BACKGROUND:Ligament rupture and defect of the lateral or medial malleolus caused by high-energy injuries are common challenges in foot and ankle surgery.Their neighboring core tendons are often used as grafts to reconstruct the deficient ligaments.It is of paramount importance to investigate the mechanical properties of such tendons in the context of ligament defects to provide a suitable donor tendon.OBJECTIVE:To investigate the interactive dynamics and biomechanical alterations among their core tendons during ankle joint motions under varying degrees of lateral or medial malleolar ligament defect.METHODS:Based on CT imaging data of the left foot of a 50-year-old healthy male,a surface stereolithography model was extracted and constructed using MIMICS software.After Geomagic Wrap software was employed to fit the surfaces,a bone-cartilage-ligament-tendon ankle complex model incorporating varying degrees of ligament deficiencies was created within SOLIDWORKS software.Finite element analysis was then conducted using Ansys Workbench software,and the model's validity was verified through a simulated anterior drawer test.Following validation,the mechanical response of the ankle under the conditions of internal and external rotation,as well as inversion and eversion,was simulated.The variation and distribution patterns of the maximum Von-Mises stress in the peroneus brevis and longus tendons,as well as the anterior and posterior tibial tendons,were observed.RESULTS AND CONCLUSION:(1)In the anterior drawer test,the maximum talar displacement reached 5.208 5 mm,which was similar to the data in the previous literature,thereby the effectiveness of the model was validated.(2)Under four loading conditions,the defect of unilateral single-bundle ligaments exerted minimal influence on the maximum stress of adjacent core tendons,whereas the defect of unilateral multi-bundle ligament significantly increased the maximum tendon stress.Except for the consistently high stress across segments of the anterior tibial tendon,the high-stress regions in the long and short peroneal tendons and posterior tibial tendon were concentrated at their distal ends near the insertions.(3)Regarding the defect of the lateral malleolar ligament,the maximum stress and its variation in the peroneus brevis tendon during inversion and internal rotation were higher than those in the peroneus longus tendon.During inversion under the condition of the defect of the anterior talofibular ligament,the maximum stress in the short peroneal tendon increased by 0.951 2 MPa compared to that of normal condition,while that in the long peroneal tendon decreased by 0.065 1 MPa.Under the condition of the defect of the calcaneofibular ligament during internal rotation,the maximum stress in the short peroneal tendon increased by 2.352 9 MPa,while the maximum stress in the long peroneal tendon decreased by 0.269 2 MPa.(4)During eversion and external rotation under the defect of medial malleolar ligament,the variations in the maximum stress of the anterior and posterior tibial tendons were complex and depended on the type of ligament defect.Notably,full-thickness ligament defect significantly augmented the maximum stress in both tendons.

Objective To explore the the detection of MMP-2,-7,-9,and-12 enzymatic activity using the CEACAM1-derived fluorescent peptide substrate Site 84,investigating the application of substrate Site 84 to distinguishing between MMP-2 and MMP-9 in the gelatinase spectrum of MMPs.Methods The fluorescent enzymatic method was employed to observe the detection of MMP-2,-7,-9,and-12 enzymatic activity using substrate Site 84;further observations were made on the sensitivity and specificity of substrate Site 84 to enzymatic activity of MMP-2 and MMP-9 within the gelatinase spectrum;the kinetic parameters(Km and Kcat)of the enzymatic reaction between substrate Site 84 and MMP-2 were obtained.Results Using Site 84 as a substrate,enzymic kinetics curves for MMP-12,-7,-2 were obtained,but no enzymatic activity curve for MMP-9 was observed.Furthermore,Site 84 specifically detected the enzymatic activity of MMP-2 within the gelatinase spectrum,capable of detecting low concentration(0.6 μM)of MMP-2 enzymatic activity,but no obvious enzymatic reaction was observed for high concentration(6 μM)of MMP-9;the kinetics parameters for the enzymatic reaction between Site 84 and MMP-2 were Km=315 μM,Kcat/Km=2 565/MS.Conclusion The CEACAM1-derived substrate Site 84 serves as a novel fluorescent peptide substrate,enabling the acquisition of enzymatic activity curves for MMP-12,-7 and-2,and specifically detecting the enzymatic activity of MMP-2 within the MMP gelatinase spectrum.

