OBJECTIVE To form an expert consensus on the clinical application of parenteral direct thrombin inhibitors （DTIs） in patients during the perioperative period. METHODS Led by Sichuan Academy of Medical Sciences & Sichuan Provincial People’s Hospital （the Affiliated Hospital of UESTC）， a multidisciplinary working group was established. Through literature review and the Delphi method， clinical questions related to the rational perioperative use of parenteral DTIs were identified. A structured design was adopted using the “Population-Intervention-Comparison-Outcome” framework； systematic searches were conducted in CNKI， Medline， Embase and other databases. Relevant evidence from randomized controlled trials and cohort studies was included and synthesized. Evidence quality was assessed using the Grades of Recommendations Assessment，Development and Evaluation （GRADE） approach， and recommendations were formulated through multiple rounds of Delphi surveys and expert consensus meetings. RESULTS &CONCLUSIONS Seven recommendations （each with an expert consensus rate exceeding 90%） on the use of parenteral DTIs in perioperative patients were developed. These recommendations specify drug selection， dosing ranges， key monitoring points， and safety management strategies for parenteral DTIs in various scenarios， including the perioperative period of ventricular assist device implantation， the perioperative period of cardiac surgery， perioperative patients with lower-extremity atherosclerotic disease， the perioperative period of percutaneous coronary intervention in patients with acute coronary syndrome， the perioperative period of carotid artery stenting in patients with carotid stenosis， the perioperative period of patients with right heart thrombosis， and patients who develop related thrombosis and dysfunction after a central venous catheter insertion. In addition， warning and management pathways for perioperative bleeding and thrombotic events were proposed. This expert consensus， which is formulated based on the best available evidence， provides evidence-based guidance for standardized and individualized use of parenteral DTIs in perioperative period.

OBJECTIVE: To evaluate the efficacy and safety of Shexiang Tongxin Dropping Pill (STDP) in treating stable angina patients with phlegm-heat and blood-stasis syndrome by exercise duration and metabolic equivalents. METHODS: This multicenter, randomized, double-blind, placebo-controlled clinical trial enrolled stable angina patients with phlegm-heat and blood-stasis syndrome from 22 hospitals. They were randomized 1:1 to STDP (35 mg/pill, 6 pills per day) or placebo for 56 days. The primary outcome was the exercise duration and metabolic equivalents (METs) assessed by the standard Bruce exercise treadmill test after 56 days of treatment. The secondary outcomes included the total angina symptom score, Chinese medicine (CM) symptom scores, Seattle Angina Questionnaire (SAQ) scores, changes in ST-T on electrocardiogram and adverse events (AEs). RESULTS: This trial enrolled 309 patients, including 155 and 154 in the STDP and placebo groups, respectively. STDP significantly prolonged exercise duration with an increase of 51.0 s, compared to a decrease of 12.0 s with placebo (change rate: -11.1% vs. 3.2%, P<0.01). The increase in METs was significantly greater in the STDP group than in the placebo group (change: -0.4 vs. 0.0, change rate: -5.0% vs. 0.0%, P<0.01). The improvement of total angina symptom scores (25.0% vs. 0.0%), CM symptom scores (38.7% vs. 11.8%), reduction of nitroglycerin consumption (100.0% vs. 11.3%), and all domains of SAQ, were significantly greater with STDP than placebo (all P<0.01). The changes in Q-T intervals at 28 and 56 days from baseline were similar between the two groups (both P>0.05). Twenty-five participants (16.3%) with STDP and 16 (10.5%) with placebo experienced AEs (P=0.131), with no serious AEs observed. CONCLUSION STDP could improve exercise tolerance in patients with stable angina and phlegm-heat and blood stasis syndrome, with a favorable safety profile. (Registration No. ChiCTR-IPR-15006020).
Humans ; Double-Blind Method ; Drugs, Chinese Herbal/adverse effects* ; Male ; Female ; Middle Aged ; Angina, Stable/physiopathology* ; Aged ; Syndrome ; Treatment Outcome ; Placebos ; Tablets

