Polymyxin serves as the"last line of defense"for treating infection with multidrug-resistant Gram-ne-gative bacteria.However,the emergence and spread of polymyxin-resistant genes such as mcr-1 severely weakens its clinical efficacy.This paper systematically summarizes the antimicrobial and resistance mechanisms of polymy-xin,comprehensively summarizes the current research progresses in polymyxin sensitizers particular focusing on three aspects:natural compounds,synthetic small molecules,and drug repurposing.Furthermore,this paper explores the innovative strategies of gene intervention,new targets,and nanotechnology-based formulations in the develop-ment of sensitizer,aiming to provide systematic theoretical support and research ideas against polymyxin resistance.

Objective:To investigate the relationship between amylase level in drainage fluid and the risk of salivary fistula(SF)after parotid benign tumor resection.Methods:106 patients underwent benign parotid tumor resection were included and divided into SF occurrence group(SF,n=31)and non-occurrence group(control,n=75).The amylase levels of drainage fluid were com-pared between the 2 groups at 24,48 and 72 h respectively after surgery,and the risk factors related to postoperative salivary fistu-la were evaluated by multivariate Logistic analysis and ROC curve.Results:The content in amylase in drainage fluid at 24,48 and 72 h after operation and partial retention of parotid masseter fascia during operation in the SF group were higher than those in the control group(P＜0.05),and the postoperative compression time was shorter than that in the control group(P＜0.05).Multiva-riate Logistic analysis showed that the amylase content of drainage fluid at 24,48 and 72 h and the complete preservation of parotid masseter fascia during operation were the influencing factors for the occurrence of postoperative SF(P＜0.05).The ROC curve showed that the AUC of amylase level of drainage fluid in predicting the risk of postoperative SF was 0.979(95％CI 0.930-0.997)at 72 h after surgery.Conclusion:The level of amylase in the drainage fluid is associated with the risk of SF after benign parotid tumor resection.The level of amylase in the drainage fluid 72h after benign parotid tumor resection can accurately predict SF after benign parotid tumor resection.

BACKGROUND:In recent years,the application of exosomes of periodontal ligament stem cells in periodontal tissue regeneration engineering has been widely studied,but the effect of exosomes on periodontal ligament stem cells derived from inflammatory environment is still unclear.OBJECTIVE:To investigate the effects of exosomes secreted by periodontal ligament stem cells from healthy and inflammatory environments on the proliferation and differentiation of periodontal ligament stem cells from inflammatory environments.METHODS:Human periodontal ligament stem cells from healthy and inflammatory tissues were isolated and cultured by enzyme digestion method.Exosomes were extracted from two kinds of periodontal ligament stem cells using ultracentrifugation.Passage 3 periodontal ligament stem cells derived from inflammatory tissue were selected and cultured in three groups.Cells in the blank group were cultured routinely.The healthy exosome group was added with exosomes secreted by peripheral ligament stem cells derived from healthy tissue.The inflammatory exosome group was added with exosomes secreted by human periodontal ligament stem cells derived from inflammatory tissue.Cell proliferation and cloning were detected.The expression of alkaline phosphatase,the formation of mineralized nodules,and the expression of mRNA and protein of genes related to osteogenesis were detected under osteogenic differentiation.RESULTS AND CONCLUSION:(1) CCK-8 assay and clonal formation test showed that compared with the blank group,two kinds of exosomes could promote the proliferation and colony formation of periodontal ligament stem cells from inflammatory tissue (P<0.05),and the effect of the healthy exosome group was stronger than that of the inflammatory exosome group (P<0.05).(2) Alkaline phosphatase and alizarin red staining showed that compared with the blank group,the two kinds of exosomes could promote the expression of alkaline phosphatase and the formation of mineralized nodules in periodontal ligament stem cells from inflammatory tissue,and the promoting effect of the healthy exosome group was stronger than that of the inflammatory exosome group.RT-PCR and western blot assay showed that compared with the blank group,the two kinds of exosomes could promote the expression of alkaline phosphatase,RUNX2,and type Ⅰ collagen mRNA and protein in periodontal ligament stem cells from inflammatory tissue (P<0.05).The promoting effect of the healthy exosome group was stronger than that of the inflammatory exosome group (P<0.05).(3) The results showed that exosomes secreted by human periodontal ligament stem cells could promote the proliferation and osteogenic differentiation of periodontal ligament stem cells derived from inflammatory environments,and the promoting effect of exosomes secreted by human periodontal ligament stem cells derived from healthy tissues was better than that from human periodontal ligament stem cells derived from inflammatory tissues.

