ObjectiveTo investigate the effects of jatrorrhizine on endogenous metabolites and metabolic pathways in the mouse model of ulcerative colitis. MethodsThirty male C57BL/6J mice were randomly divided into the normal group， the model group， the low-dose and high-dose jatrorrhizine groups （0.04， 0.16 g·kg^-1）， and the mesalazine group （0.52 g·kg^-1）The mouse model of ulcerative colitis was established with 3% dextran sulfate sodium （DSS） and treated with different doses of jatrorrhizine by gavage. The changes in body weight， colon length， disease activity index （DAI）， and colonic histopathology were analyzed to evaluate the therapeutic effects of jatrorrhizine. UPLC-Q-TOF/MS was employed to determine the serum and fecal levels of metabolites in mice. Metabolomics methods were used to screen the differential metabolites， on the basis of which the potential therapeutic mechanism of jatrorrhizine on DSS-induced ulcerative colitis in mice was investigated. ResultsAfter intervention with jatrorrhizine， the model mice showed significantly decreased DAI（P<0.05，P<0.01）， recovered colon length，（P<0.05，P<0.01） and alleviated histopathology of the colon. The metabolomics study screened out 13 differential metabolites in the serum and 8 differential metabolites in the feces. The pathway enrichment analysis predicted three potential metabolic pathways： Biosynthesis of unsaturated fatty acids， phenylalanine， tyrosine and tryptophan biosynthesis， and phenylalanine metabolism. ConclusionJatrorrhizine may treat ulcerative colitis by regulating the biosynthesis and metabolism of amino acids and the synthesis of unsaturated fatty acids.

Objective: To explore the core features of trait aggression in children and adolescents, so as to provide a theoretical basis for behavioral interventions targeting the central psychological characteristics of aggression in children and adolescents. Methods: From March to May 2020, a simple random convenience sampling method was employed to recruit 39 165 students from grades 4 to 12 in Sichuan, Chongqing, Guizhou, and Shandong. Data were collected via online questionnaires, with all participants completing the Chinese Version of the Aggression Questionnaire. Psychometric network analysis was utilized for data processing. Results: Trait aggression among Chinese children and adolescents was at a moderately low level. The core nodes of the network structure included physical aggression [if someone intentionally causes trouble for me, I will hit them severely (AGG6); if someone hits me, I will retaliate (AGG11)] and self aggression [When I am very irritable, I think of hurting myself (AGG5); when I am in a bad mood, I engage in behaviors that harm my health, such as overeating (AGG25)]. Across grade levels, core nodes primarily originated from the anger dimension [When I m angry, I feel like a powder magazine that could explode at any moment (AGG13); I can t control my temper (AGG18); I am prone to getting angry when I see things that are not pleasing to the eye (AGG23); I will get angry for no reason (AGG27)]. Except for grades 7 and 9, core nodes in other grades included the verbal aggression dimension [I am prone to arguments with people (AGG22)]. Before grade 8, core nodes incorporated the self aggression dimension (AGG 5, AGG 25); after grade 8, core nodes included the physical aggression dimension [AGG 6, AGG 11, I fight slightly more than others (AGG16), and if people around me make things difficult for me to a certain extent, I will fight with them (AGG26)]. No statistically significant differences were found in the trait aggression network structures across grades, genders, or within gender comparisons of different grades. Conclusion These findings broaden our understanding of aggression in children and adolescents, suggesting that behavioral interventions can effectively reduce aggressive behaviors in this population.

Homo- or heterodimeric compounds that affect dimeric protein function through interaction between monomeric moieties and protein subunits can serve as valuable sources of potent and selective drug candidates. Here, we screened an in-house dimeric natural product collection, and panepocyclinol A (PecA) emerged as a selective and potent STAT3 inhibitor with profound anti-tumor efficacy. Through cross-linking C712/C718 residues in separate STAT3 monomers with two distinct Michael receptors, PecA inhibits STAT3 DNA binding affinity and transcription activity. Molecular dynamics simulation reveals the key conformation changes of STAT3 dimers upon the di-covalent binding with PecA that abolishes its DNA interactions. Furthermore, PecA exhibits high efficacy against anaplastic large T cell lymphoma in vitro and in vivo, especially those with constitutively activated STAT3 or STAT3^Y640F. In summary, our study describes a distinct and effective di-covalent modification for the dimeric compound PecA to disrupt STAT3 function.

