BACKGROUND:Needle-knife release of the ligamentum flavum can effectively improve symptoms in patients with lumbar degeneration,and ultrasound guidance can increase the precision of needle-knife release;however,the specific effects of needle-knife release of the ligamentum flavum on the degenerated intervertebral discs and the possible mechanisms remain to be clarified. OBJECTIVE:To investigate the effect of ultrasound-guided needle-knife release of the ligamentum flavum. METHODS:Twenty-four New Zealand rabbits were randomized into control(n=6)and model(n=18)groups.A rabbit model of lumbar disc degeneration model was established in the model group by cutting the supraspinous and interspinous ligaments of the L5/6 and L6/7 segments to maintain a standing posture and apply axial load to the lumbar spine.After successful modeling,the model rabbits were subdivided into a control group,a model group,an ultrasonic needle-knife group,and a sham needle-knife group according to a random number table method,with six animals in each group.The ultrasonic needle-knife group underwent ultrasound-guided needle-knife release of the right yellow ligament of L7/S1,once every week,for a total of four times.The needle-knife approach in the sham needle-knife group was the same as that in the ultrasound needle-knife group,but the ligamentum flavum was not released.At 30 days after the intervention,MRI was used to observe the changes in the signal intensity of the nucleus pulposus within the L7/S1 segment.Hematoxylin-eosin staining was used to observe the morphological changes of the L7/S1 segment.Immunohistochemical staining was used to detect the expression of type I and II collagen in the nucleus pulposus of the L7/S1 segment.RT-PCR and western blot were used to detect the expression of integrin α5 and β1,p38,and nuclear factor κB in the L7/S1 segment. RESULTS AND CONCLUSION:MRI findings indicated that the nucleus pulposus of the intervertebral disc of rabbits in the model group was gray-black in color,and the gray value of the nucleus pulposus was significantly lower than that of the control group(P<0.01).The brightness of the nucleus pulposus of the intervertebral disc of the rabbits in the ultrasonic needle-knife group was elevated compared with that of the model group,and the gray value of the nucleus pulposus was higher than that of the model group(P<0.01).Results from hematoxylin-eosin staining showed that in the model group,the shape of the nucleus pulposus was irregular,the number of nucleus pulposus cells was reduced,the extracellular matrix was compressed,the fibrous ring was ruptured,the structure and boundary of the end plate were unclear,and the chondrocytes were arranged disorderly.Compared with the model group,the ultrasonic needle-knife group showed an increase in the number of the nucleus pulposus,an improvement in the rupture of the fibrous ring,and more regular arrangement of cartilage endplate cells.Results from immunohistochemical staining showed an increase in positive expression of type I collagen(P<0.01)and a decrease in positive expression of type II collagen in the nucleus pulposus of the model group compared with the control group as well as a decrease in positive expression of type I collagen and an increase in positive expression of type II collagen in the nucleus pulposus of the ultrasonic needle-knife group compared with the model group(P<0.01).RT-PCR and western blot assays showed that the mRNA and protein expression of integrin α5,integrin β1,p38,and nuclear factor κB in the intervertebral discs of rabbits in the model group were increased compared with that in the control group(P<0.01);the mRNA and protein expression of integrin α5,integrin β1,p38,and nuclear factor κB in the intervertebral discs of rabbits in the ultrasonic needle-knife group was decreased compared with that in the model group(P<0.01).To conclude,ultrasound-guided needle-knife release of the ligamentum flavum can improve the degree of lumbar disc degeneration in rabbits,which may be related to the inhibition of p38 and nuclear factor-κB expression by modulating integrin α5 and β1 expression.

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.

