Prolonged standing work can lead to various lower limb health issues. Footwear, as a convenient and noninvasive intervention, plays a key role in foot protection. The purpose of this review was to evaluate the impact of footwear characteristics on foot comfort among workers engaged in prolonged standing occupations. A systematic search of PubMed, Web of Science, Scopus, and the Cochrane Library was conducted until March 2025 for experimental and observational studies; the review is registered in International Prospective Register of Systematic Reviews (CRD420251003253).Given the diversity of study designs, participant characteristics, and outcome measures, results were synthesized narratively, organizing findings by footwear design factors. The synthesis indicated that soft soles reduce foot impact and fatigue but offer limited support, whereas hard soles enhance stability but may cause localized pressure and discomfort. Sole hardness should balance cushioning and support based on activity: hard soles for standing and soft soles for walking. Insole hardness must be carefully considered as semirigid arch supports can cause discomfort. Most insoles improve pressure distribution by adjusting arch loading, and some enhance intrinsic foot muscles by promoting toe engagement, reducing leg swelling. Custom orthotic insoles outperform standard ones in comfort and balance. Future research should promote interdisciplinary collaboration with footwear designers to explore key design parameters and establish a scientific framework for protective footwear.

To improve the consistency of outcome documentation and address the potential for outcome reporting bias in clinical trials involving integrative Chinese and Western medicine (ICWM) for ulcerative colitis (UC), we aim to develop a customized core outcome set (COS) that incorporates input from various stakeholders. The study design of this COS has been informed by the Core Outcome Measures in Effectiveness Trials Initiative Handbook, with adherence to the guidelines from the Core Outcome Set-STAndards for Reporting statement and Core Outcome Set-STAndardised Protocol Items recommendations. Five groups of stakeholders will be invited to participate in the development of COS for clinical trials with ICWM for UC, including healthcare professionals, patients, COS developers, COS users, and methodologists. The process will involve five stages: (1) conducting a systematic review of outcomes reported in clinical trials and protocols to develop a list of potential outcome domains; (2) conducting semi-structured interviews to obtain important outcomes; (3) choosing the most important outcomes by conducting three-round Delphi surveys; (4) achieving a consensus in a face-to-face meeting to discuss the final COS; and (5) publication, dissemination and implementation of COS. Consequently, this specialized COS will be applicable to clinical trials involving both traditional Chinese medicine (TCM) and ICWM interventions. Please cite this article as: Zhang X, Zhang L, Wang J, Lau CT, Wang N, Zhang X, Wang P, Li J, Han F, Bian Z. A protocol for developing, disseminating and implementing a core outcome set for clinical trials of integrative Chinese and Western medicine for ulcerative colitis. J Integr Med. 2025; 23(6):654-659.
Colitis, Ulcerative/therapy* ; Humans ; Medicine, Chinese Traditional ; Clinical Trials as Topic ; Integrative Medicine ; Research Design ; Outcome Assessment, Health Care ; Delphi Technique

Baihuasheshecao(Hedyotis diffusa) is a commonly used traditional Chinese medicine derived from the whole herb of H. diffusa and has been widely utilized in folk medicine. It possesses anti-tumor, antibacterial, and anti-inflammatory properties, making it one of the frequently used herbs in TCM clinical practice. However, Shuixiancao(H. corymbosa) and Xianhuaercao(H. tenelliflora), species of the same genus, are often used as substitutes for Baihuasheshecao. To substantiate the medicinal basis of Baihuasheshecao, this study systematically reviewed classical herbal texts and modern literature, examining its nomenclature, botanical origin, harvesting, processing, properties, meridian tropism, pharmacological effects, and clinical applications. The results indicate that Baihuasheshecao was initially recorded as "Shuixiancao" in Preface to the Indexes to the Great Chinese Botany(Zhi Wu Ming Shi Tu Kao). Based on its morphological characteristics and habitat description, it was identified as H. diffusa in the Rubiaceae family. Subsequent records predominantly refer to it as Baihuasheshecao as its official name. In most regions, Baihuasheshecao is recognized as the authentic medicinal material, distinct from Shuixiancao and Xianhuaercao. Baihuasheshecao is harvested in late summer and early autumn, and the dried whole plant, including its roots, is used medicinally. The standard processing method involves cutting. It is known for its effects in clearing heat, removing toxins, reducing swelling and pain, and promoting diuresis to resolve abscesses. Initially, it was mainly used for treating appendicitis, intestinal abscesses, and venomous snake bites, and later, it became a treatment for cancer. The excavation of its clinical value followed a process in which overseas Chinese introduced the herb from Chinese folk medicine to other countries. After its unique anti-cancer effects were recognized abroad, it was reintroduced to China and gradually became a crucial TCM for cancer treatment. The findings of this study help clarify the historical and contemporary uses of Baihuasheshecao, providing literature support and a scientific basis for its rational development and precise clinical application.
Humans ; China ; Drugs, Chinese Herbal/chemistry* ; Hedyotis/classification* ; Medicine, Chinese Traditional/history*

