Laparoscopic Anatomical Cranial Sub-segmentectomy of Segment VII (S7) with Super-Selective Intra-arterial Nano-ICG Positive Staining-Guided Trans-Parenchymal Approach.

BACKGROUND: With introduction of "cone unit," which is the smallest resectable anatomical area supplied by a tertiary branch of Glissonean pedicle, more precise subsegmental anatomical resection has been proposed.1 Super-selective intra-arterial ICG staining, delivering ICG and lipiodol mixing to arterial branch using interventional radiology, has been proved feasibility especially for complicated anatomy.2-6 It was difficult to uniformly mix water-soluble ICG with lipophilic lipiodol, rendering to inconsistency development of liver segment between angiography and laparoscopy. Nano-ICG is a uniform mixing of ICG and lipiodol.7 We demonstrated an exclusive "two-step" method to perform LAR for cranial S7 via super-selective intra-arterial nano-ICG staining guidance. METHODS: A 70-year-old male was admitted. CT scan showed tumor was located in cranial S7 with 2.1*1.9 cm. Preoperative AFP was 4.66 ng/ml and PIVKA-II was 2332 mAU/ml. The liver function was Child-Pugh class A and ICG-15R was 7.8%. Given that tumor was confined to cranial S7, precise anatomical sub-segmentectomy was warranted. This study was approved by the West China Hospital, Sichuan University Ethics Committee (approval number: 2023-2327). RESULTS: The operation was performed "two step." "First step" was super-selective intra-arterial nano-ICG embolization in intervention room, while "second step" was performed in operation room. ICG demarcation line was clearly identified even after 7 hr. After full mobilization of right hemiliver, we performed transparenchymal approach to find and clamp pedicle of cranial S7 under fluorescence guidance. Operation time was 150 min with 20 ml of blood loss with uneventful course. CONCLUSIONS: Although LAR of S7 remains challenging, super-selective intra-arterial nano-ICG positive staining guidance might be a feasible and safe option.

Efficacy and safety of drug-eluting bead transarterial chemoembolization (DEB-TACE) combined with tyrosine kinase inhibitors (TKIs) in patients with unresectable hepatocellular carcinoma (uHCC): A systematic review and meta-analysis.

BACKGROUND: The optimal management of unresectable hepatocellular carcinoma (uHCC) remains an unresolved challenge. There is ongoing debate regarding the efficacy and safety of drug-eluting bead TACE (DEB-TACE) with tyrosine kinase inhibitors (TKIs). METHODS: We searched PubMed, Embase, Web of Science and the Cochrane Library for eligible studies. The main endpoints under investigation were survival outcomes, including overall survival (OS), progression-free survival (PFS), and time to progression (TTP). Secondary outcomes encompassed tumor response rates and adverse events (AEs). Two researchers conducted the data extraction independently and assessed the quality of the studies. After pooling and analyzing the data, we assessed the heterogeneity and performed both subgroup analysis and sensitivity analysis. Additionally, we evaluated the potential for publication bias. RESULTS: Eight studies with 1513 patients were finally retrieved. Compared to monotherapy, although bigeminal therapy exhibited improved survival benefits (OS: HR: 0.56, 95 % CI 0.41-0.76, p < 0.001; TTP: HR: 0.72, 95 % CI 0.59-0.87, p = 0.001) and tumor response (ORR: RR: 1.59; 95 % CI 1.19-2.13, p = 0.002; DCR: RR: 1.14; 95 % CI 1.03-1.26, p = 0.010), the reliability of results was affected by significant heterogeneity. In the subgroup analysis, compared to DEB-TACE alone, the bigeminal therapy failed to show any statistical differences. Compared to TKIs, it demonstrated significant advantages in both survival (OS: HR: 0.49, 95 % CI 0.40-0.61, p < 0.001; TTP: HR: 0.60, 95 % CI 0.48-0.75, p < 0.001) and tumor response (ORR: RR: 2.40, 95 % CI 1.86-3.09, p < 0.001; DCR: RR: 1.36, 95 % CI 1.20-1.54, p < 0.001) while low heterogeneity was observed. Concerning safety, DEB-TACE provides no more severe AEs while TKIs-related AEs require close monitoring. CONCLUSION: Our findings suggest that DEB-TACE combined with TKIs may be a safe and effective treatment for uHCC, which is more suitable for patients in the advanced stage.

