Peptide-based radiopharmaceuticals targeting integrin α5β1 show promise for precise tumor diagnosis and treatment. However, current peptide-based radioligands that target α5β1 demonstrate inadequate in vivo performance owing to limited tumor retention. The use of PEGylation to enhance the tumor retention of radiopharmaceuticals by prolonging blood circulation time poses a risk of increased blood toxicity. Therefore, a PEGylation strategy that boosts tumor retention while minimizing blood circulation time is urgently needed. Here, we developed a PEGylation-enabled peptide multidisplay platform (PEGibody) for PR_b, an α5β1 targeting peptide. PEGibody generation involved PEGylation and self-assembly. [⁶⁴Cu]QM-2303 PEGibodies displayed spherical nanoparticles ranging from 100 to 200 nm in diameter. Compared with non-PEGylated radioligands, [⁶⁴Cu]QM-2303 demonstrated enhanced tumor retention time due to increased binding affinity and stability. Importantly, the biodistribution analysis confirmed rapid clearance of [⁶⁴Cu]QM-2303 from the bloodstream. Administration of a single dose of [¹⁷⁷Lu]QM-2303 led to robust antitumor efficacy. Furthermore, [⁶⁴Cu]/[¹⁷⁷Lu]QM-2303 exhibited low hematological and organ toxicity in both healthy and tumor-bearing mice. Therefore, this study presents a PEGibody-based radiotheranostic approach that enhances tumor retention time and provides long-lasting antitumor effects without prolonging blood circulation lifetime. The PEGibody-based radiopharmaceutical [⁶⁴Cu]/[¹⁷⁷Lu]QM-2303 shows great potential for positron emission tomography imaging-guided targeted radionuclide therapy for α5β1-overexpressing tumors.

Objective:To investigate the efficacy of self-prescribed Huoxue Shengjing Prescription as adjuvant therapy for varicocele-induced infertility and its impact on the outcomes of in vitro fertilization-embryo transfer/intracytoplasmic sperm injection (IVF-ET/ICSI).Methods:A randomized controlled trial was conducted. A total of 99 patients with varicocele-induced infertility in our hospital from January 2022 to July 2023 were selected as observation subjects and divided into three groups using a random number table method, with 33 patients in each group. The low ligation group received low ligation of varicocele under a microscope, the low ligation + conventional Western medicine treatment group received low ligation + conventional Western medicine therapy, and the combined group received low ligation + conventional Western medicine therapy + a self-prescribed Huoxue Shengjing Prescription. Among them, the low ligation of varicocele under a microscope was followed by IVF-ET/ICSI assisted reproductive technology 3 months after surgery; the conventional Western medicine therapy involved continuous administration of L-carnitine oral solution for 3 months; the self-prescribed Huoxue Shengjing Prescription was started on the first day after surgery and continued for 3 months. TCM syndrome scores were assessed before and after treatment, and semen routine analysis was performed using an automated semen quality analyzer. Mitochondrial activity of granulosa cells was measured using the Hrudka extraction method, and sperm nuclear DNA integrity was assessed using a modified alkaline single-cell gel electrophoresis method. Follow-up was conducted for 1 year to observe and record the outcomes of IVF-ET/ICSI and evaluate the clinical efficacy.Results:The total effective rate was 93.9% (31/33) in the combined group, 69.7% (23/33) in the low ligation group, and 75.8% (25/33) in the low ligation + conventional Western medicine treatment group, with statistical significance ( χ 2=6.52, P=0.039). After treatment, the scores for mild abdominal pain, testicular heavy pain, impotence, mental fatigue, and the total score in the combined group were lower than those in the low ligation + conventional Western medicine treatment group and the low ligation group ( F values were 89.29, 97.51, 136.36, 155.06, and 311.13, respectively, P<0.001). The sperm survival rate, sperm concentration, normal morphology rate, and progressive motility rate in the combined group were higher than those in the low ligation + conventional Western medicine treatment group and the low ligation group ( F values were 19.23, 11.85, 35.97, and 52.21, respectively, P<0.001). Mitochondrial grade I cell activity of granulosa cells was higher than that of the low ligation + conventional treatment group and low ligation group ( F=23.23, P<0.001), and grade Ⅲ cell activity was lower than that of the low ligation + conventional treatment group and low ligation group ( F=20.28, P<0.001). After treatment, the detection of grade Ⅰ and Ⅱ sperm nuclear DNA integrity in the combined group were higher than those in the low ligation + conventional Western medicine treatment group and the low ligation group ( F values were 17.73 and 18.39, respectively, P<0.001), while grades Ⅲ and Ⅳ were lower than those in the low ligation + conventional Western medicine treatment group and the low ligation group ( F values were 29.07 and 10.36, respectively, P<0.001). During follow-up, the excellent embryo rate and the spouse's clinical pregnancy rate in the combined group were higher than those in the low ligation + conventional Western medicine treatment group and the low ligation group ( χ2 values were 14.92 and 8.38, respectively; P values were 0.001 and 0.015, respectively). Conclusion:The adjuvant treatment with a self-prescribed Huoxue Shengjing Prescription can enhance sperm quality in patients with varicocele-related infertility, maintain DNA integrity, regulate seminal plasma mitochondrial function, increase the rate of high-quality embryos, and improve the spouse's pregnancy outcomes.

