ObjectiveTo systematically evaluate the content differences of 4 components in Leonuri Herba granules， reveal the quality fluctuation patterns of products from the same and different manufacturers， providing scientific basis for the optimization of production process and quality control. MethodsHigh performance liquid chromatography-diode array detector-charged aerosol detector（HPLC-DAD-CAD） was employed to determine the contents of 4 components（syringic acid， leonurine hydrochloride， ferulic acid， and stachydrine hydrochloride） in samples from 19 manufacturers（53 batches， 159 boxes）. Additionally， fingerprint profiles were constructed， and the fingerprint dissimilarity（P_S） and relative standard deviation（RSD） of different samples from the same manufacturer were calculated. A principal component analysis（PCA） model was established with P_S and the RSD values of the 4 components as variables to classify the manufacturers. Finally， samples from 5 manufacturers（M1-M5） covering three consistency groups were selected to calculate three quality consistency parameters， namely intra-batch consistency（P_A）， inter-batch consistency（P_B）， and P_S. Then， PCA was performed with P_A， P_B， and P_S of these 5 manufacturers as variables. ResultsThe average total content of the 4 index components per bag across the 19 manufacturers ranged from 41.10 mg to 97.54 mg. Among them， the content of stachydrine hydrochloride（a pharmacopoeial quality control component） was 32.46-72.70 mg per bag， all meeting the requirements of the 2025 edition of the Pharmacopoeia of the People's Republic of China， with RSD of 1.7%-17.1%. The content ranges of the other 3 components were as follows：syringic acid of 1.43-41.92 mg per bag， leonurine hydrochloride of 0.67-11.85 mg per bag， and ferulic acid of 0.11-3.81 mg per bag. Notably， leonurine hydrochloride exhibited the most significant content fluctuation among samples from the same manufacturer（RSD of 4.8%-59.2%）. PCA results showed that the 19 manufacturers could be classified into 3 categories. Samples from 8 manufacturers（M2， M6， M7， M8， M10， M15， M17， M18） demonstrated relatively high consistency， five manufacturers（M3， M9， M12， M13， M14） showed moderate consistency， six manufacturers（M1， M4， M5， M11， M16， M19） exhibited low consistency. The two methods yielded consistent classification results for the 5 representative manufacturers， verifying the reliability of the proposed method. Among these， manufacturer M2 showed the best quality consistency and the highest total content of indicator components among M1-M5. ConclusionThe HPLC-DAD-CAD multi-detector hyphenation technology established in this study enables the accurate detection of 4 components in Leonuri Herba granules. Significant differences in the total content of these four components are observed among products from 19 manufacturers. The application of 2 consistency evaluation methods combined with PCA can effectively classify their consistency into 3 categories， and the classification results of the 2 methods are highly consistent. This study provides scientific basis for the process optimization and quality standard improvement of Leonuri Herba granules.

ObjectiveTo systematically evaluate the content differences of 4 components in Leonuri Herba granules， reveal the quality fluctuation patterns of products from the same and different manufacturers， providing scientific basis for the optimization of production process and quality control. MethodsHigh performance liquid chromatography-diode array detector-charged aerosol detector（HPLC-DAD-CAD） was employed to determine the contents of 4 components（syringic acid， leonurine hydrochloride， ferulic acid， and stachydrine hydrochloride） in samples from 19 manufacturers（53 batches， 159 boxes）. Additionally， fingerprint profiles were constructed， and the fingerprint dissimilarity（P_S） and relative standard deviation（RSD） of different samples from the same manufacturer were calculated. A principal component analysis（PCA） model was established with P_S and the RSD values of the 4 components as variables to classify the manufacturers. Finally， samples from 5 manufacturers（M1-M5） covering three consistency groups were selected to calculate three quality consistency parameters， namely intra-batch consistency（P_A）， inter-batch consistency（P_B）， and P_S. Then， PCA was performed with P_A， P_B， and P_S of these 5 manufacturers as variables. ResultsThe average total content of the 4 index components per bag across the 19 manufacturers ranged from 41.10 mg to 97.54 mg. Among them， the content of stachydrine hydrochloride（a pharmacopoeial quality control component） was 32.46-72.70 mg per bag， all meeting the requirements of the 2025 edition of the Pharmacopoeia of the People's Republic of China， with RSD of 1.7%-17.1%. The content ranges of the other 3 components were as follows：syringic acid of 1.43-41.92 mg per bag， leonurine hydrochloride of 0.67-11.85 mg per bag， and ferulic acid of 0.11-3.81 mg per bag. Notably， leonurine hydrochloride exhibited the most significant content fluctuation among samples from the same manufacturer（RSD of 4.8%-59.2%）. PCA results showed that the 19 manufacturers could be classified into 3 categories. Samples from 8 manufacturers（M2， M6， M7， M8， M10， M15， M17， M18） demonstrated relatively high consistency， five manufacturers（M3， M9， M12， M13， M14） showed moderate consistency， six manufacturers（M1， M4， M5， M11， M16， M19） exhibited low consistency. The two methods yielded consistent classification results for the 5 representative manufacturers， verifying the reliability of the proposed method. Among these， manufacturer M2 showed the best quality consistency and the highest total content of indicator components among M1-M5. ConclusionThe HPLC-DAD-CAD multi-detector hyphenation technology established in this study enables the accurate detection of 4 components in Leonuri Herba granules. Significant differences in the total content of these four components are observed among products from 19 manufacturers. The application of 2 consistency evaluation methods combined with PCA can effectively classify their consistency into 3 categories， and the classification results of the 2 methods are highly consistent. This study provides scientific basis for the process optimization and quality standard improvement of Leonuri Herba granules.

