Conformational and static properties of tagged chains in solvents: effect of chain connectivity in solvent molecules.

Polymer chains immersed in different solvent molecules exhibit diverse properties due to multiple spatiotemporal scales and complex interactions. Using molecular dynamics simulations, we study the conformational and static properties of tagged chains in different solvent molecules. Two types of solvent molecules were examined: one type consisted of chain molecules connected by bonds, while the other type consisted of individual bead molecules without any bonds. The only difference between the two solvent molecules lies in the chain connectivity. Our results show a compression of the tagged chains with the addition of bead or chain molecules. Chain molecule confinement induces a stronger compression compared to bead molecule confinement. In chain solvent molecules, the tagged chain's radius of gyration reached a minimum at a monomer volume fraction of ∼0.3. Notably, the probability distributions of chain size remain unchanged at different solvent densities, irrespective of whether the solvent consists of beads or polymers. Furthermore, as solvent density increases, a crossover from a unimodal to a bimodal distribution of bond angles is observed, indicating the presence of both compressed and expanded regions within the chain. The effective monomer-solvent interaction is obtained by calculating the partial radial distribution function and the potential of the mean force. In chain solvents, the correlation hole effect results in a reduced number of nearest neighbors around tagged monomers compared to bead solvents. The calculation of pore size distribution reveals that the solvent nonhomogeneity induced by chain connectivity leads to a broader distribution of pore sizes and larger pore dimensions at low volume fractions. These findings provide a deeper understanding of the conformational behavior of polymer chains in different solvent environments.

Two-dimensional Janus SbTeBr/SbSI heterostructures as multifunctional optoelectronic systems with efficient carrier separation.

The stacking of two-dimensional (2D) materials is a highly effective approach in the design of high-performance optoelectronic devices. In this study, we propose a novel Janus monolayer-based 2D/2D van der Waals heterostructure (vdWH) called SbTeBr/SbSI. Starting from its most stable binding configuration, we systematically examined its electronic, optical, mechanical and dynamical properties. The SbTeBr/SbSI vdWH exhibits a type II band arrangement, with an indirect bandgap of 1.28 eV and strong light absorption capabilities in the visible range, achieving an absorption coefficient of 4 × 105 cm-1. These desirable properties suggest that SbTeBr/SbSI holds promise as a material for solar cells, potentially achieving a power conversion efficiency of 8.3%. The dipole-induced electric field in the SbTeBr/SbSI vdWH leads to significant differences in the mobilities of different carriers, which is a critical aspect in suppressing the recombination of photogenerated carriers. Additionally, according to the simulations of nonadiabatic molecular dynamics, a long electron-hole recombination time of 133 ps is predicted. Thus, the SbTeBr/SbSI heterostructure enables efficient charge separation, demonstrating its potential as a high-performance optoelectronic material.

Performance Comparison of Machine Learning Models for Concrete Compressive Strength Prediction.

This study explores the prediction of concrete compressive strength using machine learning models, aiming to overcome the time-consuming and complex nature of conventional methods. Four models-an artificial neural network (ANN), a multiple linear regression, a support vector machine, and a regression tree-are employed and compared for performance, using evaluation metrics such as mean absolute deviation, root mean square error, coefficient of correlation, and mean absolute percentage error. After preprocessing 1030 samples, the dataset is split into two subsets: 70% for training and 30% for testing. The ANN model, further divided into training, validation (15%), and testing (15%), outperforms others in accuracy and efficiency. This outcome streamlines compressive strength determination in the construction industry, saving time and simplifying the process.

[Ag4Br6] cluster-based 3D bromoargentate hybrid: crystal structure, optical/photoelectrical performance and theoretical study.

The self-assembly of cluster-based halide framework materials has been a matter of great interest but with great challenges. Herein, by exploiting hexamethylenetetramine (Hmta) with Td symmetry as a structural modifier, we successfully constructed and systematically characterized an unusual three-dimensional (3D) hybrid bromoargentate, namely K[NH4][Ag4Br6(Hmta)] (1), bearing a diamond-type [Ag4Br6(Hmta)]n2n- anionic skeleton built up from adamantane-like units of inorganic [Ag4Br6] clusters and organic Hmta ligands. UV-Vis diffuse reflectance analysis showed that the optical bandgap of the title compound was 2.68 eV, indicating a visible-light-responsive semiconductive behavior. More importantly, upon alternate light illumination, the so-designed compound exhibited remarkable photoelectric switching properties, with photocurrent densities (0.38 and 1.10 µA cm-2 for visible and full-spectrum light, respectively) that compete well with and even exceed those of some high-performance metal halide counterparts. Further theoretical calculations, including band structure, density of states, and wave functions, revealed that compound 1 has a unique valence band and conduction band distribution, rendering it with small effective masses (especially the electrons), which may be responsible for its good photoelectricity. Furthermore, in this work, Hirshfeld surface analysis, thermogravimetric analysis, and X-ray photoelectron spectroscopy (XPS) studies were performed.

