Objective To investigate the role and potential mechanism of secreted phosphoprotein 1 (SPP1)⁺ macrophages in the formation of chronic renal allograft fibrosis. Methods The expression features of SPP1⁺ macrophages in renal allografts of chronic allograft dysfunction (CAD) patients were analyzed based on single-cell transcriptome data of renal tissues from patients with CAD. Transcription factor VIPER analysis and DoRothEA transcription factor activity analysis were performed on the single-cell transcriptome data. Renal tissue samples were collected from kidney transplant recipients, including the CAD group (n=5) and the non-renal allograft fibrosis group (CTL group, n=5). A mouse model of chronic allograft rejection was established and divided into the allogeneic kidney transplantation group (CAD group, n=3) and the syngeneic kidney transplantation group (SYN group, n=3). Hematoxylin-eosin staining was used to detect renal tissue injury in mice, and Masson staining was used to detect renal tissue fibrosis. Immunofluorescence staining was performed to detect SPP1 expression in renal tissues of transplant recipients and mouse renal allografts. Bone marrow-derived macrophages (BMDMs) were extracted from mice and subjected to hypoxia stimulation. The expression of hypoxia-inducible factor (HIF)-1α and SPP1 was detected by Western blot, and SPP1 expression was detected by flow cytometry. BMDMs were transfected with HIF-1α overexpression plasmid and HIF-1α small interfering RNA (siRNA) followed by hypoxia intervention, and the expression of HIF-1α and SPP1 was detected by Western blot. Mouse aortic endothelial cells (MAECs) were co-cultured with the supernatant of BMDMs, and the expression of endothelial-mesenchymal transition (EndMT)-related markers was detected by Western blot and immunofluorescence. Results Single-cell transcriptome analysis showed that the proportion of SPP1⁺ macrophages in renal allograft tissues was significantly higher in the CAD group than in the CTL group (P<0.05). The renal injury score and the percentage of interstitial fibrotic area in the CAD group were significantly higher than those in the SYN group (both P<0.05). Immunofluorescence staining showed that the proportion of SPP1⁺ macrophages was increased in the CAD group compared with the CTL group, and also increased in the CAD group compared with the SYN group (both P<0.05). VIPER analysis and DoRothEA transcription factor activity analysis revealed activation of the hypoxia pathway and upregulated expression of transcription factors such as HIF-1α in SPP1⁺ macrophages. SPP1 expression was elevated in BMDMs under hypoxic conditions. Knockdown of HIF-1α inhibited hypoxia-induced SPP1 protein expression, whereas overexpression of HIF-1α upregulated SPP1 protein levels. After co-culture of hypoxia-induced BMDMs with MAECs, the expression levels of EndMT-related markers were increased. Conclusions SPP1⁺ macrophages differentiated under hypoxia are significantly infiltrated in the formation of chronic renal allograft fibrosis, and may promote renal allograft fibrosis by inducing EndMT in renal vascular endothelial cells.

Process analytical technology(PAT) is a key means for digital transformation and upgrading of the traditional Chinese medicine(TCM) manufacturing process, serving as an important guarantee for consistent and controllable TCM product quality. Near-infrared(NIR) spectroscopy has become the core technology for measuring the TCM manufacturing process. By incorporating NIR spectroscopy into PAT and starting from the construction of a smart platform for the TCM manufacturing process, this paper systematically described the development history and innovative application of the combination of NIR spectroscopy with chemometrics in measuring the TCM manufacturing process by the research team over the past two decades. Additionally, it explored the application of a validation method based on accuracy profile(AP) in the practice of NIR spectroscopy. Furthermore, the software development progress driven by NIR spectroscopy supported by modeling technology was analyzed, and the prospect of integrating NIR spectroscopy in smart factory control platforms was exemplified with the construction practices of related platforms. By integrating with the smart platform, NIR spectroscopy could improve production efficiency and guarantee product quality. Finally, the prospect of the smart platform application in measuring the TCM manufacturing process was projected. It is believed that the software development for NIR spectroscopy and the smart manufacturing platform will provide strong technical support for TCM digitalization and industrialization.
Spectroscopy, Near-Infrared/methods* ; Drugs, Chinese Herbal/analysis* ; Software ; Medicine, Chinese Traditional ; Quality Control

