ObjectiveTaking Aurantii Fructus Immaturus juice（AFI）-processed Atractylodis Macrocephalae Rhizoma（AMR） as an example， this study aims to systematically compare the volatile and non-volatile components of AMR and its processed products， investigate the key differential components， evaluate their anti-inflammatory activities， and elucidate the synergistic mechanism of processing. MethodsThe chemical compositions of volatile and non-volatile components in AMR and AFI-processed AMR were systematically characterized using gas chromatography-mass spectrometry（GC-MS） and ultra-performance liquid chromatography-quadrupole-time-of-flight mass spectrometry（UPLC-Q-TOF-MS）， with relative mass fractions and response values determined separately. Volatile components were identified through searches in the National Institute of Standards and Technology（NIST）17 database， comparison with retention index（RI） and fragmentation pattern matching. Non-volatile components were identified by searching Waters Traditional Chinese Medicine （TCM） spectral library， in conjunction with PubChem and MassBank， characteristic fragmentation patterns and response values were also used to support identification. Differential components were screened using principal component analysis（PCA）， orthogonal partial least squares-discriminant analysis（OPLS-DA）， with variable importance in the projection（VIP） value >1. Components with high log₂fold change（FC） among major differential groups were selected as those exhibiting significant changes before and after processing. The anti-inflammatory activity of the differential compounds was evaluated by assessing their effects on nitric oxide（NO） production in a lipopolysaccharide（LPS）-induced RAW264.7 macrophage model. Enzyme-linked immunosorbent assay（ELISA） was used to detect the effects of the differential components on tumor necrosis factor（TNF）-α， interleukin（IL）-1β， IL-6， and monocyte chemotactic protein（MCP）-1 levels， and immunofluorescence（IF） was employed to assess their effects on nuclear transcription factor（NF）-κB p65 translocation， thereby elucidating the underlying molecular mechanisms. ResultsA total of 36 compounds were identified in the volatile components of AMR and AFI-processed AMR， among which， sesquiterpenes and monoterpenes were significantly increased after processing. In the non-volatile components， 36 compounds were identified， and the main differential components were flavonoids， sesquiterpenoids， and triterpenoids. Flavonoids were the primary differential components distinguishing AMR from its processed products， representing compounds directly introduced during processing. Five compounds， including atractylenolide Ⅲ， tangeritin， nobiletin， hesperidin and narirutin， were selected as representatives of three classes based on their most prominent differential expression among different compound types for subsequent anti-inflammatory activity studies. The results showed that 100 μmol·L^-1 tangerine and narirutin could significantly inhibit LPS-induced NO production（P<0.01） in a concentration-dependent manner. Tangeritin was able to significantly inhibit the levels of TNF-α and MCP-1 secreted by RAW264.7（P<0.05）， while narirutin significantly inhibited the levels of TNF-α， IL-1β， MCP-1 and IL-6（P<0.01）. IF revealed that both tangeritin and narirutin significantly blocked the translocation of NF-κB p65 from the cytoplasm to the nucleus. ConclusionAFI-processed AMR significantly alters the chemical composition profile of AMR， and the newly introduced flavonoid components during processing may be key to its enhanced anti-inflammatory effects.