Structurally diverse cucurbitane-type triterpenoids from the tubers of Hemsleya chinensis with cytotoxic activity.

Ten previously undescribed cucurbitane-type triterpenoids, namely hemslyencins A-F (1-6) and hemslyencosides A-D (7-10), together with twenty previously reported compounds (11-30), were isolated from the tubers of Hemsleya chinensis. Their structures were elucidated by unambiguous spectroscopic data (UV, IR, HR-ESI-MS, 1D and 2D NMR data). Hemslyencins A and B (1 and 2) possessing unique 9, 11-seco-ring system with a six-membered lactone moiety, were the first examples among of the cucurbitane-type triterpenoids, and hemslyencins C and D (3 and 4) and hemslyencoside D (10) are the infrequent pentacyclic cucurbitane triterpenes featuring a 6/6/6/5/6 fused system. The cytotoxic activities of all isolated compounds were evaluated against MCF-7, HCT-116, HeLa, and HepG2 cancer cells, and their structure-activity relationships (SARs) was discussed as well. Compounds 17, 25, and 26 showed significant cytotoxic effects with IC50 values ranging from 1.31 to 9.89 µM, among which compound 25 induced both apoptosis and cell cycle arrest at G2/M phase in a dose dependent manner against MCF-7 cells.

IDD10-NAC079 transcription factor complex regulates sheath blight resistance by inhibiting ethylene signaling in rice.

INTRODUCTION: Rhizoctonia solani Kühn is a pathogen causing rice sheath blight (ShB). Ammonium transporter 1 (AMT1) promotes resistance of rice to ShB by activating ethylene signaling. However, how AMT1 activates ethylene signaling remains unclear. OBJECTIVE: In this study, the indeterminate domain 10 (IDD10)-NAC079 interaction model was used to investigate whether ethylene signaling is modulated downstream of ammonium signaling and modulates ammonium-mediated ShB resistance. METHODS: RT-qPCR assay was used to identify the relative expression levels of nitrogen and ethylene related genes. Yeast two-hybrid assays, Bimolecular fluorescence complementation (BiFC) and Co-immunoprecipitation (Co-IP) assay were conducted to verify the IDD10-NAC079-calcineurin B-like interacting protein kinase 31 (CIPK31) transcriptional complex. Yeast one-hybrid assay, Chromatin immunoprecipitation (ChIP) assay, and Electrophoretic mobility shift assay (EMSA) were used to verify whether ETR2 was activated by IDD10 and NAC079. Ethylene quantification assay was used to verify ethylene content in IDD10 transgenic plants. Genetic analysis is used to detect the response of IDD10, NAC079 and CIPK31 to ShB infestation. RESULTS: IDD10-NAC079 forms a transcription complex that activates ETR2 to inhibit the ethylene signaling pathway to negatively regulating ShB resistance. CIPK31 interacts and phosphorylates NAC079 to enhance its transcriptional activation activity. In addition, AMT1-mediated ammonium absorption and subsequent N assimilation inhibit the expression of IDD10 and CIPK31 to activate the ethylene signaling pathway, which positively regulates ShB resistance. CONCLUSION: The study identified the link between ammonium and ethylene signaling and improved the understanding of the rice resistance mechanism.

A nomogram based on CT intratumoral and peritumoral radiomics features preoperatively predicts poorly differentiated invasive pulmonary adenocarcinoma manifesting as subsolid or solid lesions: a double-center study.

Background: The novel International Association for the Study of Lung Cancer (IASLC) grading system suggests that poorly differentiated invasive pulmonary adenocarcinoma (IPA) has a worse prognosis. Therefore, prediction of poorly differentiated IPA before treatment can provide an essential reference for therapeutic modality and personalized follow-up strategy. This study intended to train a nomogram based on CT intratumoral and peritumoral radiomics features combined with clinical semantic features, which predicted poorly differentiated IPA and was tested in independent data cohorts regarding models' generalization ability. Methods: We retrospectively recruited 480 patients with IPA appearing as subsolid or solid lesions, confirmed by surgical pathology from two medical centers and collected their CT images and clinical information. Patients from the first center (n =363) were randomly assigned to the development cohort (n = 254) and internal testing cohort (n = 109) in a 7:3 ratio; patients (n = 117) from the second center served as the external testing cohort. Feature selection was performed by univariate analysis, multivariate analysis, Spearman correlation analysis, minimum redundancy maximum relevance, and least absolute shrinkage and selection operator. The area under the receiver operating characteristic curve (AUC) was calculated to evaluate the model performance. Results: The AUCs of the combined model based on intratumoral and peritumoral radiomics signatures in internal testing cohort and external testing cohort were 0.906 and 0.886, respectively. The AUCs of the nomogram that integrated clinical semantic features and combined radiomics signatures in internal testing cohort and external testing cohort were 0.921 and 0.887, respectively. The Delong test showed that the AUCs of the nomogram were significantly higher than that of the clinical semantic model in both the internal testing cohort(0.921 vs 0.789, p< 0.05) and external testing cohort(0.887 vs 0.829, p< 0.05). Conclusion: The nomogram based on CT intratumoral and peritumoral radiomics signatures with clinical semantic features has the potential to predict poorly differentiated IPA manifesting as subsolid or solid lesions preoperatively.

