[Outcomes of total knee arthroplasty combined with the modified "overlap" technique in the treatment of knee osteoarthritis with permanent patellar dislocation].

Objective: To investigate the clinical outcomes of total knee arthroplasty (TKA) combined with the modified "overlap" technique in the treatment of end-stage knee osteoarthritis with fixed patellar dislocation. Methods: This is a retrospective case series study. Clinical data of 19 patients (22 knees) who underwent TKA combined with the modified "overlap" technique for the treatment of end-stage knee osteoarthritis with permanent patellar dislocation from January 2011 to January 2022 in the Department of Orthopaedics, the First Affiliated Hospital of Xinjiang Medical University were retrospectively analyzed. The cohort included 5 males (6 knees) and 14 females (16 knees), with an age of (60.6±12.2) years (range:33 to 77 years) and a body mass index of (25.4±4.1) kg/m² (range:20.0 to 33.0 kg/m²). Among them, 11 cases (12 knee) had valgus deformity, with Keblish classification showing mild in 2 cases (2 knees), moderate in 6 cases (6 knees), and severe in 4 cases (4 knees). All cases were treated using a medial parapatellar approach, with lateral retinaculum release combined with the "overlap" technique to restore the patellar trajectory. Knee function was evaluated using the American Knee Society (KSS) Score. Paired sample t-tests were used for intergroup comparisons. Results: All patients successfully completed the surgery. Postoperatively, patellar dislocation, knee valgus deformity, flexion contracture deformity, and extensor lag were all corrected. All patients were followed up, with a follow-up duration of (63.8±35.2) months (range:24 to 136 months). One patient experienced periprosthetic infection 2 weeks postoperatively, 1 patient had recurrent patellar dislocation 2 months postoperatively, 1 patient developed knee stiffness 3 months postoperatively and underwent closed manipulation. No other patients exhibited signs of patellar dislocation or subluxation. At the last follow-up, the KSS clinical score improved from (36.4±12.7) points preoperatively to (83.4±6.3)points postoperatively (t=-15.15, P<0.01), and the KSS functional score improved from (30.7±11.1)points preoperatively to (77.6±8.3)points postoperatively (t=-14.37, P<0.01). The range of motion of the knee increased from 81.7°±19.6° preoperatively to 107.6°±12.5° postoperatively (t=-4.85, P<0.01). Conclusion: TKA combined with the modified "overlap" technique is an effective surgical option for the treatment of end-stage knee osteoarthritis with permanent patellar dislocation, demonstrating satisfactory clinical outcomes.

Borrowed dislocations for ductility in ceramics.

The inherent brittleness of ceramics, primarily due to restricted atomic motions from rigid ionic or covalent bonded structures, is a persistent challenge. This characteristic hinders dislocation nucleation in ceramics, thereby impeding the enhancement of plasticity through a dislocation-engineering strategy commonly used in metals. Finding a strategy that continuously generates dislocations within ceramics may enhance plasticity. Here, we propose a "borrowing-dislocations" strategy that uses a tailored interfacial structure with well-ordered bonds. Such an approach enables ceramics to have greatly improved tensile ductility by mobilizing a considerable number of dislocations in ceramic borrowed from metal through the interface, thereby overcoming the challenge associated with direct dislocation nucleation within ceramics. This strategy provides a way to enhance tensile ductility in ceramics.

Global Burden of Dementia Death from 1990 to 2019, with Projections to 2050: An Analysis of 2019 Global Burden of Disease Study.

BACKGROUND: Dementia is a growing global health challenge. Quantifying the current burden and predicting the future increases of dementia-related deaths are necessary to enhance effective policy decisions and health system planning. METHODS: Data on dementia mortality was derived from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019 study. The 2020-2050 dementia-related deaths were forecasted using the Bayesian age-period-cohort model. RESULTS: Globally, the number of dementia-related death increased from 0.56 million in 1990 to 1.62 million in 2019 and were estimated to increase to 4.91 million by the year 2050. Metabolic risk factors would become the most important modifiable risk factors affecting dementia death which account for 28.10% of dementia related death by the year 2050. For different Socio-demographic Index (SDI) regions, the low SDI region would have the highest age-standardized mortality rate (ASMR) (29.16 per 100,000) by 2050. Moreover, the number of dementia-related deaths under the age of 70 years was predicted to reach 0.18 million by 2050. CONCLUSIONS: Dementia related death remains a global health problem, and health policies targeting metabolic risk factors may be an important way to alleviate this problem.

[Triglyceride-glucose index in non-obese individuals: its association with and predictive value for non-alcoholic fatty liver disease].

