Triple-negative breast cancer (TNBC) is aggressive, with high recurrence rates and poor prognosis. Paclitaxel (PTX) remains a key chemotherapeutic agent for TNBC, but its efficacy diminishes due to the emergence of drug resistance, largely driven by cancer stem-like cells (CSCs), vasculogenic mimicry (VM) formation and tumor immunosuppressive microenvironment (TIME). Pyruvate kinase M2 (PKM2) is highly expressed in TNBC, and is a potential target for TNBC treatment. In this study, we developed a biomimetic codelivery system using albumin nanoparticles (termed S/P NP) to co-encapsulate PTX and shikonin (SHK), a natural inhibitor of PKM2. By inhibiting PKM2, SHK suppressed β-Catenin signaling, thereby reversing CSC stemness and preventing VM formation. The S/P NP system exhibited tumor-targeting delivery effect and significantly inhibited TNBC growth and lung metastasis. Mechanistically, the treatment reversed epithelial-mesenchymal transition (EMT) and stem-like properties of TNBC cells, suppressed VM formation, and remodeled the TIME. It reduced immunosuppressive cells (M2 macrophages, MDSCs) while promoting anti-tumor immunity (M1 macrophages, dendritic cells, cytotoxic T cells, and memory T cells). This dual-action strategy holds promise for improving TNBC therapy by targeting CSCs, VM, and the immune microenvironment, and for overcoming PTX resistance and reducing metastasis.

Intentional tooth replantation (ITR) is an advanced treatment modality and the procedure of last resort for preserving teeth with inaccessible endodontic or resorptive lesions. ITR is defined as the deliberate extraction of a tooth; evaluation of the root surface, endodontic manipulation, and repair; and placement of the tooth back into its original socket. Case reports, case series, cohort studies, and randomized controlled trials have demonstrated the efficacy of ITR in the retention of natural teeth that are untreatable or difficult to manage with root canal treatment or endodontic microsurgery. However, variations in clinical protocols for ITR exist due to the empirical nature of the original protocols and rapid advancements in the field of oral biology and dental materials. This heterogeneity in protocols may cause confusion among dental practitioners; therefore, guidelines and considerations for ITR should be explicated. This expert consensus discusses the biological foundation of ITR, the available clinical protocols and current status of ITR in treating teeth with refractory apical periodontitis or anatomical aberration, and the main complications of this treatment, aiming to refine the clinical management of ITR in accordance with the progress of basic research and clinical studies; the findings suggest that ITR may become a more consistent evidence-based option in dental treatment.
Humans ; Tooth Replantation/methods* ; Consensus ; Periapical Periodontitis/surgery*

Objective Genomic alterations and potential neoantigens for cervical cancer immunotherapy were identified in a cohort of Chinese patients with cervical squamous cell carcinoma(CSCC). Methods Whole-exome sequencing was used to identify genomic alterations and potential neoantigens for CSCC immunotherapy.RNA Sequencing was performed to analyze neoantigen expression. Results Systematic bioinformatics analysis showed that C>T/G>A transitions/transversions were dominant in CSCCs.Missense mutations were the most frequent types of somatic mutation in the coding sequence regions.Mutational signature analysis detected signature 2,signature 6,and signature 7 in CSCC samples.PIK3CA,FBXW7,and BICRA were identified as potential driver genes,with BICRA as a newly reported gene.Genomic variation profiling identified 4,960 potential neoantigens,of which 114 were listed in two neoantigen-related databases. Conclusion The present findings contribute to our understanding of the genomic characteristics of CSCC and provide a foundation for the development of new biotechnology methods for individualized immunotherapy in CSCC.

