Objective To understand the antibody levels of diphtheria and tetanus among healthy population in Shanghai Pudong New Area, and to provide a scientific basis for improving the vaccine immunization strategy. Methods Random sampling was used to select healthy people of all ages in 16 communities in Shanghai Pudong New Area from 2018 to 2024, and serum samples were collected and tested for serum anti-diphtheria and tetanus toxin IgG antibodies by enzyme-linked immunosorbent assay (ELISA) method to analyze the antibody positivity rate (≥0.1 IU/ml) and the geometric mean concentration (GMC) of antibodies. Results A total of 3 312 serum samples were included, with a male-to-female ratio of 0.76:1, and 53.77% were local residents. The seropositivity rates and geometric mean concentrations (GMC) of both diphtheria and tetanus antibodies generally declined with increasing age, but exhibited a transient rebound in the 7y-. A total of 1 175 individuals (35.48%) were seropositive for diphtheria, with a GMC of 0.054 IU/mL. For tetanus, 988 individuals (29.83%) were seropositive, with a GMC of 0.033 IU/mL. Significant differences in seropositivity rates (χ²_diphtheria=950.005,χ²_tetanus=1 324.393) and GMC (H_diphtheria=1027.160,H_tetanus=1 142.007) were observed among different age groups (P<0.001). Significant differences in seropositivity rates (χ²_diphtheria=950.005,χ²_tetanus=1324.393) and GMC (H_diphtheria=1027.160,H_tetanus=1142.007) were also found across different years (P<0.001). Conclusion The prevalence of diphtheria and tetanus antibodies in the healthy population of Pudong New Area is relatively low, particularly among adults over 20 years of age with inadequate immunization. This underscores the need to reinforce the National Immunization Program (NIP) vaccine specifications for children under 6 years of age and implement an immunization strategy for adolescents or adults against diphtheria and tetanus.

ObjectiveTo explore the current situation of forensic ethics practice and education by designing a questionnaire on forensic ethics， with a view to exploring the path of forensic ethics education construction. MethodsA total of 667 valid questionnaires were collected using the online survey method， basically covering various regions across the country and all sub-specialties of forensic medicine. Descriptive analysis was used to analyze the relevant data. ResultsMost practitioners had relevant ethical reflections in the process of forensic practice. 69.12% of the respondents indicated that they had studied the relevant rules， but approximately half stated that there were no corresponding ethical norms or standard operating manuals. The specific behaviors violating ethics in different units were diverse. 23.04% of the respondents reported that they had encountered unethical behaviors， but only 4.9% of them reported such violations. In terms of forensic ethics education， 87.75% of the respondents believed that there were issues with the current model of forensic ethics education. Meanwhile， the respondents showed a high degree of recognition for receiving forensic ethics education， with 84.15% of respondents expressing willingness to participate in relevant courses. More than half of respondents were willing to participate in forensic ethics education during undergraduate studies， new employee training， and regular post-employment training. ConclusionCurrently， there is a problem of ethical neglect in forensic work in China. Combining ethics courses with professional courses at the practitioner training stage and providing regular training at the practice stage are effective measures to popularize forensic ethics knowledge， enhance ethical awareness， and improve the quality of practice.

OBJECTIVE: To investigate the molecular mechanism and explore blood transfusion strategies for a proband exhibiting the JK (a-b-) phenotype and anti-JK³ high frequency antigen antibody and her eight family members. METHODS: The Kidd blood phenotype and irregular antibodies in a family were identified by serologic tests. Exon 4-11 and intron region of SLC14A1 gene were sequenced by Sanger method. RESULTS: The combination of the gene JK*B (c.499A>G,c.512G>A,c.588A>G) and gene JK*B (c.342-1G>A,588A>G) in this family were considered to result in the JK (a-b-) phenotype in two members. The members carrying gene JK*A(c.130G>A,588A>G) all present serological JK^a+W. Members carrying gene JK*B (c.499A>G,c.588A>G) all present serological JK^b+W, which has not been previously reported to cause antigenic weakening. The proband with JK (a-b-) phenotype produced anti-JK³ antibodies, the hospital formulated a number of blood preparation strategies for the patient and she was discharged after recovery. CONCLUSION In this study, the molecular mechanism of JK (a-b-) in this family was identified, the transfusion strategy of rare blood group was established in our institution preliminary, and the necessity of establishing a rare blood group bank was revealed in this region. It is suggested that JK*B (c.499A>G,c.588A>G) may be a new genetic pattern leading to the weakening of Kidd antigenicity, which lays a foundation for the study of population genetics.
