Yuejuwan is a classic formula widely used by doctors to relieve liver and depression， with precise clinical efficacy in traditional Chinese medicine （TCM）. The authors used bibliometric methods to collect and collate 495 ancient data related to Yuejuwan， and 105 valid data were screened out， involving 68 ancient Chinese medical books. After systematic verification of the origin of the formula of Yuejuwan， the main treatment symptoms， the principle of the formula， the composition of the drug， the dosage， the preparation method， the decoction method， and other information， the results showed that Yuejuwan originated from the Danxi Xinfa （《丹溪心法》） of the Yuan Dynasty by ZHU Zhenheng， and it is composed of five medicines， namely Atractylodis Rhizoma， Cyperi Rhizom， Chuanxiong Rhizoma， Massa Medicata Fermentata， and Gardeniae Fructus. In terms of drug base， Atractylodis Rhizoma， Cyperi Rhizom， Chuanxiong Rhizoma， and Gardeniae Fructus are in line with the records in the 2020 edition of Chinese Pharmacopoeia， and Massa Medicata Fermentata is used. The preparation method is as follows： Massa Medicata Fermentata and Gardeniae Fructus are fried， and Cyperi Rhizoma is roasted in vinegar. Chuanxiong Rhizoma is used in the raw form， and Atractylodis Rhizoma is prepared with rice swill. The formula can regulate Qi and relieve depression and broaden the middle and remove fullness. It is clinically used for the treatment of six types of depression syndromes， chest and diaphragm plumpness， abdominal distension and leg acid， acid swallowing and vomiting， eating and drinking disharmony， toothache， mouth and tongue sores， and other diseases. The most used dosage of the formula in the ancient records through the ages is converted into the modern dosage， namely 3.05 g Atractylodis Rhizoma， 3.05 g Cyperi Rhizoma， 3.05 g Chuanxiong Rhizoma， 3.05 g Massa Medicata Fermentata， and 3.05 g Gardeniae Fructus， and the daily dosage is 15.25 g. The converted dosage is similar to that recorded in the 2020 edition of the Chinese Pharmacopoeia. The formula is in pill form， and medicine should be taken with lukewarm boiled water after the meal. Through the excavation of the ancient literature related to Yuejuwan， the key information of the formula is identified， with a view to providing a more accurate reference for the clinical application of Yuejuwan and subsequent in-depth investigation.

Yuejuwan is a classic formula widely used by doctors to relieve liver and depression， with precise clinical efficacy in traditional Chinese medicine （TCM）. The authors used bibliometric methods to collect and collate 495 ancient data related to Yuejuwan， and 105 valid data were screened out， involving 68 ancient Chinese medical books. After systematic verification of the origin of the formula of Yuejuwan， the main treatment symptoms， the principle of the formula， the composition of the drug， the dosage， the preparation method， the decoction method， and other information， the results showed that Yuejuwan originated from the Danxi Xinfa （《丹溪心法》） of the Yuan Dynasty by ZHU Zhenheng， and it is composed of five medicines， namely Atractylodis Rhizoma， Cyperi Rhizom， Chuanxiong Rhizoma， Massa Medicata Fermentata， and Gardeniae Fructus. In terms of drug base， Atractylodis Rhizoma， Cyperi Rhizom， Chuanxiong Rhizoma， and Gardeniae Fructus are in line with the records in the 2020 edition of Chinese Pharmacopoeia， and Massa Medicata Fermentata is used. The preparation method is as follows： Massa Medicata Fermentata and Gardeniae Fructus are fried， and Cyperi Rhizoma is roasted in vinegar. Chuanxiong Rhizoma is used in the raw form， and Atractylodis Rhizoma is prepared with rice swill. The formula can regulate Qi and relieve depression and broaden the middle and remove fullness. It is clinically used for the treatment of six types of depression syndromes， chest and diaphragm plumpness， abdominal distension and leg acid， acid swallowing and vomiting， eating and drinking disharmony， toothache， mouth and tongue sores， and other diseases. The most used dosage of the formula in the ancient records through the ages is converted into the modern dosage， namely 3.05 g Atractylodis Rhizoma， 3.05 g Cyperi Rhizoma， 3.05 g Chuanxiong Rhizoma， 3.05 g Massa Medicata Fermentata， and 3.05 g Gardeniae Fructus， and the daily dosage is 15.25 g. The converted dosage is similar to that recorded in the 2020 edition of the Chinese Pharmacopoeia. The formula is in pill form， and medicine should be taken with lukewarm boiled water after the meal. Through the excavation of the ancient literature related to Yuejuwan， the key information of the formula is identified， with a view to providing a more accurate reference for the clinical application of Yuejuwan and subsequent in-depth investigation.

