Consensus statement on research and application of Chinese herbal medicine derived extracellular vesicles-like particles (2023 edition).

To promote the development of extracellular vesicles of herbal medicine especially the establishment of standardization, led by the National Expert Committee on Research and Application of Chinese Herbal Vesicles, research experts in the field of herbal medicine and extracellular vesicles were invited nationwide with the support of the Expert Committee on Research and Application of Chinese Herbal Vesicles, Professional Committee on Extracellular Vesicle Research and Application, Chinese Society of Research Hospitals and the Guangdong Engineering Research Center of Chinese Herbal Vesicles. Based on the collation of relevant literature, we have adopted the Delphi method, the consensus meeting method combined with the nominal group method to form a discussion draft of "Consensus statement on research and application of Chinese herbal medicine derived extracellular vesicles-like particles (2023)". The first draft was discussed in online and offline meetings on October 12, 14, November 2, 2022 and April and May 2023 on the current status of research, nomenclature, isolation methods, quality standards and research applications of extracellular vesicles of Chinese herbal medicines, and 13 consensus opinions were finally formed. At the Third Academic Conference on Research and Application of Chinese Herbal Vesicles, held on May 26, 2023, Kewei Zhao, convenor of the consensus, presented and read the consensus to the experts of the Expert Committee on Research and Application of Chinese Herbal Vesicles. The consensus highlights the characteristics and advantages of Chinese medicine, inherits the essence, and keeps the righteousness and innovation, aiming to provide a reference for colleagues engaged in research and application of Chinese herbal vesicles at home and abroad, decode the mystery behind Chinese herbal vesicles together, establish a safe, effective and controllable accurate Chinese herbal vesicle prevention and treatment system, and build a bridge for Chinese medicine to the world.

Brucea javanica derived exosome-like nanovesicles deliver miRNAs for cancer therapy.

Triple-negative breast cancer (TNBC) is characterized by complex heterogeneity, high recurrence and metastasis rates, and short overall survival, owing to the lack of endocrine and targeted receptors, which necessitates chemotherapy as the major treatment regimen. Exosome-like nanovesicles derived from medicinal plants have shown great potential as novel biotherapeutics for cancer therapy by delivering their incorporated nucleic acids, especially microRNAs (miRNAs), to mammalian cells. In this study, we isolated exosome-like nanovesicles derived from B. javanica (BF-Exos) and investigated their influence and underlying molecular mechanisms in TNBC. We found that BF-Exos delivered 10 functional miRNAs to 4T1 cells, significantly retarding the growth and metastasis of 4T1 cells by regulating the PI3K/Akt/mTOR signaling pathway and promoting ROS/caspase-mediated apoptosis. Moreover, BF-Exos were shown to inhibit the secretion of vascular endothelial growth factor, contributing to anti-angiogenesis in the tumor microenvironment. In vivo, BF-Exos inhibited tumor growth, metastasis, and angiogenesis in breast tumor mouse models, while maintaining high biosafety. Overall, BF-Exos are considered promising nanoplatforms for the delivery of medicinal plant-derived nucleic acids, with great potential to be developed into novel biotherapeutics for the treatment of TNBC.

All-in-one smart dressing for simultaneous angiogenesis and neural regeneration.

Wound repair, along with skin appendage regeneration, is challenged by insufficient angiogenesis and neural regeneration. Therefore, promoting both proangiogenic and neuro-regenerative therapeutic effects is essential for effective wound repair. However, most therapeutic systems apply these strategies separately or ineffectively. This study investigates the performance of an all-in-one smart dressing (ASD) that integrates angiogenic functional materials and multiple biological factors within a light crosslinked hydrogel, forming a multi-functional dressing capable of facilitating simultaneous micro-vascularization and neural regeneration. The ASD uses a zeolite-imidazolate framework 67 with anchored vanadium oxide (VO2@ZIF-67) that allows for the on-demand release of Co2+ with fluctuations in pH at the wound site to stimulate angiogenesis. It can simultaneously release CXCL12, ligustroflavone, and ginsenoside Rg1 in a sustained manner to enhance the recruitment of endogenous mesenchymal stem cells, inhibit senescence, and induce neural differentiation to achieve in situ nerve regeneration. The ASD can stimulate rapid angiogenesis and nerve regeneration within 17 days through multiple angiogenic and neuro-regenerative cues within one dressing. This study provides a proof-of-concept for integrating functional nanomaterials and multiple complementary drugs within a smart dressing for simultaneous angiogenesis and neural regeneration.

