This study aims to integrate data mining techniques of single cell transcriptomics and spatial transcriptomics, along with animal experiment validation, so as to systematically characterize the protective effects of Jianpi Tongluo Formula(JTF) on the cartilage in knee osteoarthritis(KOA) and elucidate the underlying molecular mechanisms. Single cell transcriptomics and spatial transcriptomics datasets(GSE254844 and GSE255460) of the cartilage tissue obtained from KOA patients were analyzed to map the single cell-spatial heterogeneity and identify key pathogenic factors. After that, a KOA rat model was established via knee joint injection of papain. The intervention effects of JTF on the expression features of these key factors were assessed through real-time quantitative polymerase chain reaction(PCR), Western blot, and immunohistochemical staining. As a result, the integrated single cell and spatial transcriptomics data identified distinct cell subsets with different pathological changes in different regions of the inflamed cartilage tissue in KOA, and their differentiation trajectories were closely related to the inflammatory fibrosis-like pathological changes of chondrocytes. Accordingly, the expression levels of the two key effect targets, namely nuclear receptor coactivator 4(NCOA4) and high mobility group box 1(HMGB1) were significantly reduced in the articular surface and superficial zone of the inflamed joints when JTF effectively alleviated various pathological changes in KOA rats, thus reversing the abnormal chondrocyte autophagy level, relieving the inflammatory responses and fibrosis-like pathological changes, and promoting the repair of chondrocyte function. Collectively, this study revealed the heterogeneous characteristics and dynamic changes of inflamed cartilage tissue in different regions and different cell subsets in KOA patients. It is worth noting that NCOA4 and HMGB1 were crucial in regulating chondrocyte autophagy and inflammatory reaction, while JTF could reverse the regulation of NCOA4 and HMGB1 and correct the abnormal molecular signal axis in the target cells of the inflamed joints. The research can provide a new research idea and scientific basis for developing a personalized therapeutic schedule targeting the spatiotemporal heterogeneity characteristics of KOA.
Animals ; Drugs, Chinese Herbal/administration & dosage* ; Rats ; Osteoarthritis, Knee/pathology* ; Humans ; Male ; Cartilage, Articular/metabolism* ; Chondrocytes/metabolism* ; Rats, Sprague-Dawley ; Female ; Protective Agents/administration & dosage* ; Single-Cell Analysis ; Middle Aged ; HMGB1 Protein/metabolism*

This study aims to investigate the polarized microscopic mineral phase characteristics, inorganic element content, and potential health risks associated with the intake of raw and calcined fossil mineral Chinese medicinal material Draconis Os. Microscopy was employed to observe the mineralogical characteristics of Draconis Os and compare the microscopic features and phase composition of raw and calcined Draconis Os under monochromatic and orthogonal polarized light. Inductively coupled plasma mass spectrometry(ICP-MS) was employed to determine the content of 30 inorganic elements. Health risk assessment was conducted by calculating the single pollution index(P_i), average daily intake of elements for adults(ADI), target hazard quotient(THQ), non-carcinogenic assessment method-hazard quotient(HQ), and the carcinogenic risk of elements(CR). The results indicated that under monochromatic polarized light, the Draconis Os powder sections exhibited light gray-brown to gray-brown irregular fragments, some with undulating textures that were slightly curved. Under crossed polarized light, they appeared dark gray, grayish-white, and yellowish-white. Clear apatite was visible in the ground sections of Draconis Os under crossed polarized light. P_i results indicated that Draconis Os samples were free from contamination and were of good quality. According to the maximum allowable limits of heavy metals stipulated in ISO Traditional Chinese Medicine: Determination of heavy metals in herbal medicines used in Traditional Chinese Medicine, ADI, THQ, HQ, and CR were taken as assessment indicators. Only the THQ value for As(arsenic) in raw Draconis Os was greater than 1, while the THQ values for other heavy metal elements in the Draconis Os samples were all less than 1. The study demonstrates that the primary mineral phase of raw and calcined Draconis Os is apatite, with some samples co-existing with calcite, which can serve as one of the means for quality control of Draconis Os. The elemental analysis results from ICP-MS provide scientific evidence for the safety assessment of Draconis Os, indicating that Draconis Os is safe in clinical application.
Drugs, Chinese Herbal/analysis* ; Risk Assessment ; Minerals/chemistry* ; Fossils ; Humans ; Drug Contamination ; Mass Spectrometry

