ObjectiveThis paper aims to clarify the material basis of Gualou Niubangtang and establish a quantitative analysis method for its main constituents， providing a reference for the overall quality control of this preparation. MethodsThe constituents in the formula were systematically characterized based on ultra-performance liquid chromatography-quadrupole time-of-flight tandem mass spectrometry （UPLC-Q-TOF-MS/MS）. Identification was performed by matching with the UNIFI 9.6 software and utilizing database platforms such as PubChem， ChemicalBook， and ChemSpider， combined with relevant literature reports. A quantitative analysis method for the seven main constituents in Gualou Niubangtang was established by using high performance liquid chromatography （HPLC）. ResultsUPLC-Q-TOF-MS/MS analysis identified 155 constituents， including 69 flavonoids， 36 terpenoids， 23 phenylpropanoids， 8 phenylethanoid glycosides， and 19 other types of constituents. In the established quantitative analysis method， the seven main constituents showed good linearity within their respective linear ranges. The precision， repeatability， stability， and spike recovery all met the required standards. The results showed that the content ranges of geniposide， liquiritin， hesperidin， arctiin， baicalin， oroxylin A-7-O-β-D-glucuronide， and wogonoside in 15 batches of Gualou Niubangtang were 13.67-21.25， 1.20-7.64， 5.45-7.45， 22.97-33.51， 29.95-39.07， 2.58-4.80， and 6.56-9.31 mg·g^-1， respectively. ConclusionThis study successfully characterizes and attributes multi-category constituents in Gualou Niubangtang， clarifying that its material basis is primarily composed of flavonoids， terpenoids， phenylethanoid glycosides， and phenylpropanoids. Furthermore， it enables the quantification of seven constituents within the formula. This work lays a foundation for research on the quality control， action mechanism， and clinical application of this formula.

ObjectiveTo integrate network pharmacology prediction with multi-level experimental verification methods， and to explore in depth the therapeutic efficacy and potential mechanism of luteolin in treating gout. MethodsDatabases were used to obtain potential pharmacodynamic targets of luteolin. Protein-protein interaction （PPI） network construction and network pharmacology analysis techniques were used to screen key core targets of luteolin in gout treatment. Further biological function enrichment analysis and signaling pathway analysis were performed on these targets. Molecular docking simulation was used to calculate the binding energy between luteolin and potential core targets， clarifying the strength of their interactions. In the in vivo experiment for hyperuricemia， 48 mice were randomly divided into a blank group， a model group， an allopurinol group （5 mg·kg^-1）， and low-dose （10 mg·kg^-1）， medium-dose （30 mg·kg^-1）， and high-dose （90 mg·kg^-1） luteolin groups. For the first three days， the blank and model groups were gavaged with an equal volume of normal saline， while the allopurinol group and luteolin groups were gavaged with corresponding drugs. From day 4 onwards， modeling was performed by intraperitoneal injection at 12：00 daily （normal saline for the blank group， and oxonic acid potassium-hypoxanthine mixture for other groups， with 300 mg·kg^-1 for each group）. Gavage intervention was administered at 18：00 daily （normal saline for the blank/model groups， and corresponding drugs for the treatment groups） until day 7. After sampling， levels