OBJECTIVE To systematically evaluate the quality of the Heat-clearing and symptom-relieving formula and screen potential marker components that influence the quality of the formula. METHODS The contents of 11 components （calycosin-7- O - β -D-glucoside， ononin， hyperoside， isoquercitrin， baicalin， baicalein， cryptotanshinone， tanshinone Ⅱ A ， tanshinone Ⅰ， senkyunolide A， ferulic acid） in the Heat-clearing and symptom-relieving formula were determined by high-performance liquid chromatography-tandem mass spectrometry （HPLC-MS/MS）. Using the contents of the aforementioned components as variables， cluster analysis （CA）， principal component analysis （PCA）， and orthogonal partial least squares-discriminant analysis （OPLS-DA） were conducted using OriginPro 2024 software and SIMCA 14.1 software； marker components affecting the quality of the Heat-clearing and symptom-relieving formula were then screened based on the criteria of variable importance in the projection （VIP） value＞1 and P ＜0.05. The comprehensive evaluation of 20 batches of samples was carried out using the entropy weight-technique for order preference by similarity to ideal solution（TOPSIS） and grey correlation analysis （GCA） methods. RESULTS The contents of the above 11 components were 7.993-72.866， 4.542-31.228， 727.666-1 901.884， 496.846-1 293.279， 1 995.501-6 779.150， 54.500-241.280， 150.302-304.339， 79.698-189.206， 257.118-682.418， 5.498-21.687， 7.524-26.935 μg/g. CA， PCA and OPLS-DA results showed that 20 batches of samples were grouped into 2 categories. Q1， Q3， Q4， Q7-Q9， Q12， Q15， Q16 were grouped into one category， and the rest were grouped into another category； VIP values of ferulic acid， tanshinone Ⅱ A ， baicalin， cryptotanshinone， calycosin-7- O - β -D-glucoside and ononin were all greater than 1 （ P ＜0.05）. Both the entropy weight-TOPSIS and GCA methods showed that the samples ranked in the top 11 according to the euclidean distance and relative correlation degree were Q2， Q5， Q6， Q10， Q11， Q13， Q14， Q17-Q20. CONCLUSIONS The established HPLC-MS/MS method is rapid， accurate and highly sens itive. Combined with chemical pattern recognition analysis， entropy weight-TOPSIS and GCA methods， this method can be used to evaluate the quality of the Heat-clearing and symptom-relieving formula. Ferulic acid， tanshinone Ⅱ A ， baicalin， cryptotanshinone， calycosin-7- O - β -D-glucoside and ononin may be the marker components that affect the quality of this formula. The overall quality of 11 batches of the Heat-clearing and symptom-relieving formula， including Q17， is relatively superior.

Objective: To investigate the causes and characteristics of immune hemolytic transfusion reactions (HTRs) triggered by anti-E antibodies, so as to provide a scientific reference for guaranteeing clinical blood transfusion safety. Methods: Five patients who experienced HTRs in our hospital from November 2023 to October 2024 were selected as the research subjects. ABO/RhD blood grouping, antibody screening, antibody identification, and the direct antiglobulin test (DAT) were conducted using the column agglutination method. The causes of HTRs in these patients were investigated using multiple techniques such as the two-step enzyme method, polyethylene glycol (PEG), acid elution technique, and capillary centrifugation method. Results: All five patients tested negative for antibody screening prior to transfusion. However, after transfusion of E+ phenotyped blood, patients 1, 2, 3, and 5 developed delayed haemolytic transfusion reaction (DHTR), while patient 4 experienced acute haemolytic transfusion reaction (AHTR). Anti-E antibodies were detected in all blood samples from the patients after the hemolytic transfusion reaction, including the enzyme-only anti-E antibody in two cases. Conclusion: Anti-E antibody can trigger both intravascular and extravascular hemolysis. It is recommended to conduct ABO/RhD and RhE antigen-matched transfusions and establish a regional blood transfusion database to reduce immune hemolytic transfusion reactions caused by anti-E antibody.

