OBJECTIVE: Benzylisoquinoline alkaloids (BIAs) have pharmacological functions and clinical use. BIAs are mainly distributed in plant species across the order Ranunculales and the genus Phellodendron from Sapindales. The BIA biosynthesis has been intensively investigated in Ranunculales species. However, the accumulation mechanism of BIAs in Phellodendron is largely unknown. The aim of this study is to unravel the biosynthetic pathways of BIAs in Phellodendron amurens. METHODS: The transcriptome and metabolome data from 18 different tissues of P. amurense were meticulously sequenced and subsequently subjected to a thorough analysis. Weighted gene co-expression network analysis (WGCNA), a powerful systems biology approach that facilitates the construction and subsequent analysis of co-expression networks, was utilized to identify candidate genes involved in BIAs biosynthesis. Following this, recombinant plasmids containing candidate genes were expressed in Escherichia coli, a widely used prokaryotic expression system. The purpose of this genetic engineering endeavor was to express the candidate genes within the bacteria, thereby enabling the assessment of the resultant enzyme activity. RESULTS: The synonymous substitutions per synonymous site for paralogs indicated that at least one whole genome duplication event has occurred. The potential BIA biosynthetic pathway of P. amurense was proposed, and two PR10/Bet v1 members, 14 CYP450s, and 33 methyltransferases were selected as related to BIA biosynthesis. One PR10/Bet v1 was identified as norcoclaurine synthase, which could catalyze dopamine and 4-hydroxyphenylacetaldehyde into (S)-norcoclaurine. CONCLUSION Our studies provide important insights into the biosynthesis and evolution of BIAs in non-Ranunculales species.

ObjectiveBased on ultra performance liquid chromatography-quadrupole-time-of-flight mass spectrometry（UPLC-Q-TOF-MS/MS）， the combination of serum pharmacochemistry， response profile of absorbed components in serum， network pharmacology and drug-likeness prediction was used to screen the potential active ingredients of Yanghetang against breast cancer. MethodsUPLC-Q-TOF-MS/MS was used to identify the main components in different solvent extracts of Yanghetang， and serum pharmacochemistry was applied to analyze the absorbed components from the serum of female SD rats after 0.5， 1， 2 h of administration. Combined with the response characteristic values of serum drug components obtained from UNIFI 1.8.2， the absorbed prototype components and metabolites were screened to get the absorbed components of Yanghetang with a significant patterns of elimination and growth. Network pharmacology was applied to construct a drug-component-pathway-target-disease network， and molecular docking was performed between absorbed components and key targets of breast cancer， and the drug similarity was analyzed by SwissADME. ResultsForty-two compounds were identified in Yanghetang samples extracted with different solvents， of which 16 compounds were common to the three different extraction solvents（methanol， 50% methanol and water）. The results of drug-containing serum analysis showed that there were 16 absorbed components in serum， including 5 prototypes and 11 metabolites. Network pharmacology results showed that Yanghetang against breast cancer involved 15 key targets such as proto-oncogene tyrosine-protein kinase Src（SRC）， epidermal growth factor receptor（EGFR） and phosphoinositide 3 kinase catalytic alpha polypeptide（PIK3CA）. Molecular docking results showed that 16 potential active ingredients were well combined with the predicted targets. Combined with drug likenesses， 12 compounds in the absorbed components of Yanghetang were considered to have potential for anti-breast cancer activity， mainly including α-pinene and γ-eudesmol and their metabolites， of which one was from Ephedrae Herba， one was from Rehmanniae Radix， and eight were from Cinnamomi Cortex. ConclusionThe chemical components of Yanghetang mainly include polysaccharides， monoterpene glycosides and coumarins， and its prototype components mainly undergo oxidation， hydrolysis and acetylation after entering the blood. Its anti-breast cancer mechanism may be related to the regulation of signaling pathways such as the mitogen-activated protein kinase（MAPK） and phosphatidylinositol 3-kinase/protein kinase B（PI3K/Akt）. The results of this study can lay a foundation for further exploration of Yanghetang in the treatment of breast cancer.