OBJECTIVE: To investigate the association of triglyceride-glucose index (TyG) with non-alcoholic fatty liver disease (NAFLD) and its diagnostic value for NAFLD in non-obese individuals. METHODS: We retrospectively collected the data of non-obese individuals (BMI < 25 kg/m2) undergoing routine health examination at Second Affiliated Hospital of Xi'an Jiaotong University between May, 2020 and December, 2023, who all received abdominal ultrasound examination for NAFLD screening. The nonlinear relationship between TyG and non-obese NAFLD was explored using restricted cubic splines (RCS), and LASSO regression was used for variable screening; the correlation between TyG and NAFLD risk was analyzed using multivariate logistic regression. The diagnostic value of TyG for non-obese NAFLD was assessed using receiver-operating characteristic (ROC) curves and sensitivity analysis. RESULTS: A total of 3723 non-obese subjects were enrolled in this study, including 432 (11.6%) patients with NAFLD. Compared with the healthy individuals, the patients with NAFLD had significant elevations of systolic and diastolic blood pressures, total cholesterol, triglycerides, LDL-C, blood uric acid, fasting blood glucose, and TyG index and a decreased HDL-C level (P < 0.05). Multivariate logistic regression revealed that for each one-unit increase of TyG, the risk of non-obese NAFLD increased by 2.2 folds (OR=3.22, 95% CI: 2.53-4.12, P < 0.001). Compared with a TyG index in the lowest quartile Q1, a TyG index in the Q2, Q3 and Q4 quartiles was associated with an increased risk of NAFLD by 1.52 folds (OR=2.52, 95% CI: 1.20-5.95), 3.56 folds (OR=4.56, 95% CI: 2.28-10.46), and 8.66-folds (OR=9.66, 95% CI: 4.83-22.18), respectively. The RCS curve demonstrated a significant linear correlation between TyG index and non-obese NALFD risk (P for nonlinear= 0.019). For diagnosing non-obese NALFD, TyG index had an area under ROC curve of 0.819 with a sensitivity of 78.0% and a specificity of 71.2%. CONCLUSION: An increase of TyG index is correlated with increased risks of NAFLD in non-obese individuals and can serve as an indicator for screening early NAFLD in healthy individuals.

[Establishment of a predictive nomogram for clinical pregnancy rate in patients with endometriosis undergoing fresh embryo transfer].

OBJECTIVE: To establish a nomogram model for predicting clinical pregnancy rate in patients with endometriosis undergoing fresh embryo transfer. METHODS: We retrospectively collected the data of 464 endometriosis patients undergoing fresh embryo transfer, who were randomly divided into a training dataset (60%) and a testing dataset (40%). Using univariate analysis, multiple logistic regression analysis, and LASSO regression analysis, we identified the factors associated with the fresh transplantation pregnancy rate in these patients and developed a nomogram model for predicting the clinical pregnancy rate following fresh embryo transfer. We employed an integrated learning approach that combined GBM, XGBOOST, and MLP algorithms for optimization of the model performance through parameter adjustments. RESULTS: The clinical pregnancy rate following fresh embryo transfer was significantly influenced by female age, Gn initiation dose, number of assisted reproduction cycles, and number of embryos transferred. The variables included in the LASSO model selection included female age, FSH levels, duration and initial dose of Gn usage, number of assisted reproduction cycles, retrieved oocytes, embryos transferred, endometrial thickness on HCG day, and progesterone level on HCG day. The nomogram demonstrated an accuracy of 0.642 (95% CI: 0.605-0.679) in the training dataset and 0.652 (95% CI: 0.600-0.704) in the validation dataset. The predictive ability of the model was further improved using ensemble learning methods and achieved predicative accuracies of 0.725 (95% CI: 0.680-0.770) in the training dataset and 0.718 (95% CI: 0.675-0.761) in the validation dataset. CONCLUSIONS: The established prediction model in this study can help in prediction of clinical pregnancy rates following fresh embryo transfer in patients with endometriosis.

Predicting the response to neoadjuvant chemoradiation for rectal cancer using nomograms based on MRI tumour regression grade.

PURPOSE: This study aimed to develop nomograms that combine clinical factors and MRI tumour regression grade to predict the pathological response of mid-low locally advanced rectal cancer to neoadjuvant chemoradiotherapy. METHODS: The retrospective study included 204 patients who underwent neoadjuvant chemoradiotherapy and surgery between January 2013 and December 2021. Based on pathological tumour regression grade, patients were categorized into four groups: complete pathological response (pCR, n=45), non-complete pathological response (non-pCR; n=159), good pathological response (pGR, n=119), and non-good pathological response (non-pGR, n=85). The patients were divided into a training set and a validation set in a 7:3 ratio. Based on the results of univariate and multivariate analyses in the training set, two nomograms were respectively constructed to predict complete and good pathological responses. Subsequently, these predictive models underwent validation in the independent validation set. The prognostic performances of the models were evaluated using the area under the curve (AUC). RESULTS: The nomogram predicting complete pathological response incorporates tumour length, post-treatment mesorectal fascia involvement, white blood cell count, and MRI tumour regression grade. It yielded an AUC of 0.787 in the training set and 0.716 in the validation set, surpassing the performance of the model relying solely on MRI tumour regression grade (AUCs of 0.649 and 0.530, respectively). Similarly, the nomogram predicting good pathological response includes the distance of the tumour's lower border from the anal verge, post-treatment mesorectal fascia involvement, platelet/lymphocyte ratio, and MRI tumour regression grade. It achieved an AUC of 0.754 in the training set and 0.719 in the validation set, outperforming the model using MRI tumour regression grade alone (AUCs of 0.629 and 0.638, respectively). CONCLUSIONS: Nomograms combining MRI tumour regression grade with clinical factors may be useful for predicting pathological response of mid-low locally advanced rectal cancer to neoadjuvant chemoradiotherapy. The proposed models could be applied in clinical practice after validation in large samples.