Aiming at the hysteresis and destructiveness of off-line static detection of critical quality attribute of the moisture content of the raw material unit of the traditional Chinese medicine manufacturing process, honey-processed Tussilago farfara, honey-processed Astragalus and honey-processed Glycyrrhiza uralensis were used as the research carriers, and the drying method was used to measure the moisture content as a reference value. The moving stage was used to simulate the movement process of samples on the conveyor belt in the actual on-site production process, and near-infrared (NIR) spectra were collected, combined with machine learning, to establish NIR on-site dynamic detection model of moisture content in multi-variety honey-processed Chinese herbal slice. The results show that the second derivative method is used to preprocess the spectrum. The number of decision trees (ntree), the number of random features (max feature), and the minimum number of samples for generating leaf nodes (node size) are selected: 46, 76, and 8, respectively. The quantitative analysis model of moisture content has the best effect. The prediction coefficient of determination (the prediction coefficient of determination, R²_pre) and the root mean square error of prediction (root mean square error of prediction, RMSEP) of the model were 0.903 2 and 0.330 2, respectively. The NIR quantitative model for the moisture content of multi-variety honey-processed Chinese herbal slice established in this study has good predictive performance, and can achieve rapid, accurate and non-destructive quantitative analysis of the moisture content of honey-processed Tussilago farfara, honey-processed Astragalus and honey-processed Glycyrrhiza uralensis at the same time, and provides a method for determining the moisture content of honey-processed Chinese herbal slice of the raw material unit of the traditional Chinese medicine manufacturing process.

Objective:To observe any effect of a half palm ankle-foot orthosis and a hollow-heel ankle-foot orthosis on the gait of stroke survivors.Methods:The walking of twenty-five stroke survivors was quantified using a gait analysis system. They walked barefoot, wearing a half palm ankle-foot orthosis and wearing a hollow-heel ankle-foot orthosis. Walking speed, step frequency, duration of the swing phase on the healthy and affected sides, risk of falling and Timed Up and Go (TUG) test times were recorded and analyzed.Results:The average gait frequency when wearing the hollow-heel ankle-foot orthosis was significantly faster than that in the other two conditions. The gait asymmetry coefficient was significantly different when the subjects wore the hollow-heel ankle-foot orthosis compared with walking barefoot. Compared with being barefoot, the average TUG time was significantly shorter when wearing either orthosis and the risk of falling was significantly less. The fall risk was significantly lower when wearing the hollow-heel orthosis compared to the half palm orthosis.Conclusion:Wearing either ankle-foot orthosis can significantly correct the gait of stroke survivors and lower their risk of falling, with better effect when wearing the hollow-heel ankle-foot orthosis.

Objective:To explore the surgical strategy of coronary artery bypass grafting(CABG) for moderate ischemic mitral regurgitation(IMR), and to clarify the impact of mitral valve surgical intervention(MVS) on the long-term prognosis of such patients.Methods:The clinical data of 234 consecutive patients with moderate IMR who received CABG from January 2013 to December 2018 were retrospectively included, with 184 males and 50 females. The age ranged from 29 to 78 years, with a mean of(61.5 ± 8.7) years old. According to whether MVS was performed at the same time, they were divided into CABG group(108 cases, CABG alone) and CABG+ MVS group(126 cases, CABG+ MVS at the same time). The long-term cardiac events, all-cause deaths, major cardiovascular and cerebrovascular adverse events(MACCE) and other end events were followed up. A matching queue was established by propensity matching score for statistical analysis.Results:After propensity matching score, a matching queue was established, including 78 pairs of patients. Survival analysis showed that the incidence of long-term cardiac events and postoperative new onset atrial fibrillation in CABG+ MVS group was significantly higher( P<0.05). However, there was no significant difference between the two groups in all-cause mortality, cardiogenic mortality, and the incidence of MACCE events( P>0.05). Cox regression analysis showed that simultaneous CABG+ MVS was a risk factor for long-term cardiac events and new postoperative atrial fibrillation. The results of subgroup studies showed that for patients without tricuspid regurgitation before operation, left ventricular end diastolic diameter>55 mm, and left ventricular ejection fraction(LVEF) ≤0.55, the probability of cardiac events after MVS at the same time of CABG was higher( P<0.05). However, patients with no tricuspid regurgitation before operation, left ventricular end diastolic diameter>55 mm, LVEF≤0.55, and left atrial diameter≥40 mm had a higher probability of atrial fibrillation after MVS at the same time of CABG( P<0.05). Conclusion:CABG can improve left ventricular remodeling in patients with moderate IMR, whether MVS intervention is performed at the same time or not, and the long-term survival rate of both is similar. CABG+ MVS in the same period can maintain a low residual reflux, but the incidence of long-term cardiac events and arrhythmias is high. The longer-term prognosis needs to be further studied. The surgical strategy of such patients should be selected individually according to the specific situation and the surgical quality in medical centers.

