Objective To explore the feasibility and reference value of allogeneic lung transplantation and postoperative monitoring in miniature pigs for lung transplantation research. Methods Two miniature pigs (R1 and R2) underwent left lung allogeneic transplantation. Complement-dependent cytotoxicity tests and blood cross-matching were performed before surgery. The main operative times and partial pressure of arterial oxygen (PaO₂) after opening the pulmonary artery were recorded during surgery. Postoperatively, routine blood tests, biochemical blood indicators and inflammatory factors were detected, and pathological examinations of multiple organs were conducted. Results The complement-dependent cytotoxicity test showed that the survival rate of lymphocytes between donors and recipients was 42.5%-47.3%, and no agglutination reaction occurred in the cross-matching. The first warm ischemia times of D1 and D2 were 17 min and 10 min, respectively, and the cold ischemia times were 246 min and 216 min, respectively. Ultimately, R1 and R2 survived for 1.5 h and 104 h, respectively. Postoperatively, in R1, albumin (ALB) and globulin (GLB) decreased, and alanine aminotransferase increased; in R2, ALB, GLB and aspartate aminotransferase all increased. Urea nitrogen and serum creatinine increased in both recipients. Pathological results showed that in R1, the transplanted lung had partial consolidation with inflammatory cell infiltration, and multiple organs were congested and damaged. In R2, the transplanted lung had severe necrosis with fibrosis, and multiple organs had mild to moderate damage. The expression levels of interleukin-1β and interleukin-6 increased in the transplanted lungs. Conclusions The allogeneic lung transplantation model in miniature pigs may systematically evaluate immunological compatibility, intraoperative function and postoperative organ damage. The data obtained may provide technical references for subsequent lung transplantation research.

Objective:To investigate the effect of early enteral nutrition on intestinal function in patients with complicated intra-abdominal infection.Methods:In this study,a prospective single-center randomized controlled trial was used to select 88 patients with severe abdominal infections in the surgical intensive care ward from January 2021 to December 2023.Among them,65 patients were eligible and were randomly divided into 33cases in the intervention group(who received early enteral nutrition),and 32cases in the control group(who did not receive early enteral nutrition).The clinical baseline characteristics of the two groups,conditions such as abdominal distension and diarrhea during enteral nutrition,intra-abdominal pressure,the time to reach the standard of complete enteral nutrition,and the indexes of pre-albumin,CRP,and leukocyte count on the third and the seventh day postoperative day were observed.The t-test was used to compare between groups for normally distributed measures.The Mann-Whitney U test was used to compare between groups for skewed measures.The χ2 test or continuity-corrected χ2 test was used to compare the count data between groups.Repeated measures data were analyzed by repeated measures ANOVA.Results:The clinical baseline characteristics of the two groups were completely matched;There were significant differences in the changes of intra-abdominal pressure over time between the two groups(Fgroup=9.665,P=0.004),There were significant differences in the changes of intra-abdominal pressure over time between the two intervention group(Ftime=64.124,P<0.001)and the control group.and the trend of intra-abdominal pressure reduction in the intervention group was more significant than that in the control group(Finteractive=3.938,P=0.023);The time required for the recovery of bowel sounds was significantly shorter in the experimental group than in the control group[(19.5±3.5)h vs(35.3±4.5)h,P<0.001,t=15.829];there was no significant difference in the frequency of abdominal distention,vomiting and aspiration between the two groups(P>0.05),and the difference in the frequency of diarrhea was statistically significant(P=0.003);The time to reach the standard of enteral nutrition in the intervention group was shorter than that in the control group[(6.3±1.2)d vs(7.4±1.5)d,P=0.002];The total hospital stay of the intervention group was significantly shorter than that of the control group[(11±3.2)d vs(14±4.1)d,P=0.007].The prealbumin(0.21±0.2,0.28±0.2)g/L,CRP(175.5±23.6,45.4±14.5)mg/L,and white blood cell count(11.7±2.9,9.1±3.5)109/L of the intervention group on the 3rd and 7th days after surgery were significantly improved compared with those of the control group(P<0.05).Conclusion:Early enteral nutrition can effectively promote the recovery of intestinal function in patients with complicated intra-abdominal infection.

