Objective:To detect the serum levels of 25(OH)D,miR-125b-5p,hypoxia-inducible factor-1α(HIF-1α)and vascular endothelial growth factor A(VEGFA)in patients with multiple myeloma(MM),and explore the role of miR-125b-5p/HIF-1α pathway in the involvement of vitamin D deficiency in the pathogenesis of MM.Methods:Fifty three newly diagnosed/relapsed MM patients admitted to the department of hematology of our hospital from October 2021 to December 2023 were included.Meanwhile,25 healthy individuals matched in gender and age from our hospital's Health Management Center were selected as controls.The serum level of 25(OH)D was monitored by mass spectrometry,the serum level of miR-125b-5p was detected by real-time fluorescence quantitative PCR,and serum levels of HIF-1α and VEGFA were measured by enzyme-linked immunosorbent assay.The levels of 25(OH)D,miR-125b-5p,HIF-1α,and VEGFA were compared between the two groups.According to the level of 25(OH)D,the MM patients were divided into vitamin D deficiency group(＜20 ng/ml)and vitamin D non-deficiency group(≥ 20 ng/ml),and the levels of miR-125b-5p,HIF-1α,and VEGFA were compared between the two groups.The correlations between 25(OH)D,miR-125b-5p,HIF-1α and VEGFA were analyzed.The receiver operating characteristic(ROC)curve analysis was used to determine the diagnostic value of25(OH)D combined with miR-125b-5p for newly diagnosed MM.Results:The level of 25(OH)D in MM patients was significantly lower than that in control group(P＜0.01).There was no significant difference in 25(OH)D level between newly diagnosed and relapsed MM patients(P＞0.05).Compared with the control group,the level of miR-125b-5p was significantly reduced in MM patients(P＜0.01),while the levels of HIF-1α and VEGFA were significantly increased(both P＜0.001).In MM patients,the miR-125b-5p level in the vitamin D deficiency group was significantly decreased than that in the non-deficiency group(P＜0.01),while the levels of HIF-1 α and VEGFA were significantly increased(both P＜0.05).In MM patients,25(OH)D was positively correlated with miR-125b-5p,while negatively correlated with HIF-1α and VEGFA(both P＜0.05).Moreover,miR-125b-5p was negatively correlated with HIF-1α and VEGFA(both P＜0.05).The area under the curve(AUC)for diagnosing MM with 25(OH)D,miR-125b-5p,and their combination were 0.699,0.751,and 0.791,respectively.Conclusion:The incidence of vitamin D deficiency is high in MM patients.Vitamin D deficiency may promote angiogenesis and participate in the occurrence and development of MM by downregulating miR-125b-5p and upregulating HIF-1α and VEGFA expression.