The gastrointestinal motility disorder of the patients with Parkinson's disease(PD)occurs in the early stages of this disease,even before the onset of motor symptoms.The gastrointestinal motility disorder is one type of gastrointestinal dysfunction,not only affect the absorption of medication,exacerbating the progression of PD,but also severely impact the quality of life of the patients.Therefore,it is essential to find new therapeutic targets to alleviate PD-induced gastrointestinal dysmotility in order to improve the progression of the disease and the quality of life of the patients.The gastrointestinal motility function is highly dependent on the health of the gut and central nervous regulating the gastrointestinal movements.A healthy gut is closely related to the integrity of the intestinal barrier,gut microbiota,neuroinflammation,and the normal function of enteric neurons responsible for the contraction and relaxation of the gastrointestinal tract.The gut function of the PD patients is compromised to some extent.This review summarizes the effects of the enteric nervous system,central nervous system,and gut microbiota on the development of gastrointestinal motility disorder of the PD patients;it also outlines the current therapeutic methods available and their limitations,with the aim of providing the new insights into the treatment of gastrointestinal motility disorder of the PD patients.

Objective To explore the efficacy and safety of ticagrelor de-escalation and nicorandil therapy in elderly patients with acute coronary syndrome(ACS)after percutaneous coronary intervention(PCI).Methods A total of 300 elderly patients with ACS were selected from the Sixth and Seventh Medical Center of Chinese PLA General Hospital and Beijing Chaoyang Integrative Medicine Emergency Rescue and First Aid Hospital from November 2016 to June 2019,including 153 males and 147 females,aged>65 years old.All the patients received PCI,and all had double antiplatelet therapy(DAPT)scores≥2 and a new DAPT(PRECISE-DAPT)score of≥25.All patients were divided into two groups by random number table method before operation:ticagrelor group(n=146,ticagrelor 180 mg load dose followed by PCI,and ticagrelor 90 mg bid after surgery)and ticagrelor de-escalation + nicorandil group(n=154,ticagrelor 180 mg load dose followed by PCI,ticagrelor 90 mg bid+nicorandil 5 mg tid after surgery,changed to ticagrelor 60 mg bid+ nicorandil 5 mg tid 6 months later).Follow-up was 12 months.The composite end points of cardiovascular death,myocardial infarction and stroke,the composite end points of mild hemorrhage,minor hemorrhage,other major hemorrhage and major fatal/life-threatening hemorrhage as defined by the PLATO study,and the composite end points of cardiovascular death,myocardial infarction,stroke and bleeding within 12 months in the two groups were observed.Results The comparison of general baseline data between the two groups showed no statistically significant difference(P>0.05).There was also no significant difference in the composite end points of cardiovascular death,myocardial infarction and stroke between the two groups(P>0.05).The cumulative incidence of bleeding events in ticagrelor de-escalation + nicorandil group was significantly lower than that in ticagrelor group(P<0.05),while the composite end points of cardiovascular death,myocardial infarction,stroke and bleeding were also significantly lower than those in tecagrelor group(P<0.05).Conclusion In elderly patients with ACS,the treatment of ticagrelor de-escalation + nicorandil after PCI may not increase the incidence of ischemic events such as cardiovascular death,myocardial infarction or stroke,and it may reduce the incidence of hemorrhagic events.

BACKGROUND:Host immune response triggered by plaque biofilm is an initiator of periodontitis progression and destruction.Macrophages are an important component of the innate immune response,which play an important role in inflammation occurrence and development. OBJECTIVE:To review the relationship between macrophage polarization and periodontitis and the related progress in the treatment of periodontitis by regulating macrophage polarization. METHODS:PubMed and CNKI databases were searched for relevant literature published from 1990 to 2023,with"macrophage polarization,M1/M2 macrophage,periodontitis,periodontitis treatment,macrophage polarization and periodontitis,osteoimmunology,ferroptosis,macrophage polarization and ferroptosis,periodontitis and ferroptosis"as the English and Chinese search terms.After the initial screening,96 articles were selected for review. RESULTS AND CONCLUSION:The switch between different phenotypes of macrophages is closely related to the tissue destruction caused by periodontitis,and various cytokines and inflammatory mediators secreted from macrophages are involved in the destruction and repair of periodontal tissue.Therefore,regulation of macrophage polarization and cytokine secretion in inflammatory state helps to alleviate periodontitis inflammation and improve the periodontal microenvironment,thereby reducing tissue destruction or promoting periodontal tissue regeneration.Many studies have been conducted to develop drugs or biomaterials to modulate macrophage function for the purpose of immunomodulatory treatment of periodontitis.However,macrophages act throughout the development of periodontitis and play an important role in the process of anti-infection,bone destruction and bone repair,and polarization is a complex and dynamic process influenced by many factors.Therefore,further exploration on possible mechanisms is still needed to clarify the interaction between materials or drugs and macrophages.

