A network pharmacology-based approach to explore mechanism of kaempferol-7 -O -neohesperidoside against prostate cancer / 中国药理学通报

Aim To explore the effect of kaempferol-7- 0-neohesperidoside (K70N) against prostate cancer (PCa) and the underlying mechanism. Methods The effect of K70N on the proliferation of PCa cell lines PC3, DU145, C4-2 and LNCaP was detected using CCK8 assay. The effect of K70N on migration ability of DU145 cells was determined by wound healing assay. The targets of K70N and PCa were screened from SuperPred and other databases. The common targets both related to K70N and PCa were obtained from the Venny online platform, a protein-protein interaction network (PPI) was constructed by the String and Cyto- scape. Meanwhile, the GO and KEGG functional enrichment were analyzed by David database. Then, a "drug-target-disease-pathway" network model was constructed. Cell cycle of PCa cells treated with K70N was analyzed by flow cytometry. The expressions of cycle-associated proteins including Skp2, p27 and p21 protein were detected by Western blot. Molecular docking between Skp2 and K70N was conducted by Sybyl X2. 0. Results K70N significantly inhibited the proliferation and migration of PCa cells. A total number of 34 drug-disease intersection targets were screened. The String results showed that Skp2 and p27, among the common targets, were the key targets of K70N for PCa treatment. Furthermore, GO and KEGG functional en-richment indicated that the mechanism was mainly related to the cell cycle. Flow cytometry showed that K70N treatment induced cell cycle arrest at the S phase. Compared with the control group, the protein expression level of Skp2 was significantly down-regulated, while the protein expression levels of p27 and p21 were up-regulated. The network molecular docking indicated that the ligand K70N had a good binding ability with the receptor Skp2. Conclusions K70N could inhibit the proliferation and migration of PCa cells, block the cell cycle in the S phase, which may be related to the regulation of cell cycle through the Skp2- p27/p21 signaling pathway.

Research progress of antineoplastic drugs targeting platelets / 中国药理学通报

Platelets have long been recognized as key players in hemostasis and thrombosis; however, there is growing evidence that they are also involved in cancer. Preclinical and clinical studies have shown that platelets can promote tumorigenesis and metastasis through various crosstalks between platelets and cancer cells. Platelets play an active role in all stages of tumorigenesis, including tumor growth, tumor cell extravasation, and metastasis. In addition, thrombocytosis in cancer patients is associated with poor patient survival. Platelets are also well-placed to coordinate local and distant tumor-host interactions due to the a- bundance of microparticles and exosomes. Therefore, antitumor drugs targeting platelets have great development and application prospects. The following will review the research progress of anti-tumor drugs targeting platelets.

Comparative study of different large language models and medical professionals of different levels responding to ophthalmology questions / 国际眼科杂志(Guoji Yanke Zazhi)

AIM: To evaluate the performance of three distinct large language models(LLM), including GPT-3.5, GPT-4, and PaLM2, in responding to queries within the field of ophthalmology, and to compare their performance with three different levels of medical professionals: medical undergraduates, master of medicine, and attending physicians.METHODS: A total of 100 ophthalmic multiple-choice tests, which covered ophthalmic basic knowledge, clinical knowledge, ophthalmic examination and diagnostic methods, and treatment for ocular disease, were conducted on three different kinds of LLM and three different levels of medical professionals(9 undergraduates, 6 postgraduates and 3 attending physicians), respectively. The performance of LLM was comprehensively evaluated from the aspects of mean scores, consistency and confidence of response, and it was compared with human.RESULTS: Notably, each LLM surpassed the average performance of undergraduate medical students(GPT-4:56, GPT-3.5:42, PaLM2:47, undergraduate students:40). Specifically, performance of GPT-3.5 and PaLM2 was slightly lower than those of master's students(51), while GPT-4 exhibited a performance comparable to attending physicians(62). Furthermore, GPT-4 showed significantly higher response consistency and self-confidence compared with GPT-3.5 and PaLM2.CONCLUSION: LLM represented by GPT-4 performs well in the field of ophthalmology, and the LLM model can provide clinical decision-making and teaching aids for clinicians and medical education.

A novel mutation in COL1A1 causing osteogenesis imperfecta/hearing loss

Abstract Objectives: To screen the COL1A1 and COL1A2 gene mutation sites in a family with type I osteogenesis imperfecta (OI)/hearing loss and analyze the characteristics and recovery of hearing loss in patients with osteogenesis imperfecta. Methods: The basic clinical data of Ol proband and her parents were collected, and the COL1A1 and COL1A2 genes were detected in peripheral blood by PCR amplification and generation Sanger sequencing. Literature of stapedial surgery in patients with osteogenesis imperfecta was collected. Results: The heterozygous mutation of the 26 exon c.1922_1923 ins C in the Ol progenitor COL1A1 gene led to the amino acid frameshift mutation of p.Pro 601FS, which was not detected in the phenotypic parents. The homozygous of exon 28 c.1782>G in COL1A2 was detected in the proband and her parents, resulting in changes in the protein p.Pro 549Ala. Conclusion: The clinical symptoms of the Ol proband is caused by heterozygous mutation of the 26 exon c.1922_1923 ins C in COL1A1 gene. Stapedial surgery can provide short-term and long-term hearing benefits for Ol patients with hearing loss. Level of evidence: Level 4.