OBJECTIVE: We aimed to investigate the patterns of fasting blood glucose (FBG) trajectories and analyze the relationship between various occupational hazard factors and FBG trajectories in male steelworkers. METHODS: The study cohort included 3,728 workers who met the selection criteria for the Tanggang Occupational Cohort (TGOC) between 2017 and 2022. A group-based trajectory model was used to identify the FBG trajectories. Environmental risk scores (ERS) were constructed using regression coefficients from the occupational hazard model as weights. Univariate and multivariate logistic regression analyses were performed to explore the effects of occupational hazard factors using the ERS on FBG trajectories. RESULTS: FBG trajectories were categorized into three groups. An association was observed between high temperature, noise exposure, and FBG trajectory ( P < 0.05). Using the first quartile group of ERS1 as a reference, the fourth quartile group of ERS1 had an increased risk of medium and high FBG by 1.90 and 2.21 times, respectively (odds ratio [ OR] = 1.90, 95% confidence interval [ CI]: 1.17-3.10; OR = 2.21, 95% CI: 1.09-4.45). CONCLUSION An association was observed between occupational hazards based on ERS and FBG trajectories. The risk of FBG trajectory levels increase with an increase in ERS.
Humans ; Male ; Adult ; Blood Glucose/analysis* ; China ; Prospective Studies ; Occupational Exposure/adverse effects* ; Risk Factors ; Middle Aged ; Steel ; Fasting/blood* ; Metal Workers ; East Asian People

OBJECTIVE: To investigate the association between ABO blood types and gestational diabetes mellitus (GDM) risk. METHODS: A prospective birth cohort study was conducted. ABO blood types were determined using the slide method. GDM diagnosis was based on a 75-g, 2-h oral glucose tolerance test (OGTT) according to the criteria of the International Association of Diabetes and Pregnancy Study Groups. Logistic regression was applied to calculate the odds ratios ( ORs) and 95% confidence intervals ( CIs) between ABO blood types and GDM risk. RESULTS: A total of 30,740 pregnant women with a mean age of 31.81 years were enrolled in this study. The ABO blood types distribution was: type O (30.99%), type A (26.58%), type B (32.20%), and type AB (10.23%). GDM was identified in 14.44% of participants. Using blood type O as a reference, GDM risk was not significantly higher for types A ( OR = 1.05) or B ( OR = 1.04). However, women with type AB had a 19% increased risk of GDM ( OR = 1.19, 95% CI = 1.05-1.34; P < 0.05), even after adjusting for various factors. This increased risk for type AB was consistent across subgroup and sensitivity analyses. CONCLUSION The ABO blood types may influence GDM risk, with type AB associated with a higher risk. Incorporating it-either as a single risk factor or in combination with other known factors-could help identify individuals at risk for GDM before or during early pregnancy.
Humans ; Female ; Pregnancy ; Diabetes, Gestational/etiology* ; ABO Blood-Group System ; Adult ; Prospective Studies ; Risk Factors ; Young Adult

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:To analyze the clinical features of patients with traumatic optic neuropathy (TON) and to explore its clinical patterns and treatment outcomes.Methods:A retrospective analysis was conducted on data from 323 patients (334 eyes) with TON, who were treated in the Department of Otorhinolaryngology Head and Neck Surgery, the Affiliated Hospital of Qingdao University from April 1999 to October 2024. Among these patients, 288 were male and 35 were female, with ages ranging from 4 to 70 years. All patients were followed up for a period of 6 to 24 months, with the final follow-up visual acuity recorded as the ultimate visual outcome. The visual acuity evaluation criteria were classified into five levels: no light perception, light perception, hand movement in front of the eye, counting fingers at 1 meter, and "chart-visible acuity". A treatment outcome was deemed effective if the post-treatment visual acuity improved by one level or more compared to pre-treatment, or if the chart-visible acuity improved by two lines or more on the logMAR chart. The clinical characteristics of patients, causes of injury, complications, treatment methods, and changes in visual acuity before and after treatment were summarized. Logistic regression analyses were performed to identify the influencing factors affecting treatment efficacy.Results:TON occurred mostly in young (215/323, 66.56%) males (288/323, 89.16%), the majority of patients came from villages and towns (236/323, 73.07%). Traffic accidents (232/323, 71.83%) remained the main etiology. Most patients had craniofacial injuries and other bodily injuries. The effective rate of vision improvement was 50.30% (168/334). Multiple logistic regression analyses identified that residual vision (light perception or better) at presentation ( OR=3.26, P<0.001) and receiving treatment within 7 days after injury ( OR=2.04, P=0.008) were protective factors on visual acuity recovery, while the presence of orbital wall fracture was a risk factor for visual acuity recovery ( OR=0.26, P<0.001). Additionally, undergoing surgical treatment was a protective factor for visual improvement in patients with no light perception ( OR=2.94, P=0.007). For patients with residual vision at presentation, orbital wall fracture was a significant risk factor ( OR=0.28, P=0.009). Conclusions:TON is more prevalent in young males and is primarily caused by traffic accidents, leading to a poor prognosis. Timely medical intervention following injury significantly influences prognostic outcomes. Early surgical intervention (within 7 days) is recommended, particularly for patients with no light perception at presentation.

