Objective: To systematically analyze the revisions content and technological development trends of microbiological standards in the Chinese Pharmacopoeia (ChP) 2025 Edition, and explore its novel requirements in risk-based pharmaceutical product lifecycle management.
Methods: A comprehensive review was conducted on 26 microbiological-related standards to summarize the revision directions and scientific implications from perspectives including the revision overview, international harmonization of microbiological standards, risk-based quality management system, and novel tools and methods with Chinese characteristics.
Results: The ChP 2025 edition demonstrates three prominent features in microbiological-related standards: enhanced international harmonization, introduced emerging molecular biological technologies, and established a risk-based microbiological quality control system.
Conclusion: The new edition of the Pharmacopoeia has systematically constructed a microbiological standard system, which significantly improves the scientificity, standardization and applicability of the standards, providing a crucial support for advancing the microbiological quality control in pharmaceutical industries of China.

OBJECTIVE: To investigate the effects of Bushen Huoxue Granule on the ubiquitin-proteasome system (UPS) in an in vitro model of Parkinson's disease. METHODS: After treated with 1-methyl-4-phenylpyridinium (MPP⁺, 1 mmol/L) for 24 h, the cells were incubated with drug-free serum, Madopar-containing serum or Bushen Huoxue Granule-containing serum (BCS, 5%, 10%, and 20%) for another 24 h. The levels of α-synuclein (α-syn), tyrosine hydroxylase (TH) and UPS-related proteins were detected by Western blot. The expression levels of α-syn in PC12 cells were also analyzed by Western blot after treated with proteasome inhibitor MG132 and WT-α-syn plasmid transfection, respectively, as well as the alterations induced by subsequent BCS intervention. Immunocytochemistry was performed to determine the changes in α-syn phosphorylation at serine 129 (pSer129-α-syn) expression. The 20S proteasome levels were measured by enzyme-linked immunosorbnent assay. RESULTS: BCS (volume fraction ⩽20%) intervention could alleviate the MMP⁺-induced cell viability decrease (P<0.05). In the MPP⁺ treated cells, α-syn was up-regulated, while TH and proteins of UPS such as ubiquitin (Ub), Ub binding with Ub-activating enzyme (UBE1), Parkin and Ub C-terminal hydrolase-1 (UCHL-1) were down-regulated (P<0.05). BCS intervention could attenuate the above changes (P<0.05). The activity of BCS on blocking α-syn accumulation was weakened by MG132 (P<0.05). While α-syn level was significantly increased in cells transfected with plasmid, and reduced by BCS intervention (P<0.05). pSer129-α-syn was increased in MPP⁺-induced PC12 cells, whereas decreased by later BCS intervention (P<0.05). The 20S proteasome activity of MPP⁺-induced PC12 cells was decreased, but increased after BCS intervention (P<0.05). CONCLUSION BCS intervention protected UPS function, increased 20S proteasome activity, promoted pathological α-syn clearance, restored cell viability, and reversed the damage caused by MPP⁺ in the in vitro model of Parkinson's disease.
PC12 Cells ; alpha-Synuclein/metabolism* ; Rats ; Animals ; 1-Methyl-4-phenylpyridinium/toxicity* ; Proteasome Endopeptidase Complex/metabolism* ; Drugs, Chinese Herbal/pharmacology* ; Ubiquitin/metabolism* ; Cell Survival/drug effects* ; Phosphorylation/drug effects* ; Tyrosine 3-Monooxygenase/metabolism*

