In this study, the pharmacokinetic characteristics and tissue distribution of cannabidiol(CBD)/γ-polyglutamic acid-g-cholesterol(γ-PGA-g-CHOL) nanomicelles [CBD/(γ-PGA-g-CHOL)NMs] were investigated by pharmacokinetic experiments, and the effect of CBD/(γ-PGA-g-CHOL)NMs on the lipopolysaccharide(LPS)-induced inflammatory damage of cells was evaluated by cell experiments. CBD/(γ-PGA-g-CHOL)NMs were prepared by dialysis. The CBD concentrations in the plasma samples of male SD rats treated with CBD and CBD/(γ-PGA-g-CHOL)NMs were investigated, and the pharmacokinetic parameters were calculated and compared. UPLC-MS/MS was employed to determine the concentration of CBD in tissue samples. The heart, liver, spleen, lung, kidney, and muscle samples were collected at different time points to explore the tissue distribution of CBD and CBD/(γ-PGA-g-CHOL)NMs. The Caco-2 cell model of LPS-induced inflammation was established, and the cell viability, transepithelial electrical resistance(TEER), and secretion levels of inflammatory cytokines were determined to compare the anti-inflammatory activity between the two groups. The results showed that CBD/(γ-PGA-g-CHOL)NMs had the average particle size of(163.1±2.3)nm, drug loading of 8.78%±0.28%, and encapsulation rate of 84.46%±0.35%. Compared with CBD, CBD/(γ-PGA-g-CHOL)NMs showed increased peak concentration(C_(max)) and prolonged peak time(t_(max)) and mean residence time(MRT_(0-t)). Within 24 h, the tissue distribution concentration of CBD/(γ-PGA-g-CHOL)NMs was higher than that of CBD. In addition, both CBD and CBD/(γ-PGA-g-CHOL)NMs significantly enhanced Caco-2 cell viability and TEER, lowered the secretion levels of inflammatory cytokines, and alleviated inflammation. Moreover, CBD/(γ-PGA-g-CHOL)NMs demonstrated stronger anti-inflammatory effect. It can be inferred that γ-PGA-g-CHOL blank nanomicelles are good carriers of CBD, being capable of prolonging the circulation time of CBD in the blood, improving the bioavailability and tissue distribution concentration of CBD, and protecting against LPS-induced inflammatory injury. The findings can provide an experimental basis for the development and clinical application of oral CBD preparations.
Animals ; Cannabidiol/administration & dosage* ; Polyglutamic Acid/analogs & derivatives* ; Humans ; Male ; Rats ; Rats, Sprague-Dawley ; Anti-Inflammatory Agents/administration & dosage* ; Micelles ; Caco-2 Cells ; Cholesterol/pharmacokinetics* ; Tissue Distribution ; Nanoparticles/chemistry*

This study aims to simultaneously detect three antibiotic resistance genes(blaNDM,mcr-1 and cfr).A triplex fluorescence quantitative PCR method was established.Plasmids,primers and probes were designed and optimized.The method could specifically detect blaNDM,mcr-1 and cfr,but not other antibiotic resistance genes.The R2 of the standard curves of the three antibiotic re-sistance genes were all greater than 0.999,and the coefficients of variation were all lower than 1％.The lowest detection limits of the plasmids were 1 × 102 copies/μL.This method was used to de-tect 800 bacterial samples.The results showed that 32 samples contained mcr-1 gene,40 samples contained blaNDM gene,2 samples contained cfr gene,8 samples contained both mcr-1 and blaNDM genes.There were no samples carrying three antibiotic resistance genes detected.The results indica-ted that the triplex fluorescence quantitative PCR method established in this experiment had the advantages of high sensitivity,specificity and stability.It was suitable for rapid detection of blaNDM,mcr-1 and cfr antibiotic resistance genes in clinical practice.It provided a convenient and quick method basis for the detection of antibiotic resistance genes.

