Guided by the concept of quality by design(QbD), this study optimizes the calcination and quenching process of calcined Magnetitum and establishes the XRD characteristic spectra of calcined Magnetitum, providing a scientific basis for the formulation of quality standards. Based on the processing methods and quality requirements of Magnetitum in the Chinese Pharmacopoeia, the critical process parameters(CPPs) identified were calcination temperature, calcination time, particle size, laying thickness, and the number of vinegar quenching cycles. The critical quality attributes(CQAs) included Fe mass fraction, Fe~(2+) dissolution, and surface color. The weight coefficients were determined by combining Analytic Hierarchy Process(AHP) and the criteria importance though intercrieria correlation(CRITIC) method, and the calcination process was optimized using orthogonal experimentation. Surface color was selected as a CQA, and based on the principle of color value, the surface color of calcined Magnetitum was objectively quantified. The vinegar quenching process was then optimized to determine the best processing conditions. X-ray diffraction(XRD) was used to establish the characteristic spectra of calcined Magnetitum, and methods such as similarity evaluation, cluster analysis, and orthogonal partial least squares-discriminant analysis(OPLS-DA) were used to evaluate the quality of the spectra. The optimized calcined Magnetitum preparation process was found to be calcination at 750 ℃ for 1 h, with a laying thickness of 4 cm, a particle size of 0.4-0.8 cm, and one vinegar quenching cycle(Magnetitum-vinegar ratio 10∶3), which was stable and feasible. The XRD characteristic spectra analysis method, featuring 9 common peaks as fingerprint information, was established. The average correlation coefficient ranged from 0.839 5-0.988 1, and the average angle cosine ranged from 0.914 4 to 0.995 6, indicating good similarity. Cluster analysis results showed that Magnetitum and calcined Magnetitum could be grouped together, with similar compositions. OPLS-DA discriminant analysis identified three key characteristic peaks, with Fe_2O_3 being the distinguishing component between the two. The final optimized processing method is stable and feasible, and the XRD characteristic spectra of calcined Magnetitum was initially established, providing a reference for subsequent quality control and the formulation of quality standards for calcined Magnetitum.
X-Ray Diffraction/methods* ; Drugs, Chinese Herbal/chemistry* ; Quality Control ; Particle Size

This study aimed to investigate the correlation between changes in intestinal toxicity and compositional alterations of Euphorbiae Ebracteolatae Radix(commonly known as Langdu) before and after milk processing, and to explore the detoxification mechanism of milk processing. Mice were intragastrically administered the 95% ethanol extract of raw Euphorbiae Ebracteolatae Radix, milk-decocted(milk-processed), and water-decocted(water-processed) Euphorbiae Ebracteolatae Radix. Fecal morphology, fecal water content, and the release levels of inflammatory cytokines tumor necrosis factor-α(TNF-α) and interleukin-1β(IL-1β) in different intestinal segments were used as indicators to evaluate the effects of different processing methods on the cathartic effect and intestinal inflammatory toxicity of Euphorbiae Ebracteolatae Radix. LC-MS/MS was employed to analyze the small-molecule components in the raw product, the 95% ethanol extract of the milk-processed product, and the milky waste(precipitate) formed during milk processing, to assess the impact of milk processing on the chemical composition of Euphorbiae Ebracteolatae Radix. The results showed that compared with the blank group, both the raw and water-processed Euphorbiae Ebracteolatae Radix significantly increased the fecal morphology score, fecal water content, and the release levels of TNF-α and IL-1β in various intestinal segments(P<0.05). Compared with the raw group, all indicators in the milk-processed group significantly decreased(P<0.05), while no significant differences were observed in the water-processed group, indicating that milk, as an adjuvant in processing, plays a key role in reducing the intestinal toxicity of Euphorbiae Ebracteolatae Radix. Mass spectrometry results revealed that 29 components were identified in the raw product, including 28 terpenoids and 1 acetophenone. The content of these components decreased to varying extents after milk processing. A total of 28 components derived from Euphorbiae Ebracteolatae Radix were identified in the milky precipitate, of which 27 were terpenoids, suggesting that milk processing promotes the transfer of toxic components from Euphorbiae Ebracteolatae Radix into milk. To further investigate the effect of milk adjuvant processing on the toxic terpenoid components of Euphorbiae Ebracteolatae Radix, transmission electron microscopy(TEM) was used to observe the morphology of self-assembled casein micelles(the main protein in milk) in the milky precipitate. The micelles formed in casein-terpenoid solutions were characterized using particle size analysis, fluorescence spectroscopy, ultraviolet spectroscopy, and Fourier-transform infrared(FTIR) spectroscopy. TEM observations confirmed the presence of casein micelles in the milky precipitate. Characterization results showed that with increasing concentrations of toxic terpenoids, the average particle size of casein micelles increased, fluorescence intensity of the solution decreased, the maximum absorption wavelength in the UV spectrum shifted, and significant changes occurred in the infrared spectrum, indicating that interactions occurred between casein micelles and toxic terpenoid components. These findings indicate that the cathartic effect of Euphorbiae Ebracteolatae Radix becomes milder and its intestinal inflammatory toxicity is reduced after milk processing. The detoxification mechanism is that terpenoid components in Euphorbiae Ebracteolatae Radix reassemble with casein in milk to form micelles, promoting the transfer of some terpenoids into the milky precipitate.
