Human umbilical cord mesenchymal stem cell （hUC-MSC） as a cell-based therapeutic strategy have demonstrated significant application potential in the field of intervention for neurodegenerative disease （NDD） due to their advantages such as self-renewal， multi-directional differentiation， and low immunogenicity. hUC-MSC effectively intervenes in the pathological features and neurological functions of various disease models such as Alzheimer disease， Parkinson’s disease， amyotrophic lateral sclerosis， and multiple sclerosis primarily through multiple mechanisms such as homing and differentiation， mediating paracrine actions and releasing exosomes， as well as immune regulation and anti-inflammation. Some clinical studies have also preliminarily verified their safety and effectiveness. Currently， its research still faces challenges such as immune rejection reactions requiring further observation， long-term safety needing evaluation， mechanisms of action not being fully elucidated， and slow progress in clinical trials. Future research needs to establish pharmaceutical standards for hUC-MSC， deepen their pharmacological mechanisms and clinical trials， ultimately providing new and effective drug treatment options for patients with NDD.

OBJECTIVE To compare the efficacy and safety of evolocumab and probucol in patients with ultra-high-risk atherosclerotic cardiovascular disease （ASCVD） following percutaneous coronary intervention （PCI）. METHODS A retrospective analysis was conducted on 156 ultra-high-risk ASCVD patients who underwent PCI in our institution between January 1， 2023 and December 31， 2024. According to the lipid-lowering regimen， the patients were categorized into evolocumab group （ n ＝86） and probucol group （ n ＝70）. Changes in lipid parameters [total cholesterol （TC）， low-density lipoprot ein cholesterol （LDL-C）， high-density lipoprotein cholesterol （HDL-C）， triglycerides， lipoprotein （a）， and lipid goal achievement rate ] ， inflammatory markers [interleukin-6 （IL-6） and C-reactive protein （CRP） ] ， and cardiac function indices （left ventricular ejection fraction， left ventricular end-systolic diameter， left ventricular end-diastolic diameter， and N-terminal pro-B-type natriuretic peptide） were compared between two groups at baseline and after 6 months of treatment. The incidence of adverse clinical events during treatment， including acute myocardial infarction， in-stent restenosis， acute heart failure， cerebral hemorrhage， and stroke， was also evaluated. RESULTS No statistically significant differences were observed between the two groups at baseline （ P ＞0.05）. After 6 months of treatment， both groups demonstrated significant improvements in lipid profiles （except HDL-C） and inflammatory markers compared to those at baseline （ P ＜0.05）. The evolocumab group exhibited greater reductions in TC， LDL-C， IL-6， and CRP， along with a higher lipid target achievement rate， compared with the probucol group （ P ＜0.05）. There were no statistically significant differences in the cardiac function-related indicators before and after treatment between the two groups， nor in the incidence of adverse events during the treatment （ P ＞0.05）. CONCLUSIONS For ultra-high-risk ASCVD patients after PCI， both of the above treatment options are associated with improvements in blood lipid and inflammatory response， with good safety during short-term follow-up. Evolocumab shows superior efficacy in TC， LDL-C and inflammatory markers reduction and lipid target achievement， compared to probucol.

From the perspective of transfusion medicine and based on the vision and framework of patient blood management, this article combines the advances in basic science, blood transfusion, laboratory, and clinical medicine. It aims to systematically review the key elements and characteristics of patient fibrinogen management by maintaining and optimizing patients' hemostatic function while reducing blood transfusions. This review enriches the connotation of transfusion medicine, especially patient blood management, and provides valuable insights for clinical practice.

