The chemical composition of Paeoniae Radix Alba(PRA) is complex, with primary secondary metabolites including monoterpenoids, tannins, triterpenoids, and flavonoids. In previous studies on the material basis of PRA, it was found that, in addition to the widely studied characteristic monoterpene glycosides, tannic acid components also play an important role in the efficacy of PRA. However, their pharmacological effects have not been thoroughly investigated. This paper reviews the tannic acid components in PRA, including pentagaloyl glucose(PGG), tetragaloyl glucose(TGG), trigaloyl glucose(TriGG), and gallic acid, along with their structures, properties, and characteristics to provide a detailed discussion of their pharmacological activities and related mechanisms, aiming to offer a theoretical basis for the material basis research and clinical application of PRA.
Paeonia/chemistry* ; Tannins/chemistry* ; Humans ; Drugs, Chinese Herbal/chemistry* ; Animals ; Plant Extracts

The translation of genetic findings from genome-wide association studies into actionable therapeutics persists as a critical challenge in Alzheimer's disease (AD) research. Here, we present PI4AD, a computational medicine framework that integrates multi-omics data, systems biology, and artificial neural networks for therapeutic discovery. This framework leverages multi-omic and network evidence to deliver three core functionalities: clinical target prioritisation; self-organising prioritisation map construction, distinguishing AD-specific targets from those linked to neuropsychiatric disorders; and pathway crosstalk-informed therapeutic discovery. PI4AD successfully recovers clinically validated targets like APP and ESR1, confirming its prioritisation efficacy. Its artificial neural network component identifies disease-specific molecular signatures, while pathway crosstalk analysis reveals critical nodal genes (e.g., HRAS and MAPK1), drug repurposing candidates, and clinically relevant network modules. By validating targets, elucidating disease-specific therapeutic potentials, and exploring crosstalk mechanisms, PI4AD bridges genetic insights with pathway-level biology, establishing a systems genetics foundation for rational therapeutic development. Importantly, its emphasis on Ras-centred pathways-implicated in synaptic dysfunction and neuroinflammation-provides a strategy to disrupt AD progression, complementing conventional amyloid/tau-focused paradigms, with the future potential to redefine treatment strategies in conjunction with mRNA therapeutics and thereby advance translational medicine in neurodegeneration.

OBJECTIVE To investigate the regulatory effect of autophagy on the resistance of human liver cancer cell Huh7 to lenvatinib. METHODS Using human liver cancer cell Huh7 as subject， the lenvatinib-resist cell model （Huh7-LR） was generated by the low-dose gradient method combined with long-term administration. The sensitivity of parental cell Huh7 and drug-resistant cell Huh7-LR to lenvatinib was detected by using CCK-8 assay and flow cytometry. Western blot assay and GFP-mCherry-LC3 plasmid transfection were performed to detect the expression levels of autophagic protein Beclin-1， autophagic adapter protein sequestosome 1 （p62）， microtubule-associated protein 1 light chain 3 （LC3） and autophagic level. Furthermore， an autophagy activation model was constructed by cell starvation， the protein expression of p62 and autophagy level were detected by using Western blot assay and GFP-mCherry-LC3 plasmid transfection， and the effect of autophagy activation on the sensitivity of Huh7-LR cells to lenvatinib was detected by flow cytometry. RESULTS Compared with parental cells， the drug resistance index of Huh7-LR cells was 6.2； protein expression of p62 was increased significantly， while apoptotic rate， protein expression of Beclin-1 and LC3Ⅱ/ LC3Ⅰ ratio were all reduced significantly （P＜0.05 or P＜0.01）； the level of autophagy was decreased to some extent. Autophagy activation could significantly increase the protein expression of p62 in Huh7-LR cells （P＜0.05） and autophagy level， and significantly increase its apoptotic rate （P＜0.05）. CONCLUSIONS Autophagy is involved in lenvatinib resistance， and activating autophagy can reverse the resistance of liver cancer cells to lenvatinib to some extent.