[Analysis of the efficacy and safety of preoperative programmed death protein-1 inhibitor combined with chemotherapy in immunotherapy-sensitive patients with locally advanced gastric cancer or adenocarcinoma of the esophagogastric junction].

Objective: To evaluate the short-term efficacy and safety of a preoperative combination of programmed cell death protein-1 (PD-1) inhibitor with either oxaliplatin + capecitabine (CapeOx) or oxaliplatin + tegafur gimeracil oteracil potassium (SOX) in the treatment of locally advanced immunotherapy-sensitive gastric cancer (LAGC) or adenocarcinoma of the esophagogastric junction (AEG). Methods: The cohort of this retrospective descriptive case series comprised patients with LAGC or AEG whose cancers had been determined to be immunotherapy- sensitive by endoscopic biopsy before treatment in the Gastrointestinal Cancer Center, Unit III, Peking University Cancer Hospital and Institute from 1 August 1 2021 to 31 January 2024. Patients with any one of the following three characteristics were immunotherapy-sensitive: (i) PD-L1 combined positive score (CPS) ≥5; (ii) microsatellite instability-high (MSI-H) / mismatch repair deficiency (dMMR); or (iii) Epstein-Barr virus-encoded RNA (EBER) positivity. All study patients received PD-1 inhibitors combined with CapeOx or SOX as a neoadjuvant or conversion treatment strategy before surgery. Patients with immune system diseases, distant metastases, or human epidermal growth factor receptor 2 positivity were excluded. Factors analyzed included pathological complete response, clinical complete response, major pathological response, R0 resection rate, surgical conversion rate, and safety of the treatment, including immune-related adverse events (irAEs) and surgical complications. Results: The study cohort comprised 39 patients (28 men and 11 women) of median age 62 (range 44-79) years. After the above-described preoperative treatment, radical resection of the 14 tumors that were initially considered unresectable was achieved (surgical conversion rate: 14/14). Twenty-three of the remaining 25 patients underwent radical resection. The last two patients achieved clinical complete responses and opted for a "non-surgical strategy" (watch and wait). Overall, 37 patients (94.9%) underwent radical resection, with an R0 resection rate of 100% (37/37), pathological complete response rate of 48.6% (18/37), and major pathological response rate of 62.2% (23/37). Of the 24 patients with CPS ≥ 5 (non-MSI-H/dMMR and non-EBER positive), 11 achieved pathological complete responses and one with CPS=95 achieved a clinical complete response. Of the eight patients with MSI-H/dMMR, six achieved pathological complete responses and one a clinical complete response. Of the seven patients with EBER positivity, one achieved a pathological complete response. After excluding patients with major pathological complete responses, there was a statistically significant difference in CPS scores between preoperative biopsy specimens and postoperative surgical specimens in 13 patients (7.769±5.570 vs. 15.538±16.870, t=2.287, P=0.041). All patients tolerated preoperative immunotherapy well; nine patients (9/39, 23.1%) had Grade I-II irAEs. There were no Grade III-IV irAEs. The five patients with pyloric obstruction before treatment tolerated normal diets after treatment. The incidence of postoperative complications among all patients who underwent surgery was 18.9% (7/37), including one case of Grade IIIA anastomotic leakage, one of Grade IIIA intestinal obstruction, one of Grade II abdominal hemorrhage, two of Grade II abdominal infection, one of Grade I intestinal obstruction. Additionally, one patient developed COVID-19 postoperatively. All patients recovered with symptomatic treatment. Conclusion: We found that preoperative treatment of patients with LAGC or AEG of one of three types (CPS≥5, dMMR+MSI-H, and EBER positivity) with a PD-1 inhibitor combined with CapeOx or SOX chemotherapy achieved promising effectiveness and safety, with high surgical conversion, R0 resection, and complete response rates.

[Deciphering the fate of granulation tissue in the human inflammatory alveolar microenvironment using single-cell RNA sequencing].

Objective: To investigate the cellular composition and heterogeneity of granulation tissue in human alveolar sockets and construct single-cell transcriptomic maps to elucidate the potential outcomes of natural resolution in the inflammatory microenvironment. Methods: Granulation tissues from 12 alveolar sockets undergoing tooth extraction due to periodontitis and scheduled for delayed site preservation or autologous tooth transplantation were collected in the Department of Oral and Maxillofacial Surgery, School of stomatology Fourth Military Medical University from September 2022 to August 2023. This study used HE staining and single-cell RNA sequencing (scRNA-seq) to observe the cellular composition and morphological changes of different types of granulation tissues. This approach enabled us to identify cellular sequence variations in the inflammatory dental alveolar granulation tissue within specific microenvironments, construct single-cell atlases for different types of human dental alveolar granulation tissues, and explore the spatiotemporal patterns of cell type distribution and key gene changes during the resolution process of inflammatory granulation tissue. Results: HE staining revealed extensive infiltration of inflammatory cells in the dental alveolar inflammatory granulation tissue. After allowing the inflammatory granulation tissue to naturally resolve for three weeks, its histological morphology was essentially consistent with that of reparative granulation tissue. ScRNA-seq captured a total of 20 448 cells from granulation tissues, and the gene expression quantification analysis revealed total gene counts of 33 835 for inflammatory granulation tissue, 36 058 for naturally resolved granulation tissue, and 34 719 for reparative granulation tissue. At the single-cell level, granulation tissue was annotated into ten cell subgroups, including vascular endothelial cells, mesenchymal stem cells, and fibroblasts. Differences were observed in the proportion of cell compositions between inflammatory and naturally resolved granulation tissues. Pseudo-temporal analysis illustrated two main outcomes in tissue resolution and healing, involving immune responses and angiogenesis. Among these, genes associated with inflammation regulation and immune response, such as Igbp5, Zfp36, and Hspa1b, as well as genes involved in extracellular matrix secretion and the formation of vessels and fibers such as Timp3, Postn, and Rgs5, showed significant differences in expression between the two types of granulation tissues. Conclusions: Inflammatory granulation tissue exhibits heterogeneity in cell composition, gene expression, and biological functions compared to naturally resolved granulation tissue. When the inflammatory granulation tissue in the alveolar socket is left undisturbed to undergo natural resolution, it displays a cellular composition similar to that of reparative granulation tissue at both the histological and single-cell levels. Moreover, it modulates the inflammatory response and the healing process through immune reactions and tissue remodeling.

