AIM:To investigate the therapeutic effects of botulinum toxin A(BTXA)injection versus strabismus surgery in the treatment of acute acquired comitant esotropia(AACE).METHODS:Patient records of AACE cases treated at First People's Hospital of Nantong from January 2019 to September 2023 were retrospectively analyzed in this study. Patients were categorized into either strabismus surgery or BTXA injection groups based on treatment modality. Further stratification was performed according to preoperative deviation angles [>35 prism diopters(PD)vs ≤35 PD] and age(≥18 years adult group vs <18 years adolescent group). The baseline patient characteristics were collected, deviation angles at multiple timepoints before and after treatment were measured, and stereopsis test results were documented. Through comparative analysis of therapeutic outcomes across subgroups, we systematically evaluated the efficacy of different treatment approaches.RESULTS:A total of 43 AACE patients were included. At the final follow-up, both the surgery and BTXA injection groups showed a statistically significant decrease in deviation angle compared to pretreatment measurements(P<0.001). Significant differences were noted between the two groups in terms of the cure rate of strabismus and the recovery rate of stereopsis(P<0.05). For patients with deviations >35 PD, surgery yielded significantly better outcomes than injection therapy in postoperative angle, success rate, and stereopsis recovery(P<0.05). Similarly, in patients aged ≥18 years, surgical treatment was superior to injections in reducing strabismus angle, improving success rates, and restoring stereopsis(P<0.05).CONCLUSION:Both BTXA injection and strabismus surgery demonstrate therapeutic efficacy in AACE. Surgical treatment demonstrated superior efficacy compared to BTXA injection therapy, particularly in patients with deviations >35 PD and those aged ≥18 years. For patients with angles ≤35 PD or under 18 years, BTXA injection remains a viable treatment option.

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.

Objective This study aimed to investigate the effects of P.odoratum extract on lactase activity and microflora diversity in mice with bacterial dysbacteriosis.Methods SPF male BALB/c mice were randomized into 4 groups:control,model,P.odoratum extract low dose(1.56 g·kg-1·d-1)and high dose(3.12 g·kg-1·d-1)treatment group.There were 8 mice in each group(5 in the blank group).In addition to the control group,after 7 days of intragastric administration of mixed antibiotics,the administration groups were given P.odoratum extract for 7 days,and the control group and the model group were given the same amount of sterile water.The changes of diarrhea,body weight and food intake of mice were recorded.The colon HE staining sections,ZO-1 protein,IL-6 expression,and serum LPS concentration were detected.Feces were collected for lactase activity and microbial diversity determination with 16S rRNA high-throughput sequencing technology.Results After 7 days of antibiotic intervention,compared with the control group,the mice in the model group had soft stool,weight loss,reduced food intake,and significantly reduced intestinal flora diversity.At the 14th day,in the model group,ulceration accompanied by slight interstitial congestion and edema was seen in the colon,ZO-1 expression was significantly reduced,IL-6 expression was significantly increased,serum LPS was significantly increased,lactase activity was significantly reduced,and intestinal flora diversity was still lower compared with the control group.After 7 days of administration,compared with the model group,P.odoratum reduced the diarrhea rate of mice,promoted a recovery of body weight and food intake,downregulated pathological colon tissue damage,significantly increased ZO-1 protein expression,and reduced colon factor IL-6 and serum LPS concentration.In addition,P.odoratum can significantly up-regulate lactase activity and improve the community richness and diversity of dysbacteriosis mice.It is shown that three phyla(up-regulated Firmicutes,down-regulated Proteobacteria and Bacteroidetes)and seven genera(up-regulated Rikenellaceae_RC9_gut_group,Rikenella,Colidextribacter,norank_f__Lachnospiraceae,norank_f__Oscillospiraceae,and Lachnospiraceae_NK4A136_group,down-regulated Alloprevotella),the abundance of which was significantly correlated with body weight and lactase activity,serum LPS,and colon factor IL-6.Conclusion P.odoratum can alleviate the gut barrier injury and dysfunction caused by antibiotic induced dysbiosis,and its mechanism may be achieved by regulating microflora structure.