Cardiac glycosides with cytotoxic activity from the seeds of Thevetia peruviana.

Phytochemical investigation on the extract of the seeds of Thevetia peruviana resulted in the isolation of six new cardiac glycosides, namely theveperosides A-F (1-6), including a rare 19-nor-cardenolide (1), together with seven known analogues (7-13). The chemical structures of these compounds were determined based on detailed spectroscopic analysis. The cytotoxic activities of 1-13 were evaluated against MCF-7, HCT-116, HeLa, and HepG2 cancer cell lines, and their structure-activity relationships (SARs) were investigated. Compound 3 exhibited the significant cytotoxic effects with IC50 values ranging from 0.032 to 0.055 µΜ, which could induce HepG2 cells apoptosis in a dose-dependent manner.

A novel approach has been developed to produce pure plant-based gel soy yogurt by combining soy proteins (7S/11S), high pressure homogenization, and glycation reaction.

This research sought to examine how the physicochemical characteristics of soy globulins and different processing techniques influence the gel properties of soy yogurt. The goal was to improve these gel properties and rectify any texture issues in soy yogurt, ultimately aiming to produce premium-quality plant-based soy yogurt. In this research study, the investigation focused on examining the impact of 7S/11S, homogenization pressure, and glycation modified with glucose on the gel properties of soy yogurt. A plant-based soy yogurt with superior gel and texture properties was successfully developed using a 7S/11S globulin-glucose conjugate at a 1:3 ratio and a homogenization pressure of 110 MPa. Compared to soy yogurt supplemented with pectin or gelatin, this yogurt demonstrated enhanced characteristics. These findings provide valuable insights into advancing plant protein gels and serve as a reference for cultivating new soybean varieties by soybean breeding experts.

Clinical study of Tongbu Qijing Acupuncture combined with metformin hydrochloride tablet in the treatment of polycystic ovary syndrome combined with insulin resistance of kidney-deficiency phlegm dampness type / 国际中医中药杂志

Objective:To evaluate the effect of Tongbu Qijing Acupuncture combined with metformin hydrochloride tablet on polycystic ovary syndrome (PCOS) combined with insulin resistance (IR) of kidney-deficiency phlegm dampness type.Methods:Randomized controlled trial. 84 patients with PCOS and IR in the hospital were enrolled as the observation objects between November 2019 and November 2021. According to random number table method, they were divided into observation group (Tongbu Qijing Acupuncture combined with metformin hydrochloride tablets) and control group (oral metformin hydrochloride tablets), 42 in each group. All were treated for 3 courses of treatment (1 month/course). TCM syndromes were scored before and after treatment. The height, weight, waist circumference and hip circumference of patients were measured to calculate body mass index (BMI) and waist-hip ratio (WHR). The levels of serum TG, TC, LDL-C and HDL-C were detected by biochemical analyzer, fasting blood glucose (FPG) was detected by glucose oxidase method, fasting insulin (FINS) was detected by electrochemiluminescence method, and insulin resistance index (HOMA-IR) was calculated. The recovery rates of menstruation and ovulation were observed and compared after treatment, and the clinical curative effect was evaluated.Results:There were significant differences in total response rate between observation group and control group [95.24% (40/42) vs. 80.95% (34/42); χ2=4.09, P=0.043]. After treatment, scores of TCM syndromes, BMI and WHR in observation group were significantly lower than those in the control group ( t=20.36, 23.77, 3.44, P<0.01). After treatment, serum FPG [(4.86±0.51) nmol/L vs. (5.41±0.55) nmol/L, t=4.75], FINS [(8.31±0.85) mU/L vs. (10.11±1.02) mU/L, t=8.79] levels and HOMA-IR [(1.88±0.19) vs. (2.44±0.25), t=11.97] in observation group were significantly lower than those in the control group ( P<0.01). After treatment, levels of serum TG, TC and LDL-C in observation group were significantly lower than those in the control group ( t=16.54, 4.81, 5.35, P<0.01), while HDL-C was significantly higher than that of the control group ( t=6.78, P<0.01). After treatment, there were significant differences in recovery rates of menstruation and ovulation between observation group and control group [57.14% (24/42), 47.62% (20/42) vs. 80.95% (34/42), 69.05% (29/42); χ2=5.57, 3.97, P<0.05]. Conclusion:Tongbu Qijing Acupuncture combined with metformin hydrochloride tablet can effectively improve syndromes and signs, regulate glucose-lipid metabolism, reduce IR and promote the recovery of menstruation and ovulation in patients with PCOS and IR.