OBJECTIVE: This study aimed to explore the association between body mass index (BMI) and mortality based on the 10-year population-based multicenter prospective study. METHODS: A general population-based multicenter prospective study was conducted at four sites in rural China between 2013 and 2023. Multivariate Cox proportional hazards models and restricted cubic spline analyses were used to assess the association between BMI and mortality. Stratified analyses were performed based on the individual characteristics of the participants. RESULTS: Overall, 19,107 participants with a sum of 163,095 person-years were included and 1,910 participants died. The underweight (< 18.5 kg/m ²) presented an increase in all-cause mortality (adjusted hazards ratio [ aHR] = 2.00, 95% confidence interval [ CI]: 1.66-2.41), while overweight (≥ 24.0 to < 28.0 kg/m ²) and obesity (≥ 28.0 kg/m ²) presented a decrease with an aHR of 0.61 (95% CI: 0.52-0.73) and 0.51 (95% CI: 0.37-0.70), respectively. Overweight ( aHR = 0.76, 95% CI: 0.67-0.86) and mild obesity ( aHR = 0.72, 95% CI: 0.59-0.87) had a positive impact on mortality in people older than 60 years. All-cause mortality decreased rapidly until reaching a BMI of 25.7 kg/m ² ( aHR = 0.95, 95% CI: 0.92-0.98) and increased slightly above that value, indicating a U-shaped association. The beneficial impact of being overweight on mortality was robust in most subgroups and sensitivity analyses. CONCLUSION This study provides additional evidence that overweight and mild obesity may be inversely related to the risk of death in individuals older than 60 years. Therefore, it is essential to consider age differences when formulating health and weight management strategies.
Humans ; Body Mass Index ; China/epidemiology* ; Male ; Female ; Middle Aged ; Prospective Studies ; Rural Population/statistics & numerical data* ; Aged ; Follow-Up Studies ; Adult ; Mortality ; Cause of Death ; Obesity/mortality* ; Overweight/mortality*

OBJECTIVE: This study was aimed at investigating the carrier rate of, and molecular variation in, α- and β-globin gene mutations in Hunan Province. METHODS: We recruited 25,946 individuals attending premarital screening from 42 districts and counties in all 14 cities of Hunan Province. Hematological screening was performed, and molecular parameters were assessed. RESULTS: The overall carrier rate of thalassemia was 7.1%, including 4.83% for α-thalassemia, 2.15% for β-thalassemia, and 0.12% for both α- and β-thalassemia. The highest carrier rate of thalassemia was in Yongzhou (14.57%). The most abundant genotype of α-thalassemia and β-thalassemia was -α ^3.7/αα (50.23%) and β ^IVS-II-654/β ^N (28.23%), respectively. Four α-globin mutations [CD108 (ACC>AAC), CAP +29 (G>C), Hb Agrinio and Hb Cervantes] and six β-globin mutations [CAP +8 (C>T), IVS-II-848 (C>T), -56 (G>C), beta nt-77 (G>C), codon 20/21 (-TGGA) and Hb Knossos] had not previously been identified in China. Furthermore, this study provides the first report of the carrier rates of abnormal hemoglobin variants and α-globin triplication in Hunan Province, which were 0.49% and 1.99%, respectively. CONCLUSION Our study demonstrates the high complexity and diversity of thalassemia gene mutations in the Hunan population. The results should facilitate genetic counselling and the prevention of severe thalassemia in this region.
Humans ; beta-Thalassemia/genetics* ; alpha-Thalassemia/genetics* ; Hemoglobinopathies/genetics* ; China/epidemiology* ; High-Throughput Nucleotide Sequencing

