The transcriptome sequencing based on Illumina Novaseq 6000 Platform was performed with the untreated seed embryo(DS), stratified seed embryo(SS), and germinated seed embryo(GS) of Zanthoxylum nitidum, aiming to explore the molecular mechanism regulating the seed dormancy and germination of Z. nitidum and uncover key differentially expressed genes(DEGs). A total of 61.41 Gb clean data was obtained, and 86 386 unigenes with an average length of 773.49 bp were assembled. A total of 29 290 DEGs were screened from three comparison groups(SS vs DS, GS vs SS, and GS vs DS), and these genes were annotated on 134 Kyoto Encyclopedia of Genes and Genomes(KEGG) pathways. KEGG enrichment analysis revealed that the plant hormone signal transduction pathway is the richest pathway, containing 226 DEGs. Among all DEGs, 894 transcription factors were identified, which were distributed across 34 transcription factor families. These transcription factors were also mainly concentrated in plant hormone signal transduction and mitogen-activated protein kinase(MAPK) signaling pathways. Further real-time quantitative polymerase chain reaction(RT-qPCR) validation of 12 DEGs showed that the transcriptome data is reliable. During the process of seed dormancy release and germination, a large number of DEGs involved in polysaccharide degradation, protein synthesis, lipid metabolism, and hormone signal transduction were expressed. These genes were involved in multiple metabolic pathways, forming a complex regulatory network for dormancy and germination. This study lays a solid foundation for analyzing the molecular mechanisms of seed dormancy and germination of Z. nitidum.
Zanthoxylum/metabolism* ; Plant Dormancy/genetics* ; Seeds/metabolism* ; Gene Expression Regulation, Plant ; Plant Proteins/metabolism* ; Transcriptome ; Gene Expression Profiling ; Germination ; Transcription Factors/metabolism* ; Plant Growth Regulators/genetics* ; Signal Transduction

OBJECTIVE: To evaluate the dynamic changes of glucocorticoid (GC) dose and the feasibility of GC discontinuation in rheumatoid arthritis (RA) patients under the background of Chinese medicine (CM). METHODS: This multicenter retrospective cohort study included 1,196 RA patients enrolled in the China Rheumatoid Arthritis Registry of Patients with Chinese Medicine (CERTAIN) from September 1, 2019 to December 4, 2023, who initiated GC therapy. Participants were divided into the Western medicine (WM) and integrative medicine (IM, combination of CM and WM) groups based on medication regimen. Follow-up was performed at least every 3 months to assess dynamic changes in GC dose. Changes in GC dose were analyzed by generalized estimator equation, the probability of GC discontinuation was assessed using Kaplan-Meier curve, and predictors of GC discontinuation were analyzed by Cox regression. Patients with <12 months of follow-up were excluded for the sensitivity analysis. RESULTS: Among 1,196 patients (85.4% female; median age 56.4 years), 880 (73.6%) received IM. Over a median 12-month follow-up, 34.3% (410 cases) discontinued GC, with significantly higher rates in the IM group (40.8% vs. 16.1% in WM; P<0.05). GC dose declined progressively, with IM patients demonstrating faster reductions (median 3.75 mg vs. 5.00 mg in WM at 12 months; P<0.05). Multivariate Cox analysis identified age <60 years [P<0.001, hazard ratios (HR)=2.142, 95% confidence interval (CI): 1.523-3.012], IM therapy (P=0.001, HR=2.175, 95% CI: 1.369-3.456), baseline GC dose ⩽7.5 mg (P=0.003, HR=1.637, 95% CI: 1.177-2.275), and absence of non-steroidal anti-inflammatory drugs use (P=0.001, HR=2.546, 95% CI: 1.432-4.527) as significant predictors of GC discontinuation. Sensitivity analysis (545 cases) confirmed these findings. CONCLUSIONS RA patients receiving CM face difficulties in following guideline-recommended GC discontinuation protocols. IM can promote GC discontinuation and is a promising strategy to reduce GC dependency in RA management. (Trial registration: ClinicalTrials.gov, No. NCT05219214).
Adult ; Aged ; Female ; Humans ; Male ; Middle Aged ; Arthritis, Rheumatoid/drug therapy* ; Glucocorticoids/therapeutic use* ; Medicine, Chinese Traditional ; Retrospective Studies