Clinical characteristics and diagnostic indicators of macrophage activation syndrome in patients with systemic lupus erythematosus and adult-onset Still's disease / 北京大学学报(医学版)

OBJECTIVE@#To analyze and compare the clinical and laboratory characteristics of macrophage activation syndrome (MAS) in patients with systemic lupus erythematosus (SLE) and adult-onset Still's disease (AOSD), and to evaluate the applicability of the 2016 European League Against Rheumatism/American College of Rheumatology/Paediatric Rheumatology International Trials Organization classification criteria for MAS complicating systemic juvenile idiopathic arthritis (sJIA) in different auto-immune diseases contexts and to propose new diagnostic predictive indicators.@*METHODS@#A retrospective analysis was conducted on the clinical and laboratory data of 24 SLE patients with MAS (SLE-MAS) and 24 AOSD patients with MAS (AOSD-MAS) who were hospitalized at Peking University People's Hospital between 2000 and 2018. Age- and sex-matched SLE (50 patients) and AOSD (50 patients) diagnosed in the same period without MAS episodes were selected as controls. The cutoff values for laboratory indicators predicting SLE-MAS and AOSD-MAS were determined using receiver operating characteristic (ROC) curves. Furthermore, the laboratory diagnostic predictive values for AOSD-MAS were used to improve the classification criteria for systemic juvenile idiopathic arthritis-associated MAS (sJIA-MAS), and the applicability of the revised criteria for AOSD-MAS was explored.@*RESULTS@#Approximately 60% of SLE-MAS and 40% of AOSD-MAS occurred within three months after the diagnosis of the underlying diseases. The most frequent clinical feature was fever. In addition to the indicators mentioned in the diagnosis criteria for hemophagocytic syndrome revised by the International Society for Stem Cell Research, the MAS patients also exhibited significantly elevated levels of aspartate aminotransferase and lactate dehydrogenase, along with a significant decrease in albumin. Hemophagocytosis was observed in only about half of the MAS patients. ROC curve analysis demonstrated that the optimal discriminative values for diagnosing MAS was achieved when SLE patients had ferritin level≥1 010 μg/L and lactate dehydroge-nase levels≥359 U/L, while AOSD patients had fibrinogen levels≤225.5 mg/dL and triglyceride levels≥2.0 mmol/L. Applying the 2016 sJIA-MAS classification criteria to AOSD-MAS yielded a diagnostic sensitivity of 100% and specificity of 62%. By replacing the less specific markers ferritin and fibrinogen in the 2016 sJIA-MAS classification criteria with new cutoff values, the revised criteria for classifying AOSD-MAS had a notable increased specificity of 86%.@*CONCLUSION@#Secondary MAS commonly occurs in the early stages following the diagnosis of SLE and AOSD. There are notable variations in laboratory indicators among different underlying diseases, which may lead to misdiagnosis or missed diagnosis when using uniform classification criteria for MAS. The 2016 sJIA-MAS classification criteria exhibit high sensitivity but low specificity in diagnosing AOSD-MAS. Modification of the criteria can enhance its specificity.

Next-generation diagnostic pathology / 中华病理学杂志

With the technological progresses and applications of human genome sequencing, bioinformatics analysis and data mining, and molecular pathology and artificial intelligence-assisted pathological diagnosis, the development of clinical medicine is moving towards the era of precision diagnosis and treatment. In the context of this era, the traditional diagnostic pathology is facing unprecedented opportunities and challenges in our history and is striving towards the "next-generation diagnostic pathology" (NGDP). NGDP is based on histomorphology and clinical data, and characterized by the combination of molecular detection and bioinformatics analysis, intelligent sampling and process quality control, intelligent diagnosis and remote consultation, lesion visualization and "non-invasive" pathology as well as other innovative cutting edge interdisciplinary technologies. The NGDP reports will include the results from multi-omics and cross-scale integrated diagnosis for final diagnosis. NGDP will also be applied for predicting disease progression and outcomes, and determining optional therapeutics as well as assessing treatment responses, so that a novel "golden standard" of disease diagnosis can be established. In the near fature, it is necessary to stimulate the innovative vitality of pathology disciplines, accelerate the maturity and application for NGDP, update the theory and technical system of pathology, and perform its important applicable role in the prevention, diagnosis, treatment of diseases so that the futher development of clinical medicine will be promoted and the strategy for maintenance of being healthy in China will be served.