Multi-point immobilization of GH 11 endo-ß-1,4-xylanase on magnetic MOF composites for higher yield of xylo-oligosaccharides.

GH 11 endo-ß-1,4-xylanase (Xy) was a crucial enzyme for xylooligosaccharides (XOS) production. The lower reusability and higher cost of purification has limited the industrial application of Xy. Addressing these challenges, our study utilized various immobilization techniques, different supports and forces for Xy immobilization. This study presents a new method in the development of Fe3O4@PDA@MOF-Xy which is immobilized via multi-point interaction forces, demonstrating a significant advancement in protein loading capacity (80.67 mg/g), and exhibiting remarkable tolerance to acidic and alkaline conditions. This method significantly improved Xy reusability and efficiency for industrial applications, maintaining 60 % activity over 10 cycles. Approximately 23 % XOS production was achieved by Fe3O4@PDA@MOF-Xy. Moreover, the yield of XOS from cobcorn xylan using this system was 1.15 times higher than that of the free enzyme system. These results provide a theoretical and applicative basis for enzyme immobilization and XOS industrial production.

Transhepatic arterial approaches for ICG injection to guide laparoscopic anatomical hepatectomy: A case series study.

BACKGROUND: Laparoscopic anatomical hepatectomy guided by near-infrared fluorescence imaging (NIR-FI) has been utilized extensively. However, it is difficult to resect "cone units" above the third branch of the Glissonean pedicle in the right posterior lobe using the laparoscopic positive or negative staining techniques. Therefore, we undertook a new laparoscopic segmentectomy based on the concept of "cone unit" assisted by interventional radiology combined with NIR-FI. METHODS: Laparoscopic segmentectomy guided by NIR-FI via super-selective hepatic arteriography and trans-arterial injection of ICG was carried out on 13 patients with early-stage HCC between September 2020 and January 2022.11 of cases were successful, and relevant pathological characteristics and perioperative outcomes were retrospectively analyzed. RESULTS: Two cases failed NIR-FI out of which one case involved over-staining to the non-target segment, and in the other case, which was to undergo laparoscopic segment V resection, only the ventral segment was stained while the imaging of the dorsal segment failed. In the intraoperative conditions, the tumor safe margin was 1.1 (0.7-1.55) cm, the interventional operation time was 50 (45.5-60.5) minutes, the operation time was 280 (242.5-307.5) minutes, the blood loss was 100 (50-200) ml, the postoperative hospital stay was 5 (4.5-5.5) days. No cases converted to laparotomy, and no serious postoperative complications developed. CONCLUSIONS: NIR-FI through super-selective hepatic arteriography and trans-arterial injection of ICG can provide a clear and lasting navigation aid for laparoscopic segmentectomy, which may have positive implication for early-stage HCC with poor preoperative liver reserves.

Liver transplantation versus resection for patients with combined hepatocellular cholangiocarcinoma: A retrospective cohort study.

Background: Combined hepatocellular cholangiocarcinoma (CHC) is a rare primary liver cancer, and whether liver transplantation should be implemented among CHC patients is still controversial. We intend to conduct a retrospective cohort study based on the Surveillance, Epidemiology, and End Results (SEER) database to investigate the prognosis of liver transplantation vs. liver resection among CHC patients. Methods: Patients diagnosed with CHC (ICD-O-3:8180/3) and treated with transplantation or hepatectomy were extracted from the SEER database (2000-2018). We utilized Propensity Score Matching to control confounding bias. Kaplan-Meier curve was used for survival analysis, and Cox regression was used to find independent factors associated with prognosis. Results: We identified 123 (transplantation: 49; resection: 74) patients with CHC who were treated between 2004 and 2015. In the entire cohort, survival analysis demonstrated transplantation group was associated with better overall survival and cancer-specific survival (log-rank p = 0.004 and p = 0.003, respectively). In addition, liver transplantation still conferred better overall and cancer-specific survival than liver resection after Propensity Score Matching (log-rank p = 0.024 and p = 0.048, respectively). However, this advantage didn't appear in the subgroup, regardless of whether the tumor size was greater than 3 cm or not. (≤3 cm: OS log-rank p = 0.230, CSS log-rank p = 0.370; >3 cm: OS log-rank p = 0.110, CSS log-rank p = 0.084). Multivariate analysis validated the finding that liver transplantation was a protective factor for overall survival (HR = 0.55 [0.31-0.95], p = 0.032). Conclusions: Liver transplantation may be an option in individuals with CHC and should be taken into consideration due to its advantages in terms of overall survival and cancer-specific survival. However, a sizable sample is required for future studies to determine which subset of CHC patients may benefit more from liver transplantation.