T-cell acute lymphoblastic leukemia (T-ALL) is a highly aggressive hematologic malignancy with a poor prognosis, despite advancements in treatment. Many patients struggle with relapse or refractory disease. Investigating the role of the super-enhancer (SE) regulated gene ubiquitin-specific protease 20 (USP20) in T-ALL could enhance targeted therapies and improve clinical outcomes. Analysis of histone H3 lysine 27 acetylation (H3K27ac) chromatin immunoprecipitation sequencing (ChIP-seq) data from six T-ALL cell lines and seven pediatric samples identified USP20 as an SE-regulated driver gene. Utilizing the Cancer Cell Line Encyclopedia (CCLE) and BloodSpot databases, it was found that USP20 is specifically highly expressed in T-ALL. Knocking down USP20 with short hairpin RNA (shRNA) increased apoptosis and inhibited proliferation in T-ALL cells. In vivo studies showed that USP20 knockdown reduced tumor growth and improved survival. The USP20 inhibitor GSK2643943A demonstrated similar anti-tumor effects. Mass spectrometry, RNA-Seq, and immunoprecipitation revealed that USP20 interacted with hypoxia-inducible factor 1 subunit alpha (HIF1A) and stabilized it by deubiquitination. Cleavage under targets and tagmentation (CUT&Tag) results indicated that USP20 co-localized with HIF1A, jointly modulating target genes in T-ALL. This study identifies USP20 as a therapeutic target in T-ALL and suggests GSK2643943A as a potential treatment strategy.

An attractive smile is the goal and challenge of oral esthetic treatment.The characteristics of lips,teeth,and gingival are the three essential elements of smile esthetics.In the past,dentists mainly focused on"white esthetics"related to the hard tissue fea-tures.But recently,scholars have found that soft tissue esthetics plays a decisive role in the overall harmony and attractiveness of a smile.Currently,there is no standardized evaluation criterion or analytical process specifically addressing soft tissue esthetics in relation to smile attractiveness.This paper aims to propose key soft tissue variables in smile esthetics,summarize the facial soft tissue features and esthetic preferences of Chinese people,sort out clinical evaluation methods,and provide a reference for the oral clinical esthetic di-agnosis and treatment.

Objective:To evaluate the effect of online and offline blended teaching in microendodontics, attempting to promote the widespread application of blended teaching mode in Operative Dentistry and Endodontics.Methods:A questionnaire survey was carried out among 865 trainees who attended the blended teaching in microendodontics combined the online theory curriculum and offline practice training from April 6 to 28 in 2022, organized by Department of Operative Dentistry and Endodontics, Hospital of Stomatotogy, Sun Yat-sen University. The content of questionnaire included trainees′ basic information as well as their perspectives and expectations on the teaching mode. Data was analyzed by SPSS 24.0 and Chi-square test was used for enumeration data.Results:A total of 855 trainees participated in the valid survey with the effective recall rate of 98.8% (855/865), 50.3% (430/855) of which were young people in 18-30 years old. Their working period ranged from 0.5 to 40 years. Physicians and physician assistants occupied 40.9% (350/855) and 32.9% (281/855), respectively. And the intermediate and senior titles accounted for 26.2% (224/855). The proportion of trainees who had used and never used dental operative microscope (DOM) were 70.5% (603/855) and 29.5% (252/855), respectively. The blended teaching in microendodontics was universally approved by the trainees, which showed more superiority in the improvement of learning efficiency and interest, comprehension of knowledge as well as practical ability, etc., compared to the traditional offline teaching. For the current stomatology education, trainees were inclined to choose the blended teaching mode combining online theory curriculum and offline practice training, whereas 41.3% (353/855) and 39.6% (339/855) of trainees agreed that the teaching effectiveness was likely influenced by the condition and frequency of the offline training, respectively. Besides, significant differences were detected in the question about the factors affecting the blended teaching effectiveness of microendodontics between the trainees who had used and not used DOM (χ2=13.37, P=0.004). Conclusions:The application of online and offline blended teaching in microendodontics was affirmed to have some advantages, and it should be considered that the discrepancy in the level of expertise among trainees probably influenced the teaching effectiveness, which may promote the quality and effect of teaching, the spread and sharing of microendodontics, and provide experience and reference for the practice teaching of Operative Dentistry and Endodontics.