Validation of the Pollard' s classification criteria (2010) for rheumatoid arthritis patients with fibromyalgia / 北京大学学报(医学版)

OBJECTIVE@#To evaluate the sensitivity and specificity of Pollard' s classification criteria(2010) for the diagnosis of rheumatoid arthritis (RA) patients withfibromyalgia (FM) in Chinese patients, and to assess the clinical features and psychological status of RA-FM patients in a real-world observational setting.@*METHODS@#Two hundred and two patients with rheumatoid arthritis were enrolled from the outpatients in Rheumatology and Immunology Department in Peking University People' s Hospital. All the patients were evaluated whether incorporating fibromyalgia translation occured using the 1990 American College of Rheumatolgy (ACR)-FM classification criteria. Forty two RA patients were concomitant with FM, while the other one hundred and sixty RA patients without FM were set as the control group.@*RESULTS@#There was no significant difference in general demography between the two groups (P>0.05). In this study, the Pollard' s classification criteria (2010) for RA-FM in Chinese patients had a high sensitivity of 95.2% and relatively low specificity of 52.6%. Compared with those patients without FM, RA patients with FM (RA-FM patients) had higher Disease Activity Scale in 28 joints (DAS-28) score (5.95 vs. 4.38, P=0.011) and much more 28-tender joint counts (TJC) (16.5 vs.4.5, P < 0.001).RA-FM patients had worse Health Assessment Questionnaire (HAQ) score (1.24 vs. 0.66, P < 0.001) and lower SF-36 (28.63 vs. 58.22, P < 0.001). Fatigue was more common in RA-FM patients (88. 1% vs. 50.6%, P < 0.001) and the degree of fatigue was significantly increased in RA-FM patients (fatigue VAS 5.55 vs. 3.55, P < 0.001). RA-FM patients also had higher anxiety (10 vs.4, P < 0.001) and depression scores (12 vs.6, P < 0.001). erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), morning stiffness time and 28-swollen joint counts (SJC) showed no difference between these two groups.@*CONCLUSION@#The Pollard' s classification criteria (2010) for RA-FM are feasible in Chinese rheumatoid arthritis patients. The Pollard' s classification criteria is highly sensitive in clinical application, while the relativelylow specificity indicates that various factors need to be considered in combination. RA patients with FM result in higher disease activity, worse function aland psychological status. RA patients with FM also have poorer quality of life. DAS-28 scores may be overestimated in RA patients with FM. In a RA patient thatdoes not reach remission, the possibility of fibromyalgia should be con-sidered.

Comparison of values of immunocytochemical P16/Ki-67 double staining, P16 INK4α single staining and high-risk human papillomavirus testing in screening of high-grade cervical lesions / 肿瘤研究与临床

Objective:To investigate the screening values of immunocytochemical P16/Ki-67 double staining, P16 INK4α single staining and high-risk human papillomavirus (HR-HPV) testing for high-grade cervical lesions. Methods:The clinical data of 622 patients who underwent cervical thin-layer liquid-based cytology (TCT) and HR-HPV testing in General Hospital of Taiyuan Iron and Steel (Group) Co., Ltd. from March 2019 to July 2021 were retrospectively analyzed. The remaining cytological specimens were detected by P16/Ki-67 double staining and P16 INK4α single staining. Among them, 334 patients with TCT results suggesting atypical squamous cell of undetermined significance (ASCUS) and above and HPV-positive underwent colposcopy pathological biopsy. Using pathological results as reference, the positive predictive value, sensitivity, specificity and accuracy of P16/Ki-67 double staining, P16 INK4α single staining and HR-HPV testing for screening of high-grade squamous intraepithelial neoplasia (HSIL) and cervical cancer were compared. Results:Taking the results of histopathology as references, combined with the results of TCT, 31 of 622 patients were HSIL, of which 22 (71.0%) were positive for P16/Ki-67 double staining, 23 (74.2%) were positive for P16 INK4α single staining, and 25 (80.6%) were positive for HR-HPV testing; 4 cases were cervical cancer, and the positive rates of the three detection methods were all 100.0% (4/4). Among 622 patients, the positive rates of P16/Ki-67 double staining, P16 INK4α single staining and HR-HPV testing for screening of HSIL and cervical cancer were 13.99% (87/622), 25.40% (158/622) and 21.38% (133/622); the positive predictive values were 29.89%, 17.09% and 21.08%; the accuracies were 91.19%, 78.94% and 83.28%; the specificities were 89.77%, 77.98% and 82.46%; the sensitivities were 74.29%, 77.14% and 82.86%. The positive rate, positive predictive value, specificity and accuracy of P16/Ki-67 double staining were higher than those of P16 INK4α single staining and HR-HPV testing, and the differences were statistically significant ( z values were -5.062 and -3.418, 2.328 and 2.450, 5.436 and 3.570, 6.043 and 4.161, all P < 0.05); the sensitivity of HR-HPV testing was higher than that of P16/Ki-67 double staining and P16 INK4α single staining, but the differences were not statistically significant ( z values were -0.890 and 1.017, both P > 0.05). Conclusions:HR-HPV testing is more suitable for primary cervical lesion screening; P16/Ki-67 double staining can be used as a potential combined cell screening tool or an effective triage tool; P16 INK4α single staining has certain limitations.