Objective: To investigate the inhibitory effect of neoeriocitrin (Neo) on ligature-induced experimental periodontitis in mice and evaluate its biosafety, providing experimental evidence for novel candidate drugs in periodontitis treatment. Methods: This study has been approved by the Animal Welfare and Ethical Safety Committee. A periodontitis model was established in C57BL/6J mice using silk ligation. The mice were divided into control, periodontitis model, and three Neo treatment groups (5, 10, 20 mg/kg Neo). After 2 weeks of intervention, alveolar bone resorption was analyzed by micro-computed tomography (micro-CT); periodontal tissue pathological changes were observed via hematoxylin-eosin (HE) and Masson staining; osteoclasts were counted using tartrate-resistant acid phosphatase staining; serum inflammatory factor levels [tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), interleukin-1β (IL-1β), interleukin-10 (IL-10)] were detected by enzyme-linked immunosorbent assay; gut microbiota changes were analyzed by 16S rRNA sequencing; and biosafety was assessed through HE staining of the heart, liver, spleen, lung, kidney, and colon, as well as zonula occludens-1 (ZO-1) immunohistochemical staining of the colon. Results: Compared with the periodontitis model group, the 10 mg/kg Neo treatment group showed significantly alleviated alveolar bone resorption, manifested as reduced cementoenamel junction to alveolar bone crest distance, increased bone mineral density, bone volume fraction, and trabecular thickness. Additionally, reduced inflammatory cell infiltration, improved collagen fiber arrangement, and a significantly decreased number of osteoclasts were observed in periodontal tissues. Serum levels of pro-inflammatory factors TNF-α and IL-6 were also reduced. Furthermore, 10 mg/kg Neo intervention modulated the gut microbiota structure without causing significant multi-organ toxicity or impairing intestinal barrier function. Conclusion Neo can effectively mitigate the progression of experimental periodontitis by inhibiting alveolar bone resorption, reducing periodontal tissue inflammation, modulating systemic immunity, and improving gut microbiota. With good biosafety, Neo is a promising candidate drug for the treatment of periodontitis.

ObjectiveTo analyze the processing mechanism underlying the enhanced effect of invigorating spleen and stopping diarrhea of soil-fried Atractylodis Macrocephalae Rhizoma（AMR） by analyzing the changes of microstructure， chemical composition and anti-ulcerative colitis（UC） activity before and after soil stir-frying. MethodsThe microstructure and elemental composition of AMR before and after soil stir-frying were analyzed by scanning electron microscopy-energy dispersive spectroscopy（SEM-EDS）， to investigate the differences in microstructure and the underlying causes. Ultra-high performance liquid chromatography-quadrupole-time-of-flight mass spectrometry（UPLC-Q-TOF-MS） coupled with UNIFI 1.9.2 natural product analysis platform were used to analyze and identify the chemical constituents in raw and soil-fried products， and multivariate statistical methods including principal component analysis（PCA） and orthogonal partial least squares-discriminant analysis（OPLS-DA） were used to explore the differences and sources of chemical constituents between them. A dextran sulfate sodium（DSS）-induced UC mouse model was established. The method of disease activity index（DAI） was used to evaluate the severity of intestinal inflammation. Hematoxylin-eosin（HE） staining was used to observe the pathological changes of colon tissue， enzyme-linked immunosorbent assay（ELISA） was used to detect the levels of inflammatory factors， Real-time quantitative polymerase chain reaction（Real-time PCR） and Western blot were used to analyze the expressions of key genes and proteins involved in the intestinal mucosal barrier. The 16S rRNA sequencing was used to evaluate the diversity of intestinal flora， headspace gas chromatography-mass spectrometry（HS-GC-MS） was used to explore the levels of short-chain fatty acids（SCFAs） in feces. Base on the above findings， this paper investigated the effects of raw and soil-fried AMR on the biological， chemical， mechanical and immune barriers of model animals， and the differences in pharmacological effects and underlying mechanisms from the perspective of regulating the intestinal mucosal barrier in UC mice. ResultsSEM observation revealed numerous hearth soil particles on the surface of soil-fried AMR， accompanied by bubble-like bulges. At the same time， there were many cracks and folds on the surface of the hearth soil. EDS analysis revealed that the contents of Si， Al， Mg and Ca in soil-fried AMR were significantly higher than those of raw products， and these elements constituted the primary components of hearth soil. UPLC-Q-TOF-MS combined with database comparison was used to identify the chemical constituents of raw and soil-fried AMR. In positive ion mode， a total of 132 components were identified， primarily comprising three categories of terpenoids， polyphenols and amino acids. In negative ion mode， a total of 40 components were identified， primarily polyphenolic and glycoside compounds. Among them， the contents of sesquiterpenes and polyphenolic acids were changed significantly before and after processing. Soil-fried AMR could reduce the DAI score of UC mice， alleviate the shortening of colon length， reduce the levels of pro-inflammatory factors such as interleukin（IL）-17， IL-18， γ-interferon（IFN-γ） and tumor necrosis factor（TNF）-α in serum， increase the levels of anti-inflammatory factors such as secretory immunoglobulin A（sIgA）， IL-10， IL-4 and transforming growth factor-β（TGF-β） in serum， increase the expressions of key genes and proteins of intestinal mucosal barrier such as tight junction protein-1（ZO-1）， Occludin， Claudin-1 and mucin 2（MUC2） in colonic mucosa， and improve the disorders of intestinal flora diversity and the levels of SCFAs（P<0.05， P<0.01）. The raw and stir-fried products of AMR also exhibited the aforementioned effects， but they were weaker than the soil-fried products. Additionally， the auxiliary material hearth soil also had a certain pharmacodynamic effect. ConclusionSoil-fried AMR can enhance the protective effect on intestinal mucosal barrier in UC mice. These changes or heating-induced alterations in the microscopic structure and chemical composition of AMR may be attributed to the dual effects of adsorption of hearth soil.