INTRODUCTION: Adolescent depression is prevalent, and teen suicide rates are on the rise locally. A systemic review to understand associated risk and protective factors is important to strengthen measures for the prevention and early detection of adolescent depression and suicide in Singapore. This systematic review aims to identify the factors associated with adolescent depression in Singapore. METHODS: A systematic search on the following databases was performed on 21 May 2020: PubMed, EMBASE and PsycINFO. Full texts were reviewed for eligibility, and the included studies were appraised for quality using the Newcastle Ottawa Scale. Narrative synthesis of the finalised articles was performed through thematic analysis. RESULTS: In total, eight studies were included in this review. The four factors associated with adolescent depression identified were: (1) sociodemographic factors (gender, ethnicity); (2) psychological factors, including childhood maltreatment exposure and psychological constructs (hope, optimism); (3) coexisting chronic medical conditions (asthma); and (4) lifestyle factors (sleep inadequacy, excessive internet use and pathological gaming). CONCLUSION The identified factors were largely similar to those reported in the global literature, except for sleep inadequacy along with conspicuously absent factors such as academic stress and strict parenting, which should prompt further research in these areas. Further research should focus on current and prospective interventions to improve mental health literacy, targeting sleep duration, internet use and gaming, and mitigating the risk of depression in patients with chronic disease in the primary care and community setting.
Humans ; Singapore/epidemiology* ; Adolescent ; Risk Factors ; Depression/etiology* ; Protective Factors ; Male ; Female ; Life Style ; Suicide

PURPOSE: We carried out the study aiming to explore and analyze the risk factors, the distribution of pathogenic bacteria, and their antibiotic-resistance characteristics influencing the occurrence of surgical site infection (SSI), to provide valuable assistance for reducing the incidence of SSI after traumatic fracture surgery. METHODS: A retrospective case-control study enrolling 3978 participants from January 2015 to December 2019 receiving surgical treatment for traumatic fractures was conducted at Tangdu Hospital of Air Force Medical University. Baseline data, demographic characteristics, lifestyles, variables related to surgical treatment, and pathogen culture were harvested and analyzed. Univariate analyses and multivariate logistic regression analyses were used to reveal the independent risk factors of SSI. A bacterial distribution histogram and drug-sensitive heat map were drawn to describe the pathogenic characteristics. RESULTS: Included 3978 patients 138 of them developed SSI with an incidence rate of 3.47% postoperatively. By logistic regression analysis, we found that variables such as gender (males) (odds ratio (OR) = 2.012, 95% confidence interval (CI): 1.235 - 3.278, p = 0.005), diabetes mellitus (OR = 5.848, 95% CI: 3.513 - 9.736, p < 0.001), hypoproteinemia (OR = 3.400, 95% CI: 1.280 - 9.031, p = 0.014), underlying disease (OR = 5.398, 95% CI: 2.343 - 12.438, p < 0.001), hormonotherapy (OR = 11.718, 95% CI: 6.269 - 21.903, p < 0.001), open fracture (OR = 29.377, 95% CI: 9.944 - 86.784, p < 0.001), and intraoperative transfusion (OR = 2.664, 95% CI: 1.572 - 4.515, p < 0.001) were independent risk factors for SSI, while, aged over 59 years (OR = 0.132, 95% CI: 0.059 - 0.296, p < 0.001), prophylactic antibiotics use (OR = 0.082, 95% CI: 0.042 - 0.164, p < 0.001) and vacuum sealing drainage use (OR = 0.036, 95% CI: 0.010 - 0.129, p < 0.001) were protective factors. Pathogens results showed that 301 strains of 38 species of bacteria were harvested, among which 178 (59.1%) strains were Gram-positive bacteria, and 123 (40.9%) strains were Gram-negative bacteria. Staphylococcus aureus (108, 60.7%) and Enterobacter cloacae (38, 30.9%) accounted for the largest proportion. The susceptibility of Gram-positive bacteria to Vancomycin and Linezolid was almost 100%. The susceptibility of Gram-negative bacteria to Imipenem, Amikacin, and Meropenem exceeded 73%. CONCLUSION Orthopedic surgeons need to develop appropriate surgical plans based on the risk factors and protective factors associated with postoperative SSI to reduce its occurrence. Meanwhile, it is recommended to strengthen blood glucose control in the early stage of admission and for surgeons to be cautious and scientific when choosing antibiotic therapy in clinical practice.
Humans ; Surgical Wound Infection/epidemiology* ; Male ; Female ; Risk Factors ; Retrospective Studies ; Middle Aged ; Adult ; Case-Control Studies ; Fractures, Bone/surgery* ; Aged ; Drug Resistance, Bacterial ; Logistic Models ; Anti-Bacterial Agents/therapeutic use* ; Incidence ; Bacteria/drug effects*