Objective:To observe the long-term effect of superficial temporal fascia flap combined with severed auricle reimplantation in emergency repair of partial auricle of complete separation.Methods:The data of patients with partial auricle of complete separation admitted to Emergency Clinic of Burn and Plastic Surgery of General Hospital of Northern Theater Command from June 2014 to August 2023 were retrospectively analyzed. All of them were repaired with a superficial temporal fascia flap combined with amputating auricle reimplantation. During the operation, the superficial temporal fascia flap was harvested, and the pedicle was preserved. Then the detached auricular cartilage was removed and used as a replantation scaffold. Then the remaining skin was thinned to create a full-thickness skin graft after cartilage detachment. Referring to the position and angle of the contralateral auricle, the cartilage scaffold was sutured and fixed at the stump of the ear cartilage. The wound was covered with a superficial temporal fascia flap and a full-thickness skin graft, and then packed and sutured. The postoperative observation indicators mainly confirm whether the surgery was successful, the healing condition of the replanted ear, and whether there were problems such as skin flap necrosis, infection, hematoma, etc. The shape, color, texture and tactile recovery of the reconstructed auricle were evaluated by long-term follow-up for more than 1 year. The Vancouver scar scale (VSS) was used to assess scarring in both donor and recipient sites (total score of 0-15 points, higher scores indicated more severe scarring). The Likert 5-level scoring method was used to evaluate the patients’ satisfaction with the surgical results (total score of 30 points, ≥27 points were very satisfied, 24-26 points were somewhat satisfied, 18-23 points were indifferent, 15-17 points were somewhat dissatisfied, ≤14 points were very dissatisfied).Results:A total of 8 patients were enrolled, including 5 males and 3 females. Their ages ranged from 26 to 65 years, with an average of 41 years. All patients had unilateral ear defects, with 3 cases in the left ear and 5 cases in the right ear. The defect areas ranged from 1.5 cm × 2.5 cm to 5.0 cm × 4.0 cm. During the surgery, the harvested superficial temporoparietal fascia flaps ranged from 4.5 cm × 6.5 cm to 15.0 cm × 10.0 cm. After surgery, both the flaps and full-thickness skin graft healed satisfactorily, with primary healing observed in both the donor and recipient sites. There were no complications such as necrosis, infection, or hematoma were observed. The follow-up period ranged from 3 to 9 years, with an average of approximately 6.3 years. Except for one case that required a defatted surgery at the second stage, the reconstructed auricles of the remaining patients were basically consistent with the healthy side, with smooth contour lines, skin color and texture close to the surrounding tissues, and improved tactile sensitivity. In the final follow-up, the VSS scores for both the donor and recipient sites were ≤3 for all patients. All patients rated the surgical outcome as very satisfied.Conclusion:For the partial auricle of complete separation that has no chance of replantation, the use of superficial temporal fascia flap and detached ear composite graft to repair is a reliable and effective surgical method. Patients have good postoperative long-term effects and high levels of satisfaction.

