BACKGROUND:Various proteins,signaling pathways,and inflammatory mediators are involved in the pathophysiological process of osteoarthritis.The development of small molecule drugs targeting these proteins,signaling pathways,and inflammatory mediators can effectively delay the progression of osteoarthritis and ameliorate its clinical manifestations. OBJECTIVE:To review the research progress of small molecule drugs in the treatment of osteoarthritis based on the pathogenesis of osteoarthritis. METHODS:PubMed,CNKI,and WanFang databases were searched with English search terms"osteoarthritis,arthritis,osteoarthrosis,degenerative,arthritides,deformans,small molecule drugs,small molecule inhibitors,small molecule agents"and Chinese search terms"osteoarthritis,small molecule drugs,small molecule inhibitors."A total of 68 articles were included for review according to the inclusion and exclusion criteria. RESULTS AND CONCLUSION:(1)Currently,studies concerning the pathogenesis of osteoarthritis remain unclear.The occurrence and development of osteoarthritis are strongly associated with proteins,cytokines,and signal transduction pathways,so its therapeutic mechanism is relatively complex.Currently,targeting proteins,cytokines,and signal transduction pathways related to osteoarthritis with small molecule drugs has become a major research focus.(2)Small molecule drugs frequently possess visible intracellular or extracellular targets and efficacy,containing enhancing cartilage repair,resisting joint degradation,attenuating inflammation,and relieving pain.Other anti-osteoarthritis small molecule drugs have shown promise in promoting stem cell chondrogenic differentiation and cartilage matrix reconstruction.(3)At present,small molecule drugs targeting the pathophysiological process of osteoarthritis to delay the progression of osteoarthritis are still in the experimental stage,but most of these small molecule drugs have shown the expected results in the experimental process,and there are no relevant studies to illustrate the efficacy of small molecule drugs in the treatment of osteoarthritis.(4)Small molecule drugs for the treatment of osteoarthritis have reached the expected experimental results in the basic experimental stage.Numerous studies have exhibited that small molecule drugs can target the suppression of specific proteins,cytokines,and signal transduction pathways that cause osteoarthritis,so as to treat osteoarthritis.Nevertheless,its safety and effectiveness still need to be identified by further basic and clinical studies.This process needs to be investigated and studied by more scholars.(5)At present,many scholars in and outside China have made contributions to the treatment of osteoarthritis.Compared with traditional treatment methods,small molecule drugs reveal better efficacy and safety in the basic experimental stage,and it is expected to become an emerging method for the treatment of osteoarthritis in the future to rid patients of pain.

