Objective: This study aims to review the application of dobutamine stress cardiac magnetic resonance imaging (DSCMR) for patients with anomalous inter-arterial coronary arteries. Materials and Methods: Consecutive adult patients (≥18 years) with anomalous inter-arterial coronary arteries and DSCMR performed in a quaternary referral center from January 2020 to December 2024 were retrospectively reviewed. Examination details, including medication and complications, were reviewed. Radiological findings, such as wall motion abnormality, perfusion defect and late myocardial enhancement were evaluated. Post-examination management and outcomes were assessed. Results: A total of 31 patients (17 females [54.8%]; age 53.6±11.7 years) with anomalous inter-arterial coronary arteries were included. Most patients (n=25, 80.6%) had anomalous right coronary artery. There were significant differences in peak heart rate (p<0.001) and blood pressure (p<0.001) when compared to the baseline. Only one patient (3.2%) experienced minor adverse event with chest pain during the examination. Her cardiac enzymes and electrocardiogram were normal. All other patients (n=30, 96.8%) had no examination-related complications. Left ventricular stroke volume (78.3 [interquartile range, IQR 15.8] mL) and ejection fraction (63.2% [IQR 9.2%]) were normal. No wall motion abnormality, perfusion defect nor late myocardial enhancement were identified. Median follow-up after DSCMR was 21.0 (IQR 28.0) months. One patient underwent reimplantation of right coronary artery due to recurrent syncope. Conservative management was adopted for all other patients (n= 30, 96.8%). Most (n=28, 90.3%) were asymptomatic post-examination. No major adverse cardiovascular events were reported. Conclusion DSCMR can be safely performed for patients with anomalous inter-arterial coronary arteries and can help guide management plan.

Background/Aims: Pancreatic stenting reduces post-endoscopic retrograde cholangiopancreatography pancreatitis (PEP) and aids in cannulation in difficult cases. However, conservative endoscopists may stop at this step, resulting in suboptimal outcomes. This study assessed the efficacy of transpancreatic precut sphincterotomy (TPS) as a rescue procedure following pancreatic stenting. Methods: Between March 2013 and November 2018, 82 patients underwent pancreatic stenting at our institution prior to successful biliary cannulation. TPS was introduced in April 2016, and patients were divided into Before TPS and After TPS groups. The outcomes included cannulation success, PEP incidence, and predictors of TPS conversion. Results: There were 43 and 39 patients in the Before TPS and After TPS groups, respectively. Twenty-two patients (56.4%) underwent conversion to TPS in the After TPS group. The After TPS group had a higher bile duct cannulation rate (89.7% vs. 72.1%) than the Before TPS group, but this difference was not statistically significant (p=0.054). Multivariate analysis showed that age >50 years (odds ratio [OR], 0.181; p=0.021) and being in the After TPS group (OR, 0.712; p=0.039) were independently associated with reduced PEP risk. Haraldsson Type 2 and Type 4 papillae carried a relatively high TPS conversion rate. Conclusions A stepwise cannulation strategy that incorporates TPS after pancreatic stenting minimizes the need for advanced techniques and improves PEP outcomes.

Background/Aims: Data from Asia regarding the short-term and long-term outcomes for acute severe ulcerative colitis (ASUC) are limited. We assessed the outcomes of ASUC, identified the risk factors for colectomy, and compared colectomy rates between the pre-biologics and post-biologics eras in Taiwan. Methods: The patients with an ASUC diagnosis between January 2013 and March 2022 at 5 tertiary medical centers were retrospectively analyzed. Results: In total, 98 patients were enrolled, with 68.4% diagnosed in the post-biologics era. In 78.6% of the ASUC patients initially received intravenous steroid therapy, for which the success rate was 74.1%. As for rescue therapy, 15 patients (93.8%) received biologics and 1 (6.3%) received cyclosporin. Biologics rescue therapy had a 93.3% success rate. One (1%) mortality due to septic shock occurred. The colectomy rate for index ASUC admission was 11.2%. Patients receiving colectomy were predominantly male (P= 0.012) and at older age (P= 0.016). Higher C-reactive protein (P= 0.035), lower albumin (P= 0.017), and hemoglobin (P= 0.023) levels were associated with colectomy risk. During a median follow-up of 24 months, 13 patients (15.1%) had recurrent ASUC and 23.1% of patients received colectomy. The accumulated colectomy rate at 3 years did not differ between the pre- and post-biologics eras (16.1% vs. 13.4%, P= 0.270). Conclusions This is the first Asian study on ASUC to compare colectomy rates between the prebiologics and post-biologics eras, revealing no significant difference. The recurrent ASUC had a higher colectomy rate than the index ASUC.

