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 Analyze the epidemiological characteristics of respiratory virus infections in Kunming area during 2023-2024,and explore the detection rates of different virus types and their distribution patterns across different time periods and age groups.Methods A total of 10354 nasopharyngeal swab or sputum samples were retrospectively collected from patients with acute respiratory infections who visited the Third People's Hospital of Kunming City between March 2023 and June 2024.Multiple pathogens were detected using real-time fluorescent quantitative polymerase chain reaction(RT-qPCR)technology.A retrospective analysis was then conducted on the clinical laboratory detection results,statistically analyzing the overall detection rates of various respiratory viruses,multiple infection phenomena,gender differences,age distribution,seasonal variations,infection site differences,and monthly infection situations.Results Among the 10354 patient respiratory samples tested,3368 pathogen infections were detected,with a detection rate of 32.53%(3368/10354).204 patients presented with mixed infections of≥2 pathogens,with a mixed detection rate of 6.06%(204/3368).The single detection rate for females was significantly higher than males(P<0.001),and the multiple infection detection rate for males is significantly higher than females(P<0.05),indicating that males may have a higher risk of concurrent infections.Among different age groups,the virus detection rate was highest in the 5-18 years age group at 55.87%.Significant differences were observed in the detection rates of FluA,FluB,and SIV-H3 across different disease types(P<0.05).In March 2023,the detection rate was highest at 54.27%(5619/10354),with Influenza A virus(FluA)and seasonal influenza H3 subtype(SIV-H3)being the most detected pathogens.Conclusion In acute respiratory infection(ARI)cases in the Kunming area,FluA,FluB,and SIV-H3 were the primary viral pathogens,with the region's viral epidemic characteristics closely related to patient age stages,seasonal changes,and infection site factors.

Objective To evaluate the efficacy and safety of polyethylene glycol electrolyte powder(PEG)combined with linaclotide(Lin)for bowel preparation in elderly constipated patients before colonoscopy.Methods In this prospective,randomized controlled trial,90 elderly patients with constipation undergoing colonoscopy were recruited at our hospital from June 2022 to December 2023.Participants were randomly assigned to three groups(n=30 each):PEG-3L alone,PEG-3L+Lin,and PEG-2L+Lin.Primary outcome was Boston Bowel Preparation Scale(BBPS)score and secondary outcomes included adverse event rates,colonoscopy completion rate,withdrawal time,and polyp detection rate.Statistical analysis was performed using independent t-tests and chi-square tests.Results The PEG-3L+Lin group achieved significantly higher BBPS scores than both PEG-3L alone and PEG-2L+Lin groups did(both P<0.001).The PEG-2L+Lin group also outperformed the PEG-3L alone group in cleansing efficacy(90.0%vs.76.7%,P=0.008).The PEG-2L+Lin group demonstrated the best tolerability and lowest adverse event rate,the PEG-3L group had the longest withdrawal time(P<0.05),but the three groups showed no significant difference in polyp detection rates.Conclusion PEG combined with linaclotide significantly improves bowel cleansing in elderly constipated patients.PEG-2L+Lin regimen provides optimal balance between efficacy,safety,and tolerability,making it a preferable choice for this population.