Exploration of construction mode of real-world data system / 中华流行病学杂志

Real-world data study evidence, as an important part of evaluating the safety and effectiveness of drugs and devices, has attracted increasing attention from regulatory agencies and scholars both at home and abroad, and has become an essential source of evidence to support the development and review of drugs and devices. This paper systematically discusses the process and mode of real-world data system construction based on the preliminary practical study of real-world data according to the guidelines/technical specifications issued by regulatory agencies and academic research results. This study result provides not only reference for the generation of clinical evaluation evidence to meet the regulatory requirements for innovative drugs and devices, but also reference for researchers, sponsors and regulators to carry out real-world data studies successfully.

Anti-hepatocarcinoma HepG2 Cell Mechanism of Jaranol： Based on PI3K/Akt Signaling Pathway / 中国实验方剂学杂志

ObjectiveTo study the in vitro anti-hepatocarcinoma HepG2 cell mechanism of Jaranol. MethodThe methyl thiazolyl tetrazolium （MTT） assay was employed to examine the inhibition of Jaranol （0， 5， 10， 25， 50， 100， 150， 300 μmol·L-1） on HepG2 cell proliferation at different time （24 ， 48 ， 72 h）， annexin V-fluorescein isothiocyante/propidium iodide （Annexin V-FITC/PI） kit to detect the effect of Jaranol （0， 3， 15， 75 μmol·L-1） on HepG2 cell apoptosis， and Western blot to determine the influence of Jaranol on the expression of B-cell lymphoma 2 （Bcl-2） and Bcl-2-associated X protein （Bax） in HepG2 cells. Transcriptome sequencing was performed to analyze the differential expression of genes and changes of related signaling pathways after the treatment of HepG2 cells with Jaranol （15 μmol·L-1）. Real-time PCR was carried out to verify the relative mRNA content of differential genes ［TEK， platelet-derived growth factor receptor α （PDGFRA）， spleen tyrosine kinase （SYK）， phosphatidylinositol-4，5-bisphosphate 3-kinase catalytic subunit gamma （PIK3CG）， Janus kinase 3 （JAK3）， membrane-associated guanylate kinase inverted 2 （MAGI2）］. ResultCompared with the blank group， Jaranol decreased HepG2 proliferation （P<0.05， P<0.01）， increased apoptosis rate of HepG2 cells （P<0.05， P<0.01）， raised Bax expression （P<0.05， P<0.01）， and reduced Bcl-2 expression （P<0.05， P<0.01）. Transcriptome sequencing yielded 59 000 regulated genes， 125 of which showed significantly different expression， with 47 up-regulated and 74 down-regulated. Kyoto Encyclopedia of Genes and Genomes （KEGG） analysis showed that the differential genes related to apoptosis in the phosphatidylinositol 3-kinase/protein kinase B （PI3K/Akt） signaling pathway changed significantly after drug addition. The mRNA expression of TEK， PDGFRA， SYK， PIK3CG， JAK3， and MAGI2 decreased in Jaranol （15 μmol·L-1） group compared with that in the control group （P<0.05）. ConclusionIn vitro cytological experiment verified that Jaranol inhibited the proliferation of HepG2 cells and promoted the apoptosis， possibly by influencing the expression of some differential genes in the PI3K/Akt signaling pathway. The result lays an experimental basis for the follow-up study of the anti-tumor effect of Jaranol， and the further development and utilization of flavonoids.

