The binding mechanism between pefloxacin mesylate (PM) and transferrin (Tf) was explored using spectral experiment combined with molecular modeling techniques. The binding parameters and thermodynamic functions of PM-Tf solution system were measured at different temperatures. The effect of PM on molecular conformation of Tf was investigated and the interaction mechanism was also discussed. The results showed that dynamic quenching mechanism occurs with PM binding to Tf. The value of binding distances (r) is low, which indicates the occurrence of energy transfer. The drug had conformational effect on Tf, which resulted in changes of hydrophobic environment of the binding domain in Tf. According to the obtained thermodynamic parameters, the main interaction force between PM and Tf is attributed to hydrophobic bonding. The results of molecular modeling revealed that hydrophobic and hydrogen bonds are main binding forces in the PM-Tf system. These results were in accordance with spectral experiments. The research results have given a better theoretical reference for the study of pharmacological mechanism between protein and quinolone.

Objective To determine the retest reliability and measurement error of walking energy consumption measurement in children with cerebral palsy in special school. Methods 13 children with cerebral palsy studying in Shanghai Pudong Special Education School from September to December in 2010 were enrolled in this study. They were asked to walk up and down continuously on a 50-meter-long walking pace in 6 minutes, while the distance of walking and the heart rate of both rest and walking were measured to calculate physical cost index (PCI). After 1 week, they took the 2nd measurement at the same time, the same location and the same condition. Then the results between the former and the later measurements were compared to identify the retest reliability and measurement error. Results The study showed a good retest reliability in heart rate of walking, distance of walking and PCI (ICC=0.77~0.83), but a low retest reliability in heart rate of rest (ICC=0.38). The study also showed a high measurement error in PCI. Conclusion PCI had good retest reliability and high measurement error, and was easily affected by the emotion of the children. So it was limited as a measurement of walking energy consumption in children with cerebral palsy.

With the development of modern sequencing techniques and bioinformatics, genomes that were once thought to be noncoding have been found to encode abundant functional micropeptides (miPs), a kind of small polypeptides. Although miPs are difficult to analyze and identify, a number of studies have begun to focus on them. More and more miPs have been revealed as essential for energy metabolism homeostasis, immune regulation, and tumor growth and development. Many reports have shown that miPs are especially essential for regulating glucose and lipid metabolism and regulating mitochondrial function. MiPs are also involved in the progression of related diseases. This paper reviews the sources and identification of miPs, as well as the functional significance of miPs for metabolism-related diseases, with the aim of revealing their potential clinical applications.
Humans ; Open Reading Frames ; Peptides ; Glucose ; Genome ; Metabolic Diseases

Objective To evaluates the impact of early application of neuromuscular electrical stimulation(NMES)on muscle strength,clinical outcomes,and long-term quality of life improvements in patients with severe acute pancreatitis(SAP)complicated with acute respiratory distress syndrome(ARDS).Methods A total of 75 patients diagnosed with SAP and ARDS admitted in Department of Critical Care Medicine of our hospital from September 2022 to August 2023 were recruited and then randomly divided into NMES group(n=37)and control group(n=38).After 16 patients were excluded,including 8 died during treatment,3 discharged and 5 received palliative care,there were finally 29 patients in the NMES group and 30 in the control group.Within 48 h after ICU admission,the NMES group received NMES 1 h per day,for 7 d in addition to standard rehabilitation intervention.While,the control group were given conventional interventions for rehabilitation.Assessments at baseline and post-treatment included the incidence of ICU-acquired weakness(ICU-AW),Medical Research Council(MRC)score,duration of mechanical ventilation,lengths of ICU and total hospital stays,and activity,thickness and thickening fraction of the diaphragm.Mortality rates and Barthel index(BI)for self-care ability in 1,3 and 6 months after discharge were recorded for follow-up assessments.Results The NMES group had significantly lower incidence of ICU-AW(P＜0.05),higher upper and lower limb MRC scores and overall MRC score at ICU discharge(P＜0.05),shorter durations of mechanical ventilation,ICU stay,and total hospital stay when compared with the control group(P＜0.05).There was no statistical difference in the BI at 1 month post-discharge between the 2 groups,but the indexes at 3 and 6 months were notably higher in the NMES group than the control group(P＜0.05).No obvious differences were observed between the 2 groups in terms of diaphragm activity,thickness,or thickening scores at enrollment,ICU discharge,or hospital discharge,nor in mortality rates at 1,3,and 6 months after discharge.Conclusion Combined NMES and early rehabilitation therapy can improve muscle strength and reduce length of hospital stay in SAP patients complicated with ARDS,and may enhance long-term quality of life.However,it does not significantly affect diaphragm function or mortality rates.

