The 2-(2-phenylethyl)chromones were separated from agarwood of Aquilaria agallocha Roxb. and their anti-KRAS mutant non-small cell lung cancer (NSCLC) activities were evaluated. 2-(2-Phenyethyl)chromones in agarwood were separated and purified by silica gel, RP-18 reverse phase silica gel, MCI gel CH20P, Diol, and semi preparative HPLC chromatography techniques, while the structures of the compounds were identified by extensive spectroscopic analysis, such as 1D and 2D NMR and ESI-MS. The cell counting kit 8 (CCK-8) assay was used to screen the anti-tumor activity of the isolated monomeric compounds on three KRAS-mutant NSCLC cells. The cell proliferation, cloning formation, adhesion ability, and cell cycle arrest activity of compound 8 were analyzed. Molecular docking and Western blot experiments were used to study the mechanism of compound 8. The in vivo anti-tumor activity of the compound 8 was evaluated by zebrafish cell derived xenograft (CDX) model. Nineteen known 2-(2-phenylethyl)chromones were isolated from the ethyl acetate extract of agarwood. On A549 (KRAS G12S) cells, compounds 8, 10, and 19 showed good inhibitory activity, on H23 (KRAS G12C) cells, compounds 7, 8, and 19 showed good inhibitory activity, and on H358 (KRAS G12C) cells, compounds 8, 10, and 16 showed good inhibitory activity. Compound 8 had the best inhibitory activity in all three cell lines. It effectively inhibited cell proliferation, clone formation, adhesion ability, and arrested the H23 cell cycle at G2/M phase. Compound 8 could also inhibit the expression of c-Met and its downstream signaling pathways, effectively inhibiting tumor growth in zebrafish CDX model. In conclusion, among the nineteen known 2-(2-phenylethyl)chromones, compound 8 had the best activity and significantly inhibited the proliferation of KRAS-mutant NSCLC cells by arresting the cells in the G2/M phase.

Dental age estimation is a crucial aspect and one of the ways to accomplish forensic age estimation,and imaging technology is an important technique for dental age estimation.In recent years,some studies have preliminarily confirmed the feasibility of magnetic resonance imaging(MRI)in evaluating dental development,providing a new perspective and possibility for the evaluation of den-tal development,suggesting that MRI is expected to be a safer and more accurate tool for dental age estimation.However,further research is essential to verify its accuracy and feasibility.This article re-views the current state,challenges and limitations of MRI in dental development and age estimation,offering reference for the research of dental age assessment based on MRI technology.

Diabetic kidney disease(DKD)is one of the most important complications of diabetes.In recent years,domestic and foreign studies have found that mammalian target protein of rapamycin(mTOR)related signaling pathway is a classic pathway involved in the regulation of autophagy,which can achieve the therapeutic effect of DKD by targeting the autophagy pathway,and plays a crucial role in the prevention and treatment of DKD.In this paper,we reviewed the mechanism of mTOR-related signaling pathway targeted autophagy in the prevention and treatment of DKD,in order to provide a new reference and basis for clinical prevention and treatment of DKD.

Objective To investigate the renal protective effect and mechanism of sodium acetate(Ace)on hyperuricemic nephropathy(HN)in mice.Methods Uric acid nephropathy mice model was prepared by intraperitoneal injection of potassium oxonate combined with adenine gavage.Mice were divided into blank control group(0.9％NaCl+0.5％carboxymethyl cellulose sodium),Ace group(200 mmol·L-1 Ace+0.5％carboxymethyl cellulose sodium),model group(0.9％NaCl+350 mg·kg-1 potassium oxonate+70 mg·kg-1 adenine),and experimental group(based on model group with additional 200 mmol·L-1 Ace).Serum and urine uric acid(UA)and serum creatinine(SCr)levels were observed in each group.Real-time fluorescence quantitative reverse transcription-polymerase chain reaction(qRT-PCR)was used to detect the expression levels of kidney injury molecule-1(Kim-1)and anti-aging gene Klotho,renal fibrosis markers Collagen Ⅰ and Fibronectin,intestinal inflammation-related factors interleukin-1 β(IL-1 β),and mRNA expression levels of tight junction proteins Zo-1.Results The serum UA levels of blank control group,Ace group,model group,and experimental group mice were(259.52±24.40),(227.71±35.91),(604.06±73.55),and(496.24±30.16)μmol·L-1,respectively;SCr levels were(16.85±0.40),(16.18±0.94),(22.38±1.56),and(19.78±1.43)μmol·L-1;Kim-1 mRNA relative expression levels were 1.04±0.25,1.17±0.28,13.00±2.87,and 4.24±3.92;Klotho mRNA relative expression levels were 1.04±0.15,1.02±0.18,0.43±0.12,and 0.69±0.12;Collagen Ⅰ mRNA relative expression levels were 1.05±0.15,1.02±0.18,3.19±1.09,and 1.61±0.55;Fibronectin mRNA relative expression levels were 1.07±0.18,1.02±0.25,7.86±2.40,and 3.34±2.10;intestinal IL-1β mRNA relative expression levels were 1.00±0.01,1.01±0.03,2.55±0.63,and 1.21±0.28;intestinal Zo-1 mRNA relative expression levels were 1.00±0.07,1.07±0.09,0.54±0.20,and 0.92±0.17.The above indicators in blank control group compared with model group,and experimental group compared with model group,all showed statistically significant differences(P＜0.05,P＜0.01,P＜0.001).Conclusion Sodium acetate can effectively reduce UA levels in HN mice,significantly improve renal injury and fibrosis,and its mechanism may be related to the improvement of intestinal inflammatory response and up-regulation of intestinal Zo-1/Occuludin pathway to reduce intestinal mucosal permeability.