Kounis syndrome is an acute coronary syndrome triggered by an allergic reaction, which is clinically rare and frequently subject to misdiagnosis or missed diagnosis. This article presents a case report of a 70-year-old male patient who developed a rash, pruritus, and chest pain following colon polyp resection. Coronary angiography revealed occlusion of the left anterior descending artery, and blood flow was restored after stent implantation. However, the patient experienced recurrent symptoms accompanied by loss of consciousness. Drug skin tests confirmed positive reactions to chlorhexidine and fondaparinux sodium, leading to a diagnosis of type Ⅱ Kounis syndrome. By avoiding allergenic drugs and combining antihistamines with symptomatic treatment to correct myocardial ischemia, the patient′s clinical symptoms significantly improved, and he eventually recovered and was discharged from the hospital. This case underscores the importance of maintaining vigilance for this syndrome in patients with allergies accompanied by chest pain and promptly identifying and avoiding allergens.

Ochratoxin A (OTA) is ubiquitous in the food and feed fields. It has strong hepatotoxicity and nephrotoxicity, seriously threatening the health of humans and animals. Enzymatic degradation of mycotoxins is considered to be a promising method to control mycotoxin contaminations. In this study, a new ochratoxin A amidohydrolase from Microbulbifer thermotolerans (MiADH) was obtained. After heterologous expression in Escherichia coli and purification, the recombinant protein was studied regarding the hydrolysis activity, hydrolysis products, enzymatic properties, and substrate binding mode. MiADH can degrade OTA into ochratoxin α (OTα) and phenylalanine, demonstrating a detoxifying ability. It demonstrated the best performance at 70 ℃ and pH 8.0, and Cu²⁺ had the strongest inhibitory effect on the activity of MiADH. MiADH with good thermal stability exhibited huge potential for industrial application. Rational design guided by three-dimensional structural models and substrate docking analysis revealed the important amino acids affecting substrate binding and obtained multiple mutants with improved activity. Among these mutants, V324A had the highest activity, which was 4.2-fold that of the wild type. The identification of MiADH enriches the ochratoxin A degradation enzyme library and provides a new candidate enzyme for the biological detoxification of ochratoxin A in the food and feed industry.
Amidohydrolases/chemistry* ; Ochratoxins/metabolism* ; Substrate Specificity ; Escherichia coli/metabolism* ; Recombinant Proteins/metabolism* ; Actinomycetales/genetics*

