[Biological characteristics and osteogenic differentiation of magnesium-doped nanoporous titanium coating].

PURPOSE: Bioactive magnesium ions were successfully incorporated into the nanoporous titanium base coating by micro-arc oxidation(MAO), and its physical properties and osteogenic effects were explored. METHODS: Non-magnesium-containing and magnesium-containing titanium porous titanium coatings(MAO, MAO-mg) were prepared by changing the composition of MAO electrolyte and controlling the doping of magnesium in porous titanium coatings. The samples were characterized by scanning electron microscope (SEM), roughness, contact angle and energy dispersive X-ray spectrometer (EDS). Mg2+ release ability of magnesium-doped nanoporous titanium coatings was determined by inductively coupled plasma/optical emission spectrometer(ICP-OES). The structure of the cytoskeleton was determined by live/dead double staining, CCK-8 detection of material proliferation-toxicity, and staining of ß-actin using FITC-phalloidin. The effects of the coating on osteogenic differentiation in vitro were determined by alizarin red (ARS), alkaline phosphatase (ALP) staining and real-time polymerase chain reaction (qRT-PCR). SPSS 25.0 software package was used for statistical analysis. RESULTS: The MAO electrolyte with magnesium ions did not change the surface characteristics of the porous titanium coating. Each group prepared by MAO had similar microporous structure(P＞0.05). There was no significant difference in surface roughness and contact angle between MAO treatment group (MAO, MAO-mg)(P＞0.05), but significantly higher than that of Ti group (P＜0.05). With the passage of cell culture time, MAO-mg group promoted cell proliferation (P＜0.05). MAO-mg group was significantly higher than other groups in ALP and ARS staining. The expression of Runx2 mRNA (P＜0.05), ALP(P＜0.05) and osteocalcin OCN(P＜0.05) in MAO-mg group was significantly higher than that in Ti and MAO groups. CONCLUSIONS: MAO successfully prepared magnesium-containing nanoporous titanium coating, and showed a significant role in promoting osteogenic differentiation.

All-In-One OsciDrop Digital PCR System for Automated and Highly Multiplexed Molecular Diagnostics.

Digital PCR (dPCR) holds immense potential for precisely detecting nucleic acid markers essential for personalized medicine. However, its broader application is hindered by high consumable costs, complex procedures, and restricted multiplexing capabilities. To address these challenges, an all-in-one dPCR system is introduced that eliminates the need for microfabricated chips, offering fully automated operations and enhanced multiplexing capabilities. Using this innovative oscillation-induced droplet generation technique, OsciDrop, this system supports a comprehensive dPCR workflow, including precise liquid handling, pipette-based droplet printing, in situ thermocycling, multicolor fluorescence imaging, and machine learning-driven analysis. The system's reliability is demonstrated by quantifying reference materials and evaluating HER2 copy number variation in breast cancer. Its multiplexing capability is showcased with a quadruplex dPCR assay that detects key EGFR mutations, including 19Del, L858R, and T790M in lung cancer. Moreover, the digital stepwise melting analysis (dSMA) technique is introduced, enabling high-multiplex profiling of seven major EGFR variants spanning 35 subtypes. This innovative dPCR system presents a cost-effective and versatile alternative, overcoming existing limitations and paving the way for transformative advances in precision diagnostics.

Blood-Brain Barrier Penetrating Nanovehicles for Interfering with Mitochondrial Electron Flow in Glioblastoma.

