Based on the pharmacokinetics theory, this study investigated the pharmacokinetic characteristics of albiflorin, paeoniflorin, wogonoside, and wogonin in normal and febrile rats and summarized absorption and elimination rules of Dayuanyin in them to provide reference for further development and clinical application of Dayuanyin. Blood samples were taken from the fundus venous plexus of normal and model rats after intragastric administration of Dayuanyin at different time points. The concentration of each substance in blood was determined by ultra performance liquid chromatography-triple quadrupole mass spectrometry(UPLC-MS/MS) technique at different time points. DAS 2.0, a piece of pharmacokinetics software, was used to calculate the pharmacokinetic parameters of each component. The results show that the 4 components had good linear relationship in their respective ranges, and the results of methodological investigation met the requirements. The pharmacokinetic parameters of C_(max), T_(max), t_(1/2), AUC_(0-t), AUC_(0-∞), and MRT_(0-t) were calculated by the DAS 2.0 non-compartmental model. Compared with those in the normal group, C_(max) and AUC_(0-t) of the 4 components in the model group were significantly increased. There were significant differences in the pharmacokinetic characteristics between the normal and model groups, suggesting that the absorption and elimination of Dayuanyin may be affected by the changes of internal environment of the body in different physiological states.
Animals ; Rats ; Drugs, Chinese Herbal/administration & dosage* ; Male ; Rats, Sprague-Dawley ; Fever/metabolism* ; Tandem Mass Spectrometry ; Chromatography, High Pressure Liquid ; Glucosides/pharmacokinetics* ; Monoterpenes

OBJECTIVE: To explore the effect of nano-hydroxyapatite/collagen composite (nHAC) on bone graft fusion after anterior cervical discectomy and fusion (ACDF) in patients with cervical spondylosis and low bone mass. METHODS: A retrospective analysis was conducted on 47 patients with low bone mass who underwent ACDF from 2017 to 2021. They were divided into the nHAC group and the allogeneic bone group according to different bone graft materials. The nHAC group included 26 cases, with 8 males and 18 females;aged 50 to 78 years old with an average of (62.81±7.79) years old;the CT value of C₂-C₇ vertebrae was (264.16±36.33) HU. The allogeneic bone group included 21 cases, with 9 males and 12 females;aged 54 to 75 years old with an average of (65.95±6.58) years old;the CT value of C₂-C₇ vertebrae was (272.39±40.44) HU. The visual analogue scale (VAS), neck disability index (NDI), and Japanese Orthopaedic Association (JOA) spinal cord function score were compared before surgery, 1 week after surgery, and at the last follow-up to evaluate the clinical efficacy. Imaging assessment included C₂-C₇ Cobb angle, surgical segment height, intervertebral fusion, and whether the cage subsidence occurred at 1 week after surgery and the last follow-up. RESULTS: The follow-up duration ranged from 26 to 39 months with an average of (33.27±3.34) months in the nHAC group and 26 to 41 months with an average of (31.86±3.57) months in the allogeneic bone group. At 1 week after surgery and the last follow-up, the VAS, NDI scores, and JOA scores in both groups were significantly improved compared with those before surgery, with statistically significant differences (P<0.05). At 1 week after surgery, the C₂-C₇ Cobb angles in the nHAC group and the allogeneic bone group were (14.26±10.32)° and (14.28±8.20)° respectively, which were significantly different from those before surgery (P<0.05). At the last follow-up, the C₂-C₇ Cobb angles in both groups were smaller than those at 1 week after surgery, with statistically significant differences (P<0.05). At 1 week after surgery, the height of the surgical segment in the nHAC group was (31.65±2.55) mm, and that in the allogeneic bone group was (33.63±3.26) mm, which were significantly different from those before surgery (P<0.05). At the last follow-up, the height of the surgical segment in both groups decreased compared with that at 1 week after surgery, with statistically significant differences (P<0.05). At the last follow-up, 39 surgical segments were fused and 6 cages subsided in the nHAC group;40 surgical segments were fused and 7 cages subsided in the allogeneic bone group;there was no statistically significant difference between the two groups (P>0.05). Compared with the CT value of vertebrae without cage subsidence, the CT value of vertebrae with cage subsidence in both groups was significantly lower, with a statistically significant difference (P<0.05). CONCLUSION The application of nHAC in ACDF for patients with low bone mass can achieve effective fusion of the surgical segment. There is no significant difference in improving clinical efficacy, intervertebral fusion, and cage subsidence compared with the allogeneic bone group. With the extension of follow-up time, the C₂-C₇ Cobb angle decreases, the height of the surgical segment is lost, and the cage subsides in both the nHAC group and the allogeneic bone group, which may be related to low bone mass. Low bone mass may be one of the risk factors for cervical spine sequence changes, surgical segment height loss, and cage subsidence after ACDF.
Humans ; Male ; Female ; Middle Aged ; Spondylosis/physiopathology* ; Spinal Fusion/methods* ; Cervical Vertebrae/surgery* ; Aged ; Diskectomy ; Durapatite ; Retrospective Studies ; Collagen/chemistry*