Objective To investigate the application of operation plan based on injury stress sequence in the treatment of degree Ⅲ and Ⅳ ankle fractures with Lange-Hansen classification of pronation and external rotation.Methods From May 2019 to May 2022,80 eligible patients of degree Ⅲand Ⅳ ankle fractures with Lange-Hansen classification were selected prospectively and randomely divided into 2 groups:40 patients in the study group were treated with surgical reduction according to the sequence of injury stress,and the other 40 patients in the control group were treated with traditional reduction sequence.The operative time,intraoperative blood loss,fracture healing time,full weight-bearing time,Ankle dorsoextension Angle,plantar flexion Angle,and American Orthopaedic Foot and Ankle Association were compared between the two groups Society,AOFAS)Ankle and posterior foot function scores and complications.Results The surgical time[(44.80±5.12)min vs.(47.61±6.42)min]and surgical bleeding volume[(43.81±9.02)ml vs.(51.50±12.01)ml]between the study group and the control group were statistically significant(all P＜0.05).Before surgery,there had no significant differences in ankle joint dorsiflexion angle,plantar flexion angle,AOFAS ankle and hind foot function score in 2 groups(all P＞0.05).The ankle dorsiflexion angle at 3 months after surgery[(16.84±1.77)° vs.(15.50±1.65)°],plantar flexion angle at 3 months after surgery[(45.64±4.10)° vs.(42.58±3.86)°]and at 6 months after surgery[(52.38±3.03)°vs.(50.64±3.74)°],the maximum walking distance score[(3.50±0.64)vs.(3.16±0.60)],ground walking score[(2.06±0.56)vs.(1.72±0.48)]and ankle joint anteroposterior activity score at 3 months after surgery[(4.96±1.38)vs.(4.16±1.07)]of the study group were all higher than those in the control group(all P＜0.05).There was no statistically significant difference in terms of fracture healing time,complete weight-bearing time,postoperative pain score,ankle joint function autonomous activity support score,abnormal gait score,maximum walking distance score at 6 months after surgery,ground walking score,ankle joint anterior and posterior activity score and surgical complications between 2 group(all P＞0.05).Conclusion According to the sequence of injury stress,surgical reduction for the treatment of grade Ⅲ and Ⅳ ankle fractures of Lange-Hansen classification of middle pronation and external rotation can shorten the operation time and promote the early recovery of joint function.

Objective To investigate the application of operation plan based on injury stress sequence in the treatment of degree Ⅲ and Ⅳ ankle fractures with Lange-Hansen classification of pronation and external rotation.Methods From May 2019 to May 2022,80 eligible patients of degree Ⅲand Ⅳ ankle fractures with Lange-Hansen classification were selected prospectively and randomely divided into 2 groups:40 patients in the study group were treated with surgical reduction according to the sequence of injury stress,and the other 40 patients in the control group were treated with traditional reduction sequence.The operative time,intraoperative blood loss,fracture healing time,full weight-bearing time,Ankle dorsoextension Angle,plantar flexion Angle,and American Orthopaedic Foot and Ankle Association were compared between the two groups Society,AOFAS)Ankle and posterior foot function scores and complications.Results The surgical time[(44.80±5.12)min vs.(47.61±6.42)min]and surgical bleeding volume[(43.81±9.02)ml vs.(51.50±12.01)ml]between the study group and the control group were statistically significant(all P＜0.05).Before surgery,there had no significant differences in ankle joint dorsiflexion angle,plantar flexion angle,AOFAS ankle and hind foot function score in 2 groups(all P＞0.05).The ankle dorsiflexion angle at 3 months after surgery[(16.84±1.77)° vs.(15.50±1.65)°],plantar flexion angle at 3 months after surgery[(45.64±4.10)° vs.(42.58±3.86)°]and at 6 months after surgery[(52.38±3.03)°vs.(50.64±3.74)°],the maximum walking distance score[(3.50±0.64)vs.(3.16±0.60)],ground walking score[(2.06±0.56)vs.(1.72±0.48)]and ankle joint anteroposterior activity score at 3 months after surgery[(4.96±1.38)vs.(4.16±1.07)]of the study group were all higher than those in the control group(all P＜0.05).There was no statistically significant difference in terms of fracture healing time,complete weight-bearing time,postoperative pain score,ankle joint function autonomous activity support score,abnormal gait score,maximum walking distance score at 6 months after surgery,ground walking score,ankle joint anterior and posterior activity score and surgical complications between 2 group(all P＞0.05).Conclusion According to the sequence of injury stress,surgical reduction for the treatment of grade Ⅲ and Ⅳ ankle fractures of Lange-Hansen classification of middle pronation and external rotation can shorten the operation time and promote the early recovery of joint function.