Animals ; Mice ; Milk/chemistry* ; Drugs, Chinese Herbal/chemistry* ; Male ; Tumor Necrosis Factor-alpha/immunology* ; Intestines/drug effects* ; Interleukin-1beta/immunology* ; Tandem Mass Spectrometry ; Female

This study aims to explore the effects and mechanisms of 4'-O-methylbavachalcone(MeBavaC), an active compound from Psoraleae Fructus, in regulating white matter neuroinflammation to improve vascular cognitive impairment. Male Sprague-Dawley(SD) rats were randomly divided into four groups: sham group, model group, high-dose MeBavaC group(14 mg·kg~(-1)), and low-dose MeBavaC group(7 mg·kg~(-1)). The rat model of chronic cerebral hypoperfusion(CCH) was established using bilateral common carotid artery occlusion. The Morris water maze test was performed to evaluate the learning and memory abilities of the rats. Luxol fast blue staining, Nissl staining, immunofluorescence, immunohistochemistry, and transmission electron microscopy were utilized to observe the morphology and ultrastructure of the white matter myelin sheaths, axon integrity, the morphology and number of hippocampal neurons, and the loss and activation of glial cells in the white matter. Transcriptome analysis was performed to explore the potential mechanisms of white matter injury induced by CCH. Western blot and quantitative real-time polymerase chain reaction(qRT-PCR) assays were conducted to measure the expression levels of NOD-like receptor protein 3(NLRP3), absent in melanoma 2(AIM2), gasdermin D(GSDMD), cysteinyl aspartate-specific proteinase-1(caspase-1), interleukin-18(IL-18), interleukin-1β(IL-1β), erythropoietin(EPO), nuclear factor erythroid 2-related factor 2(Nrf2), and heme oxygenase-1(HO-1) in the white matter of rats. The results showed that compared with the model group, MeBavaC significantly improved the learning and memory abilities of rats with CCH, improved the damage of white matter myelin sheath, maintained axonal integrity, reduced the loss of hippocampal neurons and oligodendrocytes in the white matter, inhibited the activation of microglia and the proliferation of astrocytes in the white matter, and suppressed the NLRP3/AIM2/caspase-1/GSDMD pathway. The expression levels of inflammatory cytokines IL-1β and IL-18 were significantly reduced, while EPO expression and the expression of Nrf2/HO-1 antioxidant pathway were notably elevated. In conclusion, MeBavaC can alleviate cognitive impairment in rats with CCH and suppress neuroinflammation in cerebral white matter. The mechanism of action may involve activation of EPO activity, promotion of endogenous antioxidant pathways, and inhibition of neuroinflammation in the white matter. This study suggests that MeBavaC exhibits antioxidant and anti-neuroinflammatory effects, showing potential application in improving cognitive dysfunction.