Objective:To study the influence of different region of interest (ROI) sketch on measurement results in the diagnosis of breast cancer by imaging technology of intravoxel incoherent motion (IVIM) .Methods:The clinical dataes of 84 patients with breast mass lesions from Apr. 2017 to Oct. 2021 were collected, all patients underwent IVIM-DWI. ROI was delineated at the maximum level of the mass by tumor contour method and fixed radius method. The apparent diffusion coefficient (ADC), real diffusion coefficient (D), perfusion fraction (f) and pseudo diffusion coefficient (D *) were recorded. IVIM-DWI parameters of patients with benign and malignant breast tumors were compared. The influence of ROI delineation by tumor contour method and fixed radius method on the results of IVIM related parameters were compared. Results:Forty-six of 84 patients were malignant and 38 benign masses. The ADC and D values of patients in the malignant group were (0.98±0.24) ×10 -3 mm 2/s, (0.79±0.22) ×10 -3 mm 2/s in the malignant group, significantly lower than those in the benign group [ (1.65±0.43) ×10 -3 mm 2/s, (1.41±0.35) ×10 -3 mm 2/s], and the f value and D * value were (5.65±1.13) %, (43.89±8.05) ×10 -3 mm 2/s, significantly higher than those in the benign group [ (3.84±1.57) %, (37.77±9.3) ×10 -3 mm 2/s]. The differences were statistically significant ( t=9.01, 9.89, 6.13, 3.23; all P<0.05). The results obtained by using the tumor fixed radius method to delineate ROI showed that the ADC and D values of (0.96±0.27) ×10 -3 mm 2/s (0.81±0.23) ×10 -3 mm 2/s in the malignant group were significantly lower than those in the benign group [ (1.66±0.39) ×10 -3 mm 2/s, 1.39±0.37) ×10 -3 mm 2/s], and the f and D * values were (5.69±1.15) %, (43.94±7.98) ×10 -3 mm 2/s, which were significantly higher than those in the benign group [ (3.86±1.49) %, (38.01±8.46) ×10 -3 mm 2/s]. The differences were statistically significant ( t=9.69, 8.78, 6.35, 3.30; all P<0.05) .The 95% consistency interval range of ADC difference, D value difference, f value difference, and D * value difference obtained by using tumor contour method to delineate ROI was smaller than that of tumor fixed radius method. Conclusions:The IVIM has high accuracy in the diagnosis of breast cancer, the IVIM parameters obtained from ROI delineation by tumor contour method have good repeatability.

Objective:To observe the long-term effect of superficial temporal fascia flap combined with severed auricle reimplantation in emergency repair of partial auricle of complete separation.Methods:The data of patients with partial auricle of complete separation admitted to Emergency Clinic of Burn and Plastic Surgery of General Hospital of Northern Theater Command from June 2014 to August 2023 were retrospectively analyzed. All of them were repaired with a superficial temporal fascia flap combined with amputating auricle reimplantation. During the operation, the superficial temporal fascia flap was harvested, and the pedicle was preserved. Then the detached auricular cartilage was removed and used as a replantation scaffold. Then the remaining skin was thinned to create a full-thickness skin graft after cartilage detachment. Referring to the position and angle of the contralateral auricle, the cartilage scaffold was sutured and fixed at the stump of the ear cartilage. The wound was covered with a superficial temporal fascia flap and a full-thickness skin graft, and then packed and sutured. The postoperative observation indicators mainly confirm whether the surgery was successful, the healing condition of the replanted ear, and whether there were problems such as skin flap necrosis, infection, hematoma, etc. The shape, color, texture and tactile recovery of the reconstructed auricle were evaluated by long-term follow-up for more than 1 year. The Vancouver scar scale (VSS) was used to assess scarring in both donor and recipient sites (total score of 0-15 points, higher scores indicated more severe scarring). The Likert 5-level scoring method was used to evaluate the patients’ satisfaction with the surgical results (total score of 30 points, ≥27 points were very satisfied, 24-26 points were somewhat satisfied, 18-23 points were indifferent, 15-17 points were somewhat dissatisfied, ≤14 points were very dissatisfied).Results:A total of 8 patients were enrolled, including 5 males and 3 females. Their ages ranged from 26 to 65 years, with an average of 41 years. All patients had unilateral ear defects, with 3 cases in the left ear and 5 cases in the right ear. The defect areas ranged from 1.5 cm × 2.5 cm to 5.0 cm × 4.0 cm. During the surgery, the harvested superficial temporoparietal fascia flaps ranged from 4.5 cm × 6.5 cm to 15.0 cm × 10.0 cm. After surgery, both the flaps and full-thickness skin graft healed satisfactorily, with primary healing observed in both the donor and recipient sites. There were no complications such as necrosis, infection, or hematoma were observed. The follow-up period ranged from 3 to 9 years, with an average of approximately 6.3 years. Except for one case that required a defatted surgery at the second stage, the reconstructed auricles of the remaining patients were basically consistent with the healthy side, with smooth contour lines, skin color and texture close to the surrounding tissues, and improved tactile sensitivity. In the final follow-up, the VSS scores for both the donor and recipient sites were ≤3 for all patients. All patients rated the surgical outcome as very satisfied.Conclusion:For the partial auricle of complete separation that has no chance of replantation, the use of superficial temporal fascia flap and detached ear composite graft to repair is a reliable and effective surgical method. Patients have good postoperative long-term effects and high levels of satisfaction.