Objective To evaluate the efficacy and safety of polyethylene glycol electrolyte powder(PEG)combined with linaclotide(Lin)for bowel preparation in elderly constipated patients before colonoscopy.Methods In this prospective,randomized controlled trial,90 elderly patients with constipation undergoing colonoscopy were recruited at our hospital from June 2022 to December 2023.Participants were randomly assigned to three groups(n=30 each):PEG-3L alone,PEG-3L+Lin,and PEG-2L+Lin.Primary outcome was Boston Bowel Preparation Scale(BBPS)score and secondary outcomes included adverse event rates,colonoscopy completion rate,withdrawal time,and polyp detection rate.Statistical analysis was performed using independent t-tests and chi-square tests.Results The PEG-3L+Lin group achieved significantly higher BBPS scores than both PEG-3L alone and PEG-2L+Lin groups did(both P<0.001).The PEG-2L+Lin group also outperformed the PEG-3L alone group in cleansing efficacy(90.0%vs.76.7%,P=0.008).The PEG-2L+Lin group demonstrated the best tolerability and lowest adverse event rate,the PEG-3L group had the longest withdrawal time(P<0.05),but the three groups showed no significant difference in polyp detection rates.Conclusion PEG combined with linaclotide significantly improves bowel cleansing in elderly constipated patients.PEG-2L+Lin regimen provides optimal balance between efficacy,safety,and tolerability,making it a preferable choice for this population.

Lipid nanovehicles are currently the most advanced vehicles used for RNA delivery, as demonstrated by the approval of patisiran for amyloidosis therapy in 2018. To illuminate the unique superiority of lipid nanovehicles in RNA delivery, in this review, we first introduce various RNA therapeutics, describe systemic delivery barriers, and explain the lipid components and methods used for lipid nanovehicle preparation. Then, we emphasize crucial advances in lipid nanovehicle design for overcoming barriers to systemic RNA delivery. Finally, the current status and challenges of lipid nanovehicle-based RNA therapeutics in clinical applications are also discussed. Our objective is to provide a comprehensive overview showing how to utilize lipid nanovehicles to overcome multiple barriers to systemic RNA delivery, inspiring the development of more high-performance RNA lipid nanovesicles in the future.

Objective:On the basis of post evaluation,the hospital pharmacy posts are scientifically classified and stratified,and the performance evaluation standard of pharmacy posts is constructed.Methods:The hospital pharmacy posts are classified and stratified by factor comparison method and the post value coefficient is determined.Delphi method and analytic hierarchy process are used to construct the performance evaluation index system of pharmaceutical posts and determine the performance evaluation standards.Results:Pharmacy posts in hospitals are divided into 5 categories,including clinical pharmacists,research pharmacists,static pharmacists,dispensing pharmacists and purchasing pharmacists.The indexes and weights of pharmaceutical post performance evaluation are determined from 4 dimensions:service,process,quality and cost,and the evaluation standard of pharmaceutical post performance oriented to rational drug use is established.Conclusion:The construction of pharmaceutical performance evaluation system meets the requirements of the reform of public hospitals for the transformation and development of pharmaceutical services,which is conducive to enhancing the enthusiasm of pharmaceutical personnel and improving the efficiency and benefit of pharmaceutical services.

