ObjectiveTo observe the clinical efficacy and safety of Tangning Tongluo tablets in the treatment of nonproliferative diabetic retinopathy （DR）. MethodsFourteen research centers participated in this study， which spanned a time interval from September 2021 to May 2023. A total of 240 patients with nonproliferative DR were included and randomly assigned into an observation group （120 cases） and a control group （120 cases）. The observation group was treated with Tangning Tongluo tablets， and the control group with calcium dobesilate capsules. Both groups were treated for 24 consecutive weeks. The vision， DR progression rate， retinal microhemangioma， hemorrhage area， exudation area， glycosylated hemoglobin （HbA1c） level， and TCM syndrome score were assessed before and after treatment， and the safety was observed. ResultsThe vision changed in both groups after treatment （P<0.05）， and the observation group showed higher best corrected visual acuity （BCVA） than the control group （P<0.05）. The DR progression was slow with similar rates in the two groups. The fundus hemorrhage area and exudation area did not change significantly after treatment in both groups， while the observation group outperformed the control group in reducing the fundus hemorrhage area and exudation area. There was no significant difference in the number of microhemangiomas between the two groups before treatment. After treatment， the number of microhemangiomas decreased in both the observation group （Z=-1.437， P<0.05） and the control group （Z=-2.238， P<0.05）， and it showed no significant difference between the two groups. As the treatment time prolonged， the number of microhemangiomas gradually decreased in both groups. There was no significant difference in the HbA1c level between the two groups before treatment. After treatment， the decline in the HbA1c level showed no significant difference between the two groups. The TCM syndrome score did not have a statistically significant difference between the two groups before treatment. After treatment， neither the TCM syndrome score nor the response rate had significant difference between the two groups. With the extension of the treatment time， both groups showed amelioration of TCM syndrome compared with the baseline. ConclusionTangning Tongluo tablets are safe and effective in the treatment of nonproliferative DR， being capable of improving vision and reducing hemorrhage and exudation in the fundus.

Alzheimer’s disease (AD) is a chronic, progressive, and irreversible neurodegenerative disorder that typically begins with a subtle onset and progresses slowly. Pathologically, it is characterized by two hallmark features: the extracellular accumulation of amyloid β-protein (Aβ), forming senile plaques, and the intracellular hyperphosphorylation of tau protein, resulting in neurofibrillary tangles (NFTs). These pathological changes are accompanied by substantial neuronal and synaptic loss, particularly in critical brain regions such as the cerebral cortex and hippocampus. Clinically, AD presents as a gradual decline in memory, language abilities, and spatial orientation, significantly impairing the quality of life of affected individuals. With the aging population steadily increasing in China, the incidence of AD is rising, making it a major public health concern that requires urgent attention. The growing societal and economic burden of AD underscores the pressing need to identify effective diagnostic biomarkers and develop novel therapeutic strategies. Among the various molecular signaling pathways involved in neurological disorders, the Notch signaling pathway is especially noteworthy due to its evolutionary conservation and regulatory roles in cell proliferation, differentiation, development, and apoptosis. In the central nervous system, Notch signaling is essential for neurodevelopment and synaptic plasticity and has been implicated in several neurodegenerative processes. Although some studies suggest that Notch signaling may influence AD-related pathology, its precise role in AD remains poorly understood. In particular, the interaction between Notch signaling and non-coding RNAs (ncRNAs)—key regulators of gene expression—has received limited attention. NcRNAs, including long non-coding RNAs (lncRNAs) and microRNAs (miRNAs), are known to exert extensive regulatory functions at both transcriptional and post-transcriptional levels. Dysregulation of these molecules has been widely associated with various diseases, including cancers, cardiovascular conditions, and neurodegenerative disorders. Notably, interactions between ncRNAs and major signaling pathways such as Notch can produce widespread biological effects. While such interactions have been increasingly reported in several disease models, comprehensive studies investigating the regulatory relationship between Notch signaling and ncRNAs in the context of AD remain scarce. Given the capacity of ncRNAs to modulate signaling cascades and form complex regulatory networks, a deeper understanding of their crosstalk with the Notch pathway could provide novel insights into AD pathogenesis and reveal potential targets for diagnosis and treatment. In this study, we investigated the regulatory landscape involving the Notch signaling pathway and associated ncRNAs in AD using bioinformatics approaches. By integrating data from multiple public databases, we systematically identified significantly dysregulated Notch pathway-related genes and their interacting ncRNAs in AD. Based on this analysis, we constructed a lncRNA-miRNA-mRNA regulatory network to elucidate the potential mechanisms linking Notch signaling to ncRNA-mediated gene regulation in AD pathogenesis. Furthermore, we explored the internal relationships and molecular mechanisms within this network and assessed the feasibility and clinical relevance of these molecules as early diagnostic biomarkers and potential therapeutic targets for AD. This study aims to deepen our understanding of the molecular basis of AD and offer novel strategies for its diagnosis and treatment.