Safety and efficacy of laparoscopic transperitoneal versus retroperitoneal resection for benign retroperitoneal tumors: a retrospective cohort study.

BACKGROUND AND OBJECTIVE: Benign retroperitoneal tumors (BRTs) are clinically rare solid tumors. This study aimed to compare the safety and efficacy of laparoscopic transperitoneal versus retroperitoneal resection for BRTs. METHODS: The clinical data of 43 patients who had pathologically confirmed BRTs and underwent laparoscopic resection in a single center from January 2019 to May 2022 were retrospectively analyzed. Patients were divided into two groups according to the surgical methods: the Transperitoneal approach group (n = 24) and the Retroperitoneal approach group (n = 19). The clinical characteristics and perioperative data between the two groups were compared. The baseline data and surgical variables were analyzed to determine the impact of different surgical approaches on the treatment outcomes of BRTs. RESULTS: No significant difference was observed between the two groups in gender, age, body mass index, the American Society of Anesthesiologists score, presence of underlying diseases, tumor size, tumor position, operation duration, intraoperative hemorrhage, postoperative hospital stay, intestinal function recovery time, and postoperative complication rate. The conversion rate from laparoscopic to open surgery was significantly lower in the Transperitoneal approach group than in the Retroperitoneal approach group (1/24 vs. 5/19, χ2 = 4.333, P = 0.037). Tumor size was an independent influencing factor for the effect of surgery (odds ratio = 1.869, 95% confidence interval = 1.135-3.078, P = 0.014) and had a larger efficacy on the retroperitoneal group (odds ratio = 3.740, 95% confidence interval = 1.044-13.394, P = 0.043). CONCLUSION: The laparoscopic transperitoneal approach has the inherent advantages of anatomical hierarchies and surgical space, providing a better optical perspective of the targeted mass and improved bleeding control. This approach may have better efficacy than the retroperitoneal approach, especially in cases of a large tumor or when the tumor is located near important blood vessels.

Surgical indications for solid hepatic benign tumors: An updated literature review.

Hepatic hemangioma, focal nodular hyperplasia, and hepatic adenoma are the most common benign solid liver tumors. However, their surgical indications have been the subject of debate. Minimally invasive liver resection reduces the cost of surgery and may lead to overtreatment of benign liver tumors. Recently, there has been a growing understanding of the etiology, pathogenesis, and natural history of these tumors. Great progress has also been made in imaging. The use of MRI and contrast agents has improved the accuracy of non-invasive diagnosis of these tumors, and especially in the identification of specific molecular subtypes of liver adenoma. These factors have resulted in alterations of surgical indications for these tumors. This article examines recent literature and it discusses the surgical indications for hepatic hemangioma, focal nodular hyperplasia, and hepatic adenoma while summarizing modifications in clinical management.

Propeptide-Mediated Allosteric Regulation of Xylanase Xyl-1: An Integrated Experimental and Computational Analysis.

Most GH11 family endo-ß-1,4-xylanases contain a propeptide region linked to the N-terminal region. The mechanistic basis of this region harboring key regulation information for enzyme function, however, remains poorly understood. We reported an investigation on the allosteric regulation mechanism of the propeptide based on biochemical characterization, molecular dynamics simulations, and evolutionary analysis. We discovered that the mutant of truncated propeptide shows a remarkably increased thermal stability (melting temperature increased by 11.5 °C) and catalytic efficiency (1.7-fold kcat/Km value of wild type). Molecular dynamics simulations reveal that long-range fluctuations in the propeptide lead to a conformational perturbation in the catalytic pocket and the thumb region. The probability of sampling the active conformation during the glycosylation step is reduced (i.e., catalytic efficiency). In-depth sequence analysis indicates that the propeptide has a strong plasticity and degeneration trend, and propeptide truncation experiments of the homologous enzyme XynB validated the feasibility of the truncation strategy. This work reveals the role of GH11 family propeptides in functional regulation and provides a straightforward and practical method to increase the robustness of GH11 family xylanases.

Laparoscopic Anatomical Resection of Paracaval Portion of Caudate Lobe and Segment 8 for HCC in an HCV-Related Cirrhotic Patient.