Pitavastatin ameliorates myocardial injury by inhibiting myocardial inflammation and oxidative stress by modulating the microRNA-106B-5p/mitogen-activated protein kinase kinase kinase 2 axis.

Myocarditis (MC) is a myocardial inflammatory disease that threats human life. Pitavastatin (Pit) is a unique lipophilic statin with potent effects on lowering plasma total cholesterol and triacylglycerols. It has been reported to have pleiotropic effects, such as reducing inflammation and oxidative stress. However, the regulatory mechanism of Pit in MC remains a mystery. Two MC models were established in vitro (lipopolysaccharides-(LPS)-stimulated H9c2 cells) and in vivo (intraperitoneal injection of LPS in mice). The levels of microRNA-106b-5p (miR-106b-5p) and mitogen-activated protein kinase kinase kinase 2 (MAP3K2) were detected. ELISA was used to analyze in vivo cell inflammatory factors and myocardial injury markers, kits were used to detect the expression of antioxidant enzymes, cell counting kit-8 (CCK-8) was used to detect cell proliferation, and flow cytometry was used to detect apoptosis. Hematoxylin and eosin (HE) staining was used to detect the pathological changes of myocardial tissue in mice, and TUNEL staining was used to detect in vivo tissue cell apoptosis. The regulatory mechanism of Pit on miR-106b-5p/MAP3K2 was verified by a series of functional rescue experiments. The results demonstrated that in LPS-induced H9c2 cells, antioxidant enzymes decreased and pro-inflammatory factors and cardiac injury markers increased (p<0.05). However, these phenomenons were attenuated by Pit pretreatment. LPS decreased miR-106b-5p and elevated MAP3K2 in H9c2 cells, while Pit could recover their expression patterns (p<0.05). MAP3K2 was confirmed as a target gene of miR-106b-5p. Upregulating miR-106b-5p or downregulating MAP3K2 could further promote the protective effect of Pit, and vice versa (p<0.05). In addition, in the LPS-induced MC mouse model, histological examination showed that Pit significantly improved the myocardial tissue damage in MC mice, while downregulating miR-106b-5p or upregulating MAP3K2 could suppress the ameliorative effect of Pit (p<0.05). In conclusion, our study demonstrated that Pit ameliorates myocardial injury by suppressing myocardial inflammation and oxidative stress by modulating the miR-106b-5p/MAP3K2 axis.

[Role of intercellular adhesion molecule-1 in adhesion and migration of mesenchymal stem cells in ankylosing spondylitis and its mechanisms].

Objective: To investigate the role and underlying mechanisms of intercellular adhesion molecule-1 (ICAM-1) in the adhesion and migration of mesenchymal stem cells (MSCs) in patients with ankylosing spondylitis (AS). Methods: Bone marrow and ligament tissues were collected during surgery from patients with AS and thoracolumbar fractures (as controls, HC) treated from October 2021 to October 2022 at Nanjing University Medical School Affiliated Nanjing Drum Tower Hospital. MSCs were isolated and cultured from the bone marrow using the Ficoll separation method. Cell morphology was observed under high-resolution microscopy, and differences in the cytoskeletal features between AS-and HC-MSCs were analyzed through immunofluorescence staining. The expression of ICAM-1 was quantified in both groups using real-time quantitative polymerase chain reaction (RT-qPCR) and flow cytometry. Transwell migration assays and wound healing experiments were conducted to evaluate the differences in migration rates between the two groups of MSCs. Results: The interspinous ligament and bone marrow was acquired in AS (2 males and 1 female; 33, 37, 32 years old, respectively) and no-AS patients (2 males and 1 female; 35, 32, 38 years old, respectively). AS-MSCs exhibited broader cell morphology compared to HC-MSCs under bright field and fluorescence microscopy. Immunofluorescence staining of the interspinous ligament showed higher expression of ICAM-1 (68.38±3.42 vs 48.31±2.43) and CD105 (37.97±2.16 vs 23.36±2.06) in AS patients (both P<0.001). Western blot and RT-qPCR analysis revealed significantly stronger protein expression and transcription levels of ICAM-1 in AS-MSCs when compared to those in HC-MSCs (both P<0.001). Flow cytometry confirmed greater mean fluorescence intensity of ICAM-1 in AS-MSCs than in that in HC-MSCs (924.30±54.99 vs 636.47±40.03, P=0.002). Regarding cell adhesion efficiency, it showed no significant difference between AS-MSCs and HC-MSCs in the early stage of adhesion (0.5 h: 1 496±213 vs 1 205±163, P=0.133), but they were all significantly higher in AS-MSCs in the later stage (1 h: 2 894±172 vs 1 908±155, P=0.002; 2 h: 4 540±286 vs 3 334±188, P=0.004; 3 h: 5 212±281 vs 4 208±303, P=0.014). Finally, cell migration experiments demonstrated a stronger migration capability of AS-MSCs compared to HC-MSCs (5 449±172 vs 4 016±155, P<0.001), and the inhibition efficiency of A-205804 on the migration rate of AS-MSCs was stronger than that on HC-MSCs (2 145±239 vs 3 539±316, P=0.004). Conclusions: The aberrant expression of ICAM-1 markedly influences the adhesion and migration dynamics of MSCs. Elevated ICAM-1 levels in MSCs derives from patients with AS significantly enhance their migratory capabilities.