PURPOSE: To analyze risk factors for severe trauma and establish a nomogram for early risk prediction, to improve the early identification of severe trauma. METHODS: This study was conducted on the patients treated in 81 trauma treatment institutions in Gansu province from 2020 to 2022. Patients were grouped by year, with 5364 patients from 2020 to 2021 as the training set and 1094 newly admitted patients in 2020 as the external validation set. Based on the injury severity score (ISS), patients in the training set were classified into 2 subgroups of the severe trauma group (n = 478, ISS scores ≥25) and the non-severe trauma group (n = 4886, ISS scores <25). Univariate and binary logistic regression analyses were employed to identify independent risk factors for severe trauma. Subsequently, a predictive model was developed using the R software environment. Furthermore, the model was subjected to internal and external validation via the Hosmer-Lemeshow test and receiver operating characteristic curve analysis. RESULTS: In total, 6458 trauma patients were included in this study. Initially, this study identified several independent risk factors for severe trauma, including multiple traumatic injuries (polytrauma), external hemorrhage, elevated shock index, elevated respiratory rate, decreased peripheral oxygen saturation, and decreased Glasgow coma scale score (all p < 0.05). For internal validation, the area under the receiver operating characteristic curve was 0.914, with the sensitivity and specificity of 88.4% and 87.6%, respectively; while for external validation, the area under the receiver operating characteristic curve was 0.936, with the sensitivity and specificity of 84.6% and 93.7%, respectively. In addition, a good model fitting was observed through the Hosmer-Lemeshow test and calibration curve analysis (p > 0.05). CONCLUSION This study establishes a nomogram for early risk prediction of severe trauma, which is suitable for primary healthcare institutions in underdeveloped western China. It facilitates early triage and quantitative assessment of trauma severity by clinicians prior to clinical interventions.
Humans ; Nomograms ; Male ; Female ; Wounds and Injuries/diagnosis* ; Risk Factors ; Middle Aged ; Adult ; Injury Severity Score ; Risk Assessment ; ROC Curve ; Aged ; Logistic Models ; China ; Glasgow Coma Scale

Non-small cell lung cancer (NSCLC), as the predominant histological subtype of lung cancer, accounts for approximately 85% of all lung cancer cases. In recent years, immune checkpoint inhibitors (ICIs), represented by programmed death 1/programmed death ligand 1 (PD-1/PD-L1) inhibitors, have achieved breakthrough advancements in patients with driver gene-negative NSCLC. They have been established as a key component of first-line treatment regimens and have significantly improved clinical outcomes. However, limited clinical evidence has emerged showing the phenomenon of histological transformation from NSCLC to small cell lung cancer (SCLC) in patients experiencing disease progression after ICIs monotherapy or combination therapy. Systematic research data on the clinical characteristics, molecular biological basis, and subsequent treatment strategies for such transformation events are currently lacking. This article reports a case of SCLC transformation occurring in a patient with KRAS-mutated lung adenocarcinoma after 16 months of ICIs combination therapy and provides a systematic review of 22 similar published cases. The study demonstrates that small cell transformation is a critical mechanism of immunotherapy resistance, and transformed patients exhibit poor prognosis. The research emphasizes the importance of dynamic monitoring of neuron-specific enolase (NSE) and standardized repeat biopsies during treatment, providing a basis for clinical practice. This aids in enhancing the recognition and management capabilities for this rare histological transformation, ultimately improving patient outcomes.
Humans ; Immune Checkpoint Inhibitors/therapeutic use* ; Lung Neoplasms/immunology* ; Carcinoma, Non-Small-Cell Lung/immunology* ; Small Cell Lung Carcinoma/genetics* ; Male ; Middle Aged ; Female