Objective:To investigate the clinical efficacy of Full-endoscopic pars debridement, graft with autograft and recombinant human bone morphogenetic protein 2 (rhBMP-2), and percutaneous pedicle screw (PPS) fixation for the treatment of lumbar spondylolysis.Methods:A retrospective analysis was performed for the case data of 8 patients (7 males and 1 female) of lumbar spondylolysis treated with full-endoscopic pars bone graft with autograft and rhBMP-2 combined with PPS fixation in the fourth medical center of PLA general hospital. The mean age was 21.8±4.1 years (range, 16-29 years). All cases had mono-segmental bilateral pars defects, including 2 cases of L 4 and 6 cases of L 5. The visual analogue scale (VAS) and the Oswestry disability index (ODI) were recorded before and after surgery. MacNab score was used to evaluate the final clinical outcome of lumbar function at 1 year after the removal of internal fixation. Multi-planar reconstruction of CT scans was used to evaluate the bone healing at 6 and 12 months after the operation, and par condition at 1 year after the removal of internal fixation. Pfirrmann's grading system through MRI was used to grade disc degeneration in the fixed and adjacent discs respectively before the operation, before the removal of internal fixation, and 1 year after the removal of internal fixation. Results:All the operations were successfully completed. All patients were followed up for 24-30 months, with an average follow-up time of 27.75±3.11 months. Both VAS of back pain (1.63±0.74, 1.25±0.71、1.00±0.53) and ODI (10.25%±5.17%、6.33%±5.03%、4.86%±3.35%) at 6 and 12 months after the operation and 1 year after the removal of internal fixation were improved compared with those preoperatively (7.25±1.04 and 40.67%±9.67%), with significant differences ( P<0.05). The improvement rates of VAS and ODI at one year after pars repair were 83.31%±8.85% and 85.22%±9.60%, respectively. The improvement rates of VAS and ODI at one year after the removal of internal fixation were 85.96%±6.97% and 88.05%±7.25%, respectively. At the final follow-up, 7 patients had excellent results and 1 patient had good results according to the MacNab criteria. There were 3 patients bony healed in 6 months postoperatively and the remaining 5 patients bony healed in 12 months postoperatively. There was no pars re-rupture at the one-year follow-up after the removal of internal fixation. Disc degeneration increase one grade at the fixed disc in one patient before and after the removal of internal fixation than before pars repair surgery. Disc degeneration increase one grade at the adjacent disc in one patient before and after the removal of internal fixation than before pars repair surgery. There were no intraoperative or postoperative complications, such as nerve injury, cerebrospinal fluid leakage, incision exudation, infection, or breakdown of internal fixation device. Conclusions:Full-endoscopic pars bone debridement, graft with autograft and rhBMP-2, followed by PPS fixation is a safe and effective minimally invasive spine surgery for treating lumbar spondylolysis. It has the advantages of a high fusion rate, low incidence of complications, no pars re-rupture after the removal of internal fixation and no significantly increasing intervertebral disc degeneration in fixed and adjacent discs.

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.

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/Aims: Metabolic dysfunction–associated steatotic liver disease (MASLD) is a chronic liver disease characterized by hepatic steatosis. Ubiquitin-specific protease 29 (USP29) plays pivotal roles in hepatic ischemiareperfusion injury and hepatocellular carcinoma, but its role in MASLD remains unexplored. Therefore, the aim of this study was to reveal the effects and underlying mechanisms of USP29 in MASLD progression. Methods: USP29 expression was assessed in liver samples from MASLD patients and mice. The role and molecular mechanism of USP29 in MASLD were assessed in high-fat diet-fed and high-fat/high-cholesterol diet-fed mice and palmitic acid and oleic acid treated hepatocytes. Results: USP29 protein levels were significantly reduced in mice and humans with MASLD. Hepatic steatosis, inflammation and fibrosis were significantly exacerbated by USP29 deletion and relieved by USP29 overexpression. Mechanistically, USP29 significantly activated the expression of genes related to fatty acid β-oxidation (FAO) under metabolic stimulation, directly interacted with long-chain acyl-CoA synthase 5 (ACSL5) and repressed ACSL5 degradation by increasing ACSL5 K48-linked deubiquitination. Moreover, the effect of USP29 on hepatocyte lipid accumulation and MASLD was dependent on ACSL5. Conclusions USP29 functions as a novel negative regulator of MASLD by stabilizing ACSL5 to promote FAO. The activation of the USP29-ACSL5 axis may represent a potential therapeutic strategy for MASLD.