Objective:To investigate the expression of N6-methyladenosine(m6A) modification-related genes and their possible roles in peripheral blood mononuclear cells (PBMCs) of patients with primary gouty arthritis (GA).Methods:Forty-five patients each with acute gout (AG), intermittent gout (IG), and age-and gender-matched healthy controls (HC) were collected from the outpatient clinic of the Department of Rheumatology and Immunology of the Affiliated Hospital of Chuanbei Medical College between October and December of 2023. The expression levels of m6A modification-related genes (METTL3、METTL14、WTAP、FTO、ALKBH5、IGF2BP2、IGF2BP3、YTHDF1、YTHDC2) in PBMCs among the 3 groups were detected by RT-qPCR and correlation analysis with clinical indicators was performed. Measurements conforming to normal distribution were analyzed using ANOVA or t-tests, and data were analyzed using the Kruskal-Wallis H-test and Mann-Whitney U-test for data that is not-normaly distributed. The value of m6A modification-related genes for the diagnosis of GA was evaluated using subject characterization curve ROC. Results:①There were statistically significant differences in the expression of IGF2BP2 ( Z=-3.59, P<0.001)、WTAP ( Z=-5.25, P<0.001)、METTL14 ( Z=-3.62, P<0.001)、YTHDF1 ( Z=-2.12, P=0.034)and YTHDC2 ( Z=-2.00, P=0.045) in the disease group and the normal control group. Among them, the expression of IGF2BP2 in the GA group [28.08 (17.99, 47.06)×10 -4] was significantly higher than that in the HC group [19.23 (12.90, 25.78)×10 -4], and the expressions of WTAP、METTL14、YTHDF1 and YTHDC2 in the GA group [298.61 (213.61, 377.80)×10 -4, 9.94 (6.43, 13.46)×10 -4, 52.63 (28.22, 72.77)×10 -4, 40.24 (20.74, 73.32)×10 -4] were significantly lower than those in the HC group [398.45(339.88, 454.89)×10 -4, 13.27(11.07, 15.85)×10 -4, 64.43(43.61, 87.10)×10 -4, 53.11(36.37, 79.28)×10 -4]. Further subgroup analysis revealed statistically significant differences in the expression of IGF2BP2、WTAP、METTL14、YTHDF1 and YTHDC2 among the 3 groups ( H=19.62、31.73、13.14、16.64、28.90, all P≤0.001). The expressions of WTAP and METTL14 in the AG group [311.13(234.96, 426.67)×10 -4, Z=-3.27, P=0.001; 9.64 (5.21, 15.21)×10 -4, Z=-2.71, P=0.008] and IG group [272.27 (203.29, 347.95)×10 -4, Z=-5.78, P<0.001; 10.40(6.88, 12.88)×10 -4, Z=-3.54, P=0.003] were lower than those in the HC group [398.45 (339.88, 454.89)×10 -4, 13.27(11.07, 15.85)×10 -4]. However, there was no significant difference between AG and IG group ( P>0.05). Both YTHDF1 and YTHDC2 were significantly lower in the AG group [38.10(16.19, 56.78)×10 -4, 24.31 (14.35, 42.77)×10 -4] than those in the IG group [64.13 (48.28, 74.40)×10 -4(Z=-3.54, P<0.001, 65.49 (39.89, 91.23)×10 -4(Z=-4.96, P<0.001)] and HC group [64.43 (43.61, 86.92)×10 -4(Z=-3.51, P<0.001), 53.11 (36.37, 79.28)×10 -4(Z=-4.25, P<0.001)]. But there was no statistically significant difference between IG and HC groups ( P>0.05); IGF2BP2 was significantly lower in the AG group [25.32(16.40, 40.43)×10 -4, Z=-2.46, P=0.014] and HC group [19.23 (12.90, 25.78)×10 -4, Z=-4.54, P<0.001] than in the IG group [31.10(22.60, 49.58)×10 -4], but the comparison between AG and HC showed no statistically significant difference( P>0.05). ②Spearman correlation analysis showed that in GA patients, the expression of IGF2BP2、METTL14 and YTHDF1 was positively correlated with plasma glucose、blood uric acid(sUA) and total cholesterol level respectively ( r=0.22, P=0.037; r=0.38, P=0.003; r=0.23, P=0.034), and WTAP was negatively correlated with GLU ( r=-0.25, P=0.020). ③The ROC curve for the joint prediction of the five differential genes showed that the 95% CI for area under the curve in GA was 0.90 (0.84, 0.95). Conclusion:The m6A modification-related genes are abnormally expressed in GA and are correlated with clinical indicators such as GLU and UA, which are hypothesized to be involved in the pathogenesis of GA and have a certain reference value for the evaluation of metabolism in GA patients.