Animals ; Male ; Rats, Sprague-Dawley ; NF-E2-Related Factor 2/immunology* ; Rats ; Chalcones/administration & dosage* ; Cognitive Dysfunction/metabolism* ; Signal Transduction/drug effects* ; Neuroinflammatory Diseases/drug therapy* ; Heme Oxygenase-1/metabolism* ; Humans ; Heme Oxygenase (Decyclizing)/genetics*

Sepsis is a systemic inflammatory response caused by severe infection or trauma, and is one of the common causes of acute lung injury(ALI) and acute respiratory distress syndrome(ARDS). Sepsis-acute lung injury(SALI) is a critical clinical condition with high morbidity and mortality. Its pathogenesis is complex and not yet fully understood, and there is currently a lack of targeted and effective treatment options. Pyroptosis, a novel form of programmed cell death, plays a key role in the pathological process of SALI by activating inflammasomes and releasing inflammatory factors, making it a potential therapeutic target. In recent years, the role of traditional Chinese medicine(TCM) in regulating signaling pathways related to pyroptosis through multi-components and multi-targets has attracted increasing attention. TCM may intervene in pyroptosis by inhibiting the activation of NLRP3 inflammasomes and regulating the expression of Caspase family proteins, thus alleviating inflammatory damage in lung tissues. This paper systematically reviews the molecular regulatory network of pyroptosis in SALI and explores the potential mechanisms and research progress on TCM intervention in cellular pyroptosis. The aim is to provide new ideas and theoretical support for basic research and clinical treatment strategies of TCM in SALI.
Pyroptosis/drug effects* ; Humans ; Sepsis/genetics* ; Acute Lung Injury/physiopathology* ; Animals ; Drugs, Chinese Herbal/therapeutic use* ; Medicine, Chinese Traditional ; Inflammasomes/metabolism* ; NLR Family, Pyrin Domain-Containing 3 Protein/genetics*

OBJECTIVE: To explore clinical efficacy of different technical combinations in treating ischemic diabetic foot (DF). METHODS: A retrospective analysis was conducted on 35 patients with DF who were treated with vascular interventional opening technique, periosteal distraction technique and bone cement coverage technique from January 2024 to November 2024. They were divided into comprehensive group and periosteal distraction group according to whether the vascular interventional opening technique was used in combination or not. There were 5 patients in comprehensive group, including 4 males and 1 female, aged from 59 to 73 years old with an average of (64.40±5.46) years old;the duration of diabetes ranged from 0.17 to 30.00 years with an average of (14.63±12.02) years;the courses of DF ranged from 30 to 150 days with an average of (84.00±61.48) days;2 patients were grade 2, 2 patients were grade 3, and 1 patient was grade 4 according to Wagner classification;combined vascular interventional opening, periosteal distraction and bone cement coverage surgery for treatment. There were 30 patients in periosteal stretch group, including 22 males and 8 females, aged from 58 to 86 years old with an average of (72.63±7.84) years old;the duration of diabetes was 10.00 (6.75, 16.75) years;the courses of DF was 30.00 (15.00, 37.50) days;14 patients were grade 2, 11 patients were grade 3, and 5 patients were grade 4 according to Wagner classification; combined periosteal distraction and bone cement coverage surgery for treatment. Changes of C-reactive protein (CRP), interleukin-6 (IL-6), and procalcitonin (PCT), toe skin temperature, peripheral capillary oxygen saturation (SpO₂), and visual analogue scale (VAS) for pain were compared between two groups before operation and 1 week after operation. The number of operations, healing period, healing number, toe amputation number, preoperative fever situation and the number of complications were compared between two groups. RESULTS: Both groups were followed up for at least 6 months. There were no statistically significant differences in the number of operations, healing period, toe amputation rate, wound healing rate and complications between two groups (P>0.05). Before operation, the toe skin temperature of comprehensive group (26.98±0.88) ℃ was lower than that of periosteal distraction group (28.17±1.45) ℃, and the difference was statistically significant (P<0.05);while there were no statistically significant difference in CRP, IL-6, PCT, toe SpO2 and VAS between two groups (P>0.05). At 1 week after operation, IL-6, toe skin temperature, toe SpO₂ and VAS in comprehensive group were 12.29(7.92, 22.15) pg·ml-1, (36.02±0.23) ℃, (95.80±0.84) % and(1.40±0.55) respectively, while those in periosteal distraction group were 5.49(4.36, 7.45) pg·ml^-1, (31.36±1.57) ℃, (84.53±6.38) %, (2.20±0.81);and there were statistically significant differences between two groups(P<0.05). CRP, IL-6 and VAS at 1 week after operation in both groups were decreased compared with those before operation, and the differences were statistically significant(P<0.05). The toe skin temperature and SpO₂ were increased compared with those before operation, and the differences were statistically significant(P<0.001). CONCLUSION The multi-technique combination therapy, including vascular interventional opening technique, periostealdistraction technique and bone cement covering technique, could protect each other, enhance efficacy, effectively promote the wound healing of ischemic diabetic foot ulcer, and reduce the toe amputation rate. For moderate to severe ischemic DF, the combined use of periosteal distraction and bone cement coverage techniques has a satisfactory effect. For extremely severe ischemic DF with inflow tract lesions, vascular interventional opening techniques need to be added.