Cyclin-dependent kinase 9 (CDK9) is a member of the transcription CDK subfamily and plays a role in transcriptional regulation. Selective CDK9 degraders possess potent clinical advantages over reversible CDK9 inhibitors. Herein, we report the first ATG101-recruiting selective CDK9 degrader, AZ-9, based on the hydrophobic tag kinesin degradation technology. AZ-9 showed significant degradation effects and selectivity toward other homologous cell cycle CDKs in vitro and in vivo, which could also affect downstream related phenotypes. Mechanism research revealed that AZ-9 recruits ATG101 to initiate the autophagy-lysosome pathway, and forms autophagosomes through the recruitment of LC3, which then fuses with lysosomes to degrade CDK9 and the partner protein Cyclin T1. These dates validated the existence of non-proteasomal degradation pathway of hydrophobic driven protein degradation strategy for the first time, which might provide research ideas for chemical induction intervention on other types of pathogenic proteins.

BACKGROUND:Ligament rupture and defect of the lateral or medial malleolus caused by high-energy injuries are common challenges in foot and ankle surgery.Their neighboring core tendons are often used as grafts to reconstruct the deficient ligaments.It is of paramount importance to investigate the mechanical properties of such tendons in the context of ligament defects to provide a suitable donor tendon.OBJECTIVE:To investigate the interactive dynamics and biomechanical alterations among their core tendons during ankle joint motions under varying degrees of lateral or medial malleolar ligament defect.METHODS:Based on CT imaging data of the left foot of a 50-year-old healthy male,a surface stereolithography model was extracted and constructed using MIMICS software.After Geomagic Wrap software was employed to fit the surfaces,a bone-cartilage-ligament-tendon ankle complex model incorporating varying degrees of ligament deficiencies was created within SOLIDWORKS software.Finite element analysis was then conducted using Ansys Workbench software,and the model's validity was verified through a simulated anterior drawer test.Following validation,the mechanical response of the ankle under the conditions of internal and external rotation,as well as inversion and eversion,was simulated.The variation and distribution patterns of the maximum Von-Mises stress in the peroneus brevis and longus tendons,as well as the anterior and posterior tibial tendons,were observed.RESULTS AND CONCLUSION:(1)In the anterior drawer test,the maximum talar displacement reached 5.208 5 mm,which was similar to the data in the previous literature,thereby the effectiveness of the model was validated.(2)Under four loading conditions,the defect of unilateral single-bundle ligaments exerted minimal influence on the maximum stress of adjacent core tendons,whereas the defect of unilateral multi-bundle ligament significantly increased the maximum tendon stress.Except for the consistently high stress across segments of the anterior tibial tendon,the high-stress regions in the long and short peroneal tendons and posterior tibial tendon were concentrated at their distal ends near the insertions.(3)Regarding the defect of the lateral malleolar ligament,the maximum stress and its variation in the peroneus brevis tendon during inversion and internal rotation were higher than those in the peroneus longus tendon.During inversion under the condition of the defect of the anterior talofibular ligament,the maximum stress in the short peroneal tendon increased by 0.951 2 MPa compared to that of normal condition,while that in the long peroneal tendon decreased by 0.065 1 MPa.Under the condition of the defect of the calcaneofibular ligament during internal rotation,the maximum stress in the short peroneal tendon increased by 2.352 9 MPa,while the maximum stress in the long peroneal tendon decreased by 0.269 2 MPa.(4)During eversion and external rotation under the defect of medial malleolar ligament,the variations in the maximum stress of the anterior and posterior tibial tendons were complex and depended on the type of ligament defect.Notably,full-thickness ligament defect significantly augmented the maximum stress in both tendons.