Ischemic stroke (IS) is a globally life-threatening disease. Presently, few therapeutic medicines are available for treating IS, and rt-PA is the only drug approved by the US Food and Drug Administration (FDA) in the US. In fact, many agents showing excellent neuroprotection but no blood flow-improving activity in animals have not achieved ideal clinical efficacy, while thrombolytic drugs only improving blood flow without neuroprotection have limited their wider application. To address these challenges and meet the huge unmet clinical need, we have designed and identified a novel compound AAPB with dual effects of neuroprotection and cerebral blood flow improvement. AAPB significantly reduced cerebral infarction and neural function deficit in tMCAO rats, pMCAO rats, and IS rhesus monkeys, as well as displayed exceptional safety profiles and excellent pharmacokinetic properties in rats and dogs. AAPB has now entered phase I of clinical trials fighting IS in China.

Objective:To investigate the risk factors for detecting clinically significant prostate cancer (CSPCa) in patients with Prostate Imaging Reporting and Data System (PI-RADS) score≤3 on multi-parameter magnetic resonance imaging (mpMRI).Methods:Retrospective analysis was performed on the case data of 335 patients with suspected prostate cancer and PI-RADS score ≤3 who were admitted to Beijing Friendship Hospital, Capital Medical University from January 2013 to October 2022. All patients underwent 24-needle prostate biopsy. Clinical data such as age, body mass index, past medical history, serological laboratory indicators, and mpMRI imaging data were collected. The patients were grouped according to whether the puncture pathology was CSPCa or not, and the differences in clinical data between the two groups were analyzed by t-test, rank sum test and Chi-test. Multivariate Logistic regression analysis was further used to determine independent risk factors for MRI invisible prostate cancer, and receiver operating characteristics (ROC) curves were drawn. At the same time, further subgroup analysis was conducted based on whether prostate-specific antigen (PSA) was positive before puncture and PI-RADS score, respectively, and the same statistical method was used to further determine the influence of different serological indicators and PI-RADS score on the analysis results of risk factors. Results:Among all patients, 81 were CSPCa patients and 254 were non-CSPCa patients. Multivariate Logistic regression analysis showed that prostate-specific antigen density (PSAD) and PI-RADS score of 3 were independent risk factors for MRI invisible prostate cancer. At the same time, compared with suspected lesions located only in the transitional zone, the incidence of CSPCa in patients with suspected lesions located in the peripheral zone would increase, and the incidence of CSPCa would further increase when suspected lesions were found in both the transitional zone and the peripheral zone. In PSA-negative patients, only suspected lesion location was an independent risk factor for MRI invisible prostate cancer, while in PSA-positive patients, prostate volume, PSAD, and PI-RADS scores were independent risk factors. In subgroup analysis with different PI-RADS scores, suspicious lesions in both the transitional zone and peripheral zone indicate a higher likelihood of CSPCa. For patients with PI-RADS scores of 1 to 2, suspicious lesions in the peripheral zone alone may also indicated CSPCa, while for patients with PI-RADS scores of 3, the lower free prostate-specific antigen/total prostate-specific anti-principle was more accurate in predicting CSPCa.Conclusions:For patients who are clinically suspected of prostate cancer but whose PI-RADS score is less than or equal to 3 points indicated by mpMRI, it is necessary to further focus on the results of different serological indicators according to whether their PSA is positive and PI-RADS score respectively to judge whether patients should receive systemic prostate puncture, instead of using PSA level as a single indication for puncture. At the same time, clinicians should also pay full attention to the location of suspected lesions, when they are located in the peripheral zone, or there are suspected lesions in both the peripheral zone and the transitional zone, the possibility of CSPCa should be fully considered.