Poly(ADP-ribose) polymerase 1 (PARP1) is a multifunctional protein involved in diverse cellular functions, notably DNA damage repair. Pharmacological inhibition of PARP1 has therapeutic benefits for various pathologies. Despite the increased use of PARP inhibitors, challenges persist in achieving PARP1 selectivity and effective blood-brain barrier (BBB) penetration. The development of a PARP1-specific positron emission tomography (PET) radioligand is crucial for understanding disease biology and performing target occupancy studies, which may aid in the development of PARP1-specific inhibitors. In this study, we leverage the recently identified PARP1 inhibitor, AZD9574, to introduce the design and development of its ¹⁸F-isotopologue ([¹⁸F]AZD9574). Our comprehensive approach, encompassing pharmacological, cellular, autoradiographic, and in vivo PET imaging evaluations in non-human primates, demonstrates the capacity of [¹⁸F]AZD9574 to specifically bind to PARP1 and to successfully penetrate the BBB. These findings position [¹⁸F]AZD9574 as a viable molecular imaging tool, poised to facilitate the exploration of pathophysiological changes in PARP1 tissue abundance across various diseases.

OBJECTIVE: The study aim was to investigate the effects of exposure to multiple environmental organic pollutants on cardiopulmonary health with a focus on the potential mediating role of oxidative stress. METHODS: A repeated-measures randomized crossover study involving healthy college students in Beijing was conducted. Biological samples, including morning urine and venous blood, were collected to measure concentrations of 29 typical organic pollutants, including hydroxy polycyclic aromatic hydrocarbons (OH-PAHs), bisphenol A and its substitutes, phthalates and their metabolites, parabens, and five biomarkers of oxidative stress. Health assessments included blood pressure measurements and lung function indicators. RESULTS: Urinary concentrations of 2-hydroxyphenanthrene (2-OH-PHE) ( β = 4.35% [95% confidence interval ( CI): 0.85%, 7.97%]), 3-hydroxyphenanthrene ( β = 3.44% [95% CI: 0.19%, 6.79%]), and 4-hydroxyphenanthrene (4-OH-PHE) ( β = 5.78% [95% CI: 1.27%, 10.5%]) were significantly and positively associated with systolic blood pressure. Exposures to 1-hydroxypyrene (1-OH-PYR) ( β = 3.05% [95% CI: -4.66%, -1.41%]), 2-OH-PHE ( β = 2.68% [95% CI: -4%, -1.34%]), and 4-OH-PHE ( β = 3% [95% CI: -4.68%, -1.29%]) were negatively associated with the ratio of forced expiratory volume in the first second to forced vital capacity. These findings highlight the adverse effects of exposure to multiple pollutants on cardiopulmonary health. Biomarkers of oxidative stress, including 8-hydroxy-2'-deoxyguanosine and extracellular superoxide dismutase, mediated the effects of multiple OH-PAHs on blood pressure and lung function. CONCLUSION Exposure to multiple organic pollutants can adversely affect cardiopulmonary health. Oxidative stress is a key mediator of the effects of OH-PAHs on blood pressure and lung function.
Humans ; Oxidative Stress/drug effects* ; Male ; Cross-Over Studies ; Female ; Young Adult ; Environmental Pollutants/toxicity* ; Environmental Exposure/adverse effects* ; Biomarkers/blood* ; Adult ; Blood Pressure/drug effects* ; Polycyclic Aromatic Hydrocarbons/urine* ; Beijing

Objective:To analyze the level and clinical significance of IL-18 and IL-18-binding protein (BP) in the bone marrow of patients with myelodysplastic syndrome (MDS) .Methods:A total of 43 newly diagnosed patients with MDS who were admitted to the Department of Hematology, Tianjin Medical University General Hospital, from July 2020 to February 2021 were randomly selected. The control group consisted of 14 patients with acute myeloid leukemia (AML) and 25 patients with iron-deficiency anemia (IDA). The levels of IL-18 and IL-18 BP in the bone marrow supernatant were measured, and their correlations with MDS severity, as well as the functionality of CD8 + T cells and natural killer cells, was analyzed. Results:The levels of IL-18, IL-18 BP, and free IL-18 (fIL-18) in the bone marrow supernatant of patients with MDS were higher than in the IDA group. The level of fIL-18 was linearly and negatively correlated with the MDS-International Prognostic Scoring System (IPSS) score. IL-18 receptor (IL-18Rα) expression on CD8 + T cells in the MDS group was lower than in the IDA group, and the levels of fIL-18 and IL-18Rα were positively correlated with CD8 + T-cell function in the MDS group. Conclusion:IL-18 BP antagonizes IL-18, leading to a decrease in fIL-18 in the bone marrow microenvironment of patients with MDS, affecting CD8 + T-cell function, which is closely related to MDS severity; therefore, it may become a new target for MDS treatment.

