The study aims to explore the herb-drug interaction between Xuefu Zhuyu Decoction(XFZY) and atorvastatin(AT). Reverse transcription polymerase chain reaction(RT-PCR) was used to analyze the transcription levels of proteins related to drug metabolism and transport in LS174T cells, detect the intracellular drug uptake under various substrate concentrations and incubation time, and optimize the model reaction conditions of transporter multidrug resistance protein 1(MDR1)-specific probe Rhodamine 123 and AT to establish a cell model for investigating the human intestinal drug interaction. The cell counting kit-8(CCK-8) method was adopted to evaluate the cytotoxicity of XFZY on LS174T cells. After a single and continuous 48 h culture with XFZY, AT or Rhodamine 123 was added for co-incubation. The effect and mechanism of XFZY on human intestinal absorption of AT were analyzed by measuring the intracellular drug concentrations and transcription levels of related transporters and metabolic enzymes. The results of in vitro experiments show that a single co-culture with a high concentration of XFZY significantly increases the intracellular concentrations of Rhodamine 123 and AT. A high concentration of XFZY co-culture for 48 h increases the AT uptake level, significantly induces the CYP3A4 and UGT1A1 gene expression levels, and inhibits the OATP2B1 gene expression level. To compare with the evaluation results of the in vitro human cell model, the pharmacokinetic experiment of XFZY combined with AT was carried out in rats. Sprague-Dawley(SD) rats were randomly divided into a blank control group and an XFZY group. After 14 days of continuous intragastric administration, AT was given in combination. The liquid chromatography-mass spectrometry(LC-MS)/MS method was used to detect the concentrations of AT and metabolites 2-hydroxyatorvastatin acid(2-HAT), 4-hydroxyatorvastatin acid(4-HAT), atorvastatin lactone(ATL), 2-hydroxyatorvastatin lactone(2-HATL), and 4-hydroxyatorvastatin lactone(4-HATL) in plasma samples, and the pharmacokinetic parameters were calculated. Pharmacokinetic analysis in rats shows that continuous administration of XFZY does not significantly change the pharmacokinetic characteristics of AT in rats, but the AUC_(0-6 h) values of AT and metabolites 2-HAT, 4-HAT, and 2-HATL increase by 21.37%, 14.94%, 12.42%, and 6.68%, respectively. The metabolic rate of the main metabolites shows a downward trend. The study indicates that administration combined with XFZY can significantly increase the uptake level of AT in human intestinal cells and increase the exposure level of AT and main metabolites in rats to varying degrees. The mechanism may be mainly due to the inhibition of intestinal MDR1 transport activity.
Animals ; Drugs, Chinese Herbal/administration & dosage* ; Atorvastatin/administration & dosage* ; Humans ; Rats ; Rats, Sprague-Dawley ; Male ; Intestines/cytology* ; Intestinal Mucosa/metabolism* ; Herb-Drug Interactions ; Cytochrome P-450 CYP3A/metabolism* ; Intestinal Absorption/drug effects*

OBJECTIVE: To systematically evaluate and re-evaluate the surgical outcomes of robotic-assisted total knee arthroplasty(RA-TKA) compared with to conventional total knee arthroplasty(C-TKA). METHODS: Ten databases, including PubMed, EmBase, Web of Science, Cochrane Library, CINAHL, JBI, CNKI, Wanfang, VIP, CBM, were comprehensively searched from inception to September 2024. Eligible studies included systematic reviews and meta-analysis comparing the surgical outcomes of RA-TKA and C-TKA. Two independen researchers performed data extraction and quality assessment. Methodological quality was evaluated using the AMSTAR tool, while the certainty of evidence was graded using GRADE system. The degree of overlap among primary studies included in the systematic reviews/meta-analyses was investigated using the corrected covered area (CCA). RESULTS: A total of 15 systematic reviews/Meta-analyses were included, 5 were rateak as high quality, 1 as moderate quality, and 9 as low quality. A total of 53 pieces of evidence were identified, 11 pieces of evidence were of high quality, 19 were of moderate quality, 16 were of low quality, and 7 were of very low quality. Ten studies assessed the Knee Society score(KSS) and performed a meta-analysis. Among these, seven studies reported that there was no statistically significant difference in postoperative KSS scores between the two surgical methods. Nine studies evaluated the Hospital for Special Surgery(HSS) score, with seven indicating no statistically significant difference in HSS scores following surgery. Twelve studies examined the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) score postoperatively, and five found no significant difference between the two surgical approaches. Five studies compared the hip-knee-ankle (HKA) angle deviation between the two groups, all of which demonstrated that the HKA angle deviation in RA-TKA was significantly lower than in C-TKA. Eight studies reported on the range of motion (ROM) of the knee joint after surgery, with six showing no statistically significant difference between the two methods. Finally, nine studies compared the duration of the surgical procedures, all of which concluded that RA-TKA required a longer operative time than C-TKA. CONCLUSION With regard to functional outcomes, no statistically significant difference was observed between RA-TKA and C-TKA. Nevertheless, RA-TKA demonstrates advantages in terms of surgical accuracy, precision, and alignment correction.
Humans ; Arthroplasty, Replacement, Knee/methods* ; Robotic Surgical Procedures/methods* ; Treatment Outcome ; Meta-Analysis as Topic ; Systematic Reviews as Topic