ObjectiveTo analyze the processing mechanism underlying the enhanced effect of invigorating spleen and stopping diarrhea of soil-fried Atractylodis Macrocephalae Rhizoma（AMR） by analyzing the changes of microstructure， chemical composition and anti-ulcerative colitis（UC） activity before and after soil stir-frying. MethodsThe microstructure and elemental composition of AMR before and after soil stir-frying were analyzed by scanning electron microscopy-energy dispersive spectroscopy（SEM-EDS）， to investigate the differences in microstructure and the underlying causes. Ultra-high performance liquid chromatography-quadrupole-time-of-flight mass spectrometry（UPLC-Q-TOF-MS） coupled with UNIFI 1.9.2 natural product analysis platform were used to analyze and identify the chemical constituents in raw and soil-fried products， and multivariate statistical methods including principal component analysis（PCA） and orthogonal partial least squares-discriminant analysis（OPLS-DA） were used to explore the differences and sources of chemical constituents between them. A dextran sulfate sodium（DSS）-induced UC mouse model was established. The method of disease activity index（DAI） was used to evaluate the severity of intestinal inflammation. Hematoxylin-eosin（HE） staining was used to observe the pathological changes of colon tissue， enzyme-linked immunosorbent assay（ELISA） was used to detect the levels of inflammatory factors， Real-time quantitative polymerase chain reaction（Real-time PCR） and Western blot were used to analyze the expressions of key genes and proteins involved in the intestinal mucosal barrier. The 16S rRNA sequencing was used to evaluate the diversity of intestinal flora， headspace gas chromatography-mass spectrometry（HS-GC-MS） was used to explore the levels of short-chain fatty acids（SCFAs） in feces. Base on the above findings， this paper investigated the effects of raw and soil-fried AMR on the biological， chemical， mechanical and immune barriers of model animals， and the differences in pharmacological effects and underlying mechanisms from the perspective of regulating the intestinal mucosal barrier in UC mice. ResultsSEM observation revealed numerous hearth soil particles on the surface of soil-fried AMR， accompanied by bubble-like bulges. At the same time， there were many cracks and folds on the surface of the hearth soil. EDS analysis revealed that the contents of Si， Al， Mg and Ca in soil-fried AMR were significantly higher than those of raw products， and these elements constituted the primary components of hearth soil. UPLC-Q-TOF-MS combined with database comparison was used to identify the chemical constituents of raw and soil-fried AMR. In positive ion mode， a total of 132 components were identified， primarily comprising three categories of terpenoids， polyphenols and amino acids. In negative ion mode， a total of 40 components were identified， primarily polyphenolic and glycoside compounds. Among them， the contents of sesquiterpenes and polyphenolic acids were changed significantly before and after processing. Soil-fried AMR could reduce the DAI score of UC mice， alleviate the shortening of colon length， reduce the levels of pro-inflammatory factors such as interleukin（IL）-17， IL-18， γ-interferon（IFN-γ） and tumor necrosis factor（TNF）-α in serum， increase the levels of anti-inflammatory factors such as secretory immunoglobulin A（sIgA）， IL-10， IL-4 and transforming growth factor-β（TGF-β） in serum， increase the expressions of key genes and proteins of intestinal mucosal barrier such as tight junction protein-1（ZO-1）， Occludin， Claudin-1 and mucin 2（MUC2） in colonic mucosa， and improve the disorders of intestinal flora diversity and the levels of SCFAs（P<0.05， P<0.01）. The raw and stir-fried products of AMR also exhibited the aforementioned effects， but they were weaker than the soil-fried products. Additionally， the auxiliary material hearth soil also had a certain pharmacodynamic effect. ConclusionSoil-fried AMR can enhance the protective effect on intestinal mucosal barrier in UC mice. These changes or heating-induced alterations in the microscopic structure and chemical composition of AMR may be attributed to the dual effects of adsorption of hearth soil.