Quality evaluation of Crataegus pinnatifida leaves by fingerprint combined with quantitative analysis of multi-components by single-marker / 中国药房

OBJECTIVE To establish the fingerprint and multi-component content determination method of Crataegus pinnatifida leaves from different producing areas， and to evaluate the quality of C. pinnatifida leaves and screen the differential markers. METHODS Seventy-eight batches of C. pinnatifida leaves were collected from Chengde of Hebei Province， Huludao of Liaoning Province， Yuncheng of Shanxi Province and Linyi of Shandong Province. High-performance liquid chromatography （HPLC） and Similarity Evaluation System for Traditional Chinese Medicine Chromatographic Fingerprints （2012 edition） were used to draw the fingerprints and conduct similarity evaluation. Grey correlation analysis， cluster analysis （CA）， principal component analysis （PCA） and orthogonal partial least squares-discriminant analysis （OPLS-DA） were performed by using SPSS 19.0， MetaboAnalyst 5.0 and SIMCA 14.1 software. The differential markers affecting the quality of C. pinnatifida leaves were screened with variable importance in the projection （VIP） value greater than 1 and the error line not exceeding the origin as the criterion. Using vitexin rhamnoside as an internal reference， the contents of chlorogenic acid， glucosylvitexin， hypericin and isoquercetin in 78 batches of C. pinnatifida leaves were determined by the same HPLC combined with quantitative analysis of multi- components by single-marker （QAMS）， and the results were compared with external standard method. RESULTS Eight common peaks were calibrated in the fingerprints for 78 batches of C. pinnatifida leaves from 4 producing areas. Five known components were identified， including chlorogenic acid （peak 1）， glucosylvitexin （peak 3）， vitexin rhamnoside （peak 4）， hypericin （peak 7） and isoquercetin （peak 8）； their similarities ranged from 0.871 to 0.998. Average relative correlations of samples from Chengde of Hebei Province， Huludao of Liaoning Province， Yuncheng of Shanxi Province and Linyi of Shandong Province were 0.538， 0.528， 0.462 and 0.435， respectively. CA and PCA showed that the samples from Chengde of Hebei Province and Huludao of Liaoning Province were roughly classified into one category， while the samples from Linyi of Shandong Province and Yuncheng of Shanxi Province were roughly classified into one category； VIP values of peak 1， 2， 3 and 5 were all greater than 1. By QAMS， the relative correction factors of chlorogenic acid， glucosylvitexin， hypericin and isoquercetin were 0.401， 0.993， 1.670 and 1.615 （RSD＜2%）. Compared with external standard method， except for isoquercetin in the two batches of samples （S39 and S41）， there was no significant difference in the content of each component in other batches of samples （the relative deviations≤ 5%）. CONCLUSIONS The established fingerprint and QAMS method are simple to operate and can be used to evaluate the quality of C. pinnatifida leaves. The sample from Chengde of Hebei Province is relatively good in quality. Chlorogenic acid （peak 1）， glucosylvitexin （peak 3）， and the corresponding components of peaks 2 and 5 may be differential markers affecting the quality of C. pinnatifida leaves.

Fortify clinical advantages and promote innovative development: comparison of the Chinese Colorectal Cancer Surgery Database with foreign databases / 中华外科杂志

With the continuous development of evidence-based medicine, increasing attention has been paid to the construction of a large medical database to ensure a source of high quality real-world data. The Chinese Medical Association Colorectal Surgery Group created the Chinese Colorectal Cancer Surgery Database (CCCD), whose objective is to promote the development of colorectal surgery and improve patient prognosis with evidence-based medicine theory. Compared to major databases around the world, CCCD contains more comprehensive information on colorectal cancer surgical cases, recording the main epidemiological characteristics and detailed surgical information, but perioperative treatment data still need to be strengthened. It is necessary to continuously expand the coverage, enrich perioperative data and strengthen data, quality control. In the future, CCCD is expected to play a role in promoting homogenization of medical services, promoting smooth and effective graded diagnosis and treatment, giving full role to the characteristics of each center to achieve integrated development, and connecting real-world data and artificial intelligence.

Application and thinking of acupuncture therapy in comprehensive management of hypertension / 中国针灸

The theory of disease prevention with traditional Chinese medicine is introduced into the prevention of chronic diseases such as hypertension. In order to fully implement the advantages of acupuncture, the three-level prevention strategy is strengthened on the whole-process intervention with acupuncture for hypertension, including prevention before disease onset, starting intervention at the early phase, and prevention disease from exacerbating. Moreover, the comprehensive management scheme, multidisciplinary coordination and participation mechanism are investigated in the field of traditional Chinese medicine for preventive treatment of hypertension.