Age-related T1 mapping, fat fraction, diffusion and perfusion parameters of the lumbar vertebrae in healthy children under 3.0 T MRI.

AIM: Compare the T1 mapping, fat fraction, diffusion and perfusion parameters of the lumbar vertebrae of different age groups to establish normal values for healthy children and observe the trends in these parameters with age. MATERIALS AND METHODS: A total of 146 healthy children (0-14 years) were included in this prospective study and underwent 3.0 T lumbar MRI examination. The study cohort was divided into five age groups (Group A âˆ¼ E) according to development milestones in children. T1 mapping, Dixon and IVIM (intravoxel incoherent motion)sequence images were used to measure the parameters of lumbar vertebrae 2-4. RESULTS: The normal values of each parameter were measured and compared across different age groups. The T1 value was negatively correlated with age (r=-0.619, p<0.001). The fat fraction (FF%) was positively correlated with age (r=0.635, p<0.001). There was a negative correlation between the D value and age (r=-0.406, p<0.001). The D∗ value was positively correlated with age (r=0.54, p<0.001). The f value was positively correlated with age (r=0.775, p<0.001). The inflexion points of the T1 value and FF% curves were at approximately 3 years old (36 months).The inflexion points of the IVIM-related parameter curves were approximately 5 years old (60 months). CONCLUSION: The age-dependent differences in the vertebral body parameters of this pediatric cohort suggest changes in the bone marrow composition and cellular structure of the vertebral body during physiological growth in children. The establishment of normal values of children's lumbar spine can facilitate the clinical study of diseases.

[Isolation and characterization of normal mandibular periosteal stem cells from human and macaca mulatta and cross-species single-cell analysis].

Objective: To investigate the presence of a distinct stem cell populations different from mesenchymal stem cells in the mandibular periosteum of both human and non-human primates (macaca mulatta), to explore its properties during intramembranous osteogenesis and to establish standard protocols for the isolation, culturing and expanding of mandibular periosteal stem cells (PSC) distinguished from other PSCs in other anatomical regions. Methods: Periosteum was harvested from the bone surface during flap bone removal in patients aged 18-24 years undergoing third molar extraction and from the buccal side of the mandibular premolar region of 6-year-old macaca mulatta respectively, and then subjected to single-cell sequencing using the Illumina platform Novaseq 6000 sequencer. Cross-species single-cell transcriptome sequencing results were compared using homologous gene matching. PSC were isolated from primary tissues using two digestion methods with body temperature and low temperature, and their surface markers (CD200, CD31, CD45 and CD90) were identified by cell flow cytometry. The ability of cell proliferation and three-lineage differentiation of PSC expanded to the third generation in vitro in different species were evaluated. Finally, the similarities and differences in osteogenic properties of PSC and bone marrow mesenchymal stem cells (BMSC) were compared. Results: The single-cell sequencing results indicated that 18 clusters of cell populations were identified after homologous gene matching for dimensionality reduction, and manual cellular annotation was conducted for each cluster based on cell marker databases. The comparison of different digestion protocols proved that the low-temperature overnight digestion protocol can stably isolate PSC from the human and m. mulatta mandibular periosteum and the cells exhibited a fibroblast-like morphology. This research confirmed that PSC of human and m. mulatta had similar proliferation capabilities through the cell counting kit-8 assay. Flow cytometry analysis was then used to identify the cells isolated from the periosteum expressed CD200(+), CD31(-), CD45(-), CD90(-). Then, human and m. mulatta PSC were induced into osteogenesis, adipogenesis, and chondrogenesis to demonstrate their corresponding multi-lineage differentiation capabilities. Finally, comparison with BMSC further clarified the oesteogenesis characteristics of PSC. The above experiments proved that the cells isolated from the periosteum were peiosteal cells with characteristics of stem cells evidenced by their cell morphology, proliferation ability, surface markers, and differentiation ability, and that this group of PSC possessed characteristics different from traditional mesenchymal stem cells. Conclusions: In this study, normal mandibular PSC from humans and m. mulatta were stably isolated and identified for the first time, providing a cellular foundation for investigating the mechanism of mandibular intramembranous osteogenesis, exploring ideal non-human primate models and establishing innovative strategies for clinically mandibular injury repair.