Mendelian Randomization Analysis ; Bone Density ; Genome-Wide Association Study ; Minerals ; Life Expectancy ; Polymorphism, Single Nucleotide

Objective:To observe the efficacy the application of endoscope assisted temporoparietal fascia flap harvest for the second-stage operation in auricular reconstruction of Nagata’s technique for microtia.Method:In this retrospective study, the clinical data were collected from the patients who received microtia reconstruction with autologous rib cartilage at the Department of Burns and Plastic Surgery, General Hospital of Northern Theater Command from January 2015 to January 2022. According to the surgical procedure, patients were divided into endoscopic group and open surgery group. In endoscopic group, endoscope-assisted temporoparietal fascia harvest were performed for the second-stage operation in auricular reconstruction of Nagata’s technique. In open surgery group, temporoparietal fascia flaps were harvested in open surgery for the second-stage operation in auricular reconstruction of Nagata’s technique. Regular follow-up was conducted to observe the survival of the fascia flaps, complications, patient satisfaction, and surgical scars. The patient satisfaction questionnaire for auricular reconstruction was used to assess patient satisfaction, and the patient and observer scar assessment scale (POSAS) was used to evaluate scar formation in the surgical area. Data analysis was performed using SPSS 26.0 statistical software. The measurement data were expressed by Mean ± SD, and the counting data were expressed as cases (%). The T-test was used to compare the age difference, length of hospital stay, intraoperative blood loss, scar length, patient satisfaction, and POSAS scores between the two groups. Chi-square test was used to compare the gender composition and incidence of complications between the two groups. P<0.05 was considered statistically significant. Results:A total of 51 patients were included, with 26 in the endoscopic group (14 men and 12 women) and 25 in the open surgery group (12 men and 13 women). The age of the patients in the endoscopic group was (9.8±2.9) years (ranging from 7 to 17 years), while in the open surgery group was (10.3±3.8) years (ranging from 7 to 17 years). The postoperative follow-up period was (15.4±3.4) months (1 to 2 years), and all fascia flaps survived without any severe complications. There were no statistically significant differences between the two groups in terms of age difference, length of hospital stay, intraoperative blood loss, postoperative satisfaction, sex composition ratio, and postoperative complications ( P>0.05). The scar quality in the endoscopy group was superior to that in the open surgery group, and POSAS scores of endoscopic group were lower than those in the open surgery group, and the difference was statistically significant ( P<0.05). Conclusion:Endoscope assisted temporoparietal fascia flap harvest for the second-stage operation in auricular reconstruction of Nagata’s technique for microtia can minimize scarring, improve the postoperative appearance and is not statistically associated with the appearance of reconstructed auricles or complications.