Glioblastoma multiforme (GBM) is the most aggressive and lethal form of human brain tumors. Dismantling the suppressed immune microenvironment is an effective therapeutic strategy against GBM; however, GBM does not respond to exogenous immunotherapeutic agents due to low immunogenicity. Manipulating the mitochondrial electron transport chain (ETC) elevates the immunogenicity of GBM, rendering previously immune-evasive tumors highly susceptible to immune surveillance, thereby enhancing tumor immune responsiveness and subsequently activating both innate and adaptive immunity. Here, we report a nanomedicine-based immunotherapeutic approach that targets the mitochondria in GBM cells by utilizing a Trojan-inspired nanovector (ABBPN) that can cross the blood-brain barrier. We propose that the synthetic photosensitizer IrPS can alter mitochondrial electron flow and concurrently interfere with mitochondrial antioxidative mechanisms by delivering si-OGG1 to GBM cells. Our synthesized ABBPN coloaded with IrPS and si-OGG1 (ISA) disrupts mitochondrial electron flow, which inhibits ATP production and induces mitochondrial DNA oxidation, thereby recruiting immune cells and endogenously activating intracranial antitumor immune responses. The results of our study indicate that strategies targeting the mitochondrial ETC have the potential to treat tumors with limited immunogenicity.

Percutaneous intramyocardial septal radiofrequency ablation after 5-year follow-up.

OBJECTIVE: The objective is to evaluate the 5-year follow-up results of percutaneous intramyocardial septal radiofrequency ablation (PIMSRA) for hypertrophic obstructive cardiomyopathy (HOCM), including clinical status, electrocardiographic and echocardiographic characteristics. METHODS: 27 patients (age: 44.3±15.5 years; 67% men, 33% women) with severely symptomatic HOCM who underwent PIMSRA from October 2016 to September 2017 were included. Their clinical status, resting and exercise stress echocardiography, electrocardiography and cardiac MRI (CMRI) after long-term follow-up were assessed. RESULTS: One patient died of intracerebral haemorrhage 1 year post procedurally. The New York Heart Association class, Canadian Cardiovascular Society class and exercise-induced syncopal attacks improved significantly in 26 patients (all p<0.01). Left ventricular (LV) outflow tract gradients revealed sustained reduction (resting: from 95.0 to 9.0 mm Hg, p<0.001; post exercise: from 130.5 to 21.0 mm Hg, p<0.001). The echocardiographic evaluation revealed decreased septal thickness, LV posterior wall thickness and left atrial (LA) diameter (all p<0.001). CMRI data revealed decrease in LV mass index and LA volume index and increase in LV end-diastolic volume index and stroke volume index between baseline and long-term follow-up (all p<0.05). The global longitudinal strain of LV improved from (-11.9%±3.7%) before the procedure to (-13.1%±3.9%) at the last check (p<0.001). Malignant ventricular arrhythmia and heart failure events were not observed. CONCLUSIONS: PIMSRA can effectively alleviate symptoms in patients with HOCM and improve their hemodynamics in the long term. TRIAL REGISTRATION NUMBER: NCT02888132.

Long-Chain Fluorescent Probe for Straightforward and Nondestructive Staining Mitochondria in Fixed Cells and Tissues.

Normally, small-molecule fluorescent probes dependent on the mitochondrial membrane potential (MMP) are invalid for fixed cells and tissues, which limits their clinical applications when the fixation of pathological specimens is imperative. Given that mitochondrial morphology is closely associated with disease, we developed a long-chain mitochondrial probe for fixed cells and tissues, DMPQ-12, by installing a C12-alkyl chain into the quinoline moiety. In fixed cells stained with DMPQ-12, filament mitochondria and folded cristae were observed with confocal and structural illumination microscopy, respectively. In titration test with three major phospholipids, DMPQ-12 exhibited a stronger binding force to mitochondria-exclusive cardiolipin, revealing its targeting mechanism. Moreover, mitochondrial morphological changes in the three lesion models were clearly visualized in fixed cells. Finally, by DMPQ-12, three kinds of mitochondria with different morphologies were observed in situ in fixed muscle tissues. This work breaks the conventional concept that organic fluorescent probes only stain mitochondria with normal membrane potentials and opens new avenues for comprehensive mitochondrial investigations in research and clinical settings.

"Two-Stage Rocket-Propelled" Strategy Boosting Theranostic Efficacy with Mitochondria-Specific Type I-II Photosensitizers.