AIM: To evaluate the efficacy of phacoemulsification with intraocular lens implantation(PEI)combined with goniosynechialysis(GSL)and goniotomy(GT)under direct vision with gonioscope in the treatment of advanced primary angle-closure glaucoma(PACG)combined with cataract.METHODS: Retrospective case series study. A total of 62 patients(65 eyes)with advanced PACG combined with cataract who were treated in the Second Hospital of Anhui Medical University from December 1, 2021 to March 31, 2023 were enrolled, and they were divided into two groups according to different surgical methods. The control group(32 cases, 33 eyes)received PEI+GSL, whereas the observation group(30 cases, 32 eyes)received PEI+GSL+GT. The intraocular pressure(IOP), best corrected visual acuity(BCVA)and the number of anti-glaucoma medications of the two groups before surgery and at 1 d, 1 wk, 1, 3, and 6 mo after surgery were evaluated. In addition, the visual field, cup-to-disc ratio(C/D), angle open range, anterior chamber depth, and average thickness of retinal nerve fiber layer(RNFL)were evaluated before and 6 mo after surgery.RESULTS: There were significant differences in IOP and lowering range of average IOP at 6 mo between the PEI+GSL+GT group(16.68±2.65, 11.12±8.53 mmHg)and the PEI+GSL group(18.71±2.51, 8.32±4.17 mmHg; P<0.05), and there was no difference in the rate of IOP reduction(44.57%±21.79% and 35.20%±17.94%, P>0.05). The number of anti-glaucoma medications, BCVA, anterior chamber depth, and angle closure range were improved in the two groups at 6 mo after operation(all P<0.01). The number of medication reductions and the range of angle opening at 6 mo after surgery in the PEI+GSL+GT group were significantly higher than those in the PEI+GSL group(P<0.05), and there was no difference in the other indicators between the two groups(all P>0.05). There was no difference in the mean deviation of visual field, C/D and average thickness of RNFL between the two groups at 6 mo after operation compared with those before operation(all P>0.05). The complete surgery success rate of the PEI+GSL+GT group was 81%(26/32), and the conditional success rate was 94%(30/32); while those rates of the PEI+GSL group were 58%(19/33)and 76%(25/33), respectively. There were statistical significance in the success rate of surgery between the two groups(complete success rate χ2=4.275, P=0.039; conditional success rate χ2=4.040, P=0.044). No vision-threatening complications and another surgery occurred in either group.CONCLUSION: The study showed that for patients with advanced PACG with cataract, PEI+GSL+GT is more effective than PEI+GSL.

Objective This article aimed to explore the inhibitory effect of β-ionone(BI)on the proliferation of breast canc-er cells through the nuclear factor kappa-B(NF-κB)pathway and its possible mechanism.Methods The methylene blue assay and MTT assay were used to determine the viability of breast cancer cells.The malachite green phosphate assay was used to detect the ac-tivity of protein phosphatase 2A(PP2A).Western blot was used to detect the levels of phosphorylated P65(s534 and s311)(p-P65),PP2A(A,B and C),and phosphorylated ataxia telangiectasia mutant(p-ATM)(s1981)protein.Results BI could significant-ly inhibit the proliferation of human breast cancer BT549 cells and MCF-7 cells in a time-and dose-dependent manner,and the difference was statistically significant(P<0.01).After treated with BI,NF-κB activity was significantly inhibited in MCF-7 cells,as shown by a significant decrease in the level of phosphorylated P65(s311 and s534)protein and an increase in the level of PP2A pro-tein,and the difference was statistically significant(P<0.05).In addition,BI also significantly reduced the phosphorylation of P65 protein and ATM protein in MCF-7 cells by the PP2A inhibitor-okada acid(OA).Conclusion This study shows that BI inhibits the proliferation of breast cancer cells by inhibiting NF-κB activity,and its mechanism may be achieved by increasing PP2A activity to regulate the NF-κB pathway.

Objective:To identify factors influencing orthostatic intolerance (OI) in patients during initial ambulation following minimally invasive lung surgery and develop and validate a risk prediction model to assist clinical practitioners in screening high-risk patients.Methods:Totally 1 000 patients who underwent minimally invasive lung surgery at the Department of Thoracic Surgery of Peking University Third Hospital from March 2022 to November 2023 were recruited by convenience sampling. Patients were randomly divided into a modeling group ( n=800) and an internal validation group ( n=200) in an 8∶2 ratio. Univariate analysis and logistic regression were applied to determine risk factors for OI in the modeling group. R software was utilized to construct a nomogram model. The model's predictive performance was assessed using the area under the ROC curve ( AUC) for both the modeling and validation groups. Calibration curves were plotted to evaluate consistency, and the Hosmer-Lemeshow test was conducted to confirm model fit. Results:The incidence of OI during initial ambulation was 37.2% (372/1 000). Logistic regression identified BMI, postoperative day 1 drainage volume, postoperative use of nonsteroidal anti-inflammatory drugs (NSAIDs), and initial ambulation pain score as independent risk factors for OI ( P<0.05). The AUC for the nomogram model in the modeling group was 0.645, and 0.694 in the validation group, indicating good predictive accuracy. Calibration curves showed strong agreement between predicted and observed outcomes ( P>0.05) . Conclusions:The constructed risk prediction model demonstrates good predictive ability for OI risk during initial ambulation following minimally invasive lung surgery, which can support clinical identification of high-risk patients. This tool may provide valuable guidance for implementing early, targeted preventive measures.

