxic side effects. Research demonstrates that Traditional Chinese Medicine can significantly contribute to the treatment or serve as an adjunct to chemotherapy for lung cancer and other lung-related diseases. This is achieved through mechanisms like inhibiting tumor cell proliferation, inducing tumor cell apoptosis, suppressing tumor angiogenesis, influencing the cellular microenvironment, regulating immune system function, impacting signal transduction pathways, and reversing multidrug resistance in tumor cells. In this article, we offer an overview of the advancements in research concerning Traditional Chinese Medicine extracts for the treatment or adjunctive chemotherapy of lung cancer and other lung-related conditions. Furthermore, we delve into the challenges that Traditional Chinese Medicine extracts face in lung cancer treatment, laying the foundation for the development of diagnostic, prognostic, and therapeutic targets.

The emerging role of m6A modification of non-coding RNA in gastrointestinal cancers: a comprehensive review.

Gastrointestinal (GI) cancer is a series of malignant tumors with a high incidence globally. Although approaches for tumor diagnosis and therapy have advanced substantially, the mechanisms underlying the occurrence and progression of GI cancer are still unclear. Increasing evidence supports an important role for N6-methyladenosine (m6A) modification in many biological processes, including cancer-related processes via splicing, export, degradation, and translation of mRNAs. Under distinct cancer contexts, m6A regulators have different expression patterns and can regulate or be regulated by mRNAs and non-coding RNAs, especially long non-coding RNAs. The roles of m6A in cancer development have attracted increasing attention in epigenetics research. In this review, we synthesize progress in our understanding of m6A and its roles in GI cancer, especially esophageal, gastric, and colorectal cancers. Furthermore, we clarify the mechanism by which m6A contributes to GI cancer, providing a basis for the development of diagnostic, prognostic, and therapeutic targets.

Effect of anti-skin disorders of ginsenosides- A Systematic Review.

Ginsenosides are bioactive components of Panax ginseng with many functions such as anti-aging, anti-oxidation, anti-inflammatory, anti-fatigue, and anti-tumor. Ginsenosides are categorized into dammarane, oleanene, and ocotillol type tricyclic triterpenoids based on the aglycon structure. Based on the sugar moiety linked to C-3, C-20, and C-6, C-20, dammarane type was divided into protopanaxadiol (PPD) and protopanaxatriol (PPT). The effects of ginsenosides on skin disorders are noteworthy. They play anti-aging roles by enhancing immune function, resisting melanin formation, inhibiting oxidation, and elevating the concentration of collagen and hyaluronic acid. Thus, ginsenosides have previously been widely used to resist skin diseases and aging. This review details the role of ginsenosides in the anti-skin aging process from mechanisms and experimental research.

Deficiency of BAP1 inhibits neuroblastoma tumorigenesis through destabilization of MYCN.

The transcription factor MYCN is frequently amplified and overexpressed in a variety of cancers including high-risk neuroblastoma (NB) and promotes tumor cell proliferation, survival, and migration. Therefore, MYCN is being pursued as an attractive therapeutic target for selective inhibition of its upstream regulators because MYCN is considered a "undruggable" target. Thus, it is important to explore the upstream regulators for the transcription and post-translational modification of MYCN. Here, we report that BRCA1-associated protein-1 (BAP1) promotes deubiquitination and subsequent stabilization of MYCN by directly binding to MYCN protein. Furthermore, BAP1 knockdown inhibits NB tumor cells growth and migration in vitro and in vivo, which can be rescued partially by ectopic expression of MYCN. Importantly, depletion of BAP1 confers cellular resistance to bromodomain and extraterminal (BET) protein inhibitor JQ1 and Aurora A kinase inhibitor Alisertib. Furthermore, IHC results of NB tissue array confirmed the positive correlation between BAP1 and MYCN protein. Altogether, our work not only uncovers an oncogenic function of BAP1 by stabilizing MYCN, but also reveals a critical mechanism for the post-translational regulation of MYCN in NB. Our findings further indicate that BAP1 could be a potential therapeutic target for MYCN-amplified neuroblastoma.

Multi-scale sequential feature selection for disease classification using Raman spectroscopy data.