Activity and mechanism of palbinone against hepatic fibrosis and inflammation / 药学学报

The study aims to investigate the anti-hepatic fibrosis and anti-inflammatory activities of palbinone, and to explore the internal regulatory mechanism, so as to lay an active foundation for its development as an anti-non-alcoholic steatohepatitis (NASH) candidate. First, sulforhodamine B (SRB) method was used to detect the effect of palbinone on the proliferation of human hepatic stellate cells LX-2 and rat hepatic stellate cells HSC-T6. Following, in the in vitro hepatic fibrosis cell model that activated by transforming growth factor beta 1 (TGF-β1), quantitative real-time PCR (qRT-PCR) and Western blot were used to detect the inhibitory effect of different concentrations of palbinone on the transcription level and protein expression level of hepatic fibrosis markers. And the regulating mechanism of palbinone on fibrosis-related genes was analyzed at the same time. In addition, in the inflammatory cell model that induced by lipopolysaccharide (LPS) and nigericin, ELISA was used to detect the effect of palbinone on the released interleukin-1β (IL-1β) level. At the same time, Western blot was used to detect the effect of palbinone on the related proteins of inflammatory pathway. The results showed that palbinone could significantly inhibit the proliferation activity of LX-2 and HSC-T6, and their half maximal inhibitory concentration (IC50) values ​​were (375.11 ± 55.45) and (260.27 ± 36.81) nmol·L-1, respectively. In addition, palbinone showed a dose-dependent inhibitory effect on the expression levels of TGF-β1-induced fibrosis-related genes, including collagen type Ⅰ α 1 (COL1A1), TGF-β1, α-smooth muscle actin (α-SMA) and tissue inhibitor of metalloproteinase 1 (TIMP1). Mechanism study showed that palbinone may decrease the expression level of Yes-associated protein (YAP), thereby weakening its activation effect on the downstream fibrosis pathway. In addition, palbinone also exerted an anti-inflammatory effect by inhibiting the activity of nuclear factor kappa-B (NF-κB) signaling pathway and reducing inflammatory factors cysteinyl aspartate specific proteinase-1 (caspase-1) and IL-1β release. In conclusion, palbinone can not only inhibit the proliferation and activation of hepatic stellate cells by inhibiting the expression of YAP, but also inhibit the expression and release of inflammatory factors at the same time. All these studies provide theoretical support for the development of palbinone as an anti-nonalcoholic steatohepatitis drug.

Exploration and Practice of the "One Combination, Two Highlights, Three Combinations, Four in One" Innovative Talents Training Mode in Forensic Medicine / 法医学杂志

Talent is one of the basic and strategic supports for building a modern socialist country in all aspects. Since the 1980s, the establishment of forensic medicine major and the cultivation of innovative talents in forensic medicine have become hot topics in higher education in forensic medicine. Over the past 43 years, the forensic medicine team of Shanxi Medical University has adhered to the joint education of public security and colleges, and made collaborative innovation, forming a training mode of "One Combination, Two Highlights, Three Combinations, Four in One" for innovative talents in forensic medicine. It has carried out "5+3/X" integrated reform, and formed a relatively complete talent training innovation mode and management system in teaching, scientific research, identification, major, discipline, team, platform and cultural construction. It has made a historic contribution to China's higher forensic education, accumulated valuable experience for the construction of first-class major and first-class discipline of forensic medicine, and provided strong support for the construction of the national new forensic talent training system. The popularization of this training mode is conducive to the rapid and sustainable development of forensic science, and provides more excellent forensic talents for national building, regional social development and the discipline construction of forensic science.

Comparison of HPLC fingerprints and determination of main components of Viticis Fructus from different species / 中国中药杂志

In order to comprehensively evaluate the quality of Viticis Fructus, this study established HPLC fingerprints and evaluated the quality of 24 batches of Viticis Fructus samples from different species by similarity evaluation and multivariate statistical analysis(PCA, HCA, PLS-DA). On this basis, an HPLC method was established to compare the content differences of the main components, including casticin, agnuside, homoorientin, and p-hydroxybenzoic acid. The analysis was performed on the chromatographic column(Waters Symmetry C_(18)) with a gradient mobile phase of acetonitrile(A)-0.05% phosphoric acid solution(B) at the flow rate of 1 mL·min~(-1) and detection wavelength of 258 nm. The column temperature was 30 ℃ and the injection volume was 10 μL. The HPLC fingerprint of 24 batches of Viticis Fructus samples was established with 21 common peaks, and nine peaks were identified. Similarity analysis was carried out based on chromatographic data of 24 batches of chromatographic data of Viticis Fructus, and the results showed that except for DYMJ-16, the similarity of Vitex trifolia var. simplicifolia was ≥0.900, while that of V. trifolia was ≤0.864. In addition, the similarity analysis of two different species showed that the similarity of 16 batches of V. trifolia var. simplicifolia was 0.894-0.997 and that of the eight batches of V. trifolia was between 0.990 and 0.997. The results showed that the similarity of fingerprints of these two species was different, but the similarity between the same species was good. The results of the three multivariate statistical analyses were consistent, which could distinguish the two different species. The VIP analysis results of PLS-DA showed that casticin and agnuside contributed the most to the distinction. The content determination results showed that there was no significant difference in the content of homoorientin and p-hydroxybenzoic acid in Viticis Fructus from different species, but the content of casticin and agnuside was significantly different in different species(P<0.01). The content of casticin was higher in V. trifolia var. simplicifolia, while agnuside was higher in V. trifolia. The findings of this study show that there are differences in fingerprint similarity and component content of Viticis Fructus from different species, which can provide references for the in-depth study of the quality and clinical application of Viticis Fructus.