Emerging pharmaceutical therapeutics and delivery technologies for osteoarthritis therapy.

Osteoarthritis (OA) is one of the most common joint degenerative diseases in the world. At present, the management of OA depends on the lifestyle modification and joint replacement surgery, with the lifespan of prosthesis quite limited yet. Effective drug treatment of OA is essential. However, the current drugs, such as the non-steroidal anti-inflammatory drugs and acetaminophen, as well as glucosamine, chondroitin sulfate, hyaluronic acid, are accompanied by obvious side effects, with the therapeutic efficacy to be enhanced. Recently, novel reagents such as IL-1 antagonists and nerve growth factor inhibitors have entered clinical trials. Moreover, increasing evidence demonstrated that active ingredients of natural plants have great potential for treating OA. Meanwhile, the use of novel drug delivery strategies may overcome the shortcomings of conventional preparations and enhance the bioavailability of drugs, as well as decrease the side effects significantly. This review therefore summarizes the pathological mechanisms, management strategies, and research progress in the drug molecules including the newly identified active ingredient derived from medicinal plants for OA therapy, with the drug delivery technologies also summarized, with the expectation to provide the summary and outlook for developing the next generation of drugs and preparations for OA therapy.

Plant polysaccharides as novel biomaterials for microcapsule construction and therapeutics delivery.

Natural polysaccharides derived from medicinal plants, that are Dendrobium (DPS), Lycium barbarum (LBP), Ginseng (GPS), and Poria Cocos (PCP) were firstly combined with sodium alginate (SA) to construct microcapsules and improved the morphology, encapsulation efficiency, Biocompatibility and protective capability in drug loading. Diverse typical therapeutics, including VO2@ZIF67 nanoparticles, small molecule drugs salvianolic acid B (SaB)/ginsenoside (Rg1), probiotic Bacillus bifidus, and biomacromolecules SDF-1 were wrapped into 1.5 % GPS-0.5 % SA model microcapsules, respectively. Better mobility and formability were significantly observed, and showed 75 % survival rate of probiotics in simulated gastric juice and around 99 % encapsulation efficiency which is higher than single 2 % SA microcapsules. The microcapsules also obtained a delayed release and a higher cell index for SDF-1, which indicated better stability, biocompatibility and protective effect than single 2 % SA microcapsules. This study provides a strategy in developing plant derived polysaccharides as novel materials for the construction and improvement of traditional microcapsules.

Phytochemicals as new therapeutic candidates simultaneously stimulate proliferation and counteract senescence of stem cells.

Mesenchymal stem cells (MSCs) are promising candidates for regenerative therapy. However, the research and clinical application of MSCs are greatly hindered by the limited cells proliferation and replicative senescence. Therapeutic agents that can both enhance the proliferative ability and decrease the replicative senescence of MSCs are greatly needed, however, not been reported yet. Herein, for the first time, we identified 11 natural compounds from medicinal plants with both excellent proliferative and anti-senescence abilities in MSCs. The qPCR analysis indicated underlying mechanisms associated with fibroblast growth factor, transforming growth factor, Wnt/ß-catenin and leukemia-induced factor in proliferation; the reactive oxygen species production, mitochondrial dysfunction autophagy and proteostasis are involved in cells senescence-related mechanism. Phytochemicals are demonstrated as novel therapeutic candidates with promising effects in both stimulating proliferation and retarding replicative senescence of stem cells with high safety.

Implementation of perioperative breathing exercises and its effect on postoperative pulmonary complications and long-term prognosis in elderly patients undergoing laparoscopic colorectal surgery: A randomized controlled trial.