PURPOSE: Intertrochanteric fracture (ITF) classification is crucial for surgical decision-making. However, orthopedic trauma surgeons have shown lower accuracy in ITF classification than expected. The objective of this study was to utilize an artificial intelligence (AI) method to improve the accuracy of ITF classification. METHODS: We trained a network called YOLOX-SwinT, which is based on the You Only Look Once X (YOLOX) object detection network with Swin Transformer (SwinT) as the backbone architecture, using 762 radiographic ITF examinations as the training set. Subsequently, we recruited 5 senior orthopedic trauma surgeons (SOTS) and 5 junior orthopedic trauma surgeons (JOTS) to classify the 85 original images in the test set, as well as the images with the prediction results of the network model in sequence. Statistical analysis was performed using the SPSS 20.0 (IBM Corp., Armonk, NY, USA) to compare the differences among the SOTS, JOTS, SOTS + AI, JOTS + AI, SOTS + JOTS, and SOTS + JOTS + AI groups. All images were classified according to the AO/OTA 2018 classification system by 2 experienced trauma surgeons and verified by another expert in this field. Based on the actual clinical needs, after discussion, we integrated 8 subgroups into 5 new subgroups, and the dataset was divided into training, validation, and test sets by the ratio of 8:1:1. RESULTS: The mean average precision at the intersection over union (IoU) of 0.5 (mAP50) for subgroup detection reached 90.29%. The classification accuracy values of SOTS, JOTS, SOTS + AI, and JOTS + AI groups were 56.24% ± 4.02%, 35.29% ± 18.07%, 79.53% ± 7.14%, and 71.53% ± 5.22%, respectively. The paired t-test results showed that the difference between the SOTS and SOTS + AI groups was statistically significant, as well as the difference between the JOTS and JOTS + AI groups, and the SOTS + JOTS and SOTS + JOTS + AI groups. Moreover, the difference between the SOTS + JOTS and SOTS + JOTS + AI groups in each subgroup was statistically significant, with all p < 0.05. The independent samples t-test results showed that the difference between the SOTS and JOTS groups was statistically significant, while the difference between the SOTS + AI and JOTS + AI groups was not statistically significant. With the assistance of AI, the subgroup classification accuracy of both SOTS and JOTS was significantly improved, and JOTS achieved the same level as SOTS. CONCLUSION In conclusion, the YOLOX-SwinT network algorithm enhances the accuracy of AO/OTA subgroups classification of ITF by orthopedic trauma surgeons.
Humans ; Hip Fractures/diagnostic imaging* ; Orthopedic Surgeons ; Algorithms ; Artificial Intelligence