Objective:To examine the long-term efficacy and complications of fecal microbiota transplantation (FMT) for the treatment of diseases related to intestinal dysbiosis.Methods:This was a retrospective descriptive study. Relevant data were collected from the records of 15 000 patients who had undergone FMT and been followed up for more than 3 months during the period from May 2017 to September 2024. The patient cohort comprised 3746 male and 11 254 female patients aged (45.3±12.2) years. The inclusion criterion was meeting the indications for FMT. Application of this criterion yielded 8258 patients with constipation, 684 with Clostridium difficile infection, 1730 with chronic diarrhea, 510 with inflammatory bowel disease, 432 with radiation enteritis, 1940 with irritable bowel syndrome, 365 with autism, 870 with postoperative gastrointestinal dysfunction, and 211 with neurodegenerative diseases. The three routes of delivering FMT comprised infusion of an enterobacterial solution through a nasoenteric tube into the jejunum for 6 consecutive days (upper gastrointestinal FMT group, 11 125 patients), oral intake of enterobacterial capsules for 6 consecutive days (oral capsule FMT, 3597 patients), and a single injection of a bacterial solution into the colon via colonoscopy (lower gastrointestinal FMT group, 278 patients). Other treatments were discontinued during the treatment and follow-up period and administration of other medications was not recommended unless absolutely necessary. The primary outcomes were the efficacy of FMT after 3, 12 and 36 months of treatment, and improvement in chronic constipation, C. difficile infection, chronic diarrhea, inflammatory bowel disease, radiation enteritis, irritable bowel syndrome, post-surgery gastrointestinal dysfunction, and autism. Other outcomes included the occurrence of short-term (within 2 weeks after treatment) and long-term (within 36 months after treatment) adverse reactions.Results:At 3, 12 and 36 months after treatment, the overall rates of effectiveness of treatment were 71.8% (10 763/15 000), 64.4% (7600/11 808) and 58.8% (3659/6218), respectively. Specifically, the rates of clinical improvement were 70.3% (5805/8258), 62.6% (3970/6345), and 56.5% (1894/3352), respectively, for constipation; 85.8% (587/684), 72.3% (408/564), and 67.3% (218/324), respectively, for C.difficile infection; 81.0% (1401/1730), 78.1% (1198/1534), and 72.3% (633/876), respectively, for chronic diarrhea; 64.3% (328/510), 52.3% (249/476), and 46.6 % (97/208), respectively, for inflammatory bowel disease; 77.3% (334/432), 65.4% (212/324), and 53.6% (82/153), respectively, for radiculitis; 70.6% (1370/1940), 64.5% (939/1456), and 60.4% (475/786), respectively, for irritable bowel syndrome; 75.3% (275/365), 70.0% (201/287), and 63.6% (112/176), respectively, for autism; 65.3% (568/870), 54.3% (355/654), and 46.5% (114/245), respectively, for post-surgical gastrointestinal dysfunction; and 45.0% (95/211), 40.5% (68/168), and 34.7% (34/98), respectively, for neurodegenerative diseases. At 3, 12, and 36 months post-treatment, clinical improvement rates were 77.1% (8580/11 125), 67.1% (6437/9595), and 62.1% (3196/5145), respectively, in the upper gastrointestinal route group; and 57.3% (2062/3597), 53.6% (1115/2081), and 45.0% (453/1006), respectively, in the oral capsule group; and 43.5% (121/278) , 36.4% (48/132) and 14.9% (10/67), respectively, in the lower gastrointestinal route group. No serious adverse reactions occurred during treatment or follow-up. The most common adverse reactions in the upper gastrointestinal route group, oral capsule group, and lower gastrointestinal route group were respiratory discomfort (20.4%, 2269/11 125), nausea and vomiting on swallowing the capsule (7.6%, 273/3597), and diarrhea (47.5%, 132/278), respectively; these symptoms resolved at the end of treatment. At 36 months of follow-up, 19 patients reported exacerbation of symptoms of pre-existing diseases and there had been 16 deaths that were not directly related to FMT. Additionally, no systemic diseases had developed after FMT.Conclusion:FMT for the treatment of intestinal dysfunction associated with disorders of the intestinal flora and related extraintestinal diseases is effective and not associated with serious adverse events.

Polymyxin serves as the"last line of defense"for treating infection with multidrug-resistant Gram-ne-gative bacteria.However,the emergence and spread of polymyxin-resistant genes such as mcr-1 severely weakens its clinical efficacy.This paper systematically summarizes the antimicrobial and resistance mechanisms of polymy-xin,comprehensively summarizes the current research progresses in polymyxin sensitizers particular focusing on three aspects:natural compounds,synthetic small molecules,and drug repurposing.Furthermore,this paper explores the innovative strategies of gene intervention,new targets,and nanotechnology-based formulations in the develop-ment of sensitizer,aiming to provide systematic theoretical support and research ideas against polymyxin resistance.