Objective To study the change of common bile duct pressure after laparoscopic common bile duct exploration in patients with common bile duct stones.Methods Clinical data of 17 patients with common bile duct stones treated in our hospital from January 2022 to December 2022 were collected.All patients underwent laparoscopic common bile duct exploration and common bile duct pressure measurement.The patients were followed up for 8 weeks after operation,and the common bile duct pressure was measured by indwelling T tube at 2,3,4 and 8 weeks.Results Among the 17 patients,1 patient showed persistent high common bile duct pressure due to residual common bile duct stones.In the remaining 16 patients,there were no significant difference between the initial common bile duct pressure(19.7 cm H2O)and the common bile duct pressure at postoperative(17.0 cm H2O)and week 1(15.5cmH2O)(P＞0.05).There were significant differences between the initial common bile duct pressure and the common bile duct pressure at week 2(13.5 cm H2O),3(12.2 cm H2O),4(11.1 cm H2O)and 8(10.0cmH2O)(P＜0.05).Conclusion Compared to initial common bile duct pressure,the pressure of common bile duct began to decrease significantly from 2 weeks after laparoscopic common bile duct exploration in patients with common bile duct stones.

Tuberculosis is a zoonotic disease posing a substantial public health threat.Immunological diagnosis and vaccine im-munization are both necessary to control tuberculosis prevalence.However,the identical antigenic components in diagnostic reagents and vaccines hinder the use of animal vaccines and limit the specificity of clinical diagnosis in humans.Differentiating infected from vaccinated animals can overcome these problems.This article reviews the progress in differential diagnosis research from three as-pects:the diagnostic effects of antigens,methods for discovering new antigens,and screening of new host immune markers,to provide a theoretical basis for future research.

Objective We aimed to evaluate the efficacy and safety of Shengxuebao Mixture in the treatment of cancer-related anemia(CRA)presenting with syndrome of deficiency of liver and kidney combined with syndrome of deficiency of both qi and blood.Methods A randomized,double-blind,placebo-controlled,multicenter clinical trial was conducted.Eligible patients with malignant tumors meeting the inclusion and exclusion criteria were enrolled from 26 hospitals,including Dongzhimen Hospital,Beijing University of Chinese Medicine,Xiaogan Central Hospital,and Yangzhou Hospital of Traditional Chinese Medicine,from June 1,2022,to September 30,2024.Patients were allocated 1:1 to either the experimental group receiving Shengxuebao Mixture or the control group receiving its simulator(placebo)using a block randomization method under double-blind conditions.Both groups received 15 mL orally three times daily for 28 consecutive days.The primary efficacy indicators included the hemoglobin(Hb)improvement rate(RHb)and the traditional Chinese medicine(TCM)syndrome improvement rate(RTCM)at week 4 of treatment.The secondary efficacy indicators encompassed Hb and red blood cell(RBC)count,Karnofsky Performance Status(KPS)score,TCM syndrome score,individual TCM symptom scores,and changes in each of these indicators compared to the baseline period at weeks 2,4,and 6 of treatment.Safety evaluations were conducted at week 4 of treatment.Results A total of 239 patients were enrolled,with 225 cases included in the Full Analysis Set(FAS)(109 in the experimental group vs.116 control group),163 in the Per Protocol Set(PPS)(77 vs.86),and 225 in the Safety Set(SS)(109 vs.116).Baseline characteristics between groups showed no significant differences.Significant differences were observed between the experimental and control groups in RHb at week 4(FAS:49.51%vs.35.24%,P<0.05;PPS:53.25%vs.36.05%,P<0.05)and RTCM at week 4(FAS:61.54%vs.39.62%,P<0.01;PPS:64.94%vs.40.70%,P<0.01).At weeks 2,4,and 6,the experimental group showed greater improvements in Hb and RBC counts than the control group.Additionally,the TCM syndrome scores were lower in the experimental group than in the control group at these time points.Except for week 2 in PPS,the KPS improvement was better in the experimental group than in the control group(P<0.05).The experimental group also demonstrated a greater reduction in scores for individual TCM symptoms such as spiritlessness and weakness,poor appetite and reduced food intake at weeks 4 and 6 compared to the control group(P<0.05,P<0.01).Furthermore,the reduction in vertigo score was more pronounced in the experimental group at week 6(P<0.01).For the score of pale and lusterless complexion,only in the PPS was the reduction from baseline more significant in the experimental group than in the control group at weeks 4 and 6(P<0.05).No significant differences were observed between the experimental and control groups in the incidence of all adverse events or drug-related adverse reactions.Conclusion Shengxuebao Mixture demonstrates significant efficacy in patients with CRA presenting syndrome of deficiency of liver and kidney combined with syndrome of deficiency of both qi and blood,effectively increasing Hb levels,ameliorating TCM syndromes,alleviating clinical symptoms,and enhancing functional status,with no significant difference in adverse drug reactions compared to the placebo.

