Peptide receptor radionuclide therapy (PRRT) with radiolabeled SSTR2 agonists is a treatment option that is highly effective in controlling metastatic and progressive neuroendocrine tumors (NETs). Previous studies have shown that an SSTR2 agonist combined with albumin binding moiety Evans blue (denoted as ¹⁷⁷Lu-EB-TATE) is characterized by a higher tumor uptake and residence time in preclinical models and in patients with metastatic NETs. This study aimed to enhance the in vivo stability, pharmacokinetics, and pharmacodynamics of ¹⁷⁷Lu-EB-TATE by replacing the maleimide-thiol group with a polyethylene glycol chain, resulting in a novel EB conjugated SSTR2-targeting radiopharmaceutical, ¹⁷⁷Lu-LNC1010, for PRRT. In preclinical studies, ¹⁷⁷Lu-LNC1010 exhibited good stability and SSTR2-binding affinity in AR42J tumor cells and enhanced uptake and prolonged retention in AR42J tumor xenografts. Thereafter, we presented the first-in-human dose escalation study of ¹⁷⁷Lu-LNC1010 in patients with advanced/metastatic NETs. ¹⁷⁷Lu-LNC1010 was well-tolerated by all patients, with minor adverse effects, and exhibited significant uptake and prolonged retention in tumor lesions, with higher tumor radiation doses than those of ¹⁷⁷Lu-EB-TATE. Preliminary PRRT efficacy results showed an 83% disease control rate and a 42% overall response rate after two ¹⁷⁷Lu-LNC1010 treatment cycles. These encouraging findings warrant further investigations through multicenter, prospective, and randomized controlled trials.

Copper death plays a significant regulatory role in biological processes. An increasing number of studies have revealed the mechanism, function, and potential clinical application value of copper death in bladder cancer. The emergence of copper death can provide new ideas for the treatment of bladder cancer. This article summarizes the role and regulation mechanism of copper death in bladder cancer, and reviews the research progress of copper-related proteins, copper death-related signaling pathways, copper nanoparticles, and copper carriers in bladder cancer, which is expected to provide new ideas and directions for the treatment of bladder cancer.

Objective To investigate the biomechanical differences in plantar pressure,postural stability,and plantar Visual Analogue Scale(VAS)scores between normal feet and unilateral/bilat-eral pes cavus,reveal their unique neuromechanical compensation mechanisms,and construct a sta-bility early warning model based on the minimum center of pressure(COP)trajectory classification.Methods A total of 70 patients with pes cavus from December 2023 to October 2024 were selected as study subjects,including 33 patients in the unilateral pes cavus group and 37 patients in the bilat-eral pes cavus group.During the same period,32 normal feet were included as normal foot group.A flat-panel plantar pressure testing system was used to collect dynamic plantar pressure data and COP trajectories from three groups at a self-selected walking speed.There were no statistically significant differences in baseline data such as age,gender,and body mass index among the three groups(P＞0.05).One-way analysis of variance and the Wilcoxon rank-sum test were used to compare the differences in maximum pressure,contact area,VAS scores,and the 95％confidence ellipse area of the COP among the three groups in 10 plantar regions.Results Patients with pes cavus exhibited lower peak pressure in the MF region compared to normal feet,while higher peak pressure in the M2,M3,and MH regions.Patients with bilateral pes cavus showed lower peak pressure in the T1 region compared to normal feet,and patients with unilateral pes cavus had lower peak pressure in the LH region compared to the normal group(P＜0.05).The plantar contact area in patients with pes cavus was reduced in the T1,M2,M3,M4,MF,and MH regions compared to normal feet(P＜0.05).The 95％confidence ellipse area of the COP was larger in both the bilateral and uni-lateral pes cavus groups compared to the normal foot group(P＜0.001).Unilateral pes cavus pres-ented a specific lateral COP drift(amplitude of 3 to 4 cm),which is a biomechanical manifestation of compensatory eversion of the unaffected foot.Patients with bilateral pes cavus exhibited a"bimod-al oscillation"trajectory(amplitude of 6 to 8 cm),suggesting possible vestibular-spinal regulatory dysfunction and the poorest postural stability.In the pes cavus group,there was a significant in-crease in pressure in the M2,M3,and MH regions,with peak pressures exceeding 190 kPa in pa-tients with bilateral pes cavus,which was highly correlated with plantar pain and could serve as a pain early warning threshold.Conclusion Unilateral and bilateral pes cavus exhibit significantly different neuromechanical compensation patterns.The classification based on the"lateral drift"and"bimodal oscillation"characteristics of the COP trajectory can serve as a stability early warning indi-cator for assessing fall risk.Decompression interventions targeting the key pressure regions of M2,M3,and MH(such as customized orthotic insoles)are the core strategies for alleviating pain and optimizing dynamic gait stability.

