Objective:To investigate the safety and efficacy of a modified radiofrequency ablation（RFA）treatment method for primary great saphenous vein varicose.Methods:Clinical data of 90 patients with primary great saphenous vein varicose treated with ultrasound-guided RFA from January 2021 to April 2024 in the Ultrasound Department of the First Affiliated Hospital of Zhengzhou University were retrospectively analyzed. Among them，45 patients were treated with traditional RFA treatment method（traditional group）and 45 patients were treated with improved RFA treatment method（improved group）. Number of punctures，operation time，foam hardener dosage，intraoperative and postoperative complications were recorded in the two groups. The preoperative and postoperative venous clinical severity score（VCSS）and chronic venous insufficiency questionnaire（CIVIQ-14）were compared. The closure rate and recurrence rate of great saphenous vein varicose were followed up and the efficacy of the two methods were analyzed.Results:The success rate of the improved group and the traditional group was 100%.The number of punctures in the improved group was less than those of the traditional group［1（1，1） vs. 2（2，3）， Z = -7.431， P<0.001］，and the operation time of the modified group was shorter than that of the traditional group［（15.89 ± 3.63）min vs.（30.91 ± 5.58）min， t=-15.145， P<0.001］，the average volume of lauryl foam was lower than that of the traditional RFA group［（7.96 ± 2.36）ml vs.（15.69 ± 2.89）ml， t=-13.892， P<0.001］. The incidence of complications was similar between the two groups，with no statistical significance（all P>0.05）. Postoperative VCSS and CIVIQ-14 scores were significantly improved compared with before（all P<0.001），with no statistical significance between the two groups（all P>0.05）. At 12 months after the operation，there was no significant difference in the closure rate of the saphenous vein between the improved group and the traditional group（ P>0.05），and the recurrence rate of varicose veins in both groups was 0. Conclusions:This modified RFA treatment method for the treatment of lower extremity varicose veins is minimally invasive，safe，and has the same efficacy as the traditional RFA treatment method. Compared with the traditional RFA treatment method，the modified RFA treatment method has the advantages of convenient operation，less puncture times and shorter operation time，and is worthy of clinical promotion.

BACKGROUND:The stiffness of muscle fibers and tendons within skeletal muscles is regulated by the neuromuscular system and remains variable.However,observing the mechanical properties of muscle fibers and tendons during complex multi-joint movements is challenging,and the real-time variation patterns of their stiffness are not yet clear.OBJECTIVE:Taking the open-access simulation data of triceps surae at different running speeds and gait phases as an example,to explore the real-time stiffness change rules of muscle fiber stiffness and tendon stiffness.METHODS:OpenSim simulation results of muscle fiber activation,length,velocity parameters,and tendon length parameters of the triceps surae in five long-distance runners at different running speeds were collected from the Website of Stanford University.The instantaneous slope of the force-length relationship curve of muscle fibers and tendons in the Hill-Zajac muscle model used in the simulation was extracted as the real-time stiffness of the triceps surae muscle fibers and tendons.The temporal changes of stiffness indicators of muscle fibers and tendons during gait were analyzed.RESULTS AND CONCLUSION:The regulation of muscle fiber activation-length-velocity status and tendon strain resulted in the stiffness of muscle fibers and tendons changing in the same trend as the applied force.Compared with lower running speeds,the stiffness of the gastrocnemius muscle fibers was higher in the early support phase at higher running speeds(P ≤ 0.01),and the tendon stiffness of the medial head of the gastrocnemius was higher in the early support phase(P≤ 0.02).The stiffness of the gastrocnemius muscle fibers and tendons was lower from the mid-support to the mid-swing phase(P≤ 0.03),and the stiffness of the soleus muscle fibers was higher during the support phase(P ≤ 0.02).Under all running speeds,the stiffness of the triceps surae muscle fibers and tendons showed a trend of being higher during the support phase than during the pre-swing phase(P ≤ 0.03),and the stiffness of the gastrocnemius muscle fibers and tendons increased again in the late swing phase(P ≤ 0.05).These findings indicate that increasing running speed can increase the stiffness of triceps surae muscle fibers and tendons during the stance phase;when running speed and gait phase change,gastrocnemius and soleus muscles have different patterns of muscle fiber and tendon stiffness changes,whereas gastrocnemius can increase its muscle fiber stiffness and tendon stiffness in the late swing phase through pre-activation phenomenon.