Chronic disease is a major threat to human health. Fundus disease has become a major ophthalmic disease affecting daily life. Although great breakthroughs have been made in the treatment, compared with other chronic disease management, the management of patients with fundus disease is still in its infancy. To strengthen the management exploration of patients with fundus diseases, establish a management model of fundus diseases and strive to improve patients' awareness of fundus diseases and adherence to treatment and follow-up are the great challenges at present. All ophthalmic centers should strengthen patient education, establish a regional cooperation network, support the construction of grassroots medical capacity, cultivate talents, enhance training, promote the standardized treatment of fundus diseases, standardize fundus imaging inspection and diagnosis, and promote the homogeneous construction of diagnosis and treatment of chronic fundus diseases. We will accelerate the construction of a hierarchical diagnosis and treatment system and the ability to link consultation and referral. Through systematic management and intervention of fundus diseases, a large number of patients with fundus diseases will receive early screening, diagnosis, standardized continuous treatment and systematic management, and improve the quality of life of patients with fundus diseases.

Humans ; RNA-Binding Protein EWS/genetics* ; Melanoma/genetics* ; Oncogene Proteins, Fusion/genetics*

Humans ; Microcephaly ; Pedigree ; Nervous System Malformations ; Glucose

OBJECTIVES: To investigate the risk factors for neonatal asphyxia in Hubei Enshi Tujia and Miao Autonomous Prefecture and establish a nomogram model for predicting the risk of neonatal asphyxia. METHODS: A retrospective study was conducted with 613 cases of neonatal asphyxia treated in 20 cooperative hospitals in Enshi Tujia and Miao Autonomous Prefecture from January to December 2019 as the asphyxia group, and 988 randomly selected non-asphyxia neonates born and admitted to the neonatology department of these hospitals during the same period as the control group. Univariate and multivariate analyses were used to identify risk factors for neonatal asphyxia. R software (4.2.2) was used to establish a nomogram model. Receiver operator characteristic curve, calibration curve, and decision curve analysis were used to assess the discrimination, calibration, and clinical usefulness of the model for predicting the risk of neonatal asphyxia, respectively. RESULTS: Multivariate logistic regression analysis showed that minority (Tujia), male sex, premature birth, congenital malformations, abnormal fetal position, intrauterine distress, maternal occupation as a farmer, education level below high school, fewer than 9 prenatal check-ups, threatened abortion, abnormal umbilical cord, abnormal amniotic fluid, placenta previa, abruptio placentae, emergency caesarean section, and assisted delivery were independent risk factors for neonatal asphyxia (P<0.05). The area under the curve of the model for predicting the risk of neonatal asphyxia based on these risk factors was 0.748 (95%CI: 0.723-0.772). The calibration curve indicated high accuracy of the model for predicting the risk of neonatal asphyxia. The decision curve analysis showed that the model could provide a higher net benefit for neonates at risk of asphyxia. CONCLUSIONS The risk factors for neonatal asphyxia in Hubei Enshi Tujia and Miao Autonomous Prefecture are multifactorial, and the nomogram model based on these factors has good value in predicting the risk of neonatal asphyxia, which can help clinicians identify neonates at high risk of asphyxia early, and reduce the incidence of neonatal asphyxia.
Infant, Newborn ; Humans ; Male ; Pregnancy ; Female ; Nomograms ; Retrospective Studies ; Cesarean Section ; Risk Factors ; Asphyxia Neonatorum/etiology*