Acute cerebral infarction(ACI)has the characteristics of onset nasty and high mortality,and thus the rapid determination of the occurrence and development of ACI plays a key role in the diagnosis,treatment and prognosis of ACI patients.It has shown that the serum level of human haptoglobin(Hp)is related to ACI.In this study,surface enhanced Raman scattering(SERS)combined with immune recognition was applied to establish a quantitative analysis method for serum Hp.Firstly,the SERS substrate of silver nanoparticles was prepared on silicon wafer,and 4-mercaptobenzoic Acid(MBA)was used as a Raman probe by forming Ag—S bond and connecting it on the surface of nanoparticles.The carboxyl group of MBA was linked to amino group of self-made high-affinity antibody through forming CO—NH structure thus forming a SERS self-assembled chip of Hp(Ag/MBA/anti-Hp).Hp in serum could be specifically captured by antibodies on SERS substrate,which caused the shift of SERS characteristic peak of MBA.The results showed that there was a good linear relationship between the logarithm of Hp concentration and the SERS characteristic peak shift of MBA.The detection range was 1-1000 ng/mL(R2=0.988).The Hp concentrations in serum of 90 ACI patients were determined by this method,and the results were consistent with those of ELISA method,which proved the practicability and accuracy of this method.This method was highly specific,simple and convenient,which could realize the specific recognition and quantitative analysis of serum Hp,so as to be an effective means for clinical detection of serum Hp,thus providing a reference for the treatment and prognosis of ACI.

Objective To explore dose-effect relationship of biomechanical parameters in treating atlantoaxial joint disor-der by slimming manipulation.Methods From October 2022 to May 2023,18 patients with atlantoaxial joint disorders were treated,including 10 males and 8 females;aged from 24 to 27 years old with an average of(25.50±l.10)years old;CT of cer-vical vertebra showed 16 patients with right side distortion and 2 patients with left side distortion.The mechanical parameters of treatment of atlantoaxial joint disorder by tendon relaxation manipulation were measured by wearing massage manipulation gloves.The magnitude,frequency and mechanical curve of force during tendon relaxation and starting force,pulling force,pulling time and mechanical curve during rehabilitation were quantified,the differences between the affected and contralateral manipulations were compared.Results The maximum force and frequency of Fengchi(GB20)on the affected side were(19.82±2.02)N and(116.83±14.49)times/min,and opposite side were(13.87±2.19)N and(188.89±16.03)times/min,re-spectively.There were statistically difference in the maximum force and frequency of both sides(P＜0.05).The maximum force and frequency of Quepen(ST12)on the affected side were(14.44±3.27)N and(139.06±28.47)times/min,and those on the opposite side were(9.41±1.38)N and(142.50±28.47)times/min.There was difference in maximum force on both sides(P＜0.05).The starting force,turning force and turning time of the affected side were(14.16±5.98)N,(11.56±6.63)N,(0.14±0.03)S,and the contralateral side were(8.94±3.39)N,(8.30±4.64)N,(0.18±0.04)S,respectively.The difference of starting force,turning force and turning time on both sides were statistically significant(P＜0.05).Conclusion By applying a light re-laxation force on the affected side,the mechanical balance between cervical vertebrae could be restored,and recovery trend of atlantoaxial joint disorder could be strengthened.On this basis,the atlantoaxial odontoid process could be reversed by applying a light rotation force,which reflects the characteristics of high safety of the manipulation.