[Analysis of 10 cases of brentuximab vedotin combined with chemotherapy in the treatment of children with refractory and or relapsed classic Hodgkin lymphoma].

Objective: To evaluate the efficacy and safety of CD30 antibody-drug conjugates (ADC) brentuximab vedotin (BV) combined with chemotherapy in children with refractory or relapsed classic Hodgkin's lymphoma (R/R cHL). Methods: Clinical data (including age, gender, B symptoms, clinical stage, previous treatment, etc.) of the 10 R/R cHL children diagnosed and treated at Beijing Children's Hospital Affiliated to Capital Medical University from October 2021 to August 2023 were analyzed retrospectively. According to the different intensity of chemotherapy drugs, the dose of BV applied in the same course of treatment was 1.8 mg/kg for BV applied once every 3 weeks, and 1.2 mg/kg for BV applied once every 2 weeks. All 10 patients received at least 2 cycles of BV combined with chemotherapy and were evaluated every 2 cycles. The patients were followed up until May 31, 2024. The infusion reactions and adverse reactions after treatment were recorded. Results: In all 10 patients, there were 7 males and 3 females, the age ranged from 5.3-16.9 years, and there were 6 cases of refractory and 4 cases of relapsed. There were 6 cases of nodular sclerosis type, 2 cases of mixed cell type, 1 case of lymphocyte-rich type, and 1 case of lymphodepletion type. There were 5 cases of stage Ⅳ and 5 cases of stage Ⅲ. Previous treatment was mainly chemotherapy, 4 cases received radiotherapy and 1 case received programmed cell death protein 1 (PD-1) antibody therapy. The follow-up time ranged from 9 to 27 months. A total of 43 courses with 49 doses of BV alone or combined with chemotherapy were recorded, and the number of courses was 2 to 10 times. All 10 children responded to the treatment, and 9 achieved complete remission. BV infusion was successfully completed in all cases. A total of 28 cases of grade 3 or above adverse events were recorded, mainly myelosuppression, all of which were related to chemotherapy and did not affect sequential treatment. Conclusion: Brentuximab vedotin has demonstrated efficacy and a tolerable safety profile in the treatment of refractory and relapsed CD30-positive Hodgkin's lymphoma in children.

[Analysis of one-year outcomes after cochlear implantation in adults with single-sided deafness].

Objectives: To investigate the outcomes of cochlear implantation in Mandarin-speaking cochlear implant (CI) users with single-sided deafness (SSD). Methods: This study was a single-center prospective cohort study. Eleven Mandarin-speaking adult SSD patients who underwent CI implantation at Capital Medical University Beijing Tongren Hospital from August 2020 to October 2021 were recruited, including 6 males and 5 females, with the age ranging from 24 to 50 years old. In a sound field with 7 loudspeakers distributed at 180°, we measured root-mean-square error(RMSE)in SSD patients at the preoperative, 1-month, 3-month, 6-month, and 12-month after switch-on to assess the improvement of sound source localization. The Mandarin Speech Perception (MSP) was used in the sound field to test the speech reception threshold (SRT) of SSD patients under different signal-to-noise locations in a steady-state noise under conditions of CI off and CI on, to reflect the head shadow effect(SSSDNNH), binaural summation effect(S0N0) and squelch effect(S0NSSD). The Tinnitus Handicap Inventory (THI) and the Visual Analogue Scale (VAS) were used to assess changes in tinnitus severity and tinnitus loudness in SSD patients at each time point. The Speech, Spatial and Qualities of Hearing Scale(SSQ) and the Nijmegen Cochlear Implantation Scale (NCIQ) were used to assess the subjective benefits of spatial speech perception and quality of life in SSD patients after cochlear implantation. SPSS 19.0 software was used for statistical analysis. Results: SSD patients showed a significant improvement in the poorer ear in hearing thresholds with CI-on compared with CI-off; The ability to localize the sound source was significantly improved, with statistically significant differences in RMSE at each follow-up time compared with the preoperative period (P<0.05). In the SSSDNNH condition, which reflects the head shadow effect, the SRT in binaural hearing was significantly improved by 6.5 dB compared with unaided condition, and the difference was statistically significant (t=6.25, P=0.001). However, there was no significant improvement in SRT between the binaural hearing condition and unaided conditions in the S0N0 and S0NSSD conditions (P>0.05). The total score of THI and three dimensions were significant decreased (P<0.05). Tinnitus VAS scores were significantly lower in binaural hearing compared to the unaided condition (P<0.001). The total score of SSQ, and the scores of speech and spatial dimensions were significant improved in binaural hearing compared to the unaided condition (P<0.001). There was no statistical difference in NCIQ questionnaire scores between preoperative and postoperative (P>0.05), and only the self-efficacy subscore showed a significant increase(Z=-2.497,P=0.013). Conclusion: CI could help Mandarin-speaking SSD patients restore binaural hearing to some extent, improve sound localization and speech recognition in noise. In addition, CI in SSD patients could suppress tinnitus, reduce the loudness of tinnitus, and improve subjective perceptions of spatial hearing and quality of life.

[Analysis of risk factors and construction of nomogram model for local lymph node metastasis in salivary gland mucoepidermoid carcinoma].