Acceleration of tooth movement during orthodontic treatment is challenging,with osteoclast-mediated bone resorption on the compressive side being the rate-limiting step.Recent studies have demonstrated that mechanoreceptors on the surface of monocytes/macrophages,especially adhesion G protein-coupled receptors(aGPCRs),play important roles in force sensing.However,its role in the regulation of osteoclast differentiation remains unclear.Herein,through single-cell analysis,we revealed that CD97,a novel mechanosensitive aGPCR,was expressed in macrophages.Compression upregulated CD97 expression and inhibited osteoclast differentiation;while knockdown of CD97 partially rescued osteoclast differentiation.It suggests that CD97 may be an important mechanosensitive receptor during osteoclast differentiation.RNA sequencing analysis showed that the Rap1a/ERK signalling pathway mediates the effects of CD97 on osteoclast differentiation under compression.Consistently,we clarified that administration of the Rap1a inhibitor GGTI298 increased osteoclast activity,thereby accelerating tooth movement.In conclusion,our results indicate that CD97 suppresses osteoclast differentiation through the Rap1a/ERK signalling pathway under orthodontic compressive force.

Objective:To explore the early effects and safety of using a hybrid fixation strategy with 3D-printed porous tantalum metal augments to reconstruct substantial bone defects in complex primary total knee arthroplasty (TKA).Methods:A retrospective analysis was performed on the clinical data from August 2019 to September 2023, encompassing 20 patients (21 knees) with significant bone loss who underwent hybrid fixation with 3D-printed porous tantalum augments. The procedures were conducted at two medical centers: the First Affiliated Hospital, School of Medicine, Zhejiang University (11 cases) and Xiangya Hospital of Central South University (9 cases). The study cohort comprised 6 males (6 knees) and 14 females (15 knees), with a mean age of 61.05±11.23 years (range, 42-80 years). The distribution of cases was 7 on the left side and 14 on the right side. All cases were categorized as type 3 according to the Anderson Orthopaedic Research Institute (AORI) classification system. The cohort included 19 unilateral and 1 bilateral case, with 5 involving complex primary replacements (3 with Charcot arthropathy, 1 with syphilitic arthropathy, and 1 with severe valgus deformity) and 16 revision surgeries (13 for aseptic loosening and 3 for infection). Preoperative assessments included routine CT scans and digital three-dimensional reconstructions to identify large metaphyseal defects exceeding 50% of the metaphyseal area or those thicker than 10 mm. For such defects, 3D-printed standardized porous tantalum augments were implemented. In cases of extensive cavitary bone defects or severe metaphyseal defects where the medial and lateral defects collectively exceeded 80% of the metaphyseal region or where the residual bone stock was insufficient for screw fixation of standardized augments, 3D-printed personalized custom-made porous tantalum augments were employed for hybrid fixation and repair. Comparative analyses were conducted on pre- and postoperative imaging data (prosthesis positioning and complications), knee range of motion (ROM), visual analogue scale (VAS) for pain, and Knee Society score (KSS).Results:Of the cases, 17 were repaired using standardized 3D-printed porous tantalum augments, while 4 underwent repairs with customized augments for hybrid fixation. Follow-up averaged 26.5±15.0 months (range, 12-62 months). There was a significant increase in knee ROM, improving from 72.8°±31.9° preoperatively to 113.2°±6.8° at 12 months postoperatively ( P<0.05). VAS scores decreased from 6.6±1.4 preoperatively to 2.5±1.0 at 12 months postoperatively ( P<0.05). Similarly, KSS improved from 52.8±6.4 preoperatively to 80.7±7.9 at 12 months postoperatively ( P<0.05). There were no incidences of prosthesis displacement, poor bone integration, or postoperative infections. Conclusion:The hybrid fixation strategy employing 3D-printed porous tantalum augments has been found to be effective in addressing significant bone defects in TKA. The follow-up results indicate a satisfactory biological integration of the porous tantalum metal augments with the host bone, which has resulted in substantial improvements in pain relief and knee joint functionality.