This study explored three molecular typing methods for Vibrio parahaemolyticus(VP)in Liaoning Province in 2020,to assess the correlation among the three methods and the genetic relationships among between strains;analyze the epi-demic trends and distribution patterns of VPin Liaoning Province;and provide reliable technical support for the prevention and control of foodborne diseases.Serum typing,PFGE,REP-PCR,and ERIC-PCR molecular typing and cluster analysis were performed on 44 VP isolates from Liaoning Province in 2020.A total of 44 isolated strains were divided into 15 serotypes,and 8 isolated strains could not be classified.The serotypes were primarily O3 group,O1 group,and O2 group.Clinical isolates had high molecular similarity,whereas food isolates had low molecular similarity.The resolution(DI)of PFGE was 0.986,that of REP-PCR was 0.947,and that of ERIC-PCR was 0.935.The molecular similarity between serotype O3 and O1 group strains was high.The epidemic serotypes of isolated VP strains in Liaoning Province in 2020 were consistent with those from the past 5 years.The resolution of the PFGE typing method was better than that of REP-PCR and ERIC-PCR;moreover,REP-PCR had better resolution than ERIC-PCR.These three typing methods showed good intercorrelation.The O3 group strains are likely to originate from the O1 group strains.When a foodborne disease outbreak is caused by VP,laboratories with conditions can apply these three methods to trace the source of the pathogenic bacteriaquickly and effectively.

Abstract: Objective　To detect the distribution of CYP2A6∗2, CYP2A6∗10, CYP2A6∗17, CYP2B6∗4, CYP2B6∗6, and CYP2B6∗18 loci affecting the metabolism of artemisinins in Kazak population in Xinjiang. To explore the pharmacogenetic background of the Kazak population in Xinjiang for artemisinin drugs and provide clinical decision support for the treatment and prevention of malaria based on artemisinin drugs. Methods　Six SNPs including CYP2A6∗2, CYP2A6∗10, CYP2A6∗17, CYP2B6∗4, CYP2B6∗6, and CYP2B6∗18 were selected for the sequencing experiment. 330 whole blood samples were collected from the Kazak population in Xinjiang. After extracting the whole blood DNA genome, multiplex PCR and high-throughput sequencing were used for genotyping. The allele frequencies were analyzed using the Hardy-Weinberg equilibrium. Results　In this study all SNPs follow the Hardy-Weinberg equilibrium (P>0.05), there was no significant difference in the distribution of SNPs between different genders (P>0.05). The number of successfully sequenced samples of CYP2A6∗2, CYP2A6∗10, CYP2A6∗17, CYP2B6∗4, CYP2B6∗6, and CYP2B6∗18 were 326, 319, 328, 318, 322 and 328 respectively. The frequencies of variant alleles of CYP2A6∗2, CYP2A6∗10, CYP2A6∗17, CYP2B6∗4, CYP2B6∗6, and CYP2B6∗18 in Kazak population are: 0.61%, 0%, 0%, 30.97%, 22.98%, 0%. Conclusions　Mutation alleles affecting the metabolism of artemisinins exist in the Kazak population in Xinjiang. When using artemisinins, the relationship between the drug effect and individual pharmacogenetic background should be further explored.