Objective: To analyze the risk factors affecting regional lymph node metastasis in salivary gland mucoepidermoid carcinoma (MEC) and to establish a nomogram model for individually predicting lymph node metastasis in salivary gland MEC. Methods: The clinical data of 2 152 patients with salivary gland MEC from 1975 to 2020 were collected from the Surveillance, Epidemiology, and End Results (SEER) database of the National Cancer Institute. The collected data were divided into training cohort (1 506 cases) and validation cohort (646 cases) according to the ratio of 7∶3. Single-factor regression and multi-factor logistic regression were used to screen factors related to local lymph node metastasis in salivary gland MEC, with constructing of a nomogram. Calibration curve, receiver operating characteristic (ROC) curve, area under the ROC curve (AUC) and decision curve analysis were used to evaluate model performance in the validation cohort and the total cohort. Statistical tests were performed using SPSS (26.0) and R (4.3.0) software. Results: Multivariate logistic regression results showed that M stage [OR(95%CI):12.360(3.295-46.365), P=0.014], pathological grade Ⅱ、Ⅲ、Ⅳ[OR(95%CI): 1.956(1.329-2.879), 9.654(6.309-14.772), 9.298(6.072-14.238), P<0.001], T staging T2, T3, T4[OR(95%CI): 1.706(0.932-3.124), 3.021(1.790-5.096), 3.311(1.925-5.695), P<0.001], and gender [OR(95%CI):0.759(0.593-0.972), P=0.029] were independent factors affecting local lymph node metastasis in salivary gland MEC. Through verification in the validation cohort and the total cohort, the AUC values were greater than 0.8, and the calibration curve was close to the perfect reference line, proving that the constructed nomogram model had good specificity and sensitivity for predicting local lymph node metastasis in salivary gland MEC. Conclusion: M stage, pathological grade, T stage, and gender are risk factors for predicting regional lymph node metastasis and the established-nomogram has good predictive performance for local lymph node metastasis in salivary gland MEC.

[Efficacy of venetoclax-based induction regimen in newly diagnosed pediatric acute myeloid leukemia].

Objective: To explore the efficacy of venetoclax-based induction regimen for children with newly diagnosed acute myeloid leukemia (AML). Methods: Children with newly diagnosed AML in Beijing Children's Hospital Affiliated to Capital Medical University and Baoding Hospital Affliliated to Capital Medical University from November 2019 and December 2023 were prospectively included. The patients were divided into DAH group (daunorubicin, cytarabine and homoharringtonine) and VAH group (venetoclax, cytarabine and homoharringtonine) according to induction regimen. The clinical data of the children were collected, the clinical characteristics and induced remission rate between the two groups were compared, and multivariate logistic regression was used to analyze the related factors affecting the induced remission rate. Results: A total of 135 patients were enrolled, including 96 cases in the DAH group (54 males and 42 females), aged [M (Q1, Q3)] 6.4 (3.9, 11.6) years and 39 cases in the VAH group (26 males and 13 females), aged 8.0 (6.2, 13.2) years. Among patients initially diagnosed with low-medium risk AML, the morphologic complete remission rates were 94.7% (18/19) in the VAH group and 84.4% (38/45) in the DAH group, respectively, and the negativity conversion rates of minirnal residual disease (MRD) were 57.9% (11/19) and 46.7% (21/45), respectively, with no statistically difference (all P>0.05). Among patients initially diagnoised with high-risk AML, the morphologic complete remission rates in the VAH group was higher than that in the DAH group [95.0% (19/20) vs 70.6% (36/51), P=0.027], and negativity conversion rates of MRD were 45.0% (9/20) and 33.3% (17/51), respectively, with no statistically difference (P=0.359). The induction regimen (venetoclax, cytarabine and homoharringtonin) was beneficial to morphological remission (OR=0.126, 95%CI: 0.025-0.629). FLT3 mutation was not conducive to morphological remission (OR=5.832, 95%CI: 1.778-19.124) and negative MRD (OR=4.166, 95%CI: 1.396-12.433). Conclusion: Venetoclax-based induction regimen is more effective than traditional chemotherapy regimen for newly diagnosed pediatric AML.

Intrapatient variation in PD-L1 expression and tumor mutational burden and the impact on outcomes to immune checkpoint inhibitor therapy in patients with non-small cell lung cancer.

BACKGROUND: PD-L1 tumor proportion score (TPS) and tumor mutational burden (TMB) are key predictive biomarkers for immune checkpoint inhibitors (ICI) efficacy in non-small cell lung cancer (NSCLC). Data on their variation across multiple samples are limited. METHODS: Patients with NSCLC and multiple PD-L1 TPS and/or TMB assessments were included. Clinicopathologic and genomic data were analyzed according to PD-L1 and TMB variation. RESULTS: In total, 402 PD-L1 sample pairs and 413 TMB sample pairs were included. Concordance between pairs was moderate for PD-L1 (ρ=0.53, P<0.0001) and high for TMB (ρ=0.80, P<0.0001). Shorter time between biopsies correlated with higher concordance in PD-L1, but not in TMB. Major increases (ΔTPS≥+50%) and decreases (ΔTPS≤-50%) in PD-L1 were observed in 9.7% and 8.0% of cases, respectively. PD-L1, but not TMB, decreased with intervening ICI (P=0.02). Acquired copy number loss of CD274, PDCD1LG2, and JAK2 were associated with major decrease in PD-L1 (q<0.05). Among patients with multiple PD-L1 assessments before ICI, cases where all samples had a PD-L1 ≥1%, compared to cases with at least one sample with PD-L1 <1% and another with PD-L1 ≥1%, achieved improved objective response rate and progression-free survival (PFS). Among patients with at least one PD-L1 <1% and one ≥1% before ICI, cases where the most proximal sample was PD-L1 ≥1% had longer median PFS compared to cases where the most proximal PD-L1 was <1%. Among patients with multiple TMB assessments before ICI, patients with a TMB ≥10 mut/Mb based on the most recent assessment, as compared to those with a TMB <10 mut/Mb, achieved improved PFS and OS to ICI; instead, no differences were observed when patients were categorized using the oldest TMB assessment. CONCLUSION: Despite intrapatient concordance in PD-L1 and TMB, variation in these biomarkers can influence ICI outcomes, warranting consideration for reassessment prior to ICI initiation when feasible.