Objective:To evaluate the relationship between postoperative delirium(POD) and preoperative frailty in elderly patients undergoing spinal surgery.Methods:Two hundred and twenty patients of both sexes, aged ≥65 yr, of American Society of Anesthesiologists Physical Status classification Ⅱ-Ⅳ, undergoing elective posterior lumbar decompression, bone grafting and internal fixation under general anesthesia, were selected. Frailty was measured using the FRAIL (fatigue, resistance, ambulation, illness, and loss of weight) scale on 1 day before surgery. POD was assessed twice a day within 3 days by Confusion Assessment Method. Patients were divided into POD group and non-POD group according to whether POD occurred within 3 days after surgery. Multivariate logistic regression analysis was used to identify the risk factors for POD in elderly patients undergoing spinal surgery, and the value of preoperative frailty in predicting POD was analyzed using the receiver operating characteristic curve.Results:A total of 190 patients were finally enrolled, among which 55 patients presented with frailty before surgery, and the incidence was 29.0%. Forty-six patients developed POD, and the incidence was 24.2%. Multivariate logistic regression analysis showed that aging ( OR=1.15, 95% confidence interval [ CI] 1.03-1.29, P=0.017), preoperative frailty ( OR=2.35, 95% CI 1.24-4.43, P=0.009), increase in surgical segments ( OR=4.14, 95% CI 1.71-10.05, P=0.002) and increase in postoperative 24-h pain VAS score ( OR=1.38, 95% CI 1.07-1.78, P=0.013) were independent risk factors for POD in elderly patients undergoing spinal surgery. The area under receiver operating characteristic curve of preoperative frailty in predicting POD was 0.702 (95% CI 0.608-0.796, P<0.001). Conclusions:Preoperative frailty is an independent risk factor for POD in elderly patients undergoing spinal surgery. Preoperative frailty can predict the occurrence of POD in elderly patients undergoing spinal surgery to some extent.

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:To analyze the clinical characteristics of novel coronavirus (COVID-19) infection in liver transplant recipients.Methods:Clinical data of 130 liver transplant recipients with COVID-19 infection followed in Hebei Medical University Third Hospital from November 2022 to January 2023 were retrospectively collected, including 103 males and 27 females, aged (53.6±11.4) years. The severity of COVID-19 infection, its clinical symptoms, and negative conversion time for each recipient were analyzed and compared.Results:For the disease severity, 121 (93.1%) were mild, 5 (3.8%) were moderate, 3 (2.3%) were severe, and 1 (0.8%) was critically severe. The most common symptoms in the 126 patients with mild to moderate COVID-19 infection were successively fever, fatigue, cough and myalgia, with a negative conversion time of (10.1±4.5) (3.0-29.0)d. In those who underwent transplantation less than 12 months ( n=28), those who were taking mycophenolate mofetil ( n=53) and those who were taking methylprednisolone ( n=10), the negative conversion time was (11.6±5.1) d, (11.4±5.4) d, and (13.4±6.4) d, respectively, longer compared to those who underwent transplantation more than 12 months (9.7±4.2 d, n=98), and who were not taking mycophenolate mofetil (9.2±3.4 d, n=73) or methylprednisolone (9.8±4.2 d, n=116, all P<0.05). The negative conversion times were longer in recipients with symptoms (eg. fatigue and cough) than those in asymptomatic recipients (11.0±5.1 d vs. 9.0±3.3 d, t=2.64, P=0.009, and 11.4±5.2 d vs. 9.0±3.4 d, t=2.92, P=0.004). Conclusion:The COVID-19 infection in liver transplant recipients was mainly mild and moderate. The most common symptoms are fever, fatigue, cough and myalgia. The short time (less than 12 months) after liver transplantation, oral mycophenolate mofetil and methylprednisolone, with symptoms (fatigue and cough) could be associated with a prolonged negative conversion time.