Objective: To reclassify the flat type sudden deafness according to the types of audiogram shape, and to explore the correlation between different pattern of hearing loss and prognosis. Methods: All of 1 024 patients with unilateral sudden deafness (492 males and 532 females, aged from 19 to 65 years, with an average age of 41.2 years old) admitted to 33 hospitals nationwide from August 2007 to October 2011 were divided into four types according to Chinese Guideline of Sudden Deafness(2015): low-frequency, high-frequency, flat and total deafness. Then, 402 patients with flat type sudden deafness were further divided into ascending type, descending type and consistent type according to the audiogram shapes. First, we compared the clinical characteristics and prognosis among these three subtypes of flat deafness, then compared the clinical characteristics and prognosis between ascending flat deafness and low-frequency deafness, descending flat deafness and high-frequency deafness, consistent flat deafness and total deafness, explored the factors related to the prognosis of flat deafness. SPSS 21.0 software, ANOVA, χ² test, t-test and Logistic regression were used to analyze the data. Results: The cure rates of flat ascending, flat descending and flat consistent sudden deafness groups were 70.7%, 17.1% and 34.0% respectively, with a statistically significant difference (χ²=33.984, P<0.001); However, there was no significant difference in age, sex and affected side (all P>0.05). The independent related factors for the recovery of flat type sudden deafness were as follows: whether there was dizziness [OR=0.459; 95% confidence interval (CI): 0.271-0.777], the type of audiogram shape (OR=0.721; 95%CI: 0.530-0.981), and days from onset to therapy (OR=0.903, 95%CI: 0.835-0.978), all of which had P values<0.05. There was no significant difference in the cure rates between ascending flat sudden deafness and low-frequency descending sudden deafness, descending flat sudden deafness and high-frequency descending sudden deafness (all P>0.05). The pure tone average(PTA) of flat consistent sudden deafness and total deafness were (69.1±18.9) and (101.7±17.7) dB HL, respectively, with a statistically significant difference (t=20.890, P<0.001), and the cure rates were 34.0% and 14.5%, respectively, with a statistically significant difference (χ²=29.012, P<0.001). Conclusion: According to the audiogram shape, the flat type sudden deafness can be further divided into ascending flat sudden deafness, descending flat sudden deafness and consistent flat sudden deafness, which can more effectively evaluate the prognosis. The cure rate of ascending flat sudden deafness is similar to that of low-frequency sudden deafness, and the prognosis is well; The cure rate of descending flat sudden deafness is similar to that of high-frequency descending sudden deafness, and the prognosis is poor. The cure rate of consistent flat sudden deafness is higher than that of total deafness. PTA plays an important role in the prognosis of consistent flat sudden deafness and total deafness. Total deafness can be regarded as a single type of sudden deafness.
Male ; Female ; Humans ; Adult ; Young Adult ; Middle Aged ; Aged ; Hearing Loss, Sudden ; Deafness ; Hearing Tests ; Prognosis ; Vertigo ; Hearing Loss, Unilateral ; Hearing Loss, Sensorineural

OBJECTIVES: To investigate the clinical treatment outcomes and the changes of the outcomes over time in extremely preterm twins in Guangdong Province, China. METHODS: A retrospective analysis was performed for 269 pairs of extremely preterm twins with a gestational age of <28 weeks who were admitted to the department of neonatology in 26 grade A tertiary hospitals in Guangdong Province from January 2008 to December 2017. According to the admission time, they were divided into two groups: 2008-2012 and 2013-2017. Besides, each pair of twins was divided into the heavier infant and the lighter infant subgroups according to birth weight. The perinatal data of mothers and hospitalization data of neonates were collected. The survival rate of twins and the incidence rate of complications were compared between the 2008-2012 and 2013-2017 groups. RESULTS: Compared with the 2008-2012 group, the 2013-2017 group (both the heavier infant and lighter infant subgroups) had lower incidence rates of severe asphyxia and smaller head circumference at birth (P<0.05). The mortality rates of both of the twins, the heavier infant of the twins, and the lighter infant of the twins were lower in the 2013-2017 group compared with the 2008-2012 group (P<0.05). Compared with the 2008-2012 group, the 2013-2017 group (both the heavier infant and lighter infant subgroups) had lower incidence rates of pulmonary hemorrhage, patent ductus arteriosus (PDA), periventricular-intraventricular hemorrhage (P-IVH), and neonatal respiratory distress syndrome (NRDS) and a higher incidence rate of bronchopulmonary dysplasia (P<0.05). CONCLUSIONS There is a significant increase in the survival rate over time in extremely preterm twins with a gestational age of <28 weeks in the 26 grade A tertiary hospitals in Guangdong Province. The incidences of severe asphyxia, pulmonary hemorrhage, PDA, P-IVH, and NRDS decrease in both the heavier and lighter infants of the twins, but the incidence of bronchopulmonary dysplasia increases. With the improvement of diagnosis and treatment, the multidisciplinary collaboration between different fields of fetal medicine including prenatal diagnosis, obstetrics, and neonatology is needed in the future to jointly develop management strategies for twin pregnancy.
Bronchopulmonary Dysplasia/epidemiology* ; Female ; Gestational Age ; Humans ; Infant ; Infant, Extremely Premature ; Infant, Newborn ; Pregnancy ; Respiratory Distress Syndrome, Newborn/epidemiology* ; Retrospective Studies ; Treatment Outcome