Background/Aims: Liver transplantation (LT) following total hepatectomy is a life-saving treatment for hepatocellular carcinoma (HCC). The HCC recurrence after LT hinders the effectiveness of the procedure. The objective of this study is to develop a pre-operative risk stratification model based on a liquid biopsy. Methods: We conducted a comprehensive multi-omics study of 260 HCC patients from three centers, including clinical data, low-coverage whole-genome sequencing of cell-free DNA (cfDNA) from plasma, as well as whole-exome, single-nucleus RNA, and spatial transcriptomics from matched tumor and non-tumor tissues. Results: We identified cfDNA-derived copy number alteration (CNA) signatures associated with post-transplant recurrence. By integrating cfDNA-derived CNA profiles with single-cell transcriptomic data, we traced recurrence-associated cfDNA to a distinct subpopulation of malignant cells within the primary tumor. These cells were embedded in a pro-metastatic microenvironment of specialized endothelial subtypes and cancer-associated fibroblasts. Notably, most recurrence-associated lesions were detectable in cfDNA prior to liver transplantation (LT). Building on these insights, we developed the ZJU Criteria based on CNA fragments and tumor markers, a pre-LT risk prediction tool that integrates conventional clinical factors with cfDNA-derived CNA signatures, and validated it using internal and independent external cohorts. Conclusion Our findings suggest that post-transplant recurrence commonly originates from advanced subclones that emerge late during tumor evolution. The ZJU Criteria provides an accurate, non-invasive strategy that significantly improves pre-LT risk stratification and clinical decision-making for patients with HCC.

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.

PURPOSE: To evaluate the diagnostic accuracy of the observational chart for traumatic limb swelling (OCTLS) for osteofascial compartment syndrome (OCS). METHODS: This was a descriptive-longitudinal study. Data of 316 patients who underwent surgical treatment for tibial fractures in our department from January 2015 to December 2023 were collected. Patients with Gustilo type II or higher open fractures, vascular injury, or bilateral fractures were excluded from the study. Two groups of double-blinded investigators independently assessed patients for the presence of OCS using 2 distinct diagnostic methods. Three senior orthopedic trauma surgeons evaluated patients with post-fracture calf swelling for OCS and the need for fasciotomy based on clinical signs and their extensive clinical experience. Subsequently, fasciotomy was performed according to their judgment, followed by postoperative examination of muscle and soft tissue conditions. Additionally, a follow-up evaluation was conducted to assess for complications such as ischemic muscle contracture. Another 3 trained researchers used OCTLS to grade swelling severity and determine the need for fasciotomy. The final diagnostic gold standard of OCS was determined by referring to whether there was escape of muscles at fasciotomy and/or color change in the muscles or muscle necrosis intraoperatively, and neurological abnormality or contracture at the last follow-up. The results of the 2 diagnostic methods were compared with the final diagnostic result. Kappa consistency test, paired χ² test (McNemar test), and receiver operating characteristic curve were used to evaluate the diagnostic efficacy of the 2 diagnostic methods. RESULTS: Of the 316 patients, 211 were finally included in the study, including 160 males and 51 females, with an average follow-up time of (14.5 ± 2.7) months. Among the 211 patients with tibial fracture-associated swelling, 42 were definitively diagnosed with OCS. Based on clinical symptoms and signs judgment, among the 65 fasciotomy patients, 38 were confirmed as correct, while among the 146 non-fasciotomy patients, 4 developed ischemic muscle contractures. Based on the OCTLS for assessment, fasciotomy was correctly recommended in 36 out of 43 cases, while 6 out of 168 non-fasciotomy patients developed OCS. Compared to the use of the gold standard, clinical signs judgment showed moderate consistency (McNemar's test p < 0.001, Kappa = 0.618, p < 0.001), whereas OCTLS demonstrated strong agreement (McNemar's test p = 1.000, Kappa = 0.808, p < 0.001). Receiver operating characteristic analysis revealed higher diagnostic accuracy for OCTLS (area under curve = 0.908, 95% CI: 0.843 - 0.972) compared to clinical signs judgment (area under curve = 0.872, 95% CI: 0.812 - 0.933). OCTLS achieved superior accuracy (93.8% vs. 85.3%, χ² = 8.221, p < 0.001) and a lower fasciotomy rate (20.4% vs. 30.8%, χ² = 6.023, p = 0.014). CONCLUSION Compared to clinical signs judgment, OCTLS significantly reduces unnecessary fasciotomy, improves diagnostic accuracy for OCS, and enables non-invasive, dynamic, and quantitative assessment, making it a valuable tool for clinical practice.
Humans ; Compartment Syndromes/etiology* ; Male ; Female ; Adult ; Tibial Fractures/surgery* ; Middle Aged ; Fasciotomy ; Edema/etiology* ; Longitudinal Studies ; Aged ; Young Adult

