Objective: To investigate the efficacy of magnesium-strontium co-doped hydroxyapatite mineralized collagen (MSHA/Col) in improving the bone repair microenvironment and enhancing bone regeneration capacity, providing a strategy to address the insufficient biomimetic composition and limited bioactivity of traditional hydroxyapatite mineralized collagen (HA/Col) scaffolds. Methods: A high-molecular-weight polyacrylic acid-stabilized amorphous calcium magnesium strontium phosphate precursor (HPAA/ACMSP) was prepared. Its morphology and elemental distribution were characterized by high-resolution transmission electron microscopy (TEM) and energy-dispersive spectroscopy. Recombinant collagen sponge blocks were immersed in the HPAA/ACMSP mineralization solution. Magnesium-strontium co-doped hydroxyapatite was induced to deposit within collagen fibers (experimental group: MSHA/Col; control group: HA/Col). The morphological characteristics of MSHA/Col were observed using scanning electron microscopy (SEM). Its crystal structure and chemical composition were analyzed by X-ray diffraction and Fourier transform infrared spectroscopy, respectively. The mineral phase content was evaluated by thermogravimetric analysis. The scaffold's porosity, ion release, and in vitro degradation performance were also determined. For cytological experiments, CCK-8 assay, live/dead cell staining, alkaline phosphatase staining, alizarin red S staining, RT-qPCR, and western blotting were used to evaluate the effects of the MSHA/Col scaffold on the proliferation, viability, early osteogenic differentiation activity, late mineralization capacity, and gene and protein expression levels of key osteogenic markers [runt-related transcription factor 2 (Runx2), collagen type Ⅰ (Col-Ⅰ), osteopontin (Opn), and osteocalcin (Ocn)] in mouse embryonic osteoblast precursor cells (MC3T3-E1). Results: HPAA/ACMSP appeared as amorphous spherical nanoparticles under TEM, with energy spectrum analysis showing uniform distribution of carbon, oxygen, calcium, phosphorus, magnesium, and strontium elements. SEM results of MSHA/Col indicated successful complete intrafibrillar mineralization. Elemental analysis showed the mass fractions of magnesium and strontium were 0.72% (matching the magnesium content in natural bone) and 2.89%, respectively. X-ray diffraction revealed characteristic peaks of hydroxyapatite crystals (25.86°, 31°-34°). Infrared spectroscopy results showed characteristic absorption peaks for both collagen and hydroxyapatite. Thermogravimetric analysis indicated a mineral phase content of 78.29% in the material. The scaffold porosity was 91.6% ± 1.1%, close to the level of natural bone tissue. Ion release curves demonstrated sustained release behavior for both magnesium and strontium ions. The in vitro degradation rate matched the ingrowth rate of new bone tissue. Cytological experiments showed that MSHA/Col significantly promoted MC3T3-E1 cell proliferation (130% increase in activity at 72 h, P < 0.001). MSHA/Col exhibited excellent efficacy in promoting osteogenic differentiation, significantly upregulating the expression of osteogenesis-related genes and proteins (Runx2, Col-Ⅰ, Opn, Ocn) (P < 0.01). Conclusion The MSHA/Col scaffold achieves dual biomimicry of natural bone in both composition and structure, and effectively promotes osteogenic differentiation at the genetic and protein levels, breaking through the functional limitations of pure hydroxyapatite mineralized collagen. This provides a new strategy for the development of functional bone repair materials