Objective To evaluate the impact of an integrated management mode of prenatal diagnosis-postnatal treatment for congenital heart disease (CHD) on perioperative and long-term outcomes of the arterial switch operation (ASO), and to analyze the efficacy of ASO in a single center. Methods This retrospective study analyzed the clinical data of 183 children who underwent ASO at Guangdong Provincial People’s Hospital from 2018 to 2024. The cohort included 106 (57.9%) patients of transposition of the great arteries with intact ventricular septum (TGA/IVS), 61 (33.3%) patients of transposition of the great arteries with ventricular septal defect (TGA/VSD), and 16 (8.7%) patients of Taussig-bing anomaly (TBA). Perioperative indicators were compared between 91 patients in the prenatal-postnatal integrated management group (an integrated group) and 92 patients in the traditional management group (a non-integrated group). Long-term survival and reoperation rates were analyzed using Kaplan-Meier curves. Results The overall perioperative mortality rate was 4.9% (9/183), showing a downward trend year by year. The primary cause of perioperative mortality was low cardiac output syndrome (LCOS), which occurred in 12 patients (6.6% incidence) with a mortality rate of 75.0%. The integrated group had a higher proportion of males (89.0% vs. 72.8%, P<0.05) and lower body weight [3.1 (2.7, 3.3) kg vs. 3.3 (3.0, 3.7) kg, P<0.05] compared to the non-integrated group. The age at surgery was significantly earlier in the integrated group [7 (3, 10) d vs. 14 (9, 48) d, P<0.05], and all children in the integrated group underwent ASO within the optimal surgical window (100.0% vs. 82.6%, P<0.05). Intraoperatively, cardiopulmonary bypass time [173 (150, 207) min vs. 186 (159, 237) min, P<0.05] and aortic cross-clamp time [100 (90, 117) min vs. 116 (97, 142) min, P<0.05] were significantly shorter in the integrated group. Although the integrated group had longer postoperative mechanical ventilation time [145 (98, 214) h vs. 116 (77, 147) h, P<0.05] and higher 48-hour maximum vasoactive inotropic score [15 (10, 21) points vs. 12 (8, 16) points, P<0.05], there was no statistically significant difference in the incidence of severe complications (LCOS, necrotizing enterocolitis, extracorporeal membrane oxygenation) or mortality rate (3.3% vs. 6.5%, P=0.51) between the two groups, despite earlier surgical intervention and a higher proportion of critically ill cases in the integrated group. The length of hospital stay in the emergency surgery group was significantly shorter than that in the elective surgery group [20 (15, 28) d vs. 25 (21, 30) d, P<0.05], suggesting that early surgery may be of potential benefit. A total of 163 patients were successfully followed up for a median of 4.7 years, with a 5-year survival rate of 95.1% and a freedom from reintervention survival rate of 95.1%. There were no late deaths, and the most common postoperative complication was pulmonary artery stenosis. Conclusion The integrated management model allowed critically ill children with lower body weights to safely undergo surgery, significantly optimizing the timing of surgery and shortening intraoperative times. The long-term risk of reoperation after ASO is primarily concentrated on pulmonary artery stenosis, necessitating long-term follow-up and monitoring.