Hepatocellular carcinoma(HCC),which is essentially primary liver cancer,is closely related to CD8+T cell immune infiltration and immune suppression.We constructed a CD8+T cells related risk score model to pre-dict the prognosis of HCC patients and provided therapeutic guidance based on the risk score.Using integrated bulk RNA sequencing(RNA-seq)and single-cell RNA sequencing(scRNA-seq)datasets,we identified stable CD8+T cell signatures.Based on these signatures,a 3-gene risk score model,comprised of KLRB1,RGS2,and TN-FRSF1B was constructed.The risk score model was well validated through an independent external validation co-hort.We divided patients into high-risk and low-risk groups according to the risk score and compared the differ-ences in immune microenvironment between these two groups.Compared with low-risk patients,high-risk patients have higher M2-type macrophage content(P＜0.0001)and lower CD8+T cells infiltration(P＜0.0001).High-risk patients predict worse response to immunotherapy treatment than low-risk patients(P＜0.01).Drug sensitivity a-nalysis shows that PI3K-β inhibitor AZD6482 and TGFβRII inhibitor SB505124 may be suitable therapies for high-risk patients,while the IGF-1R inhibitor BMS-754807 or the novel pyrimidine-based anti-tumor metabolic drug Gemcitabine could be potential therapeutic choices for low-risk patients.Moreover,expression of these 3-gene mod-el was verified by immunohistochemistry.In summary,the establishment and validation of a CD8+T cell-derived risk model can more accurately predict the prognosis of HCC patients and guide the construction of personalized treatment plans.

Objective To study the change of common bile duct pressure after laparoscopic common bile duct exploration in patients with common bile duct stones.Methods Clinical data of 17 patients with common bile duct stones treated in our hospital from January 2022 to December 2022 were collected.All patients underwent laparoscopic common bile duct exploration and common bile duct pressure measurement.The patients were followed up for 8 weeks after operation,and the common bile duct pressure was measured by indwelling T tube at 2,3,4 and 8 weeks.Results Among the 17 patients,1 patient showed persistent high common bile duct pressure due to residual common bile duct stones.In the remaining 16 patients,there were no significant difference between the initial common bile duct pressure(19.7 cm H2O)and the common bile duct pressure at postoperative(17.0 cm H2O)and week 1(15.5cmH2O)(P＞0.05).There were significant differences between the initial common bile duct pressure and the common bile duct pressure at week 2(13.5 cm H2O),3(12.2 cm H2O),4(11.1 cm H2O)and 8(10.0cmH2O)(P＜0.05).Conclusion Compared to initial common bile duct pressure,the pressure of common bile duct began to decrease significantly from 2 weeks after laparoscopic common bile duct exploration in patients with common bile duct stones.

Tuberculosis is a zoonotic disease posing a substantial public health threat.Immunological diagnosis and vaccine im-munization are both necessary to control tuberculosis prevalence.However,the identical antigenic components in diagnostic reagents and vaccines hinder the use of animal vaccines and limit the specificity of clinical diagnosis in humans.Differentiating infected from vaccinated animals can overcome these problems.This article reviews the progress in differential diagnosis research from three as-pects:the diagnostic effects of antigens,methods for discovering new antigens,and screening of new host immune markers,to provide a theoretical basis for future research.