Objective:To observe the efficacy the application of endoscope assisted temporoparietal fascia flap harvest for the second-stage operation in auricular reconstruction of Nagata’s technique for microtia.Method:In this retrospective study, the clinical data were collected from the patients who received microtia reconstruction with autologous rib cartilage at the Department of Burns and Plastic Surgery, General Hospital of Northern Theater Command from January 2015 to January 2022. According to the surgical procedure, patients were divided into endoscopic group and open surgery group. In endoscopic group, endoscope-assisted temporoparietal fascia harvest were performed for the second-stage operation in auricular reconstruction of Nagata’s technique. In open surgery group, temporoparietal fascia flaps were harvested in open surgery for the second-stage operation in auricular reconstruction of Nagata’s technique. Regular follow-up was conducted to observe the survival of the fascia flaps, complications, patient satisfaction, and surgical scars. The patient satisfaction questionnaire for auricular reconstruction was used to assess patient satisfaction, and the patient and observer scar assessment scale (POSAS) was used to evaluate scar formation in the surgical area. Data analysis was performed using SPSS 26.0 statistical software. The measurement data were expressed by Mean ± SD, and the counting data were expressed as cases (%). The T-test was used to compare the age difference, length of hospital stay, intraoperative blood loss, scar length, patient satisfaction, and POSAS scores between the two groups. Chi-square test was used to compare the gender composition and incidence of complications between the two groups. P<0.05 was considered statistically significant. Results:A total of 51 patients were included, with 26 in the endoscopic group (14 men and 12 women) and 25 in the open surgery group (12 men and 13 women). The age of the patients in the endoscopic group was (9.8±2.9) years (ranging from 7 to 17 years), while in the open surgery group was (10.3±3.8) years (ranging from 7 to 17 years). The postoperative follow-up period was (15.4±3.4) months (1 to 2 years), and all fascia flaps survived without any severe complications. There were no statistically significant differences between the two groups in terms of age difference, length of hospital stay, intraoperative blood loss, postoperative satisfaction, sex composition ratio, and postoperative complications ( P>0.05). The scar quality in the endoscopy group was superior to that in the open surgery group, and POSAS scores of endoscopic group were lower than those in the open surgery group, and the difference was statistically significant ( P<0.05). Conclusion:Endoscope assisted temporoparietal fascia flap harvest for the second-stage operation in auricular reconstruction of Nagata’s technique for microtia can minimize scarring, improve the postoperative appearance and is not statistically associated with the appearance of reconstructed auricles or complications.

China has entered the task stage of comprehensive medical insurance payment reform, but there are problems restricting the development of innovative medical technology in the reform of diagnosis-related groups(DRG) payment system. The author introduced the international definition and scope of innovative medical technology, and summarized the preconditions and payment policy of short-term payment of innovative medical technology under the DRG payment system; And put forward suggestions in line with China′s actual situation, including clarifying the definition of innovative medical technology, setting access conditions for additional payment or actual payment, setting up special transition funds for high-value innovative drugs, clarifying the payment amount of innovative medical technology, and formulating payment strategies for innovative medical technology.

Sequencing-based spatial transcriptomics(ST)is an emerging technology to study in situ gene expression patterns at the whole-genome scale.Currently,ST data analysis is still complicated by high technical noises and low resolution.In addition to the transcriptomic data,matched histopathological images are usually generated for the same tissue sample along the ST experiment.The matched high-resolution histopathological images provide complementary cellular phenotypi-cal information,providing an opportunity to mitigate the noises in ST data.We present a novel ST data analysis method called transcriptome and histopathological image integrative analysis for ST(TIST),which enables the identification of spatial clusters(SCs)and the enhancement of spatial gene expression patterns by integrative analysis of matched transcriptomic data and images.TIST devises a histopathological feature extraction method based on Markov random field(MRF)to learn the cellular features from histopathological images,and integrates them with the transcrip-tomic data and location information as a network,termed TIST-net.Based on TIST-net,SCs are identified by a random walk-based strategy,and gene expression patterns are enhanced by neighborhood smoothing.We benchmark TIST on both simulated datasets and 32 real samples against several state-of-the-art methods.Results show that TIST is robust to technical noises on multiple analysis tasks for sequencing-based ST data and can find interesting microstructures in dif-ferent biological scenarios.TIST is available at http://lifeome.net/software/tist/and https://ngdc.cncb.ac.cn/biocode/tools/BT007317.