Clinical data of 3 patients with linezolid-induced lactic acidosis treated in 2 hospitals in Beijing and Shandong were retrospectively analyzed,and relevant literatures at home and abroad were retrieved.The pathogene-sis,risk factors,clinical manifestations,and treatment scheme were valuated.Three patients received linezolid anti-infection treatment due to their disease condition.At different phases of treatment,they developed lactic acidosis that was difficult to be explained with septic shock.After discontinuing linezolid and receiving bedside continuous veno-venous hemofiltration(CVVH)treatment,patient's blood lactate levels decreased significantly.It is clinically diagnosed linezolid-induced lactic acidosis finally,but the initial diagnosis was septic shock by all doctors.After ac-tive treatment,2 patients recovered and 1 patient died.Linezolid-induced lactic acidosis is easily to be misdiagnosed as septic shock.Clinicians should enhance their understanding and recognition of the early diagnosis of the adverse reactions,take effective measures,so as to improve patient prognosis.

Objective:To investigate the value of the American College of Radiology Thyroid Imaging, Reporting and Data System (ACR TI-RADS), real-time ultrasound elastography (RTE), and contrast-enhanced ultrasound (CEUS), individually and in combination, in the diagnosis of TBSRTC Ⅲ-Ⅴ thyroid nodules.Methods:A retrospective analysis was performed on 106 patients with TBSRTC Ⅲ-Ⅴ thyroid nodules who were pathologically diagnosed by fine needle aspiration cytology at Bao Ji People's Hospital between February 2022 and December 2023. All patients were assessed using ACR TI-RADS grading, RTE, and CEUS, with postoperative pathological diagnosis serving as the gold standard. The diagnostic effectiveness of ACR TI-RADS, RTE, and CEUS, individually and in combination, for TBSRTC Ⅲ-Ⅴ thyroid nodules was analyzed using the receiver operating characteristic (ROC) curve.Results:There were statistically significant differences in nodule size, blood supply, and proportion of TBSRTC Ⅲ-Ⅴ nodule between the two groups ( χ2 = 4.67, 42.56, 26.09, all P < 0.05), while there was no statistical significance in other general data (all P > 0.05). Of the 106 patients with TBSRTC Ⅲ-Ⅴ nodules, 69 patients were diagnosed with malignant nodules and 37 with benign nodules. The area under the curve (95% CI) of ACR-TIRADS, RTE, and CEUS in identifying malignant nodules were 0.860 [95% CI (0.779-0.920)], 0.712 [95% CI (0.616-0.796)], and 0.788 [95% CI (0.698-0.862)], respectively, with sensitivities of 85.51%, 66.67%, and 73.91%, respectively and specificities of 86.49%, 75.68%, and 83.78%, respectively. The Youden indices were 0.719, 0.423, and 0.577, respectively. Among the three diagnostic methods, ACR TI-RADS had the highest diagnostic efficiency, while RTE had the lowest. Pairwise comparisons in ROC analysis revealed statistically significant differences between ACR TI-RADS and RTE, ACR TI-RADS and CEUS, as well as RTE and CEUS ( Z = 4.22, 3.02, 2.78, all P < 0.05). The ACR TI-RADS + RTE + CEUS combination had the highest sensitivity, specificity, Youden index, and AUC (95% CI) values: 94.20%, 89.19%, 0.834, and 0.917 (95% CI: 0.847-0.962). The RTE + CEUS combination had the lowest values: 76.81%, 78.38%, 0.552, and 0.776 (95% CI: 0.685-0.851). The pairwise comparison results in the ROC curve revealed that significant differences were observed between ACR TI-RADS + RTE and RTE + CEUS, ACR TI-RADS + RTE and ACR TI-RADS + RTE + CEUS, ACR TI-RADS + CEUS and ACR TI-RADS + RTE + CEUS, RTE + CEUS and ACR TI-RADS + RTE + CEUS, and ACR TI-RADS + CEUS and RTE + CEUS ( Z = 3.13, 2.40, 2.16, 4.07, 3.32, all P < 0.05). However, there was no significant difference between ACR TI-RADS + RTE and ACR TI-RADS + CEUS in ROC analysis ( Z = 0.06, P > 0.05). Conclusion:The combined utilization of ACR TI-RADS, RTE, and CEUS offers enhanced information on thyroid nodules, encompassing malignant risk stratification, nodular elasticity, and contrast agent perfusion, thereby aiding in improving the diagnostic precision of TBSRTC Ⅲ-Ⅴ malignant nodules.