ObjectiveThis study aims to investigate whether Xixintang could ameliorate cognitive dysfunction in an Alzheimer's disease （AD） rat model induced by D-galactose and β-amyloid （Aβ_25-35）， by means of repairing the colonic mucosal barrier， regulating the Toll-like receptor 4 （TLR4）/nuclear factor-κB p65 （NF-κB p65） signaling pathway， and intervening in the pathological process mediated by the gut-brain axis. MethodsSixty specific pathogen-free （SPF） male Sprague-Dawley （SD） rats were randomly divided to five groups （n=12）： A control group， a model group， a donepezil group， an Xixintang group， and a probiotic group. Except for those in the control group， rats in all other groups received daily intraperitoneal injections of D-galactose for six consecutive weeks. Subsequently， aggregated Aβ_25-35 was injected stereotactically into the bilateral ventricles to establish the AD model. During the intervention periods， the rats in all groups were administered their respective drugs and normal saline by gavage. The Morris water maze test was used to assess the capacity for spatial learning and memory. Hematoxylin-eosin （HE） staining was employed to observe the histopathological changes in the colon tissues. Immunofluorescence was used to detect Aβ_1-41 deposition in the hippocampal region and Mucin 2 （MUC2） expression in the colonic mucosa. Western blot was performed to measure the protein expression levels of FFAR2，TLR4， NF-κB p65， occludin （OCLN）， zonula occludens-1 （ZO-1）， and MUC2 in the colonic tissues. Enzyme-linked immunosorbent assay （ELISA） was used to determine the contents of interleukin-6 （IL-6）， tumor necrosis factor-α （TNF-α）， serum amyloid A （SAA）， and Aβ_1-42 in the hippocampal region from the colonic tissues. The lipopolysaccharide （LPS） concentrations in colon tissues of rats were measured by using a dynamic chromogenic limulus assay. ResultsCompared with those in the control group， the rats in the model group exhibited a significantly prolonged escape latency and a markedly shorter duration in the target quadrant （P<0.01）. The integrity of the colonic mucosal structure was compromised， with disordered gland arrangement and a reduced number of goblet cells. The Aβ_1-42 deposition in the hippocampal region was significantly increased （P<0.01）. The protein expression levels of TLR4 and NF-κB p65 in colonic tissues were significantly upregulated （P<0.01）， while those of occludin and ZO-1 were downregulated （P<0.01）. The contents of inflammatory factors such as IL-6， TNF-α， and SAA were significantly elevated （P<0.01）， and the LPS level in the serum was markedly increased （P<0.01）. In comparison to those in the model group， the rats in the Xixintang group showed a significantly shortened escape latency and a prolonged duration in the target quadrant （P<0.01）. The colonic mucosal structure was ameliorated， with neat gland arrangement and an increased number of goblet cells. The Aβ_1-42 deposition in the hippocampal region was reduced （P<0.01）. The protein expressions of TLR4 and NF-κB p65 in the colon tissues were decreased （P<0.05，P<0.01）， while the protein levels of occludin and ZO-1 were increased （P<0.01）. The contents of IL-6， TNF-α， and serum amyloid A （SAA） were decreased （P<0.01）， and the LPS level was reduced （P<0.01）. ConclusionXixintang can significantly ameliorate cognitive dysfunction of AD model rats， by means of restoring the colonic mucosal barrier structure， reducing cerebral Aβ deposition， and suppressing peripheral and central inflammatory response. Its mechanism of action may be closely associated with the suppression of the TLR4/NF-κB signaling pathway activation， reduction of endotoxin levels， and regulation of the gut-brain axis.