Objective To systematically evaluate the efficacy of different analgesic methods in re-lieving the pain in hip and femoral shaft fractures patients during spinal anesthesia position by using network meta-analysis.Methods The articals of randomized controlled trials(RCTs)that analgesia was performed in patients with hip and femoral shaft fractures during the spinal anesthesia position placement were retrieved from the following database from the establishment of the database to August 2022,PubMed,the Cochrane Library,Web of Science,EMbase,China Biology Medicine(CBM),CNKI,VIP,and Wanfang databases.Literature screening,data extraction and bias risk assessment were conducted by two researchers separately.Stata 17.0 and RevMan 5.3 software were used for statistical analysis.Results A total of 28 RCTs with 1 773 patients were included.The surface under the cumulative ranking(SUCRA)curve showed that and PENG block(94.4%)had the best effect on reducing the VAS pain score of placement position,followed by FIBcombinedwith IVA(83.8%)and FIB(71.1%),and PENG block(98.2%)had the best effect on reducing VAS pain score during spinal anesthesia,followed by FIB(71.1%)and FNB(55.6%),and PENG block(84.1%)had the best effect on shortening the time of spinal anesthesia operation,followed by FNB(70.7%)and FIB(68.5%),and PENG block(99.1%)had the best effect on improving the quality of positioning,followed by FIB(73.1%)and FNB(52.9%).Conclusion Nerve blocks or the combina-tion with IVA can reduce pain scores during position placement and spinal anesthesia,shorten anesthesia operation time,and improve quality of position placement in patients with hip and femoral shaft fractures.PENG block has the best analgesic effect in patients with hip or femoral shaft fractures during positioning and spinal anesthesia.

Objective To systematically evaluate the efficacy and safety of electroacupuncture(EA)in the treatment of postoperative nausea and vomiting(PONV)after gynecological surgery.Methods PubMed,Cochrane Library,Web of Science,Embase,China national knowledge infrastructure(CNKI),Wanfang database,and China biomedical literature database(CBM)were systematically searched.The re-trieval period was from the establishment of the database to December 2022.Relevant randomized controlled trials on EA for the treatment of PONV in gynecological surgery were collected.RevMan 5.3 software was used for meta-analysis.Results Fourteen randomized controlled trials were accommodated,including 958 patients,477 patients in the EA group and 481 patients in the control group.Compared with the control group,the incidence of PONV was significantly lower in group EA at 0-48 hours postoperatively(RR=0.55,95％CI 0.47 to 0.65,P＜0.001),and the PONV scores were significantly lower in the postopera-tive period within 48 hours in group EA(MD=-0.40 scores,95％CI-0.65 to-0.16 scores,P=0.004),the incidence of postoperative remedial antiemetic were significantly lower(RR=0.28,95％CI 0.16 to 0.51,P＜0.001).Conclusion EA can reduce the incidence of PONV and the incidence of re-medial antiemetic after gynecologic surgery.

Cannabinoid type 1 receptor(CB1R)is one of the most widely studied endocannabinoid receptors in recent years,which is expressed in both central and peripheral nerve systems.CBIR is located in the presynaptic membrane,and regulates the release of neurotransmitters through retrograde inhibitory synaptic transmission,which is an effective target for the treatment of pain.Activation of CB1R has analgesic effect on injurious,pathological,and inflammatory pain,and antagonism of CB1R can cause pain sensitization.This article describes CB1R from the aspects of structure and function,signal transduction,and analgesic mechanism,so as to provide reference for further understanding the pathophysiology of pain and exploring better pain treatment methods.