Objective:To construct a nomogram prediction model for 28-day mortality in septic shock patients based on routine laboratory data mining and verify its predictive value.Methods:The clinical data of patients with septic shock admitted to Anhui Medical University Affiliated Fuyang Hospital from January 2018 to November 2023 were retrospectively analyzed. The patients were randomly divided into training set and validation set according to the ratio of 8∶2. The patient's gender, age, body mass index, underlying disease, smoking history, alcohol history, infection site, acute physiology and chronic health evaluation Ⅱ (APACHEⅡ), sequential organ failure assessment (SOFA), respiratory rate, heart rate, mean arterial pressure, blood lactate, procalcitonin, C-reactive protein, white blood cell count, platelet count, serum alanine aminotransferase, aspartate aminotransferase, urea nitrogen, serum creatinine, fibrinogen, D-dimer, albumin on the first day of admission to the intensive care unit (ICU), duration of mechanical ventilation, and length of ICU stay were collected. The patients were divided into survival and death groups based on their 28-day prognosis. The factors influencing 28-day mortality were analyzed, and routine laboratory data were used to develop a nomogram model for predicting the risk of 28-day mortality in septic shock patients. The model was validated and assessed using the Bootstrap method, calibration curve, and receiver operator characteristic curve (ROC curve).Results:Finally, 128 patients with septic shock were enrolled, and 32 (31.07%) death within 28-day of 103 patients in the training set, 8 (32.00%) death within 28-day of 25 patients in the validation set. Logistic regression analysis showed that APACHEⅡ score [odds ratio ( OR) = 5.254, 95% confidence interval (95% CI) was 2.161-12.769], SOFA score ( OR = 4.909, 95% CI was 2.020-11.930), blood lactate ( OR = 4.419, 95% CI was 1.818-10.741), procalcitonin ( OR = 4.358, 95% CI was 1.793-10.591) were significant factors influencing 28-day mortality in septic shock patients (all P < 0.01). Taking the above influencing factors as predictors, a nomogram model was established, with a total score of 89-374, corresponding to a mortality risk of 0.07-0.89. The results of nomogram model validation showed that the C-index was 0.801 (95% CI was 0.759-0.832), and the correction curve for predicting 28-day mortality in patients with septic shock was close to the ideal curve, Hosmer-Lemeshow test showed that χ 2 = 0.263, P = 0.512. The results of the ROC curve of the training set showed that the nomogram model had a sensitivity of 78.13% (95% CI was 59.57%-90.06%), a specificity of 80.28% (95% CI was 68.80%-88.43%) and area under the curve (AUC) of 0.854 (95% CI was 0.776-0.937) in predicting 28-day mortality in patients with septic shock. The results of the validation set ROC curve showed that the nomogram model had a sensitivity of 75.00% (95% CI was 35.58%-95.55%), a specificity of 88.23% (95% CI was 62.25%-97.94%) and AUC of 0.871 (95% CI was 0.793-0.946) in predicting 28-day mortality in patients with septic shock. Conclusion:A nomogram prediction model constructed based on routine laboratory data mining can effectively predict 28-day mortality in septic shock patients, and its prediction performance is good.