of serum uric acid （UA）， alanine aminotransferase （ALT）， and aspartate aminotransferase （AST） were measured. Levels of xanthine oxidase （XO） in the liver and kidney， ATP-binding cassette transporter G2 （ABCG2） and malondialdehyde （MDA） in the kidney， and superoxide dismutase （SOD） in the liver were determined. Renal HE staining was also performed. In the pharmacodynamic study of gouty arthritis， 36 rats were randomly divided into a blank group， a model group， a colchicine group （0.315 mg·kg^-1）， and low-dose （7 mg·kg^-1）， medium-dose （21 mg·kg^-1）， and high-dose （63 mg·kg^-1） luteolin groups. The model was established by vertically injecting 100 µL of 25 g·L^-1 monosodium urate suspension into the posterior lateral aspect of the right ankle joint （the blank group was injected with an equal volume of normal saline）， with repeated injections every two days for reinforcement. From day 2 after modeling， daily gavage administration was performed （normal saline for the blank/model groups， and corresponding drugs for the treatment groups） for a total of 16 days. During the experiment， ankle swelling and pain threshold were measured regularly. After sampling， levels of serum tumor necrosis factor-α （TNF-α）， interleukin-6 （IL-6）， and interleukin-1β （IL-1β） were determined. Ankle joints were subjected to HE， Masson， and safranin O-fast green staining， and HE staining was also performed on ankle synovial tissue and various organs. Western blot was used to determine the expression levels of key proteins in gout-related signaling pathways. ResultsNetwork pharmacology analysis predicted that luteolin may regulate over 20 core targets， such as XO， ABCG2， nuclear factor erythroid 2-related factor 2 （Nrf2）， and SOD， through acting on signaling pathways including NF-κB， phosphoinositide 3-kinase/protein kinase B （PI3K/Akt）， and ABC transporters， thereby affecting uric acid metabolism and inflammatory responses. In the hyperuricemia model， compared with the blank group， the model group showed significantly increased serum UA level， liver and kidney XO activity， renal ABCG2 expression， and liver SOD activity （P<0.01）. Compared with the model group， the high-dose luteolin group significantly reduced serum UA level （P<0.01）， inhibited liver and kidney XO activity （P<0.01）， and significantly increased renal ABCG2 expression and liver SOD activity （P<0.01）， effectively alleviating renal oxidative stress damage and improving renal histopathological status. In the gouty arthritis model， compared with the blank group， the model group showed significant ankle swelling， decreased pain threshold， and significantly increased levels of IL-6， IL-1β， and TNF-α in serum and synovial tissue （P<0.01）. The high-dose luteolin group significantly reduced ankle swelling， prolonged hot plate pain threshold， effectively decreased the levels of the above inflammatory factors in serum and synovial tissue （P<0.01）， and significantly improved ankle pathological damage， showing good analgesic and anti-inflammatory effects. Western blot results further confirmed that luteolin significantly upregulated Nrf2 protein expression and downregulated XO and nucleotide-binding oligomerization domain （NOD）-like receptor protein 3 （NLRP3） expression in animals. ConclusionLuteolin can improve symptoms of hyperuricemia and gouty arthritis， and its potential mechanism may be related to inhibiting XO activity， increasing ABCG2 and SOD levels， and regulating Nrf2-mediated oxidative stress-related pathways.