[摘 要] 目的：探讨麻疹-流行性腮腺炎-风疹联合减毒活疫苗（MMR）通过诱导免疫原性细胞死亡（ICD）对三阴性乳腺癌（TNBC）的免疫调节机制。方法：体外实验采用CCK-8法检测MMR对TNBC细胞4T1和MDA-MB-231存活率的影响，免疫荧光法检测MDA-MB-231细胞中钙网蛋白（CALR）表达，磷钼酸比色法检测MDA-MB-231细胞内ATP的含量，ELISA检测细胞上清液中高迁移率族蛋白B1（HMGB1）的表达水平，通过GEPIA网站分析CALR和HMGB1对乳腺癌患者生存期的影响。体内实验中经皮下注射4T1-Luc细胞于雌性BALB/c小鼠乳腺脂肪垫构建TNBC小鼠模型。设Control组、盐酸阿霉素（Dox）组、MMR组，按照分组每两天静脉给药1次，连续给药3次。动物活体成像系统观察肿瘤体积变化；记录小鼠体质量及各器官指数初步评估疫苗安全性；H-E染色观察肿瘤病理变化；免疫组化和Western blotting检测肿瘤中CALR和HMGB1蛋白的表达。流式细胞术分析小鼠脾T淋巴细胞亚群及肿瘤树突状细胞和巨噬细胞比例；免疫组化检测肿瘤CD8+ T淋巴细胞浸润；ELISA检测血清中促炎细胞因子IL-6和TNF-α含量。结果：MMR对4T1细胞的活性抑制作用较弱；MMR对MDA-MB-231细胞抑制率达90.39%（P < 0.001）。与Control组相比，MMR组MDA-MB-231细胞中ICD相关蛋白（CALR、ATP、HMGB1）表达上调（P < 0.001）。GEPIA网站分析表明，CALR和HMGB1高表达的患者总生存期有所延长。MMR延缓了荷瘤小鼠肿瘤体积增长（P < 0.001），延长小鼠的生存期，且28 d内MMR组荷瘤小鼠体重与Control组无显著性差异（P > 0.05）；H-E染色显示，与Control组相比，MMR组小鼠肿瘤组织坏死区域扩大且有免疫细胞浸润；MMR上调肿瘤ICD相关蛋白CALR、HMGB1的表达水平；MMR组脾CD4+、CD8+ T淋巴细胞及肿瘤树突状细胞和M1型巨噬细胞的比例增加（P < 0.05），CD8+ T淋巴细胞在肿瘤组织中的浸润增加（P < 0.001），且促炎细胞因子IL-6和TNF-α水平升高（P < 0.01）。结论：MMR减毒活疫苗对TNBC的抗肿瘤作用可能与诱导肿瘤发生ICD进而激活抗肿瘤免疫相关。

OBJECTIVE: To evaluate the dynamic changes of glucocorticoid (GC) dose and the feasibility of GC discontinuation in rheumatoid arthritis (RA) patients under the background of Chinese medicine (CM). METHODS: This multicenter retrospective cohort study included 1,196 RA patients enrolled in the China Rheumatoid Arthritis Registry of Patients with Chinese Medicine (CERTAIN) from September 1, 2019 to December 4, 2023, who initiated GC therapy. Participants were divided into the Western medicine (WM) and integrative medicine (IM, combination of CM and WM) groups based on medication regimen. Follow-up was performed at least every 3 months to assess dynamic changes in GC dose. Changes in GC dose were analyzed by generalized estimator equation, the probability of GC discontinuation was assessed using Kaplan-Meier curve, and predictors of GC discontinuation were analyzed by Cox regression. Patients with <12 months of follow-up were excluded for the sensitivity analysis. RESULTS: Among 1,196 patients (85.4% female; median age 56.4 years), 880 (73.6%) received IM. Over a median 12-month follow-up, 34.3% (410 cases) discontinued GC, with significantly higher rates in the IM group (40.8% vs. 16.1% in WM; P<0.05). GC dose declined progressively, with IM patients demonstrating faster reductions (median 3.75 mg vs. 5.00 mg in WM at 12 months; P<0.05). Multivariate Cox analysis identified age <60 years [P<0.001, hazard ratios (HR)=2.142, 95% confidence interval (CI): 1.523-3.012], IM therapy (P=0.001, HR=2.175, 95% CI: 1.369-3.456), baseline GC dose ⩽7.5 mg (P=0.003, HR=1.637, 95% CI: 1.177-2.275), and absence of non-steroidal anti-inflammatory drugs use (P=0.001, HR=2.546, 95% CI: 1.432-4.527) as significant predictors of GC discontinuation. Sensitivity analysis (545 cases) confirmed these findings. CONCLUSIONS RA patients receiving CM face difficulties in following guideline-recommended GC discontinuation protocols. IM can promote GC discontinuation and is a promising strategy to reduce GC dependency in RA management. (Trial registration: ClinicalTrials.gov, No. NCT05219214).
Adult ; Aged ; Female ; Humans ; Male ; Middle Aged ; Arthritis, Rheumatoid/drug therapy* ; Glucocorticoids/therapeutic use* ; Medicine, Chinese Traditional ; Retrospective Studies