Background: and Purpose Previous research on patients with acute ischemic stroke (AIS) has shown a 0.5% incidence of major gastrointestinal bleeding (GIB) requiring blood transfusion during hospitalization. The existing literature has insufficiently explored the long-term incidence in this population despite the decremental impact of GIB on stroke outcomes. Methods: We analyzed the data from a cohort of patients with AIS admitted to 14 hospitals as part of a nationwide multicenter prospective stroke registry between 2011 and 2013. These patients were followed up for up to 6 years. The occurrence of major GIB events, defined as GIB necessitating at least two units of blood transfusion, was tracked using the National Health Insurance Service claims data. Results: Among 10,818 patients with AIS (male, 59%; mean age, 68±13 years), 947 (8.8%) experienced 1,224 episodes of major GIB over a median follow-up duration of 3.1 years. Remarkably, 20% of 947 patients experienced multiple episodes of major GIB. The incidence peaked in the first month after AIS, reaching 19.2 per 100 person-years, and gradually decreased to approximately one-sixth of this rate by the 2nd year with subsequent stabilization. Multivariable analysis identified the following predictors of major GIB: anemia, estimated glomerular filtration rate <60 mL/min/1.73 m2 , and a 3-month modified Rankin Scale score of ≥4. Conclusion Patients with AIS are susceptible to major GIB, particularly in the first month after the onset of AIS, with the risk decreasing thereafter. Implementing preventive strategies may be important, especially for patients with anemia and impaired renal function at stroke onset and those with a disabling stroke.

Background: The 16S rRNA-targeted next-generation sequencing (NGS) has been widely used as the primary tool for microbiome analysis. However, whether the sequenced microbial diversity absolutely represents the original sample composition remains unclear. This study aimed to evaluate whether 16S rRNA gene-targeted NGS accurately captures bacterial community composition. Methods: Mock communities were constructed using equal amounts of DNA from 18 bacterial strains in three formats: genomic DNA, recombinant plasmids, and polymerase chain reaction (PCR) templates. The V3V4 region of the 16S rRNA gene was amplified and sequenced using the Illumina MiSeq. Results: Data regression analysis revealed that the recombinant plasmid produced more accurate and precise correlation curve than that by the gDNA and PCR products, with a slope closest to 1 (1.0082) and the highest R² value (0.9975). Despite the same input amount of bacterial DNA, the NGS read distribution varied across all three mock communities. Using multiple regression analysis, we found that the guanine-cytosine (GC) content of the V3V4 region, 16S rRNA gene, size of gDNA, and copy number of 16S rRNA were significantly associated with the NGS output of each bacterial species. Conclusion This study demonstrated that recombinant plasmids are the preferred option for quality control and that NGS output is biased owing to certain bacterial characteristics, such as %GC content, gDNA size, and 16S rRNA gene copy number. Further research is required to develop a system that compensates for NGS process biases using mock communities.

Background: The 16S rRNA-targeted next-generation sequencing (NGS) has been widely used as the primary tool for microbiome analysis. However, whether the sequenced microbial diversity absolutely represents the original sample composition remains unclear. This study aimed to evaluate whether 16S rRNA gene-targeted NGS accurately captures bacterial community composition. Methods: Mock communities were constructed using equal amounts of DNA from 18 bacterial strains in three formats: genomic DNA, recombinant plasmids, and polymerase chain reaction (PCR) templates. The V3V4 region of the 16S rRNA gene was amplified and sequenced using the Illumina MiSeq. Results: Data regression analysis revealed that the recombinant plasmid produced more accurate and precise correlation curve than that by the gDNA and PCR products, with a slope closest to 1 (1.0082) and the highest R² value (0.9975). Despite the same input amount of bacterial DNA, the NGS read distribution varied across all three mock communities. Using multiple regression analysis, we found that the guanine-cytosine (GC) content of the V3V4 region, 16S rRNA gene, size of gDNA, and copy number of 16S rRNA were significantly associated with the NGS output of each bacterial species. Conclusion This study demonstrated that recombinant plasmids are the preferred option for quality control and that NGS output is biased owing to certain bacterial characteristics, such as %GC content, gDNA size, and 16S rRNA gene copy number. Further research is required to develop a system that compensates for NGS process biases using mock communities.