Humans ; Blood Transfusion ; Female ; Kidd Blood-Group System/genetics* ; Phenotype ; Pedigree

OBJECTIVES: To explore the underlying pharmacological mechanisms and its potential effects of Chinese medicine herbal formula Sini Powder (SNP) on hepatocellular carcinoma (HCC). METHODS: The active components of SNP and their in vivo distribution were identified using ultraperformance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry. Construction of component-target-disease networks, protein-protein interaction network, Gene Ontology function and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis, and molecular docking were employed to analyze the active components and anti-HCC mechanisms of SNP. Cell viability assay and wound healing assay were utilized to confirm the effect of SNP-containing serum (2.5%, 5.0%, 10%, 20%, and 40%), isoprenaline or propranolol (both 10, 100, and 1,000 µ mol/L) on proliferation and migration of HepG 2 or Huh7 cells. Meanwhile, the effect of isoprenaline or propranolol on the β 2 adrenergic receptor (ADRB2) mRNA expression on HepG2 cells were measured by real-time quantitative reverse transcription (RT-qPCR). Mice with subcutaneous tumors were either subjected to chronic restraint stress (CRS) followed by SNP administration (364 mg/mL) or directly treated with SNP (364 mg/mL). These two parallel experiments were performed to validate the effects of SNP on stress responses. Stress-related proteins and hormones were quantified using RT-qPCR, enzyme-linked immunosorbent assay, and immunohistochemistry. Metagenomic sequencing was performed to confirm the influence of SNP on the gut microbiota in the tumor-bearing CRS mice. RESULTS: The distribution of the 12 active components of SNP was confirmed in various tissues and feces. Network pharmacology analysis confirmed the anti-HCC effects of the 5 active components. The potential anti-HCC mechanisms of SNP may involve the epidermal growth factor receptor (EGFR), proto-oncogene tyrosine-protein kinase Src (SRC) and signal transducer and activator of transcription 3 (STAT3) pathways. SNP-containing serum inhibited the proliferation of HepG2 and Huh7 cells at concentrations of 2.5% and 5.0%, respectively, after 24 h of treatment. Furthermore, SNP suppressed tumor progression in tumor-bearing mice exposed to CRS. SNP treatment also downregulated the expressions of stress-related proteins and pro-inflammatory cytokines, primarily by modulating the gut microbiota. Specifically, the abundance of Alistipes and Prevotella, which belong to the phylum Bacteroidetes, increased in the SNP-treated group, whereas Lachnospira, in the phylum Firmicutes, decreased. CONCLUSION SNP can combat HCC by alleviating stress responses through the regulation of gut microbiota.