[Venetoclax combined with dose-reduced HAD as induction treatment for patients with de-novo acute myeloid leukemia].

The efficacy and safety of venetoclax combined with reduced dose HAD regimen in the treatment of newly diagnosed acute myeloid leukemia (AML) was investigated. From May 2022 to January 2023, a total of 25 patients with newly diagnosed AML were treated with venetoclax combined with reduced-dose HAD regimen as induction therapy. Accoding to the 2017 ELN recommendations, 13 (52.0%) in favoable, 3 (12.0%) in intemediate, and 9 (36.0%) in adverse. The ORR (CR rate+PR rate) was 88.0%, and the CR rate was 84.0%. By May 30, 2023, with a median follow-up of 9 months, 1 year overall survival, event-free survival, and relapse-free survival were 100%, 94.7%, and 94.7%, respectively. All patients received 1-5 cycles of consolidation therapy and two median cycles. Treatment with venetoclax and reduced dose of HAD regimen in the treatment of patients with newly diagnosed AML was high effective and safe.

[Analysis of risk factors for venous thromboembolism in patients with polycythemia vera and establishment of a prediction model].

Objective: To investigate the risk factors of venous thrombosis in patients with polycythemia vera (PV) and establish a prediction model for venous thrombosis. Methods: PV patients with JAK2V617F gene mutation positive in the Second Hospital of Tianjin Medical University from September 2017 to November 2023 were retrospectively included. The patients were divided into groups according to whether they had venous thrombosis. After matching age and gender factors with propensity scores, 102 patients were included in the venous thrombosis group [46 males, 56 females, with a median age M (Q1, Q3) of 52 (44, 60) years] and 204 cases were included in the group without venous thrombosis [92 males, 112 females, with a median age of 52 (44, 59) years]. The clinical and laboratory characteristics, disease progression and incidence of gene mutation were compared between the two groups. The follow-up cohort ended on November 20, 2023, with a median follow-up [M (Q1, Q3)] of 11 (1, 53) years. Multivariate Cox risk model was used to analyze the influencing factors of venous thrombosis in PV patients, and establish a scoring system for the venous thrombosis risk factor prediction model of PV patients. Receiver operating characteristic (ROC) curve was used to evaluate the predictive efficiency of the model. Results: Hemoglobin concentration, the ratio of hematopoietic volume≥55%, neutrophil to lymphocyte ratio≥5, hypertension, subcostal spleen≥5 cm and secondary myelofibrosis in venous thrombosis group were higher than those in non-venous thrombosis group (all P<0.05). In addition, the proportion of history of thromboembolism, V617F gene mutation load (V617F%)≥50%, diabetes mellitus, ASXL1 mutation and secondary reticular silver staining≥3 in the venous thrombosis group were higher than those in the non-venous thrombosis group (all P<0.05). The proportion of PV patients with 3 or more gene mutations was 44.1% (45/102) in venous thrombosis group, which was higher than that of PV patients without venous thrombosis 29.9% (61/204) (P=0.014). The proportion of ASXL1 gene mutation in venous thrombosis group was 17.6% (18/102), which was higher than the 4.9% (10/204) in non-venous thrombosis group (P<0.001). Multivariate Cox risk model analysis showed that previous thromboembolism history (HR=2.031, 95%CI: 1.297-3.179, P=0.002), V617F%≥50% (HR=2.141, 95%CI: 1.370-3.347, P=0.001), ASXL1 mutation (HR=4.632, 95%CI: 1.497-14.336, P=0.008), spleen subcostal≥5 cm (HR=1.771, 95%CI: 1.047-2.996, P=0.033) are the risk factors of venous thrombosis in PV patients. According to HR values, a score system for predicting risk of venous thrombosis in PV patients was established: previous history of thromboembolism, V617F%≥50% and spleen subcostoal≥5 cm were assigned 1 point respectively, and ASXL1 mutation was assigned 2 points. Low risk group: score 0, medium risk group: score 1-2, high risk group: score≥3. The ROC curve analysis of the model for predicting venous thrombosis in PV patients showed that the area under the curve (AUC) was 0.807 (95%CI: 0.755-0.860), with the sensitivity of 88.2% and the specificity of 59.8% when the Youden index was 0.48. Conclusions: Previous thromboembolism history, V617F%≥50%, ASXL1 mutation, spleen subcostoal≥5 cm are risk factors of venous thrombosis in PV patients. The established prediction model has good prediction efficiency.