A scoping review was performed to systematically search and summarize the clinical research in the treatment of dysmenorrhea with oral Chinese patent medicines. The oral Chinese patent medicines for treating dysmenorrhea in three major drug lists, guidelines, and textbooks were screened, and the relevant clinical trials were retrieved from eight Chinese and English databases. The key information of the included trials was extracted and visually analyzed. A total of 50 Chinese patent medicines were included, among which oral Chinese patent medicines for the dysmenorrhea patients with the syndrome of Qi stagnation and blood stasis accounted for the highest proportion, and the average daily cost varied greatly among Chinese patent medicines. A total of 150 articles were included, involving 22 Chinese patent medicines, among which Guizhi Fuling Capsules/Pills, Sanjie Zhentong Capsules, and Dan'e Fukang Soft Extract were the most frequently studied. These articles mainly reported randomized controlled trial(RCT), which mainly focused on the comparison of the intervention effect between Chinese patent medicines combined with western medicine and western medicine alone, and the sample size was generally 51-100 cases. The high-frequency outcome indicators belonged to nine domains such as effective rate, adverse reactions, and laboratory examinations. This study showed that oral Chinese patent medicines had advantages in the treatment of dysmenorrhea, and the annual number of related clinical trials showed an overall growing trend. However, there were still problems such as insufficient safety information and vague description of traditional Chinese medicine(TCM) syndromes types in the instructions of Chinese patent medicines. The available clinical research had shortcomings such as uneven distribution of Chinese patent medicines, limited research scale, poor methodological rigor, and insufficient standardization of outcome indicators. In the future, it is necessary to deepen the development of high-quality clinical research and improve the contents of the instructions to ensure the effectiveness and safety of the clinical application of oral Chinese patent medicines in the treatment of dysmenorrhea.
Dysmenorrhea/drug therapy* ; Humans ; Drugs, Chinese Herbal/administration & dosage* ; Female ; Administration, Oral ; Nonprescription Drugs/administration & dosage*

This study aims to systematically review and evaluate the quality of clinical research on the treatment of adenomyosis(AM) with traditional Chinese medicine(TCM) in recent ten years, using evidence graphs. Computer searches were conducted on eight Chinese and English databases, commonly used guideline databases, and guideline-related websites, covering the period from January 1, 2014, to October 1, 2024. Two researchers independently screened, extracted information, and evaluated the quality of the evidence. The distribution and quality of the clinical research evidence were presented using both text and charts. A total of 565 articles were included in the study, comprising 523 intervention studies, 23 observational studies, 18 systematic reviews/Meta-analysis, and 1 guideline. The overall publication volume has shown a downward trend in past two years. The sample sizes of the intervention and observational studies primarily focused on 60 to 120 cases. The intervention schemes mainly involved multi-therapy combinations, including 33 classic prescriptions and 25 Chinese patent medicines. Among these, 48 studies related to 17 classic prescriptions and 45 studies related to 10 types of Chinese patent medicines involved TCM syndrome types. Randomized controlled trial(RCT) tended to focus on overall clinical efficacy and the degree of dysmenorrhea as key outcome measures. Methodological quality issues were found in 97 RCTs related to TCM decoctions and 131 RCTs related to Chinese patent medicines, primarily involving unclear explanations of some information. The AMSTAR scores for the 18 systematic reviews/Meta-analysis ranged from 1 to 8 points, with 16 studies suggesting "evidence of potential therapeutic efficacy". The recommended level for the one included guideline was B-level. TCM shows significant advantages in treating AM. Future clinical research should further standardize study designs, reference relevant reporting guidelines, improve the quality of clinical research, generate higher-level evidence-based results, and promote the high-quality development of clinical research on TCM for treating AM.
Humans ; Adenomyosis/drug therapy* ; Drugs, Chinese Herbal/therapeutic use* ; Female ; Medicine, Chinese Traditional ; Randomized Controlled Trials as Topic