Objective To explore accuracy and clinical effect of robot-assisted implantation of sacroiliac penetrating screw in orthopedic surgery for posterior pelvic ring fracture.Methods The clinical data of 24 patients with posterior pelvic ring frac-ture treated with robot-assisted sacroiliac penetration screws from August 2022 to August 2023 were retrospectively analyzed,including 10 males and 14 females;aged from 21 to 73 years old with an average of(49.29±14.48)years old;according to Tile pelvic fractures,13 patients were type B and 11 were type C.The effect of screw placement was evaluated according to Gras criteria based on postoperative CT scan results.At the final follow-up,fracture healing was evaluated according to Matta score,and functional recovery was evaluated by Majeed score.Results All patients were followed up for 3 to 13 months with an aver-age of(6.00±3.28)months.Totally 36 sacroiliac penetrating screws,18 S1 penetrating screws,18 S2 penetrating screws were inserted,a total of 29 were excellent and 7 good according to Gras standard.Screw adjustment times was 0.00(0.00,0.75)times.At the final follow-up,Matta score was excellent in 18 patients,5 good and 1 moderate,and the maximum displacement distance was 2.55(0.00,5.65)mm.Majeed score was 84.37±8.38,15 patients were excellent,7 good and 2 moderate.Con-clusion Robot could accurately and safely assist in the placement of sacroiliac joint screws for the treatment of posterior pelvic ring fractures,and promote postoperative functional recovery of patients.

Objective To explore clinical effect of vancomycin calcium sulfate combined with internal fixation on cal-caneal beak-like fracture secondary to calcaneal osteomyelitis caused by diabetic foot.Methods From April 2018 to October 2021,a retrospective analysis was performed on 5 patients with calcaneal bone osteomyelitis secondary to diabetic foot,includ-ing 2 males and 3 females,aged from 48 to 60 years old;diabetes course ranged from 5 to 13 years;the courses of diabetic foot disease ranged from 18 to 52 days;5 patients were grade Ⅲ according to Wagner classification.All patients were treated with debridement,vancomycin bone cement implantation,negative pressure aspiration at stage Ⅰ,vancomycin calcium sulfate and internal fixation at stage Ⅱ for calcaneal beak-like fracture.Surgical incision and fracture healing time were recorded,and the recurrence of osteomyelitis was observed.American Orthopedic Foot Andankle Society(AOFAS)score and exudation at 12 months after operation were evaluated.Results Five patients were successfully completed operation without lower extremity vascular occlusion,and were followed up for 16 to 36 months.The wound healing time after internal fixation ranged from 16 to 26 days,and healing time of fractures ranged from 16 to 27 weeks.AOFAS score ranged from 65 to 91 at 12 months after oper-ation,and 2 patients got excellent result,2 good and 1 fair.Among them,1 patient with skin ulcer on the back of foot caused by scalding at 5 months after operation(non-complication),was recovered after treatment;the wound leakage complication oc-curred in 2 patients,and were recovered after dressing change.No osteomyelitis or fracture occurred in all patients.Conclusion Vancomycin calcium sulfate with internal fixation in treating calcaneal osteomyelitis secondary to calcaneal osteomyelitis caused by diabetic foot could not only control infection,but also promote fracture healing,and obtain good clinical results.

Taking Kunming Medical University as an example, we explore the mechanism for the separation and coordination of supervision, management, and evaluation, establish and implement a course quality rating system, and strengthen the course quality evaluation. The course quality rating system mainly consists of merit evaluation for courses of grades A and B and admittance evaluation for courses of grades C and D. Through the course quality rating, courses are diagnosed and compared, with the aim to improve course connotation construction (labeling, setting an example, promoting excellent courses, and removing inferior courses), achieve "good pay for good courses", encourage the faculty to strengthen curriculum quality, and measure ourselves with our own ruler. We discussed the problems about the difference in evaluation indicators, the professionality of evaluators, and the incentive effect of evaluation results, and also proposed strategies for improving course quality rating in medical colleges from the perspectives of deepening the content of evaluation indices, ensuring the effectiveness after evaluation, and ascertaining the main body of course construction in daily work.