Objective To observe the value of nomogram of ultrasound combined with laboratory indexes for predicting axillary lymph node metastasis(ALNM)of stage cT1N0 breast invasive ductal carcinoma(IDC).Methods A total of 77 cases with pathologically diagnosed stage cT1N0 single breast IDC were retrospectively collected,including 23 cases with and 54 cases without ALNM.Univariate and multivariate binary logistic regression analysis were used to analyze clinical data,laboratory indicators and ultrasonic manifestations,then the independent predictors of ALNM of stage cT1N0 breast IDC were screened to establish laboratory indexes model,ultrasound model and combined model,respectively,and nomogram of the combined model was drawn.Receiver operating characteristic(ROC)curves were plotted to evaluate the predictive efficacy of each model.The consistency of results of combined model and actual results was analyzed using calibration curve.Decision curve analysis(DCA)was used to explore the clinical value of each model.Results Serum carbohydrate antigen 153(CA153)(OR=1.132),platelet-to-lymphocyte ratio(PLR)(OR=1.020)and echo attenuation behind the lesion on ultrasound(OR=8.789)were all independent predictors of ALNM in stage cT1N0 breast IDC(all P＜0.05),and the area under the curve(AUC)of laboratory indexes model,ultrasound model and combined model for predicting ALNM of stage cT1N0 breast IDC was 0.757,0.616 and 0.836,respectively.The consistency of the predicted results of combined model and actual results was good.When the threshold was higher than 0.15,the net benefit of combined model was higher than that of the other 2 models.Conclusion Nomogram of ultrasound combined with laboratory indexes could effectively predict ALNM of stage cT1N0 breast IDC.

This study aims to simultaneously detect three antibiotic resistance genes(blaNDM,mcr-1 and cfr).A triplex fluorescence quantitative PCR method was established.Plasmids,primers and probes were designed and optimized.The method could specifically detect blaNDM,mcr-1 and cfr,but not other antibiotic resistance genes.The R2 of the standard curves of the three antibiotic re-sistance genes were all greater than 0.999,and the coefficients of variation were all lower than 1％.The lowest detection limits of the plasmids were 1 × 102 copies/μL.This method was used to de-tect 800 bacterial samples.The results showed that 32 samples contained mcr-1 gene,40 samples contained blaNDM gene,2 samples contained cfr gene,8 samples contained both mcr-1 and blaNDM genes.There were no samples carrying three antibiotic resistance genes detected.The results indica-ted that the triplex fluorescence quantitative PCR method established in this experiment had the advantages of high sensitivity,specificity and stability.It was suitable for rapid detection of blaNDM,mcr-1 and cfr antibiotic resistance genes in clinical practice.It provided a convenient and quick method basis for the detection of antibiotic resistance genes.

Objective To observe the value of nomogram of ultrasound combined with laboratory indexes for predicting axillary lymph node metastasis(ALNM)of stage cT1N0 breast invasive ductal carcinoma(IDC).Methods A total of 77 cases with pathologically diagnosed stage cT1N0 single breast IDC were retrospectively collected,including 23 cases with and 54 cases without ALNM.Univariate and multivariate binary logistic regression analysis were used to analyze clinical data,laboratory indicators and ultrasonic manifestations,then the independent predictors of ALNM of stage cT1N0 breast IDC were screened to establish laboratory indexes model,ultrasound model and combined model,respectively,and nomogram of the combined model was drawn.Receiver operating characteristic(ROC)curves were plotted to evaluate the predictive efficacy of each model.The consistency of results of combined model and actual results was analyzed using calibration curve.Decision curve analysis(DCA)was used to explore the clinical value of each model.Results Serum carbohydrate antigen 153(CA153)(OR=1.132),platelet-to-lymphocyte ratio(PLR)(OR=1.020)and echo attenuation behind the lesion on ultrasound(OR=8.789)were all independent predictors of ALNM in stage cT1N0 breast IDC(all P＜0.05),and the area under the curve(AUC)of laboratory indexes model,ultrasound model and combined model for predicting ALNM of stage cT1N0 breast IDC was 0.757,0.616 and 0.836,respectively.The consistency of the predicted results of combined model and actual results was good.When the threshold was higher than 0.15,the net benefit of combined model was higher than that of the other 2 models.Conclusion Nomogram of ultrasound combined with laboratory indexes could effectively predict ALNM of stage cT1N0 breast IDC.

Patients with severe trauma require an extremely timely treatment and transfusion plays an irreplaceable role in the emergency treatment of such patients. An increasing number of evidence-based medicinal evidences and clinical practices suggest that patients with severe traumatic bleeding benefit from early transfusion of low-titer group O whole blood or hemostatic resuscitation with red blood cells, plasma and platelet of a balanced ratio. However, the current domestic mode of blood supply cannot fully meet the requirements of timely and effective blood transfusion for emergency treatment of patients with severe trauma in clinical practice. In order to solve the key problems in blood supply and blood transfusion strategies for emergency treatment of severe trauma, Branch of Clinical Transfusion Medicine of Chinese Medical Association, Group for Trauma Emergency Care and Multiple Injuries of Trauma Branch of Chinese Medical Association, Young Scholar Group of Disaster Medicine Branch of Chinese Medical Association organized domestic experts of blood transfusion medicine and trauma treatment to jointly formulate Chinese expert consensus on blood support mode and blood transfusion strategies for emergency treatment of severe trauma patients ( version 2024). Based on the evidence-based medical evidence and Delphi method of expert consultation and voting, 10 recommendations were put forward from two aspects of blood support mode and transfusion strategies, aiming to provide a reference for transfusion resuscitation in the emergency treatment of severe trauma and further improve the success rate of treatment of patients with severe trauma.