OBJECTIVE: This study was to investigate the impact of breathing exercises on recovery in elderly patients receiving laparoscopic colorectal surgery. DESIGN: A prospective randomized controlled trial. SETTING: University hospital. SUBJECT: A total of 264 elder patients undergoing laparoscopic colorectal surgery participated in this study. INTERVENTION: Patients in intervention group received respiratory-related exercises based on standardized enhanced recovery after surgery strategies from admission to 90 days after surgery. The control group received perioperative standardized enhanced recovery after surgery strategies without formatted breathing exercises. MAIN MEASURES: The primary outcome was the incidence of postoperative pulmonary complications. The secondary outcomes included 6-minute walking distance, surgery-related complications, length of stay, mortality postoperatively, and hospitalization costs. RESULTS: Completion rate of breathing exercise in intervention group was over 80% till 90 days postoperatively. The incidence of postoperative pulmonary complications was lower in breathing exercises group (17/132 [12.9%] vs. 43/132 [32.6%], p < 0.001). The mean value of 6-minute walking distance increased more in intervention group compared with baseline values preoperatively (44.2 ± 4.3 vs. 3.2 ± 0.2, p < 0.001). On 90 days postoperatively, the mean value of 6-minute walking distance in breathing exercises group increased by 18.8 m compared with its baseline (557.0 ± 133.5 vs. 538.2 ± 112.7, p = 0.022), while that of control group decreased by 53.2 m from baseline (481.9 ± 102.5 vs. 535.1 ± 123.4, p < 0.001). Patients who received breathing exercises had shorter length of stay and lower hospitalization costs (p < 0.050). CONCLUSIONS: Perioperative breathing exercises helped prevent postoperative pulmonary complications and improve long-term prognosis in elderly patients undergoing laparoscopic colorectal surgery.

[Research progress on role of Chinese medicinal materials and their topical preparations in wound healing by regulating cytokines and growth factors].

Delayed-or non-healing wounds caused by trauma, surgical procedures, acute diseases, or chronic diseases, and proli-ferating scar have a serious impact on patients' quality of life and increase the economic and psychological burden on their families. Therefore, how to accelerate wound healing and obtain satisfactory aesthetic results is of great concern to researchers and is an urgent clinical problem to be solved. In recent years, the mechanisms of Chinese medicinal materials in accelerating wound healing and inhi-biting scar formation by regulating cytokines have been clarified, which provides a scientific basis for revealing the efficacy of Chinese medicinal materials against clinical trauma. This review focuses on the therapeutic effects of active ingredients, extracts, and topical preparations of Chinese medicinal materials through regulating cytokines in the inflammation, proliferation, and remodeling phases of wound healing. It is expected to provide evidence for the application of Chinese medicinal materials in wound therapy.

The crude ethanol extract of Periplaneta americana L. stimulates wound healing in vitro & in vivo.

Periplaneta americana L. is a Traditional Chinese Medicine that has been used in clinic treatment of various diseases for a long history. However, the therapeutic potential and the underlying mechanism of Periplaneta americana L. in the skin wound therapy was not investigated comprehensively yet. This study aims to investigate the influence of the crude ethanol extract of PAL in the different wound stages including: (1) the migration and chemotaxis to skin cells in the first stage; (2) proliferation and cells cycle of skin cells in the second stage; (3) remodeling effect and secretion of growth factors, collagens in the third stage; (4) as well as the influence in the blood vessels regeneration in the late stage. The crude ethanol extract of PAL was shown to (1) promote the keratinocytes proliferation and regulate the cells cycle of fibroblasts significantly; (2) stimulate the migration of keratinocytes and fibroblasts obviously; (3) enhance the EGF and VEGF secretion both in vitro & in vivo; (4) accelerate the wound healing, collagen synthesis and angiogenesis. The crude ethanol extract of KFX was shown a promising therapeutic agent for the wound therapy with great efficacy to accelerate the wound healing with improved quality.