Imaging-guided photodynamic therapy (PDT) holds great potential for tumor therapy. However, achieving the synergistic enhancement of the reactive oxygen species (ROS) generation efficiency and fluorescence emission of photosensitizers (PSs) remains a challenge, resulting in suboptimal image guidance and theranostic efficacy. The hypoxic tumor microenvironment also hinders the efficacy of PDT. Herein, we propose a "two-stage rocket-propelled" photosensitive system for tumor cell ablation. This system utilizes MitoS, a mitochondria-targeted PS, to ablate tumor cells. Importantly, MitoS can react with HClO to generate a more efficient PS, MitoSO, with a significantly improved fluorescence quantum yield. Both MitoS and MitoSO exhibit less O2-dependent type I ROS generation capability, inducing apoptosis and ferroptosis. In vivo PDT results confirm that this mitochondrial-specific type I-II cascade phototherapeutic strategy is a potent intervention for tumor downstaging. This study not only sheds light on the correlation between the PS structure and the ROS generation pathway but also proposes a novel and effective strategy for tumor downstaging intervention.

Aggregation-induced emission-active iridium (III)-based mitochondria-targeting nanoparticle for two-photon imaging-guided photodynamic therapy.

The efficacy of imaging-guided photodynamic therapy (PDT) is compromised by the attenuation of fluorescence and decline in reactive oxygen species (ROS) generation efficiency in the physiological environment of conventional photosensitizers, limited near-infrared (NIR) absorption, and high systemic cytotoxicity. This paper presents the synthesis of two cyclometalated Ir (III) complexes (Ir-thpy and Ir-ppy) by using a triphenylamine derivative (DPTPA) as the primary ligand and their encapsulation into an amphiphilic phospholipid to form nanoparticles (NPs). These complexes exhibit aggregation-induced emission features and remarkably enhanced ROS generation compared to Chlorin e6 (Ce6). Moreover, Ir-thpy NPs possess the unique ability to selectively target mitochondria, leading to depolarization of the mitochondrial membrane potential and ultimately triggering apoptosis. Notably, Ir-thpy NPs exhibit exceptional photocytotoxicity even towards cisplatin-resistant A549/DDP tumor cells. In vivo two-photon imaging verified the robust tumor-targeting efficacy of Ir-thpy NPs. The in vivo results unequivocally demonstrate that Ir-thpy NPs exhibit excellent tumor ablation along with remarkable biocompatibility. This study presents a promising approach for the development of multifunctional Ir-NPs for two-photon imaging-guided PDT and provides novel insights for potential clinical applications in oncology.

Validation of a one-step genomics-based molecular classifier for endometrial carcinoma in a large Chinese population.

OBJECTIVE: The aim of this study is to delineate the molecular classification features within Chinese endometrial cancer (EC) patients and to evaluate the concurrence between two widely employed methods for diagnosing EC molecular subtypes. METHODS: This retrospective observational cohort study encompassed 479 cases of EC for analysis. Utilizing next-generation sequencing (NGS) panels targeting POLE, TP53, and microsatellite instability (MSI) status, four subtypes [POLE ultramutated (POLE mut), MMR-deficient (MMRd), p53 abnormal (p53abn), and no specific molecular profile (NSMP)] were classified. Immunohistochemistry (IHC) was employed to ascertain the expression of p53 and MMR proteins. RESULTS: Among the 479 patients, the distribution of EC subtypes was as follows: 28 (5.85%) POLE mut, 67 (13.99%) MMRd, 60 (12.53%) p53abn, and 324 (67.64%) NSMP. When compared to published findings on EC subtypes in the Caucasian population, our real-world data on Chinese ECs revealed a notably higher proportion of NSMP/CNL (copy number low). The evaluation of MSI/MMR status through NGS-based and IHC-based methods displayed substantial concordance (Kappa = 0.91). Slight discordance between the two techniques in identifying p53 abnormalities (Kappa = 0.83) might stem from TP53 truncating mutations, cytoplasmic p53 expression, null TP53 mutants, and well-documented challenges in interpreting p53 IHC. CONCLUSIONS: Chinese ECs exhibit distinctive molecular attributes. For accurate molecular subtyping of Chinese ECs, additional molecular markers that align with the Chinese population's characteristics should be incorporated into existing classifiers. The study's outcomes underscore a strong agreement between NGS and IHC in TP53/p53 detection and MSI assessment.

