3ʹ-Hydroxy-4ʹ-methoxy-2-hydroxy-5-bromochalcone (hereinafter referred to as C13) is a novel chalcone derivative obtained in the process of structural modification of DHMMF, the antitumor active compound of Resina Draconis, in our laboratory. In this study, we investigated the effects of C13 on the proliferation and apoptosis of human gastric cancer HGC-27 and AGS cells and its potential mechanism of action. Firstly, through methyl thiazolyl tetrazolium (MTT), colony formation assay, and 5-ethynyl-2'-deoxyuridine (EdU) staining, we found that C13 inhibited the proliferation ability of human gastric cancer HGC-27 and AGS cells. Using flow cytometry and Western blot, it was found that C13 induced apoptosis in human gastric cancer HGC-27 and AGS cells, and up-regulated the protein level of cleaved poly ADP-ribose polymerase (cleaved-PARP). The results of RNA sequencing analysis showed that the Erb-b2 receptor tyrosine kinase 4/phosphoinositide 3-kinases/AKT (ErbB4/PI3K/AKT) signaling pathway may be involved in anti-gastric cancer activity of C13. Finally, the results of immunoblotting assay showed that C13 treatment down-regulated the protein levels of ErbB4 and phospho-ErbB4, as well as down-regulated the phosphorylation levels of PI3K and AKT in human gastric cancer HGC-27 and AGS cells, which verified the results from RNA-seq analysis. In conclusion, C13 inhibited the proliferation and induced apoptosis of human gastric cancer cells, which may be related to the down-regulation of ErbB4/PI3K/AKT signaling pathway. This study may provide a candidate drug for the treatment of gastric cancer.

AIM To investigate the effects of different compatibility ratios and processing method on the content of rutin,isoquercetin,ferulic acid,quercetin,isotoosendanin,kaempferol,toosendanin,α-pinene,trans-anethole in the combination use of Toosendan Fructus and Foeniculi Fructus,and to explore the optimal compatibility ratio for its use.METHODS The analysis of HPLC-DAD was performed on a 30℃thermostatic ZORBAX SB C18 column(4.6 mm×250 mm,5 μm),with the mobile phase comprising of acetonitrile-0.1%phosphoric acid flowing at 1.0 mL/min in a gradient elution manner,and the use of DAD detector.SPSS 24.0 software was used to analyze the data differences.RESULTS Nine constituents showed good linear relationships within their own ranges(r≥0.999 1),whose average recoveries were 96.19%-103.13%with the RSDs of 1.86%-2.67%.Generally higher total content of nine constituents were detected in the combination use groups when Toosendan Fructus-Foeniculi Fructus were at ratios of 1 ∶ 1,1 ∶ 2,and 2 ∶ 1 than those single uses(P<0.05),and among which the 1 ∶ 1 ratio contributed the highest total content.After salt processing,decreased content of toosendanin and isotoosendanin,α-pinene and trans-anethole(P<0.05,P<0.01)),increased isoquercetin content(P<0.01),and no significant content changes of other ingredients were detected.CONCLUSION Through this method of high accuracy and good reproducibility,we learn that the combination use of Toosendan Fructus and Foeniculi Fructus promotes the dissolution of the nine constituents,and the maximum content is achieved at ratio of 1 ∶ 1.

Most chemical medicines have polymorphs. The difference of medicine polymorphs in physicochemical properties directly affects the stability, efficacy, and safety of solid medicine products. Polymorphs is incomparably important to pharmaceutical chemistry, manufacturing, and control. Meantime polymorphs is a key factor for the quality of high-end drug and formulations. Polymorph prediction technology can effectively guide screening of trial experiments, and reduce the risk of missing stable crystal form in the traditional experiment. Polymorph prediction technology was firstly based on theoretical calculations such as quantum mechanics and computational chemistry, and then was developed by the key technology of machine learning using the artificial intelligence. Nowadays, the popular trend is to combine the advantages of theoretical calculation and machine learning to jointly predict crystal structure. Recently, predicting medicine polymorphs has still been a challenging problem. It is expected to learn from and integrate existing technologies to predict medicine polymorphs more accurately and efficiently.

Resident training is a necessary path to cultivate excellent clinical doctors. Based on the Consensus on Core Competency Framework for Residency Education Among China Consortium of Elite Teaching Hospitals for Residency Education, Department of Neurology from Peking Union Medical College Hospital has established a training program for neurology residents with a graded evaluation system and a progressive clinical responsibility concept guided by core competency. Overcoming the teaching difficulties of neurology and considering the clinical characteristics of neurology, we have established a series of replicable and promotable neurology residency training curriculum through inheritance and innovation, which provides reference for the continuous improvement of China's neurology residency training program.