Objective: To investigate the prevalence of Dengue virus (DENV) infection among voluntary blood donors in Xishuangbanna Dai Autonomous Prefecture, and to evaluate the necessity of implementing nucleic acid testing (NAT) for blood donors during the rainy season (May-October). Methods: Prior to initiating donor screening, the Xishuangbanna Central Blood Center conducted in-house validation of reagent performance and participated in external quality assessment (EQA) organized by the National Center for Clinical Laboratories (NCCL). During the surveillance period (August-October 2024), a total of 2 919 donor samples were screened using a 6-sample mini-pool NAT strategy. Daily internal quality controls were recorded. Samples that tested positive in pooled screening were deconvoluted and retested in duplicate; only those reactive in both replicate wells were sent to the NCCL for confirmatory testing. At NCCL, samples underwent re-testing using five domestic NAT reagents, as well as serological assays for NS1 antigen and DENV-specific IgG/IgM. Confirmed positive samples were further characterized by serotyping, envelope (E) gene sequencing, and phylogenetic analysis using the maximum likelihood method. Results: The DENV NAT reagent demonstrated consistent detection of 40 copies/mL controls in individual donor (ID)-NAT test (mean CT: 35.61±0.40). During the 63-day quality control monitoring, DENV detection remained stable (mean CT: 22.53±0.72). The center achieved full marks in EQA assessments for 2023 and 2024. Three reactive pools were identified in initial screening, and subsequent individual testing confirmed three DENV RNA-positive donors (sample numbers: 2401, 2402, and 2403). The confirmatory test results from NCCL were: all five NAT platforms consistently detected DENV RNA in the three samples; for serological tests, 2 samples (2402, 2403) were positive for NS1 antigen, while all three samples were negative for both IgG and IgM antibodies. DENV serotyping reagents identified DENV-2 in all cases, which were further confirmed as DENV-2 Genotype Ⅱ-Cosmopolitan by E gene sequencing. Phylogenetic analysis indicated that samples 2401 and 2402 clustered with Southeast Asian strains (Thailand/MZ636802.1, Laos/PQ775621.1), while sample 2403 closely matched a previously reported local Yunnan strain (PV544686.1). Conclusion: DENV-2 infection was detected among blood donors in Xishuangbanna during the rainy season, indicating concurrent risks of imported and local transmission. We recommend implementing pooled NAT screening for blood donors in high-risk areas during dengue epidemic seasons, along with strengthened laboratory quality control, to enhance blood safety.

Objective:To investigate the relationship between the in vivo metabolic ratio (MR) of Aripiprazole (ARI) and CYP2D6 gene polymorphism in children with tic disorders (TD) and its effect on dose-exposure (DE), so as to promote precision drug use. Methods:In this study, a real-world observational study design was used to collect 81 children with TD who visited the Department of Neurology of Wuhan Children′s Hospital from January 2021 to January 2024, the concentration of the prototype drug and the main metabolite Dehydroaripiprazole (DARI), the detection data of CYP2D6 single nucleotide gene polymorphism (SNP) and clinical data were collected, and the relationship between the DARI/ARI metabolic ratio (MR) and CYP2D6 metabolic type was analyzed by the receiver operating characteristic (ROC) curve.A DE model between ARI dose and steady-state trough concentration was established by population modeling, and the effects of CYP2D6 metabolic type, MR and body weight on DE were analyzed.Goodness-of-fit diagram (GOF), visual predictive check (VPC) and prediction error analysis were used to verify the prediction performance of the DE model.Results:ROC analysis showed that there was a correlation between MR and CYP2D6 metabolic type, the MR sensitivity cut-point of CYP2D6 ultrafast metabolic (UM) patients was 0.399, and the cut-point of MR in intermediate metabolic (IM) patients was 0.252.Based on this, the patients were divided into three categories: MR TYPE Ⅰ: MR≥0.399, MR TYPE Ⅱ: 0.252

Objective:To analyze the neurocognitive abnormalities and related emotional and behavioral problems in 410 adolescent patients with Turner syndrome (TS) managed in Henan Children′s Hospital in the past 5 years, and to explore the relationship between neurocognitive abnormalities and chromosome karyotype, pubertal development, hormone replacement therapy.Methods:A retrospective case series study.A total of 410 adolescent patients who were diagnosed with TS by karyotype or fluorescence in situ hybridization in the outpatient or inpatient Department of Endocrinology, Genetics and Metabolism at Henan Children′s Hospital from June 2018 to June 2023 were selected and divided into 2 groups according to age: < 12 years old and 12-18 years old.Neurocognitive assessments were performed based on the results of the Wechsler Intelligence Scale (4 th edition) for children and behavior scales for children, SPSS 22.0 software was used for data processing and statistical analysis, and chi-square test was used to analyze the correlation between chromosome karyotype, intelligence development level, pubertal development status, hormone therapy status and the occurrence of neuropsychiatric diseases. Results:Among the 410 TS patients, 207 cases had the karyotype of 45, X0/46, XX, accounting for 50.49%, 94 cases had the monosomic karyotype of 45, X0, accounting for 22.93%.Forty-six patients completed the Wechsler intelligence test, with the intelligence quotient (IQ) score ranging from 70 to 105, with high verbal comprehension and perceptual reasoning scores and low processing speed and working memory scores on all assessments.Fifty-two patients completed the hyperactivity scale assessment, and 43 cases had a predisposition to attention deficit hyperactivity disorder (ADHD).There were no significant differences in total IQ, perceptual reasoning and processing speed among the children with karyotype 45, X0, chimeric, and X chromosome structural abnormalities ( H=3.161, 1.955, 5.890, all P>0.05), while there were significant differences in verbal comprehension and working memory among the three groups ( H=7.697, 9.694, all P<0.05).Among TS patients 12-18 years old, 68 cases completed the depression scale self-assessment, of which 23 cases had depressive tendencies.There was no correlation between depressive tendency and chromosome karyotype, pubertal development and hormone replacement therapy ( P>0.05). Conclusions:TS patients generally have low intelligence levels and tend to have ADHD in childhood.TS patients in the pubertal development have a high incidence of depression.Pubertal development status and hormone replacement therapy show no correlation with the occurrence of neuropsychiatric diseases in TS patients.