The incidence of chronic diarrhea decreases with increasing serum calcium levels: a cross-sectional study based on NHANES 2005-2010.

BACKGROUND: Chronic diarrhea is difficult to prevent and treat due to its complex etiology and pathogenesis. It places a huge burden on patients and public healthcare. It is known that the regulation of body homeostasis relies heavily on calcium. However, in the general population, the relationship between calcium and chronic diarrhea remains uncertain. METHODS: We assessed the association between serum calcium and diarrhea using data from the 2005-2010 National Health and Nutrition Examination Survey (NHANES). Serum calcium level was measured from collected blood samples. Diarrhea was assessed using the Bristol Stool Scale (BSFS) (types 1-7). The stability of the results was assessed using logistic regression and sensitivity analysis. The dose-response association between serum calcium and the risk of diarrhea was analyzed using a restricted cubic spline plot. RESULTS: This study included 12,342 participants. In each of the five models, an increased calcium level was negatively associated with the incidence of diarrhea (OR[95%CI]:0.26 [0.13-0.53], 0.28 [0.14-0.58], 0.4 [0.19-0.82], 0.27 [0.11-0.64] and 0.24 [0.10-0.59], respectively). When serum calcium was analyzed as a categorical variable, a significant association between serum calcium and diarrhea prevalence was found. The restricted cubic spline plot showed a linear relationship between serum calcium and diarrhea. Sensitivity analysis confirmed that the results were stable. CONCLUSION: The results of our cross-sectional study suggest that a higher level of serum calcium may reduce the incidence of diarrhea. In the future, this finding should be further validated in a randomized controlled trial.

Mitochondrial nucleoid condensates drive peripheral fission through high membrane curvature.

Mitochondria are dynamic organelles that undergo fusion and fission events, in which the mitochondrial membrane and DNA (mtDNA) play critical roles. The spatiotemporal organization of mtDNA reflects and impacts mitochondrial dynamics. Herein, to study the detailed dynamics of mitochondrial membrane and mtDNA, we rationally develop a dual-color fluorescent probe, mtGLP, that could be used for simultaneously monitoring mitochondrial membrane and mtDNA dynamics via separate color outputs. By combining mtGLP with structured illumination microscopy to monitor mitochondrial dynamics, we discover the formation of nucleoid condensates in damaged mitochondria. We further reveal that nucleoid condensates promoted the peripheral fission of damaged mitochondria via asymmetric segregation. Through simulations, we find that the peripheral fission events occurred when the nucleoid condensates interacted with the highly curved membrane regions at the two ends of the mitochondria. Overall, we show that mitochondrial nucleoid condensates utilize peripheral fission to maintain mitochondrial homeostasis.

Reliability and validity of the Chinese version of the Early-Onset Scoliosis Self-Report Questionnaire in children aged 8 to 18 years with early-onset scoliosis.