The major components of Olaflur raw material were characterized using ultra performance liquid chromatography-quadrupole time-of-flight-mass spectrometry(UPLC-Q-TOF/MS).The results revealed that cetyl amine fluoride(C16-AmF),octadecene amine fluoride(C18:1-AmF),and octadecyl amine fluoride(Olaflur)were the main components.The contents of C16-AmF,C18:1-AmF,and Olaflur in oral care products were determined via ultra performance liquid chromatography-charged aerosol detector coupled with solid-phase extraction(SPE-UPLC-CAD).The oral care sample was dispersed evenly with a 50%ethanol aqueous solution,and then vortexed with ethanol.The supernatant was collected by centrifugation,concentrated to near dryness,and redissolved with ultrapure water.The re-dissolved sample was loaded onto a Poly-Sery HLB Pro SPE column for purification and elution.The acetonitrile eluate was collected and concentrated to 1.0 mL.Finally,a prepared test solution was separated on a Thermo Acclaim Surfactant Plus chromatographic column(2.1 mm×150 mm,3 μm).Acetonitrile and 100 mmol/L acetic acid-ammonium acetate aqueous solution(pH=4.8)were used as the mobile phases for gradient elution.The flow rate was 0.3 mL/min and cloumn temperature was maintained at 40℃.The sample was detected using a charged aerosol detector,and quantified using an external standard method.The experimental results indicated that the three organic fluorinated amines showed good linear relationship in their respective concentration ranges.The correlation coefficients(r)were greater than 0.99.The limit of detection(LOD)and the limit of quantification(LOQ)of C16-AmF were 2.0 and 8.0 μg/mL,respectively.The LOD and LOQ of C18:1-AmF were 2.0 and 8.0 μg/mL,respectively.The LOD and LOQ of Olaflur were 3.0 μg/mL and 10.0 μg/mL,respectively.The spiked recoveries of the three organic fluorinated amines were 84.3%-104.2%,with relative standard deviations(RSDs)of 4.93%-5.82%.The 28 batches of commercial oral care samples were detected by this method and the results indicated that three organic fluorinated amines were detected in 18 samples and the total content were 22.2-11477.8 μg/g.This method had high sensitivity and good reproducibility.It was suitable for verifying the authenticity of the claims of oral care products promoted with Olaflur as the main efficacy ingredient and selling point,and provided a valuable reference for establishing and improving the standard analytical method for Olaflur.

Objective To investigate the potential association between methylation levels of CpG locus of brain-derived neurotrophic factor(BDNF)gene and risk of acute stress disorder(ASD)[post-traumatic stress disorder(PTSD)or post-traumatic depression].Methods(1)30 specific pathogen-free(SPF)-grade male ICR mice were randomly divided into control group,24 h restraint stress(Res)group,and Res+5-Aza-2'deoxycytidine(Res+5-Aza-cdR)group,with 10 mice in each group.An ASD mouse model was established using 24h restraint stress.The body weight of the mice was recorded daily.At 24 h and 48 h after the successful establishment of the model,open field tests were conducted to evaluate locomotor activity level and anxiety-like behavior of the mice.Reverse transcription-polymerase chain reaction(RT-PCR)and Western blotting were used to detect BDNF mRNA and protein expression levels in the hippocampus of mice in each group.(2)Relevant genome-wide association study(GWAS)summary data were utilized for instrumental variable(IV)selection.A two-sample Mendelian randomization(TSMR)approach was applied to analyze the causal relationship between CpG site methylation of BDNF gene and ASD risk.The leave-one-out method was used to verify the results.Results(1)The results of body weight monitoring and the open field test showed that compared with control group,the body weight,the residence time in the central area,the total movement distance,and the activity times of mice in Res group were significantly decreased(P＜0.001).Compared with Res group,the body weight,the residence time in the central area,the total movement distance and activity times of mice in Res+5-Aza group were significantly increased(P＜0.00l).The results of RT-qPCR and Western blotting showed that compared with control group,the expression levels of BDNF mRNA and protein in the hippocampus of the mice in Res group were significantly decreased(P＜0.05).Compared with Res group,the expression level of BDNF mRNA and protein in Res+5-Aza group was significantly higher(P＜0.001).(2)TSMR analysis results showed that the cg10635145 site in BDNF gene(OR=0.862,95％CI 0.793-0.938,P=0.043)was negatively correlated with the risk of PTSD.The cg08362738 site(OR=0.975,95％CI 0.960-0.992,P=0.003)was negatively correlated with the risk of trauma-related depression,whereas the cg18117895 site(OR=1.008,95％CI 1.000-1.016,P=0.047)was positively correlated with the risk of trauma-related depression.The results of Leave-one-out test showed that the causal relationship between the single nucleotide polymorphism(SNP)of CpG site in BDNF gene and ASD was not affected by a strong Ⅳ.Conclusion The CpG loci cg1063145 and cg08362738 of BDNF gene maybe protective factors for ASD-related diseases,while cg18117895 maybe a riskfactor.