OBJECTIVE: To investigate the genetic causal relationship of leukocyte telomere length (LTL) with prostatitis, orchitis and epididymitis by two-sample Mendelian randomization (MR). METHODS: Using LTL as the exposure factor and prostatitis, orchitis and epididymitis as outcome factors, we mined the Database of Genome-Wide Association Studies (GWAS). Then, we analyzed the causal relationship of LTL with prostatitis, orchitis and epididymitis by Mendelian randomization using inverse variance weighting (IVW) as the main method and weighted median and MR-Egger regression as auxiliary methods, determined the horizontal multiplicity by MR-Egger intercept test, and conducted sensitivity analysis using the leaving-one-out method. RESULTS: A total of 121 related single nucleotide polymorphisms (SNPs) were identified in this study. IVW showed LTL to be a risk factor for prostatitis (OR = 1.383, 95% CI: 1.044－1.832, P = 0.024), and for orchitis and epididymitis as well (OR = 1.770, 95% CI: 1.275－2.456, P = 0.000 6). CONCLUSION Genetic evidence from Mendelian randomized analysis indicates that shortening of LTL reduces the risk of prostatitis, orchitis and epididymitis.
Humans ; Male ; Mendelian Randomization Analysis ; Epididymitis/genetics* ; Prostatitis/genetics* ; Polymorphism, Single Nucleotide ; Leukocytes ; Orchitis/genetics* ; Genome-Wide Association Study ; Telomere ; Risk Factors

Paroxysmal nocturnal hemoglobinuria (PNH) is an acquired clonal hematopoietic stem cell disease caused by abnormal expression of glycosylphosphatidylinositol (GPI) on the cell membrane due to mutations in the phosphatidylinositol glycan class A(PIGA) gene. It is commonly characterized by intravascular hemolysis, repeated thrombosis, and bone marrow failure, as well as multiple systemic involvement symptoms such as renal dysfunction, pulmonary hypertension, swallowing difficulties, chest pain, abdominal pain, and erectile dysfunction. Due to the rarity of PNH and its strong heterogeneity in clinical manifestations, multidisciplinary collaboration is often required for diagnosis and treatment. Peking Union Medical College Hospital, relying on the rare disease diagnosis and treatment platform, has invited multidisciplinary clinical experts to form a unified opinion on the diagnosis and treatment of PNH, and formulated the Expert Consensus of Multidisciplinary Diagnosis and Treatment for Paroxysmal Nocturnal Hemoglobinuria (2024), with the hope of promoting the standardization of PNH diagnosis and treatment.

Healthy lifestyles and good living habits are effective strategies and important approaches to prevent chronic non-communicable diseases. With the development of evidence-based medicine, the evidence translation system has made some achievements in clinical practice. There is, however, no comprehensive, professional and efficient system for translating lifestyle evidence globally. Therefore, the Health Lifestyle Evidence (HLSE) Group of Lanzhou University constructed the HLSE Evidence Translation System (https://hlse.cn/), with the aim of synthesizing, evaluating, translating, and applying lifestyle-related evidence resources. This paper aims to introduce the functional module design of the evidence translation system, the system development process and testing, introduce the interface design and function demonstration, and explain the significance of constructing the HLSE.