Genetically modified (GM) crops, as a pivotal innovation in modern agriculture, exhibit significant advantages such as pest and disease resistance, herbicide tolerance, stress tolerance, and yield enhancement. However, their widespread adoption has been associated with potential ecological risks, including weediness of transgenic plants, gene flow, emergence of novel viral strains in virus-resistant crops, impacts on non-target organisms and soil ecosystems, and evolution of target pest resistance. This review focuses on the dual characteristics of GM crops, systematically examining their agronomic benefits and the underlying mechanisms of ecological risks. This review provides a theoretical foundation for optimizing the development of GM crops and ecological risk management, facilitating sustainable agricultural practices.
Plants, Genetically Modified/growth & development* ; Crops, Agricultural/growth & development* ; Ecosystem ; Ecology

ObjectiveTo investigate the mechanism of Forsythiae Fructus-Lonicerae Japonicae Flos（FF） in the treatment of acute lung injury（ALI） by investigating the effects of FF on serum metabolomics of rats with ALI. MethodsThirty male SD rats were acclimated for 1 week， and 6 rats were randomly selected as the blank group. The other 24 rats were injected with lipopolysaccharide（LPS） solution by tracheal drip to establish an ALI model. After successful model establishment， the rats were randomly divided into the model group， the FF low-dose group（3.0 g·kg^-1）， the FF high-dose group（6.0 g·kg^-1）， and the dexamethasone group（5 mg·kg^-1）， with six rats in each group. The FF low- and high-dose groups and the dexamethasone group were received daily oral administration of the corresponding drug solution， and the blank group and the model group were gavaged with an equal amount of saline， treatment was administered continuously for 3 d. The pathological conditions of rat lung tissues were evaluated by hematoxylin-eosin（HE） staining， wet/dry mass ratio（W/D） of the lung tissues， and protein concentration in rat bronchoalveolar lavage fluid（BALF）. Metabolomic analysis of rat serum was performed by ultra-performance liquid chromatography-quadrupole-time-of-flight mass spectrometry（UPLC-Q-TOF-MS）， combined with multivariate statistical analysis， the potential biomarkers of FF in treating ALI were screened by variable importance in the projection（VIP） value>1， P<0.05 from t-test， and log₂fold change（FC）>1 or log₂FC<-1. Kyoto Encyclopedia of Genes and Genomes（KEGG） database combined with MetaboAnalyst were used for pathway analysis of the screened differential metabolites. The protein expression levels of sphingosine-1-phosphate（S1P）， phosphatidylinositol 3-kinase（PI3K）， protein kinase B1（Akt1）， and phosphorylated Akt1（p-Akt1） were examined by Western bolt. The expression levels of interleukin（IL）-6， IL-1β， and tumor necrosis factor（TNF）-α in BALF were detected by enzyme-linked immunosorbent assay（ELISA）. ResultsCompared with the blank group， rats in the model group showed ALI pathological features such as alveolar lumen dilatation， interstitial hemorrhage and massive inflammatory cell infiltration， and the protein concentration in BALF and W/D of the lung tissues were significantly elevated（P<0.01）. Compared with the model group， the low- and high-dose groups of FF as well as the dexamethasone group exhibited reduced pulmonary bronchial hemorrhage in rats， and the protein concentration in BALF and W/D were significantly decreased（P<0.05）， and the lung injury was significantly alleviated. Analysis of rat serum metabolomics revealed that FF downregulated 38 biomarkers. Pathway enrichment analysis showed that FF primarily exerted therapeutic effects through 7 key metabolic pathways， including arginine biosynthesis， sphingomyelin metabolism， alanine， aspartate and glutamate metabolism， taurine and hypotaurine metabolism， α-linolenic acid metabolism， niacin and nicotinamide metabolism， and retinol metabolism. The results of Western bolt and ELISA showed that， compared with the blank group， the model group exhibited significantly elevated expression levels of S1P， PI3K， Akt1 and p-Akt1 proteins in the lung tissues， as well as increased expression levels of IL-6， IL-1β and TNF-α in BALF（P<0.01）. Compared with the model group， the expression levels of the aforementioned indicators were significantly downregulated in the low- and high-dose FF groups as well as the dexamethasone group（P<0.05， P<0.01）. ConclusionFF may play a role in ALI by regulating amino acid metabolism and lipid metabolism， and its mechanism may be related to the inhibition of S1P/PI3K/Akt1 signaling pathway to attenuate the inflammatory response caused by ALI.

Abstract Alzheimer′s disease(AD) is a common neurodegenerative disease. It has been found that AD is related to various pathogenic factors such as genetics, cardiovascular and cerebrovascular disease, and excessive phosphorylation of tau protein. However, no definitive conclusions on its pathogenesis have been reached. In this paper, the research progress on the pathogenesis of AD inC.elegansmodel and the therapeutic effects of traditional Chinese medicine extracts on AD are reviewed, providing a basis for further research on the alleviating effects of Chinese medicine extracts on AD.