Objective:To observe the effects of acupuncture on the motor function of Parkinson disease(PD)model mice and to investigate the neuroprotective effects of acupuncture on PD from the perspective of cellular senescence.Methods:C57BL/6J mice were randomly divided into a normal control(NC)group,a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine(MPTP)group,an acupuncture(ACU)group,and a rasagiline(RAS)group,with 6 mice in each group.Except for the mice in the NC group,all mice were injected intraperitoneally with MPTP[30 mg/(kg·bw)]to establish a PD mouse model.After the models were successfully established,mice in the ACU group received acupuncture at Baihui(GV20)and bilateral Yanglingquan(GB34)for 15 min,once a day for 14 consecutive days.Mice in the RAS group were treated with gavage of rasagiline mesylate[0.5 mg/(kg·bw)],once daily for 14 d.Mouse balance and motor functions were detected using the mouse fatigue rotating rod apparatus.Immunohistochemistry staining was used to detect the number of tyrosine hydroxylase(TH)-positive neurons and the protein expression levels of special AT-rich sequence-binding protein 1(SATB1),p21,and p53 in the substantia nigra(SN)region of the mouse brain in each group.The glutathione peroxidase(GSH-Px)activity of mouse brain SN tissue was detected by enzyme-linked immunosorbent assay.The protein expression levels of interleukin(IL)-6 and senescence-associated β-galactosidase(SA-β-gal)in the SN tissue of mice in each group were detected by Western blotting.The relative expression of SATB1,p21,and p53 mRNA in the SN of each group was detected by real-time quantitative polymerase chain reaction.Results:Compared to the NC group,the overall rod performance(ORP)score,the number of TH-positive neurons,and GSH-Px activity in the SN region were significantly lower in the mice in the MPTP group(P<0.01);compared to the MPTP group,the ORP score,the number of TH-positive neurons,and GSH-Px activity were significantly increased in the ACU group and the RAS group(P<0.01 or P<0.05).Compared to the NC group,the protein levels of IL-6 and SA-β-gal in the SN tissue,the protein and mRNA expression levels of p21 and p53 were significantly increased(P<0.01);compared to the MPTP group,the protein levels of IL-6 and SA-β-gal in the SN tissue,the protein and mRNA expression levels of p21 and p53 were significantly decreased in the ACU group and the RAS group(P<0.01 or P<0.05).Compared to the NC group,the relative expression of SATB1 protein and mRNA in the SN of mice in the MPTP group was significantly decreased(P<0.01);compared to mice in the MPTP group,mice in the ACU group and the RAS group showed significant increases in the relative expression of SATB1 protein and mRNA(P<0.01 or P<0.05).Conclusion:Acupuncture can improve motor function and increase the number of TH-positive neurons in the SN of PD model mice.Its neuroprotective effect may relate to the regulation of the SATB1/p21 signaling pathway and the inhibition of cellular senescence-related biomarker expression in the SN.

BACKGROUND: The clinical impact of post-percutaneous coronary intervention (PCI) quantitative flow ratio (QFR) in patients treated with PCI for chronic total occlusion (CTO) was still undetermined. METHODS: All CTO vessels treated with successful anatomical PCI in patients from PANDA III trial were retrospectively measured for post-PCI QFR. The primary outcome was 2-year vessel-oriented composite endpoints (VOCEs, composite of target vessel-related cardiac death, target vessel-related myocardial infarction, and ischemia-driven target vessel revascularization). Receiver operator characteristic curve analysis was conducted to identify optimal cutoff value of post-PCI QFR for predicting the 2-year VOCEs, and all vessels were stratified by this optimal cutoff value. Cox proportional hazards models were employed to calculate the hazard ratio (HR) with 95% CI. RESULTS: Among 428 CTO vessels treated with PCI, 353 vessels (82.5%) were analyzable for post-PCI QFR. 31 VOCEs (8.7%) occurred at 2 years. Mean value of post-PCI QFR was 0.92 ± 0.13. Receiver operator characteristic curve analysis shown the optimal cutoff value of post-PCI QFR for predicting 2-year VOCEs was 0.91. The incidence of 2-year VOCEs in the vessel with post-PCI QFR < 0.91 (n = 91) was significantly higher compared with the vessels with post-PCI QFR ≥ 0.91 (n = 262) (22.0% vs. 4.2%, HR = 4.98, 95% CI: 2.32-10.70). CONCLUSIONS Higher post-PCI QFR values were associated with improved prognosis in the PCI practice for coronary CTO. Achieving functionally optimal PCI results (post-PCI QFR value ≥ 0.91) tends to get better prognosis for patients with CTO lesions.

