Objective: This prospective study evaluated the feasibility of chemical exchange saturation transfer (CEST) MRI for assessing disease activity in thyroid-associated ophthalmopathy (TAO). Materials and Methods: A total of 88 patients with active TAO, 76 with inactive TAO, and 30 healthy controls were enrolled. CEST MRI-derived magnetization transfer ratio (MTR) and MTR asymmetry (MTRasym) at 1 ppm, 2 ppm, and 3.5 ppm were calculated. Clinical data, MTR, and MTRasym values for the extraocular muscles (one representative muscle per eye, yielding two measurements per participant) were compared among the groups. Spearman’s correlation was used to examine associations between imaging parameters and the clinical activity score (CAS) in patients with TAO. Logistic regression analysis was used to identify independent associations between imaging parameters and disease activity in patients with TAO (active vs. inactive). Receiver operating characteristic (ROC) analysis was conducted to evaluate the diagnostic performance for discriminating active from inactive TAO. Results: Patients with active TAO showed lower MTR values (P < 0.001) and higher MTRasym (1 ppm), MTRasym (2 ppm), and MTRasym (3.5 ppm) (all P < 0.001) compared with those with inactive TAO. MTR was negatively correlated with CAS (r = -0.402; P < 0.001), while MTRasym (1 ppm), MTRasym (2 ppm), and MTRasym (3.5 ppm) were positively correlated with CAS (r = 0.369, 0.350, and 0.349, respectively;all P < 0.001). MTR and MTRasym (1 ppm) were independently associated with TAO activity. The areas under the ROC curve (AUCs) for MTR and MTRasym (1 ppm) in discriminating active from inactive TAO were 0.772 and 0.730, respectively. Combining MTR with MTRasym (1 ppm) significantly improved diagnostic performance compared with either parameter alone, achieving an AUC of 0.805 (P = 0.029 and 0.001). Conclusion MTR and MTRasym (1 ppm) were independently associated with TAO activity. Their combination further enhanced diagnostic performance in distinguishing active from inactive TAO, suggesting their potential as quantitative imaging biomarkers to guide treatment in patients with TAO.

Objective To explore and verify the protective and therapeutic effects and possible mechanisms of Zukamu granules on hypoxia alone and hypoxia+Su5416-induced hypoxic pulmonary hypertension(HPH)in mice.Methods Multiple databases and related literature were used to collect the active ingredients data in Zukamu granules and the HPH-related targets were predicted and obtained.The network construction and enrichment analysis were performed.The HPH mouse models were es-tablished by two-week hypoxia and four-week hypoxia+Su5416 induction,and the relevant indicators and the main pharmacodyna-mic indexes such as right ventricular pressure were tested.Masson staining was used to observe the pathological changes in lung tissues,and Western blotting was used to detect the expression levels of bax,bcl-2,PI3K,p-PI3K,eNOS,and HIF-1α in lung tis-sues.Results A total of 167 active ingredients of Zukamu granules were screened,with 179 intersecting targets with HPH,in-cluding targets like PIK3CA and HIF-1.The validation experimental results showed that Zukamu granules could significantly re-duce right ventricular systolic pressure and right ventricular hypertrophy in HPH mice,and down-regulate the expression of bcl-2 and HIF-1α and up-regulate the expression of bax,PI3K,p-PI3K and eNOS in mice lung tissues.Conclusion Zukamu gran-ules may act against HPH by modulating bax/bcl and PI3K-eNOS/HIF-1α signaling pathways.

Aldehyde dehydrogenase 2 (ALDH2) is one of important factors against from the damage under oxidative stress in human body. A high proportion of East Asians carry ALDH2 inactive mutation gene. There are many diseases closely related to ALDH2, such as cardiovascular diseases, neurodegenerative diseases and liver diseases. Recent studies also have found that ALDH2 is associated with ferroptosis. Therefore, ALDH2 has becoming a potential target for the treatment of the above related diseases. Several types of small molecule activators with potential value of clinical application have been reported. The research progress on the structure and function of ALDH2 , the relationship with human diseases and its activators were summarized in this paper.

BACKGROUND: LY01005 (Goserelin acetate sustained-release microsphere injection) is a modified gonadotropin-releasing hormone (GnRH) agonist injected monthly. This phase III trial study aimed to evaluated the efficacy and safety of LY01005 in Chinese patients with prostate cancer. METHODS: We conducted a randomized controlled, open-label, non-inferiority trial across 49 sites in China. This study included 290 patients with prostate cancer who received either LY01005 or goserelin implants every 28 days for three injections. The primary efficacy endpoints were the percentage of patients with testosterone suppression ≤50 ng/dL at day 29 and the cumulative probability of testosterone ≤50 ng/dL from day 29 to 85. Non-inferiority was prespecified at a margin of -10%. Secondary endpoints included significant castration (≤20 ng/dL), testosterone surge within 72 h following repeated dosing, and changes in luteinizing hormone, follicle-stimulating hormone, and prostate specific antigen levels. RESULTS: On day 29, in the LY01005 and goserelin implant groups, testosterone concentrations fell below medical-castration levels in 99.3% (142/143) and 100% (140/140) of patients, respectively, with a difference of -0.7% (95% confidence interval [CI], -3.9% to 2.0%) between the two groups. The cumulative probabilities of maintaining castration from days 29 to 85 were 99.3% and 97.8%, respectively, with a between-group difference of 1.5% (95% CI, -1.3% to 4.4%). Both results met the criterion for non-inferiority. Secondary endpoints were similar between groups. Both treatments were well-tolerated. LY01005 was associated with fewer injection-site reactions than the goserelin implant (0% vs . 1.4% [2/145]). CONCLUSION: LY01005 is as effective as goserelin implants in reducing testosterone to castration levels, with a similar safety profile. TRIAL REGISTRATION ClinicalTrials.gov, NCT04563936.
Humans ; Male ; Antineoplastic Agents, Hormonal/therapeutic use* ; East Asian People ; Gonadotropin-Releasing Hormone/agonists* ; Goserelin/therapeutic use* ; Prostate-Specific Antigen ; Prostatic Neoplasms/drug therapy* ; Testosterone