OBJECTIVE: To investigate the association between long-term glycemic control and cerebral infarction risk in patients with diabetes through a large-scale cohort study. METHODS: This prospective, community-based cohort study included 12,054 patients with diabetes. From 2006 to 2012, 38,272 fasting blood glucose (FBG) measurements were obtained from these participants. FBG trajectory patterns were generated using latent mixture modelling. Cox proportional hazards models were applied to assess the subsequent risk of cerebral infarction associated with different FBG trajectory patterns. RESULTS: At baseline, the mean age of the participants was 55.2 years. Four distinct FBG trajectories were identified based on FBG concentrations and their changes over the 6-year follow-up period. After a median follow-up of 6.9 years, 786 cerebral infarction events were recorded. Different trajectory patterns were associated with significantly varied outcome risks (Log-Rank P < 0.001). Compared with the low-stability group, Hazard Ratio ( HR) adjusted for potential confounders were 1.37 for the moderate-increasing group, 1.23 for the elevated-decreasing group, and 2.08 for the elevated-stable group. CONCLUSION Sustained high FBG levels were found to play a critical role in the development of ischemic stroke among patients with diabetes. Controlling FBG levels may reduce the risk of cerebral infarction.
Humans ; Cerebral Infarction/blood* ; Middle Aged ; Male ; Female ; Blood Glucose/analysis* ; Fasting/blood* ; Aged ; Prospective Studies ; Risk Factors ; Diabetes Mellitus/blood* ; Adult ; Proportional Hazards Models

Objective:To compare the prognostic value of two predictive models based on C-reactive protein(CRP)and albumin(ALB),namely the CRP to ALB ratio(CAR)and the Glasgow prognostic score(GPS),in newly diagnosed patients with diffuse large B-cell lymphoma(DLBCL).Methods:The data of newly diagnosed DLBCL patients admitted to our center from May 2014 to January 2022 were reviewed.A total of 111 patients who completed at least 4 cycles of R-CHOP or R-CHOP-like chemotherapy with detailed clinical,laboratory data and follow-up information were included.The receiver operating characteristic(ROC)curve was performed to evaluate the predictive value of pre-treatment CAR on disease progression and survival.Furthermore,the association between CAR and baseline clinical,laboratory characteristics of patients was evaluated,and progression-free survival(PFS)and overall survival(OS)were compared between different CAR and GPS subgroups.Finally,the univariate and multivariate COX propor-tional hazard regression models were used to analyze the factors affecting disease outcomes.Results:ROC curve showed that the area under the curve(AUC)of CAR predicting PFS and OS in DLBCL patients was 0.687(P=0.002)and 0.695(P=0.005),respectively,with the optimal cut-off value of 0.11 for both predicting PFS and OS.Compared with the lower CAR(＜0.11)group,the higher CAR(≥0.11)group had more clinical risk factors,including age＞60 years(P=0.025),ECOG score ≥2(P=0.004),Lugano stage Ⅲ-Ⅳ(P＜0.001),non-germinal center B-cell-like(non-GCB)subtype(P=0.035),elevated lactate dehydrogenase(LDH)(P＜0.001),extranodal involved site＞1(P=0.004)and IPI score＞2(P＜0.001).The interim response evaluation of patients showed that the overall response rate(ORR)and complete response rate(CRR)in the lower CAR group were both significantly better than those in the higher CAR group(ORR:96.9％vs 80.0％,P=0.035;CRR:63.6％vs 32.5％,P=0.008).With a median follow-up of 24 months,patients with lower CAR had significantly longer median PFS and OS than those with higher CAR(median PFS:not reached vs 67 months,P=0.0026;median OS:not reached vs 67 months,P=0.002),while there was no statistical difference in PFS(P=0.11)and OS(P=0.11)in patients with GPS of 0,1,and 2.Multivariate Cox regression analysis indicated that only sex(male)and IPI score＞2 were independent risk factors for both PFS and OS.Conclusion:CAR is significantly correlated with disease progression and survival in DLBCL patients;And compared with GPS,CAR has more advantages in predicting disease outcomes in DLBCL patients.