Objective To investigate the effect of ankyrin-repeat domain-containing protein 22(ANKRD22)on the proliferation,invasion,and migration of human hepatoma cells and its molecular mechanism.Methods The TCGA database was used to analyze the expression level of ANKRD22 in normal liver tissue and hepatocellular carcinoma tissue and its association with prognosis.Western Blot and qRT-PCR were used to measure the expression of ANKRD22 in human normal liver cells(L-02)and human hepatoma cells(Huh7,HepG2,MHCC-97H,SK-HEP-1,and SMMC-7721);CCK-8 assay,EdU,wound healing assay,and Transwell assay were used to observe the effect of ANKRD22 on the proliferation,invasion,and migration of hepatoma cells;Western Blot was used to investigate the association of ANKRD22 with cyclins and EMT-related proteins;KEGG and ssGSEA analyses were performed to investigate the mechanism of action of ANKRD22 in hepatoma cells,and related experiments were conducted for validation.The independent-samples t-test was used for comparison of continuous data between two groups;a one-way analysis of variance was used for comparison between multiple groups,and the least significant difference t-test was used for further comparison between two groups.Results In the TCGA database,the expression level of ANKRD22 in hepatoma tissue was significantly higher than that in normal liver tissue(t=5.083,P<0.05),and the patients with a high expression level of ANKRD22 had longer overall survival and disease-related survival than those with a low expression level of ANKRD22(P<0.05).The expression level of ANKRD22 in various human hepatoma cell lines was higher than that in human normal liver cells(all P<0.05).Cell proliferation assay showed that the ANKRD22 overexpression group had significantly higher EdU positive rate and proliferation rate than the Vector group(t=19.60 and 6.72,both P<0.001),and compared with the si-NC group,the si-ANKRD22#2 group and the si-ANKRD22#3 group had significantly lower EdU positive rate and proliferation rate(all P<0.001).Compared with the Vector group,the overexpression group had significantly higher expression levels of Cyclin E1,Cyclin D1,CDK7,and CDK4(t=3.54,4.95,6.34,and 5.19,all P<0.01),and the si-ANKRD22#2 group and the si-ANKRD22#3 group had significantly lower expression levels than the si-NC group(all P<0.001).The overexpression group had a significantly lower expression level of P27 than the Vector group(t=6.12,P<0.001),and the si-ANKRD22#2 group and the si-ANKRD22#3 group had a significantly higher expression level than the si-NC group(both P<0.001).Invasion and migration experiments showed that compared with the Vector group,the ANKRD22 overexpression group had significantly higher migration rate and number of crossings through the membrane(migration group and invasion group)(t=5.01,25.60,and 3.67,all P<0.05),and compared with the si-NC group,thesi-ANKRD22#2 group and the si-ANKRD22#3 group had significantly lower migration rate and number of crossings through the membrane(migration group and invasion group)(all P<0.01).The overexpression group had significantly higher expression levels of N-cadherin,Vimentin,and Snail than the Vector group(t=12.13,8.85,and 13.97,all P<0.001),and the si-ANKRD22#2 group and the si-ANKRD22#3 group had significantly lower expression levels than the si-NC group(all P<0.001);the overexpression group had a significantly lower expression level of E-cadherin than the Vector group(t=4.98,P<0.01),and the si-ANKRD22#2 group and the si-ANKRD22#3 group had a significantly higher expression level than the si-NC group(both P<0.001).The KEGG enrichment analysis and the ssGSEA analysis showed that ANKRD22 was associated with the PI3K/AKT/mTOR signaling pathway in hepatocellular carcinoma,and the overexpression group had significantly higher expression levels of p-AKT/AKT,p-PI3K/PI3K,and p-mTOR/mTOR than the Vector group(t=12.21,3.43,and 9.75,all P<0.01),and the si-ANKRD22#2 group and the si-ANKRD22#3 group had significantly lower expression levels than the si-NC group(all P<0.001).Conclusion ANKRD22 is highly expressed in hepatoma cells and can promote the proliferation,invasion,and migration of hepatoma cells and the activation of the PI3K/AKT/mTOR signaling pathway.