Objective:To investigate the effect and mechanism of injectable photopolymerizable porous gelatin methacrylate anhydride (Porous GelMA)/methacrylated silk fibroin (SilMA) composite hydrogel (PSE) loaded with human umbilical cord mesenchymal stem cell-derived exosomes (hUCMSC-Exos) in promoting knee joint cartilage regeneration.Methods:The porous GelMA solution (60 g/L) was mixed with SilMA solution (200 g/L) at a volume ratio of 6∶1 . The mixture was ultraviolet-irradiated for 30 seconds to form a cured Porous GelMA/SilMA hydrogel (P/S6). The hUCMSC-Exos was isolated via differential centrifugation coupled with ultrafiltration and then was incorporated into the Porous GelMA/SilMA composite solution at 200 μg/ml, followed by ultraviolet irradiation for 30 seconds to generate Exos-loaded PSE. Primary rat chondrocytes (P1) were divided into control group, P/S6 group, and PSE group to characterize the porosity, compressive strength, and sustained exosome release kinetics of PSE hydrogel. Chondrocytes were allocated to control group, interleukin-1β (IL-1β) group, P/S6 group, and PSE group, among which the last three groups were preconditioned with 10 ng/ml IL-1β for 24 hours, and then cultured in complete medium, P/S6 extract and PSE extract for 3 days, respectively, to establish in vitro cartilage defect models, while the control group remained untreated. Western blot and qRT-PCR analysis were conducted to quantify the expression levels of antibody to aggrecan core protein (ACAN), sex-determining region Y-box transcription factor 9 (SOX9), matrix metalloproteinase-13 (MMP13) and collagen type II (COL II). Murine monocyte-macrophage leukemia cells (RAW264.7) were divided into control group, P/S6 group, and PSE group, which were then cultured in complete medium, PSE extract, and PSE extract medium for 3 days, respectively. qRT-PCR was employed to detect the expression levels of recombinant arginase-1 protein (ARG1), mannose receptor (CD206), and inducible nitric oxide synthase (iNOS). Transcriptomic sequencing was used to identify differentially expressed genes during PSE-mediated chondrocyte regeneration, followed by functional enrichment analysis of key signaling pathways. Twenty-four SD rats were selected to establish cartilage defect models and assigned to injury control group, P/S6 group, and PSE group according to the random number table (8 rats per group). The right knee joints of the rats were surgically exposed, and cylindrical osteochondral defects (a diameter of 2.0 mm× a depth of 1.0 mm) were surgically created in the center of the femoral trochlear groove using a drill bit. The injury control group received phosphate-buffered saline, while the P/S6 group and PSE group were injected with corresponding hydrogels followed by photo-crosslinking. Incisions then were closed in layers. At 6 and 10 weeks after injury, specimens were harvested for HE staining and safranin O-fast green staining to evaluate cartilage regeneration and immunohistochemistry staining to quantify the positive area fractions for COL II, MMP13, ARG1, and CD206 in the defect areas. Results:PSE hydrogel exhibited compressive strength matching native cartilage (0.41 MPa), high porosity (85%), and sustained exosome release capacity (cumulative release rate of approximately 85% over 14 days). In chondrocyte repair experiments, compared to the IL-1β group, the PSE group demonstrated significantly upregulated expression of anabolic markers of cartilage (COL II expression increased by 2.1-fold, ACAN by 1.8-fold, and SOX9 by 1.5-fold) ( P<0.01) as well as significantly suppressed expression of catabolic markers (MMP13 expression decreased by 52%) ( P<0.01). In macrophage polarization assays, the PSE group exhibited ARG1 expression increased by 68% when compared to the control group ( P<0.01), thus promoting M2 polarization of macrophages. Transcriptomic analysis revealed that PSE enhanced extracellular matrix (ECM) synthesis by activating the phosphatidylinositol 3-kinase/protein kinase B (PI3K/Akt) pathway and ECM-receptor interaction pathway, as well as by suppressing inflammation-related gene expression. Histological evaluation in animal experiments revealed regeneration of hyaline cartilage with smooth, continuous surfaces in the defect areas in the PSE group. At 10 weeks after surgery, the neocartilage-positive area in the PSE group was (9.94±0.26)%, significantly larger than (1.67±0.11)% in the injury control group ( P<0.01). Besides, the CD206? M2 macrophage-positive area reached (14.44±0.23)% in the PSE group, significantly larger than (3.41±0.36)% in the injury control group ( P<0.01). Conclusions:The PSE hydrogel successfully engineered in the study can significantly promote regenerative repair of knee cartilage defects through a dual mechanism of enhanced ECM anabolism and remodeled inflammatory microenvironment. The core mechanisms involve specific activation of the PI3K/Akt pathway (boosting chondrocyte proliferation and survival) and ECM-receptor interaction pathway (driving ECM synthesis and assembly) by exosome-loaded PSE, while effectively polarizing macrophages toward an anti-inflammatory M2 phenotype so as to coordinately regulate cartilage ECM metabolism and suppress inflammatory responses.