Objectives:Present study analyzed the efficacy and safety of percutaneous coronary intervention(PCI)using the distal transradial access(dTRA)for patients with complex coronary lesions. Methods:A total of 10 033 patients with complex coronary artery lesions(type B2 and type C lesions)who underwent percutaneous coronary intervention(PCI)via dTRA or conventional transradial access(TRA)at Fuwai Hospital between June 2021 and May 2022 were included(9 625 patients in the TRA group and 408 patients in the dTRA group).After propensity score matching,391 patients were included in each group.Baseline data,PCI intraoperative data(including lesion characteristics,intervention success rate,etc.),and incidence of major bleeding related to the access were compared between the two groups before and after propensity score matching. Results:Before propensity score matching,the proportions of patients with hypertension,hyperlipidemia,family history of coronary heart disease,history of myocardial infarction,and history of coronary artery bypass grafting were significantly higher in the dTRA group than in the TRA group(all P<0.05).After propensity score matching,the baseline data of the two groups were similar(all P>0.05).Before propensity score matching,compared with the TRA group,patients in the dTRA group had a higher proportion of patients with type B2 lesions,while the proportions of patients with type C lesions and those using intravascular ultrasound(IVUS)were lower(all P<0.05).The proportion of patients with chronic complete occlusion was similar between the two groups(P>0.05).After propensity score matching,compared with the TRA group,patients in the dTRA group had a lower proportion using IVUS and had a higher percent of stent implantation(both P<0.05).There was no statistically significant difference between the two groups in terms of SYNTAX score,guide catheter size,target lesion distribution,proportion of patients using intra-aortic balloon counterpulsation,success rate of intervention procedures,and incidence of major bleeding events related to the access(all P>0.05). Conclusions:Compared with the conventional TRA,interventional treatment of complex lesions through dTRA is equally safe and effective for patients with complex coronary lesions.

Objective:To investigate the clinical efficacy of over-the-top reconstruction combined with the modified Lemaire technique in the treatment of anterior cruciate ligament (ACL) injuries with pivot-shift positive.Methods:From March 2020 to October 2021, a total of 46 patients with ACL injury and pivot-shift test grade II or above were admitted to Xinhua Hospital Affiliated to Dalian University. There were 28 males and 18 females, aged 28.0±10.5 years (range, 15-45 years). All cases were unilateral, including 17 cases of left knee and 29 cases of right knee. The pivot-shift test showed that 30 cases were grade II and 16 cases were grade III, and the cause of injury was sports injury. The semitendinosus muscle and gracilis muscle were harvested, and the ACL was reconstructed with the over-the-top combined modified Lemaire technique. The International Knee Documentation Committee (IKDC) score, Lysholm score and KT-2000 side-to-side difference before and after operation were compared.Results:All patients successfully completed the operation and were followed up for 26.6±2.3 months (range, 24-28 months). The Lysholm scores of the patients at 3 months and 24 months after operation were 73.6±4.3 and 91.6±2.8, which were higher than those before operation (58.5±4.6), and the difference was statistically significant ( F=18.351, P<0.001). The IKDC scores of patients at 3 months and 24 months after operation were 59.0±2.0 and 91.8±3.2, respectively, which were higher than those before operation 50.3±2.8, and the difference was statistically significant ( F=17.290, P<0.001). The side-to-side difference of KT-2000 was 1.7±0.8 mm and 1.5±0.4 mm at 3 and 24 months after operation, respectively, which was lower than that before operation (5.9±1.1 mm), and the difference was statistically significant ( F=14.192, P<0.001). At 24 months after operation, 3 patients had pivot shift test grade I and 4 patients had Lachman test grade I, but they complained of good knee stability and did not receive further treatment. At the last follow-up, there were no complications such as incision and intra-articular infection, deep vein thrombosis, knee stiffness, quadriceps musculus ossificans myositis, and reconstruction ligament rupture. All patients returned to sports with an average time of 15.7±2.6 months (range, 12-24 months). Conclusion:Over-the-top reconstruction combined with the modified Lemaire technique for the treatment of ACL injury with positive pivot shift test effectively improves knee function and promotes the patient's return to sports, with a low incidence of surgical complications.