Purpose::Cerebral edema (CE) is the main secondary injury following traumatic brain injury (TBI) caused by road traffic accidents (RTAs). It is challenging to be predicted timely. In this study, we aimed to develop a prediction model for CE by identifying its risk factors and comparing the timing of edema occurrence in TBI patients with varying levels of injuries.Methods::This case-control study included 218 patients with TBI caused by RTAs. The cohort was divided into CE and non-CE groups, according to CT results within 7 days. Demographic data, imaging data, and clinical data were collected and analyzed. Quantitative variables that follow normal distribution were presented as mean ± standard deviation, those that do not follow normal distribution were presented as median (Q 1, Q 3). Categorical variables were expressed as percentages. The Chi-square test and logistic regression analysis were used to identify risk factors for CE. Logistic curve fitting was performed to predict the time to secondary CE in TBI patients with different levels of injuries. The efficacy of the model was evaluated using the receiver operator characteristic curve. Results::According to the study, almost half (47.3%) of the patients were found to have CE. The risk factors associated with CE were bilateral frontal lobe contusion, unilateral frontal lobe contusion, cerebral contusion, subarachnoid hemorrhage, and abbreviated injury scale (AIS). The odds ratio values for these factors were 7.27 (95% confidence interval ( CI): 2.08 -25.42, p = 0.002), 2.85 (95% CI: 1.11 -7.31, p = 0.030), 2.62 (95% CI: 1.12 -6.13, p = 0.027), 2.44 (95% CI: 1.25 -4.76, p = 0.009), and 1.5 (95% CI: 1.10 -2.04, p = 0.009), respectively. We also observed that patients with mild/moderate TBI (AIS ≤ 3) had a 50% probability of developing CE 19.7 h after injury (χ 2= 13.82, adjusted R2 = 0.51), while patients with severe TBI (AIS > 3) developed CE after 12.5 h (χ 2= 18.48, adjusted R2 = 0.54). Finally, we conducted a receiver operator characteristic curve analysis of CE time, which showed an area under the curve of 0.744 and 0.672 for severe and mild/moderate TBI, respectively. Conclusion::Our study found that the onset of CE in individuals with TBI resulting from RTAs was correlated with the severity of the injury. Specifically, those with more severe injuries experienced an earlier onset of CE. These findings suggest that there is a critical time window for clinical intervention in cases of CE secondary to TBI.

Objective:To observe the projections from tyrosine hydroxylase(TH)positive neurons in locus coerule-us(LC)to tachykinin-1(TAC1)neurons in paraventricular nucleus of the thalamus(PVT),and morphologically determine whether they are involved in transmission and modulation of nociceptive information.Methods:TAC1-ires-Cre mice were hybridized with Rosa26:CAG-LSL-tdTomato(Ai9)mice.And spared nerve injury(SNI)induced neu-ropathic pain model was established with TAC1-ires-Cre::Ai9 mice to observe the colocalization of TAC1 and Fos and the close appositions between TAC1/FOS double-labeled neurons and TH positive axonal terminals.The distribution of the TH positive neurons and FG retrogradely labeled neurons were observed in the LC after Fluorogold(FG)was injec-ted into the PVT.Finally,the coexistences of TH positive neurons and RV labeled neurons in the LC were observed after injection of RV-mediated retrograde tracing system.Results:TAC1 positive neurons were shown with red fluores-cence in TAC1-ires-Cre::Ai9 mice.TAC1/FOS double-labeled neurons were found in the PVT of the SNI model.Some TAC1/FOS double labeled neurons made close appositions with TH positive axonal terminals.FG retrogradely labeled neurons were observed in the LC after FG injected into the PVT,and some of the FG labeled neurons coexisted with TH positive neurons.Using RV retrograde transsynaptic tracing virus,the results showed that presynaptic neurons of TAC1 positive neurons in the PVT were found in the LC,and most of the presynaptic neurons were TH positive neu-rons.Conclusion:TH positive neurons in the LC project to TAC1 positive neurons of the PVT,forming LCTH+-PVTTAC1+neural circuit,which were activated by nociceptive information.It demonstrates that this pathway plays a role in pain transmission or regulation.