Objective To systematically evaluate the effect of transcutaneous electrical acupoint stimulation(TEAS)in the treatment of postoperative nausea and vomiting(PONV)after laparoscopic non-gastrointestinal surgery.Methods Databases such as PubMed,Cochrane library,Web of Science,Embase,CNKI,Wanfang,and Chinese biomedical database(CBM)were searched to find and screen ran-domized controlled trials(RCTs)of TEAS in the prevention and treatment of PONV after laparoscopic non-gastrointestinal surgery.The retrieval time was from the establishment of the database to July 2023.Meta-a-nalysis was performed using RevMan 5.3 software.Results Twenty-two RCTs involving 3 538 patients were included,including 1 799 in the TEAS group and 1 739 in the control group.The results of meta-analysis showed that the total incidence of PONV in the TEAS group was significantly lower than that in the control group 0-24 hours after operation(RR=0.54,95％CI 0.44-0.68,P＜0.001),and the incidence of postoperative remedial antiemetic was significantly reduced(RR=0.54,95％CI 0.38-0.77,P＜0.001).There was no significant difference in the incidence of postoperative acupoint stimulation-related adverse reactions between the two groups(RR=0.62,95％CI 0.15-2.51,P=0.500).Conclusion TEAS has good clinical efficacy and safety in the treatment of PONV after laparoscopic non-gastrointestinal surgery.

Background/Aims: Four-week treatment of linvencorvir (RO7049389) was generally safe and well tolerated, and showed anti-viral activity in chronic hepatitis B (CHB) patients. This study evaluated the efficacy, safety, and pharmacokinetics of 48-week treatment with linvencorvir plus standard of care (SoC) in CHB patients. Methods: This was a multicentre, non-randomized, non-controlled, open-label phase 2 study enrolling three cohorts: nucleos(t)ide analogue (NUC)-suppressed patients received linvencorvir plus NUC (Cohort A, n=32); treatment-naïve patients received linvencorvir plus NUC without (Cohort B, n=10) or with (Cohort C, n=30) pegylated interferon-α (Peg-IFN-α). Treatment duration was 48 weeks, followed by NUC alone for 24 weeks. Results: 68 patients completed the study. No patient achieved functional cure (sustained HBsAg loss and unquantifiable HBV DNA). By Week 48, 89% of treatment-naïve patients (10/10 Cohort B; 24/28 Cohort C) reached unquantifiable HBV DNA. Unquantifiable HBV RNA was achieved in 92% of patients with quantifiable baseline HBV RNA (14/15 Cohort A, 8/8 Cohort B, 22/25 Cohort C) at Week 48 along with partially sustained HBV RNA responses in treatment-naïve patients during follow-up period. Pronounced reductions in HBeAg and HBcrAg were observed in treatment-naïve patients, while HBsAg decline was only observed in Cohort C. Most adverse events were grade 1–2, and no linvencorvir-related serious adverse events were reported. Conclusions 48-week linvencorvir plus SoC was generally safe and well tolerated, and resulted in potent HBV DNA and RNA suppression. However, 48-week linvencorvir plus NUC with or without Peg-IFN did not result in the achievement of functional cure in any patient.

Enamel formation is a series of complex physiological processes, which are regulated by critical genes spatially and temporally. These processes involve multiple developmental stages covering ages and are prone to suffer signal interference or gene mutations, ultimately leading to developmental defects of enamel (DDE). Epigenetic modifications have important regulatory roles in gene expression during enarnel development. New technologies including high-throughput sequencing, chromatin immunoprecipitation sequencing (ChIP-seq), and DNA methylation chip are emerging in recent years, making it possible to establish genome-wide epigenetic modification profiles during developmental processes. The regulatory role of epigenetic modification with spatio-temporal pattern, such as DNA methylation, histone modification and non-coding RNA, has significantly expanded our understanding of the regulatory network of enamel formation, providing a new theoretical basis of clinical management and intervention strategy for DDE. The present review briefly describes the enamel formation process of human beings' teeth as well as rodent incisors and summarizes the dynamic characteristics of epigenetic modification during enamel formation. The functions of epigenetic modification in enamel formation and DDE are also emphatically discussed.
Humans ; Epigenesis, Genetic ; Developmental Defects of Enamel ; DNA Methylation ; Oligonucleotide Array Sequence Analysis ; Dental Enamel