BACKGROUND: Laparoscopic anatomical resection of caudate lobe remains poorly described due to deep location and connection with major vascular structures. The anterior transparenchymal approach might be safter and provide a better surgical view in cirrhotic cases.1,2 This report demonstrated this approach for anatomic laparoscopic resection of paracaval portion and segment eight (S8) for HCC in an HCV-related cirrhotic patient. METHODS: A 58-year-old man was admitted. The preoperative magnetic resonance imaging indicated that the mass with pseudo capsule was located in paracaval portion and S8 closed to IVC, RHV, and MHV with atrophic left lobe. The preoperative ICG-15R test was 16.2%. In this regard, right hemihepatectomy combined with caudate resection was aborted. We decided to perform an anatomical resection via anterior transparenchymal approach to reserve liver parenchyma as much as possible.3,4 RESULTS: After right lobe mobilization and cholecystectomy, the anterior transparenchymal approach was performed along Rex-Cantlie line by using Harmonic (Johnson & Johnson, USA). With the dissection and clamping of the Glissonean pedicles of S8, anatomical segmentectomy was performed according to the ischemic line and parenchymal transection was performed along hepatic veins. Finally, paracaval portion combined with S8 was en bloc resected. The operating time was 300 minutes with 150 ml of blood loss. The histopathologic report demonstrated the mass as HCC with negative resection margin. Furthermore, it showed a medium-to-high differentiation with no MVI and no microscopic satellite. CONCLUSIONS: The anterior transparenchymal approach for anatomic laparoscopic resection of paracaval portion and S8 might be a feasible and safe option for severe cirrhotic cases.

The prophylactic role of mitomycin C-based hyperthermic intraperitoneal chemotherapy (MMC-based HIPEC) on peritoneal metastasis of spontaneously ruptured hepatocellular carcinoma (srHCC): A pilot study.

Hepatocellular carcinoma (HCC) was featured as spontaneous rupture hemorrhage under intratumoral overpressure. Spontaneous rupture hepatocellular carcinoma (srHCC) has a high propensity for peritoneal metastasis (PM). Although HIPEC has become standard treatment for malignancies with PM, it has been poorly described in srHCC. We conducted a single-arm, open-label, single-center, prospective study to explore the prophylactic role of MMC-based HIPEC on PM of srHCC. A total of 7 patients were collected from April 1, 2021 to April 30, 2022. HIPEC was conducted 3 times on the first, third and fifth postoperative days. 15 mg/m2 of MMC was used with 60 minutes perfusion at 43°C. The primary end-point was local peritoneum recurrence free survival (RFS), whereas the secondary end-point was systemic RFS and overall survival (OS). The mean hepatectomy operation time was 232 minutes (SD: 124.08 minutes). The median bleeding loss was 200 mL (range 50-400 mL). The mean hospital stay was 13 days (SD: 3.42 days). Only mild abdominal distension was reported in 4 patients (57%). There were no patients who suffered from life-threatening intra-abdominal and extra-abdominal complications (EAC). At the data cut-off (April 30, 2023), one patient (14%) had died due to cachexia. Local peritoneal recurrence occurred in three patients (43%). Median follow-up was 16.1 months (IQR: 12.8-16.6 months). Median local peritoneum RFS was 12.3 months (95% CI: 7.0- 17.5; 4 events) and median overall RFS was 7.5 months (95% CI: 4.2-10.8; 6 events). MMC-based HIPEC was safe and feasible in selected patients of srHCC. It showed a positive tendency in preventing PM, but large-scale research should be continued.

Identification of diagnostic markers related to fecal and plasma metabolism in primary Sjögren's syndrome.