Objective:To evaluate the testing capability of urinary iodine laboratories in Gansu Province and analyze the existing problems.Methods:Z-score method and uncertainty analysis were used to analyze the external quality control assessment results of urinary iodine laboratories in Gansu Province from 2017 to 2021 (data were collected from Gansu Center for Disease Prevention and Control).Results:From 2017 to 2021, the participation rate in the assessment of urinary iodine laboratories in the province was 100.0% (473/473), the feedback rate was 99.8% (472/473), and the pass rate was 91.9% (434/472). The pass rates for assessment from 2017 to 2021 were 82.7% (62/75), 93.9% (93/99), 94.9% (93/98), 92.0% (92/100), and 94.0% (94/100), respectively. The pass rates for provincial, municipal, and county assessments were 5/5, 98.6% (69/70), and 90.7% (360/397), respectively. The proportions of │Z│≤2, 2 <│Z│ < 3, and│Z│≥3 between laboratories in the province were 84.5% (399/472), 9.3% (44/472), and 6.2% (29/472), respectively. The proportions of│Z│≤2, 2 <│Z│ < 3, and│Z│≥3 within the laboratories were 88.6% (418/472), 9.1% (43/472), and 2.3% (11/472), respectively. There was a significant difference in the composition of │Z│ scores between laboratories annually (χ 2 = 24.60, P = 0.002), the proportion of│Z│≤2 increased from 66.7%(50/75) in 2017 to 90.0% (90/100) in 2021. The│Z│ scores between and within provincial laboratories were both ≤2. The proportion of │Z│≤2 between municipal and county-level laboratories was 91.4% (64/70) and 83.1% (330/397), respectively, the proportion of│Z│≤2 within laboratories was 92.9% (65/70) and 87.7% (348/397), respectively. There was no difference in the composition of│Z│ scores between and within provincial, municipal, and county-level laboratories( P < 0.05). The proportion of two concentration quality control blind sample results in the province that were both within the uncertainty range was 89.2% (421/472). From 2017 to 2021, they were 81.3% (61/75), 91.9% (91/99), 84.7% (83/98), 92.0% (92/100), and 94.0% (94/100), respectively, with statistically significant differences (χ 2 = 9.69, P = 0.021); provinces, cities, and counties were 5/5, 95.7% (67/70), and 87.9% (349/397), respectively, with statistically significant differences (χ 2 = 23.60, P = 0.023). Conclusions:Through continuous external quality control assessments of all established urinary iodine laboratories in Gansu Province, the overall testing capacity of urinary iodine laboratories at all levels has been continuously improved. However, in the future, it is still necessary to strengthen laboratory testing capabilities and improve the level of urine iodine detection.