Objective:To detect the serum levels of 25(OH)D,miR-125b-5p,hypoxia-inducible factor-1α(HIF-1α)and vascular endothelial growth factor A(VEGFA)in patients with multiple myeloma(MM),and explore the role of miR-125b-5p/HIF-1α pathway in the involvement of vitamin D deficiency in the pathogenesis of MM.Methods:Fifty three newly diagnosed/relapsed MM patients admitted to the department of hematology of our hospital from October 2021 to December 2023 were included.Meanwhile,25 healthy individuals matched in gender and age from our hospital's Health Management Center were selected as controls.The serum level of 25(OH)D was monitored by mass spectrometry,the serum level of miR-125b-5p was detected by real-time fluorescence quantitative PCR,and serum levels of HIF-1α and VEGFA were measured by enzyme-linked immunosorbent assay.The levels of 25(OH)D,miR-125b-5p,HIF-1α,and VEGFA were compared between the two groups.According to the level of 25(OH)D,the MM patients were divided into vitamin D deficiency group(＜20 ng/ml)and vitamin D non-deficiency group(≥ 20 ng/ml),and the levels of miR-125b-5p,HIF-1α,and VEGFA were compared between the two groups.The correlations between 25(OH)D,miR-125b-5p,HIF-1α and VEGFA were analyzed.The receiver operating characteristic(ROC)curve analysis was used to determine the diagnostic value of25(OH)D combined with miR-125b-5p for newly diagnosed MM.Results:The level of 25(OH)D in MM patients was significantly lower than that in control group(P＜0.01).There was no significant difference in 25(OH)D level between newly diagnosed and relapsed MM patients(P＞0.05).Compared with the control group,the level of miR-125b-5p was significantly reduced in MM patients(P＜0.01),while the levels of HIF-1α and VEGFA were significantly increased(both P＜0.001).In MM patients,the miR-125b-5p level in the vitamin D deficiency group was significantly decreased than that in the non-deficiency group(P＜0.01),while the levels of HIF-1 α and VEGFA were significantly increased(both P＜0.05).In MM patients,25(OH)D was positively correlated with miR-125b-5p,while negatively correlated with HIF-1α and VEGFA(both P＜0.05).Moreover,miR-125b-5p was negatively correlated with HIF-1α and VEGFA(both P＜0.05).The area under the curve(AUC)for diagnosing MM with 25(OH)D,miR-125b-5p,and their combination were 0.699,0.751,and 0.791,respectively.Conclusion:The incidence of vitamin D deficiency is high in MM patients.Vitamin D deficiency may promote angiogenesis and participate in the occurrence and development of MM by downregulating miR-125b-5p and upregulating HIF-1α and VEGFA expression.

Objective Based on the national drug sampling inspection program,this study aims to comprehensively and systematically evaluate the quality of Xuanmai Ganjie preparations,analyze existing quality issues,and provide references and suggestions for quality control of this variety.Methods A total of 237 batches of Xuanmai Ganjie preparations were tested using legal standards,and methods were established for detecting adulteration of Ophiopogon japonicus with counterfeit varieties,paclobutrazol residue levels,and determining the content of platycodin D in Xuanmai Ganjie preparations.These methods were applied to the quality control and evaluation of Xuanmai Ganjie preparations.Results Through statutory inspection,one batch of Xuanmai Ganjie granules was found non-compliant.Specific batches were identified to contain the following irregularities:adulteration of Ophiopogon japonicus with counterfeit varieties,paclobutrazol residue levels exceeding proposed limits,and platycodin D content below the established threshold.Conclusion The overall quality of Xuanmai Ganjie granules was average,while the overall quality of Xuanmai Ganjie capsules and lozenges was relatively good.Manufacturing enterprises should strengthen their sense of primary responsibility and enhance control over the entire drug production process.

Objective To assess the accuracy and consistency of point-of-care testing(POCT)technology in detecting D-dimer(DDI),Procalcitonin(PCT),and N-terminal pro B-type natriuretic peptide(NT-proBNP)in whole blood samples,as well as to validate its feasibility for rapid clinical diagnosis.Methods From July 8 to August 22,2022,a total of 104 paired DDI whole blood and plasma samples,496 paired PCT whole blood and serum samples,and 77 paired NT-proBNP whole blood and serum samples were collected.The consistency and accuracy of test results between whole blood and plasma/serum samples were assessed using the Mann-Whitney U test,regression analysis,relative sensitivity,relative specificity,Youden's index,and Kappa value.Results The test results of DDI,PCT,and NT-proBNP in whole blood and plasma/serum samples demonstrated excellent consistency,with correlation coefficients of r2=0.951 2,r2=0.942 8,and r2=0.991 6,respectively,and all P-values exceeding 0.05.At the medical decision levels,for DDI(0.55 μg/mL),the relative sensitivity,rela-tive specificity,Youden index,and Kappa value were 94.3%,94.1%,0.88,and 0.87,respectively.For PCT(0.5 ng/mL and 2.0 ng/mL),the relative sensitivities were 97.4%and 89.0%,the relative specificities were 95.8%and 98.3%,the Youden indices were 0.93 and 0.87,and the Kappa values were 0.93 and 0.89,respectively.For NT-proBNP(125 pg/mL),the relative sensitivity was 94.1%,the relative specificity was 100%,the Youden index was 0.94,and the Kappa value was 0.87.These findings confirm the high accuracy of whole blood sample testing and the strong concordance between the two methods.Conclusions This study confirmed the efficacy of POCT technology for detecting DDI,PCT,and NT-proBNP in whole blood samples.The results showed a high level of consistency compared to traditional plasma/serum methods,thereby reinforcing the clinical applicability of POCT for rapid diagnosis.