BACKGROUND: Accurate diagnostic techniques for patients with primary Sjögren's syndrome (pSS) are needed. This study aimed to investigate new biomarkers related to fecal and plasma metabolism from pSS patients. METHODS: The feces and plasma of 21 pSS patients and 18 controls admitted to the Second Hospital of Shanxi Medical University were collected for analysis. Metabolites in feces and plasma were quantified using liquid chromatography-mass spectrometry. The metabolic pathway alterations caused by pSS were studied and the expression of metabolites in the intersecting pathway was analyzed in the feces and plasma of pSS patients. Metabolites that showed the same alterations in feces and plasma in pSS patients were considered as diagnostic markers and receiver operating characteristic curves were generated to analyze the sensitivity of these markers in diagnosing pSS. RESULTS: There were 114 and 92 upregulated metabolites and 54 and 125 downregulated metabolites in the feces and plasma of pSS patients, respectively. These metabolites were enriched in 8 pathways for feces and 12 pathways for plasma. Arginine biosynthesis, Linoleic acid metabolism, Tyrosine metabolism, Taurine and hypotaurine metabolism were pathways enriched by metabolites in both samples. Twelves metabolites were enriched in the above four pathways, while only 9,10-12,13-Diepoxyoctadecanoate, Tyramine, 9-OxoODE and 2-Hydroxyethanesulfonate showed the same trend. The candidate diagnostic markers were all predictive, with better diagnostic sensitivity in plasma samples. CONCLUSIONS: 9,10-12,13-Diepoxyoctadecanoate, Tyramine, 9-OxoODE, 2-Hydroxyethanesulfonate were metabolism-related diagnostic markers for pSS feces and plasma.

Trocar layouts in laparoscopic liver surgery.

BACKGROUND: Since the first laparoscopic wedge resection reported by Reich, laparoscopic liver resection (LLR) has been progressively developed, acquiring safety and feasibility. The time has witnessed a milestone leap for laparoscopic hepatectomy from pure laparoscopic partial hepatectomy to anatomical hepatectomy and from minor liver resection to major liver resection. The numerous previous studies have paid more attention to the short-time and long-time surgical outcomes caused by surgical techniques corresponding to various segments and approaches. However, focus on trocar layouts remains poorly described, but it plays an indispensable role in surgical process. METHODS: We have searched PubMed for English language articles with the key words "trocar," "laparoscopic liver resection," and "liver resection approaches." RESULTS: This review highlighted each type of trocar layouts corresponding to specific circumstances, including targeted resection segments with various approaches. Notably, surgeon preferences and patients body habitus affect the trocar layouts to some extent as well. CONCLUSIONS: Although there were fewer researches focus on trocar layouts, they determine the operation field and manipulation space and be likely to have an impact on outcomes of surgery. Therefore, further studies are warranted to firm the role of trocar layouts in LLR.

Liver transplantation in China: Achievements over the past 30 years and prospects for the future.

Over the last three decades, liver transplantation (LT) in China has made breakthroughs from scratch. Now, new techniques are being continuously incorporated. However, LT in China differs from that in other countries due to cultural differences and the disease burden. The advances made in and the current issues with LT in China need to be summarized. Living donor LT (LDLT) has developed dramatically in China over the last 30 years, with the goal of increasing transplant opportunities and dealing with the shortage of donors. Western candidate selection criteria clearly are not appropriate for Chinese patients. Thus, the current authors reviewed the literature, and this review has focused on the topics of technological advancements in LDLT and Chinese candidate selection. The Milan criteria in wide use emphasize tumor morphology rather than pathology or biomarkers. α-fetoprotein (AFP) and pathology were incorporated as predictors for the first time in the Hangzhou criteria. Moreover, Xu et al. divided the Hangzhou criteria into type A (tumor size ≤ 8 cm or tumor size > 8 cm but AFP ≤ 100 ng/mL) and type B (tumor size > 8 cm but AFP between 100 and 400 ng/mL), with type B serving as a relative contraindication in the event of a liver donor shortage. In addition, surgeons in Chengdu and Shanghai have the ability to perform a laparoscopic hepatectomy for right and left lobe donors, respectively. China has established a complete LT system, including recipient criteria suitable for Chinese people, a fair donor allocation center, a transplant quality monitoring platform, and mature deceased donor or living donor LT techniques.

Use of chemotherapy to treat hepatocellular carcinoma.