Objective:To investigate the diagnostic value of serum serine protease (Corin) in chronic renal failure (CRF) complicated with heart failure.Methods:A retrospective analysis was conducted on 120 patients, (64.05±13.89) years old, 77 male (64.17%), with chronic renal failure combined with heart failure admitted to Zhengzhou People′s Hospital from January 1, 2023, to December 31, 2023. The control group consisted of 87 patients, (60.59±8.78) years old, 54 male (62.07%), with simple chronic renal failure. Clinical information, laboratory test indicators and echocardiographic parameters were collected. Serum Corin concentration was measured using enzyme-linked immunosorbent assay (ELISA). The experimental group was divided into grade Ⅱ(31 cases), grade Ⅲ(47 cases) and grade Ⅳ(42 cases) according to the New York College of Cardiology heart function classification system. Serum Corin levels were compared between the experimental group and the control group and among different cardiac function grades. Spearman correlation analysis was performed to evaluate the relationship between serum Corin and brain natriuretic peptide (BNP), D-dimer. ROC analysis was conducted to assess the predictive value of serum Corin in CRF complicated with heart failure and cardiac function classification; Binary Logistic regression was used to construct a multi-index joint prediction model, the joint prediction probability was obtained, and ROC curve was drawn to compare the diagnostic value of serum Corin and BNP in CRF combined with heart failure and the diagnostic value of serum Corin combined with D-dimer and BNP in CRF combined with heart failure.Results:The serum Corin level[2 568.97±477.70 pg/ml vs. 1 727.81±480.60 pg/ml, t=12.47, P<0.001], BNP [700.00(256.00, 2 089.75) pg/ml compared with 88.00 (43.00, 230.00) pg/ml, Z=-9.00, P<0.001], D-dimer [1 150.00(643.00, 1 874.75)μg/L compared with 556.00 (301.00, 865.00)μg/L, Z=-6.57, P<0.001] in chronic renal failure complicated with heart failure group was higher than that in simple CRF group, and the difference was statistically significant. Among patients with CRF complicated with heart failure, serum Corin[2 231.74±311.39 pg/ml vs. 2 562.09±365.30 pg/ml vs. 2 825.57±536.83 pg/ml, F=74.33, P<0.001], BNP [234.00(168.00, 612.00) pg/ml compared with 514.00(260.00, 1 455.00) pg/ml compared with 2 200.00(640.50, 4 682.75) pg/ml, H=29.42, P<0.001], D-dimer [753.00(514.00, 1 280.00) μg/L compared with 1 187.00(590.00, 1 840.00) μg/L compared with 1 603.00(810.00, 3 313.25) μg/L, H=14.98, P<0.001] increased with the increase of cardiac function grade, and the difference was statistically significant. According to Spearman correlation analysis, serum Corin was positively correlated with BNP ( r=0.409) and D-dimer ( r=0.299), P<0.001. According to the ROC analysis, the AUC of serum Corin in the diagnosis of CRF complicated with heart failure and cardiac function grade Ⅱ, Ⅲ, Ⅳ were 0.890(95% CI 0.846-0.935), 0.807 (95% CI 0.728-0.885), 0.911 (95% CI 0.864-0.959), 0.927 (95% CI 0.882-0.972) respectively; the AUC of BNP in the diagnosis of CRF complicated with heart failure was 0.867 (95% CI 0.817-0.916), the AUC of serum Corin combined with D-dimer, BNP combined with D-dimer, serum Corin combined with D-dimer and BNP in the diagnosis of CRF complicated with heart failure were respectively 0.930 (95% CI 0.897-0.962), 0.892 (95% CI 0.847-0.936), 0.952 (95% CI 0.927-0.977). Conclusions:Serum Corin expression is elevated in patients with CRF complicated with heart failure, and the degree of elevation is related to cardiac function grade. Serum Corin has a good diagnostic value for CRF complicated with heart failure and its severity. Serum Corin is expected to become a new biomarker for diagnosis of CRF complicated with heart failure.