AIM: To investigate the efficacy and safety of ZKY001 eye drops with different concentrations in the treatment of corneal epithelial defects(CED)after primary pterygium excision.METHODS: This was a multicenter, randomized, double-blinded, placebo-controlled phase II clinical trial. From March 15, 2022 to November 14, 2022, patients with primary pterygium who had undergone surgery were recruited from 12 tertiary hospitals across China. Using block randomization, 178 patients(178 eyes)were randomly assigned to 3 groups in a 1:1:1 ratio: 0.002% ZKY001 group(n=59), 0.004% ZKY001 group(n=59), and placebo group(n=60, receiving ZKY001 sham eye drops). Subjects in each group received 1 drop of the study drug 4 times per day for 4 d. The percentage of CED area recovery from baseline, the first complete healing time of CED area, the number of first complete healing cases of CED, and changes in visual analogue scale(VAS)scores for eye discomfort including eye pain, foreign body sensation, tearing and photophobia were observed.RESULTS: In terms of improvement in CED, there were no statistically significant differences among the three groups including the first healing time of CED, the percentage improvement in CED area compared to baseline, and the percentage of first healing cases at different follow-up visits(all P>0.05). Numerically, the first healing time of CED was shorter in the test groups compared to the placebo group(67.87±21.688 h for the 0.002% ZKY001 group, 61.48±22.091 h for the 0.004% ZKY001 group, and 68.85±20.851 h for the placebo group). On D1 morning, the percentage improvement in CED area compared to baseline was maximally different from the placebo group, and the numerical difference advantage was maintained at subsequent follow-up visits. The number of first healing cases in the CED area at different follow-up visits was higher in the test groups than the placebo group. In terms of improvement in ocular discomfort, the total VAS scores were lower in the test groups compared to the placebo group, mainly due to reductions in foreign body sensation and pain scores. At D3, the 0.004% ZKY001 group showed statistically significant improvement in foreign body sensation(P<0.017). In terms of safety, the overall incidence of adverse events was low(9.0%)and similar among groups.CONCLUSION: The use of ZKY001 eyedrops after primary pterygium surgery can safely improve the CED repair, and alleviate postoperative symptoms caused by CED.

The dosage， dose and administration method of decoctions are important factors affecting the efficacy of prescriptions. By analyzing 35 decoction formulas from the Ming and Qing dynasties within the Catalogue of Ancient Classic Famous Formulas （First Batch）， it was found that the average dosage was equivalent to about 65 g， of which 71.4% （25/35） of the prescriptions had a dosage ≤60 g. And among them， the dosage of decoctions in the Ming dynasty was significantly smaller than that in the Qing dynasty. Considering the characteristics of formulas in Song dynasty， it is believed that decoctions in Ming and Qing dynasties were influenced by the popular use of decoctions during the Song， Jin， and Yuan dynasties. Some decoctions recorded a dosage of one dose instead of one day， which was more evident in the Ming dynasty. However， by the Qing dynasty， the usage of prescriptions with a dosage of one day gradually became more common. Therefore， in the practical research and application of classic famous formulas from the Ming and Qing dynasties， it is advised to pay attention to the difference between the dosage， one dose and the daily dosage. It is necessary to determine whether to double the dosage of the original formula based on the actual use， in order to ensure the clinical efficacy.

Objective To summarize the experience and practical value of living donor kidney harvesting in Bama miniature pigs with six gene modified. Methods The left kidney of Bama miniature pigs with six gene modified was obtained by living donor kidney harvesting technique. First, the ureter was occluded, and then the inferior vena cava and abdominal aorta were freed. During the harvesting process, the ureter, renal vein and renal artery were exposed and freed in sequence. The vascular forceps were used at the abdominal aorta and inferior vena cava, and the renal artery and vein were immediately perfused with 4℃ renal preservation solution, and stored in ice normal saline for subsequent transplantation. Simultaneously, the donor abdominal aorta and inferior vena cava gap were sutured. The operation time, blood loss, warm and cold ischemia time, postoperative complications and the survival of donors and recipients were recorded. Results The left kidney of the genetically modified pig was successfully harvested. Intraoperative bleeding was 5 mL, warm ischemia time was 45 s, and cold ischemia time was 2.5 h. Neither donor nor recipient pig received blood transfusion, and urinary function of the kidney transplanted into the recipient was recovered. The donor survived for more than 8 months after the left kidney was resected. Conclusions Living donor kidney harvesting is safe and reliable in genetically modified pigs. Branch blood vessels could be processed during kidney harvesting, which shortens the process of kidney repair and the time of cold ischemia. Living donor kidney harvesting contributes to subsequent survival of donors and other scientific researches.