Hepatocellular carcinoma （HCC） is the sixth most common cancer in the world. In recent years， the clinical early diagnosis and treatment protocols of HCC have been improved， whereas the prognosis of patients is still not satisfactory， which is due to the fact that the mechanism of HCC development has not been fully elucidated. Therefore， it is of great significance to explore the molecular mechanisms and key regulatory links of hepatocellular carcinoma development to further improve the diagnosis and treatment of HCC in China. Epigenetics has become a research hotspot because of its reversibility and easy regulation. According to relevant studies， HCC involves the accumulation of multiple genetic and epigenetic changes during the initiation， promotion， and progression stages. HCC is categorized as infantile malnutrition with accumulation， hypochondriac pain， tympan ites， and abdominal mass in traditional Chinese medicine （TCM）. In the treatment of HCC， TCM with low toxicity， multi-targets， and multi-mechanisms can inhibit tumor growth， alleviate the clinical symptoms， and enhance the quality of life of the patients. Chinese medicines and their active ingredients exert anti-HCC effects through epigenetic regulation of DNA methylation， histone modification， and non-coding RNA. Abnormal gene expression due to epigenetic regulation disorders is involved in all stages of HCC development. There are few studies on epigenetic regulation in TCM treatment of HCC， and there is still much room for development in basic and clinical trials. This paper reviews the mechanism of epigenetic regulation in HCC and summarizes the experimental results of TCM research on the related mechanism， with a view to providing a theoretical basis for future research on the mechanism of HCC development and clinical diagnosis and treatment of hepatocellular carcinoma with TCM.

ObjectiveTo explore the effect of core stability training on dynamic balance and surface electromyography (sEMG) after anterior cruciate ligament reconstruction (ACLR), and to analyze the correlation between balance index and sEMG. MethodsFrom March to December, 2022, 32 patients with ACLR in Yantai Affiliated Hospital of Binzhou Medical University were randomly divided into control group (n = 16) and experimental group (n = 16). The control group accepted routine rehabilitation treatment, and the experimental group added core stability training, for six weeks. They were evaluated with American Hospital for Special Surgery Knee Score (HSS) and International Knee Documentation Committee Knee Score (IKDC), and the dynamic balance function and sEMG were measured before and after treatment, and the correlation between dynamic balance index and root mean square (RMS) of sEMG was analyzed. ResultsAfter treatment, the scores of HSS and IKDC increased significantly in both groups (|Z| > 3.526, |t| > 63.544, P < 0.001), and were better in the experimental group than in the control group (Z = -2.392, t = 2.650, P < 0.05); the length of gait line and single support line increased significantly, the medial-lateral displacement displacement decreased (|t| > 2.368, Z = -3.516, P < 0.05), and they were better in the experimental group than in the control group (|t| > 2.497, Z = -3.091, P < 0.05); the RMS of gluteus maximus and gluteus medius increased in the experimental group (t = -5.900, Z = -2.741, P < 0.01), and were better than those in the control group (t = 3.930, Z = -3.260, P < 0.01). After treatment, the RMS of gluteus maximus and gluteus medius in both groups were positively correlated with gait line length and single support line length, and were negatively correlated with medial-lateral displacement (|r| > 0.502, P < 0.01). ConclusionCore stability training could significantly improve knee joint function and dynamic balance, and enhance the activation of gluteus maximus and gluteus medius. Dynamic balance is highly correlated with sEMG.

H 1-antihistamines are widely used in the treatment of various allergic diseases, but there are still many challenges in the safe and rational use of H 1-antihistamines in pediatrics, and there is a lack of guidance on the prescription review of H 1-antihistamines for children.In this paper, suggestions are put forward from the indications, dosage, route of administration, pathophysiological characteristics of children with individual difference and drug interactions, so as to provide reference for clinicians and pharmacists.