Raman spectroscopy (RS) optical technology promises non-destructive and fast application in medical disease diagnosis in a single step. However, achieving clinically relevant performance levels remains challenging due to the inability to search for significant Raman signals at different scales. Here we propose a multi-scale sequential feature selection method that can capture global sequential features and local peak features for disease classification using RS data. Specifically, we utilize the Long short-term memory network (LSTM) module to extract global sequential features in the Raman spectra, as it can capture long-term dependencies present in the Raman spectral sequences. Meanwhile, the attention mechanism is employed to select local peak features that were ignored before and are the key to distinguishing different diseases. Experimental results on three public and in-house datasets demonstrate the superiority of our model compared with state-of-the-art methods for RS classification. In particular, our model achieves an accuracy of 97.9 ± 0.2% on the COVID-19 dataset, 76.3 ± 0.4% on the H-IV dataset, and 96.8 ± 1.9% on the H-V dataset.

Circulating microRNAs as diagnostic biomarkers for melanoma: a systematic review and meta-analysis.

BACKGROUND: Recent studies have shown that circulating microRNAs (miRNAs) can be used as diagnostic biomarkers for melanoma. This study aimed to evaluate the diagnostic value of circulating miRNAs for melanoma. METHODS: A comprehensive literature search was conducted and the quality of the included literature was evaluated using QUADAS-2 (Quality Assessment for diagnostic accuracy studies), and the diagnostic accuracy was assessed by pooled sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic odds ratio (DOR), and area under the curve (AUC). We used Deeks' funnel plot to evaluate publication bias. RESULTS: The meta-analysis included 10 articles covering 16 studies, and the results showed that circulating miRNAs provide high diagnostic accuracy for melanoma. The overall pooled sensitivity was 0.87 (95% CI: 0.82-0.91), specificity was 0.81 (95% CI: 0.77-0.85), PLR was 4.6 (95% CI: 3.7-5.8), NLR was 0.16 (95% CI: 0.11-0.23), DOR was 29 (95% CI: 18-49), and AUC was 0.90 (95% CI: 0.87-0.92), respectively. Subgroup analysis showed better diagnostic value in miRNA clusters, European population, plasma miRNAs, and upregulated miRNAs compared to other subgroups. CONCLUSIONS: The results indicated that circulating microRNAs can be used as a non-invasive biomarker for the diagnosis of melanoma.

Patients with melanoma treated with immune checkpoint inhibitors who had non-thyroid endocrine and skin immune-related adverse events have better prognosis: A systematic review and meta-analysis.

Background: Several studies have reported an association between the occurrence of immune-related adverse events (irAEs) and prognosis in patients with melanoma treated with immune checkpoint inhibitors (ICIs), but the results remain controversial. We conducted a systematic review and meta-analysis to investigate the association between irAEs and survival in patients with melanoma treated with ICIs. Methods: We searched the PubMed, Web of Science, and China National Knowledge Infrastructure databases through May 5, 2022 for clinical studies evaluating the association between irAEs and in melanoma patients treated with ICIs. Combined hazard ratios (HRs) for overall survival (OS) and progression-free survival (PFS) were calculated using fixed- or random-effects models based on heterogeneity. Results: A total of 60 articles were included, with 16,520 patients. In patients with melanoma treated with ICIs, the occurrence of irAEs was significantly associated with better OS (HR, 0.58; 95% confidence interval [CI], 0.51-0.66; P<0.00001) and PFS (HR, 0.61; 95%CI, 0.51-0.72; P<0.00001). Endocrine irAEs (OS, HR, 0.81; 95%CI, 0.72-0.92; P=0.001; PFS: HR, 0.84; 95%CI, 0.73-0.96, P=0.009), skin irAEs (OS, HR, 0.59; 95%CI, 0.41-0.85; P=0.004; PFS: HR, 0.43; 95%CI, 0.36-0.52; P<0.00001), vitiligo (OS, HR, 0.22; 95%CI, 0.15-0.31; P<0.00001; PFS, HR, 0.33; 95%CI, 0.25-0.44; P<0.00001), and grade 1-2 irAEs (OS, HR, 0.67; 95%CI, 0.58-0.78; P<0.00001; PFS, HR, 0.62; 95%CI, 0.51-0.76; P<0.00001) showed similar results. However, thyroid, lung, gastrointestinal, liver, and grade 3-4 irAEs were not significantly associated with OS and PFS. The occurrence of non-thyroid endocrine irAEs was significantly associated with better OS (HR, 0.22; 95%CI, 0.15-0.31; P<0.00001). In patients with melanoma treated with anti-programmed cell death protein 1 (OS, HR, 0.61; 95%CI, 0.51-0.72; P<0.00001; PFS, HR, 0.59; 95%CI, 0.47-0.74; P<0.00001), the association between irAEs and clinical benefit was clearer than in patients treated with anti-cytotoxic T-lymphocyte-associated protein 4 (OS, HR, 0.68; 95%CI, 0.52-0.89; P=0.005; PFS, HR, 0.93; 95%CI, 0.49-1.78; P=0.83). Conclusion: Among patients with melanoma treated with ICIs, those who developed non-thyroid endocrine irAEs and cutaneous irAEs have better prognosis. This suggests that non-thyroid endocrine irAEs and cutaneous irAEs may be a prognostic biomarker for patients with melanoma treated with ICIs. Systematic review registration: https://www.crd.york.ac.uk/PROSPERO/, identifier CRD42022338308.