Identification of the metabolites from co-cultures of marine Streptomyces sp. IMB18-531 and Cladosporium sp. IMB19-099 / 药学学报

A new siderophore chelate (1) and 8 known compounds were identified from the liquid co-cultures of the marine-derived Streptomyces sp. IMB18-531 and Cladosporium sp. IMB19-099 by a combination of chromatography methods, including C18 reversed-phase medium pressure chromatography, gel column chromatography and HPLC. Their structures were determined by spectroscopic analysis and chemical methods as aluminioxamine E (1), desferrioxamine E (2), ferrioxamine E (3), terragine E (4), capsimicin (5), cyclo(L-prolinyl-L-tyrosine) (6), anthranilic acid (7), (Z)-14-methylpentadec-9-enoic acid (8), and (Z)-hexadec-8-enoic acid (9). Compound 2 showed inhibitory activities against the expression of liver fibrosis related genes COL1A1, MMP2, and TIMP2. Compounds 5, 8, and 9 displayed antibacterial activities against methicillin-resistant Staphylococcus aureus, S. epidermidis and Bacillus subtilis, with MICs of 16-64 μg·mL-1. Compound 5 showed cytotoxicities against human pancreatic cancer MIA Paca-2 and human colon cancer HT-29 cell lines with IC50 of 2.9 and 6.3 μmol·L-1, respectively.

Diagnostic Value of American Thyroid Association Guidelines,American College of Radiology Thyroid Imaging Reporting and Data System,and Chinese Thyroid Imaging Reporting and Data System Alone and Combined With BRAFV600E Mutation in Atypia of Undetermined Significance/Follicular Lesion of Undetermined Significance / 中国医学科学院学报

Objective To explore the diagnostic efficacy of American Thyroid Association(ATA)guidelines,American College of Radiology Thyroid Imaging Report and Data System(ACR-TIRADS),and Chinese Thyroid Imaging Reporting and Data System(C-TIRADS)alone and combined with BRAFV600E mutation in atypia of undetermined significance/follicular lesion of undetermined significance(AUS/FLUS).Methods A total of 138 patients who underwent ultrasound-guided fine needle aspiration(FNA)in the Chinese PLA General Hospital from January 2020 to May 2023 were selected.The clinicopathological and ultrasound characteristics were retrospectively analyzed for each nodule.Each nodule underwent preoperative BRAFV600E mutation testing and was diagnosed according to the ATA guidelines,ACR-TIRADS,and C-TIRADS.The diagnostic efficacy of ATA guidelines,ACR-TIRADS,and C-TIRADS alone and combined with BRAFV600E mutation was assessed based on the results of histopathological diagnosis.Results The 138 AUS/FLUS thyroid nodules included 45(32.6%)benign ones and 93(67.4%)malignant ones.The patient age(t=1.444,P=0.151),gender(χ2=0.259,P=0.611),and location of nodules(χ2=2.055,P=0.358)had no statistical significance for the differentiation between benign and malignant nodules,while nodule size(Z=2.500,P=0.012),echo(χ2=14.693,P<0.001),composition(χ2=17.075,P<0.001),aspect ratio ≥1(χ2=9.477,P=0.002),and microcalcification(χ2=6.892,P=0.009)were of significance for the differentiation.When applied alone,BRAFV600E mutation showed high specificity(95.56%)and positive predictive value(95.65%).Among the three ultrasound grading systems,ACR-TIRADS had the highest sensitivity(χ2=37.923,P<0.001;χ2=40.462,P<0.001)and accuracy(χ2=81.595,P<0.001;χ2=76.912,P<0.001),while C-TIRADS had the highest specificity(χ2=11.746,P<0.001;χ2=21.235,P<0.001).However,the three systems showed no statistically significant difference in the diagnostic efficiency when applied alone(Z=1.177,P=0.239;Z=0.213,P=0.831;Z=1.016,P=0.310).The combination of BRAFV600E mutation with ACR-TIRADS or C-TIRADS improved the diagnostic efficacy of BRAFV600E mutation in distinguishing the benign and malignant AUS/FLUS nodules(Z=2.107,P=0.035;Z=2.752,P=0.006).The combination of ATA guidelines with BRAFV600E mutation increased the diagnostic accuracy of BRAFV600E mutation(χ2=20.679,P<0.001),while it had no statistically significant difference in distinguishing the benign and malignant AUS/FLUS nodules(Z=1.321,P=0.186).The combination of ATA guidelines,ACR-TIRADS,or C-TIRADS with BRAFV600E mutation improved the diagnostic efficacy of ultrasound grading systems for AUS/FLUS nodules(Z=2.770,P=0.006;Z=2.770,P=0.006;Z=2.890,P=0.004).Specifically,ACR-TIRADS combined with BRAFV600E mutation showed the highest sensitivity(χ2=4.712,P=0.030;χ2=4.712,P=0.030),while C-TIRADS combined with BRAFV600E mutation showed the highest accuracy(χ2=77.627,P<0.001;χ2=85.827,P<0.001).However,there were no statistically significant differences in diagnostic performance between the combinations(Z=1.276,P=0.202;Z=0.808,P=0.419;Z=1.615,P=0.106).Conclusion ATA guidelines,ACR-TIRADS,and C-TIRADS combined with BRAFV600E mutation can improve the diagnostic efficacy of BRAFV600E mutation or ultrasound grading system alone in AUS/FLUS nodules,which can facilitate the further management and treatment of such patients.