OBJE CTIVE To establish a method for quality evaluation of Xin ’an capsule by combining fingerprint ， multi-component quantitative analysis and chemical pattern recognition analysis. METHODS High performance liquid chromatography（HPLC）combined with Similarity Evaluation System of TCM Chromatogram Fingerprint （2012 edition）were used to establish the fingerprints of 24 batches of Xin ’an capsules and evaluate the similarity. The common peaks were determined. The contents of glucosylvitexin ，rhamnosylvitexin，vitexin，hyperoside and isoquercetin in Xin ’an capsules were determined by the same HPLC method. Taking the common peak area of fingerprint as the variable ，MetaboAnalyst 5.0 tool was used to draw the cluster analysis （CA）heat map. SIMCA 14.1 software was used to perform principle component analysis （PCA）and partial least squares-discriminant analysis （PLS-DA）. RESULTS Twelve common peaks were identified with the similarity greater than 0.97. Six common peaks were identified as chlorogenic acid ，glucosylvitexin，rhamnosylvitexin，vitexin，hyperoside and isoquercetin.The linear range of glucosylvitexin ，rhamnosylvitexin，vitexin， hyperoside and isoquercetin were 2.36-151.35，9.15-585.20， 1.20-76.50， 0.68-43.20， 0.44-27.90 µg/mL（all r＞0.999）.RSDs of precision ，repeatability and stability （24 h）tests were 163.com all less than 2.00％ . The average recoveries were 95.80％（RSD＝0.96％ ，n＝6），102.10％ （RSD＝0.93％ ，n＝6）， 103.26％（RSD＝1.28％，n＝6），103.89％（RSD＝0.73％，n＝6） and 102.09％（RSD＝1.79％，n＝6），respectively. The contents of the five components were 0.988 8-1.559 1，4.336 6-11.220 1， 0.065 1-0.830 5，0.043 8-0.692 5 and 0.023 2-0.427 2 mg/grain，respectively. The results of CA and PCA showed that 24 batches of samples could be divided into three categories ，i.e. S 1-S15，S16-S18 and S 19-S24. PLS-DA showed that variable importance in projection values of the corresponding component of peak 6 and glucosylvitexin （peak 7），rhamnosylvitexin（peak 8），hyperoside （peak 10） and isoquercetin （peak 11） were greater than 1. CONCLUSIONS The established HPLC fingerprint and multi-component quantitative method are simple and feasible. Combined with chemical pattern recognition analysis ，it can be used for the quality control of Xin ’an capsules. Glucosylvitexin ，rhamnosylvitexin and other components may be differentital markers affecting the quality of each batch of samples.

Objective:To investigate the value of multimodal MRI radiomics in the preoperative prediction of Fuhrman nuclear grade of clear cell renal cell carcinoma (ccRCC).Methods:A total of 129 patients with ccRCC confirmed by pathology from April 2011 to April 2021 in Third Affiliated Hospital of Soochow University were collected, and the imaging and clinicopathological data were retrospectively analyzed. All patients were divided into training set ( n=90) and validation set ( n=39) at the ratio of 7∶3 using random indicator method. According to the postoperative pathological results, Fuhrman grades Ⅰ and Ⅱ were included in the low grade group (96 cases, 65 cases in the training set and 31 cases in the validation set), and Fuhrman grades Ⅲ and Ⅳ were included in the high grade group (33 cases, 25 cases in the training set and 8 cases in the validation set). Two radiologists manually delineated regions of interest (ROI) on T 1WI, T 2WI, Dixon-water, Dixon-fat, susceptibility weighted imaging (SWI), blood oxygen level dependent (BOLD) images, and 396 texture features were extracted from each ROI. In the training set, intra-class correlation coefficient, Mann-Whitney U test, minimum redundancy maximum relevance and least absolute shrinkage and selection operator method were used to reduce the dimension of features to obtain the best texture features. The logistic regression was used to develop the multimodal radiomics model, and the receiver operating characteristic (ROC) curve was used to evaluate the effectiveness of the model in identifying high and low-grade ccRCC in training set and validation set. Results:Four SWI, one T 2WI and one BOLD texture features were selected for modeling. The areas under the ROC curve (95%CI) of the multimodal radiomics model for identifying high and low grade ccRCC in the training and validation sets were 0.859 (0.770-0.923) and 0.883 (0.740-0.964), with the specificity at 95.4% and 87.1%, the sensitivity at 68.0% and 87.5%, the accuracy at 87.8% and 87.2%, respectively. Conclusion:The multimodal MRI radiomics model based on T 2WI, SWI and BOLD images has high effectiveness in preoperative predicting Fuhrman nuclear grade of ccRCC.