Glutamine provides carbon and nitrogen to support the proliferation of cancer cells. However, the precise reason why cancer cells are particularly dependent on glutamine remains unclear. In this study, we report that glutamine modulates the tumor suppressor F-box and WD repeat domain-containing 7 (FBW7) to promote cancer cell proliferation and survival. Specifically, lysine 604 (K604) in the sixth of the 7 substrate-recruiting WD repeats of FBW7 undergoes glutaminylation (Gln-K604) by glutaminyl tRNA synthetase. Gln-K604 inhibits SCFFBW7-mediated degradation of c-Myc and Mcl-1, enhances glutamine utilization, and stimulates nucleotide and DNA biosynthesis through the activation of c-Myc. Additionally, Gln-K604 promotes resistance to apoptosis by activating Mcl-1. In contrast, SIRT1 deglutaminylates Gln-K604, thereby reversing its effects. Cancer cells lacking Gln-K604 exhibit overexpression of c-Myc and Mcl-1 and display resistance to chemotherapy-induced apoptosis. Silencing both c-MYC and MCL-1 in these cells sensitizes them to chemotherapy. These findings indicate that the glutamine-mediated signal via Gln-K604 is a key driver of cancer progression and suggest potential strategies for targeted cancer therapies based on varying Gln-K604 status.
Glutamine/metabolism* ; Myeloid Cell Leukemia Sequence 1 Protein/genetics* ; Humans ; Proto-Oncogene Proteins c-myc/genetics* ; Cell Proliferation ; Signal Transduction ; Neoplasms/pathology* ; F-Box-WD Repeat-Containing Protein 7/genetics* ; Cell Survival ; Cell Line, Tumor ; Apoptosis

OBJECTIVE: The study aim was to investigate the effects of exposure to multiple environmental organic pollutants on cardiopulmonary health with a focus on the potential mediating role of oxidative stress. METHODS: A repeated-measures randomized crossover study involving healthy college students in Beijing was conducted. Biological samples, including morning urine and venous blood, were collected to measure concentrations of 29 typical organic pollutants, including hydroxy polycyclic aromatic hydrocarbons (OH-PAHs), bisphenol A and its substitutes, phthalates and their metabolites, parabens, and five biomarkers of oxidative stress. Health assessments included blood pressure measurements and lung function indicators. RESULTS: Urinary concentrations of 2-hydroxyphenanthrene (2-OH-PHE) ( β = 4.35% [95% confidence interval ( CI): 0.85%, 7.97%]), 3-hydroxyphenanthrene ( β = 3.44% [95% CI: 0.19%, 6.79%]), and 4-hydroxyphenanthrene (4-OH-PHE) ( β = 5.78% [95% CI: 1.27%, 10.5%]) were significantly and positively associated with systolic blood pressure. Exposures to 1-hydroxypyrene (1-OH-PYR) ( β = 3.05% [95% CI: -4.66%, -1.41%]), 2-OH-PHE ( β = 2.68% [95% CI: -4%, -1.34%]), and 4-OH-PHE ( β = 3% [95% CI: -4.68%, -1.29%]) were negatively associated with the ratio of forced expiratory volume in the first second to forced vital capacity. These findings highlight the adverse effects of exposure to multiple pollutants on cardiopulmonary health. Biomarkers of oxidative stress, including 8-hydroxy-2'-deoxyguanosine and extracellular superoxide dismutase, mediated the effects of multiple OH-PAHs on blood pressure and lung function. CONCLUSION Exposure to multiple organic pollutants can adversely affect cardiopulmonary health. Oxidative stress is a key mediator of the effects of OH-PAHs on blood pressure and lung function.
Humans ; Oxidative Stress/drug effects* ; Male ; Cross-Over Studies ; Female ; Young Adult ; Environmental Pollutants/toxicity* ; Environmental Exposure/adverse effects* ; Biomarkers/blood* ; Adult ; Blood Pressure/drug effects* ; Polycyclic Aromatic Hydrocarbons/urine* ; Beijing