OBJECTIVE To investigate the mechanism of glucose -6-phosphate dehydrogenase （G6PD）-induced sorafenib - resistance in hepatocarcinoma cell based on phoshorylated 3-kinase/protein kinase B （PI3K/Akt）signaling pathway . METHODS Cell lines including hepatocarcinoma cell Huh 7，sorafenib-resistant cell Huh 7-SR，G6PD overexpressed cell Huh 7-G6PD and its control cell Huh 7-CT，and compounds including G 6PD inhibitor （6-Aminonicotinamide，6AN）and sorafenib were used as objects or intervention drugs in these research . CCK8 assay was applied to evaluate cell viability . The protein levels of G 6PD and the phosphorylation levels of PI 3K/Akt signaling pathway were detected by Western blot . Flow cytometry was utilized to investigate cell apoptosis. RESULTS Compared with Huh 7 cells，the protein level of G 6PD was significantly increased in Huh 7-SR cells （P＜ 0.05）. The combination of 6AN and sorafenib reduced cell viability of Huh 7-SR cells （P＜0.01）. However，compared with Huh 7- CT，increased cell viability and decreased cell apoptosis rate were observed in Huh 7-G6PD cells while cells were treated with sorafenib（P＜0.01）. Mechanistically，the phosphorylation levels of PI 3K and Akt were significantly decreased in Huh 7-SR cells that were treated with 6AN（P＜0.05）. Moreover，under the condition of no drug intervention ，the phosphorylation levels of PI 3K and Akt were significantly elevated in Huh 7-G6PD cells when compared with Huh 7-CT（P＜0.01）. CONCLUSION G6PD could induce sorafenib -resistance in hepatocarcinoma cell by activating PI 3K/Akt signaling pathway .

Squalene is widely used in pharmaceutical, nutraceutical, cosmetics and other fields because of its strong antioxidative, antibacterial and anti-tumor activities. In order to produce squalene, a gene ispA encoding farnesyl pyrophosphate synthase was overexpressed in a previously engineered Escherichia coli strain capable of efficiently producing terpenoids, resulting in a chassis strain that efficiently synthesizes triterpenoids. Through phylogenetic analysis, screening, cloning and expression of squalene synthase derived from different prokaryotes, engineered E. coli strains capable of efficiently producing squalene were obtained. Among them, squalene produced by strains harboring squalene synthase derived from Thermosynechococcus elongatus and Synechococcus lividus reached (16.5±1.4) mg/g DCW ((167.1±14.3) mg/L broth) and (12.0±1.9) mg/g DCW ((121.8±19.5) mg/L broth), respectively. Compared with the first-generation strains harboring the human-derived squalene synthase, the squalene synthase derived from T. elongatus and S. lividus remarkably increased the squalene production by 3.3 times and 2.4 times, respectively, making progress toward the cost-effective heterologous production of squalene.
Cloning, Molecular ; Escherichia coli/genetics* ; Humans ; Phylogeny ; Squalene ; Synechococcus

Cognition ; Cognitive Dysfunction ; Humans ; Presbycusis