Although a single nucleotide polymorphism for N-acetyltransferase 10 (NAT10) has been identified in patients with early-onset stroke, the role of NAT10 in ischemic injury and the related underlying mechanisms remains elusive. Here, we provide evidence that NAT10, the only known RNA N4-acetylcytidine (ac4C) modification "writer", is increased in the damaged cortex of patients with acute ischemic stroke and the peri-infarct cortex of mice subjected to photothrombotic (PT) stroke. Pharmacological inhibition of NAT10 with remodelin on Days 3-7 post-stroke or astrocytic depletion of NAT10 via targeted virus attenuates ischemia-induced infarction and improves functional recovery in PT mice. Mechanistically, NAT10 enhances ac4C acetylation of the inflammatory cytokine tissue inhibitor of metalloproteinase 1 (Timp1) mRNA transcript, which increases TIMP1 expression and results in the accumulation of microtubule-associated protein 1 light chain 3 (LC3) and progression of astrocyte autophagy. These findings demonstrate that NAT10 regulates astrocyte autophagy by targeting Timp1 ac4C after stroke. This study highlights the critical role of ac4C in the regulation of astrocyte autophagy and proposes a promising strategy to improve post-stroke outcomes via NAT10 inhibition.

Objective To explore the relationship between bedtime procrastination and fear of missing out and the intervention effect of aerobic exercise on bedtime procrastination,so as to provide a theoretical basis and practical reference for remedying bedtime procrastination.Methods Totally 988 students were selected through random sampling and then surveyed with the bedtime procrastination scale and the fear of missing out scale.Correlation and regression analyses were performed to explore the relationship between bedtime procrastination and fear of missing out.A total of 36 students were recruited from the 988 students to participate in the exercise intervention and they were assigned into an exercise group and a control group by the random number table method,with 18 students in each group.The exercise group performed aerobic exercise for 12 weeks,while the control group maintained daily activities.The participants' scores on the bedtime procrastination scale and the fear of missing out scale were recorded before and after the intervention and compared.Results The fear of missing out was positively correlated with bedtime procrastination among college students(r=0.214,P<0.001),and it was an important predictive factor for bedtime procrastination(β=0.241,P<0.001).After the intervention,the scores of bedtime procrastination scale decreased in the exercise group(t=2.277,P=0.036),while there was no significant difference in the scores of the control group before and after intervention(t=-0.787,P=0.442).Conclusions A high level of fear of missing out indicates severe bedtime procrastination.And 12-week exercise intervention could remedy bedtime procrastination.
Humans ; Fear ; Exercise ; Male ; Female ; Procrastination ; Young Adult ; Cross-Sectional Studies ; Students/psychology* ; Adult ; Surveys and Questionnaires ; Adolescent

Emodin is a hydroxyanthraquinone compound that is widely distributed and has multiple pharmacological activities, including anti-diarrheal, anti-inflammatory, and liver-protective effects. Research indicates that emodin may be one of the main components responsible for inducing hepatotoxicity. However, studies on the mechanisms of liver injury are relatively limited, particularly those related to bile acids(BAs) metabolism. This study aims to systematically investigate the effects of different dosages of emodin on BAs metabolism, providing a basis for the safe clinical use of traditional Chinese medicine(TCM)containing emodin. First, this study evaluated the safety of repeated administration of different dosages of emodin over a 5-week period, with a particular focus on its impact on the liver. Next, the composition and content of BAs in serum and liver were analyzed. Subsequently, qRT-PCR was used to detect the mRNA expression of nuclear receptors and transporters related to BAs metabolism. The results showed that 1 g·kg~(-1) emodin induced hepatic damage, with bile duct hyperplasia as the primary pathological manifestation. It significantly increased the levels of various BAs in the serum and primary BAs(including taurine-conjugated and free BAs) in the liver. Additionally, it downregulated the mRNA expression of farnesoid X receptor(FXR), retinoid X receptor(RXR), and sodium taurocholate cotransporting polypeptide(NTCP), and upregulated the mRNA expression of cholesterol 7α-hydroxylase(CYP7A1) in the liver. Although 0.01 g·kg~(-1) and 0.03 g·kg~(-1) emodin did not induce obvious liver injury, they significantly increased the level of taurine-conjugated BAs in the liver, suggesting a potential interference with BAs homeostasis. In conclusion, 1 g·kg~(-1) emodin may promote the production of primary BAs in the liver by affecting the FXR-RXR-CYP7A1 pathway, inhibit NTCP expression, and reduce BA reabsorption in the liver, resulting in BA accumulation in the peripheral blood. This disruption of BA homeostasis leads to liver injury. Even doses of emodin close to the clinical dose can also have a certain effect on the homeostasis of BAs. Therefore, when using traditional Chinese medicine or formulas containing emodin in clinical practice, it is necessary to regularly monitor liver function indicators and closely monitor the risk of drug-induced liver injury.
Emodin/administration & dosage* ; Bile Acids and Salts/metabolism* ; Animals ; Male ; Liver/injuries* ; Chemical and Drug Induced Liver Injury/genetics* ; Drugs, Chinese Herbal/adverse effects* ; Humans ; Rats, Sprague-Dawley ; Mice ; Rats