Varicocele (VC) is a common cause of male infertility, yet there is a lack of molecular information for VC-associated male infertility. This study investigated alterations in the seminal plasma metabolomic and lipidomic profiles of infertile male VC patients. Twenty infertile males with VC and twenty-three age-matched healthy controls (HCs) were recruited from Peking Union Medical College Hospital (Beijing, China) between October 2019 and April 2021. Untargeted metabolite and lipid profiles from seminal plasma were analyzed using mass spectrometry. Four hundred and seventy-six metabolites and seventeen lipids were significantly different in infertile male VC patients compared to HCs. The top enriched pathways among these significantly different metabolites are protein digestion and absorption, aminoacyl-transfer RNA (tRNA) biosynthesis, and biosynthesis of amino acids. Different key lipid species, including triglyceride (TG), diacylglycerol (DG), ceramides (Cer), and phosphatidylserine (PS), varied between VC and HC groups. The distinct metabolites and lipids were moderately correlated. DL-3-phenyllactic acid is a potential diagnostic biomarker for VC-related male infertility (area under the curve [AUC] = 0.893), positively correlating with sperm count, concentration, and motility. Furthermore, DL-3-phenyllactic acid is the only metabolite shared by all four comparisons (VC vs HC, VC-induced oligoasthenospermia [OAS] vs VC-induced asthenospermia [AS], OAS vs HC, and AS vs HC). DL-3-phenyllactic acid significantly decreased in OAS than AS. Metabolite-targeting gene analysis revealed carbonic anhydrase 9 (CA9) might be the strongest candidate associated with the onset and severity of VC. The seminal plasma metabolite and lipid profiles of infertile males with VC differ significantly from those of HCs. DL-3-phenyllactic acid could be a promising biomarker.
Humans ; Male ; Varicocele/complications* ; Infertility, Male/etiology* ; Semen/metabolism* ; Lipidomics ; Adult ; Metabolomics ; Case-Control Studies ; Biomarkers/metabolism*