Background Shoemaking industry workers are prone to work-related musculoskeletal disorders (WMSDs) due to long-term awkward postures during the work process. There is little research on the prevalence and influencing factors of WMSDs in the knee region of this industry, and it should be taken seriously. Objective To estimate the prevalence of work-related knee pain among shoemaking workers and analyze the related influencing factors. Methods A total of 6982 shoemaking workers were selected from 26 shoemaking factories in Guangdong, Hubei, Fujian, Chongqing, Shandong, Zhejiang, and Jingxi by convenience sampling. Prevalence of work-related knee pain in past year, demographic characteristics, occupational related factors, and work posture were collected by a cross-sectional survey using the electronic version of Musculoskeletal Disorder Questionnaire. Logistic regression analysis was used to analyze the influencing factors that may lead to work-related knee pain. Results This survey collected 6982 valid questionnaires with a recovery rate of 98.3%. The prevalence of work-related knee pain of shoemaking workers in the past 12 months was 13.0% (908/6982). According to the results of logistic regression analysis, compared with workers with less than 5 years of service, workers with 5-10 years of service (OR=1.21, 95%CI: 1.02, 1.45) and more than 10 years (1.53, 95%CI: 1.27, 1.83) showed a higher risk of knee WMSDs; sometimes, often and very frequent (reference : rarely or never) long-term standing (OR=1.33, 95%CI: 1.08, 1.64; OR=2.67, 95%CI: 2.10, 3.39; OR=2.75, 95%CI: 2.08, 3.63) and sometimes, often and very frequent (reference: rarely or never) long-term squatting or kneeling (OR=1.80, 95%CI: 1.47, 2.21; OR=2.43, 95%CI: 1.58, 3.75; OR=3.22, 95%CI: 1.66, 6.24) increased the risk of knee pain: long-term bending (OR=1.59, 95%CI: 1.34, 1.89) and often repeated movement of lower limbs and ankles (OR=1.48, 95%CI: 1.25, 1.75) were also risk factors for knee WMSDs among shoemaking industry workers (P<0.05). Adequate rest time (OR=0.58, 95%CI: 0.49, 0.68) and able to stretch or change leg posture (OR=0.75, 95%CI: 0.64, 0.88) reduced the risk of knee WMSDs (P<0.05). Conclusion In the shoemaking industry, length of service and awkward postures are risk factors for knee pain. The shoemaking enterprises should ensure that workers have sufficient rest time, reduce long-term standing, squatting, kneeling, and bending postures, as well as lower limbs repetition in order to reduce the occurrence of knee WMSDs of workers.

Objective To investigate the relationship between thyroid function and brain volume in patients with Alzheimer's disease(AD).Methods A total of 64 AD patients(AD group)and 36 patients with mild cognitive impairment(MCI group)admitted in our department from January 2020 to March 2022 were enrolled in this study.Another 19 healthy individuals who had no cogni-tive impairment or psychiatric disorders were enrolled and served as normal control group.Their levels of free triiodothyronine(FT3),free thyroxine(FT4)and thyroid stimulating hormone(TSH)were detected by electrochemical luminescence assay.Results FT3 level was significantly decreased in the MCI group and AD group than the normal control group[2.50(2.28,2.60)ng/L and 2.07(1.97,2.30)ng/L vs 2.76(2.55,2.93)ng/L,P＜0.05],and the decrease in the AD group was more obvious than that in the MCI group.The volumes of the midbrain,pons,medulla oblon-gata,hippocampus,amygdala and temporal lobe were significantly smaller in the AD group than the MCI group(P＜0.05,P＜0.01).Spearman correlation analysis and multivariate linear regres-sion analysis showed that in the AD patients,FT3 and FT4 levels were positively while TSH level was negatively correlated with the volumes of both right and left hippocampus and amygdala(P＜0.05,P＜0.01),and TSH level was also negatively correlated with the left temporal lobe volume(P＜0.05).Conclusion Thyroid dysfunction is associated with reduced brain volume in AD patietns,and may contribute to the progression of AD cognitive dysfunction and brain atrophy.

Objective To investigate the efficacies of proximal femoral nail anti-rotation(PFNA)internal fixation in traction bed supine position and non-traction bed lateral position in the treatment of elderly unstable femoral intertrochanteric fractures.Methods The clinical data of patients with unstable femoral intertrochanteric fractures treated with PFNA internal fixation in our hospital were retrospec-tively analyzed,41 patients received treatment in traction bed supine position were included in the supine position group,and 55 patients treated received treatment in non-traction bed lateral position were included in the lateral position group.The perioperative related indicators,surgical reduction,hip Harris score,and incidence of complications in the two groups were analyzed.Results The operation time and incision length of patients in the lateral position group were shorter than those in the supine position group,and the intraoperative blood loss and fluoroscopy times were less than those in the supine position group,with statistically significant differences(P<0.05).There was no significant difference in the anesthesia mode,blood transfusion or hospital stay of patients between the two groups(P>0.05).There was no significant difference in the incidence of postoperative complications of patients between the two groups(P>0.05).There was no significant difference in neck-shaft angle,tip-apex distance or hip Harris score of patients between the two groups(P>0.05).Conclusion PFNA internal fixation in traction bed supine position and non-traction bed lateral position have the same effect in the treatment of elderly unstable femoral intertrochanteric fractures,while the non-traction bed lateral position for treatment has more advantages in shortening operation time,decreasing intraoperative blood loss,and reducing radiation exposure.