Objective:To compare the efficacy and safety of flumatinib (FM)and imatinib (IM)as first-line treatment in newly-diagnosed patients with chronic myeloid leukemia in chronic phase (CML-CP ) in real world. Methods:A total of 84 newly-diagnosed CP-CML patients in our center from December 2019 to December 2022 were retrospectively analyzed.Among them,32 cases received FM as first-line treatment,and 52 cases received IM. Molecular response (MR),disease progression,survival and incidence of adverse events (AEs)were compared between the two groups.Results:At 3 months of treatment,the incidences of early molecular response (EMR ),MR2.0 and MR3.0 were 96.7％,70.0％ and 20.0％ in FM group,respectively,which were significantly higher than 77.1％,29. 2％ and 0 in IM group (all P<0.05 ).At 6,9 and 12 months of treatment,the incidences of major molecular response (MMR)in FM group were 68.2％,85.7％ and 90.0％,respectively,which were significantly higher than 22.9％,34.0％ and 51.1％ in IM group (all P<0.01).The median time to achieve MMR in FM group was 6(6-9)months,which was significantly shorter than 18(12-22)months in IM group (P<0.001 ).The 3-year progression-free survival rate and 3-year event-free survival rate in FM group were 100％ and 68.8％,respectively,while in IM group were 98.1％ and 55.8％.There were no significant differences between the two groups (P>0.05). The incidence of grade 3-4 hematologic AEs in FM group was 21 .9％,which was slightly lower than 25.0％ in IM group,but the difference was not significant (P>0.05 ).Conclusion:In real clinical practice,FM as first-line treatment achieves MMR earlier than IM,and exhibits good safety profile in newly-diagnosed CML-CP patients,which potentially leads to improved long-term survival and treatment-free remission.

AIM:To establish a severe pneumonia mouse model induced by bacterial infection.METHODS:A total of 102 male SPF C57BL/6J mice were randomly divided into a control group and a model group.Klebsiella pneu-moniae was administered via tracheal instillation at a concentration of 5×109 CFU.Mice were euthanized on days 1,2,4,8,and 14 post-infection to assess general condition,body weight,mortality,white blood cell and neutrophil counts,in-flammatory markers,and pathological changes in lung,heart,liver,spleen,kidney,and intestinal tissues.RESULTS:Mice in the model group exhibited symptoms such as dyspnea and huddling from 6 hours to 4 days post-infection,which progressively worsened,accompanied by continuous weight loss(P<0.01).These symptoms gradually resolved between days 5 and 14.Arterial oxygen saturation in the model group dropped to 80.7%from days 1 to 8(P<0.01)but returned to normal from days 9 to 14.A total of 23 model mice died between days 1 and 9,with no deaths thereafter,resulting in a mortality rate of 31.9%(P<0.01).Pathological examination revealed inflammatory cell infiltration,congestion,and ede-ma in lung tissue from days 1 to 2,with continued inflammatory cell infiltration,alveolar structural disorganization from days 4 to 8,and alveolar rupture and fusion by day 14(P<0.05 or P<0.01).Additionally,model mice showed significant increases in neutrophil count,white blood cell count,protein content in bronchoalveolar lavage fluid,total cell count,neutrophil ratio,and levels of inflammatory factors tumor necrosis factor-α(TNF-α),interleukin-1β(IL-1β)and IL-6 in peripheral blood from days 1 to 8(P<0.05 or P<0.01).No significant pathological changes were observed in heart and liver tissues,while spleen,kidney,and intestinal tissues exhibited notable pathological changes:indistinct boundaries be-tween red and white pulp in the spleen,significant congestion and edema around renal glomeruli,renal tubules,and col-lecting ducts,and extensive inflammatory cell infiltration in the colonic mucosa.CONCLUSION:Tracheal instillation of 5×109 CFU Klebsiella pneumoniae induces severe pathological changes in the lungs of mice,offering a robust model for studying the pathogenesis and treatment of severe pneumonia.

AIM To establish an LC-MS/MS method for the simultaneous content determination of forsythin,forsythoside A,chlorogenic acid,neochlorogenic acid,amygdalin,emodin,rhein and salidroside in Lianhua Qingwen Capsules.METHODS The analysis was performed on a 35℃thermostatic ACQUITY UPlC-HSS T3 column(100 mm×2.1 mm,1.8 μm),with the mobile phase comprising of 0.1%formic acid-acetonitrile flowing at 0.3 mL/min in a gradient elution manner,and electron spray ionization source was adopted in negative ion scanning with multiple reaction monitoring mode.RESULTS Eight constituents showed good linear relationships within their own ranges(r≥0.999 5),whose average recoveries were 99.20%-100.96%with the RSDs of 0.62%-1.23%.CONCLUSION This simple,sensitive and reliable method can be used for the quality control of Lianhua Qingwen capsules.