Objective An exploration of the molecular mechanism of microRNA-146a(miR-146)inter-vention in Sepsis-induced cardiomyopathy(SIC)using P38MAPK/NF-κB.Methods SD rats were divided into four groups by the random number table method:the normal control group,the SIC model group,the miR-146a agonist group,and the miR-146a inhibitor group.Rats in the normal control group and SIC model group were injected intraperitoneally with 0.2 μL/g saline,rats in the miR-146a agonist group were injected intraperitoneally with 0.2 μL/g miR-146a agonist,rats in the miR-146a inhibitor group were injected intraperitoneally with 0.2 μL/g miR-146a inhibitor;24 h later,rats in the SIC model group,miR-146a agonist group,and miR-146a inhibitor group were injected intraperitoneally with lipopolysaccharide(LPS)to prepare the SIC rat model,and the normal control group was injected with an equal amount of saline.Histopathological morphology was observed by HE staining;apoptosis rate of cardiomyocytes was detected by TUNEL;cardiac troponin I(cTnI)and B-type brain natriuretic peptide(BNP)contents were detected by ELISA;creatine kinase cardiac muscle binding(CK-MB)and myoglobin(Mb)contents were detected by chemiluminescence;p38 mitogen activation in rat myocardial tissue was detected by Western blot protein kinase(p38MAPK),nuclear factor-kB(NF-κB),tumor necrosis factor-α(TNF-α)and intercellular adhesion molecule-1(ICAM-1)by Western-Blot;miR-146a,TNF-α,interleukin-1α(IL-1α)and interleukin-1β(IL-1β)mRNA by reverse transcription quantitative(RT-q)PCR.Results Myocardial cells in the normal control group were uniform in size,neatly arranged,with distinct transverse lines,and had normal structure;myocardial cells in the SIC model group and miR-146a inhibitor group were disordered,with myocardial fibers fragmented and expanded at intervals.Myocardial structural damage was minimized in the miR-146a agonist group compared to the SIC model group.Compared with the normal control group,the apoptosis rate,serum cTnI,BNP,CK-MB,Mb levels,myocardial tissue p-p38 MAPK,p-NF-κB p65,TNF-α,ICAM-1 protein expression levels,TNF-α,IL-1α,miR-146a mRNA levels were significantly higher in the SIC model group,miR-146a agonist group and miR-146a inhibitor group,IL-1β mRNA levels were significantly increased and miR-146a mRNA levels were decreased.Compared with the SIC model group,the apoptosis rate,serum cTnI,BNP,CK-MB,Mb levels,myocardial tissue p-p38 MAPK,p-NF-κB p65,TNF-α,ICAM-1 protein expression in the miR-146a agonist group of rats levels,TNF-α,IL-1α,IL-1β mRNA levels were significantly reduced,and miR-146a mRNA levels were increased.Conclusion miR-146a has the ability to modulate the p38 MAPK/NF-κB signaling axis and the release of inflammatory factors.High miR-146a expression has some negative influence on the inflammatory response,reducing the onset and development of the inflammatory response while improving it.It can offer SIC early interven-tion therapy with a pre-study mechanism and theoretical support.

Amblyopia is the common disease in the children's growth. There are some disadvantages in traditional treatment to amblyopia, such as poor compliance, easily leading to the healthy eye eyesight problem, the poor recovery of binocular and stereoscopy vision, etc. This paper put forward a new individual amblyopia treatment system to solve these problems. It combined pattern reversal visual evoked potential (P_VEP) feedback and dichoptic training theory and then developed the EEG data acquisition and synchronized trigger circuit using and I/O data col ecting card, realized the raw EEG signal real-time sampling, extracted VEP waveform from the raw EEG data by using digital filtering algorithm, average superposition algorithm and wavelet an lgorithm, finally,the latency and peak of P_VEP wave shape were accurately measured. This system also present an individual treatment solution based on dichoptic training model by searching and obtaining the best spatial frequency of the treatment training picture and combining with 3D display technology.

Objective To summarize the diagnosis and treatment of urethral injury in children ,and to discuss the effective treat-ment method .Methods The retrospective analysis was performed on the data of 73 cases of children urethral injury in this hospital during recent 10 years .Results 66 cases were male ,7 cases were female ,aged 1-15 years old(average 7 years old) .In the male ca-ses ,there were 8 cases of anterior urethral injury ,10 cases of bulbous urethral injury ,44 cases of posterior urethral injuries and 4 cases of bladder neck injury ;in the female cases ,there were 6 cases of urethral injury and 1 case of bladder neck injury .The once cure rate of urethral realignment was 78 .6% ,which of stageⅠ urethral anastomosis was 80% and which of stage Ⅱurethral repair was 69 .6% .Conclusion Different operation modes have their advantages and disadvantages .The corresponding treatment scheme should be formulated according to the comprehensive assessment of the patient′s general condition and damage types .