Objective:To retrospectively analyze the viral levels and associated factors in patients with hepatitis B virus (HBV)-related primary liver cancer (PHC) in real-world settings and further explore the correlation between low viral load (LVL) and/or low-level viremia (LLV) and PHC.Methods:Five hundred twenty-four cases with HBV-related PHC with complete pathologically confirmed data from 2013 to 2020 were included. Percentages (%) were used to express their viral load, antiviral (oral) status, patient compliance, presence or absence of cirrhosis, family history of liver cancer, and others. LVL definition: After excluding detection errors by PCR method, serum HBV DNA <50-2 000 IU/ml, and those who had received antiviral drug treatment were called LLV. Antiviral treatment (AVT) rate definition: As of the confirmed diagnosis of PHC, those who had been regularly treated using oral antiviral drugs for six months or more (≥6 months).Results:General situation: The ratio of male to female enrolled patients was 15.90:1 (493/31). Patients aged >40 years accounted for 91.98% (482 cases). Hepatitis B surface antigen (HBsAg) positivity condition: The ratio of HBsAg-positive to HBsAg-negative/anti-HBc-positive (HBsAg-/anti-HBc+) PHC patients was 5.89:1 (448/76). Among the 76 HBsAg-/anti-HBc+patients, the ratio of HBsAg-/anti-HBs+/anti-HBc+ to HBsAg-/anti-HBs-/anti-HBc+ patients was 0.95:1 (37/39). Hepatitis B e antigen (HBeA) positivity condition: The ratio of HBeAg-negative to HBeAg-positive cases was 3.23:1 (400/124). HBV DNA level condition: The medical history records of 75.00% of patients (393/524) had traceable HBV DNA test reports. Out of 393 patients, 45.04% (177/393) accounted for undetectable HBV DNA, 13.49% (53/393) accounted for LVL, 41.48% (163/393) accounted for HBV DNA exceeding the upper limit of LVL, and 4.07% (16/393) accounted for LLV. Among HBsAg-positive and HBsAg-/anti-HBc+ patients, the HBV DNA positivity rates were 59.12% (214/362) and 6.45% (2/31), respectively. Antiviral treatment condition: Among the 448 HBsAg-positive PHC patients, the total AVT rate was 18.08% (81/448), of which seven patients did not have their HBV DNA results traced back. Among them, the AVT rate of 148 patients with HBV DNA lower than the lowest detection value was 41.22% (61/148); the AVT rate of 53 patients with LVL was 18.87% (10/53); and the AVT rate of 163 patients with HBV DNA≥LVL upper limit was 1.84% (3/163). Liver cirrhosis and family history condition: 348 patients (66.41%) had liver cirrhosis. 67 patients (12.79%) had a distinct family history of HBV-related liver cirrhosis and liver cancer. Alpha-fetoprotein (AFP) condition: 514 patients underwent AFP testing, with 30.93% of the patients had normal AFP levels, and 69.07% had AFP levels exceeding the upper limit of normal values (355/514). Among them, 10 μg/L400 μg/L accounted for 34.44% (177/514) and 34.63% (178/514), respectively. Tissue typing condition: 99.05% (519/524) were hepatocellular carcinoma, and well-differentiated and moderately differentiated cases accounted for only 8.59%.Conclusions:In the real world, comprehensive, timely screening, standardized, and effective antiviral treatment have not yet been achieved for patients with chronic hepatitis B, resulting in the persistence of HBsAg and/or HBV DNA positivity (especially LVL and/or LLV). Although LVL does not account for a high proportion among all HBV-related PHC populations, the vast majority of LVL populations have not received any antiviral treatment. In addition, some PHC populations with HBV DNA>2 000 IU/ml have not received standard antiviral treatment before the onset of the disease, which should be paid attention to. At the same time, HBsAg-/anti-HBc+ populations may have latent HBV infection and may even progress to PHC. Notably, PHC may still occur after HBeAg seronegative conversion.

In vivo confocal microscopy of the cornea is a non-invasive, rapid, and comprehensive technique for real-time, dynamic observation of all layers of the cornea. Confocal microscopy allows the examination of the morphology and cell density in the different layers of the cornea through direct visualization. With the increasing prevalence of diabetes, ocular complications have become common and have garnered more interest and in-depth research from clinical and scientific communities. This paper provides a comprehensive review of research progress made using in vivo confocal microscopy to observe various layers of cornea tissue in diabetic patients.

Objective To investigate the molecular typing,virulence,and drug resistance features of bacterial strains in a simultane-ous outbreak of paratyphoid fever A and B,and then provide evidence for the prevention and treatment of the simultaneous transmission of different types of paratyphoid fever.Methods The clinical data of 31 patients confirmed as paratyphoid fever in the Hospital of Xin-jiang Production and Construction Corps from September 2018 to November 2018 were retrospectively analyzed.The isolated strains were performed serotyping and drug sensitivity tests.The molecular typing and the detection of virulence and drug resistance genes were carried out by multiplex PCR,pulsed-field gel electrophoresis(PFGE),and multilocus sequence typing(MLST).Results A total of 32 strains of Salmonella paratyphi were isolated from 31 patients,with 19 strains classified as type A and 13 as type B.The intermedi-ate rates of all strains against ciprofloxacin were 100%.The molecular typing and serotyping results of 11 representative strains were consistent.The PFGE fingerprints of Salmonella paratyphi A and B were also consistent.The MLST of Salmonella paratyphi A was ST85,and that of Salmonella paratyphi B was ST86.All strains carried virulence island SPI1-SPI5 representative genes such as invA,sitC,sseL,sifA,mgtC,siiE,and sopB,and regulatory gene phoP.Salmonella paratyphi A also carried cytolethal distending toxin(CDT)genes with trimeric structure such as cdtB,pltA,and pltB.The virulence plasmid genes such as pefA,prot6E,and spvB were all negative.Conclusion The simultaneous transmission of Salmonella paratyphi A and B has the characteristics of high pathogenicity and poor sensitivity to ciprofloxacin,which should be highly concerned by clinical and laboratory personnel.