Objective:To investigate the value of ultrasound findings in the diagnosis of lower extremity arterial disease in patients with type 2 diabetes mellitus and correlate it with clinical factors.Methods:A total of 535 patients with type 2 diabetes mellitus who received treatment in Taiyuan Second People's Hospital from January 2016 to June 2019 underwent color Doppler ultrasound examination (T2DM group). Vascular inner diameter, intima-media thickness, atherosclerotic plaque formation, lumen stenosis or occlusion, and hemodynamic characteristics were determined in patients with type2 diabetes mellitus compared with those in 107 patients with non-type 2 diabetes mellitus (non-T2DM group). These parameters were correlated with the course of the disease, blood glucose level, concomitant hypertension or not, and clinical Wagner grade.Results:The incidences of intima-media thickening, atherosclerotic plaque, stenosis, and occlusion of lower extremity arteries were 69.9%, 89.0%, 77.0% and 11.6% respectively, in the T2DM group, which were significantly higher than 41.1%, 78.5%, 72.0%, and 1.9% respectively in the non-T2DM group ( χ2 = 32.52, P < 0.001; χ2 = 8.76, P = 0.003; χ2 = 27.77, P < 0.001). With the prolongation of the course of T2DM, the incidence of arterial lesions in the lower extremities increased ( P < 0.001). The incidences of intima-media thickening, atherosclerotic plaque, stenosis, and occlusion of lower extremity arteries were significantly greater in the poor blood glucose control group and non-hypertension group compared with the good blood glucose control group and hypertension group (all P < 0.05). The degree of lower extremity arterial stenosis in T2DM patients was related to Wagner's grade. As the degree of stenosis increased, Wagner's grade increased correspondingly and significantly ( P < 0.001). Conclusion:Color Doppler ultrasound examination has an important value in evaluating lower extremity arterial lesions in patients with T2DM. The degree of arterial lesions in the lower extremities of T2DM patients is correlated with the course of the disease, blood glucose levels, concomitant hypertension, and clinical Wagner grade. Color Doppler ultrasound examination has an important clinical significance in evaluating the degree of vascular lesions and guiding early interventions in the clinic.

AIM: To compare the accuracy between Wang-Koch axial length adjustment formulas(SRK/TWK, Holladay ⅠWK)and SRK/T, Haigis, Holladay Ⅰ, Hoffer Q in calculating intraocular lens power of cataract patients with high myopia.METHODS: A total of 42 cataract patients with high myopia(57 eyes)were collected. All eyes underwent phacoemulsification combined with intraocular lens implantation surgery in our Hospital from September 2019 to March 2022. They were divided into two groups according to the axial length(AL): group A(27mm≤AL<30mm, 31 eyes)and group B(AL≥30mm, 26 eyes). Patients were followed up at 3mo. The actual postoperative diopter was recorded, and then the refractive mean numerical error(MNE)and mean absolute error(MAE)were calculated.RESULTS: MAE of each formulas was statistically different after surgery(P<0.01), among which the MAE of Holladay ⅠWK and SRK/TWK [0.31(0.08, 0.57), 0.34(0.17, 0.63)D] was lower than other formulas. However, there were no statistical difference between SRK/TWK, Holladay ⅠWK and SRK/T, Haigis formulas [0.61(0.27, 1.02), 0.63(0.22, 1.01)D](P>0.05). MAE were statistically different among the formulas in group A(27mm≤AL<30mm; P<0.01). The MAE of Holladay ⅠWK and SRK/TWK was lower than other formulas [0.18(0.05, 0.51), 0.28(0.16, 0.52)D], but there were no statistical difference with SRK/T and Haigis formulas [0.45(0.18, 0.65), 0.50(0.14, 0.75)D](P>0.05). In group B(AL≥30mm), the MAE of each formulas was statistically different after surgery(P<0.01), among which MAE of Holladay IWK and SRK/TWK was the lowest, followed by SRK/T and Haigis, whereas, Holladay I and Hoffer Q ranked the highest. Furthermore, there were statistical differences between MAE of SRK/TWK, Holladay ⅠWK [0.44(0.23, 0.67), 0.41(0.22, 0.66)D] and SRK/T, Haigis formulas [0.78(0.55, 1.07), 0.75(0.45, 1.25)D](all P<0.05).CONCLUSION: For cataract patients with AL ≥30mm, the Wang-Koch axial length adjustment formulas were relatively accurate in calculating diopter of intraocular lens, and had clinical application value to some extent.