Research model integrating "both medicinal and adjuvant properties" for essential oils from Chinese medicinal: based on characterization of medicinal properties / 中国中药杂志

Essential oils(EOs) from Chinese medicinals, which can be used as adjuvants and exert certain therapeutic effect, are directly used in Chinese medicine formulas. Conventional research strategy for EOs from Chinese medicinals is to compare the efficacy of the prescriptions before and after the addition of EOs, and the penetration-enhancing mechanisms of EOs remain unclear. In modern research on EOs from Chinese medicinals, the method for studying chemical penetration enhancers is often used, which fails to reflect the overall efficacy of EOs. This study clarified the property regularity of EOs from Chinese medicinals as transdermal penetration enhancers, and thereby proposed a research model which integrated the medicinal and adjuvant properties of EOs from Chinese medicinals via "component-delivery-effect" characterization route. The core concept is that constituents of EOs from Chinese medicinals and their delivery process play a key role in their external application. This research model is expected to serve as a reference for further research on EOs from Chinese medicinals for transdermal application.

Clinical Efficacy of Modified Huqianwan Combined with Auricular Acupressure with Seeds on Central Precocious Puberty due to Yin Deficiency and Fire Hyperactivity / 中国实验方剂学杂志

Objective:To observe the clinical efficacy of modified Huqianwan combined with auricular acupressure with seeds on girls with central precocious puberty （CPP） due to Yin deficiency and fire hyperactivity. Method:A total of 150 cases were randomly divided into three groups （A group，B group， and C group），with 50 cases in each group. The cases received modified Huqianwan，Zhibo Dihuangwan，and modified Huqianwan combined with auricular acupressure with seeds， respectively， for 12 weeks. The traditional Chinese medicine （TCM） symptoms，bone age difference/chronological age difference （ΔBA/ΔCA）， predicted adult height （PAH），ovarian volume，uterine volume，breast nodule index，serum sex hormones ［follicle-stimulating hormone （FSH），luteinizing hormone （LH），and estradiol （E₂）］，and serum kisspeptin-1 （KISS-1）/G protein-coupled receptor 54 （GPR54）/hypothalamic gonadotropin-releasing hormone （GnRH） signaling pathway of the three groups were observed before and after treatment. The clinical efficacy and safety of the three groups were evaluated. Result:The total effective rate was 97.9% in the C group， which was higher than 81.3% in the A group （<italic>χ</italic>²=4.516，<italic>P</italic><0.05） and 71.4% in the B group （<italic>χ</italic>²=5.162，<italic>P</italic><0.05）. Compared with the results in the A group after treatment，TCM syndrome，ΔBA/ΔCA，E₂，LH，KISS-1，GPR54，and GnRH decreased（<italic>P</italic><0.05），and ovarian volume，uterine volume，and breast nodule index were reduced （<italic>P</italic><0.05），but PAH increased in the C group （<italic>P</italic><0.05）. Compared with the B group after treatment，the C group showed decreased TCM syndrome，ΔBA/ΔCA， FSH，E₂，LH，KISS-1，GPR54，and GnRH （<italic>P</italic><0.05），reduced ovarian volume，uterine volume，and breast nodule index （<italic>P</italic><0.05），and increased PAH（<italic>P</italic><0.05）. During the study，there was one case of anorexia in the A group，and no obvious adverse reactions were found in the B group and the C group. Conclusion:Modified Huqianwan combined with auricular acupressure with seeds can significantly increase the PAH of girls with CPP due to Yin deficiency and fire hyperactivity and improve the serum sex hormones and the KISS-1/GPR54/GnRH signaling pathway.

Effect of Modified Fuyuanwan Combined with Auricular Acupressure Bean on Stage Ⅱ， Ⅲ Diabetic Nephropathy and Its Effect on Serum JAK/STAT Signaling Pathway / 中国实验方剂学杂志