ObjectiveTo analyze the factors influencing meropenem-related liver injury （MRLI） and to explore their clinical predictive value. MethodsA retrospective case-control study was conducted， and the Chinese Hospital Pharmacovigilance System （CHPS） was used to establish a retrieval scheme. A total of 1 625 hospitalized cases using meropenem from January 2018 to December 2022 were collected. Patients were divided into case group （n=62） and control group （n=1 563） based on the presence or absence of liver injury. Clinical data and laboratory indicators from both groups were collected and analyzed. The t-test was used for comparison of normally distributed continuous data between the two groups， while the Mann-Whitney U test was used for comparison of continuous data not conforming to a normal distribution. The chi-square test was used for comparison of categorical data between the two groups. A multivariate Logistic regression analysis was performed to identify the influencing factors for MRLI. A Logistic regression equation was established， and the predictive value of these factors was assessed using the receiver operating characteristic （ROC） curve. ResultsThe results of univariate analysis indicated that the rates of male patients， hypoproteinemia， shock， intensive care unit （ICU） admissions， sepsis， and liver， gallbladder， and cardiovascular diseases， the levels of alanine aminotransferase （ALT）， alkaline phosphatase （ALP）， gamma-glutamyl transpeptidase （GGT）， aspartate aminotransferase （AST）， creatinine （CREA）， and procalcitonin （PCT）， and the number of hospitalization days were significantly higher in the case group than in the control group （P<0.05）， and that the platelet levels in the case group were significantly lower than those in the control group （P<0.05）. The multivariate Logistic regression analysis showed that male sex （odds ratio ［OR］=2.080， 95% confidence interval ［CI］： 1.050 — 4.123， P=0.036）， admission to the ICU （OR=8.207， 95%CI： 4.094‍ ‍—‍ ‍16.453， P<0.001）， comorbidity with gallbladder disease （OR=8.240， 95%CI： 3.605‍ ‍—‍ ‍18.832， P<0.001）， ALP （OR=1.012， 95%CI： 1.004‍ ‍—‍ ‍1.019， P=0.004）， GGT （OR=1.010， 95%CI： 1.005‍ ‍—‍ ‍1.015， P<0.001）， and PLT （OR=0.997， 95%CI： 0.994‍ ‍—‍ ‍0.999， P=0.020） were the influential factors for MRLI. The areas under the ROC curve of ALP， GGT， and PLT were 0.589， 0.637， and 0.595， respectively， and the AUC of them combined was 0.837. ConclusionMale sex， ICU admission， comorbidity with gallbladder disease， increased ALP， increased GGT， and decreased PLT were influencing factors for MRLI， and a combination of factors has a better predictive value for the occurrence of MRLI.

The pandemic of the COVID-19 accelerated the research and developing process of nucle-ic acid vaccines worldwide.Biopharmaceutical companies represented by Pfizer BioNTech and Mod-erna of the United States completed the marketing of the COVID-19 mRNA vaccine at an aston-ishing speed.In a short time,COVID-19 nucleic acid vaccine from development to commercial pro-duction,and then to the rapid expansion of the industry,giving researchers great shock and inspira-tion.Can we utilize advanced technology platforms and develop veterinary nucleic acid vaccines un-der the concept of One Health to ensure the common health of animals and humans.This article summarizes the research progress of nucleic acid vaccines in companion animals and foodborne ani-mal diseases in recent years,and puts forward prospects for the application of nucleic acid vac-cines,especially mRNA vaccines.