Objective:To perform routine plasma test, SARS-CoV-2 nucleic acid test, and respiratory pathogenic microorganism nucleic acid test on plasma samples collected from 1 040 healthy plasma donors in winter.Methods:Plasma samples were collected from 1 040 healthy plasma donors at Yunmeng Plasma Collection Station in the winter of 2020. Routine plasma test, HBV/HCV/HIV nucleic acid test, SARS-CoV-2 nucleic acid test, and 22 respiratory pathogenic microorganism nucleic acid test were performed to analyze the quality of blood plasmas.Results:All plasma samples were qualified in the routine tests, meeting the requirements of the Chinese Pharmacopoeia, and tested negative for SARS-CoV-2 nucleic acid. Respiratory pathogenic microorganism nucleic acids were detected in 29 samples with a positive rate of 2.79% (29/1 040). There were 21 cases of simple virus infections, including 17 cases of coronavirus subtype infection, three cases of parainfluenza virus type 2 infection, and one case of human bocavirus infection. Eight cases were mixed infections of viruses and bacteria, four of which were viral infection combined with Bordetella pertussis. The 29 positive samples were collected from people of different age groups, including two from 31-40 years old (1.96%, 2/102 ), three from 41-50 years old (1.59%, 3/189), five from 51-55 years old (1.94%, 5/257), and 19 from 56-60 years old (4.59%, 19/414). Samples from the people aged 56-60 years accounted for the most (39.81%, 414/1 040), as well as the infection rate in this age group. Conclusions:In autumn and winter, respiratory pathogenic microorganism nucleic acid test should be performed when collecting plasma samples from donors aged 56-60 years in addition to meeting the requirements of the Chinese Pharmacopoeia. It is also suggested to conduct respiratory pathogenic microorganism nucleic acid test on pooled plasma and blood products.

Objective:To analyze the detection status and its influencing factors of ovarian-adnexal masses in the physical examination population based on the Ovarian-Adnexal Imaging Reporting and Data System (O-RADS) of the American College of Radiology.Methods:This cross-sectional study retrospectively analyzed the clinical data of 24 316 physical examination participants who underwent gynecological color Doppler ultrasound examinations at the Health Management Center of Tianjin Medical University General Hospital from January to December 2021. The subjects were classified and followed-up according to O-RADS, and the detection rate and malignancy rate of ovarian-adnexal masses in different classifications were compared. According to O-RADS classification criteria, the physical examination population were divided into healthy control group (without ovarian-adnexal masses and O-RADS 1 class, 23 188 cases), benign group (O-RADS 2 class, 946 cases) and malignant group (O-RADS 3-5 class, 182 cases). The basic information of the three groups were compared, including age, body mass index (BMI), menopausal status, marital status, smoking history, drinking history, physical exercise, complete blood count, blood glucose, blood lipids, tumor markers, etc. The logistic regression was used to analyze the factors affecting the detection of ovarian-adnexal masses.Results:A total of 24 316 individuals were included, 1 678 with ovario-adnexal masses were screened, among the cases, there were 550 normal premenopausal ovaries (32.78%), and 1 128 cases were confirmed with pathological masses (67.22%). Of the 318 cases with follow-up records, the malignancy rate for O-RADS 4 class was 50%, and for O-RADS 5 class, it was 100%, according to the follow-up results. The age ( OR=1.320, 95% CI: 1.055-1.653), BMI ( OR=0.972, 95% CI: 0.954-0.989), carbohydrate antigen 125(CA125) ( OR=1.090, 95% CI: 1.023-1.161), postmenopausal ( OR=0.919, 95% CI: 0.892-0.947) and married and cohabiting ( OR=0.921, 95% CI: 0.895-0.949) were positively correlated with risk of ovarian-adnexal masses (all P0.05). Conclusions:The O-RADS classification system has high application value in evaluating the malignant risk of ovarian-adnexal masses; the age, BMI, CA125 levels, menopausal status, and marital status are significant influencing factors for the detection of ovarian-adnexal masses.