Abstract OBJECTIVE Neuroblastoma(NB) is a prevailing pediatric extracranial solid tumor that accounts for 10%-15% of all childhood cancer-related fatalities. Despite significant strides made in NB therapy through multimodal approaches, the survival rate of high-risk NB patients remains at approximately 50%. Consequently, there is an urgent need to identify novel molecular targets for NB treatment. Recent studies have shown that MYCN oncogene amplification is present in about 25% of NB cases and is a crucial determinant of poor prognosis for high-risk NB patients. Since MYC family proteins, including MYCN, are inherently disordered proteins, MYCN lacks a defined ligand binding site along with a large protein-protein interaction surface. Current treatment approaches for MYCN-amplified NB patients do not include direct targeting of MYCN itself, since the absence of a “drugable” pocket renders it challenging. Notably, no direct MYC-targeting drugs are currently available. There is an existing association between Aurora A kinase(AURKA) and MYCN, whereby they form a complex to fortify MYCN stability. However, MYCN is inherently unstable, with a half-life of only 30 min, but AURKA intervenes by facilitating its stability through a direct protein-protein interaction, hence protecting it from proteasomal degradation. This interaction potentially augments tumor cell proliferation and invasiveness. Notably, AURKA has been verified as a transcriptional target of MYCN. The present study endeavors to employ computer-aided drug design technology to probe AURKA inhibitors discerned from a natural product library of traditional Chinese medicine(TCM), thereby identifying a novel drug for treating NB. METHODS Collected from the YaTCM database, a total of 47 696 natural compounds from TCM were subjected to preprocessing including protonation, deionization, hydrogenation, stereoisomerism, conformation generation, and energy minimization. Of these, 58 048 compounds were initially screened as potential ligands for the library. Utilizing “Lipinski Ro5” and “Verber Ro3” guidelines, 22 227 hit compounds were selected from the library that met the screening criteria. Initially, crystal structures of AURKA and its inhibitor AA35 were downloaded from the RCSB PDB database. The spatial coordinates of AA35 were set as the center of the binding pocket for AURKA, and a 10 Å * 10 Å * 10 Å space around the pocket was designated as the active space. A comprehensive drug screening platform integrating lead-likeness filtering, pharmacokinetic prediction, molecular docking, flexible docking, and molecular dynamics(MD) simulations were established to excavate potential aurora kinase A inhibitors from the TCM compound library, which were further validated by MD simulations. RESULTS A grand total of 6 220 Chinese herbal remedies had been meticulously curated within the YaTCM database. Out of these, an impressive 47 696 Chinese herbal monomers had undergone a rigorous series of flexible docking tests, resulting in the selection of the top ten molecules with the most favorable docking scores. The aforementioned molecules underwent AMDE parameter and toxicity predictions. It was discovered that with the exception of a few compounds such as Tryptophane, 3'-Methoxydaidzein, and Burttinol D(which might elicit liver toxicity), 3'-Methoxydaidzein and Pratensein(which might elicit kidney toxicity), and 3-Deoxysappanone B(which had moderate oral toxicity), as well as Tryptophane(with an oral bioavailability of less than 50%), five compounds including Compound X, (+)-Sesamin dicatechol, Tuberosin, Abrine, and Maackiain, displayed favorable pharmacokinetic parameters and low toxicity predictions. Moreover, all of these compounds exhibited a high binding affinity with the inhibitor active pocket of AURKA. In this study, Compound X, despite its cumbersome name, was referred to as “Compound X”. Upon focusing on Compound X as the subject of investigation, it was discovered that its phenolic framework could readily interact with the hydrophobic cavity constituted of hydrophobic amino acids, namely TYR199, VAL182, LEU178, LEU208, and VAL206. Notably, Compound X could partake in Pi-Pi interactions with TYR199 and create hydrogen bonds with HIS201, GLU175, and LYS166. Computational studies via MD simulations confirmed that Compound X could form a stable receptor-ligand complex with the receptor. Impressively, the inclusion of Compound X significantly reduced the stability of the AURKA-MYCN complex. CONCLUSION This study concludes that Compound X can be used as an AURKA inhibitor for the treatment of NB, which is a novel finding based on the combination of various virtual screening techniques from the natural product database of TCM.