Objective:To investigate the clinical efficacy of Full-endoscopic pars debridement, graft with autograft and recombinant human bone morphogenetic protein 2 (rhBMP-2), and percutaneous pedicle screw (PPS) fixation for the treatment of lumbar spondylolysis.Methods:A retrospective analysis was performed for the case data of 8 patients (7 males and 1 female) of lumbar spondylolysis treated with full-endoscopic pars bone graft with autograft and rhBMP-2 combined with PPS fixation in the fourth medical center of PLA general hospital. The mean age was 21.8±4.1 years (range, 16-29 years). All cases had mono-segmental bilateral pars defects, including 2 cases of L 4 and 6 cases of L 5. The visual analogue scale (VAS) and the Oswestry disability index (ODI) were recorded before and after surgery. MacNab score was used to evaluate the final clinical outcome of lumbar function at 1 year after the removal of internal fixation. Multi-planar reconstruction of CT scans was used to evaluate the bone healing at 6 and 12 months after the operation, and par condition at 1 year after the removal of internal fixation. Pfirrmann's grading system through MRI was used to grade disc degeneration in the fixed and adjacent discs respectively before the operation, before the removal of internal fixation, and 1 year after the removal of internal fixation. Results:All the operations were successfully completed. All patients were followed up for 24-30 months, with an average follow-up time of 27.75±3.11 months. Both VAS of back pain (1.63±0.74, 1.25±0.71、1.00±0.53) and ODI (10.25%±5.17%、6.33%±5.03%、4.86%±3.35%) at 6 and 12 months after the operation and 1 year after the removal of internal fixation were improved compared with those preoperatively (7.25±1.04 and 40.67%±9.67%), with significant differences ( P<0.05). The improvement rates of VAS and ODI at one year after pars repair were 83.31%±8.85% and 85.22%±9.60%, respectively. The improvement rates of VAS and ODI at one year after the removal of internal fixation were 85.96%±6.97% and 88.05%±7.25%, respectively. At the final follow-up, 7 patients had excellent results and 1 patient had good results according to the MacNab criteria. There were 3 patients bony healed in 6 months postoperatively and the remaining 5 patients bony healed in 12 months postoperatively. There was no pars re-rupture at the one-year follow-up after the removal of internal fixation. Disc degeneration increase one grade at the fixed disc in one patient before and after the removal of internal fixation than before pars repair surgery. Disc degeneration increase one grade at the adjacent disc in one patient before and after the removal of internal fixation than before pars repair surgery. There were no intraoperative or postoperative complications, such as nerve injury, cerebrospinal fluid leakage, incision exudation, infection, or breakdown of internal fixation device. Conclusions:Full-endoscopic pars bone debridement, graft with autograft and rhBMP-2, followed by PPS fixation is a safe and effective minimally invasive spine surgery for treating lumbar spondylolysis. It has the advantages of a high fusion rate, low incidence of complications, no pars re-rupture after the removal of internal fixation and no significantly increasing intervertebral disc degeneration in fixed and adjacent discs.

Background/Aims: Metabolic dysfunction–associated steatotic liver disease (MASLD) is a chronic liver disease characterized by hepatic steatosis. Ubiquitin-specific protease 29 (USP29) plays pivotal roles in hepatic ischemiareperfusion injury and hepatocellular carcinoma, but its role in MASLD remains unexplored. Therefore, the aim of this study was to reveal the effects and underlying mechanisms of USP29 in MASLD progression. Methods: USP29 expression was assessed in liver samples from MASLD patients and mice. The role and molecular mechanism of USP29 in MASLD were assessed in high-fat diet-fed and high-fat/high-cholesterol diet-fed mice and palmitic acid and oleic acid treated hepatocytes. Results: USP29 protein levels were significantly reduced in mice and humans with MASLD. Hepatic steatosis, inflammation and fibrosis were significantly exacerbated by USP29 deletion and relieved by USP29 overexpression. Mechanistically, USP29 significantly activated the expression of genes related to fatty acid β-oxidation (FAO) under metabolic stimulation, directly interacted with long-chain acyl-CoA synthase 5 (ACSL5) and repressed ACSL5 degradation by increasing ACSL5 K48-linked deubiquitination. Moreover, the effect of USP29 on hepatocyte lipid accumulation and MASLD was dependent on ACSL5. Conclusions USP29 functions as a novel negative regulator of MASLD by stabilizing ACSL5 to promote FAO. The activation of the USP29-ACSL5 axis may represent a potential therapeutic strategy for MASLD.

The pandemic of the COVID-19 accelerated the research and developing process of nucle-ic acid vaccines worldwide.Biopharmaceutical companies represented by Pfizer BioNTech and Mod-erna of the United States completed the marketing of the COVID-19 mRNA vaccine at an aston-ishing speed.In a short time,COVID-19 nucleic acid vaccine from development to commercial pro-duction,and then to the rapid expansion of the industry,giving researchers great shock and inspira-tion.Can we utilize advanced technology platforms and develop veterinary nucleic acid vaccines un-der the concept of One Health to ensure the common health of animals and humans.This article summarizes the research progress of nucleic acid vaccines in companion animals and foodborne ani-mal diseases in recent years,and puts forward prospects for the application of nucleic acid vac-cines,especially mRNA vaccines.