This paper summarizes the academic thought and clinical experience of Professor Gu Ning in diagnosing and treating hy-peruricemia(HUA)based on the Waterway Theory.He proposes that the waterway is a pathway regulated by the Sanjiao and multiple organs,responsible for body fluid metabolism,and that turbid fluids produced after metabolism must be excreted through this pathway.Based on the Water Theory,Professor Gu Ning proposes that the pathogenesis of HUA involves dysfunction of the organs and impaired waterway due to external exposure to the six exogenous pathogens or internal injuries from the seven emotions.The key patho-logical mechanism lies in the accumulation of dampness-turbidity,which subsequently gives rise to various syndrome patterns.Profes-sor Gu Ning developed a therapeutic strategy of eliminating dampness and reducing turbidity for HUA based on the Waterway Theory.By combining and modifying two classical prescriptions,Simiao San and Wuling San,he formulated the Huashi Jiangzhuo For-mula,offering a novel diagnostic and therapeutic approach as well as a theoretical foundation for the treatment of HUA.

This paper summarizes the academic thought and clinical experience of Professor Gu Ning in diagnosing and treating hy-peruricemia(HUA)based on the Waterway Theory.He proposes that the waterway is a pathway regulated by the Sanjiao and multiple organs,responsible for body fluid metabolism,and that turbid fluids produced after metabolism must be excreted through this pathway.Based on the Water Theory,Professor Gu Ning proposes that the pathogenesis of HUA involves dysfunction of the organs and impaired waterway due to external exposure to the six exogenous pathogens or internal injuries from the seven emotions.The key patho-logical mechanism lies in the accumulation of dampness-turbidity,which subsequently gives rise to various syndrome patterns.Profes-sor Gu Ning developed a therapeutic strategy of eliminating dampness and reducing turbidity for HUA based on the Waterway Theory.By combining and modifying two classical prescriptions,Simiao San and Wuling San,he formulated the Huashi Jiangzhuo For-mula,offering a novel diagnostic and therapeutic approach as well as a theoretical foundation for the treatment of HUA.

Objective:To examine the long-term efficacy and complications of fecal microbiota transplantation (FMT) for the treatment of diseases related to intestinal dysbiosis.Methods:This was a retrospective descriptive study. Relevant data were collected from the records of 15 000 patients who had undergone FMT and been followed up for more than 3 months during the period from May 2017 to September 2024. The patient cohort comprised 3746 male and 11 254 female patients aged (45.3±12.2) years. The inclusion criterion was meeting the indications for FMT. Application of this criterion yielded 8258 patients with constipation, 684 with Clostridium difficile infection, 1730 with chronic diarrhea, 510 with inflammatory bowel disease, 432 with radiation enteritis, 1940 with irritable bowel syndrome, 365 with autism, 870 with postoperative gastrointestinal dysfunction, and 211 with neurodegenerative diseases. The three routes of delivering FMT comprised infusion of an enterobacterial solution through a nasoenteric tube into the jejunum for 6 consecutive days (upper gastrointestinal FMT group, 11 125 patients), oral intake of enterobacterial capsules for 6 consecutive days (oral capsule FMT, 3597 patients), and a single injection of a bacterial solution into the colon via colonoscopy (lower gastrointestinal FMT group, 278 patients). Other treatments were discontinued during the treatment and follow-up period and administration of other medications was not recommended unless absolutely necessary. The primary outcomes were the efficacy of FMT after 3, 12 and 36 months of treatment, and improvement in chronic constipation, C. difficile infection, chronic diarrhea, inflammatory bowel disease, radiation enteritis, irritable bowel syndrome, post-surgery gastrointestinal dysfunction, and autism. Other outcomes included the occurrence of short-term (within 2 weeks after treatment) and long-term (within 36 months after treatment) adverse reactions.Results:At 3, 12 and 36 months after treatment, the overall rates of effectiveness of treatment were 71.8% (10 763/15 000), 64.4% (7600/11 808) and 58.8% (3659/6218), respectively. Specifically, the rates of clinical improvement were 70.3% (5805/8258), 62.6% (3970/6345), and 56.5% (1894/3352), respectively, for constipation; 85.8% (587/684), 72.3% (408/564), and 67.3% (218/324), respectively, for C.difficile infection; 81.0% (1401/1730), 78.1% (1198/1534), and 72.3% (633/876), respectively, for chronic diarrhea; 64.3% (328/510), 52.3% (249/476), and 46.6 % (97/208), respectively, for inflammatory bowel disease; 77.3% (334/432), 65.4% (212/324), and 53.6% (82/153), respectively, for radiculitis; 70.6% (1370/1940), 64.5% (939/1456), and 60.4% (475/786), respectively, for irritable bowel syndrome; 75.3% (275/365), 70.0% (201/287), and 63.6% (112/176), respectively, for autism; 65.3% (568/870), 54.3% (355/654), and 46.5% (114/245), respectively, for post-surgical gastrointestinal dysfunction; and 45.0% (95/211), 40.5% (68/168), and 34.7% (34/98), respectively, for neurodegenerative diseases. At 3, 12, and 36 months post-treatment, clinical improvement rates were 77.1% (8580/11 125), 67.1% (6437/9595), and 62.1% (3196/5145), respectively, in the upper gastrointestinal route group; and 57.3% (2062/3597), 53.6% (1115/2081), and 45.0% (453/1006), respectively, in the oral capsule group; and 43.5% (121/278) , 36.4% (48/132) and 14.9% (10/67), respectively, in the lower gastrointestinal route group. No serious adverse reactions occurred during treatment or follow-up. The most common adverse reactions in the upper gastrointestinal route group, oral capsule group, and lower gastrointestinal route group were respiratory discomfort (20.4%, 2269/11 125), nausea and vomiting on swallowing the capsule (7.6%, 273/3597), and diarrhea (47.5%, 132/278), respectively; these symptoms resolved at the end of treatment. At 36 months of follow-up, 19 patients reported exacerbation of symptoms of pre-existing diseases and there had been 16 deaths that were not directly related to FMT. Additionally, no systemic diseases had developed after FMT.Conclusion:FMT for the treatment of intestinal dysfunction associated with disorders of the intestinal flora and related extraintestinal diseases is effective and not associated with serious adverse events.