Objective:To assess the efficacy and safety of common medication treatments on Kaposiform hemangioendothelioma (KHE) and tufted angioma (TA).Methods:PubMed, Embase, Web of Science, CNKI and Wanfang database were searched to find out the observational studies on medication treatment of KHE and TA. R-3.6.2 was used for calculate the pooled response rate and pooled adverse events rate. Meta analyses were performed according to KHE and TA with and without Kasabach-Merritt phenomenon (KMP) respectively. SPSS 22.0 was used to compare the pooled rates among each therapy.Results:A total of 30 studies regarding the medication treatment of KHE and TA were identified in this meta-analysis. Analyzed medicines included glucocorticoid, vincristine, sirolimus, propranolol, combination therapy of vincristine and glucocorticoid. The pooled results indicated that when referring therapy on KHE and TA with KMP, the pooled response rate of combination therapy (98.34%) and sirolimus (96.43%) was higher than that of other therapies, and the difference was statistically significant. The pooled adverse events rate of sirolimus (5.53%) was relatively higher than other modalities, with no statistically significance. As for therapy on KHE and TA without KMP, sirolimus (94.23%) had higher pooled response rate than glucocorticoid (31.25%), vincristine (46.15%) and propranolol (22.86%), with statistically significant differences. The pooled adverse events rate of sirolimus was 23.81%.Conclusions:Our findings indicate that for KHE and TA with KMP, combination therapy (sirolimus + glucocorticoid) and vincristine have the best efficacy, while the adverse events rate of sirolimus is relatively high. For KHE and TA without KMP, sirolimus has the highest response rate, but there is also a risk of serious adverse events. Glucocorticoid and vincristine have comparable response rate, which both inferior to sirolimus.

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 assess the efficacy and safety of common medication treatments on Kaposiform hemangioendothelioma (KHE) and tufted angioma (TA).Methods:PubMed, Embase, Web of Science, CNKI and Wanfang database were searched to find out the observational studies on medication treatment of KHE and TA. R-3.6.2 was used for calculate the pooled response rate and pooled adverse events rate. Meta analyses were performed according to KHE and TA with and without Kasabach-Merritt phenomenon (KMP) respectively. SPSS 22.0 was used to compare the pooled rates among each therapy.Results:A total of 30 studies regarding the medication treatment of KHE and TA were identified in this meta-analysis. Analyzed medicines included glucocorticoid, vincristine, sirolimus, propranolol, combination therapy of vincristine and glucocorticoid. The pooled results indicated that when referring therapy on KHE and TA with KMP, the pooled response rate of combination therapy (98.34%) and sirolimus (96.43%) was higher than that of other therapies, and the difference was statistically significant. The pooled adverse events rate of sirolimus (5.53%) was relatively higher than other modalities, with no statistically significance. As for therapy on KHE and TA without KMP, sirolimus (94.23%) had higher pooled response rate than glucocorticoid (31.25%), vincristine (46.15%) and propranolol (22.86%), with statistically significant differences. The pooled adverse events rate of sirolimus was 23.81%.Conclusions:Our findings indicate that for KHE and TA with KMP, combination therapy (sirolimus + glucocorticoid) and vincristine have the best efficacy, while the adverse events rate of sirolimus is relatively high. For KHE and TA without KMP, sirolimus has the highest response rate, but there is also a risk of serious adverse events. Glucocorticoid and vincristine have comparable response rate, which both inferior to sirolimus.

There is an accumulating body of evidence implicating the muscarinic acetylcholine receptor 4 (M₄) in schizophrenia and dementia with Lewy bodies, however, a clinically validated M₄ positron emission tomography (PET) radioligand is currently lacking. As such, the aim of this study was to develop a suitable M₄ PET ligand that allows the non-invasive visualization of M₄ in the brain. Structure-activity relationship studies of pyrazol-4-yl-pyridine derivates led to the discovery of target compound 12 - a subtype-selective positive allosteric modulator (PAM). The radiofluorinated analogue, [¹⁸F] 12, was synthesized in 28 ± 10% radiochemical yield, >37 GBq/μmol and an excellent radiochemical purity >99%. Initial in vitro autoradiograms on rodent brain sections were performed in the absence of carbachol and showed moderate specificity as well as a low selectivity of [¹⁸F] 12 for the M₄-rich striatum. However, in the presence of carbachol, a significant increase in tracer binding was observed in the rat striatum, which was reduced by >60% under blocking conditions, thus indicating that orthosteric ligand interaction is required for efficient binding of [¹⁸F] 12 to the allosteric site. Remarkably, however, the presence of carbachol was not required for high specific binding in the non-human primate (NHP) and human striatum, and did not further improve the specificity and selectivity of [¹⁸F] 12 in higher species. These results pointed towards significant species-differences and paved the way for a preliminary PET study in NHP, where peak brain uptake of [¹⁸F] 12 was found in the putamen and temporal cortex. In conclusion, we report on the identification and preclinical development of the first radiofluorinated M₄ PET radioligand with promising attributes. The availability of a clinically validated M₄ PET radioligand harbors potential to facilitate drug development and provide a useful diagnostic tool for non-invasive imaging.