BACKGROUND:The stiffness of muscle fibers and tendons within skeletal muscles is regulated by the neuromuscular system and remains variable.However,observing the mechanical properties of muscle fibers and tendons during complex multi-joint movements is challenging,and the real-time variation patterns of their stiffness are not yet clear.OBJECTIVE:Taking the open-access simulation data of triceps surae at different running speeds and gait phases as an example,to explore the real-time stiffness change rules of muscle fiber stiffness and tendon stiffness.METHODS:OpenSim simulation results of muscle fiber activation,length,velocity parameters,and tendon length parameters of the triceps surae in five long-distance runners at different running speeds were collected from the Website of Stanford University.The instantaneous slope of the force-length relationship curve of muscle fibers and tendons in the Hill-Zajac muscle model used in the simulation was extracted as the real-time stiffness of the triceps surae muscle fibers and tendons.The temporal changes of stiffness indicators of muscle fibers and tendons during gait were analyzed.RESULTS AND CONCLUSION:The regulation of muscle fiber activation-length-velocity status and tendon strain resulted in the stiffness of muscle fibers and tendons changing in the same trend as the applied force.Compared with lower running speeds,the stiffness of the gastrocnemius muscle fibers was higher in the early support phase at higher running speeds(P ≤ 0.01),and the tendon stiffness of the medial head of the gastrocnemius was higher in the early support phase(P≤ 0.02).The stiffness of the gastrocnemius muscle fibers and tendons was lower from the mid-support to the mid-swing phase(P≤ 0.03),and the stiffness of the soleus muscle fibers was higher during the support phase(P ≤ 0.02).Under all running speeds,the stiffness of the triceps surae muscle fibers and tendons showed a trend of being higher during the support phase than during the pre-swing phase(P ≤ 0.03),and the stiffness of the gastrocnemius muscle fibers and tendons increased again in the late swing phase(P ≤ 0.05).These findings indicate that increasing running speed can increase the stiffness of triceps surae muscle fibers and tendons during the stance phase;when running speed and gait phase change,gastrocnemius and soleus muscles have different patterns of muscle fiber and tendon stiffness changes,whereas gastrocnemius can increase its muscle fiber stiffness and tendon stiffness in the late swing phase through pre-activation phenomenon.

Objective:To investigate the safety and efficacy of a modified radiofrequency ablation（RFA）treatment method for primary great saphenous vein varicose.Methods:Clinical data of 90 patients with primary great saphenous vein varicose treated with ultrasound-guided RFA from January 2021 to April 2024 in the Ultrasound Department of the First Affiliated Hospital of Zhengzhou University were retrospectively analyzed. Among them，45 patients were treated with traditional RFA treatment method（traditional group）and 45 patients were treated with improved RFA treatment method（improved group）. Number of punctures，operation time，foam hardener dosage，intraoperative and postoperative complications were recorded in the two groups. The preoperative and postoperative venous clinical severity score（VCSS）and chronic venous insufficiency questionnaire（CIVIQ-14）were compared. The closure rate and recurrence rate of great saphenous vein varicose were followed up and the efficacy of the two methods were analyzed.Results:The success rate of the improved group and the traditional group was 100%.The number of punctures in the improved group was less than those of the traditional group［1（1，1） vs. 2（2，3）， Z = -7.431， P<0.001］，and the operation time of the modified group was shorter than that of the traditional group［（15.89 ± 3.63）min vs.（30.91 ± 5.58）min， t=-15.145， P<0.001］，the average volume of lauryl foam was lower than that of the traditional RFA group［（7.96 ± 2.36）ml vs.（15.69 ± 2.89）ml， t=-13.892， P<0.001］. The incidence of complications was similar between the two groups，with no statistical significance（all P>0.05）. Postoperative VCSS and CIVIQ-14 scores were significantly improved compared with before（all P<0.001），with no statistical significance between the two groups（all P>0.05）. At 12 months after the operation，there was no significant difference in the closure rate of the saphenous vein between the improved group and the traditional group（ P>0.05），and the recurrence rate of varicose veins in both groups was 0. Conclusions:This modified RFA treatment method for the treatment of lower extremity varicose veins is minimally invasive，safe，and has the same efficacy as the traditional RFA treatment method. Compared with the traditional RFA treatment method，the modified RFA treatment method has the advantages of convenient operation，less puncture times and shorter operation time，and is worthy of clinical promotion.