Objective:To investigate the effect of Notch on periprosthetic fracture (PPF) of the femoral prosthesis after primary total knee arthroplasty.Methods:A total of 34 patients diagnosed with femoral PPF at Xi'an Honghui Hospital were retrospectively collected from January 2013 to December 2020. There were 4 males and 30 females with a mean age of 69.2±7.2 years (range, 55-84 years). A total of 102 patients without PPF were matched by gender and age as the control group in a ratio of 1∶3. There were 12 males and 90 females with a mean age of 69.2±7.2 years (range, 55-84 years). The main observation indexes included patients' general information and factors such as coronal alignment, prosthesis design and Notch conditions. Then, subgroup analysis was performed with the depth and Tayside classification of Notch to analyze their effects on PPF.Results:The PPF and control groups were comparable in terms of baseline information such as gender, age, body mass index (BMI), and surgical side. There was no significant difference between the two groups in coronal alignment (χ 2=1.019, P=0.601) and prosthesis design (χ 2=1.545, P=0.214). There was no statistical difference in Notch between the PPF and control groups (χ 2=3.548, P=0.060). The mean length of Notch in the PPF group was 4.5±2.7 mm, compared with 4.9±2.8 mm in the control group, with no significant difference between the two groups ( t=0.732, P=0.465). Further subgroup analysis using a Notch depth of 3 mm as a cut-off and Tayside classification revealed a statistical difference between the two groups (χ 2=11.262, P=0.004; χ 2=14.601, P=0.003). Compared with patients without Notch, the risk of PPF was higher when the depth of Notch exceeded 3 mm, with an odds ratio ( OR) of 4.88 (95% CI: 1.76, 13.51). The incidence of PPF was higher when Notch depth reached Tayside grade 3 or 4. Compared with patients without Notch, the risk of PPF would be 6.99-fold (95% CI: 1.85, 26.32) higher when Notch depth reached grade 3. In female patients, there was a significant difference in Notch status between the PPF and control groups (χ 2=3.956, P=0.047), with a higher risk of PPF in female patients with Notch, OR 2.33 (95% CI: 1.01, 5.43). In patients who underwent right-sided TKA, the risk of PPF was higher in patients with Notch compared to those without Notch (χ 2=5.502, P=0.019), with an OR of 3.58 (95% CI: 1.19, 10.75). Conclusion:The Notch has no significant effect on the femoral PPF after primary total knee arthroplasty. However, the risk of PPF will increase significantly when the Notch depth exceeds 3 mm or is above Tayside grade 3.

Objective:To explore a fast and accurate method to diagnose children's pneumonia according to respiratory signals, so as to avoid the cancer induction caused by traditional X-ray examination.Methods:A Mach Zehnder optical fiber sensor was used to build a respiratory signals(RSPs) detection system, and the RSPs of the monitored children were extracted according to the vibration signal generated by the children's lung rales. Preprocessing methods such as the discrete cosine transform(DCT) were used to compress and denoise the RSPs. Multi-feature extraction of RSPs was conducted through signal processing methods such as the Hilbert transform and autoregressive (AR) model spectrum estimation. A support vector machine (SVM) classification model was constructed to classify the collected RSPs.Results:The accuracy rate of the proposed RSP classification of children with or without pneumonia was 94.41%, which was higher than the previous methods.Conclusions:The children's pneumonia diagnosis system based on an optical fiber sensor has a higher detection accuracy, and is expected to be widely used in clinical practice.