Objective:To investigate the clinical features of nontuberculous mycobacteria (NTM) disease patients with positive anti-interferon γ (IFN-γ) autoantibody.Methods:Forty-three adult human immunodeficiency virus-uninfected patients with NTM disease hospitalized in Huashan Hospital, Fudan University and Jing′an Branch, Huashan Hospital, Fudan University from July 2021 to August 2023 were included. Clinical data and NTM strain information of the patients were collected. The plasma levels of anti-IFN-γ autoantibodies were detected by enzyme-linked immunosorbent assay, and the patients were divided into antibody positive group and antibody negative group. The clinical characteristics and laboratory examination results between the two groups were compared. The independent sample t test, Mann-Whitney U test and chi-square test were used for statistical analysis. Multivariate logistic regression analysis was used to determine the correlation factors of positive anti-IFN-γ autoantibodies. Results:Among the 43 patients, 13 cases (30.2%) were positive for anti-IFN-γ autoantibodies and 30 cases (69.8%) were negative. The proportions of patients with NTM disseminated infection (9/13 vs 30.0%(9/30))and combined bacterial infection (5/13 vs 6.7%(2/30)) in antibody positive group were both higher than those in antibody negative group, and the differences were both statistically significant ( χ2=5.74 and 6.73, respectively, both P<0.05). The white blood cell count, platelet count, the proportion of platelet count >350×10 9/L of antibody positive patients were all higher than those of antibody negative group, while the white sphere ratio was lower than that of antibody negative group, with statistical significance ( t=2.42, 3.02, χ2=9.77 and t=3.66, respectively, all P<0.05). Erythrocyte sedimentation rate, C-reactive protein, procalcitonin, globulin, immunoglobulin G, immunoglobulin A and immunoglobulin M in antibody positive patients were all higher than those in antibody negative group, and the differences were all statistically significant ( U=99.50, 112.00, 115.50, 61.50, 76.50, 99.00 and 83.00, respectively, all P<0.05). Mycobacterium abscessus complex (seven cases and 11 cases, respectively) and Mycobacterium avium complex (five cases and 13 cases, respectively) were the main isolated strains in antibody positive and antibody negative patients. Multivariate logistic regression analysis showed that combined with bacterial infection (odds ratio ( OR)=21.83, 95% confidence interval ( CI) 1.94 to 245.71), NTM disseminated infection ( OR=7.64, 95% CI 1.10 to 53.26), platelet count>350×10 9/L ( OR=14.31, 95% CI 1.91 to 107.04) were risk factors for anti-IFN-γ autoantibodies positive (all P<0.05). Conclusions:Patients with positive anti-IFN-γ autoantibodies have higher probability of having elevated levels of systemic inflammation. Anti-IFN-γ autoantibody test is recommended for patients with NTM disease who present with co-bacterial infection, NTM disseminated infection, or elevated platelet count (>350×10 9/L).

This study aimed to investigate the prevalence and clinical characteristics of epilepsy in patients with patent foramen ovale (PFO) and the effect of PFO closure on seizures. Patients diagnosed with PFO were recruited and underwent brain magnetic resonance imaging, electrocardiography, transesophageal echocardiography, and transthoracic echocardiography with right ventriculography. In patients with epilepsy, electroencephalography was performed. A total of 110 patients completed the assessment. A chief complaint of chest tightness or palpitations was proportionately higher in patients aged<18 years, whereas headaches and seizures were higher in patients aged≥18 years ( χ2=4.69 ,P<0.05). Comorbid epilepsy was observed in 20.9% of patients with PFO. The age at admission in the epileptic group (14-66(27±14)years) was significantly lower than that in the non-epileptic group (16-81(38±21)years) and that in patients with headache as the chief complaint (16-68(39±12)years) ( t=3.29, P<0.05). The multivariate analysis found no risk factors related to the prognosis of epilepsy. The incidence of epilepsy was significantly higher in patients with PFO than in the general population.