Hepatic malignancies remain a global challenge. Hepatocellular carcinoma (HCC) accounts for around 90% of patients with liver cancer and is the sixth most common neoplasm worldwide and the fourth leading cause of cancer-related death. However, the long-term prognosis for HCC remains far from satisfactory, with a late diagnosis and limited treatment. DOX has served as conventional chemotherapy with the longest history of use. Although conventional chemotherapy is being challenged by molecular therapy and immune therapy, there is renewed optimism and interest in both systematic and locoregional therapy. Combined chemotherapy is widely used in clinical practice. In specific terms, FOLFOX can serve as a first-line (category 2B) option as recommended by the 2021 NCCN guidelines, while the efficacy of LTLD plus RFA has been confirmed in the phase III HEAT study. These approaches have challenged the dominant status of molecular therapy in terms of health economics and they have potential benefits in Asia, where HBV-related hepatocellular carcinoma is prevalent. Moreover, locoregional chemotherapy can be achieved with TACE and HAIC (possibly involving FOLFOX, DOX, mitomycin C, cisplatin, epirubicin, etc.). TACE was officially recommended by the 2021 NCCN guidelines for patients with Child-Pugh class B liver disease. In addition, HAIC has demonstrated a potential advantage in preliminary clinical practice, although it hasn't been included in any guidelines. Hence, this review summarizes large-scale trials and studies examining the development and innovative use of chemotherapeutic agents. Mounting clinical evidence warrants an exploration of the efficacy of chemotherapy.

MicroRNA-1 promotes cartilage matrix synthesis and regulates chondrocyte differentiation via post-transcriptional suppression of Ihh expression.

Indian hedgehog signaling molecule (Ihh) is known to play critical roles in chondrogenesis and cartilage development. However, it remains largely unknown how Ihh is regulated during the process. Previous studies suggest that Ihh plays an important regulatory role in the growth and development of articular cartilage, but whether it is regulated by miRNAs is unclear. The present study aimed to investigate the effects of miR­1 on chondrocyte differentiation and matrix synthesis, and to determine whether miR­1 can regulate the Ihh signaling pathway. In the present study, the expression level of miR­1 was altered via transfection of the miR­1 mimic or inhibitor in mouse thorax chondrocytes, and the impact on chondrocyte phenotypes and Ihh expression was examined. Overexpression of miR­1 promoted the expression of the matrix synthesis­associated molecules collagen (Col)­II and aggrecan, two key components in cartilage matrix. Conversely, overexpression of miR­1 significantly downregulated the expression of chondrocyte differentiation markers Col­X and matrix metallopeptidase 13. Moreover, overexpression of miR­1 dose­dependently inhibited endogenous Ihh expression, and an association was observed between miR­1 and Ihh expression. The 3' untranslated region (UTR) of Ihh from various species contains two miR­1 binding sites. Luciferase reporter assays indicated that miR­1 post­transcriptionally suppressed Ihh expression, which was dependent on the binding of miR­1 to one of the two putative binding sites of the Ihh 3'UTR. Furthermore, via inhibition of Ihh expression, miR­1 decreased the expression of molecules downstream of Ihh in the Hedgehog signaling pathway in mouse thorax chondrocytes. This study provided new insight into the molecular mechanisms of miR­1 in regulating chondrocyte phenotypes via targeting the Ihh pathway.

The fecal metabolome is associated with gestational diabetes mellitus.

Dysbiosis of gut microbiota has been linked to gestational diabetes mellitus (GDM), and grows as a resource for GDM biomarkers. However, the contributions of gut microbiota to GDM remain incompletely understood. Metabolites are key messengers in the interactions between gut microbiota and the host. Metabolomics is emerging as an essential tool in exploring the contributions of gut microbiota to diseases. In this study, we performed 1H-NMR based metabolomics on the feces of 62 pregnant women, including 31 women with GDM, and 31 women as the non-diabetes (NDM) control. Using Principle Component Analysis (PCA) and Orthogonal Projection to Latent Structures Discrimination Analysis (OPLS-DA), we observed clear cluster separation of the fecal metabolome between women with GDM and the NDM control. We further applied several feature selection methods to find five fecal metabolites contributing to the cluster separation of the fecal metabolome. These five metabolites, namely dibutyl decanedioate, N-acetylgalactosamine-4-sulphate, homocysteine, l-malic acid, and butanone, were significantly correlated with the clinical indices of GDM. Metabolite enrichment and pathway analysis on the five metabolites suggested that the fecal citrate cycle and sulfur metabolism were correlated with GDM. The results of this study demonstrated that disorders in the fecal metabolome are associated with GDM.

[Progress in antimicrobial substances of endophytes].

Isolation and characterization of metabolites produced by endophytes are significant ways to search for novel natural active substances, proving that the endophytes are the unique resources of newer and more effective compounds. Many new compounds with antimicrobial activity from different endophytes have been isolated so far. These new compounds provide alternatives to fight against multi-drug resistance of microorganisms. This review outlined the major achievements and latest developments of endophytes, including the diversity of endophytes and antimicrobial activity of endophytes, as well as its development in China.