ObjectiveThis study aims to investigate whether Xixintang could ameliorate cognitive dysfunction in an Alzheimer's disease （AD） rat model induced by D-galactose and β-amyloid （Aβ_25-35）， by means of repairing the colonic mucosal barrier， regulating the Toll-like receptor 4 （TLR4）/nuclear factor-κB p65 （NF-κB p65） signaling pathway， and intervening in the pathological process mediated by the gut-brain axis. MethodsSixty specific pathogen-free （SPF） male Sprague-Dawley （SD） rats were randomly divided to five groups （n=12）： A control group， a model group， a donepezil group， an Xixintang group， and a probiotic group. Except for those in the control group， rats in all other groups received daily intraperitoneal injections of D-galactose for six consecutive weeks. Subsequently， aggregated Aβ_25-35 was injected stereotactically into the bilateral ventricles to establish the AD model. During the intervention periods， the rats in all groups were administered their respective drugs and normal saline by gavage. The Morris water maze test was used to assess the capacity for spatial learning and memory. Hematoxylin-eosin （HE） staining was employed to observe the histopathological changes in the colon tissues. Immunofluorescence was used to detect Aβ_1-41 deposition in the hippocampal region and Mucin 2 （MUC2） expression in the colonic mucosa. Western blot was performed to measure the protein expression levels of FFAR2，TLR4， NF-κB p65， occludin （OCLN）， zonula occludens-1 （ZO-1）， and MUC2 in the colonic tissues. Enzyme-linked immunosorbent assay （ELISA） was used to determine the contents of interleukin-6 （IL-6）， tumor necrosis factor-α （TNF-α）， serum amyloid A （SAA）， and Aβ_1-42 in the hippocampal region from the colonic tissues. The lipopolysaccharide （LPS） concentrations in colon tissues of rats were measured by using a dynamic chromogenic limulus assay. ResultsCompared with those in the control group， the rats in the model group exhibited a significantly prolonged escape latency and a markedly shorter duration in the target quadrant （P<0.01）. The integrity of the colonic mucosal structure was compromised， with disordered gland arrangement and a reduced number of goblet cells. The Aβ_1-42 deposition in the hippocampal region was significantly increased （P<0.01）. The protein expression levels of TLR4 and NF-κB p65 in colonic tissues were significantly upregulated （P<0.01）， while those of occludin and ZO-1 were downregulated （P<0.01）. The contents of inflammatory factors such as IL-6， TNF-α， and SAA were significantly elevated （P<0.01）， and the LPS level in the serum was markedly increased （P<0.01）. In comparison to those in the model group， the rats in the Xixintang group showed a significantly shortened escape latency and a prolonged duration in the target quadrant （P<0.01）. The colonic mucosal structure was ameliorated， with neat gland arrangement and an increased number of goblet cells. The Aβ_1-42 deposition in the hippocampal region was reduced （P<0.01）. The protein expressions of TLR4 and NF-κB p65 in the colon tissues were decreased （P<0.05，P<0.01）， while the protein levels of occludin and ZO-1 were increased （P<0.01）. The contents of IL-6， TNF-α， and serum amyloid A （SAA） were decreased （P<0.01）， and the LPS level was reduced （P<0.01）. ConclusionXixintang can significantly ameliorate cognitive dysfunction of AD model rats， by means of restoring the colonic mucosal barrier structure， reducing cerebral Aβ deposition， and suppressing peripheral and central inflammatory response. Its mechanism of action may be closely associated with the suppression of the TLR4/NF-κB signaling pathway activation， reduction of endotoxin levels， and regulation of the gut-brain axis.

OBJECTIVE To analyze the selection and rationales of comparators for pharmaceutical enterprises in their medical insurance access application， so as to provide a reference for promoting communication and consensus between enterprises and medical insurance authorities in this process. METHODS The application materials for drugs outside the catalogue that passed formal review published by the National Healthcare Security Administration from 2021 to 2025 were extracted， and then content analysis was used to systematically sort out relevant information of the declared drugs and comparators； the specific situations and rationales of pharmaceutical enterprises’ selection of comparators were analyzed. RESULTS A total of 1 341 declared drug documents were collected. Data analysis showed that 1 035 （77.18%） were submitted with positive comparators and 306 （22.82%） used blank comparators； 58 drugs （4.33%） took combination therapy as the reference， and 5 drugs （0.37%） referred to non-pharmacological （or non-single pharmacological） treatment regimens. Among competitive drugs declared by multiple enterprises， 50.00% of the enterprises submitted different comparators. A total of 4 basic conditions and 39 additional conditions were extracted as the rationales for selecting positive comparators. For blank comparators， 12 drug-related factors， 2 administrative factors， and 1 other factor were identified. More than 10% of the drugs did not state the rationale for comparator selection， and over 44% of drugs using blank comparators provided only one justification. CONCLUSIONS Pharmaceutical enterprises mainly select comparators based on their own interests in the medical insurance access application， and there are deficiencies in the adequacy and standardization of their selection basis and reasoning. It is recommended that enterprises follow the principled requirements of medical insurance authorities， and fully and normatively explain the reasons for selecting comparators in combination with the characteristics of their own products. Meanwhile， it is advisable to change the current open-ended statement form of selection reasons into a closed-ended answering mode， so as to highlight the priority of selection， standardize the declaration behavior of enterprises， and reduce communication divergences between the two parties.