Objective:This study aims to evaluate the quality and explore the preliminary clinical applications of a domestically developed hepatitis D virus nucleic acid quantification reagent (abbreviated as"domestic HDV RNA reagent").Methods:The sensitivity and accuracy of the reagent were evaluated in accordance with the WHO HDV RNA international standard, employing the Bio-Rad CFX Opus 96 real-time fluorescence quantitative PCR analysis system. Serial dilutions of pseudo-viruses or cell culture-derived virus were used to determine the linear range of the domestic HDV RNA reagent. Specificity was assessed using positive samples of HAV, HBV, HCV infection, and HEV national reference materials. Precision was evaluated with samples at both high and low concentrations. In a comparative analysis, 30 HDV IgG positive samples were tested using both the domestic HDV RNA reagent and the RoboGene HDV RNA kit based on the ABI 7500 FAST DX system. The Pearson correlation coefficient (r) was used to examine the correlation between the two reagents.Results:The domestic HDV RNA reagent demonstrated a high sensitivity of up to 6 IU/ml, consistent with that of the comparator reagent. The calibration curve for WHO HDV RNA standards had a slope of -3.286, with an amplification efficiency of 101.6%. The linear detection range spanned from 10 to 10 8 IU/ml for eight HDV genotypes. The domestic HDV RNA reagent exhibited exceptional specificity, without cross-reactivity observed with HAV, HBV, HCV, or HEV. Accuracy assessments at five concentration levels met the required standards, with intra-assay precision coefficient of variation ( CV) ranging from 1.20% to 4.20%, and inter-assay precision CV from 1.20% to 7.90%. The detection results for HDV IgG positive samples were highly correlated with the comparator reagent ( r=0.984, P<0.001), achieving a diagnostic accuracy of 100% compared to sequencing results. Conclusion:In this study, the domestic HDV RNA reagent possesses excellent specificity, accuracy, precision, and a broad linear range, attaining a sensitivity level on par with international reagents of the same type.

The adulteration and counterfeiting of herbal ingredients in medicinal and food homology (MFH) have a serious impact on the quality of herbal materials, thereby endangering human health. Compared to pharmaceutical drugs, health products derived from traditional Chinese medicine (TCM) are more easily accessible and closely integrated into consumers' daily life. However, the authentication of the authenticity of TCM ingredients in MFH has not received sufficient attention. The lack of clear standards emphasizes the necessity of conducting systematic research in this area. This study utilized DNA barcoding technology, combining ITS2, psbA-trnH, matK as universal barcode sequences, and DX, HH, JYH as specific barcode sequences, to identify the authenticity of commercial medicinal and food homology scented herbal teas. The aim was to investigate the authenticity of scented herbal tea products circulating in the market. The research results revealed that among 180 scented herbal tea samples, DNA barcodes were successfully obtained from 164 samples, while the remaining samples either lacked the target components or suffered severe DNA degradation, resulting in failed amplification. Combined with morphological identification studies, it was found that out of the 180 samples, 141 were authentic, accounting for 78.33% of the total samples, while 31 samples showed adulteration and 8 samples lacked the target components, accounting for 21.67% of the total samples. Additionally, water testing revealed that 5 samples of Carthamus tinctorius herbal tea exhibited the phenomenon of weight adulteration. This study exposed the presence of adulteration and weight adulteration in scented herbal tea products, highlighting the need for regulatory authorities to expedite the establishment of quality standards in scented herbal tea industry. These findings provide valuable insights for the rapid development of the scented herbal tea industry.