Modulating Tankyrases (TNKS), interactions with USP25 to promote TNKS degradation, rather than inhibiting their enzymatic activities, is emerging as an alternative/specific approach to inhibit the Wnt/β-catenin pathway. Here, we identified UAT-B, a novel neoantimycin analog isolated from Streptomyces conglobatus, as a small-molecule inhibitor of TNKS-USP25 protein-protein interaction (PPI) to overcome multi-drug resistance in colorectal cancer (CRC). The disruption of TNKS-USP25 complex formation by UAT-B led to a significant decrease in TNKS levels, triggering cell apoptosis through modulation of the Wnt/β-catenin pathway. Importantly, UAT-B successfully inhibited the CRC cells growth that harbored high TNKS levels, as demonstrated in various in vitro and in vivo studies utilizing cell line-based and patient-derived xenografts, as well as APC^min/+ spontaneous CRC models. Collectively, these findings suggest that targeting the TNKS-USP25 PPI using a small-molecule inhibitor represents a compelling therapeutic strategy for CRC treatment, and UAT-B emerges as a promising candidate for further preclinical and clinical investigations.

Objective:To investigate the value of the combined ultrasound imaging radiomics model for predicting progression-free survival in endocrine therapy for prostate cancer.Methods:A total of 283 prostate cancer patients who received endocrine treatment at the Inner Mongolia Autonomous Region People′s Hospital and the First Hospital of Hohhot from July 2018 to January 2023 were retrospectively collected, of which 198 patients from the Inner Mongolia Autonomous Region People′s Hospital were randomly divided into the training set and the validation set according to the ratio of 7∶3, and 85 patients from the First Hospital of Hohhot served as an independent external test set. They were classified into a progression group and a non-progression group based on whether the patients progressed to desmoplasia-resistant prostate cancer 18 months after the start of endocrine treatment.Based on the two-dimensional ultrasound images, the imaging radiomics features were extracted and the imaging radiomics score (Rad-score) were constructed, the immunopathology and other clinical data were analysed, and three prediction models were constructed using logistic regression: the clinical model, the ultrasonography model, and the ultrasonography-clinical combined model, respectively. The predictive efficacy and clinical utility of the models were assessed by the ROC curves and clinical decision curves.Results:Five ultrasonographic features were included in the ultrasound model; the prostate-specific antigen nadir, the neutrophil-to-lymphocyte ratio before treatment, and the expression level of tumour proliferating cell nuclear antigen 67 (Ki-67) were incorporated into the clinical model; and the Rad score computed from the output of the ultrasound model for the screening features, together with the prostate-specific antigen nadir (PSA nadir), the neutrophil to lymphocyte ratio (NLR) before treatment, and the expression level of Ki-67 were used to construct the ultrasound-clinical joint model. The joint model achieved the highest predictive performance in both the training and validation sets of the three groups of models, with the area under the curve of 0.85 and 0.84, and the clinical decision curve showed good clinical benefit.Conclusions:The combined ultrasound-clinical model constructed in this study based on two-dimensional ultrasound images of prostate cancer before endocrine therapy can predict progression-free survival of endocrine therapy for prostate cancer more accurately.