Objective:To observe the therapeutic effect of modified Fuyuanwan combined with auricular acupressure bean on stage Ⅱ， Ⅲ diabetic nephropathy and its effect on serum janus kinase （JAK）/ signal transducer and activator of tranions （STAT） signaling pathway. Method:A total of 180 cases were randomly divided into control group and observation group， 90 cases in each group. Losartan potassium， modified Fuyuanwan combined with auricular acupressure bean were given respectively for 12 weeks. Renal function indexes ［blood urea nitrogen （BUN）， serum creatinine （SCr）， urinary albumin excretion rate （UAER）， 24 h urinary protein quantitative （24 h Upor）］， relative abundance of intestinal flora （verruca microflora， scleriobacteriae， deferribacter， proteobacteria）， oxidative stress indicators ［advanced oxidation protein products （AOPPs）， reactive oxygen species （ROS）， glutathione peroxidase （GSH-Px）， total superoxide dismutase （TSOD）］， renal blood flow index ［end-diastolic blood flow velocity （EDV）， peak systolic value （PSV）， pulse index （PI）， blood flow resistance index （RI）］， JAK/STAT signaling pathway ［JAK， phosphorylated JAK （p-JAK）， STAT， phosphorylated STAT （p-STAT） were observed before and after treatment. The safety indexes of two groups were evaluated after treatment. The efficacy was observed after treatment and followed up for 1 years and 2 years. Result:After treatment and follow-up for 1， 2 years， the total effective rates of patients in observation group were 97.8% （87/89）， 81.6% （71/87）， 59.8% （49/82）， respectively， observation group which were significantly higher than those in control group of 79.3%（69/87），57.8%（48/83），37.2%（29/78） （<italic>χ</italic>²=4.016， <italic>χ</italic>²=4.503， <italic>χ</italic>²=4.769， <italic>P</italic><0.05）. Compared with control group after treatment， UAER， BUN， SCr， 24 h Upor， firmicutes， actinobacillus， proteobacteria， AOPPs， ROS， PI， RI， p-JAK， p-STAT3 in observation group were significantly decreased （<italic>P</italic><0.05，<italic>P</italic><0.01）， microflora verruca， GSH-PX， TSOD， JAK， STAT3 were significantly increased （<italic>P</italic><0.05，<italic>P</italic><0.01）， EDV and PSV were significantly accelerated （<italic>P</italic><0.05，<italic>P</italic><0.01）. The incidence of adverse reactions was 1.1% （1/89） in observation group， lower than 13.8% （12/87） in control group （<italic>χ</italic>²=5.127， <italic>P</italic><0.05）. Conclusion:Modified Fuyuanwan combined with auricular acupressure bean can significantly improve the curative effect of stage Ⅱ， Ⅲ diabetic nephropathy， and its mechanism of action may be related to the serum JAK/STAT signaling pathway.

Effect of Modified Huangqi Biejiatang Combined with Auricular Acupressure on Diabetic Peripheral Neuropathy of Qi-Yin Deficiency Syndrome and Serum MyD88/IκB Signaling Pathway / 中国实验方剂学杂志

Objective:To observe the effects of modified Huangqi Biejiatang combined with auricular acupressure on diabetic peripheral neuropathy （DPN） due to Qi and Yin deficiency and serum myeloid differentiation factor 88/inhibitor of nuclear factor-<italic>κ</italic>B （MyD88/I<italic>κ</italic>B） signaling pathway. Method:One hundred and forty cases were randomly divided into an observation group （<italic>n</italic>=70） and a control group （<italic>n</italic>=70）. In addition to routine treatments like dietary intervention and the regulation of fasting blood glucose （FBG） and blood pressure， the modified Huangqi Biejiatang combined with auricular acupressure was further provided in the observation group， while mecobalamine was administered in the control group. After four-week intervention， the toronto clinical scoring system （TCSS） score， traditional Chinese medicine （TCM） syndrome score， the conduction velocities of motor and sensory nerves （median nerve， common peroneal nerve， tibial nerve， and ulnar nerve）， glucose metabolism indexes ［fasting plasma glucose （FPG）， 2 h postprandial blood glucose （2 h PG）， and hemoglobin A1c （HbA1c）］， intestinal genera （<italic>Clostridium</italic>， <italic>Prauserella</italic>， <italic>Bacteroides</italic>， and <italic>Faecalibacterium</italic>）， as well as the serum MyD88， I<italic>κ</italic>B<italic>α</italic>， and phosphorylated I<italic>κ</italic>B<italic>α </italic>（p-I<italic>κ</italic>B<italic>α</italic>） levels in the MyD88/I<italic>κ</italic>B signaling pathway before and after treatment were observed in the two groups， for comparing their clinical efficacy and safety. Result:The total effective rate of the observation group was 85.3% （58/68）， which was higher than 48.5% （32/66） of the control group （<italic>χ</italic>²=6.143， <italic>P</italic><0.05）. The comparison with the control group revealed that the scores of TCSS and TCM syndrome， the levels of FPG， 2 h PG， HbA1c， MyD88， and p-I<italic>κ</italic>B<italic>α</italic>， as well as the abundances of <italic>Clostridium</italic> and <italic>Prauserella</italic> in the observation group were decreased （<italic>P</italic><0.05）， while the conduction velocities of motor and sensory nerves （median nerve， common peroneal nerve， tibial nerve， and ulnar nerve） were significantly accelerated （<italic>P</italic><0.05）. Besides， the abundances of <italic>Bacteroides</italic> and <italic>Faecalibacterium</italic> and I<italic>κ</italic>B<italic>α</italic> level were significantly elevated （<italic>P</italic><0.05）. The incidence of adverse reactions in the observation group was 1.5% （1/68）， lower than 12.1% （8/66） in the control group （<italic>χ</italic>²=4.328， <italic>P</italic><0.05）. Conclusion:The modified Huangqi Biejiatang combined with auricular acupressure alleviates DPN due to Qi and Yin deficiency， which may be attributed to the regulation of serum MyD88/I<italic>κ</italic>B signaling pathway.