BACKGROUND:In recent years,the application of exosomes of periodontal ligament stem cells in periodontal tissue regeneration engineering has been widely studied,but the effect of exosomes on periodontal ligament stem cells derived from inflammatory environment is still unclear.OBJECTIVE:To investigate the effects of exosomes secreted by periodontal ligament stem cells from healthy and inflammatory environments on the proliferation and differentiation of periodontal ligament stem cells from inflammatory environments.METHODS:Human periodontal ligament stem cells from healthy and inflammatory tissues were isolated and cultured by enzyme digestion method.Exosomes were extracted from two kinds of periodontal ligament stem cells using ultracentrifugation.Passage 3 periodontal ligament stem cells derived from inflammatory tissue were selected and cultured in three groups.Cells in the blank group were cultured routinely.The healthy exosome group was added with exosomes secreted by peripheral ligament stem cells derived from healthy tissue.The inflammatory exosome group was added with exosomes secreted by human periodontal ligament stem cells derived from inflammatory tissue.Cell proliferation and cloning were detected.The expression of alkaline phosphatase,the formation of mineralized nodules,and the expression of mRNA and protein of genes related to osteogenesis were detected under osteogenic differentiation.RESULTS AND CONCLUSION:(1) CCK-8 assay and clonal formation test showed that compared with the blank group,two kinds of exosomes could promote the proliferation and colony formation of periodontal ligament stem cells from inflammatory tissue (P<0.05),and the effect of the healthy exosome group was stronger than that of the inflammatory exosome group (P<0.05).(2) Alkaline phosphatase and alizarin red staining showed that compared with the blank group,the two kinds of exosomes could promote the expression of alkaline phosphatase and the formation of mineralized nodules in periodontal ligament stem cells from inflammatory tissue,and the promoting effect of the healthy exosome group was stronger than that of the inflammatory exosome group.RT-PCR and western blot assay showed that compared with the blank group,the two kinds of exosomes could promote the expression of alkaline phosphatase,RUNX2,and type Ⅰ collagen mRNA and protein in periodontal ligament stem cells from inflammatory tissue (P<0.05).The promoting effect of the healthy exosome group was stronger than that of the inflammatory exosome group (P<0.05).(3) The results showed that exosomes secreted by human periodontal ligament stem cells could promote the proliferation and osteogenic differentiation of periodontal ligament stem cells derived from inflammatory environments,and the promoting effect of exosomes secreted by human periodontal ligament stem cells derived from healthy tissues was better than that from human periodontal ligament stem cells derived from inflammatory tissues.