OBJECTIVE: In Pakistan, traditional medicines are an important component of the medical system, with numerous varieties and great demands. However, due to the scattered resources and the lack of systematic collection and collation, adulteration of traditional Pakistani medicine (TPM) is common, which severely affects the safety of their medicinal use and the import and export trades. Therefore, it is urgent to systematically organize and unify the management of TPM and establish a set of standards and operable methods for the identification of TPM. METHODS: We collected and organized the information on 128 TPMs with regard to their medicinal parts, efficacy, usage, and genetic material, based on Pakistan Hamdard Pharmacopoeia of Eastern Medicine: Pharmaceutical Codex. The genetic information of TPM is summarized from national center for biotechnology information (NCBI) and global pharmacopoeia genome database (GPGD). Furthermore, we utilized bioinformatics technology to supplement the chloroplast genome (cp-genome) data of 12 TPMs. To build the web server, we used the Linux + Apache + MySQL + PHP (LAMP) system and constructed the webpage on a PHP: Hypertext Preprocessor (PHP) model view controller (MVC) framework. RESULTS: We constructed a new genomic database, the traditional Pakistani medicine genomic database (TPMGD). This database comprises five entries, namely homepage, medicinal species, species identification, basic local alignment search tool (BLAST), and download. Currently, TPMGD contains basic profiles of 128 TPMs and genetic information of 102 TPMs, including 140 cytochrome c oxidase subunit I (COI) sequences and 119 mitochondrial genome sequences from Bombyx mori, 1 396 internal transcribed spacer 2 (ITS2) sequences and 1 074 intergenic region (psbA-trnH) sequences specific to 92 and 83 plant species, respectively. Additionally, TPMGD includes 199 cp-genome sequences of 82 TPMs. CONCLUSION TPMGD is a multifunctional database that integrates species description, functional information inquiry, genetic information storage, molecular identification of TPM, etc. The database not only provides convenience for TPM information queries but also establishes the scientific basis for the medication safety, species identification, and resource protection of TPM.

Traditional Chinese medicine (TCM) serves as a treasure trove of ancient knowledge, holding a crucial position in the medical field. However, the exploration of TCM's extensive information has been hindered by challenges related to data standardization, completeness, and accuracy, primarily due to the decentralized distribution of TCM resources. To address these issues, we developed a platform for TCM knowledge discovery (TCMKD, https://cbcb.cdutcm.edu.cn/TCMKD/). Seven types of data, including syndromes, formulas, Chinese patent drugs (CPDs), Chinese medicinal materials (CMMs), ingredients, targets, and diseases, were manually proofread and consolidated within TCMKD. To strengthen the integration of TCM with modern medicine, TCMKD employs analytical methods such as TCM data mining, enrichment analysis, and network localization and separation. These tools help elucidate the molecular-level commonalities between TCM and contemporary scientific insights. In addition to its analytical capabilities, a quick question and answer (Q&A) system is also embedded within TCMKD to query the database efficiently, thereby improving the interactivity of the platform. The platform also provides a TCM text annotation tool, offering a simple and efficient method for TCM text mining. Overall, TCMKD not only has the potential to become a pivotal repository for TCM, delving into the pharmacological foundations of TCM treatments, but its flexible embedded tools and algorithms can also be applied to the study of other traditional medical systems, extending beyond just TCM.