Background: The Early-Onset Scoliosis Self-Report Questionnaire (EOSQ-SELF) is a novel self-report instrument to evaluate the health-related quality of life (HRQoL) of early onset scoliosis (EOS) patients, as a complementary HRQoL assessment tool for the proxy-repot 24-item Early-Onset Scoliosis Questionnaire (EOSQ-24). This study aimed to translate and adapt the EOSQ-SELF into a Chinese version and evaluate its reliability and validity in EOS patients. Methods: A cross-sectional study was performed from July 2022 to September 2022. Patients aged 8 to 18 years with EOS were recruited. Forwards-backwards translation and cross-cultural adaptation of the original EOSQ-SELF were performed. The Chinese EOSQ-SELF was administered and collected twice through social media, with a 2 weeks interval. Reliability was evaluated by using internal consistency, and test-retest reliability was assessed by the intraclass correlation coefficient (ICC) of data between the two time points. A Delphi survey in the expert committee was used to investigate the content validity. SRS-22r, PedsQL4.0, and EQ-5D-Y scales were used to assess the criterion-related validity. Nonparametric tests and multiple linear regression were performed to evaluate the discriminative ability. Results: A total of 101 valid responses from EOS patients were received. The mean age was 12.08±2.19 years, and 53.47% were female. The mean Cobb angle was 60.56°±19.48°. Floor effects of 0.00% to 7.92% and ceiling effects of 0.00% to 52.48% were observed. Excellent internal consistency and test-retest reliability of the Chinese EOSQ-SELF was observed, with a Cronbach's α coefficient of 0.942, McDonald's ω coefficient of 0.940, and ICC of 0.930. All domains of the Chinese EOSQ-SELF were significantly correlated with SRS-22r (0.709 to 0.878), PedsQL4.0 (0.568 to 0.718), and EQ-5D-Y (-0.598 to -0.625), depicting excellent criterion-related validity. Discriminative ability was validated in aetiology (P<0.001), severity of spinal deformity (P<0.001), treatment status (P<0.001), and ambulatory ability (P<0.001). Conclusions: The Chinese EOSQ-SELF is a reliable and valid tool for the assessment of self-report HRQoL in patients aged 8 to 18 years with EOS. It can be easily applied in clinical settings and for research purposes, as a complementary tool for the proxy-report EOSQ-24.

Jian-Pi-Yin decoction attenuates lactose-induced chronic diarrhea in rats by regulating GLP-1 and reducing NHE3 ubiquitination and phosphorylation.

Objectives: Jian-Pi-Yin decoction (JPY), a prescription derived from the traditional Chinese medicine Shen-Ling-Bai-Zhu-San, has shown good clinical efficacy in the treatment of diarrhea caused by lactose intolerance. However, the mechanism of action of JPY in the treatment of diarrhea is not fully understood. Design: In this study, a rat diarrhea model was induced by high lactose feeding combined with standing on a small platform to investigate the ameliorating effect of JPY on hyper lactose-induced diarrhea in rats and its possible mechanism. Methods: The rat model of hyper lactose diarrhea was given high, medium, and low doses of JPY and the positive control drug Smida by gavage for 1 week. At the same time, NA+-H+ exchanger 3 (NHE3) inhibitor Tenapanor was administered orally for 3 weeks. Body weight, food intake, water intake, grip strength, and severity of diarrhea symptoms were measured in rats throughout the study. The serum, colon, and jejunum tissues of the model and drug-treated rats were collected for histopathological examination and analysis of relevant indicators. Results: JPY significantly alleviated the symptoms of fatigue, diet reduction and diarrhea in the model group. Glucagon-like peptide-1 (GLP-1) and cyclic adenosine monophosphate (cAMP) expression were also down-regulated after JPY treatment. JPY can significantly promote NHE3 in intestinal tissues of rats with diarrhea, and the mechanism is related to the decrease of GLP-1, inhibition of cAMP/PKA pathway activation, an increase of ubiquitin-specific protease 7 (USP7) and USP10 expression, and decrease of NHE3 ubiquitination and phosphorylation. Conclusion: JPY can reduce the expression of GLP-1, reduce the ubiquitination and phosphorylation of NHE3, regulate the expression of NHE3, at least partly improve ion transport in the intestinal epithelium, and improve the imbalance of electrolyte absorption, thus significantly reducing the diarrhea symptoms of rats with high lactose combined with small platform standing. Innovation: In this study, we explored the mechanism of intestinal GLP-1 activation of cAMP/PKA signaling pathway from multiple dimensions, and increased its expression by reducing phosphorylation and ubiquitination of NHE3, thereby treating chronic diarrhea associated with lactose intolerance.