Background: and Purpose Treatments for neuromyelitis optica spectrum disorder (NMOSD) such as eculizumab, ravulizumab, satralizumab, and inebilizumab have significantly advanced relapse prevention, but they remain expensive. Rituximab is an off-label yet popular alternative that offers a cost-effective solution, but its real-world efficacy needs better quantification for guiding the application of newer approved NMOSD treatments (ANTs). This study aimed to determine real-world rituximab failure rates to anticipate the demand for ANTs and aid in resource allocation. Methods: We conducted a nationwide retrospective study involving 605 aquaporin-4-antibody-positive NMOSD patients from 22 centers in South Korea that assessed the efficacy and safety of rituximab over a median follow-up of 47 months. Results: The 605 patients treated with rituximab included 525 (87%) who received continuous therapy throughout the follow-up period (median=47 months, interquartile range=15–87 months). During this period, 117 patients (19%) experienced at least 1 relapse. Notably, 68 of these patients (11% of the total cohort) experienced multiple relapses or at least 1 severe relapse.Additionally, 2% of the patients discontinued rituximab due to adverse events, which included severe infusion reactions, neutropenia, and infections. Conclusions This study has confirmed the efficacy of rituximab in treating NMOSD, as evidenced by an 87% continuation rate among patients over a 4-year follow-up period. Nevertheless, the occurrence of at least one relapse in 19% of the cohort, including 11% who experienced multiple or severe relapses, and a 2% discontinuation rate due to adverse events highlight the urgent need for alternative therapeutic options.

Background: The 16S rRNA-targeted next-generation sequencing (NGS) has been widely used as the primary tool for microbiome analysis. However, whether the sequenced microbial diversity absolutely represents the original sample composition remains unclear. This study aimed to evaluate whether 16S rRNA gene-targeted NGS accurately captures bacterial community composition. Methods: Mock communities were constructed using equal amounts of DNA from 18 bacterial strains in three formats: genomic DNA, recombinant plasmids, and polymerase chain reaction (PCR) templates. The V3V4 region of the 16S rRNA gene was amplified and sequenced using the Illumina MiSeq. Results: Data regression analysis revealed that the recombinant plasmid produced more accurate and precise correlation curve than that by the gDNA and PCR products, with a slope closest to 1 (1.0082) and the highest R² value (0.9975). Despite the same input amount of bacterial DNA, the NGS read distribution varied across all three mock communities. Using multiple regression analysis, we found that the guanine-cytosine (GC) content of the V3V4 region, 16S rRNA gene, size of gDNA, and copy number of 16S rRNA were significantly associated with the NGS output of each bacterial species. Conclusion This study demonstrated that recombinant plasmids are the preferred option for quality control and that NGS output is biased owing to certain bacterial characteristics, such as %GC content, gDNA size, and 16S rRNA gene copy number. Further research is required to develop a system that compensates for NGS process biases using mock communities.

Background: The 16S rRNA-targeted next-generation sequencing (NGS) has been widely used as the primary tool for microbiome analysis. However, whether the sequenced microbial diversity absolutely represents the original sample composition remains unclear. This study aimed to evaluate whether 16S rRNA gene-targeted NGS accurately captures bacterial community composition. Methods: Mock communities were constructed using equal amounts of DNA from 18 bacterial strains in three formats: genomic DNA, recombinant plasmids, and polymerase chain reaction (PCR) templates. The V3V4 region of the 16S rRNA gene was amplified and sequenced using the Illumina MiSeq. Results: Data regression analysis revealed that the recombinant plasmid produced more accurate and precise correlation curve than that by the gDNA and PCR products, with a slope closest to 1 (1.0082) and the highest R² value (0.9975). Despite the same input amount of bacterial DNA, the NGS read distribution varied across all three mock communities. Using multiple regression analysis, we found that the guanine-cytosine (GC) content of the V3V4 region, 16S rRNA gene, size of gDNA, and copy number of 16S rRNA were significantly associated with the NGS output of each bacterial species. Conclusion This study demonstrated that recombinant plasmids are the preferred option for quality control and that NGS output is biased owing to certain bacterial characteristics, such as %GC content, gDNA size, and 16S rRNA gene copy number. Further research is required to develop a system that compensates for NGS process biases using mock communities.

Background: and Purpose Previous research on patients with acute ischemic stroke (AIS) has shown a 0.5% incidence of major gastrointestinal bleeding (GIB) requiring blood transfusion during hospitalization. The existing literature has insufficiently explored the long-term incidence in this population despite the decremental impact of GIB on stroke outcomes. Methods: We analyzed the data from a cohort of patients with AIS admitted to 14 hospitals as part of a nationwide multicenter prospective stroke registry between 2011 and 2013. These patients were followed up for up to 6 years. The occurrence of major GIB events, defined as GIB necessitating at least two units of blood transfusion, was tracked using the National Health Insurance Service claims data. Results: Among 10,818 patients with AIS (male, 59%; mean age, 68±13 years), 947 (8.8%) experienced 1,224 episodes of major GIB over a median follow-up duration of 3.1 years. Remarkably, 20% of 947 patients experienced multiple episodes of major GIB. The incidence peaked in the first month after AIS, reaching 19.2 per 100 person-years, and gradually decreased to approximately one-sixth of this rate by the 2nd year with subsequent stabilization. Multivariable analysis identified the following predictors of major GIB: anemia, estimated glomerular filtration rate <60 mL/min/1.73 m2 , and a 3-month modified Rankin Scale score of ≥4. Conclusion Patients with AIS are susceptible to major GIB, particularly in the first month after the onset of AIS, with the risk decreasing thereafter. Implementing preventive strategies may be important, especially for patients with anemia and impaired renal function at stroke onset and those with a disabling stroke.