Objective:To investigate the association between blood selenium levels and sex hormones in Chinese men aged 18-79 years.Methods:Data were derived from the China National Human Biomonitoring survey conducted in 2017-2018, with a final sample size of 5 414 men. General demographic characteristics, behavioral habits, and dietary frequency were collected through questionnaires and physical examinations. Fasting blood samples were collected to measure blood lead, serum testosterone, and estradiol levels. Complex sampling linear regression models were used to analyze the associations between blood selenium levels and testosterone, estradiol, and the testosterone/estradiol ratio, adjusting for confounding factors including age, education level, marital status, smoking status, alcohol consumption, seafood intake, soy product intake, protein supplement intake, BMI, and diabetes status.Results:The mean age of the 5 414 participants was (46.85±27.91) years; 4 774 (91.65%) were of Han ethnicity and 4 505 (86.68%) were married. The median ( Q1, Q3) blood selenium concentration in men was 97.80 (80.64, 116.99) μg/L. After adjusting for confounding factors, the complex sampling linear regression model revealed negative associations between blood selenium levels and both testosterone levels and the testosterone/estradiol ratio, with a significant linear trend ( Ptrend<0.05). Compared with the Q1 group, the β (95% CI) values for testosterone in the Q2, Q3, and Q4 groups were -0.02 (-0.06 to 0.02), -0.03 (-0.08 to 0.01), and -0.06 (-0.09 to -0.02), respectively. Similarly, the β (95% CI) values for the testosterone/estradiol ratio in the Q2, Q3, and Q4 groups were -0.01 (-0.03 to 0.02), -0.01 (-0.04 to 0.04), and -0.03 (-0.06 to -0.01), respectively. Subgroup analysis indicated stronger associations between blood selenium levels and testosterone/estradiol levels in non-smoking and obese men (BMI≥28 kg/m2). Conclusion:Blood selenium levels are negatively associated with testosterone levels and the testosterone/estradiol ratio in Chinese adult males.

Objective To assess the accuracy and consistency of point-of-care testing(POCT)technology in detecting D-dimer(DDI),Procalcitonin(PCT),and N-terminal pro B-type natriuretic peptide(NT-proBNP)in whole blood samples,as well as to validate its feasibility for rapid clinical diagnosis.Methods From July 8 to August 22,2022,a total of 104 paired DDI whole blood and plasma samples,496 paired PCT whole blood and serum samples,and 77 paired NT-proBNP whole blood and serum samples were collected.The consistency and accuracy of test results between whole blood and plasma/serum samples were assessed using the Mann-Whitney U test,regression analysis,relative sensitivity,relative specificity,Youden's index,and Kappa value.Results The test results of DDI,PCT,and NT-proBNP in whole blood and plasma/serum samples demonstrated excellent consistency,with correlation coefficients of r2=0.951 2,r2=0.942 8,and r2=0.991 6,respectively,and all P-values exceeding 0.05.At the medical decision levels,for DDI(0.55 μg/mL),the relative sensitivity,rela-tive specificity,Youden index,and Kappa value were 94.3%,94.1%,0.88,and 0.87,respectively.For PCT(0.5 ng/mL and 2.0 ng/mL),the relative sensitivities were 97.4%and 89.0%,the relative specificities were 95.8%and 98.3%,the Youden indices were 0.93 and 0.87,and the Kappa values were 0.93 and 0.89,respectively.For NT-proBNP(125 pg/mL),the relative sensitivity was 94.1%,the relative specificity was 100%,the Youden index was 0.94,and the Kappa value was 0.87.These findings confirm the high accuracy of whole blood sample testing and the strong concordance between the two methods.Conclusions This study confirmed the efficacy of POCT technology for detecting DDI,PCT,and NT-proBNP in whole blood samples.The results showed a high level of consistency compared to traditional plasma/serum methods,thereby reinforcing the clinical applicability of POCT for rapid diagnosis.