BACKGROUND:As tissue engineering brings new hope to the worldwide problem of articular cartilage repair,the construction of light-curing 3D printed hydrogel scaffolds with biomimetic composition is of great significance for cartilage tissue engineering. OBJECTIVE:To construct a biomimetic methacryloylated hyaluronic acid/acellular Wharton's jelly composite hydrogel scaffold by digital light processing 3D printing technology,and to evaluate its biocompatibility. METHODS:Wharton's jelly was isolated and extracted from human umbilical cord,then decellulated,freeze-dried,ground into powder,and dissolved in PBS to prepare 50 g/L acellular Wharton's jelly solution.Methylallylated hyaluronic acid was prepared,lyophilized and dissolved in PBS to prepare 50 g/L methylallylated hyaluronic acid solution.Acellular Wharton's jelly solution was mixed with methacrylyacylated hyaluronic acid solution at a volume ratio of 1:1,and was used as bio-ink after adding photoinitiator.Methylacrylylated hyaluronic acid hydrogel scaffolds(labeled as HAMA hydrogel scaffolds)and methylacrylylated hyaluronic acid/acellular Wharton's jelly gel scaffolds(labeled as HAMA/WJ hydrogel scaffolds)were prepared by digital light processing 3D printing technology,and the microstructure,swelling performance,biocompatibility,and cartilage differentiation performance of the scaffolds were characterized. RESULTS AND CONCLUSION:(1)Under scanning electron microscope,the two groups of scaffolds showed a three-dimensional network structure,and the fiber connection of HAMA/WJ hydrogel scaffold was more uniform.Both groups achieved swelling equilibrium within 10 hours,and the equilibrium swelling ratio of HAMA/WJ hydrogel scaffold was lower than that of HAMA hydrogel scaffold(P＜0.05).(2)CCK-8 assay showed that HAMA/WJ hydrogel scaffold could promote the proliferation of bone marrow mesenchymal stem cells compared with HAMA hydrogel scaffold.Dead/live staining showed that bone marrow mesenchymal stem cells grew well on the two groups of scaffolds,and the cells on the HAMA/WJ hydrogel scaffolds were evenly distributed and more cells were found.Phalloidine staining showed better adhesion and spread of bone marrow mesenchymal stem cells in HAMA/WJ hydrogel scaffold than in HAMA.(3)Bone marrow mesenchymal stem cells were inoculated into the two groups for chondrogenic induction culture.The results of qRT-PCR showed that the mRNA expressions of agglutinoglycan,SOX9 and type Ⅱ collagen in the HAMA/WJ hydrogel scaffold group were higher than those in the HAMA hydrogel scaffold group(P＜0.05,P＜0.01).(4)These findings indicate that the digital light processing 3D bioprinting HAMA/WJ hydrogel scaffold can promote the proliferation,adhesion,and chondrogenic differentiation of bone marrow mesenchymal stem cells.

Here,5 important pathogens carried by ticks in Maanshan City,Anhui Province,China were identified.In to-tal,642 ticks were collected from 13 villages around Maanshan City and identified by morphological and mitochondrial COI genes.The 16S rRNA gene of Francisella tularensis,ssrA gene of Bartonella,16S rRNA,ompA and ompB genes of Rickett-sia,16S rRNA and gltA genes of Anaplasma,and groEL and rpoB genes of Coxiella were sequenced.Reference sequences were retrieved from a public database.Phylogenetic trees were constructed with MEG A1 1.0 software.In total,36 Rickettsiae isolates were detected in 640 Haemaphysalis longicornis ticks,which included 20 isolates of Rickettsia heilongjian-gensis,16 of Candidatus Rickettsia jingxinensis,2 of Ana-plasma bovis,and 186 of Coxiella-like endosymbiont.R.hei-longjiangensis HY2 detected in this study and Anhui B8 strain,Ca.R.jingxinensis QL3 and those from Shanxi Prov-ince and Jiangsu Province,A.bovis JX4 and those from Shanxi Province were clustered on the same branch.Overall,17 ticks had combined infections and none of the 5 bacteria were detected in two Amblyomma testudinarium ticks.This is the first report of Ca.R.jingxinensis detected in H.longicornis ticks from Anhui Province.It is recommended that the two types of Rickettsia that cause spotted fever and A.bovis should be reported to local health authorities to initiate appropriate prevention and control measures.

A boy,aged 14 years,was admitted due to recurrent cough and expectoration for more than 1 month,with aggravation and fever for 2 days. After admission,he presented with tachypnea and a significant reduction in transcutaneous oxygen saturation,and emergency chest CT examination showed large patchy exudation and consolidation of both lungs. The boy was given tracheal intubation and invasive mechanical ventilation immediately,and his condition was improved after active symptomatic treatment. On the 10th day of hospitalization,the boy experienced fever again,and the laboratory tests showed positive results for Epstein-Barr virus and Mycoplasma antibody IgM,along with pancytopenia,elevated triglycerides,decreased fibrinogen,and increased levels of ferritin and soluble CD25. The boy was diagnosed with hemophagocytic lymphohistiocytosis. Bone marrow biopsy showed the presence of atypical lymphocytes,and aggressive natural killer cell leukemia was considered according to clinical manifestations and flow cytometry immunophenotype. Therefore,the possibility of hemophagocytic lymphohistiocytosis should be suspected in case of severe infection with pancytopenia and rapid disease progression,and hematological malignancies should also be ruled out. Bone marrow biopsy should be performed as early as possible to make a confirmed diagnosis and perform timely treatment.