Effects of anti-H. pylori triple therapy and a probiotic complex on intestinal microbiota in duodenal ulcer.

This study aimed to investigate the intestinal microbiota in duodenal ulcer (DU) patients, effects of proton pump inhibitors,clarithromycin and amoxicillin, PCA) for Helicobacter pylori (H. pylori) and Bacillus subtilis and Enterococcus faecium (BSEF) on intestinal microbiota. DU patients were randomly assigned to receive either PCA (group TT) or PCA plus BSEF(group TP). The fecal microbiome was conducted using high throughput 16S rDNA gene and internal transcribed spacer sequencings. The diversity and abundance of intestinal bacteria in the DU were significantly lower than health check control (HC) group. In the TT group, the abundance and diversity of both intestinal bacteria and fungi decreased after PCA treatment, compared with those before treatment, whereas in the TP group no obvious changes were observed. In the TT group at all the time points, both the intestinal bacteria and fungi were different from those in the HC group. However, in the TP group, at 10w the bacterial flora abundance was close to that in the HC group. The results indicate that anti- H. pylori treatment induced significant decrease in the diversity of intestinal microbiota, while the combined therapy supplemented with BSEF could protect and restore the intestinal microbiota.

Nanoscaled pearl powder accelerates wound repair and regeneration in vitro and in vivo.

Pearl powder has been used to treat many diseases like palpitations, insomnia, and epilepsy for thousands of years in Chinese medicine. It has demonstrated antioxidant, antiaging, antiradiative, and tonic activities. Pearl powder contains multiple active proteins, which are nutritious for skin cells and might be advantageous for wound repair and regeneration. However, its healing effect in vivo was not reported yet. This study aims to investigate the effects and the underlying mechanism of the pearl powders with different particle sizes in wound treatment. Briefly, the pearl powder with different sizes was characterized for their particle sizes and morphology. The protein release profiles of these powders were also studied. The influence of the different size of pearl powder in the proliferation, migration of skin cells was evaluated. Then, with the rat skin excision model, the effect of pearl powder on wound repair and regeneration was investigated. It was demonstrated that, all the micro and nanosized pearl powders could both increase the proliferation and migration of skin cells and accelerate the wound closure, as well as significantly enhanced the biomechanic strength of the healed skins. Moreover, the pearl powder treatment could improve the formation and regular deposition of collagen, and enhance the skin angiogenesis. Among all these in vitro and in vivo investigations, nanoscale pearl powder expressed the highest efficiency for healing. The mechanism might be contributed to the increased release of active proteins, enhanced tissue attachment, and the increased cellular uptake for the nano powder at the topical site.

Periplaneta Americana L. as a novel therapeutics accelerates wound repair and regeneration.

Kangfuxin (KFX) is the ethanol extract of Periplaneta Americana L., which has been widely used in Traditional Chinese Medicine for the treatment of injury in clinic with a long history. However, the biological influence of KFX in the different wound stages was not investigated comprehensively yet. This study aims to investigate the influence of KFX in the various wound healing activities with cellular and animal models, including the influence of KFX in 1) proliferation and cells cycle of kerationcytes and fibroblasts; 2) migration and chemotaxis of these skin cells; 3) secretion of EGF and VEGF; 4) the healing rate; 5) synthesis and deposition of different types of collagen; 6) as well as the pro-angiogenesis effect. KFX was shown to/for 1) promote the kerationcytes proliferation and regulate the cells cycle of skin fibroblasts significantly; 2) obviously stimulate the migration of kerationcytes and chemotaxis of fibroblasts; 3) the trend to promote EGF and VEGF secretion both in vitro & in vivo; 4) accelerate the wound closure, collagen synthesis and angiogenesis. KFX was demonstrated to accelerate wound healing and improve the healing quality by multiple regulation. Results of this study provide the comprehensive evidence for the application of KFX as a novel therapeutics for wound treatment.

Synthesis, characterization and inhibitory effects of crocetin derivative compounds in cancer and inflammation.