Effect of K­line on posterior cervical surgery versus anterior cervical surgery in patients with multi-level ossification of posterior longitudinal ligament.

PURPOSE: To evaluate the influence of K-line on the outcome of open-door laminoplasty versus anterior cervical corpectomy decompression and fusion (ACCF) for patients with more than two levels of ossification of the posterior longitudinal ligament (OPLL). METHODS: 60 patients undergoing open-door laminoplasty and 62 patients undergoing ACCF from January 2013 to January 2020 with more than 2 years of follow-up were included. Eighty-four cases with the ossification mass not beyond the K-line were grouped as K-line (+), while thirty-eight cases were grouped as K-line (-). The operation time, intraoperative blood loss, hospital stay, preoperative, postoperative, and last follow-up JOA scores, and postoperative complications were investigated. RESULTS: The improvement rate of JOA scores after posterior approaches in cases of group K-line (+) and K-line (-) was 72.4% and 53.1%, respectively, which showed a significant difference (P < 0.01). In group K-line (+), the improvement of JOA scores for open-door laminoplasty was 73.4% and 71.8% for ACCF, which showed no significant difference (P > 0.05). In group K-line (-), the improvement of JOA scores for ACCF was 52.1% and 42.9% for open-door laminoplasty, which showed a significant difference (P < 0.05). The incidence of C5 palsy was significantly lower in cases with ACCF than in cases with open-door laminoplasty (P < 0.05). CONCLUSION: For patients with more than two levels of OPLL, preoperative K-line (+) predicates a better outcome than K-line (-). For cases with K-line (-), ACCF provides better neurologic function recovery. For patients with K-line (+), open-door laminoplasty provides the same neurologic function recovery of ACCF.

A two-photon iridium(III) complex probe for sensitive detection of SO2 derivatives in living cell mitochondria.

The derivatives of sulfur dioxide (HSO3-) formed in the biological environment play a vital role in the circulation system. Excessive SO2 derivatives will cause serious damage to the living system. Herein, a two-photon phosphorescent probe based on Ir(III) complex (named as Ir-CN) was designed and synthesized. Ir-CN is extremely selective and sensitive to SO2 derivatives with significant phosphorescent enhancement and increased phosphorescent lifetime. The detection limit of Ir-CN for SO2 derivatives reaches 0.17 µM. More importantly, Ir-CN preferentially accumulates in mitochondria, so bisulfite derivatives can be detected at subcellular level, which enriching the application of metal complex probe in biological detection. In addition, both single-photon and two-photon images can clearly show that Ir-CN is targeted to mitochondria. Benefits from its good biocompatibility, Ir-CN may be used as a reliable tool to detect SO2 derivatives in mitochondrion of living cells.

Distal foundation augmentation enhances the "Bridge" role of single traditional growing rods in the treatment of severe early-onset scoliosis: a retrospective comparative cohort study.