Glutamine deficiency promotes recurrence and metastasis in colorectal cancer through enhancing epithelial-mesenchymal transition.

BACKGROUND: Glutamine is the most abundant amino acid in the body and plays a vital role in colorectal cancer (CRC) cell metabolism. However, limited studies have investigated the clinical and prognostic significance of preoperative serum glutamine levels in patients with colorectal cancer, and the underlying mechanism has not been explored. METHODS: A total of 121 newly diagnosed CRC patients between 2012 and 2016 were enrolled in this study. Serum glutamine levels were detected, and their associations with clinicopathological characteristics, systemic inflammation markers, carcinoembryonic antigen (CEA) and prognosis were analysed. In addition, the effect of glutamine depletion on recurrence and metastasis was examined in SW480 and DLD1 human CRC cell lines, and epithelial-mesenchymal transition (EMT)-related markers were detected to reveal the possible mechanism. RESULTS: A decreased preoperative serum level of glutamine was associated with a higher T-class and lymph node metastasis (P < 0.05). A higher serum level of glutamine correlated with a lower CEA level (r = - 0.25, P = 0.02). Low glutamine levels were correlated with shorter overall survival (OS) and disease-free survival (DFS). Multivariate Cox regression analysis showed that serum glutamine was an independent prognostic factor for DFS (P = 0.018), and a nomogram predicting the probability of 1-, 3- and 5-year DFS after radical surgery was built. In addition, glutamine deficiency promoted the migration and invasion of CRC cells. E-cadherin, a vital marker of EMT, was decreased, and EMT transcription factors, including zeb1and zeb2, were upregulated in this process. CONCLUSIONS: This study elucidated that preoperative serum glutamine is an independent prognostic biomarker to predict CRC progression and suggested that glutamine deprivation might promote migration and invasion in CRC cells by inducing the EMT process.

Role of Circular RNAs in the Pathogenesis of Malignant Melanoma.

Malignant melanoma is one of the most aggressive types of skin cancer. Thus, efficient diagnosis and treatment methods are crucial for advanced melanoma. Circular RNAs (circRNAs) have been regarded as a 'splicing noise' in the past decades. However, several circRNAs have been recently reported to be differentially expressed in melanoma, and the cell or tissue-specific expression makes these suitable candidate diagnostic or therapeutic biomarkers. In addition, emerging studies have confirmed that circular RNAs play pivotal roles in the proliferation, invasion, metastasis, and migration of malignant melanoma. However, specific pathogenic mechanisms between melanoma and circRNAs remain unclear. In the present study, it was summarized that circRNAs are associated with the pathogenesis of melanoma, including hsa_circ_0083444, hsa_circ_0005320, hsa_circ_0067531, hsa_circ_0084043, hsa_circ_0000082, hsa_circ_0016418, hsa_circ_0085533 and hsa_circ_0025039, hsa_circ_0001946, hsa_circ_0002770, hsa_circ_0079593, hsa_circ_0027247, hsa_circ_0017247, hsa_circ_0020710. These can provide potential diagnosis, treatment, and prognostication biomarkers for advanced melanoma in clinical applications.

Genetics of autism spectrum disorder: an umbrella review of systematic reviews and meta-analyses.