OBJECTIVES: To explore the measures to improve the follow-up rate of preterm infants after discharge, and to evaluate the effectiveness of these measures using quality improvement methodology. METHODS: The follow-up status of preterm infants discharged from March to May 2017 was used as the baseline before quality improvement, and a specific quality improvement goal for the follow-up rate was proposed. The Pareto chart was used to analyze the causes of follow-up failure, and a key driver diagram was constructed based on the links involved in improving follow-up rate. The causes of failure were analyzed to determine the key links and intervention measures for quality improvement, and the follow-up rate was monitored weekly using a control chart until the quality improvement goal was achieved. RESULTS: The follow-up rate of preterm infants after discharge was 57.92% (117/202) at baseline before quality improvement, and the quality improvement goal was set to increase the follow-up rate of preterm infants from baseline to more than 80% within 12 months. The Pareto chart analysis showed that the main causes of follow-up failure were deficiencies in follow-up file management and irregular follow-up times (33.70%, 31/92), insufficient follow-up education and poor communication (25.00%, 23/92), and the inability to meet the diverse needs of parents (18.48%, 17/92). Based on the key links for quality improvement and the main causes of follow-up failure, the following intervention measures were adopted: (1) strengthen follow-up publicity and education; (2) build a follow-up team; and (3) establish a follow-up platform and system. The control chart indicated that with the implementation of the above intervention measures, the weekly follow-up rate increased to 74.09% (306/413) in July 2017 and 83.09% (511/615) in December 2017, finally achieving the quality improvement goal. During the COVID-19 pandemic, the follow-up rate of preterm infants fluctuated between 23.54% (460/1 954) and 70.97% (1 931/2 721), and subsequently, it returned to pre-pandemic levels starting in February 2023. CONCLUSIONS The application of quality improvement methodology can help to formulate intervention measures based on the main causes of follow-up failure, thereby improving the follow-up rate of preterm infants after discharge. This quality improvement method is feasible and practical and thus holds promise for clinical application.
Humans ; Quality Improvement ; Infant, Premature ; Infant, Newborn ; Patient Discharge ; Follow-Up Studies ; Female ; Male

OBJECTIVE: Blood culture remains the gold standard for diagnosing bloodstream infections. Clinical laboratories must ensure the quality of blood culture processes from receipt to obtaining definitive results. We examined laboratory analytical indicators associated with positive blood culture results. METHODS: Blood cultures collected from Peking Union Medical College Hospital between January 1, 2020, and December 31, 2022, were retrospectively analyzed. The mode of transportation (piping logistics delivery vs. staff), source of blood cultures (outpatient/emergency department vs. inpatient department), rotation of personnel, and time of reception (8:00-19:59 vs. 20:00-07:59) were compared between blood culture-positive and -negative results. RESULTS: Between 2020 and 2022, the total positive rate of blood culture was 8.07%. The positive rate of blood cultures in the outpatient/emergency department was significantly higher than that in the inpatient department (12.46% vs. 5.83%; P < 0.0001). The time-to-detection of blood cultures was significantly affected by the delivery mode and personnel rotation. The blood culture positive rate of the total pre-analytical time within 1 h was significantly higher than that within 1-2 h or > 2 h ( P < 0.0170). CONCLUSION Laboratory analytical indicators such as patient source, transportation mode, and personnel rotation significantly impacted the positive detection rate or time of blood culture.
Blood Culture/statistics & numerical data* ; Humans ; Retrospective Studies ; Emergency Service, Hospital/statistics & numerical data*

OBJECTIVE: This study aimed to explore the association between body mass index (BMI) and mortality based on the 10-year population-based multicenter prospective study. METHODS: A general population-based multicenter prospective study was conducted at four sites in rural China between 2013 and 2023. Multivariate Cox proportional hazards models and restricted cubic spline analyses were used to assess the association between BMI and mortality. Stratified analyses were performed based on the individual characteristics of the participants. RESULTS: Overall, 19,107 participants with a sum of 163,095 person-years were included and 1,910 participants died. The underweight (< 18.5 kg/m ²) presented an increase in all-cause mortality (adjusted hazards ratio [ aHR] = 2.00, 95% confidence interval [ CI]: 1.66-2.41), while overweight (≥ 24.0 to < 28.0 kg/m ²) and obesity (≥ 28.0 kg/m ²) presented a decrease with an aHR of 0.61 (95% CI: 0.52-0.73) and 0.51 (95% CI: 0.37-0.70), respectively. Overweight ( aHR = 0.76, 95% CI: 0.67-0.86) and mild obesity ( aHR = 0.72, 95% CI: 0.59-0.87) had a positive impact on mortality in people older than 60 years. All-cause mortality decreased rapidly until reaching a BMI of 25.7 kg/m ² ( aHR = 0.95, 95% CI: 0.92-0.98) and increased slightly above that value, indicating a U-shaped association. The beneficial impact of being overweight on mortality was robust in most subgroups and sensitivity analyses. CONCLUSION This study provides additional evidence that overweight and mild obesity may be inversely related to the risk of death in individuals older than 60 years. Therefore, it is essential to consider age differences when formulating health and weight management strategies.
Humans ; Body Mass Index ; China/epidemiology* ; Male ; Female ; Middle Aged ; Prospective Studies ; Rural Population/statistics & numerical data* ; Aged ; Follow-Up Studies ; Adult ; Mortality ; Cause of Death ; Obesity/mortality* ; Overweight/mortality*