Objective: To investigate the distribution characteristics of Kidd blood group antigens, phenotypes and genotypes in Xinjiang and their influence on the risk of coronary heart disease. Methods: Samples from 7 981 patients treated at People's Hospital of Xinjiang Uygur Autonomous Region from August 1, 2023 to May 31, 2024 were collected for Jk(a-b-) phenotype screening via urea hemolysis test, followed by the third-generation sequencing (TGS). Kidd blood group Jk and Jk antigens in 1 081 patients with coronary heart disease and 1 021 healthy people were detected, and their phenotype frequency distribution was analyzed and corresponding gene frequencies were calculated. Correlation analysis and logistic regression were used to evaluate the influence of Kidd blood group antigen expression on coronary heart disease risk. Results: Two Jk(a-b-) phenotype samples were detected, both resulting from novel gene mutation combinations. Comparative analysis of two groups revealed a higher proportion of the Jk(a-b+) phenotype in the case group (22.5%, 243/1 081) than in the control group (18.5%, 189/1 021). Moreover, Kidd blood group phenotype distribution varied significantly across all ethnic groups in the case group (P<0.05). In the control group, the Hui ethnic group exhibited the highest JK JK genotype frequency 64.15% (34/53). In the case group, the highest JK allele frequency was observed in Mongol ethnic group 56.31% (125/222), and the lowest in Han patients 45.71% (341/746). The expression of Jk antigen was negatively correlated with coronary heart disease (P<0.05). Conclusion: The distribution of Kidd blood group system varied across ethnic groups in Xinjiang. The expression of Jk antigen may have protective effect on coronary heart disease, which provides a basis for future clinical blood transfusion treatment and the mechanism study of the correlation between Kidd blood group and coronary heart disease.

Tumorigenesis， invasion， and metastasis occur in the context of a persistent inflammatory microenvironment， and a variety of inflammatory factors can lead to the development of various tumors. Guided by the thought of "preventive treatment of disease" in TCM and the concept of tertiary prevention in modern medicine， it is of great significance to effectively intervene in the inflammatory stage of the disease， interrupt disease progression， prevent the occurrence of malignant tumors， and reverse the process of "inflammation-to-cancer transformation". Sinisan， a commonly used prescription in the Treatise on Febrile Diseases， has been widely applied in the treatment of precancerous lesions of the digestive system， demonstrating considerable advantages. This article reviewed literature from the past 20 years， summarizing the application of Sinisan in precancerous lesions of the digestive system from three aspects： the exploration of its prescription-syndrome relationship， clinical application， and mechanistic study. It is found that basic syndrome indications of Sinisan include harmonizing the Earth element to promote spleen-stomach transportation and transformation， soothing the liver and nourishing the Wood element to restore the smooth flow of Qi， and regulating Yin and Yang to relieve stagnation within the system. In clinical application， Sinisan has shown significant efficacy in atrophic gastritis and precancerous conditions such as intestinal metaplasia， gastric ulcer， ulcerative colitis， esophagitis， and pancreatitis. Mechanistic studies have revealed that Sinisan can inhibit inflammatory factors and improve the inflammatory microenvironment， inhibit cell proliferation and regulate apoptosis， exhibit anti-angiogenic and antitumorigenic effects， modulate immune function， and exert antioxidant effects. These mechanisms can be achieved by regulating pathways such as nuclear factor erythroid 2-related factor 2/heme oxygenase-1 （Nrf2/HO-1）， farnesoid X receptor （FXR）/Nrf2， phosphatidylinositol 3-kinase/protein kinase B （PI3K/Akt）， Takeda G protein-coupled receptor 5/cyclic adenosine monophosphate/protein kinase A （TGR5/cAMP/PKA）， interleukin-4/signal transducer and activator of transcription 6 （IL-4/STAT6）， Janus kinase/signal transducer and activator of transcription （JAK/STAT）， RhoA/Rho-associated protein kinase （RhoA/ROCK）， and transforming growth factor-β/Smad proteins （TGF-β/Smads）， confirming Sinisan's role in reversing the inflammation-to-cancer transformation. The current research status of Sinisan in precancerous lesions of the digestive system was thoroughly examined through the above three aspects， along with the identification of limitations and areas for improvement in current research. The aim is to provide a basis and support for future in-depth research on Sinisan， promote the development of new integrated treatment models combining TCM and Western medicine for precancerous lesions， and aid in the research and development of drugs related to precancerous lesions.