Animals ; Gastrointestinal Microbiome/drug effects* ; Liver Neoplasms/microbiology* ; Carcinoma, Hepatocellular/microbiology* ; Humans ; Drugs, Chinese Herbal/therapeutic use* ; Powders ; Cell Proliferation/drug effects* ; Mice ; Molecular Docking Simulation ; Cell Line, Tumor ; Hep G2 Cells ; Receptors, Adrenergic, beta-2/genetics* ; Stress, Physiological/drug effects* ; Cell Movement/drug effects* ; Male ; Protein Interaction Maps/drug effects* ; Cell Survival/drug effects* ; Proto-Oncogene Mas

Homo- or heterodimeric compounds that affect dimeric protein function through interaction between monomeric moieties and protein subunits can serve as valuable sources of potent and selective drug candidates. Here, we screened an in-house dimeric natural product collection, and panepocyclinol A (PecA) emerged as a selective and potent STAT3 inhibitor with profound anti-tumor efficacy. Through cross-linking C712/C718 residues in separate STAT3 monomers with two distinct Michael receptors, PecA inhibits STAT3 DNA binding affinity and transcription activity. Molecular dynamics simulation reveals the key conformation changes of STAT3 dimers upon the di-covalent binding with PecA that abolishes its DNA interactions. Furthermore, PecA exhibits high efficacy against anaplastic large T cell lymphoma in vitro and in vivo, especially those with constitutively activated STAT3 or STAT3^Y640F. In summary, our study describes a distinct and effective di-covalent modification for the dimeric compound PecA to disrupt STAT3 function.

Delirium is a common cause and complication of hospitalization in the elderly and is associated with higher risk of future dementia and progression of existing dementia, of which 70% is Alzheimer's disease (AD). AD and delirium, which are known to be aggravated by one another, represent significant societal challenges, especially in light of the absence of effective treatments. The intricate biological mechanisms have led to numerous clinical trial setbacks and likely contribute to the limited efficacy of existing therapeutics. Artificial intelligence (AI) presents a promising avenue for overcoming these hurdles by deploying algorithms to uncover hidden patterns across diverse data types. This review explores the pivotal role of AI in revolutionizing drug discovery for AD and delirium from target identification to the development of small molecule and protein-based therapies. Recent advances in deep learning, particularly in accurate protein structure prediction, are facilitating novel approaches to drug design and expediting the discovery pipeline for biological and small molecule therapeutics. This review concludes with an appraisal of current achievements and limitations, and touches on prospects for the use of AI in advancing drug discovery in AD and delirium, emphasizing its transformative potential in addressing these two and possibly other neurodegenerative conditions.

OBJECTIVE: To investigate the relationship between the trajectories of serum potassium changes after intensive care unit (ICU) admission and 30-day death risk in patients with sepsis. METHODS: A retrospective cohort study was conducted, including adult patients with sepsis admitted to the comprehensive ICU, medical intensive care unit (MICU) and emergency intensive care unit (EICU) of Guizhou Medical University Affiliated Hospital from January 2020 to January 2024. The patients who had a minimum of 5 days' hospitalisation in the ICU and who had at least 7 consecutive days of the serum potassium measurements were classified into five trajectories groups according to group-based trajectory modelling (GBTM) using SAS software. This was based on tendency changes in serum potassium levels in patients after admission to the ICU, which was categorized as follows: slowly increased from a low level group, slowly increased from a medium level of normal range group, slowly decreased from a medium level of normal range group, slowly decreased from a high level group, and slowly increased from a high level of normal range group. The patient's gender, age, medical history, and white blood cell count (WBC), platelet count (PLT), procalcitonin (PCT), activated partial thromboplastin time (APTT), prothrombin time (PT), blood sodium, and serum creatinine (SCr) at the time of admission to the ICU were collected. At the same time, the patient's worst sequential organ failure assessment (SOFA) score within 24 hours of admission to the ICU, length of ICU stay, and 30-day outcome were record. The differences in clinical data among different groups of patients were compared. The 30-day cumulative survival rates of the various serum potassium trajectories were plotted using Kaplan-Meier survival curves, the groups were then compared using the Log-Rank test. A multivariate Cox proportional risk regression analysis was developed to evaluate the independent effect of serum potassium trajectory on 30-day death risk. RESULTS: Finally, 342 ICU sepsis patients were enrolled, of which 42 patients in the slowly increased from a low level group (12.28%), 127 patients in the slowly increased from a medium level of normal range group (37.14%), 118 patients in the slowly decreased from a medium level of normal range group (34.50%), 28 patients in the slowly decreased from a high level group (8.19%), and 27 patients in the slowly increased from a high level of normal range group (7.89%). Except for age and APTT differences, there were no statistically significant differences in other clinical characteristics among the patients in the different serum potassium trajectories groups. Kaplan-Meier survival curves showed that there was statistically significant difference in the 30-day cumulative survival rate among the patients in the different serum potassium trajectories groups (Log-Rank test: χ² = 14.696, P = 0.005), with the lowest in the slowly increased from a high level of normal range group (39.3%). Multivariate Cox proportional risk regression analysis showed that the patients with the serum potassium trajectory of slowly increased from a high level of normal range had the highest 30-day death risk [hazard ratio (HR) = 2.341, 95% confidence interval (95%CI) was 1.049-5.226, P = 0.038]. This association persisted after adjustment for variables such as gender, age, medical history, SOFA score, WBC, PLT, PCT, APTT, PT, blood sodium, and SCr (HR = 3.058, 95%CI was 1.249-7.488, P = 0.014). CONCLUSION Compared with the patients whose serum potassium fluctuated within the normal range, the sepsis patients in the ICU with a serum potassium trajectory that slowly increased from a high level of normal range had a significantly higher 30-day death risk.