Objective:To explore the influencing factors and effectiveness of community follow-up in patients with cardiac implantable electronic device (CIED) implantation.Method:A total of 132 patients who received CIED implantation in the Department of Cardiology of Tongren Hospital, Shanghai Jiao Tong University School of Medicine from February 2021 to February 2022 were enrolled in this prospective cohort study. Among them 33 patients were followed up in community health service centers associated with Tongren Hospital (community follow-up group) and 99 matched patients were followed up in the CIED outpatient clinic of the hospital (outpatient follow-up group) with a ratio of 1∶3. The clinical data of the selected patients were collected through a questionnaire survey; the follow-up data were extracted through the CarelinkExpress electronic follow-up platform and the CIED outpatient information system of Tongren Hospital. Adjustment of the treatment protocol or CIED parameters at follow-up, and the referral from the community health service centers were defined as visit with-an-action (VWA). The endpoint of follow-up was the occurrence of major adverse events. The multivariate logistic regression model was used to analyze the factors influencing patient selection for community follow-up.Results:The univariate analysis showed that the frequency of visits to community health service centers and the service contracting rate in community follow-up group were higher than those of outpatient follow-up group ( P<0.05). The multivariate logistic regression analysis showed that the contracted community physician service was an independent influencing factor of patient choosing community follow-up ( OR=2.143, 95% CI: 1.103-4.166, P=0.025). A total of 469 visits of followed up occurred in 132 patients, including 45 community visits and 424 outpatient visits. VWA accounted for 22.2% (10/45) in the community follow-up group, and 17.2% (73/424) in the outpatient follow-up group ( P>0.05). There was no significant difference in the safety and effectiveness indicators (VWA, major adverse events, and unplanned follow-up) between the two groups ( P>0.05). More patients in the community follow-up group walked to the hospital than the outpatient follow-up group ( P<0.05);and the main transportation for the later was by bus or taxi(42(42.4%)or 41(41.4%)). The average waiting time in the community follow-up group was significantly shorter than that in outpatient follow-up group ( P<0.05). The total time required for a single follow-up in the community follow-up group was 50.0 (45.0, 59.5) minutes, which was significantly shorter than that in the routine outpatient follow-up group (107.0 (90.0, 135.0) minutes, P<0.05). Conclusions:The contracting with community physicians is an independent influencing factor for CIED implanted patients to choose community follow-up. The safety and effectiveness of community follow-up are comparable to routine outpatient follow-up, and community follow-up is more convenient.

Objective:To study the anatomy of the perforator propeller flap of superior lateral genicular artery, and to explore a surgical method and clinical application in repair of the soft tissue defect of anterolateral knee with the flap.Methods:From September 2019 to September 2021, 8 knees of 4 chilled fresh specimen of adults were studied. The perforators of the superior lateral genicular artery were observed. The length, outer diameter of the perforators, and the locations of the skin perforation were recorded. The superior lateral genicular artery perforator propeller flaps were then applied clinically to 5 patients(3 males and 2 females) with soft tissue defects of anterolateral knee. Two of the patients had combined ligament injury and(or) bone joint exposure. The age of patients ranged from 25 to 48 years old, at 33.4 years old in average. The sizes of soft tissue defects ranged from 4.0 cm×4.0 cm to 8.0 cm×5.0 cm. The sizes of perforator propeller flaps of superior lateral genicular artery were 10.0 cm×5.0 cm to 13.0 cm×6.0 cm. The superior perforating vessels of the superior lateral genicular artery were found and marked at the points of skin perforation. Preoperative contrast-enhanced ultrasound were performed to confirm the dominant perforating vessels and had the skin perforating points marked. Intraoperative CDU were further performed to confirm the points of dominant perforating vessels. Perforator propeller flaps were designed depending on the size of the anterolateral soft tissue defect, and flaps were prepared and transferred to the defect sites. Postoperative follow-ups were conducted at outpatient clinic. The survival of the flap and knee function were observed according to the Bai-ly knee scoring.Results:The anatomy showed that an average pedicle length of the superior lateral genicular artery perforator was(8.2±0.9) cm, with an average starting outer diameter at(1.1±0.2) mm. All 5 flaps survived during the follow-up that lasted for 10 to 24 months, with an average of 15.3 months. All flaps healed in 2 weeks after surgery without complications such as soft tissue infection, bone and joint infection were observed. At the last follow-up, no obvious bloated appearance of the flaps were observed. The colour and elasticity of the flaps were similar to the surrounding skin. The knee function was assessed: 4 patients were in excellent and 1 in good. The range of knee flexion and extension was from 100° to 150°. The patients were satisfied with the appearance and function of the knees.Conclusion:The size of the perforator of superior lateral genicular artery and the pedicle length are ideal. The propeller flap can be used to repair the soft tissue defect around the anterolateral knee, with satisfactory functional recovery of a knee. It is a good method to repair the soft tissue defect around anterolateral knee.