Background The current oil production determines oil workers’ occupational noise exposure. Without effective protection, noise will affect various aspects of worker’s body functions, including acting on the adrenal cortex system and resulting in renal function damage. Objective To evaluate the associations of noise exposure and its cumulative exposure level with renal function impairment of oil workers. Methods Oil workers from a collective medical examination in a hospital were selected as the study subjects. In accordance with the national standard Measurement of Physical Agents in the Workplace Part 8: Noise (GBZ/T 189.8—2007), noise exposure was measured three times at the oil workers' work site, and their average value was calculated to obtain the cumulative noise exposure (CNE). A questionnaire survey was conducted to collect general information such as socio-demographic characteristics, family history, lifestyles, and occupational history. All blood biochemical indicators were measured in the fasting state. Renal function impairment was judged based on the glomerular filtration rate. The relationship between CNE and renal function was analyzed using receiver operating characteristic curve (ROC) for workers with noise exposure. Results A total of 2 917 subjects were included in the study and their prevalence of renal function impairment was 14.2%. The univariate analysis results suggested statistically significant differences in the prevalence of renal function impairment among the oil workers grouped by having hypertension or not, gender, age, marital status, marital status, smoking, and alcohol consumption (P＜0.05); the prevalence of renal impairment was significantly higher in those with abnormal values of uric acid, total cholesterol, triglycerides, high-density lipoprotein, and fasting glucose than in those with normal values (P＜0.05); the oil workers with noise exposure [n=1565, 53.7%, equivalent sound level ≥80 dB(A)] showed a higher prevalence of renal function impairment than those without (P＜0.05). The results of multiple logistic regression analysis showed that being female (OR=2.811, 95%CI: 1.960-4.030), age at 31 years and above (OR_31-40=3.502, 95%CI: 1.402-8.751; OR_41-50=4.255, 95%CI: 1.759-10.291; OR_≥51=7.179, 95%CI: 2.864-17.996), showing abnormal uric acid (OR=5.932, 95%CI: 4.486-7.843), having hypertension (OR=1.593, 95%CI: 1.230-2.063), alcohol consumption (OR=2.648, 95%CI: 1.346-5.212), and smoking (OR=1.816, 95%CI: 1.133-2.911) had higher risks of developing renal function impairment; besides, those exposed to noise had 1.351 times (95%CI: 1.073-1.702) higher risks of developing renal function impairment than non-exposed individuals. Noise-exposed oil workers in the renal impairment group had higher noise exposure intensity and CNE compared to the noise-exposed oil workers in the normal renal function group (P＜0.05), and the workers had an increased risk of renal function impairment when the CNE was >95.85 dB(A)·year versus CNE ≤ 95.85 dB(A)·year (OR=2.583, 95%CI: 1.956-3.411). Conclusion Exposure to noise, higher noise exposure intensity, and higher level of CNE may be associated with developing renal function impairment in oil workers. Oil workers with CNE above 95.85 dB(A)·year are at an increased risk of renal impairment.