Objective:To explore the effect of tyrosine kinase inhibitor (TKI) dose reduction regimen in patients with chronic-phase chronic myeloid leukemia (CML) and its prognostic impact.Methods:A retrospective cohort study was conducted. The clinical data of patients with chronic-phase CML treated with reduced-dose TKI in the First Affiliated Hospital of Soochow University between January 2018 and December 2022 were collected. Patients were divided into groups based on Sokal score, European Treatment and Outcome Study long-term survival (ELTS) score, TKI drug classification and dose reduction, and treatment phase. The overall survival (OS), the cumulative incidence of major molecular response (MMR), the cumulative molecular recurrence rate and event-free survival (EFS) among patients in different strata were compared. Kaplan-Meier method was used for survival analysis.Results:Among 154 patients with chronic-phase CML, the median duration [ M ( IQR)] of reduced-dose TKI therapy was 35.4 months (34.9 months); Sokal score high-risk and low-/intermediate-risk groups comprised 20 cases (12.99%) and 134 cases (87.01%), respectively; ELTS score high-risk and low-/intermediate-risk groups comprised 14 cases (9.09%) and 140 cases (90.91%), respectively. Among 154 patients, 83 cases (53.90%) received imatinib therapy, while 71 cases (46.10%) received second-generation TKI; 138 patients (89.61%) maintained stable TKI dosing at the first dose level, and 16 patients (10.39%) maintained it at the second dose level. The induction therapy group comprised 33 patients (21.43%), while the maintenance therapy group included 121 patients (78.57%). The 3-year OS rate of all 154 patients was 90.6%. Patients in the Sokal score high-risk group demonstrated a lower 3-year OS rate compared to those in the low-/intermediate-risk group (64.1% vs. 96.7%) ( P < 0.001); patients in the ELTS score high-risk group had a lower 3-year OS rate compared to those in the low-/intermediate-risk group (62.9% vs. 95.8%) ( P = 0.002). There was no statistically significant difference in the 3-year OS rate of patients receiving the first dose level and those receiving the second dose level (90.6% vs. 90.0%, P = 0.478); there was no statistically significant difference in the 3-year OS rate of the induction therapy group and the maintenance therapy group (88.9% vs. 91.4%, P = 0.868). Among the 33 patients in the induction therapy group, all received the first dose level. After treatment, 28 achieved MMR, and 2 achieved molecular response 4.0 (MR4.0). The cumulative 1-year MMR rate of all patients in reduction therapy group was 95.8%, with a median time to MMR of 8.4 months; patients in the high-risk Sokal score group had a 1-year cumulative MMR rate of 50.0%, which was lower than that of the low-/intermediate-risk group (95.3%) ( P = 0.014); the median time to MMR was 14.7 months and 7.8 months, respectively. The cumulative 1-year MMR rate of patients treated with first-generation TKI was lower than that in those treated with second-generation TKI (65.0% vs. 100.0%, P = 0.034), and the median time to MMR of patients treated with first-generation TKI was longer than that those treated with second-generation TKI (9.1 months vs. 6.9 months). Among the 149 patients who achieved MMR, 5 experienced molecular relapse, resulting in a 3-year cumulative molecular relapse rate of 8.3%. In the Sokal score low-/intermediate-risk group, the 3-year cumulative molecular relapse rate (1.5% vs. 39.8%, P < 0.001), EFS rate (92.3% vs. 57.1%, P < 0.001), and OS rate (100.0% vs. 62.8%, P < 0.001) were better than those in the Sokal score high-risk group. The 3-year cumulative molecular relapse rate and 3-year EFS rate in patients receiving first dose level therapy were better than those in patients receiving second dose level therapy, and the differences were statistically significant (all P < 0.001). Conclusions:Patients with chronic-phase CML can still obtain good outcomes when receiving dose-reduced TKI, while the prognosis of patients in high-risk group is relatively poor. The choice of TKI and the dosage reduction should be individualized based on patients' characteristics.

Prepubertal-type testicular neuroendocrine tumor is a rare neoplasm of low malignant potential, which is classified as germ cell tumors unrelated to germ cell neoplasia in situ, and needs to be differentiated from metastatic neuroendocrine tumor, postpubertal-type testicular neuroendocrine tumor, and testicular seminoma. The clinicopathological and molecular features of a case of prepubertal-type testicular neuroendocrine tumor were reported. The tumour cells were uniform in size and arranged in nested and insular pattern. The tumor was positive for CgA and Syn, and the Ki-67 index was less than 2% by immunostaining. Next-generation sequencing identified no variants of pathogenicity, potential pathogenicity or uncertain significance. The patient was followed without evidence of recurrence and metastasis 56 months after surgery.

Purpose To investigate the clinicopathological features and prognosis of alpha-fetoprotein-producing colorectal carcinoma(AFPCRC).Methods 42 cases of AFPCRC from 2 012 colorectal carcinomas of preoperative serum AFP detected and surgically resected were identified.The clinicopathological data of AFPCRC and other 42 cases of conventional colorectal carcinoma exactly matched for age,gender,stage were also col-lected.Immunohistochemical EnVision method was performed to detect the expression of HER2,MMR,p53,AFP,Glypican3,and SALL4.Cases presenting HER2 2+were further analyzed by fluorescence in situ hybridization.Elastic staining was per-formed in cases with ambiguous extramural venous invasion.The clinicopathlogical features and prognosis between two groups were compared.Cases with AFPCRC were divided into high-AFP group and low-AFP group.The clinicopathological features and prognosis of the two groups were compared.Results AF-PCRC accounted for 2.1％(42/2 012)of colorectal carcinoma in the same period.The frequency of extramural vascular inva-sion and moderate/high grade of tumor budding of AFPCRC was 35.7％and 61.9％,while that of control group was 14.3％and 40.5％respectively.The 5-year survival rate of AFPCRC and control group was 66.8％and 85.1％respectively.The differ-ence of aforementioned clinicopathological features between 2 groups was significant(P＜0.05).The proportion of tumor in rectum in the high-AFP group was significantly higher than that in the low-AFP group(61.9％vs 23.8％,P＜0.05).Conclu-sion AFPCRC is a rare subset of colorectal carcinoma,which has a propensity for extramural vessel invasion,moderate-or high-grade of tumor budding and poor prognosis.