Objective:To investigate the safety and efficacy of ultrasound-guided percutaneous radiofrequency ablation in the treatment of plasma cell mastitis.Methods:A retrospective analysis was performed for the clinical data of 10 patients with plasma cell mastitis treated with ultrasound-guided percutaneous radiofrequency ablation in the First Affiliated Hospital of Zhengzhou University from January 2021 to December 2022. The postoperative complications, symptoms and signs of the patients, ultrasound imaging manifestations, treatment efficacy at 3 months after surgery, the reduction rate of ablation lesions at 1 month, 3 months, 6 months, and 12 months after surgery, the recurrence status within 1 year after surgery, and the satisfaction with the treatment effect were observed.Results:The reduction rates of ablation lesions at 1 month, 3 months, 6 months, and 12 months were 32.31%-51.00%[(42.78±4.48)%], 70.66%-86.68%[(70.45±12.43)%], 72.31%-100%[(86.91±7.45)%], 89.13%-100%[(96.07±7.45)%], respecctively. The symptoms and signs of 10 patients improved significantly 3 months after surgery, and there was no recurrence of the disease during the follow-up period, and the treatment effect was significant and satisfactory.Conclusions:Ultrasound-guided percutaneous radiofrequency ablation for the treatment of plasma cell mastitis is a minimally invasive, effective and safe treatment.

DNA-encoded chemical library (DEL) links the power of amplifiable genetics and the non-self-replicating chemical phenotypes, generating a diverse chemical world. In analogy with the biological world, the DEL world can evolve by using a chemical central dogma, wherein DNA replicates using the PCR reactions to amplify the genetic codes, DNA sequencing transcripts the genetic information, and DNA-compatible synthesis translates into chemical phenotypes. Importantly, DNA-compatible synthesis is the key to expanding the DEL chemical space. Besides, the evolution-driven selection system pushes the chemicals to evolve under the selective pressure, i.e., desired selection strategies. In this perspective, we summarized recent advances in expanding DEL synthetic toolbox and panning strategies, which will shed light on the drug discovery harnessing in vitro evolution of chemicals via DEL.

Objective:To assess the prognostic value of methylation of interferon regulatory factor 6 ( IRF6) gene promoter in patients diagnosed with Kidney renal clear cell carcinoma (KIRC). Methods:The primary lesions of fifty KIRC patients who were diagnosed at the First Affiliated Hospital of Nanjing Medical University from January 2016 to January 2020 were collected. The expression of IRF6 protein was determined with an immunohistochemical method. The correlation between the level of IRF6 expression and survival and/or metastasis status was analyzed. The mRNA and protein levels of the IRF6 in KIRC and normal renal tissues were compared by using bioinformatic tools. The difference in the methylation rate of the IRF6 gene promoter between tumor and adjacent tissues was analyzed by searching the online databases. Statistical analysis was carried out for the methylation status of the IRF6 gene promoter region to select those negatively correlated with the overall survival (OS) among the patients. In vitro experiments were conducted with cell lines to verify the correlation between the status of promoter methylation and transcription level of the IRF6 gene. Results:The mRNA and protein levels of the IRF6 gene in KIRC tissues were significantly lower than those of the normal controls, and this was more prominent in patients who had died or developed metastasis. The extent of IRF6 gene promoter methylation in the KIRC tissues was much higher compared with that of the adjacent normal renal tissues. There was a significant negative correlation between the methylation of the IRF6 gene promoter and mRNA level of the IRF6 ( R= -0.52). The higher methylation degree in the IRF6 gene promoter regions cg12034118 and cg16030177, the shorter the OS and worse prognosis in the patients. Only twenty CpG sites in cg12034118 were confirmed to be highly methylated in KIRC cell lines. The transcription level of the IRF6 gene was upregulated in a time- and dose-dependent manner after the treatment with demethylation reagent 5-azadeoxycytidine. Conclusion:The methylation of IRF6 gene promoter in the renal tissues of KIRC patients is closely correlated with the OS. Cg12034118 may provide a promising biomarker for laboratory detection, and its high methylation rate has certain reference value for the prognosis.