OBJECTIVE: To compare the effectiveness of a zero-profile three-dimensiaonal (3D)-printed microporous titanium alloy Cage and a conventional titanium plate combined with a polyether-ether-ketone (PEEK)-Cage in the treatment of single-segment cervical spondylotic myelopathy (CSM) by anterior cervical discectomy and fusion (ACDF). METHODS: The clinical data of 83 patients with single-segment CSM treated with ACDF between January 2022 and January 2023 were retrospectively analyzed, and they were divided into 3D-ZP group (35 cases, using zero-profile 3D-printed microporous titanium alloy Cage) and CP group (48 cases, using titanium plate in combination with PEEK-Cage). There was no significant difference in gender, age, disease duration, surgical intervertebral space, and preoperative Japanese Orthopaedic Association (JOA) score, visual analogue scale (VAS) score, neck disability index (NDI), vertebral height at the fusion segment, Cobb angle, and other baseline data between the two groups (P>0.05). The operation time, intraoperative blood loss, hospital stay, complications, interbody fusion, and prosthesis subsidence were recorded and compared between the two groups. VAS score, NDI, and JOA score were used to evaluate the improvement of pain and function before operation, at 3 months after operation, and at last follow-up, and the vertebral height at the fusion segment and Cobb angle were measured by imaging. The degree of dysphagia was assessed by the Bazaz dysphagia scale at 1 week and at last follow-up. RESULTS: The operation was successfully completed in all the 83 patients. There was no significant difference in intraoperative blood loss and hospital stay between the two groups (P>0.05), but the operation time in the 3D-ZP group was significantly shorter than that in the CP group (P<0.05). Patients in both groups were followed up 24-35 months, with an average of 25.3 months, and there was no significant difference in the follow-up time between the two groups (P>0.05). The incidence and grade of dysphagia in CP group were significantly higher than those in 3D-ZP group at 1 week after operation and at last follow-up (P<0.05). There was no dysphagia in 3D-ZP group at last follow-up. There was no complication such as implant breakage or displacement in both groups. The intervertebral fusion rates of 3D-ZP group and CP group were 65.71% (23/35) and 60.42% (29/48) respectively at 3 months after operation, and there was no significant difference between the two groups [OR (95%CI)=1.256 (0.507, 3.109), P=0.622]. The JOA score, VAS score, and NDI significantly improved in the 3D-ZP group at 3 months and at last follow-up when compared with preoperative ones (P<0.05), but there was no significant difference between the two groups (P>0.05). There was no significant difference in the improvement rate of JOA between the two groups at last follow-up (P>0.05). At 3 months after operation and at last follow-up, the vertebral height at the fusion segment and Cobb angle significantly improved in both groups, and the two indexes in 3D-ZP group were significantly better than those in CP group (P<0.05). At last follow-up, the incidence of prosthesis subsidence in 3D-ZP group (8.57%) was significantly lower than that in CP group (29.16%) (P<0.05). CONCLUSION The application of zero-profile 3D-printed Cage and titanium plate combined with PEEK-Cage in single-segment ACDF can both reconstruct the stability of cervical spine and achieve good effectiveness. Compared with the latter, the application of the former in ACDF can shorten the operation time, reduce the incidence of prosthesis subsidence, and reduce the incidence of dysphagia.
Humans ; Spinal Fusion/instrumentation* ; Titanium ; Cervical Vertebrae/surgery* ; Diskectomy/instrumentation* ; Bone Plates ; Male ; Printing, Three-Dimensional ; Female ; Retrospective Studies ; Middle Aged ; Treatment Outcome ; Benzophenones ; Adult ; Spondylosis/surgery* ; Aged ; Polymers ; Ketones ; Polyethylene Glycols

Hypertrophic cardiomyopathy (HCM) is a major contributor to cardiovascular diseases (CVD), the leading cause of death globally. HCM can precipitate heart failure (HF) by causing the cardiac tissue to weaken and stretch, thereby impairing its pumping efficiency. Moreover, HCM increases the risk of atrial fibrillation, which in turn elevates the likelihood of thrombus formation and stroke. Given these significant clinical ramifications, research into the etiology and pathogenesis of HCM is intensifying at multiple levels. In this review, we discuss and synthesize the latest findings on HCM pathogenesis, drawing on key experimental studies conducted both in vitro and in vivo. We also offer our insights and perspectives on these mechanisms, while highlighting the limitations of current research. Advancing fundamental research in this area is essential for developing effective therapeutic interventions and enhancing the clinical management of HCM.
Cardiomyopathy, Hypertrophic/physiopathology* ; Humans ; Animals