Objective: To analyze the nucleic acid load of human parvovirus B19 in major commercially available blood products in China, including human albumin, human intravenous immunoglobulin, human rabies immunoglobulin and various coagulation factor products, aiming to provide evidence for improving blood product manufacturing processes and quality control of source plasma. Methods: A total of 98 batches of coagulation factor products were tested for human parvovirus B19 nucleic acid using real-time fluorescent quantitative PCR, including 42 batches of human prothrombin complex, 35 batches of human coagulation factor Ⅷ, and 21 batches of human fibrinogen. Additionally, 6 batches of human albumin, 6 batches of human intravenous immunoglobulin, and 38 batches of human rabies immunoglobulin were tested for human parvovirus B19 nucleic acid. Results: Human parvovirus B19 nucleic acid were undetectable in human albumin, human intravenous immunoglobulin and human rabies immunoglobulin. Among the 98 batches of coagulation factor products tested for human parvovirus B19 nucleic acid, B19 nucleic acid reactivity rate was 69.0% (29/42) for human prothrombin complex batches, but nucleic acid concentration were all significantly lower than 10 IU/mL. The reactivity rate of B19 nucleic acid in 35 batches of human coagulation factor Ⅷ was 48.6% (17/35), with nucleic acid concentration all below 10 IU/mL. The reactivity rate of B19 nucleic acid in 21 batches of human fibrinogen was 61.9% (13/21), with nucleic acid concentration all below 10 IU/mL. Conclusion: No human parvovirus B19 has been detected in human albumin, human intravenous immunoglobulin, or human rabies immunoglobulin. Human parvovirus B19 nucleic acid may exist in commercially available coagulation factor products, highlighting the need for enhanced screening of human parvovirus B19 nucleic acid in these products. It is also recommended that B19 viral nucleic acid testing be conducted on source plasma, particularly for coagulation factor products.

Objective: To analyze the nucleic acid load of human parvovirus B19 in major commercially available blood products in China, including human albumin, human intravenous immunoglobulin, human rabies immunoglobulin and various coagulation factor products, aiming to provide evidence for improving blood product manufacturing processes and quality control of source plasma. Methods: A total of 98 batches of coagulation factor products were tested for human parvovirus B19 nucleic acid using real-time fluorescent quantitative PCR, including 42 batches of human prothrombin complex, 35 batches of human coagulation factor Ⅷ, and 21 batches of human fibrinogen. Additionally, 6 batches of human albumin, 6 batches of human intravenous immunoglobulin, and 38 batches of human rabies immunoglobulin were tested for human parvovirus B19 nucleic acid. Results: Human parvovirus B19 nucleic acid were undetectable in human albumin, human intravenous immunoglobulin and human rabies immunoglobulin. Among the 98 batches of coagulation factor products tested for human parvovirus B19 nucleic acid, B19 nucleic acid reactivity rate was 69.0% (29/42) for human prothrombin complex batches, but nucleic acid concentration were all significantly lower than 10 IU/mL. The reactivity rate of B19 nucleic acid in 35 batches of human coagulation factor Ⅷ was 48.6% (17/35), with nucleic acid concentration all below 10 IU/mL. The reactivity rate of B19 nucleic acid in 21 batches of human fibrinogen was 61.9% (13/21), with nucleic acid concentration all below 10 IU/mL. Conclusion: No human parvovirus B19 has been detected in human albumin, human intravenous immunoglobulin, or human rabies immunoglobulin. Human parvovirus B19 nucleic acid may exist in commercially available coagulation factor products, highlighting the need for enhanced screening of human parvovirus B19 nucleic acid in these products. It is also recommended that B19 viral nucleic acid testing be conducted on source plasma, particularly for coagulation factor products.