Objective To explore clinical efficacy of osteoplasty combined with percutaneous vertebroplasty(PVP)and percutaneous kyphoplasty(PKP)alone in treating osteoporosis vertebral compression fractures(OVCFs).Methods The clini-cal data of 80 patients with single-level OVCFs treated from January 2021 to June 2022 were retrospectively analyzed,and were divided into treatment group and control group according to different surgical methods,40 patients in each group.In treatment group,there were 24 males and 16 females,aged from 60 to 83 years old with an average of(70.43±7.31)years old;bone min-eral density ranged from-3.30 to-2.50 SD with an average of(-2.84±0.24)SD;1 patient with T10,4 patients with T11,11 pa-tients with T12,7 patients with L1,7 patients with L2,5 patients with L3,3 patients with L4,2 patients with L5;bone setting tech-nique combined with PVP were performed.In control group,there were 27 males and 13 females,aged from 60 to 82 years old with an average of(68.98±6.94)years old;bone mineral density ranged from-3.40 to-2.50 SD with an average of(-2.76±0.23)SD;2 patients with T10,3 patients with T11,13 patients with T12,11 patients with L1,5 patients with L2,3 patients with L3,2 patients with L4,1 patient with L5;simple PKP were peformed.Visual analogue scale(VAS)and lumbar Oswestry disability in-dex(ODI)were compared between two groups before operation,3 days,3 and 12 months after operation.The changes of local kyphotic angle,vertebral wedge angle and vertebral anterior margin height ratio were compared between two groups before op-eration,3 days and 12 months after operation.Results All patients were successfully completed operation.Treatment group were followed up from 13 to 22 months with an average of(16.82±2.14)months,and control group were followed up from 13 to 23 months with an average of(16.45±2.56)months.Three patients were occurred bone cement leakage in treatment group,while 1 patient were occurred bone cement leakage and 1 patient occurred sensory disturbance of lower limb skin in control group;there were no significant difference in complications between two groups(P＞0.05).There were no significant difference in preoperative VAS and ODI between two groups(P＞0.05).At 3 days after operation,VAS of treatment group 3.68±0.62 was significantly higher than that of control group 4.00±0.72(P＜0.05).There were no significant difference in VAS and ODI be-tween two groups at 3 and 12 months after operation(P＞0.05).There were no significant difference in local kyphotic angle,vertebral wedge angle and vertebral anterior margin height between two groups at 3 days and 12 months after operation(P＞0.05).Conclusion Compared with PKP,bone setting manipulation combined with PVP for the treatment of OVCFs has advan-tages in early postoperative pain relief.In terms of vertebral height recovery,bone setting manipulation combined with PVP and PKP alone have similar clinical effects.

Objective To investigate the effect of varying ureteral wall thickness(UWT)at the site of ureteral stones on the clinical efficacy of ureteroscopic lithotripsy(URL).Methods The clinical data of 164 patients with ureteral stones in our hospital were retrospectively analyzed.According to different UWT,the patients were divided into the mild thickening group(84 cases,UWT<3.16 mm),the moderate thickening group(31 cases,UWT 3.16 to 3.49 mm),and the severe thickening group(49 cases,UWT>3.49 mm),and the differences of clinical related indicators among the three groups were compared.Results The incidence of postoperative renal colic and leukocyte disorder in the mild thickening group and the moderate thickening group were lower than those in the severe thickening group,and the differences were statistically significant(P<0.05).The postoperative catheterization time in the mild thickening group and the moderate thickening group were shorter than that in the severe thickening group,and the incidences of secondary lithotripsy,residual stones and stone return to kidney in the mild thickening group and the moderate thickening group were lower than those in the severe thickening group,with statistically significant differences(P<0.05).The length of hospital stay and hospitalization cost in the mild thickening group and the moderate thickening group were shorter/less than those in the severe thickening group,with statistically significant differences(P<0.05).Conclusion With the increase of UWT(especially when UWT>3.49 mm),the incidence of postoperative complications and hospitalization cost of URL increase to varying degrees,and the surgical efficacy decreases.In clinical work,UWT measurement holds potential value in predicting the surgical efficacy and complications of URL.

Post-endoscopic retrograde cholangiopancreatography pancreatitis(PEP)is one of the most common complications after endoscopic retrograde cholangiopancreatography(ERCP).Numerous PEP prediction models have been established based on different statistical methods at home and abroad.The PEP prediction model,as a tool for evaluating and screening high-risk populations,can provide a basis for medical staff to find high-risk PEP patients early and take effective preventive measures.In recent years,new PEP prediction models have appeared one after another,but there is still a lack of recognized reliable prediction models in clinic.This article reviews the research status of PEP risk prediction models,aim to provide a direction for establishing a more reliable,accurate,and practical PEP risk prediction model in the later period.