Clinical features and risk factors of left ventricular hypertrophy in children with primary hypertension / 中华儿科杂志

Objective: To assess the clinical features and relative factors of left ventricular hypertrophy (LVH) in children with primary hypertension. Methods: In this retrospective cohort study, 430 children diagnosed with primary hypertension in Children's Hospital, Capital Institute of Pediatrics from January 2019 to September 2022 were enrolled. Their clinical data was analyzed and LVH was assessed by echocardiography. According to left ventricular geometry, these children were assigned to the LVH group and normal geometry group. General conditions, laboratory indicators and ambulatory blood pressure parameters between two groups were compared by independent sample t-test or Mann-Whitney U test. Spearman correlation coefficient was used to analyze the correlation between LVH and clinical indicators including blood pressure, biochemical and metabolic indicators. The independent risk factors of LVH were analyzed by multivariable logistic regression. The receiver operating characteristic (ROC) curve was used to explore the value of risk factors in the diagnosis of LVH. Results: Among the 430 children with primary hypertension, 342 (79.5%) were males and 88 (20.5%) females. Their age was (12.6±2.3) years, and 123 children (28.6%) of them had LVH. Body mass index (BMI) ((30.0±5.2) vs. (26.2±4.3) kg/m2), ratio of stage 2 hypertension (75.6% (93/123) vs. 59.6% (183/307)), 24-hour systolic blood pressure (24 h SBP)((131±10) vs. (128±10) mmHg,1 mmHg=0.133 kPa), daytime systolic blood pressure (SBP) ((135±11) vs. (131±11) mmHg), nighttime SBP ((128±11) vs. (123±10) mmHg), cholesterol level ((4.0±0.7) vs. (3.9±0.7) mmol/L), serum uric acid level ((447±81) vs. (426±91) μmol/L) and incidence of hyperinsulinemia (69.9% (86/123) vs.59.0% (181/307)) were significantly elevated in the LVH group compared with those in the normal geometry group (all P<0.05). There were more patients with a disease course over 5 years in the LVH group than in the normal geometry group, with a statistically significant difference (χ2=8.90,P=0.031). Spearman correlation analysis showed that BMI, 24 h SBP, daytime SBP, nighttime SBP, triglyceride, uric acid, and serum sodium level were positively correlated with LVMI (r=0.43, 0.20, 0.18, 0.18, 0.18, 0.16, and 0.12, all P<0.05). BMI, hyperinsulinemia, and cholesterol level were positively correlated with relative wall thickness (RWT) (r=0.22, 0.12, and 0.16, all P<0.05). The multivariate logistic regression analysis showed that BMI (OR=1.17, 95%CI 1.10-1.25) and 24 h SBP (OR=1.04, 95%CI 1.01-1.08) were the independent risk factors for LVH (both P<0.05). The area under the receiver operator characteristic curve, combined with BMI and 24 h SBP, was 0.72 (95%CI 0.67-0.77, P<0.05), with a sensitivity and specificity of 71.5% and 64.8%, respectively. Conclusions: BMI and 24 h SBP are the independent risk factors for LVH in children with primary hypertension, and the combination of BMI and 24 h SBP has an acceptable diagnostic value for LVH. Early monitoring of these indexes is necessary to predict preclinical cardiac damage.

Establishment and digital simulation of upper airway in patients with adenoid hypertrophy / 中华口腔医学杂志

Objective: To analyze the flow field characteristics of the upper airway in patients with different adenoid hypertrophy using computational fluid dynamics (CFD). Methods: From November 2020 to November 2021, the cone-beam CT (CBCT) data of 4 patients [2 males and 2 females,age range 5-7 years, mean (6.0±1.2) years] with adenoid hypertrophy who were hospitalized in the Department of Orthodontics and the Department of Otolaryngology at Hebei Eye Hospital were selected. The degree of adenoid hypertrophy in the 4 patients was divided into normal S1 (A/N<0.6), mild hypertrophy S2 (0.6≤A/N<0.7), moderate hypertrophy S3 (0.7≤A/N<0.9) and severe hypertrophy S4 (A/N≥0.9) according to the ratio of adenoid thickness to the width of nasopharyngeal cavity (A/N). The CFD model of the upper airway was established using ANSYS 2019 R1 software, and the internal flow field of the CFD model was numerically simulated. Eight sections were selected as observation and measurement planes for flow field information. Relevant flow field information includes airflow distribution, velocity variation, and pressure variation. Results: In the S1 model, the maximum pressure difference occurred in the 4th and 5th observation planes (ΔP=27.98). The lowest pressures and the maximum flow rates of S2 and S3 were located in the 6th observation plane. The airflow in S1 and S2 models completely passed through the nasal cavity. In the S3 model, the mouth-to-nasal airflow ratio was close to 2∶1. In S4 model, the airflow completely passed through the mouth; in the S1 and S2 models, hard palates were subjected to a downward positive pressure with a pressure difference of 38.34 and 23.31 Pa, respectively. The hard palates in S3 and S4 models were subjected to a downward negative pressure with a pressure difference of -2.95 and -21.81 Pa, respectively. Conclusions: The CFD model can objectively and quantitatively describe the upper airway airflow field information in patients with adenoid hypertrophy. With the increasing degree of adenoid hypertrophy, the nasal ventilation volume gradually decreased, whereas the oral space ventilation volume gradually increased, and the pressure difference between the upper and lower surfaces of the palate gradually decreased until the pressure became negative.