Objective:To evaluate the effect of extraction treatment on orthodontic patients with Stage Ⅳ/Grade C periodontitis.Methods:Eight orthodontic patients with Stage Ⅳ/Grade C periodontitis (3 males, 5 females, 25~38 years old) who had finished extraction treatment during January 2003 and December 2013 were included in the study. The patients accepted periodontal treatment and extraction orthodontic treatment in the Department of Periodontology and Department of Orthodontics at Peking University School and Hospital of Stomatology. Clinical examination records and periapical films of 34 teeth adjacent to extraction sites (TAES) and 34 teeth non-adjacent to extraction sites (TNES) were evaluated and compared. Probing depth (PD) and relative bone height (RBH) before and after orthodontic treatment were also compared.Results:No significant difference was found between PD of TAES and that of TNES ( P>0.05). After orthodontic treatment, RBH of TAES was increased by 8.19% (-3.36%,14.01%) ( P<0.05). RBH of TAES far from extraction sites was elevated by 7.73% (-1.52%, 21.55%)( P<0.05). Tooth resorption rate of TAES was 13.1% (1.3%, 23.9%)and TNES was 4.3% (-8.19%, 12.5%) after orthodontic treatment, and the difference was statistically significant. Conclusions:Under proper combined periodontal and orthodontic treatment, stability of periodontal status in patients with Stage Ⅳ/Grade C periodontitis can be maintained. Relative bone height of extraction sites can be elevated after orthodontic treatment.

Objective:To investigate the clinical value of free-talk language functional cortex mapping methods based on high frequency response in epileptic foci resection.Methods:Twenty patients with intractable epilepsy admitted to our hospital from January 2016 to May 2019 were chosen in our study. According to the different intraoperative mapping methods of language functional region, these patients were divided into test group ( n=10, using free-talk language function localization based on high frequency response [new method]+ electrical cortical stimulation [ECS]) and control group ( n=10, using ECS localization only). The overlap rate of the two methods in the test group were calculated and the postoperative follow-up results of patients in the two groups were analyzed. Results:In 10 patients from the test group, 33 positive loci in the Broca's area and 33 positive loci in the Wernicke's area were detected by new method; at the meantime, 16 positive loci in the Broca's area and 8 positive loci in the Wernicke's area were detected by ECS method, which had a overlap rate of 93.75% (15/16) in the Broca's area and 75.00% (6/8) in the Wernicke's area, respectively, as compared with the new method. In the 10 patients from the control group, 18 positive loci in the Broca's area and 3 positive loci in the Wernicke's area were detected by ECS method. In the test group, 7 patients achieved Engel grading I and 2 patients developed transient language function impairment after surgery; while in the control group, 5 patients achieved Engel grading I and 4 patients developed transient language function impairment after surgery.Conclusion:The new method has a high overlap rate with ECS method; the combination of the two methods can help to decrease the speech function impairment after excision of epileptogenic foci in patients with epilepsy.