Humans ; Retrospective Studies ; Intensive Care Units ; Sepsis/blood* ; Potassium/blood* ; Male ; Female ; Middle Aged ; Aged ; Risk Factors ; Hospital Mortality ; Prognosis

BACKGROUND: A growing body of research is exploring the role of antioxidant and anti-inflammatory dietary supplements in the treatment of osteoarthritis, highlighting an increasing emphasis on non-pharmacological interventions. Although more patients are turning to supplements to manage osteoarthritis, their actual effectiveness remains uncertain. OBJECTIVE: This study aims to provide a comprehensive evaluation of the available evidence concerning the efficacy of various dietary supplements in osteoarthritis treatment. SEARCH STRATEGY: We searched PubMed, Embase, Cochrane Library and Web of Science for studies on the use of various dietary supplements in the treatment of osteoarthritis from the creation of each database until Jan 20, 2025. INCLUSION CRITERIA: (1) Research object: osteoarthritis. (2) Intervention measures: patients in the treatment group received dietary supplements, while the control group received placebos. (3) Research type: randomized controlled trials (RCTs). DATA EXTRACTION AND ANALYSIS: Two researchers independently examined the literature and retrieved data based on predefined criteria. The information gathered included the first author, year of publication, sample size, participant demographics, length of the follow-up period, intervention and control measures, and inclusion indications. RCTs comparing dietary supplements to placebo with the pain and function subscales of the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) among patients with osteoarthritis were included. The optimal dietary supplement was identified based on the total ranking by summing the surface under the cumulative ranking curve (SUCRA) of these two scores. Furthermore, the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) was used to confirm the quality of the evidence. RESULTS: Overall, 23 studies covering 21 dietary supplements and involving 2455 participants met the inclusion criteria. In the WOMAC pain score, the SUCRA of passion fruit peel extract was 91% (mean difference [MD]: -9.2; 95% confidence interval [CI]: [-16.0, -2.3]), followed by methylsulfonylmethane (89%), undenatured type II collagen (87%), collagen (84%), and Lanconone (82%). The SUCRA (99%) of passion fruit peel extract (MD: -41.0; 95% CI: [-66.0, -16.0]) ranked first in terms of the WOMAC function score, followed by Lanconone (95%), collagen (86%), ParActin (84%), and Lactobacillus casei strain Shirota (83%). The top three total rankings are passion fruit peel extract (95.0%), Lanconone (88.5%), and collagen (85.0%). However, the GRADE revealed low evidence quality. CONCLUSION Passion fruit peel extract was the best supplement for improving WOMAC pain and function scores in patients with osteoarthritis, followed by Lanconone and collagen. However, further large-scale, well designed RCTs are required to substantiate these promising findings. Please cite this article as: Chen CS, Wen L, Yang F, Deng YC, Ji JH, Chen RJ, Chen Z, Chen G, Gu JY. Effects of dietary supplements on patients with osteoarthritis: A systematic review and network meta-analysis. J Integr Med. 2025; 23(4): 357-369.