Crocetin is a natural product possessing extraordinary therapeutic effects for various diseases. However, its extremely low solubility limits its application greatly. Conjugation of organic compounds containing heteroatoms such as N to poor soluble molecules can help the synthesized derivative to form stable hydrogen bonds by lowering the salvation energy, which will improve the solubility of the synthesized compounds. Herein, crocetin was modified by conjugating with piperidyl, diethylin and benzylamine to improve their solubility and bioactivities. In the present study, the conjugation of crocetin with piperidyl, diethylin and benzylamine and their influence on the solubility and the pharmacological effects of crocetin were investigated. With the described strategy, crocetin derivatives were synthesized and their structures were elucidated by 1H NMR, 13C NMR and UPLC-MS spectroscopic analysis. The solubility of crocetin and its derivatives were identified. Upon that, the pharmacological effects of the crocetin derivatives on the tumor and inflammation treatment were investigated. It was shown that, in contrast to crocetin, of which, the solubility and pharmacological effects were low and limited, the synthesized compounds have significantly higher solubility and possess broad spectrum of anticancer effects in multiple tumor cell lines, including B16F10, MCF-7, A549 and SKOV3, as well as enhanced anti-inflammation efficacy in macrophage (RAW264.7) without causing cells damage. Conjugation of piperidyl, diethylin and benzylamine with the crocetin was demonstrated to be a highly efficient strategy to improve the solubility of crocetin. The synthesized crocetin derivatives were shown the promising therapeutics for the tumor and inflammation treatment with high safety.

Effect of transcutaneous electrical nerve stimulation for pain control after total knee arthroplasty: A systematic review and meta-analysis.

INTRODUCTION: Transcutaneous electrical nerve stimulation is a possible adjunctive therapy to pharmacological treatment for controlling pain after total knee arthroplasty. However, the results are controversial. A systematic review and meta-analysis was conducted to explore the effect of transcutaneous electrical nerve stimulation on patients with total knee arthroplasty. METHODS: PubMed, Embase, Web of Science, EBSCO, and Cochrane Library databases were searched systematically. Randomized controlled trials assessing the effect of transcutaneous electrical nerve stimulation on patients with total knee arthroplasty were included. Two investigators independently searched articles, extracted data, and assessed the quality of included studies. Primary outcome was visual analogue scale (VAS) score over a period of 24 h. Meta-analysis was performed using a random-effect model. RESULTS: Six randomized controlled trials involving 529 patients were included in the meta-analysis. Overall, compared with control intervention, transcutaneous electrical nerve stimulation supplementation intervention was found to significantly reduce VAS scores and total postoperative morphine dose over a period of 24 h, and to improve active range of knee motion (standard mean difference (SMD) = 0.37; 95% confidence interval (95% CI) = 0.06-0.68; p = 0.02), but had no effect on VAS scores at 2 weeks (SMD = 0.20; 95% CI = -0.07 to 0.48; p = 0.15). CONCLUSION: Compared with control intervention, transcutaneous electrical nerve stimulation supplementation intervention was found to significantly reduce pain and morphine requirement over a period of 24 h and to promote functional recovery in patients who have undergone total knee arthroplasty.

Evidence based anti-osteoporosis effects of Periplaneta americana L on osteoblasts, osteoclasts, vascular endothelial cells and bone marrow derived mesenchymal stem cells.

BACKGROUND: Kangfuxin (KFX) is the ethanol extract of Periplaneta americana L, which has been widely used in the Traditional Chinese Medicine for the repair and regeneration of injured organ and tissues with long history. This study is to investigate the influence of KFX in the various cellular activities and evaluate the anti-osteoporosis potential of KFX. METHODS: The influence of the KFX in the cellular activities, including: 1) migration, osteocalcin secretion of osteoblasts; 2) apoptosis of osteoclasts; 3) migration and tube formation of human umbilical vein endothelial cell (HUVEC); and 4) proliferation, cell cycle regulation and migration of bone marrow mesenchymal stem cells (BMSCs), were investigated systematically. RESULTS: KFX was shown to significantly 1) Promote of the migration of osteoblasts, HUVEC, and BMSCs; 2) Increase the secretion of osteocalcin and mineralization of osteoblasts; 3) Accelerate the apoptosis of osteoclasts; 4) Stimulate the proliferation and regulate the cell cycle of BMSCs. CONCLUSION: Taken together, these results provide the evidence for the osteogenesis, anti-osteoporosis and angiogenesis effects of KFX, with the mechanism of activating the bone formation through stimulating the osteoblasts and HUVECs, as well as inhibiting the bone absorption by inhibiting the osteoclasts activities. The KFX was definitely shown a promising bone turnover agent with great potential for anti-osteoporosis treatment.