Background: Dual traditional growing rod (dTGR) implantation may not always be feasible for patients with severe early-onset scoliosis (EOS). The concave single traditional growing rod (sTGR) can serve as a starting construct. Distal foundation augmentation (DFA) with four pedicle screws with a cross-link can increase the spinal control provided by a dTGR. However, DFA has yet to be used with a sTGR. This study investigated the efficiency of DFA in patients with severe EOS who underwent sTGR implantation. Methods: From 2010 to 2021, 74 consecutive patients with severe EOS (major curve ≥80°) who underwent traditional growing rod implantation (48 sTGR and 26 dTGR) with a minimum 24-month follow-up were recruited. The sTGR cohort was further divided into two groups by whether or not DFA was performed. In our center, patients who were admitted for sTGR implantation after 2018 routinely underwent DFA. The implantation of a dTGR was based on the severity of thoracic torsion and BMI. Baseline clinical characteristics, complications, and radiographic parameters preoperatively, postoperatively, and at the last follow-up before conversion to a dual rod instrumentation were compared between the three groups. Results: There was no significant difference in baseline clinical characteristics between the three groups (P>0.05). Twenty-four patients in the sTGR cohort underwent DFA. There was no significant difference in preoperative radiographic parameters between the DFA and non-DFA group (P>0.05). Compared with the non-DFA group, the DFA group had superior results at the last follow-up in terms of maintaining the correction of the major curve (P=0.001), maximal kyphosis correction (P=0.001), the distance between the C7 plumb line and the central sacral vertical line (P=0.036), and distracting the growing thorax (P=0.032) and trunk (P=0.044). Furthermore, the incidence of implant-related complications (P=0.019), especially at the distal foundation (P=0.033), was significantly lower in the DFA group. There was no significant difference between the DFA and dTGR groups in radiographic outcomes or complications at the final follow-up (P>0.05). Conclusions: For patients with severe EOS who undergo sTGR implantation, DFA might better maintain the deformity correction, distract the growing spine, preserve balance, and decrease the incidence of implant-related complications. The efficiency of sTGR with DFA was comparable to that of the gold-standard dTGR treatment. Further multicenter randomized controlled trials are needed for more convincing conclusions.

Long-Term Radiographic and Pulmonary Function Outcomes After Dual Growing-Rod Treatment for Severe Early-Onset Scoliosis.

BACKGROUND: We evaluated long-term outcomes (radiographic parameters and pulmonary function) at a minimum follow-up of 5 years after use of dual growing rods (DGRs) to treat severe early-onset scoliosis (sEOS). METHODS: Among a total of 112 patients who were diagnosed with early-onset scoliosis (EOS) and were treated with DGRs between 2006 and 2015, 52 patients had sEOS, with a major Cobb angle of >80°. Of these patients, 39 with a minimum follow-up of 5 years had complete radiographic and pulmonary function test results and were included. The Cobb angle of the major curve, T1-S1 height, T1-T12 height, and maximum kyphosis angle in the sagittal plane were measured on radiographs. Pulmonary function test results were collected in all patients before the initial operation (preoperatively), 12 months after the initial operation (postoperatively), and at the last follow-up. The changes in pulmonary function and complications during treatment were analyzed. RESULTS: The mean age of patients before the initial operation was 7.7 ± 1.2 years, and the mean follow-up period was 75.0 ± 14.1 months. The mean number of lengthenings was 4.5 ± 1.3, and the mean interval between lengthenings was 11.2 ± 2.1 months. The Cobb angle improved from 104.5° ± 18.2° preoperatively to 38.1° ± 10.1° after the initial surgical procedure (postoperatively) and 21.9° ± 8.6° at the final follow-up. The T1-S1 height increased from 25.1 ± 4.0 cm preoperatively to 32.4 ± 3.5 cm postoperatively and to 39.5 ± 4.0 cm at the final follow-up. However, no significant difference was detected between the increased pulmonary function parameters at 1 year and those before the operation (p > 0.05), except for residual volume, whereas pulmonary function parameters had significantly increased at the final follow-up (p < 0.05). During the treatment period, 17 complications occurred in 12 patients. CONCLUSIONS: DGRs are effective in treating sEOS in the long term. They allow longitudinal growth of the spine, and the correction of the spinal deformity can provide conditions that make improving pulmonary function possible in patients with sEOS. LEVEL OF EVIDENCE: Therapeutic Level IV . See Instructions for Authors for a complete description of levels of evidence.

Influence of preoperative simulation on the reduction quality and clinical outcomes of open reduction and internal fixation for complex proximal humerus fractures.