Proanthocyanidin (PA), as a kind of natural plant polyphenol, have a variety of biological functions, such as promoting remineralization, inducing collagen cross-linking, inhibiting protease activity and inhibiting bacteria. Therefore, PA could be broadly used in the clinical application of treatment and repair of deep caries in the future; for example, PA could promote dentin remineralization, improve resin-dentin bonding durability and improve the dentin acid erosion effect. This application potential of PA arises from several features, firstly, PA can not only promote dentin remineralization on its own or with other remineralizers but also exhibits antibacterial effects, which can inhibit acid production while reducing the formation of cariogenic pathogens and their biofilms. Based on the above features, PA can reduce the incidence of caries disease; thus, PA improves deep caries and long-term effects after treatment. In addition, PA added to adhesives or etch agents can improve the etching and bonding effect of dentin by inducing collagen cross-linking and inhibiting protease activity, thus achieving the ultimate goal of improving the bonding performance of deep caries. This paper summarizes recent progress of research on PA for the treatment and repair of deep caries, including the promotion of dentin remineralization and antibacterial activity as well as the improvement in dentin bonding and acid etching effect, to provide a more comprehensive reference for treating and restoring deep caries in clinical practice.

Objective:To investigate the efficacy of shoulder arthroscopic balance point compaction with cross suture-bridge technique inr the treatment of avulsion fracture of the greater tuberosity of the humerus.Methods:A retrospective case series study was conducted on 14 patients with avulsion fracture of the greater tuberosity of the humerus treated in Affiliated Xinhua Hospital of Dalian University from March 2021 to March 2022, including 8 males and 6 females; aged 30-58 years [(40.2±10.5)years]. Among them, 5 patients had fracture in the left shoulder and 9 in the right shoulder. The fracture was classified as the avulsion type according to Mutch classification. All the patients were treated with shoulder arthroscopic balance point compaction with cross suture-bridge technique. The anteroposterior X-ray of the shoulder joint was taken at 1 week, 3 months, and 6 months after surgery to evaluate fracture reduction and fixation. The operative time and intraoperative blood loss were recorded. Fracture healing was evaluated by shoulder MRI at 6 months after surgery. The visual analog score (VAS), Constant shoulder joint score, American Shoulder and Elbow Surgeons (ASES) score, and shoulder range of motion (active abduction angle, active lateral external rotation angle, and active lateral internal rotation) preoperatively, at 3, 6 months after surgery and at the last follow-up were compared. The postoperative complications were observed.Results:All the patients were followed up for 12-15 months [(12.5±0.8)months]. The operative time and intraoperative blood loss were (67.0±10.5)minutes and (20.0±3.8)ml. The anteroposterior X-ray of the shoulder joint showed good reduction and fixation at 1 week, 3 months and 6 months after surgery. MRI T1 image at 6 months after surgery showed locally evenly distributed high signal, suggesting that the fracture was healed well. The values of VAS were (3.2±0.4)points, (2.5±0.5)points, and (0.7±0.3)points at 3, 6 months after surgery and at the last follow-up, which were lower than (7.2±0.6)points preoperatively; the values of Constant joint shoulder score were (53.2±5.3)points, (81.1±4.4)points, and (92.8±5.3)points, which were higher than (42.3±7.6)points preoperatively; the values of ASES score were (55.6±3.6)points, (77.1±3.2)points, and (90.8±3.5)points, which were higher than (45.8±4.2)points preoperatively; the active abduction angles were (60.5±2.5)°, (107.8±6.6)°, and (168.5±3.5)°, which were higher than (18.3±3.3)°preoperatively; the active lateral external rotation angles were (25.8±2.5)°, (30.8±2.2)°, and (63.8±2.8)°, which were higher than (15.6±3.2)°preoperatively ( P<0.05 or 0.01). The level of active internal rotation was L 5, L 1, and T 10, which was better than S 3 before surgery. The VAS, Constant shoulder joint score, ASES score, active abduction and active external rotation were significantly improved at the last follow-up compared with those at 3, 6 months after surgery (all P<0.05), with markedly improved level of active internal rotation. No major complications such as infection, instability of the shoulder joint or acromial impingement were found after surgery. Conclusion:Shoulder arthroscopic balance point compaction with cross suture-bridge technique for the treatment of avulsion fracture of the greater tuberosity of the humerus has advantages of decreased intraoperative blood loss, good reduction and healing, shoulder pain relief, early restoration of shoulder function and mobility, and few complications.