A systematic study of the dissolution and relative bioavailability of four ginsenosides in the form of ultrafine granular powder, common powder and traditional pieces of Panax quinquefolius L, in vitro and in beagles.

ETHNOPHARMACOLOGICAL RELEVANCE: Panax quinquefolius L (PQ), also known as American ginseng, has been used as a medicinal herb for thousands of years in the Far East, which was wildly used actively in healing the cardiovascular, endocrine and immune systems, in supporting chemoprevention of cancer. MATERIALS AND METHODS: An integrated, rapid, sensitive and reliable UHPLC-ESI-QQQ MS/MS method was validated and successfully applied in a pharmacokinetics study in which four representative ginsenosides were measured in beagle plasma following oral administration of Panax quinquefolius L (PQ) in the form of ultrafine granular powder, standard powder and an extract. RESULTS: Two paired ions ([M+Na](+) in the positive MS process, and two characteristic ions [Q3](+) in the positive MS/MS process) of the target compounds were optimized and selected for improved qualitative and quantitative analysis of ginsenosides in beagle plasma. The relative bioavailability of the target ginsenosides in these three formulations was measured by the pharmacokinetic parameters, including Cmax, Tmax, AUC0-∞ and so on. The ultrafine granular powder had the highest bioavailability, as well as the greatest extent of and fastest dissolution in vitro. CONCLUSION: Our results show that improved formulations of PQ could facilitate the dissolution and promote absorption of the important compounds it contains.

Dissolution difference of ginsenosides from ultrafine granular powder and common powder traditional pieces of Panacis Quinquefolii Radix in vitro.

The dissolution of Panacis Quinquefolii Radix ultrafine granular powder and common powder, traditional pieces in water and simulated gastric juice in vitro was compared, and the effect of particles size of Panacis Quinquefolii Radix on the dissolution was studied. HPLC method was used for determination of five ginsenosides including Rg1, Re, Rb1, Rc and Rd from ultrafine granular powder and common powder, traditional pieces of Panacis Quinquefolii Radix at different points in time, furthermore, the dissolution curves of Panacis Quinquefolii Radix ultrafine granular powder and common powder, traditional pieces were obtained. The dissolution characteristics of the three Panacis Quinquefolii Radix forms were also compared in this study. According to the results, the dissolution rates of ginsenosides from ultrafine granular powder exceeded 90% of the total content with 5 min, significantly higher than that of the other two forms in water in vitro. At the same time, the dissolved amount of the ultrafine granular powder was fourteen percent higher than that of the traditional pieces and eight percent higher than that of the common powder. Under the condition of simulated gastric juice in vitro, the dissolution rates of ginsenosides from ultrafine granular powder were little lower than that of the other two, but the maximum dissolved amount of the former was fourteen percent higher than that of the common powder and five percent higher than that of the extracts. Therefore the conclusion is that micronization of Panacis Quinquefolii Radix contributed to dissolution of effective components.

[Preliminary study on effect of Rhodiolae Crenulatae Radix et Rhizoma cell wall-broken decoction pieces on intestinal flora of mice].