Antipyretic-analgesics are currently one of the most prescribed drugs in children.The clinical application of antipyretic-analgesics for children in our country still have irrational phenomenon, which affects the therapeutic effect and even poses hidden dangers to the safety of children.In this paper, suggestions were put forward from the indications, dosage form/route, dosage suitability, pathophysiological characteristics of children with individual differences and drug interactions in the symptomatic treatment of febrile children, so as to provide reference for the general pharmacists when conducting prescription review.

OBJECTIVE: To analyze the clinical and genetic characteristics of a patient with congenital isolated adrenocorticotropic hormone deficiency (IAD). METHODS: Clinical characteristics of the patient was reviewed. Genomic DNA of the child was subjected to whole exome sequencing. RESULTS: Genetic testing has confirmed the diagnosis of congenital IAD by identification of compound heterozygous variants of the TBX19 gene, which included a pathogenic nonsense c.535C>T (p.R179X) variant inherited from his father and a novel missense c.298C>T (p.R100C) variant inherited from his mother. CONCLUSION Congenital IAD due to variants of the TBX19 gene is a rare autosomal recessive disease. It is characterized by low plasma adrenocorticotropic hormone and cortisol levels but normal levels of other pituitary hormones. Delayed diagnosis may lead to severe early-onset adrenal failure and wrong treatment which may result in neonatal mortality. Hydrocortisone replacement is effective. Detection of pathogenic variant of TBX19 gene is the key to diagnosis.
Adrenal Insufficiency/genetics* ; Child ; Homeodomain Proteins/genetics* ; Humans ; T-Box Domain Proteins/genetics*

Drug delivery with customized combinations of drugs, controllable drug dosage, and on-demand release kinetics is critical for personalized medicine. In this study, inspired by successive opening of layered structures and compartmentalized structures in plants, we designed a multiple compartmentalized capsular structure for controlled drug delivery. The structure was designed as a series of compartments, defined by the gradient thickness of their external walls and internal divisions. Based on the careful choice and optimization of bioinks composed of gelatin, starch, and alginate, the capsular structures were successfully manufactured by fused deposition modeling three-dimensional (3D) printing. The capsules showed fusion and firm contact between printed layers, forming complete structures without significant defects on the external walls and internal joints. Internal cavities with different volumes were achieved for different drug loading as designed. In vitro swelling demonstrated a successive dissolving and opening of external walls of different capsule compartments, allowing successive drug pulses from the capsules, resulting in the sustained release for about 410 min. The drug release was significantly prolonged compared to a single burst release from a traditional capsular design. The bioinspired design and manufacture of multiple compartmentalized capsules enable customized drug release in a controllable fashion with combinations of different drugs, drug doses, and release kinetics, and have potential for use in personalized medicine.

OBJECTIVE: To analyze the clinical and genetic characteristics of a patient with dihydrolipoamide dehydrogenase deficiency. METHODS: Potential variants of the DLD gene were detected by whole exome sequencing and verified by Sanger sequencing. RESULTS: Compound heterozygous variants, c.704_705delTT (p.Leu235Argfs*8) and c.1058T>C (p.Ile353Thr), were detected in the DLD gene. The c.1058T>C (p.Ile353Thr) variant was derived from his mother and known to be pathogenic. The c.704_705delTT (p.Leu235Argfs*8) variant was derived from his father and was unreported previously. CONCLUSION The compound heterozygous variants of c.704_705delTT (p.Leu235Argfs*8) and c.1058T>C (p.Ile353Thr) of the DLD gene probably underlay the disease in this patient. Above finding has facilitated genetic counseling and prenatal diagnosis for the family.
Acidosis, Lactic/genetics* ; Dihydrolipoamide Dehydrogenase/genetics* ; Female ; Genetic Testing ; Genetic Variation ; Humans ; Male ; Maple Syrup Urine Disease/genetics* ; Pregnancy ; Whole Exome Sequencing