OBJECTIVES: To evaluate the osteogenic efficacy of three-dimensional printing individualized titanium mesh (3D-PITM) as a scaffold material in guided bone regeneration (GBR). METHODS: 1) Patients undergoing GBR for alveolar bone defects were enrolled as study subjects, and postoperative healing complications were recorded. 2) Postoperative cone beam computed tomography (CBCT) scans acquired at least 6 months post-surgery were used to calculate the percentage of actual bone formation volume. 3) Alveolar bone specimens were collected during the first-stage implant surgery for histomorphometric analysis. This analysis quantitatively measured the proportions of newly formed bone and newly formed unmineralized bone within the specimens. Specimens were categorized into three groups based on healing complications (good healing group, wound dehiscence group, 3D-PITM exposure group) to compare differences in the proportions of newly formed bone and newly formed unmineralized bone. RESULTS: 1) Twelve patients were included. Guided bone regeneration failed in one patient, and 3D-PITM exposure occurred in three patients (exposure rate: 25%). 2) The mean percentage of actual bone formation volume in the 11 successful guided bone regeneration cases was 95.23%±28.85%. 3) Histomorphometric analysis revealed that newly formed bone constituted 40.35% of the alveolar bone specimens, with newly formed unmineralized bone accounting for 13.84% of the newly formed bone. Intergroup comparisons showed no statistically significant differences (P>0.05) in the proportions of newly formed bone or newly formed unmineralized bone between the good healing group and the wound dehiscence group or the 3D-PITM exposure group. CONCLUSIONS 3D-PITM enables effective bone augmentation. Radiographic assessment demonstrated favorable bone formation volume, while histological analysis confirmed substantial formation of newly formed mineralized bone within the surgical site.
Humans ; Printing, Three-Dimensional ; Titanium ; Cone-Beam Computed Tomography ; Bone Regeneration ; Osteogenesis ; Surgical Mesh ; Tissue Scaffolds ; Alveolar Process/surgery* ; Adult ; Male ; Middle Aged ; Female ; Wound Healing ; Guided Tissue Regeneration, Periodontal/methods* ; Alveolar Bone Loss/surgery*

Objectives:To evaluate the clinical value of the Paris system for reporting urinary cytology (TPS) in the diagnosis of urothelial carcinoma (UC).Methods:A total of 1 744 cytological diagnostic records (from 751 cases) were collected retrospectively. All specimens were voided urines and histopathology as the gold standard. The sensitivity and specificity of urinary cytological diagnosis of UC and risk of high grade malignant (ROHM) in each diagnostic category were compared.Results:There were 360 cases with histopathology. The percentage of negative for high-grade urothelial carcinoma (NHGUC) was 30.1% (226/751), atypical urothelial cells (AUC) was 29.8% (224/751), suspicious for high-grade urothelial carcinoma (SHGUC) was 16.8% (126/751), high grade urothelial carcinoma (HGUC) was 21.2% (159/751), and non-urothelial malignancy (NUM) was 2.1% (16/751). The histpathologic ROHM corresponding to each cytological diagnosis category were 27.3% for NHGUC, 32.7% for AUC, 74.7% for SHGUC, 96.6% for HGUC and 100.0% for NUM, respectively. ROHM of SHGUC was significantly higher than that of AUC group, and the difference between the two groups was statistically significant ( P＜0.001). ROHM of HGUC group was significantly higher than that of SHGUC group, and the difference was statistically significant ( P＜0.001). With SHGUC as the cut-off value, the sensitivity and specificity of cytological diagnosis of HGUC were 76.7% (165/215) and 85.7% (18/21), and with HGUC as the cut-off value, the sensitivity and specificity of cytological diagnosis of HGUC were 53.0% (114/215) and 100.0% (21/21), respectively. Conclusions:Urine cytology has high sensitivity and specificity in the diagnosis of HGUC. The malignant risk of TPS varies with different diagnosis category. The high malignant risk population in cancer hospital leads to the relatively high malignant proportion and ROHM in each diagnosis category. Urinary cytology TPS reporting system is helpful to clinical management and has good clinical application value.