This study aims to analyze and compare the effect of cell wall-broken decoction pieces, conventional decoction pieces and conventional powder of Rhodiolae Crenulatae Radix et Rhizoma on the intestinal flora of normal mice. The conventional bacterial culture and PCR-DGGE (polymerase chain reaction-denaturing gradient gel electrophoresis) were adopted for the mice after the oral administration for 14 days. According to the bacterial culture results, the 1/8 dose cell wall-broken decoction pieces group showed fewer Enterococcus and Escherichia coli bacillus but more Lactobacillus and Bifidobacterium than the conventional decoction pieces group and the traditional powder group (P <0.05). Meanwhile, on the basis of the PCR-DGGE results, the 1/8 dose cell wall-broken decoction pieces group revealed the highest Shannon-Wiener index (H) and species richness (S) among the seven groups, with extremely significant differences compared with the normal group (P <0.01), significant differences compared with the conventional decoction pieces group and the conventional powder group (P <0.05) and a high intra-group similarity. In conclusion, the long-term intake of 1/8 dose Rhodiolae Crenulatae Radix et Rhizoma cell wall-broken decoction pieces showed a certain effect in regulating intestinal tract by promoting the growth of Lactobacillus and Bifidobacterium. Furthermore, the intestinal flora community will become more stable.

[A pilot study of treating ulcerative colitis with fecal microbiota transplantation].

OBJECTIVE: To explore the procedure, effectiveness and safety of fecal microbiota transplantation (FMT) in patients with ulcerative colitis (UC). METHODS: Seven patients (6 men and 1 woman, aged 17-66 years) with active UC were treated with FMT through endoscopic duodenal infusion or combined endoscopic duodenal and colonic approaches. The clinical manifestations and laboratory results were recorded before and after FMT respectively. Disease response was evaluated with Mayo scores. Fresh fecal suspension prepared from healthy donors who were strictly screened, was infused into patients' intestinal tracts within 6 hours. RESULTS: The average disease duration of 7 patients with UC was (9.1 ± 8.5) years (range 0.5-24.0 years). One patient underwent FMT for three times and one for twice, while the other five were treated for once. The follow-up time was (98.6 ± 70.8) days (30-210 days). All patients achieved some extent of improvements with the reduction of Mayo scores 7, 4, 6, 5, 6, 9 and 9, respectively. Transient fever, diarrhea and abdominal distension were observed in some patients after FMT, while alleviated spontaneously 2-3 days after the procedure. One patient had high fever and mild ascites caused by secondary infections, which were controlled by the symptomatic treatment and antibiotics. Severe adverse reactions were not found. CONCLUSIONS: FMT is effective to active UC, the short-term side effects and complications are basically acceptable and controllable. The long-term efficacy and risks of FMT need to be verified further.

Adjuvant chemoradiation plus intraoperative radiotherapy versus adjuvant chemoradiation alone in patients with locally advanced rectal cancer.

OBJECTIVES: To document the efficacy of intraoperative radiotherapy (IORT) followed by adjuvant chemoradiation in the management of locally advanced rectal cancer. MATERIALS AND METHODS: A total of 148 patients with pT4N0/T1-4N+ rectal adenocarcinoma were enrolled. Seventy-seven patients received total mesorectal excision surgery followed by adjuvant chemoradiation alone, 71 patients received total mesorectal excision surgery followed by IORT (range, 10 to 20 Gy) and adjuvant chemoradiation. RESULTS: The 5-year local control (LC) and disease-free survival were 79.2% versus 89.7% (P=0.032), 58.5% versus 69.0% (P=0.049) for external-beam radiation (EBRT) and IORT+EBRT groups, respectively. Multivariate analysis revealed that adjuvant IORT has a trend toward improvement of LC (P=0.079); 5 (3%) patients (EBRT n=2; IORT n=3) experienced incomplete intestinal obstruction and 3 patients had chronic diarrhea. There was no clinically relevant neuropathy or sacral osteoradionecrosis. Hydronephrosis occurred in 13 patients (EBRT n=8; IORT+EBRT n=5), 8 of whom had documented concomitant disease recurrence. CONCLUSIONS: For patients with locally advanced rectal cancer, higher radiation dose may contribute to the improvement of both LC and disease-free survival, without significantly increasing the incidence of acute and long-term complications compared with adjuvant chemoradiotherapy alone.