Humans ; Male ; Female ; Middle Aged ; Aged ; Diabetic Foot/surgery* ; Retrospective Studies ; Aged, 80 and over ; Ischemia/surgery* ; Interleukin-6/metabolism*

Objective To investigate the risk factors for bronchopulmonary dysplasia(BPD)in twin preterm infants with a gestational age of<34 weeks,and to provide a basis for early identification of BPD in twin preterm infants in clinical practice.Methods A retrospective analysis was performed for the twin preterm infants with a gestational age of<34 weeks who were admitted to 22 hospitals nationwide from January 2018 to December 2020.According to their conditions,they were divided into group A(both twins had BPD),group B(only one twin had BPD),and group C(neither twin had BPD).The risk factors for BPD in twin preterm infants were analyzed.Further analysis was conducted on group B to investigate the postnatal risk factors for BPD within twins.Results A total of 904 pairs of twins with a gestational age of<34 weeks were included in this study.The multivariate logistic regression analysis showed that compared with group C,birth weight discordance of>25%between the twins was an independent risk factor for BPD in one of the twins(OR=3.370,95%CI:1.500-7.568,P<0.05),and high gestational age at birth was a protective factor against BPD(P<0.05).The conditional logistic regression analysis of group B showed that small-for-gestational-age(SGA)birth was an independent risk factor for BPD in individual twins(OR=5.017,95%CI:1.040-24.190,P<0.05).Conclusions The development of BPD in twin preterm infants is associated with gestational age,birth weight discordance between the twins,and SGA birth.

In this paper, the antitussive and expectorant activity of platycodin D (PD) were studied by constructing a mouse cough induced by concentrated ammonia water and a mouse trachea phenol red excretion model. The mechanism of antitussive and expectorant effect of PD was studied by metabolomics. The animal experiment was approved by the Animal Ethics Committee of Jiangxi University of Chinese Medicine (approval number: JZLLSC-20220739). Then mice were randomly divided into the normal, model, positive drug, PD low-dose, PD medium-dose and PD high-dose group. The antitussive and expectorant effects of PD were evaluated using a cough mouse model induced by concentrated ammonia water and a mouse tracheal phenol red excretion model, respectively. UHPLC-LTQ-Orbitrap-MS was used to identify the metabolites of mouse lung tissue, and multivariate statistical analysis method of orthogonal partial least squares discriminant analysis (OPLS-DA) was used for metabolites profile analysis. The differential metabolites were screened by variable projected importance value (VIP) and t-test results. Pathways for enrichment of differentiated metabolites were analyzed using the MetaboAnalyst platform. The comparative method was applied to analyze the differences in mechanisms of PD, Deapio-platycodin D (DPD) and total platycosides fraction. The results showed that PD at different concentrations could significantly prolong (P < 0.05) the incubation period of cough mice induced by ammonia water, reduce the coughs frequency, and significantly increase (P < 0.05) the amount of phenol red excretion in phenol red excretion model mice. PD could regulate 6 metabolic pathways of phenylalanine, tyrosine and tryptophan biosynthesis, linoleic acid metabolism, phenylalanine metabolism, glycerophospholipid metabolism, and tyrosine metabolism to exert antitussive effect. It could also regulate 8 metabolic pathways of linoleic acid metabolism, glyoxylic acid and dicarboxylic acid metabolism, glycerol phospholipid metabolism, citric acid cycle and arachidonic acid metabolism to exert an expectorant effect. However, only linoleic acid metabolism and glycerophospholipid metabolism could be regulated by the PD, total platycosides fraction and DPD, which may be ascribed to the structural difference of the platycosides and the interaction between platycosides and the intestinal microbiota. Functional analysis showed that these metabolic pathways are closely related to the regulatory mechanisms of anti-inflammatory response, immune function regulation, neurotransmitter release, cell signal transduction, energy metabolism and cell apoptosis. This study shows that PD possesses good antitussive and expectorant activities. In addition, the mechanism difference of PD, total platycosides fraction and DPD imply that the apiose in PD and the interaction between PD and intestinal microbiota could exert an important effect on the antitussive and expectorant mechanism of the platycosides.