Objective:To compare the therapeutic effects of ultrasound-guided radiofrequency ablation (RFA) and surgical resection on salivary gland mixed tumor with diameter ≤3 cm, and to analyze the feasibility and clinical value of RFA in the treatment of salivary gland mixed tumor.Methods:A retrospective study was conducted on 43 patients with salivary gland mixed tumor whose diameter ≤3 cm were treated in the First Affiliated Hospital of Zhengzhou University from March 2020 to March 2022.According to the treatment method, they were divided into an ablation group of 20 cases and a resection group of 23 cases. The complete ablation rate of the ablation group was evaluated, the postoperative absorption of ablation foci in the ablation group was recorded, and the perioperative indexes and the incidence of postoperative complications of the two groups were compared. The long-term prognosis of the two groups was followed up, and the incidence of recurrence, malignant metastasis and appearance recovery were evaluated.Results:In the ablation group, the complete ablation rate was 100.00% (20/20). The lesion volume reduction rates at 1, 3, 6 and 12 months after operation were -(39.60±16.18)%, (8.61±8.10)%, (31.87±14.68)% and (58.64±14.82)%, respectively. The operation time, recovery feeding time, postoperative hospital stay and intraoperative bleeding in the ablation group were less than those in the resection group, and the differences were statistically significant (all P<0.001). Postoperative complications occurred in 2 cases in the ablation group and 9 cases in the resection group. There was significant difference in the total incidence of postoperative complications between the two groups(χ 2=4.768, P=0.029). There was 1 case of recurrence in the ablation group, and no facial depression or protuberance occurred 1 year after operation. There was no recurrence in the resection group, one year after operation, the incidence of facial depression and facial protuberance was 13.04%(3/23) and 0, respectively.There was no malignant metastasis in both groups. Conclusions:Ultrasound-guided RFA is safe and effective in the treatment of mixed tumors of salivary gland with diameter ≤3 cm, and the therapeutic effect is not significantly different from that of surgery. With minimal trauma and good cosmetic effect, it has a great application prospect.

Objective:To investigate the safety and efficacy of ultrasound-guided percutaneous radiofrequency ablation in the treatment of nonmetastatic pheochromocytoma.Methods:A retrospective analysis was performed on 7 patients with nonmetastatic pheochromocytoma admitted to the First Affiliated Hospital of Zhengzhou University from January 2018 to June 2020, all of whom underwent ultrasound-guided percutaneous radiofrequency ablation. The changes of postoperative blood pressure, improvement of symptoms, intraoperative and postoperative complications were observed.Plasma free methoxypinephrine (MN) and normetanephrine (NMN) levels were recorded before and 2 weeks after operation. The reduction rate of ablation lesion volume at 1, 3 and 6 months after operation was calculated.Results:Postoperative blood pressure of all 7 patients was reduced to the normal range within 3 days, and symptoms such as headache were significantly relieved immediately after operation.No serious complications occurred during or after operation. Plasma free MN and NMN levels decreased to normal levels 2 weeks after operation. The mean reduction rates of the ablation lesions at 1, 3 and 6 months after operation were (46.61±13.42)%, (67.21±10.54)% and (85.73±4.15)%, respectively. Postoperative follow-up of 12-30 months showed that the blood pressure, plasma free MN and NMN levels of the patients were all in the normal range, and no symptoms such as headache and palpitation occurred again. All the tumors were completely ablated, and no recurrence was observed.Conclusions:Ultrasound-guided percutaneous radiofrequency ablation in the treatment of nonmetastatic pheochromocytoma is minimally invasive, safe and effective, and can retain adrenal cortex function, which is worthy of clinical promotion.

Combination of passive targeting with active targeting is a promising approach to improve the therapeutic efficacy of nanotherapy. However, most reported polymeric systems have sizes above 100 nm, which limits effective extravasation into tumors that are poorly vascularized and have dense stroma. This will, in turn, limit the overall effectiveness of the subsequent uptake by tumor cells via active targeting. In this study, we combined the passive targeting via ultra-small-sized gemcitabine (GEM)-based nanoparticles (NPs) with the active targeting provided by folic acid (FA) conjugation for enhanced dual targeted delivery to tumor cells and tumor-associated macrophages (TAMs). We developed an FA-modified prodrug carrier based on GEM (PGEM) to load doxorubicin (DOX), for co-delivery of GEM and DOX to tumors. The co-delivery system showed small particle size of ∼10 nm in diameter. The ligand-free and FA-targeted micelles showed comparable drug loading efficiency and a sustained DOX release profile. The FA-conjugated micelles effectively increased DOX uptake in cultured KB cancer cells that express a high level of folate receptor (FR), but no obvious increase was observed in 4T1.2 breast cancer cells that have a low-level expression of FR. Interestingly, in vivo, systemic delivery of FA-PGEM/DOX led to enhanced accumulation of the NPs in tumor and drastic reduction of tumor growth in a murine 4T1.2 breast cancer model. Mechanistic study showed that 4T1.2 tumor grown in mice expressed a significantly higher level of FOLR2, which was selectively expressed on TAMs. Thus, targeting of TAM may also contribute to the improved in vivo targeted delivery and therapeutic efficacy.