The value of transanal multipoint full-layer puncture biopsy in determining the response degree of rectal cancer following neoadjuvant therapy: a prospective multicenter study / 中华外科杂志

Objective: To verify the feasibility and accuracy of the transanal multipoint full-layer puncture biopsy (TMFP) technique in determining the residual status of cancer foci after neoadjuvant therapy (nCRT) in rectal cancer. Methods: Between April 2020 and November 2022, a total of 78 patients from the Beijing Chaoyang Hospital of Capital Medical University, the Beijing Friendship Hospital of Capital Medical University, the Qilu Hospital of Shandong University, the Zhongnan Hospital of Wuhan University with advanced rectal cancer received TMFP after nCRT participated in this prospective multicenter trial. There were 53 males and 25 females, aged (M(IQR)) 61 (13) years (range: 35 to 77 years). The tumor distance from the anal verge was 5 (3) cm (range: 2 to 10 cm). The waiting time between nCRT and TMFP was 73 (26) days (range: 33 to 330 days). 13-point transanal puncture was performed with a 16 G tissue biopsy needle with the residual lesion as the center. The specimens were submitted for independent examination and the complications of the puncture were recorded. The consistency of TMFP and radical operation specimen was compared. The consistency of TMPF with clinical remission rates for the diagnosis of complete pathological remission was compared by sensitivity, specificity, negative predictive value, positive predictive value and accuracy. Statistical analysis between groups was performed using the χ2 analysis, and a paired χ2 test was used to compare diagnostic validity. Results: Before TMFP, clinical complete response (cCR) was evaluated in 27 cases. Thirty-six cases received in vivo puncture, the number of punctures in each patient was 13 (8) (range: 4 to 20), 24 cases of tumor residue were found in the puncture specimens. The sensitivity to judgment (100% vs. 60%, χ2=17.500, P<0.01) and accuracy (88.5% vs. 74.4%, χ2=5.125, P=0.024) of TMFP for the pathologic complete response (pCR) were significantly higher than those of cCR. Implement TMFP based on cCR judgment, the accuracy increased from 74.4% to 92.6% (χ2=4.026, P=0.045). The accuracy of the in vivo puncture was 94.4%, which was 83.3% of the in vitro puncture (χ2=1.382, P=0.240). Overall, the accuracy of TMFP improved gradually with an increasing number of cases (χ2=7.112, P=0.029). Conclusion: TMFP is safe and feasible, which improves the sensitivity and accuracy of rectal cancer pCR determination after nCRT, provides a pathological basis for cCR determination, and contributes to the safe development of the watch and wait policy.

Circular RNA expression profiles and circRNA-miRNA-mRNA crosstalk in pre-eclamptic placenta / 中华妇产科杂志

Objective: To identify the expression profile of circular RNA (circRNA) in placenta of pre-eclampsia (PE) pregnant women by high-throughput sequencing, and to construct the circRNA-microRNA (miRNA)-messenger RNA (mRNA) interaction network, so as to reveal the related pathways and regulatory mechanisms of PE. Methods: The clinical data and placentas of 42 women with PE (PE group) and 30 normal pregnant women (control group) who delivered in West China Second University Hospital from November 2019 to June 2021 were collected. (1) High-throughput sequencing was used to establish the differentially expressed circRNA profiles in placental tissues of 5 pairs of PE group and the control group. (2) Real-time quantitative PCR (qRT-PCR) was used to verify the expression levels of 6 differentially expressed circRNAs in placental tissues of PE group and control group. (3) Bioinformatics analysis was used to predict the target miRNA and analyze the co-expressed mRNA to construct a competitive endogenous RNA (ceRNA) network. The differentially expressed circRNAs were analyzed by Gene ontology (GO) and Kyoto encyclopedia of genes and genomes (KEGG) pathways. (4) Logistic regression analysis, Pearson correlation and Kendall's tau-b correlation analysis were used to test the correlation between the three differentially expressed circRNAs and the risk of PE and clinical characteristics. (5) circRNA_05393 was selected for subsequent functional study. Small interfering RNA (siRNA) and overexpression plasmid were used to knock down or increase the expression level of circRNA_05393 in trophoblast cell line HTR-8/SVneo cells, respectively. Transwell assay was used to detect the migration and invasion ability of the trophoblasts in vitro. Cell counting kit-8 assay was used to detect the proliferation ability of the trophoblasts. Results: (1) Seventy-two differentially expressed circRNAs were identified by high-throughput sequencing, of which 35 were up-regulated and 37 were down-regulated. (2) qRT-PCR showed that compared with the control group, circRNA_00673 (1.306±0.168 vs 2.059±0.242; t=2.356, P=0.021) and circRNA_07796 (1.275±0.232 vs 1.954±0.230; t=2.018, P=0.047) were significantly increased, while circRNA_05393 (1.846±0.377 vs 0.790±0.094; t=3.138, P=0.002) was significantly decreased. (3) The circRNA-miRNA-mRNA interaction network contained 3 circRNAs, 8 miRNAs and 53 mRNAs. GO functional annotation analysis showed that the biological process was mainly enriched in iron ion homeostasis, membrane depolarization during action potential and neuronal action potential. In terms of cellular components, they were mainly enriched in cytoskeleton and membrane components. In terms of molecular function, they were mainly enriched in the activity of voltage-gated sodium channel and basic amino acid transmembrane transporter. KEGG pathway enrichment analysis showed that mRNAs in the interaction network were mainly enriched in complement and coagulation cascade, glycine, serine and threonine metabolism, p53 signaling pathway and peroxisome proliferators-activated receptors (PPAR) signaling pathway. (4) Logistic regression analysis showed that down-regulation of circRNA_05393 expression was a risk factor for PE (OR=0.044, 95%CI: 0.003-0.596; P=0.019). Correlation analysis showed that circRNA_05393 was significantly correlated with systolic blood pressure and diastolic blood pressure in PE pregnant women (both P<0.05). (5) Knock down or overexpression of circRNA_05393 significantly reduced or increased the migration and invasion abilities of HTR-8/SVneo cells (all P<0.05), but had no significant effect on the ability of tube formation and proliferation (all P>0.05). Conclusions: The construction of circRNA expression profile in placenta and the exploration of circRNA-miRNA-mRNA interaction network provide the possibility to reveal the regulatory mechanism of specific circRNA involved in PE. Inhibition of circRNA_05393 may induce the progression of PE by reducing the migration and invasion of trophoblasts.