Humans ; Dietary Supplements ; Osteoarthritis/drug therapy* ; Randomized Controlled Trials as Topic

Objective : To investigate the protective effect of total glucosides of paeony ( TGP) on dexamethasone(DEX) ⁃induced liver injury in rats. Methods: Thirty SD rats were randomly divided into normal ( N) , DEX ,DEX + TGP (50 mg/kg) , DEX + TGP ( 100 mg/kg) , and DEX + TGP (200 mg/kg) groups , with 6 rats in each group. A rat model of liver injury was established by intraperitoneal injection of DEX ( 17. 5 mg/kg) . Serum levels of alanine aminotransferase ( ALT) , aspartate aminotransferase ( AST) , and alkaline phosphatase ( ALP) were measured , and the liver⁃to⁃body weight ratio was calculated. HE staining was performed to observe histopathological changes in the liver. The contents of malondialdehyde ( MDA) , superoxide dismutase ( SOD) , and glutathione (GSH) in liver tissues were determined. Western blot analysis was conducted to detect the expression levels of NADPH oxidase 4 ( NOX4 ) and endoplasmic reticulum stress⁃related proteins : glucose regulatory protein 94 homologous protein (CHOP) expression level in liver tissues. Results: Compared with the normal group , the DEX group exhibited significantly elevated serum levels of ALT , AST , ALP and liver⁃to⁃body weight ratio ( t = 14. 96 ,ing, degeneration , and necrosis ( t = 15. 49 , P < 0. 01) . Compared with the DEX group , there was no significant change in liver function biochemical indexes and liver histopathology in the TGP (50 mg/kg) treatment group. TGP treatment at 100 mg/kg and 200 mg/kg significantly attenuated these effects : both doses reduced ALT , AST , ALP and liver⁃to⁃body weight ratio( t = 3. 30 , 4. 13 , 7. 45 , 2. 97 , P < 0. 05 ; t = 8. 92 , 6. 45 , 8. 65 , 7. 47 , P < 0. 01) ,vealed that DEX administration significantly increased hepatic MDA levels ( t = 7. 06 , P < 0. 01) and NOX4 ex⁃pression ( t = 4. 23 , P < 0. 01) , whereas SOD activity ( t = 7. 78 , P < 0. 01) and GSH content ( t = 7. 92 , P <0. 01) were markedly suppressed. There was no significant change in the TGP (50 mg/kg) treatment group , TGP intervention at 100 mg/kg and 200 mg/kg effectively reversed these changes , lowering MDA and NOX4 levels( t = 3. 35 , 4. 30 , P < 0. 05 ; t = 5. 44 , 7. 44 , P < 0. 01) , while restoring SOD ( t200 mg/kg = 4. 04 , P < 0. 05) and GSH ( t = 4. 70 , P < 0. 05 ; t = 5. 50 , P < 0. 01) . Endoplasmic reticulum stress markers , including GRP94、GRP78、p- elF2α、CHOP ( t = 3. 31 , 6. 53 , 5. 18 , 3. 09 ; P < 0. 05 , 0. 01 , 0. 01 , 0. 05 ) , were significantly upregulated in the DEX group compared to the normal group. However, TGP treatment at 100 mg/kg and 200 mg/kg dose-dependent- ly suppressed the expression of GRP94、GRP78、p-elF2α、CHOP ( t = 3. 14 ,4. 95 , 3. 13 ,4. 25 , P < 0. 05 ; t = 4. 03 , 7. 48 ,4. 68 ,5. 10 ,P < 0. 01) expression levels were significantly reduced compared to the DEX group , and there was no significant change in the TGP (50 mg/kg) treatment group. Conclusion TGP exerts protective effects a- gainst DEX-induced liver injury , and its mechanism is likely mediated by suppressing hepatic oxidative stress and endoplasmic reticulum stress triggered by DEX in rats.