Autism spectrum disorder (ASD) is a class of neurodevelopmental conditions with a large epidemiological and societal impact worldwide. To date, numerous studies have investigated the associations between genetic variants and ASD risk. To provide a robust synthesis of published evidence of candidate gene studies for ASD, we performed an umbrella review (UR) of meta-analyses of genetic studies for ASD (PROSPERO registration number: CRD42021221868). We systematically searched eight English and Chinese databases from inception to March 31, 2022. Reviewing of eligibility, data extraction, and quality assessment were performed by two authors. In total, 28 of 5062 retrieved articles were analyzed, which investigated a combined 41 single nucleotide polymorphisms (SNPs) of nine candidate genes. Overall, 12 significant SNPs of CNTNAP2, MTHFR, OXTR, SLC25A12, and VDR were identified, of which associations with suggestive evidence included the C677T polymorphism of MTHFR (under allelic, dominant, and heterozygote models) and the rs731236 polymorphism of VDR (under allelic and homozygote models). Associations with weak evidence included the rs2710102 polymorphism of CNTNAP2 (under allelic, homozygote, and recessive models), the rs7794745 polymorphism of CNTNAP2 (under dominant and heterozygote models), the C677T polymorphism of MTHFR (under homozygote model), and the rs731236 polymorphism of VDR (under dominant and recessive models). Our UR summarizes research evidence on the genetics of ASD and provides a broad and detailed overview of risk genes for ASD. The rs2710102 and rs7794745 polymorphisms of CNTNAP2, C677T polymorphism of MTHFR, and rs731236 polymorphism of VDR may confer ASD risks. This study will provide clinicians and healthcare decision-makers with evidence-based information about the most salient candidate genes relevant to ASD and recommendations for future treatment, prevention, and research.

Signal transducer and activator of transcription 3 cooperates with androgen receptor/cell cycle-related kinase signalling pathway in the progression of hepatitis B virus infection and gender differences.

The study aimed to investigate the role of androgen receptor (AR)/cell cycle-related kinase (CCRK) signalling pathway in chronic hepatitis B virus (HBV) infection and gender differences, and the contribution of AR regulatory factor signal transducer and activator of transcription 3 (STAT3) in it. AR, CCRK, and phosphorylated STAT3 expressions in liver tissues of chronic HBV-infected patients and non-HBV controls were determined by western blot and compared between genders. The relationships of expression levels with serum HBV DNA levels, liver inflammation activity, and fibrosis score were analysed in chronic HBV-infected patients. The relationships between expression levels of three proteins were also analysed. HBV-infected patients had significantly higher expression levels of AR, CCRK, and p-STAT3Tyr705 compared with controls (p < .01). The expression levels of AR, CCRK, and p-STAT3Tyr705 in chronic HBV-infected patients with severe inflammation were significantly higher than those with mild inflammation (p < .05). Expression levels in patients with heavier fibrosis (stage F4) were higher than in those with less fibrosis (stages F0-3) (p < .01). No gender differences were observed in AR, CCRK, and p-STAT3Tyr705 levels in non-HBV controls; higher levels were observed in HBV-infected males than in HBV-infected females (p < .05). AR, CCRK, and p-STAT3Tyr705 levels in liver tissues positively correlated with each other (p < .0001) and with serum HBV DNA levels (p < .0001). In conclusion, in this study, we first found concordant over-expression of AR, CCRK, and STAT3 in liver tissues of chronic HBV-infected patients who have not yet developed HCC, significantly correlated with the severity of the disease and showed gender differences. STAT3 may be a potential therapeutic co-target for chronic HBV infection.

A Meta-analysis of 37 Studies on the Effectiveness of Microsurgical Techniques for Lymphedema.

BACKGROUND: Microsurgery is a new technique for lymphedema treatment. Its advantages and disadvantages remain controversial. This study is sought to collect clinical data from patients who underwent lymphovenous bypass and vascularized lymph node transplantation to explore whether surgical procedures can effectively treat lymphedema. METHODS: We performed a meta-analysis of the effectiveness of lymphatic microsurgery. We searched the databases of literature for articles in Chinese and English. These articles were graded for quality. Report details and outcomes were recorded. Data extraction, systematic review, and meta-analysis were performed. RESULTS: Thirty-seven studies were included. Patients who underwent microsurgery had a significantly better chance of achieving an excellent result than patients who received conservative treatment (odds ratio = 7.07). The affected limb circumference was reduced by approximately, 44.68% after the microsurgery. After the microsurgery, 63% of the patients did not need physiotherapy, and 96% were free from painful skin infections. Lymphography showed that lymphatic transport capacity was enhanced. Moreover, 12% of the patients reported that edema reappeared in the long-term, 26% required reoperation for unsatisfactory results, and 32% experienced lymphatic leakage. CONCLUSIONS: A vast majority of patients derive more benefit from lymphatic microsurgery than from conventional treatment. The advantages of lymphatic microsurgery outweigh the disadvantages for patients in the early and middle stages of chronic secondary lymphedema and patients in whom conventional treatment failed.