OBJECTIVE: To explore the clinical effect of personalized puncture planning before surgery using Picture Archiving and Communication System (PACS) in the treatment of osteoporotic vertebral compression fractures in the elderly. METHODS: A total of 69 elderly patients with osteoporotic vertebral compression fractures treated by percutaneous vertebroplasty from January 2020 20 to December 2021 with more than 1 year of follow-up were analyzed retrospectively. Thirty-four patients were individualized for preoperative planning with PACS software (observation group), including 8 males and 26 females, with a mean age of (73.30±7.96) years old;and 35 patients were treated with conventional treatment (control group), including 7 males and 28 females, with a mean age of (77.30±7.84) years old. The operation time, the amount of cement injection, cement leakage rate, bone watertight diffusion and refracture within 1 year between two groups were observed and compared. The Cobb's angle, low back pain visual analogue scale(VAS) and the modified Oswsetry disability indexes(ODI) before surgery and 1 day, 1 year after surgery were compared between two groups. RESULTS: Both groups successfully completed the operation without serious surgical complications, 2 refractures occurred in the control group. The operation time in the observation group was(41.9±11.9) min, which was less than that in the control group (52.7±13.6) min (P<0.05). There was no significant difference in the cement injection volume between two groups (P>0.05). Two cases of cement leakage in the observation group was less than 8 in the control group (P<0.05). The bone cement distribution index of two groups had significant difference(P<0.05). There were no significant differences between two groups in Cobb's angle of the injured vertebras and ODI before and 1 day after surgery(P>0.05), however, the comparative differences were statistically significant at 1 year after surgery(P<0.05). There was no significant difference in the VAS between two groups at each time period(P>0.05). CONCLUSION Using the PACS software to plan personalized puncture scheme can reduce the operation time, reduce the cement leakage rate, improve the diffusion of bone cement and longer maintain the postoperative form of vertebral body and the functional state of patients' lumbar back.
Humans ; Male ; Female ; Aged ; Vertebroplasty/methods* ; Fractures, Compression/diagnostic imaging* ; Spinal Fractures/diagnostic imaging* ; Osteoporotic Fractures/diagnostic imaging* ; Aged, 80 and over ; Retrospective Studies ; Radiology Information Systems

Objective To construct a library of human-derived anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) single-chain variable fragments (scFv) and screen for broad-spectrum neutralizing antibodies to identify candidate molecules for the development of diagnostic and therapeutic agents. Methods Peripheral blood mononuclear cells (PBMCs) were isolated from the peripheral blood of patients who had recovered from novel coronavirus infection. Total RNA was extracted from these PBMCs and reverse transcribed into cDNA, which was used as a template for constructing a human anti-SARS-CoV-2 scFv library. Phage display technology was used to screen for scFv antibodies specific to the SARS-CoV-2 S protein. Full-length IgG antibodies were synthesized through sequence analysis and human IgG expression, and their binding capacity and neutralizing activity against SARS-CoV-2 were evaluated. Results A human-derived scFv antibody library against SARS-CoV-2 with a capacity of 1.56×10⁷ CFU was successfully constructed. Two specific scFv antibodies were screened from this library and expressed as full-length IgG antibodies (IgG-A10 and IgG-G6). IgG-A10 exhibited strong neutralizing activity against both the original SARS-CoV-2 strain (WT) and the XBB subvariant of the Omicron variant. However, the neutralizing activity of this antibody against the JN.1 sub lineage of the Omicron BA.2.86 variant was moderate. Conclusion This study has successfully constructed a human anti-SARS-CoV-2 scFv antibody library from the peripheral blood of recovered patients, and screened and expressed anti-SARS-CoV-2 IgG antibodies with neutralizing activity, laying a foundation for the prevention, diagnosis, and treatment of SARS-CoV-2 infection.
Humans ; Single-Chain Antibodies/genetics* ; SARS-CoV-2/immunology* ; COVID-19/immunology* ; Immunoglobulin G/genetics* ; Antibodies, Viral/genetics* ; Peptide Library ; Spike Glycoprotein, Coronavirus/immunology* ; Antibodies, Neutralizing/immunology* ; Leukocytes, Mononuclear/immunology* ; Broadly Neutralizing Antibodies/immunology*

Nonobstructive azoospermia (NOA), one of the most severe types of male infertility, etiology often remains unclear in most cases. Therefore, this study aimed to detect four biallelic detrimental variants (0.5%) in the minichromosome maintenance domain containing 2 ( MCMDC2 ) genes in 768 NOA patients by whole-exome sequencing (WES). Hematoxylin and eosin (H&E) demonstrated that MCMDC2 deleterious variants caused meiotic arrest in three patients (c.1360G>T, c.1956G>T, and c.685C>T) and hypospermatogenesis in one patient (c.94G>T), as further confirmed through immunofluorescence (IF) staining. The single-cell RNA sequencing data indicated that MCMDC2 was substantially expressed during spermatogenesis. The variants were confirmed as deleterious and responsible for patient infertility through bioinformatics and in vitro experimental analyses. The results revealed four MCMDC2 variants related to NOA, which contributes to the current perception of the function of MCMDC2 in male fertility and presents new perspectives on the genetic etiology of NOA.
Humans ; Male ; Azoospermia/genetics* ; Meiosis/genetics* ; Spermatogenesis/genetics* ; Adult ; Exome Sequencing ; Microtubule-Associated Proteins/genetics* ; Alleles ; Infertility, Male/genetics*