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*

Objective:To evaluate the levels and source of cadmium exposure by dietary pathway among middle-aged and elderly people ≥40 in cadmium-contaminated areas of China.Methods:A total of 7 193 people aged 40-89 years from four typical cadmium-contaminated areas in China were selected as the study subjects. Food Frequency Questionnaire (FFQ), Total Diet Study (TDS) and a 3-day-24-hour dietary recall survey were conducted. Dietary cadmium intake and food sources through dietary pathways were assessed based on cadmium content in foods, consumption amounts and intake frequencies.Results:The mean age of the participants was 63.39±12.21 years, with 50.05% being males. The average monthly dietary cadmium intake was 7.39 μg/(kg·BW). Staple foods and vegetables were the primary sources of dietary cadmium intake, accounting for 57.51% and 32.48%, respectively. The monthly dietary cadmium intake in all surveyed regions did not exceed the Provisional Tolerable Monthly Intake (PTMI) recommended by the Joint FAO/WHO Expert Committee on Food Additives (JECFA).Conclusion:The monthly dietary cadmium intake among middle-aged and elderly people in cadmium-contaminated areas of China is relatively low, with the risk remaining at an acceptable level. Staple foods and vegetables are the most significant contributors to dietary cadmium intake.

For middle-aged and elderly patients with conditions such as spinal fractures and degenerative spinal diseases, spinal internal fixation is a core surgical procedure for reconstructing spinal stability, heavily relying on the biomechanical stability provided by pedicle screw systems. Whereas, these patients are often complicated by osteoporosis that can significantly compromise the stability of the bone-pedicle screw interface, leading to a marked increase in pedicle screw loosening and surgical failure rates. The bone cement-augmented pedicle screw technique, which involves injecting bone cement into the vertebral body or screw trajectory to optimize the mechanical properties of the bone-pedicle screw composite, has been proven to significantly enhance fixation strength and effectively prevent screw-related failures, thereby reducing the incidence of internal fixation failure in high-risk populations undergoing spinal fusion. However, the widespread clinical application of this technique has faced challenges such as inaccurate clinical decision-making (indication and contraindication selection), non-standardized operative practices, and insufficient awareness of complication prevention, resulting in considerable variability in clinical outcomes and even severe complications. To address this, Prof. Luo Fei from First Affiliated Hospital of Army Medical University initiated the project and the Chinese Association Orthopaedic Surgeons organized relevant experts to develop the Evidence-based clinical practice guideline for bone cement-augmented pedicle screw technique ( version 2025), based on current evidence. The guidelines put forward 8 recommendations regarding the clinical value, scope of application, and operational standards of the technique, aiming to provide evidence-based medical support and technical standardization for clinical decision-making.

[This corrects the article DOI: 10.1016/j.jpha.2023.08.006.].

The dysregulation of cyclin-dependent kinase 12 (CDK12), which may result from genomic alterations or modulation by upstream effectors, is implicated in cancer oncogenesis and progression. CDK12 overexpression or activation is sufficient to induce tumor initiation, recurrence, and therapeutic resistance. However, CDK12 may also exert tumor-suppressive functions in a context-dependent manner. Therefore, caution is warranted when targeting CDK12 in future clinical trials. A comprehensive elucidation of the dual roles and underlying mechanisms of CDK12 in carcinogenesis is urgently needed to advance precision oncology. This review provides an overview of the current understanding of the dysregulation and biological roles of CDK12 in cancer. Subsequently, we systematically summarize the functions and mechanisms of the oncogenic and tumor-suppressive roles of CDK12 in different contexts. Finally, we discuss the potential of CDK12 as a novel therapeutic target and its implications in clinical oncology, offering insights into future directions for innovative cancer treatment strategies.

OBJECTIVE: To investigate the association between long-term glycemic control and cerebral infarction risk in patients with diabetes through a large-scale cohort study. METHODS: This prospective, community-based cohort study included 12,054 patients with diabetes. From 2006 to 2012, 38,272 fasting blood glucose (FBG) measurements were obtained from these participants. FBG trajectory patterns were generated using latent mixture modelling. Cox proportional hazards models were applied to assess the subsequent risk of cerebral infarction associated with different FBG trajectory patterns. RESULTS: At baseline, the mean age of the participants was 55.2 years. Four distinct FBG trajectories were identified based on FBG concentrations and their changes over the 6-year follow-up period. After a median follow-up of 6.9 years, 786 cerebral infarction events were recorded. Different trajectory patterns were associated with significantly varied outcome risks (Log-Rank P < 0.001). Compared with the low-stability group, Hazard Ratio ( HR) adjusted for potential confounders were 1.37 for the moderate-increasing group, 1.23 for the elevated-decreasing group, and 2.08 for the elevated-stable group. CONCLUSION Sustained high FBG levels were found to play a critical role in the development of ischemic stroke among patients with diabetes. Controlling FBG levels may reduce the risk of cerebral infarction.
Humans ; Cerebral Infarction/blood* ; Middle Aged ; Male ; Female ; Blood Glucose/analysis* ; Fasting/blood* ; Aged ; Prospective Studies ; Risk Factors ; Diabetes Mellitus/blood* ; Adult ; Proportional Hazards Models