Objective:To identify factors influencing orthostatic intolerance (OI) in patients during initial ambulation following minimally invasive lung surgery and develop and validate a risk prediction model to assist clinical practitioners in screening high-risk patients.Methods:Totally 1 000 patients who underwent minimally invasive lung surgery at the Department of Thoracic Surgery of Peking University Third Hospital from March 2022 to November 2023 were recruited by convenience sampling. Patients were randomly divided into a modeling group ( n=800) and an internal validation group ( n=200) in an 8∶2 ratio. Univariate analysis and logistic regression were applied to determine risk factors for OI in the modeling group. R software was utilized to construct a nomogram model. The model's predictive performance was assessed using the area under the ROC curve ( AUC) for both the modeling and validation groups. Calibration curves were plotted to evaluate consistency, and the Hosmer-Lemeshow test was conducted to confirm model fit. Results:The incidence of OI during initial ambulation was 37.2% (372/1 000). Logistic regression identified BMI, postoperative day 1 drainage volume, postoperative use of nonsteroidal anti-inflammatory drugs (NSAIDs), and initial ambulation pain score as independent risk factors for OI ( P<0.05). The AUC for the nomogram model in the modeling group was 0.645, and 0.694 in the validation group, indicating good predictive accuracy. Calibration curves showed strong agreement between predicted and observed outcomes ( P>0.05) . Conclusions:The constructed risk prediction model demonstrates good predictive ability for OI risk during initial ambulation following minimally invasive lung surgery, which can support clinical identification of high-risk patients. This tool may provide valuable guidance for implementing early, targeted preventive measures.

As numerous connections between oncogenic signalling pathways and metabolic activities emerge, the importance of metabolic reprogramming in cancer is being increasingly recognized. During tumorigenesis, breast cancer cells undergo metabolic reprogramming, which generally includes enhanced glycolysis, tricarboxylic acid cycle activity, glutaminolysis and fatty acid biosynthesis. The extension and functional importance of these metabolic alterations may diverge according to breast cancer subtypes.Besides, aberrant metabolism of breast cancer cells remodels tumor microenvironment, promoting cancer vascularization and inhibiting anti-tumor immunity, and thus accelerates tumor progression.This review addresses current knowledge on the metabolic reprogramming and breast cancer microenvironment, which provides some reference for the development of metabolic target drugs for each breast cancer subtype.

The epidemic of COVID-19 has lasted for nearly a year, the number of confirmed cases worldwide is still rising, and the trend of the epidemic is unclear. How will be the further development of COVID-19 epidemic? What is the current status of research on new drugs for coronary virus disease? Will the vaccine currently used change the epidemic pattern? In the context of the normalization of the epidemic, whether the epidemiology of other respiratory viruses will change? This article will discuss and analyze these hot and difficult issues.

Objective To investigate the evaluation and suggestion of the courses of Chinese Medicine for clinical students majoring in medical college. Methods In January 2017, at the end of the Chinese Medicine courses, a total of 35 clinical students of Capital Medical University were investigated through a questionnaire, mainly related to students' understanding of Chinese medicine; evaluation and suggestions for Chinese Medicine education and teaching. Results The majority of students believed that Chinese medicine was safe and effective. The proportion of believing worthing learning that the Chinese medicine accounted for 94.3% (33/35), and who believed Chinese medicine helpful for the clinical work accounted for 82.9% (29/35). However, the proportion of satisfaction with the current teaching method was 60% (21/35). Conclusions Most of the clinical students in this investigation have recognized the role of Chinese medicine, and have shown great interest in studying the course, but they are not satisfied with the current teaching. To improve the teaching quality of Chinese Medicine through the reform should be the direction of teachers' efforts in the future.

Objective To assess and compare the incidence,clinical characteristics,treatment,and prognosis of acute heart failure patients from different grades hospitals in Beijing.Methods In this prospective internet prognosis registered study (Beijing AHF Registry),a total of 3 335 consecutive patients admitted to 14 emergency departments in Beijing from January 1st 2011 to September 23rd 2012 were enrolled.According to hospital grade,these patients were divided into two groups,349 patients were from secondary hospitals,and 2 956 patients were from tertiary hospitals.Results Among the 3 335 patients,the medium age was 71 (58,79) years,and male accounted for 53.16％.The most common underlying disease were coronary disease (43.27％),hypertension (17.73％),cardiomyopathy (16.07％) etc.The average treatment time in Emergency Department was 66.82 h.The emergency department mortality rate was 3.81％ (127 cases).The 30-day and 1-year cumulative all-cause mortality were 15.3％ and 32.27％,respectively.The 30-day and 1-year cumulative all-cause readmission were 15.64％ and 46.89％,respectively.Compared with patients in tertiary hospitals,patients in secondary hospitals had more onset acute heart failure patients (63.64％ vs.49.93％),shorter emergency department treatment time (12 h vs.41 h),lower discharge rate (3.43％ vs.37.45％) and emergency department mortality(1.58％ vs.4.09％).Compared with those in tertiary hospitals,1-year cumulative all-cause mortality (25.6％ vs.33.2％),cardiovascular disease mortality (20.2％ vs.26.0％),aggravated heart failure mortality (22.4％ vs.28.8％) were lower in secondary hospitals.Following propensity score matching,compared to tertiary hospitals,patients in secondary hospitals showed lower utilization rate of beta-blockers and ACEFARB (4.51％ vs.28.17％,1.41％ vs.9.58％),except the pironolactone.Conclusion Acute heart failure in emergency department is associated with a high mortality rate and readmission rate.There is still a big gap between guidelines recommend medication current treatments for acute heart failure.