Objective To analyze the morphological alterations of corpus callosum in children with spastic cerebral palsy(SCP)using three-dimensional magnetization prepared rapid acquisition gradient echo(3D-MPRAGE)technology and to investigate the correlation between morphological indexes and gross motor function.Methods Sagittal T1WI 3D-MPRAGE data was collected from 136 children with SCP(SCP group)and 132 age-and gender-matched healthy controls(HC)(HC group),and the gross motor function measure-88(GMFM-88)was applied to assess the gross motor function.Independent sample t-test was used to compare the corpus callosum surface area,volume,maximum anterior-posterior diameter,median sagittal area(total area and area of Ⅰ-Ⅴ zone)between the two groups.Partial correlation analysis was performed to calculate the correlation between morphological indexes of the corpus callosum and GMFM-88 with age as a covariate.Results Children under 3 years old,the corpus callosum surface area of the SCP group(3 914.51 mm2±1 207.97 mm2)was lower than that of the HC group(5 725.51 mm2±1 412.66 mm2).The volume of the corpus callosum(6 108.46 mm3±2 803.97 mm3)in the SCP group was lower than that of the HC group(11 297.96 mm3±4 109.02 mm3).Also,the maximum anterior-posterior diameter of the corpus callosum in the SCP group(53.40 mm±6.31 mm)was lower than that of the HC group(57.74 mm±6.04 mm)(all P<0.05).Children over 3 years old,the corpus callosum surface area of the SCP group(4 970.06 mm2±1 191.31 mm2)was lower than that of the HC group(6 372.55 mm2±1 445.59 mm2).The volume of the corpus callosum(8 330.20 mm3±2 888.20 mm3)in the SCP group was lower than that of the HC group(13 599.82 mm3±3 429.81 mm3)(all P<0.05).Partial correlation analysis showed significant correlation between corpus callosum volume,median sagittal area and gross motor score(P<0.01)with age as a covari-ate.Conclusion The 3D-MPRAGE technology can be useful for the comprehensive assessment of morphological alterations of the corpus callosum in SCP.The corpus callosum volume,and median sagittal area may become neuroimaging references for the assess-ment of motor development in cerebral palsy(CP).

Objective:To validate the morphological changes of the parieto-occipital sulcus on the transcalvarial axial plane between 20 and 32 weeks of gestation, simplify grade for assessing fetal parieto-occipital sulcus development, and confirm its clinical feasibility.Methods:This was a cross-sectional study analysis that included 550 cases of normal singleton fetuses between 20 and 32 weeks of gestation, who underwent routine ultrasound examinations at Shenzhen Maternity and Child Healthcare Hospital from September 2019 to June 2022. The morphological changes of the bilateral parieto-occipital sulci on the transcalvarial axial plane were observed. The development of the parieto-occipital sulcus was classified into 6 grades based on the developmental features of angulation, progressive closure, and curvilinear growth: straight or shallow arcuate (Grade 0), shallow and wide V-shaped (Grade 1), deep and narrow V-shaped (Grade 2), Y-shaped (Grade 3), I-shaped (Grade 4), and curvilinear (Grade 5). The gestational age at examination and pregnancy outcomes were recorded. The distribution of gestational weeks for fetuses with different grades of parieto-occipital sulci on the left and right sides was analyzed. The symmetry between bilateral parieto-occipital sulcus gradings within individuals, as well as the inter-observer and intra-observer reliability were assessed using the Weighted Kappa coefficient. The gender differences in asymmetry of parieto-occipital sulci grades between the left and right sides was analyzed. Moreover, a model for predicting the grade of the parieto-occipital sulcus based on gestational week was established.Results:Grade for the left parieto-occipital sulcus was obtained for 549 fetuses, while grade for the right was obtained for 550 fetuses. From 20 to 32 weeks of gestation, the morphology of the fetal parieto-occipital sulcus was divided into Grade 0-5, progressing from low to high with gestational development. Grade 0 showed that the sulcus was not visible or only had a slight arcuate indentation, occurring at 20-22 weeks; Grade 1 presented as a shallow and wide "V" shape with an obtuse angle at the top, appearing from 20 to 27 weeks; Grade 2 