Objective:To evaluate the value of vasoactive-inotropic Score (VIS) at different time points in predicting the 28-day mortality of patients with septic shock, so as to reduce the risk of death and improve the prognosis of patients.Methods:This experiment was a single-center retrospective cohort study. The clinical data of 275 adult patients with septic shock who were treated with vasoactive drugs in the intensive care unit of the Affiliated Hospital of Xuzhou Medical University from February 2016 to February 2020 were collected. According to the 28-day survival condition, all recruited patients were divided into the death group and the survival group, and the maximum vasoactive-inotropic score of all patients at the first 24 h and the second 24 h were calculated, which were expressed as VIS max24 and VIS max48. Multivariate logistic regression analysis was used to find the independent risk factors that influencing the prognosis. The receiver operating characteristic curve was used to analyze the predictive value of VIS. Results:There was no significant difference between the death group and the survival group in the characteristics including age, sex, weight, infection sites, blood culture results, cardiac arrest, hormone use, and 24 h rehydration volume ( P>0.05). APACHE II score, basic lactic acid, and lactic acid after 24 h of treatment were increased significantly in the death group ( P<0.05). VIS max24 could accurately predict the 28-day mortality (AUC=0.953, 95% CI: 0.924-0.982), which were more efficent compared to VIS max48 (AUC=0.919, 95% CI: 0.881-0.957), basic lactic acid (AUC=0.937, 95% CI: 0.900-0.966) and APACHEⅡ score (AUC=0.865, 95% CI: 0.818-0.913). Conclusion:VIS max24 can more accurate predict the 28-day mortality in patients with septic shock.

Objective:To prospectively analyze the early clinical effects of 3D-printed porous metal cup with hip dual-mobility revision (HDR) system in treating severe acetabular bone defects.Methods:A total of 17 patients with severe acetabular defects (15 patients in Allan-Gross type 4 and 2 patients in type 5; 2 patients in Paprosky type 2B, 4 patients in type 3A and 11 patients in type 3B) who underwent revision hip arthroplasty between July 2019 and May 2020 were analyzed. There were 7 males and 10 females (mean age 67.3±9.3 years; range 42-80 years). The average body mass index was 22.2±3.8 kg/m 2 (range 17.7-33.3 kg/m 2). The preoperative mean leg length discrepancy (LLD) was 42.9±31.1 mm (range 10-160 mm) . One patient presented positive Trendelenburg sign. The follow-up duration was 12.1±3.0 months (range 6-16 months). The clinical and radiographic hip scores in all patients were evaluated. Results:The mean Harris Hip Score (HHS) was 31.2±11.3 points at preoperatively, 63.5±10.0, 68.7±10.4 and 70.2±10.1 points at 3 days, 7 days and 1 month postoperatively. At the latest follow-up, HHS was increased to 81.6±7.0 points. The outer cup mean abduction angle was 48.1°±10.6° and the mean inclination angle was 10.8°±6.0° postoperatively. The inner cup mean abduction angle was 45.0°±6.2° and the mean inclination angle was 10.8°±3.7°. The mean LLD decreased to 11.1±3.8 mm (range: 0-15 mm) after surgery. At the latest follow-up, all acetabular components were radiologically stable without displacement. No osteolysis or absorption was observed. There was no infection, loosening or nerve injury in all cases.Conclusion:During short-term follow-up, the 3D-printed porous metal HDR system can effectively enhance the stability of implants with satisfied quality of life. It can provide a good result for the revision of total hip arthroplasty with severe acetabular defects.