Objective:To analyze pathogenic variant s of KMT2A gene in a child with Wiedemann-Steiner syndrome (WDSTS) and provide reliable evidences for clinical diagnosis of WDSTS. Methods:Whole-DNAs were extracted from an 9 years-old boy and his parents. Trio-whole exome sequencing (trio-WES) was performed to identify candidate pathogenic variants that can explain the boy’s condition and sanger sequencing was conducted to prove it. The impact of detected variants were predicted and validated by bioinformatics tools.Results:A de novo frameshift variant c. 10488dupG (p.Leu3498Thrfs*41) in exon 27 of KMT2A gene was detected and this de novo variant (PS2) had not been reported in the world previously. This frameshift variant was absent in major allele frequency databases (PM2) and had been predicted to be pathogenic based on MutationTaster. Through HomoloGene and CD-search system, the 3498 locus (Leu) in KMT2A protein, which was an important histone modifying enzyme that regulated gene expression in early embryonic development and encoded by the KMT2A gene, was predicted as a high conserved locus (PP3), and that replacement of Lue3498 may result in frame-shifts with premature termination in 3539 locus by introducing stop codon, causing deletion of multiple functional domains which all played important roles on histone modifications and recognition (PVS1+ PM1). According to the American College of Medical Genetics and Genomics variant classification guideline, the variant c. 10488dupG (p.Leu3498Thrfs*41) in KMT2A was classified as pathogenic variant (PVS1+ PS2+ PM1+ PM2+ PP3). Conclusion:The patient’s condition may be attributed to the de novo frameshift variant c. 10488dupG (p.Leu3498Thrfs*41) in KMT2 A gene. This study reported a pathogenic KMT2A variant that had not been reported previously in WDSTS, it expanded the genotypic spectrums of KMT2A variants.

Artemisia Argyi Folium, a traditional Chinese medicine of important medicinal and economic value, sees increasing demand in medicinal and moxibustion product market. Screening stable and reliable reference genes for quantitative real-time PCR(qRT-PCR) is a prerequisite for the analysis of gene expression in Artemisia argyi. In this study, eight commonly used reference genes, Actin, 18s, EF-1α, GAPDH, SAND, PAL, TUA, and TUB, from the transcriptome of A. argyi, were selected as candidate genes. The expression of each gene in different tissues(roots, stems, and leaves) of A. argyi and in leaves of A. argyi after treatment with methyl jasmonate(MeJA) for different time(0, 4, 8, 12 h) was detected by qRT-PCR. Then, geNorm, NormFinder, BestKeeper, ΔCT, and RefFinder were employed to evaluate their expression stability. The results demonstrated that Actin was the most stable reference gene in different tissues and in leaves treated with MeJA, and coming in the second was SAND. Furthermore, the expression of DXS and MCT which are involved in terpenoid backbone biosynthesis was detected in different tissues and after MeJA treatment. The results showed that the expression patterns of DXS and MCT in different tissues and under MeJA treatment calculated with Actin and SAND as internal reference genes were consistent, which validated the screening results. In conclusion, Actin is the most suitable reference gene for the analysis of gene expression in different tissues of A. argyi and after MeJA treatment. This study provides valuable information for gene expression analysis in A. argyi and lays a foundation for further research on molecular mechanism of quality formation of Artemisia Argyi Folium.
Artemisia/genetics* ; Gene Expression Profiling ; Genes, Plant/genetics* ; Plant Leaves/genetics* ; Real-Time Polymerase Chain Reaction ; Reference Standards ; Transcriptome

Drug instructions,the statutory and technical documents recording effectiveness and safety information,are an important basis for guiding doctors,pharmacists,and patients to use drugs rationally,and their scientificity,standardization,and accuracy directly affect the medication safety of the public. The sections of adverse drug events,contraindications,precautions,warnings,and application for specific populations in drug instructions directly express safety information and measures for rational use of drugs. In the drug life cycle,marketing authorization holders( MAHs) need to update safety information in the instructions promptly to ensure the safety and effectiveness of clinical drug medication. At present,revising instructions is an important measure to control drug risks. In the drug life cycle,in order to standardize the revision of safety information in the instructions by MAHs and eliminate inexact terms such as " unclear",the Technical Specifications for Revision of Safety Information in Marketed Chinese Patent Medicine Instructions,a series of group standards,have been established under the guidance of Standardization Department,China Association of Chinese Medicine. Therefore,on the basis of the existing rules and regulations,the standardized technical procedures for revising instructions came into being to help clinical safe and rational medication of drugs,and implement the strategy of " Healthy China".
China ; Drug-Related Side Effects and Adverse Reactions ; Drugs, Chinese Herbal/adverse effects* ; Humans ; Medicine, Chinese Traditional ; Nonprescription Drugs/adverse effects* ; Reference Standards