Enterococcus faecalis is the main pathogen causing refractory apical periodontitis(RAP).This bacterium can tolerate harsh environments and trigger periapical immune inflammatory responses that result in persistent infection inside and outside the root canal.Adhesion to the dentin wall of root canals and the subsequent formation of biofilms significantly enhances the drug resistance and anti-erosion ability of Enterococcus faecalis,which is the key factor medi-ating its pathogenesis.The adhesion of Enterococcus faecalis to dentin involves non-specific adhesion and specific adhe-sion,and the latter is mediated by adhesion-related virulence factors,mainly including the adhesin of collagen from en-terococci(Ace),extracellular surface protein(Esp),gelatinase(GelE),serine protease(SprE),endocarditis and biofilm associated pilus(Ebp)and aggregation substance(AS),which is regulated by multiple two-component systems.The two-component system Fsr can promote the expression of gelE and sprE when the cell population density increases.GelE can further reduce Ace,while the two-component system GrvRS directly downregulates ace expression in response to the serum environment.The two-component systems CroRS and WalRK may also promote and inhibit the expression of vari-ous virulence factors,including ace and gelE,thus affecting the adhesion of Enterococcus faecalis.In addition,the mech-anochemical preparation and the internal environment of the root canal can also influence the adhesion of Enterococcus faecalis to dentin.Avoiding the introduction of Enterococcus faecalis and using adhesion-interfering medications during root canal treatment can effectively prevent the adhesion of Enterococcus faecalis,and a variety of activated irrigation protocols can also be effective at increasing the clearance of Enterococcus faecalis from the root canal.The design of ra-tional drugs targeting key factors involved in and regulators of the adhesion of Enterococcus faecalis to dentin is expected to provide new ideas and strategies for root canal infection control.The present paper reviews the adhesion of Enterococ-cus faecalis to dentin and its influencing factors.

Objective:To systematically assess the efficacy and safety of acupuncture therapy for essential hypertension.Methods:A computerized literature search of the Chinese National Knowledge Infrastructure(CNKI),Chongqing VIP Database(CQVIP),Wanfang Academic Journal Full-text Database(Wanfang),China Biology Medicine Disc(CBM),PubMed,Excerpta Medica Database(EMBASE),and Cochrane Library was conducted to retrieve randomized controlled clinical trials on acupuncture as the main intervention for the treatment of essential hypertension published from the inception of the database to 30 January 2021.The risk-of-bias assessment was carried out for each included study according to the Cochrane Handbook.Data analysis was performed using Review Manager 5.4.1 and Stata 15.0.Results:After the screening,46 randomized controlled trials involving a total of 3 859 subjects were included.Primary outcomes included changes in the diastolic blood pressure after intervention[eight studies showed that the acupuncture plus antihypertensive drug group was better than the antihypertensive drug monotherapy group[mean difference(MD)=1.45,95%confidence interval(CI)(0.48,2.43),P=0.004,fixed effects model;I2=39%]and changes in the systolic blood pressure after intervention{11 studies showed that the acupuncture plus antihypertensive drug group was better than the antihypertensive drug monotherapy group[MD=8.60,95%CI(7.12,10.07),P<0.00001,fixed effects model;I2=26%]}.The secondary outcome was antihypertensive efficacy,12 studies of acupuncture monotherapy group[risk ratio(RR)=1.20,95%CI(1.12,1.28),P<0.00001,fixed effects model;I2=36%]and 15 studies of acupuncture combined with antihypertensive drug group[RR=1.27,95%CI(1.20,1.34),P<0.00001,fixed effects model;I2=6%]showed better results than the antihypertensive drug monotherapy group in antihypertensive efficacy.In terms of the adverse events,four studies showed that the acupuncture monotherapy group had fewer adverse events than the antihypertensive drug monotherapy group[RR=0.10,95%CI(0.04,0.25),P<0.00001,fixed effects model;I2=0%].Conclusion:Acupuncture combined with antihypertensive drugs is superior to antihypertensive drugs alone in reducing blood pressure,and acupuncture therapy is effective and safe for the treatment of essential hypertension with fewer side effects.However,there is still a lack of high-quality multicenter randomized double-blinded controlled trials in this field.Rigorous large-sample clinical trials are needed to validate these findings.