Objective:To explore the survival and prognostic factors of a long-course venetoclax-based(VEN-based)regimen in patients with de novo acute myeloid leukemia(AML)and provide evidence for the maintenance treatment of AML.Methods:A retrospective study was conducted in patients who received a VEN-based regimen and completed at least four courses of efficacy evaluation at The First Affiliated Hospital of Nanchang University from May 2021 to January 2024.The composite complete response rate(cCR),minimal residual disease(MRD)-negative rate,overall survival(OS)time,relapse-free survival(RFS)time,and adverse events were analyzed.Results:Overall,30 newly diagnosed patients with AML were enrolled in this study.The median age was 65(range,53-78)years,and the median number of treat-ment cycles was 7(range,4-20)years.After one cycle,the CR-and MRD-negative rates were 80.0%and 63.3%,respectively.The cumulative cCR was 96.7%,and MRD negative rate was 80.0%,respectively.The median follow-up time was 21.3(95%confidence intervals 14.7-27.9)months.The median OS time was 32.3 months and RFS time was not reached.The 2-year OS and RFS rates were 70.6%and 54.8%,respect-ively.Univariate analysis suggested that ELN2017 risk stratification and relapse status affected RFS and OS(P<0.05).However,the multivari-ate analysis failed to reveal any relationship between these factors and survival(P>0.05).In terms of safety,hematological adverse events were the most common,followed by infections.Overall,the VEN-based regimen was tolerated for patients with AML.Conclusions:A long-course VEN-based regimen is effective and safe.More than half of patients survive for>2 years,and it can be used as an effective mainten-ance treatment option for patients with AML.

Objective To investigate the effects of indirect moxibustion on the expressions of DNA methyltransferases(DNMT)and methylation of the brain-derived neurotrophic factor(BDNF)promoter region in uterine tissues of rats with primary dysmenorrhea(PD);To explore the mechanism of epigenetic regulation of indirect moxibustion on PD model rats.Methods A total of 32 female SD rats were randomly divided into blank group,model group,indirect moxibustion group and Western medicine group,with 8 rats in each group.The PD model with cold dampness stagnation syndrome was established using ice-water baths combined with estradiol benzoate and oxytocin.Starting from the first day of modeling,the indirect moxibustion group received salt-partitioned moxibustion at"Shenque"and ginger-partitioned moxibustion at"Guanyuan"for 20 min,while the Western medicine group was gavaged ibuprofen solution.Both interventions were given once a day for 10 days.On day 11,writhing responses were observed and scored after oxytocin injection,Western blot and RT-qPCR were used to detect protein and mRNA expression of BDNF,DNMT3A and DNMT3B in uterine tissue,immunohistochemical staining was used to detect the positive expressions of DNMT3A and DNMT3B in uterine tissue.The DNA methylation of BDNF promoter region in uterine tissue was detected by sulfite sequencing.Results Compared with the blank group,the writhing latency was shortened and the writhing score increased in the model group(P<0.01);the protein and mRNA expressions of BDNF,DNMT3A and DNMT3B in uterine tissue increased(P<0.01),the positive expressions of DNMT3A and DNMT3B increased(P<0.01),and the DNA methylation rate in BDNF promoter region decreased(P<0.01).Compared with the model group,the writhing latency was lengthened and the writhing score decreased in the indirect moxibustion group and Western medicine group(P<0.05,P<0.01);the protein and mRNA expressions of BDNF,DNMT3A and DNMT3B in uterine tissue decreased(P<0.05,P<0.01),the positive expressions of DNMT3A and DNMT3B decreased(P<0.01),and the DNA methylation rate in BDNF promoter region increased(P<0.01).Conclusion Indirect moxibustion at"Shenque"and"Guanyuan"may inhibit the transcription of BDNF by increasing the DNA methylation level of BDNF promoter region,and reduce the expression of BDNF,so as to relieve the pain of PD rats.