BACKGROUND:Most of the silver coating materials prepared using active screen plasma technology in the past do not involve the nanotechnology field.The formed silver coating is in a"thin film"form,which is coated on the surface of the substrate,and the distribution of silver particles on the surface is uneven.Its long-term antibacterial ability is challenged. OBJECTIVE:To prepare nano silver coatings capable of being"buried"within stainless steel(SS)substrates using active screen plasma surface modification(ASPSM)and to observe antibacterial activity. METHODS:The nano-silver coating was prepared by ASPSM technique on stainless steel substrate.Three groups of coating samples were prepared by adjusting the bombardment time(1,2,and 4 hours),which were denoted as 1 h-Ag-ASPSM@SS,2 h-Ag-ASPSM@SS and 4 h-Ag-ASPSM@SS,respectively.The antibacterial activity of the coatings was analyzed by antibacterial ring test and Gram staining.The antibiotic coating samples of gentamicin combined with vancomycin were prepared by using stainless steel as substrate and were recorded as ACNs.Stainless steel,2 h-Ag-ASPSM@SS,and ACNs were inserted into Staphylococcus aureus or Pseudomonas aeruginosa suspension,respectively.The long-acting(84 days)antibacterial activity of the samples was analyzed by coating plate method.Bone marrow mesenchymal stem cells were co-cultured with stainless steel,2 h-Ag-ASPSM@SS,and ACNs,respectively.CCK-8 assay,dead/alive staining,and lactate dehydrogenase activity of cell supernatant were detected.Stainless steel,2 h-Ag-ASPSM@SS,and ACNs were taken after continuous exposure to Staphylococcus aureus suspension for 12 weeks.The amount of residual viable bacteria on the surface of the material was evaluated by spread plate method.Vancomycin drug sensitive disk method was used to evaluate the resistance of residual live bacteria on the surface of materials. RESULTS AND CONCLUSION:(1)With increasing bombardment time,the diameter of nano silver on the sample surface and the silver content in the coating gradually increased.Among them,the 2 h-Ag-ASPSM@SS exhibited the highest surface silver content while forming uniformly spherical nanoparticles.(2)Antibacterial ring test and Gram staining results demonstrated that compared with 1 h-Ag-ASPSM@SS and 4 h-Ag-ASPSM@SS,the 2 h-Ag-ASPSM@SS exhibited better inhibitory effect on Staphylococcus aureus and pseudomonas aeruginosa.After co-culturing with bacteria for 42 and 84 days,the number of viable bacteria on the spread plate method was significantly lower in the 2 h-Ag-ASPSM@SS group compared to the stainless steel and ACNs groups.After co-culturing with Staphylococcus aureus for 84 days and Pseudomonas aeruginosa for 42 days,the number of viable bacteria on the surface of the eluate from the ACNs group was higher than that of the stainless steel group.(3)CCK-8 assay,live/dead staining and lactate dehydrogenase activity of cell supernatant displayed that 2 h-Ag-ASPSM@SS did not have obvious cytotoxicity.ACNs showed obvious cytotoxicity.(4)After co-culture with Staphylococcus aureus for 12 weeks,the residual viable bacteria on the surface of 2 h-Ag-ASPSM@SS group was less than that of stainless steel group,and the residual viable bacteria on the surface of the ACNs group was more than that of stainless steel group.Compared with the stainless steel group,the sensitivity to vancomycin was significantly decreased in the ACNs group(P＜0.001),and there was no significant change in sensitivity to vancomycin in 2 h-Ag-ASPSM@SS group(P＞0.05).(5)The above results indicate that the silver nanoparticle coated stainless steel greatly improves the deposition efficiency of silver nanoparticles on the stainless steel surface and has long-lasting antibacterial properties and good cell compatibility.

Objective:This investigation sought to delineate the associations among colorectal adenomatous polyps, diabetes, and biomolecules involved in glucose metabolism.Method:Data were collected from 40 patients who underwent endoscopic polypectomy at the Endoscopy Department of Shandong Cancer Hospital between June 2019 and September 2021. This cohort included 27 patients with inflammatory polyps and 13 with adenomatous polyps. We assessed fasting insulin (Fins), fasting blood glucose (FBG), and the mRNA expressions of fibroblast growth factor 19 (FGF-19) and insulin-like growth factor 1 (IGF-1) in the polyp tissues. Both univariate and multivariate logistic regression analyses were employed to ascertain the determinants influencing the emergence of adenomatous polyps. From these analyses, a predictive nomogram was constructed to forecast the occurrence of adenomatous polyps, and evaluations on the discriminative capacity, calibration, and clinical utility of the model were conducted.Results:The adenomatous polyp group exhibited markedly elevated levels of glucose, insulin, FGF-19, and IGF-1, with respective concentrations of (8.67±2.70) mmol/L, (12.72±7.69) μU/L, 2.20±1.88, and 1.36±0.69. These figures were significantly higher compared to the inflammatory polyp group, which showed levels of (5.51±0.72) mmol/L, (5.49±2.68) μU/L, 0.53±0.97, and 0.41±0.46, respectively, P=0.001. Multivariate logistic regression revealed that the relative expression of IGF-1 served as an independent risk factor for the development of colorectal adenomatous polyps ( OR=5.622, 95% CI:1.085-29.126). The nomogram displayed a C-index of 0.849, indicating substantial discriminative capability. The calibration curve affirmed the model's accuracy in aligning predicted probabilities with actual outcomes, and the clinical decision curve demonstrated thepractical clinical applicability of the model. Conclusions:There was a significant correlation between the occurrence of colorectal adenomatous polyps and glucose metabolic pathways. Individuals with diabetes showed a higher propensity to develop such polyps.