Objectives:To evaluate the clinical value of the Paris system for reporting urinary cytology (TPS) in the diagnosis of urothelial carcinoma (UC).Methods:A total of 1 744 cytological diagnostic records (from 751 cases) were collected retrospectively. All specimens were voided urines and histopathology as the gold standard. The sensitivity and specificity of urinary cytological diagnosis of UC and risk of high grade malignant (ROHM) in each diagnostic category were compared.Results:There were 360 cases with histopathology. The percentage of negative for high-grade urothelial carcinoma (NHGUC) was 30.1% (226/751), atypical urothelial cells (AUC) was 29.8% (224/751), suspicious for high-grade urothelial carcinoma (SHGUC) was 16.8% (126/751), high grade urothelial carcinoma (HGUC) was 21.2% (159/751), and non-urothelial malignancy (NUM) was 2.1% (16/751). The histpathologic ROHM corresponding to each cytological diagnosis category were 27.3% for NHGUC, 32.7% for AUC, 74.7% for SHGUC, 96.6% for HGUC and 100.0% for NUM, respectively. ROHM of SHGUC was significantly higher than that of AUC group, and the difference between the two groups was statistically significant ( P＜0.001). ROHM of HGUC group was significantly higher than that of SHGUC group, and the difference was statistically significant ( P＜0.001). With SHGUC as the cut-off value, the sensitivity and specificity of cytological diagnosis of HGUC were 76.7% (165/215) and 85.7% (18/21), and with HGUC as the cut-off value, the sensitivity and specificity of cytological diagnosis of HGUC were 53.0% (114/215) and 100.0% (21/21), respectively. Conclusions:Urine cytology has high sensitivity and specificity in the diagnosis of HGUC. The malignant risk of TPS varies with different diagnosis category. The high malignant risk population in cancer hospital leads to the relatively high malignant proportion and ROHM in each diagnosis category. Urinary cytology TPS reporting system is helpful to clinical management and has good clinical application value.

Background::Genetic variants of dopaminergic transcription factor-encoding genes are suggested to be Parkinson’s disease (PD) risk factors; however, no comprehensive analyses of these genes in patients with PD have been undertaken. Therefore, we aimed to genetically analyze 16 dopaminergic transcription factor genes in Chinese patients with PD.Methods::Whole-exome sequencing (WES) was performed using a Chinese cohort comprising 1917 unrelated patients with familial or sporadic early-onset PD and 1652 controls. Additionally, whole-genome sequencing (WGS) was performed using another Chinese cohort comprising 1962 unrelated patients with sporadic late-onset PD and 1279 controls.Results::We detected 308 rare and 208 rare protein-altering variants in the WES and WGS cohorts, respectively. Gene-based association analyses of rare variants suggested that MSX1 is enriched in sporadic late-onset PD. However, the significance did not pass the Bonferroni correction. Meanwhile, 72 and 1730 common variants were found in the WES and WGS cohorts, respectively. Unfortunately, single-variant logistic association analyses did not identify significant associations between common variants and PD. Conclusions::Variants of 16 typical dopaminergic transcription factors might not be major genetic risk factors for PD in Chinese patients. However, we highlight the complexity of PD and the need for extensive research elucidating its etiology.

Objective To observe the expression and localization of group Ⅰ metabotropic glutamate receptors (mGluR1/ 5) in rat superior cervical ganglion (SCG) and the effect of chronic intermittent hypoxia (CIH) on mGluR1/ 5 protein level. Methods Twelve male SD rats were randomly divided into control group(Ctrl)and CIH group(CIH), 6 rats in each group. After 6 weeks of modeling, the effect of CIH on mGluR1/ 5 protein level was detected by Western blotting, the expression and distribution of mGluR1/ 5 in SCG were detected by immunohistochemistry and double-immunofluorescent staining. Results mGluR1/ 5 was expressed in rat SCG. mGluR1 was distributed in neurons and small intensely fluorescent (SIF) cells, but not in satellite glial cells (SGCs), nerve fibers and blood vessels, whereas mGluR5 was mainly distributed in nerve fibers and a little in neurons, but not in SGCs, SIF cells and blood vessels. CIH increased the protein levels of mGluR1/ 5 (P<0. 01) in rat SCG. Conclusion Both mGluR1 and mGluR5 are expressed in the rat SCG, but their distribution are different, and the increased protein levels of both may be involved in CIH-induced hypertension.