Objective To investigate the drug-drug interaction between donepezil hydrochloride and moxifloxacin hydrochloride during combined administration through in vitro liver microsomal metabolism and changes in pharmacokinetic characteristics in rats.Methods A rat liver microsomal incubation system was constructed and optimized.Liquid chromatography-tandem mass spectrometry(LC-MS/MS)analysis of donepezil hydrochloride and high-performance liquid chromatography(HPLC)analysis of moxifloxacin hydro-chloride were performed.The pharmacokinetic and metabolic characteristics of the two drugs,alone and in combination,were compared in vitro using rat liver microsomes and in vivo using rats.Results In the liver microsomal system,the half-life(T1/2)of donepezil hydro-chloride in the combined administration 1 group was prolonged by 29.892％(P＜0.01)and the intrinsic clearance(CLint)was reduced by 23.194％(P＜0.01)compared with the donepezil hydrochloride group.Conversely,the metabolic parameters of moxifloxacin hydrochlo-ride in the combined administration 2 group did not differ significantly from that of the moxifloxacin hydrochloride group(P＞0.05).In the in vivo study,the AUC0～t and AUC0～∞ of donepezil hydrochloride in the combined administration 1 group increased by 44.259％and 44.496％,respectively,maximum plasma concentration(Cmax)increased by 117.723％,T1/2 was prolonged by 98.063％,and CLint was reduced by 35.293％,compared with that in the donepezil hydrochloride group.Moreover,the differences were all statistically significant(P＜0.05).The in vivo study findings were consistent with the results of the in vitro study.Conclusion A drug-drug interaction occurs when moxifloxacin hydrochloride is used in combination with donepezil hydrochloride.Moxifloxacin hydrochloride promotes the absorption of donepezil hydrochloride,inhibits its metabolism,slows its CLint,and increases donepezil exposure in the body.

Objective:To compare the efficacy of inverted triangular and equilateral triangular cannulated screw internal fixation (CSIF) in the treatment of femoral neck fracture (FNF) in young and middle-aged patients.Methods:A retrospective cohort study was conducted to analyze the clinical data of 52 patients with FNF admitted to Qingdao Central Hospital of Rehabilitation University from January 2020 to January 2022, including 18 males and 34 females, aged 28-60 years [(45.7±9.3)years]. Based on the Garden classification, the fractures were classified as type I in 11 patients, type II in 34, and type III in 7. According to Pauwels classification, the fractures were classified as type I in 33 patients, type II in 13, and type III in 6. Among them, 28 patients received inverted triangular CSIF (inverted triangle group) and 24 received equilateral triangular CSIF (equilateral triangle group). Before surgery and at 3 months after surgery, nuclear medicine three-phase bone scan and bone tomography imaging were performed to evaluate the proximal blood supply recovery in the fractured sites in the two groups. The Harris hip joint function scores before surgery, at 1 day, 3 months after surgery, and at the last follow-up, the posterior tilt angles of the femoral head before surgery and at 3 months after surgery, and the fracture nonunion rate and ischemic necrosis rate of the femoral head at the last follow-up were compared between the two groups.Results:All the patients were followed up for 18-30 months [(24.2±5.6)months]. Before surgery, the fracture of both groups showed extensive blood supply defects at the proximal end. At 3 months after surgery, the excellent and good rate of the proximal blood supply recovery in the inverted triangle group was 92.9% (26/28), significantly higher than 70.8% (17/24) in the equilateral triangle group ( P<0.05). The Harris hip joint function scores before surgery were (44.1±4.1)points and (43.5±5.1)points in the inverted triangle group and equilateral triangle group ( P>0.05). At 1 day, 3 months after surgery, and at the last follow-up, the Harris hip joint function scores in the inverted triangle group were (71.7±3.6)points, (87.0±3.6)points, and (88.7±2.6)points respectively, higher than those in the equilateral triangle group [(65.0±5.4)points, (80.5±5.2)points, and (82.6±4.0)points] ( P<0.05). In both groups, there were no significant differences between the Harris hip joint function scores at the last follow-up and those at 3 months after surgery ( P>0.05), which were all higher than those at 1 day after surgery ( P<0.05). The posterior tilt angles of the femoral head were (16.9±4.4)° and (16.8±5.0)° in the inverted triangle group and equilateral triangle group preoperatively ( P>0.05). At 3 months after surgery, the posterior tilt angles of the inverted femoral head were (8.9±1.9)° and (9.0±1.8)° in the inverted triangle group and equilateral triangle group ( P>0.05). The posterior tilt angles of the femoral head at 3 months after surgery were lower than those before surgery in both groups ( P<0.05). At the last follow-up, there were no statistically significant differences in the fracture nonunion rate and ischemic necrosis rate of the femoral head between the two groups ( P>0.05). Conclusion:Compared with equilateral triangle CSIF, inverted triangle CSIF achieves better recovery of the proximal blood supply and hip joint function in the treatment of femoral neck fracture in young and middle-aged patients.