PURPOSE: Proximal humerus fractures (PHFs) are common. With the development of locking plates, open reduction and internal fixation (ORIF) of the proximal humerus can provide excellent clinical outcomes. The quality of fracture reduction is crucial in the locking plate fixation of proximal humeral fractures. The purpose of this study was to determine the impact of 3-dimensional (3D) printing technology and computer virtual technology assisted preoperative simulation on the reduction quality and clinical outcomes of 3-part and 4-part proximal humeral fractures. METHOD: A retrospective comparative analysis of 3-part and 4-part PHFs undergoing open reduction internal fixation was performed. Patients were divided into 2 groups according to whether computer virtual technology and 3D printed technology were used for preoperative simulation: the simulation group and the conventional group. Operative time, intraoperative bleeding, hospital stay, quality of fracture reduction, Constant scores, American Society for Shoulder and Elbow Surgery (ASES) scores, shoulder range of motion, complications, and revision surgeries were assessed. RESULTS: This study included 67 patients (58.3%) in the conventional group and 48 patients (41.7%) in the simulation group. The patient demographics and fracture characteristics were comparable in these groups. Compared with the conventional group, the simulation group had shorter operation time and less intraoperative bleeding (P < 0.001, both). Immediate postoperative assessment of fracture reduction showed a higher incidence of greater tuberosity cranialization of < 5 mm, neck-shaft angle of 120° to 150°, and head shaft displacement of < 5 mm in the simulation group. The incidence of good reduction was 2.6 times higher in the simulation group than in the conventional group (95% CI, 1.2-5.8). At the final follow-up, the chance of forward flexion > 120° (OR 5.8, 95% CI 1.8-18.0) and mean constant score of > 65 (OR 3.4, 95% CI 1.5-7.4) was higher in the simulation group than the conventional group, as well as a lower incidence of complications in the simulation group was obtained (OR 0.2, 95% CI 0.1-0.6). CONCLUSIONS: This study identified that preoperative simulation assisted by computer virtual technology and 3D printed technology can improve reduction quality and clinical outcomes in treatment of 3-part and 4-part PHFs.

Genomic and Transcriptomic Characterization Revealed the High Sensitivity of Targeted Therapy and Immunotherapy in a Subset of Endometrial Stromal Sarcoma.

PURPOSE: The unique chromosomal rearrangements of endometrial stromal sarcoma (ESS) make it possible to distinguish high-grade ESS (HGESS) and low-grade ESS (LGESS) from the molecular perspective. Analysis of ESS at the genomic and transcriptomic levels can help us achieve accurate diagnosis of ESS and provide potential therapy options for ESS patients. Materials and Methods: A total of 36 ESS patients who conducted DNA- and/or RNA-based next-generation sequencing were retrospectively enrolled in this study. The molecular characteristics of ESS at genomic and transcriptomic levels, including mutational spectrum, fusion profiles, gene expression and pathway enrichment analysis and features about immune microenvironment were comprehensively explored. RESULTS: TP53 and DNMT3A mutations were the most frequent mutations. The classical fusions frequently found in HGESS (ZC3H7B-BCOR and NUTM2B-YWHAE) and LGESS (JAZF1-SUZ12) were detected in our cohort. CCND1 was significantly up-regulated in HGESS, while the expression of GPER1 and PGR encoding estrogen receptor (ER) and progesterone receptor (PR) did not differ significantly between HGESS and LGESS. Actionable mutations enriched in homologous recombination repair, cell cycle, and phosphoinositide 3-kinase/AKT/mammalian target of rapamycin pathways were detected in 60% of HGESS patients. Genes with up-regulated expression in HGESS were significantly enriched in five immune-related pathways. Most HGESS patients (85.7%) had positive predictors of immunotherapy efficacy. Moreover, immune microenvironment analysis showed that HGESS had relatively high immune infiltration. The degree of immune infiltration in HGESS patients with ZC3H7B-BCOR fusion was relatively higher than that of those with NUTM2B-YWHAE fusion. CONCLUSION: This study investigated the molecular characteristics of ESS patients at the genomic and transcriptomic levels and revealed the potentially high sensitivity of targeted therapy and immunotherapy in a subset of HGESS with specific molecular features, providing a basis for guiding decision-making of treatment and the design of future clinical trials on precision therapy.