Reference values for carotid artery intima-media thickness among community adult dwellers in Shenzhen City / 中华预防医学杂志

Objective: To establish reference values for carotid intima-media thickness (CIMT) of adult dwellers in Shenzhen City. Methods: The study was conducted based on the Shenzhen heart failure epidemiological survey from 2021 to 2022. In this survey, residents aged 18 years and above in Shenzhen were selected by using a multi-stage stratified random sampling method. General information, cardiovascular disease (CVD) related behavior and carotid ultrasound examination and etc. were collected from the participants. People with CVD factors, a history of atherosclerotic cardiovascular disease, carotid plaque or having no carotid ultrasound examination results were excluded. The parameter regression model based on fractional polynomial was used to establish the reference values of CIMT by age and sex. Results: A total of 2 163 healthy individuals were enrolled in the final analysis, including 576 males (26.6%) and 1 587 females (73.4%). The fractional polynomial regression of the CIMT mean and standard deviation was obtained. For men, the regression was meanCIMT=0.324 7+0.006 9×age and SDCIMT=0.076 9+0.001 2×age. For women, the regression was meanCIMT=0.354 9+0.005 4×age and SDCIMT=0.041 6+0.002 0×age. Conclusion: The age and sex reference values for CIMT of adult people in Shenzhen established in this study could provide the latest reference standards for early screening of subclinical CVD.

Establishment of a novel co-cultured liver cancer model based on tumor microenvironment / 中华肿瘤杂志

Objective: To construct a new co-cultured liver cancer research model composed of activated hepatic stellate cells (aHSC) and liver cancer cells, explore the efficacy difference between it and traditional model, so as to establish a liver cancer research model in vitro and in vivo that can reflect the real clinical efficacy. Methods: A new co-culture model of liver cancer consisting of aHSC and liver cancer cells was constructed. The differences in efficacy between the new co-culture model and the traditional single cell model were compared by cytotoxicity test, cell migration test, drug retention test and in vivo tumor inhibition test. Western blot was used to detect the drug-resistant protein P-gp and epithelial-mesenchymal transition-related proteins. Masson staining was used to observe the deposition of collagen fibers in tumor tissues of tumor-bearing mice. CD31 immunohistochemical staining was used to observe the microvessel density in tumor tissues of tumor-bearing mice. Results: The cytotoxicity of single cell model and co-culture model was dose-dependent. With the increase of curcumin (CUR) concentration, the cell viability decreased, but the cell viability of single cell model decreased faster than that of co-culture model. When the concentration of CUR was 10 μg/ml, the cell viability of the co-culture model was 62.3% and the migration rate was (28.05±3.68)%, which were higher than those of the single cell model [38.5% and (14.91±5.92)%, both P<0.05]. Western blot analysis showed that the expressions of P-gp and vimentin were up-regulated in the co-culture model, which were 1.55 and 2.04 fold changes of the single cell model, respectively. The expression of E-cadherin was down-regulated, and the expression level of E-cadherin in the single cell model was 1.17 fold changes of the co-culture model. Drug retention experiment showed that the co-culture model could promote drug efflux and reduce drug retention. In vivo tumor inhibition experiment showed that the m-HSC+ H22 co-transplantation model had faster tumor growth and larger tumor volume than those of the H22 single cell transplantation model. After CUR treatment, the tumor growths of m-HSC+ H22 co-transplantation model and H22 single cell transplantation model were inhibited. Masson staining showed that the deposition of collagen fibers in tumor tissues of m-HSC+ H22 co-transplantation model mice was more than that of H22 single cell transplantation model. CD31 immunohistochemical staining showed that the microvessel density in tumor tissue of m-HSC+ H22 co-transplantation model was higher than that of H22 single cell transplantation model. Conclusions: The aHSC+ liver cancer cell co-culture model has strong proliferation and metastasis ability and is easy to be resistant to drugs. It is a new type of liver cancer treatment research model superior to the traditional single cell model.