Objective Based on the national drug sampling inspection program,this study aims to comprehensively and systematically evaluate the quality of Xuanmai Ganjie preparations,analyze existing quality issues,and provide references and suggestions for quality control of this variety.Methods A total of 237 batches of Xuanmai Ganjie preparations were tested using legal standards,and methods were established for detecting adulteration of Ophiopogon japonicus with counterfeit varieties,paclobutrazol residue levels,and determining the content of platycodin D in Xuanmai Ganjie preparations.These methods were applied to the quality control and evaluation of Xuanmai Ganjie preparations.Results Through statutory inspection,one batch of Xuanmai Ganjie granules was found non-compliant.Specific batches were identified to contain the following irregularities:adulteration of Ophiopogon japonicus with counterfeit varieties,paclobutrazol residue levels exceeding proposed limits,and platycodin D content below the established threshold.Conclusion The overall quality of Xuanmai Ganjie granules was average,while the overall quality of Xuanmai Ganjie capsules and lozenges was relatively good.Manufacturing enterprises should strengthen their sense of primary responsibility and enhance control over the entire drug production process.

Cemental tear is a rare and indetectable condition unless obvious clinical signs present with the involvement of surrounding periodontal and periapical tissues. Due to its clinical manifestations similar to common dental issues, such as vertical root fracture, primary endodontic diseases, and periodontal diseases, as well as the low awareness of cemental tear for clinicians, misdiagnosis often occurs. The critical principle for cemental tear treatment is to remove torn fragments, and overlooking fragments leads to futile therapy, which could deteriorate the conditions of the affected teeth. Therefore, accurate diagnosis and subsequent appropriate interventions are vital for managing cemental tear. Novel diagnostic tools, including cone-beam computed tomography (CBCT), microscopes, and enamel matrix derivatives, have improved early detection and management, enhancing tooth retention. The implementation of standardized diagnostic criteria and treatment protocols, combined with improved clinical awareness among dental professionals, serves to mitigate risks of diagnostic errors and suboptimal therapeutic interventions. This expert consensus reviewed the epidemiology, pathogenesis, potential predisposing factors, clinical manifestations, diagnosis, differential diagnosis, treatment, and prognosis of cemental tear, aiming to provide a clinical guideline and facilitate clinicians to have a better understanding of cemental tear.
Humans ; Dental Cementum/injuries* ; Consensus ; Diagnosis, Differential ; Cone-Beam Computed Tomography ; Tooth Fractures/therapy*

OBJECTIVE To explore the optimal parameters of simmered Rhei Radix et Rhizoma and the correlation between the chroma values and the intrinsic composition of simmered Rhei Radix et Rhizoma decoction pieces powder.METHODS The single-factor-response surface method was used to investigate the simmering temperature,simmering time,paper dosage and plant ash dos-age,the response surface experiment was carried out on the basis of the single factor experiment,the appearance traits,total anthraqui-nones,free anthraquinones,leachables,sennoside A and B contents were taken as indicators,the analytic hierarchy process(AHP)was used to give weights to each index,and the process was optimized.The chroma values of raw and simmered products were deter-mined by electronic eye,the correlation and regression analysis were carried out by SPSS22.0 software,and the chroma-component re-gression equation was constructed.RESULTS The optimal process of simmering Rhei Radix et Rhizoma was 140 ℃,5 times of plant ash,2 layers of wet paper wrapped and being simmered for 2.5 h.CONCLUSION The simmering process of Rhei Radix et Rhizoma optimized by AHP combined with response surface method is reasonable and feasible,the color of decoction pieces has a significant correlation with the component content,and the regression equation constructed is reliable,which can predict the intrinsic component content of decoction pieces through chroma values.