was a deep and narrow "V" shape with an acute angle at the top, appearing from 24 to 29 weeks; Grade 3 appeared as a "Y" shape with the top part partially closed and the bottom still open, occurring between 26 to 30 weeks; Grade 4 was a fully closed "I" shape, appearing at 29-32 weeks; Grade 5 presented as a curved shape, indicating the parieto-occipital sulcus was approaching maturity, appearing from 31 to 32 weeks. There was no statistically significant difference in the distribution of gestational weeks for bilateral parieto-occipital sulcus developmental grade ( P>0.05). Bilateral parieto-occipital sulcus grade could be assessed in 549 fetuses, of which 43 cases (7.83%) exhibited grade asymmetry with a one-grade difference between sides; such asymmetry showed no significant difference between male and female genders ( P=0.647). The weighted kappa coefficient analysis results indicated a strong consistency in the development of the parieto-occipital sulci on both sides within individuals, generally demonstrating symmetrical development ( P<0.001). The intra-observer and inter-observer weighted kappa coefficients were 0.92 and 0.75, respectively, with good consistency. Conclusions:Prenatal ultrasound via the transcalvarial axial plane enables a preliminary and rapid assessment of the development of bilateral parieto-occipital sulci, facilitating early evaluation of fetal cortical maturation.

Objective:To study the stability and morphological changes of the convexity sulci in normal fetuses between 20 and 32 weeks, and to explore the simplified grade for evaluating the convexity sulci development and analyzing its clinical significance.Methods:This study was a cross-sectional analysis. A total of 551 cases of normal singleton pregnancies between 20 and 32 weeks of gestation were retrospectively collected, who underwent routine ultrasound examinations at Shenzhen Maternity and Child Healthcare Hospital from September 2019 to June 2022. The display of the far-field convexity sulci on the transcalvarial axial plane was observed as 0 for not displayed and 1 for displayed.Further, based on the morphology and number of convexity sulci, they were classified into five grades: no sulcus displayed (grade 0), one sulcus (grade 1), two sulci (grade 2), three sulci (grade 3), and four or more sulci (grade 4). The gestational age at examination and pregnancy outcomes were recorded. The distribution characteristics of gestational weeks for each grade of the convexity sulci were analyzed, and the gestational week distribution of the left and right convexity sulci was compared to analyze bilateral symmetry. The Weighted Kappa coefficient was used to analyze inter-observer and intra-observer consistency, and curve regression analysis was employed to establish a model for predicting grade based on gestational weeks.Results:Before 25 weeks of gestation, the convexity of the fetal cranial vertex was completely smooth.The central sulcus consistently appeared after 26 weeks, while the superior frontal sulcus, intraparietal sulcus, postcentral sulcus, and precentral sulcus consistently appeared between 28 and 31 weeks. Among these, the superior frontal sulcus had a lower display rate before 29 weeks. By 32 weeks, all convexity sulci of the cranial vertex should be visible. Three hundred and eleven fetuses were graded for the left, and 240 fetuses were graded for the right. The developmental grade of the convexity sulci increased from Grade 0 to Grade 4 as the gestational age progressed. Grade 0 appeared between 20-26 weeks, grade 1 between 25-28 weeks, grade 2 between 26-28 weeks, grade 3 between 27-30 weeks, and grade 4 between 27-32 weeks. The distribution of grade did not differ significantly between the left and right sides of grade 0, 1, 3 and 4 (all P>0.05), while there was a significant difference in the distribution of gestational age between the convexity sulci of grade 2 ( P<0.05). The Weighted Kappa coefficients for intra-observer and inter-observer consistency were 0.94 and 0.86, respectively, indicating strong consistency. Conclusions:The simplified grade for assessing the development of convexity sulci in normal fetuses on the transcalvarial axial plane via prenatal ultrasound can provide a preliminary evaluation of the maturation of convexity sulci in fetuses between 20 and 32 weeks of gestation.