Conservative treatment of supination and external rotation for type Ⅲ and Ⅳankle fracture by bone setting / 中国骨伤

OBJECTIVE@#To explore curative effect of conservative treatment of supination-lateral rotation (SER) with type Ⅲ and Ⅳ ankle fracture by bone setting technique.@*METHODS@#From January 2017 to December 2019, 64 patients diagnosed with SER with type Ⅲ and Ⅳ ankle fracture were treated with manipulative reduction and conservative treatment (manipulation group) and surgical treatment with open reduction and internal fixation (operation group), 32 patients in each group. In manipulation group, there were 17 males and 15 females, aged from 15 to 79 years old with an average of (51.42±13.68) years old;according to Lauge-Hansen classification, there were 8 patients with supination external rotation type Ⅲ and 24 patients with type Ⅳ. In operation group, there were 13 males and 19 females, aged from 18 to 76 years old with an average of (47.36±15.02) years old;7 patients with type Ⅲ and 25 patients with type Ⅳ. Displacement of ankle fracture was measured by Digimizer software, and compared before treatment, 3 and 12 months after treatment between two groups. Lateral medial malleolus displacement, lateral medial malleolus displacement, lateral malleolus displacement, lateral malleolus displacement, lateral malleolus contraction displacement and posterior malleolus displacement were measured and compared between two groups. Mazur score was used to evaluate ankle joint function.@*RESULTS@#All patients were followed up from 12 to 36 months with an average of (17.16±9.36) months. There were statistical differences in lateral medial malleolus displacement, lateral medial malleolus displacement, lateral malleolus displacement, lateral malleolus displacement, lateral malleolus contraction displacement and posterior malleolus displacement in manipulation group before and after reduction(P<0.05). Compared with operation group, there were no statistically significant differences in lateral malleolus shift, lateral malleolus shift, lateral malleolus contraction shift(P>0.05), while there were statistically significant differences in lateral malleolus shift, posterior malleolus shift up and down (P<0.05). Mazur scores of ankle joint at 3 months after treatment in manipulation group and operation group were 68.84±13.08 and 82.53±7.31, respectively, and had statistical differences(P<0.05), while there was no difference in evaluation of clnical effect(P>0.05). There were no differences in Mazur score and evaluation of clnical effect between two groups at 12 months after treatment (P>0.05).@*CONCLUSION@#Bone setting technique could effectively correct lateral displacement of medial malleolus, lateral displacement of medial malleolus, lateral displacement of lateral malleolus and lateral contraction displacement of lateral malleolus in supination lateral rotation type Ⅲ and Ⅳ ankle fracture, and has good long-term clinical effect, which could avoid operation for some patients and restore ankle function after fracture.

Comparison of chemical compositions of different parts of Xanthoceras sorbifolium seeds based on UHPLC-Q-Orbitrap HRMS / 中国中药杂志

Xanthoceras sorbifolium seeds have a wide range of applications in the food and pharmaceutical industries. To compare and analyze the chemical compositions of different parts of X. sorbifolium seeds and explore the potential value and research prospects of non-medicinal parts, this study used ultra-high-performance liquid chromatography quadrupole Orbitrap high-resolution mass spectrometry(UHPLC-Q-Orbitrap HRMS) to detect the chemical composition of various parts of the seeds. A total of 82 components were preliminary identified from X. sorbifolium seeds, including 5 amino acids, 4 polyphenols, 3 phenylpropionic acids, 7 organic acids, 15 flavonoids, 6 glycosides, and 23 saponins. Mass spectrometry molecular networking(MN) analysis was conducted on the results from different parts of the seeds, revealing significant differences in the components of the seed kernel, seed coat, and seed shell. The saponins and flavonoids in the seed kernel were superior in terms of variety and content to those in the seed coat and shell. Based on the chromatographic peaks of different parts from multiple batches of samples, multivariate statistical analysis was carried out. Four differential components were determined using HPLC, and the average content of these components in the seed kernel, seed coat, and seed shell were as follows: 0.183 6, 0.887 4, and 1.440 1 mg·g~(-1) for fraxin; 0.035 8, 0.124 1, and 0.044 5 mg·g~(-1) for catechin; 0.032 9, 0.072 0, and 0.221 5 mg·g~(-1) for fraxetin; 0.435 9, 2.114 7, and 0.259 7 mg·g~(-1) for epicatechin. The results showed that catechin and fraxetin had relatively low content in all parts, while fraxin had higher content in the seed coat and seed shell, and epicatechin had higher content in the seed kernel and seed coat. Therefore, the seed coat and seed shell possess certain development value. This study provides rapid analysis and comparison of the chemical compositions of different parts of X. sorbifolium seeds, which offers an experimental basis for the research and clinical application of medicinal substances in X. sorbifolium seeds.