As a common clinical treatment technique, nasogastric tube insertion plays an important role in assisting in disease diagnosis and treatment, and promoting patient recovery. Nasogastric tubes currently used in clinical practice are packaged individually without accompanying sterile materials, hence additional materials need to be prepared before operation, which is complicated and prone to omission, consumes clinical manpower, and increases the proportion of departmental consumption. The operator needs to hold the nasogastric tube with one hand and place it with the other hand during operation, the lack of auxiliary tool for uniformly controlling the placement of gastric tubes may easily lead to tube failure due to patient intolerance, agitation, or uneven force exerted by the operator, and improper force may even result in violent tube placement, leading to adverse outcomes such as mucosal bleeding and aspiration into the airway. Medical staff of intensive care unit of department of infectious diseases of Tongji Hospital, Tongji Medical College of Huazhong University of Science and Technology have designed a nasogastric tube auxiliary pushing device and an intubation kit to overcome the above problems, and obtaining National Utility Model Patent of China (patent number: ZL 2024 2 0300856.X). The device consists of two parts: a nasogastric tube auxiliary pushing device and a nasogastric tube insertion kit. Nasogastric tube auxiliary pushing device mainly consists of a nasogastric tube with guide wire, a circular wire harness, and a booster base with a pushing element. The tube insertion kit includes sterile treatment trays, main placement slots, and other operational accessory slots. The new nasogastric tube auxiliary pushing device and tube insertion kit integrates packaging and portable design, providing stable and uniform assistance for safe insertion of nasogastric tubes by a single person, which is able to reduce the occurrence of complications, ensure patient safety, improve patient comfort, and reduce occupational exposure risks, making it suitable for clinical promotion.
Intubation, Gastrointestinal/methods* ; Equipment Design ; Humans

OBJECTIVE: To identify prognostic genes associated with lysosome-dependent cell death (LDCD) in patients with gastric cancer (GC). METHODS: Differentially expressed genes (DEGs) were identified using The Cancer Genome Atlas - Stomach Adenocarcinoma. Weighted gene co-expression network analysis was performed to identify the key module genes associated with LDCD score. Candidate genes were identified by DEGs and key module genes. Univariate Cox regression analysis, and least absolute shrinkage and selection operator regression and multivariate Cox regression analyses were performed for the selection of prognostic genes, and risk module was established. Subsequently, key cells were identified in the single-cell dataset (GSE183904), and prognostic gene expression was analyzed. Cell proliferation and migration were assessed using the Cell Counting Kit-8 assay and the wound healing assay. RESULTS: A total of 4,465 DEGs, 95 candidate genes, and 4 prognostic genes, including C19orf59, BATF2, TNFAIP2, and TNFSF18, were identified in the analysis. Receiver operating characteristic curves indicated the excellent predictive power of the risk model. Three key cell types (B cells, chief cells, and endothelial/pericyte cells) were identified in the GSE183904 dataset. C19orf59 and TNFAIP2 exhibited predominant expression in macrophage species, whereas TNFAIP2 evolved over time in endothelial/pericyte cells and chief cells. Functional experiments confirmed that interfering with C19orf59 inhibited proliferation and migration in GC cells. CONCLUSION C19orf59, BATF2, TNFAIP2, and TNFSF18 are prognostic genes associated with LDCD in GC. Furthermore, the risk model established in this study showed robust predictive power.
Stomach Neoplasms/pathology* ; Humans ; Prognosis ; Lysosomes/physiology* ; RNA-Seq ; Cell Death ; Single-Cell Analysis ; Gene Expression Regulation, Neoplastic ; Cell Proliferation ; Single-Cell Gene Expression Analysis

In recent years, the reform of the registration, evaluation, and approval system for traditional Chinese medicine(TCM) has been promoted at the national level, with establishment of an evaluation evidence system for TCM registration that combines TCM theory, human use experience, and clinical trials(known as the "three-combined" evaluation evidence system). This system, which aligns with the characteristics of TCM clinical practice and the laws of TCM research and development, recognizes the unique value of human use experience in medicine and returns to the essence of medicine as an applied science, thus receiving widespread recognition from both academia and industry. However, it meanwhile poses new and higher challenges. This article delves into the value and challenges faced by the "three-combined" evaluation evidence system from three perspectives: registration management, medical institutions, and the TCM industry. Furthermore, it discusses how the China Association of Chinese Medicine, leveraging its academic platform advantages and leading roles, has made exploratory and practical efforts to facilitate the research and development of new TCM drugs and the implementation of the "three-combined" evaluation evidence system.
Drugs, Chinese Herbal/standards* ; Humans ; Medicine, Chinese Traditional/standards* ; China ; Drug Development

This study investigated the effects and underlying mechanisms of vanillic acid(VA) against cardiac fibrosis(CF) induced by isoproterenol(ISO) in mice. Male C57BL/6J mice were randomly divided into control group, VA group(100 mg·kg~(-1), ig), ISO group(10 mg·kg~(-1), sc), ISO + VA group(10 mg·kg~(-1), sc + 100 mg·kg~(-1), ig), ISO + dynamin-related protein 1(Drp1) inhibitor(Mdivi-1) group(10 mg·kg~(-1), sc + 50 mg·kg~(-1), ip), and ISO + VA + Mdivi-1 group(10 mg·kg~(-1), sc + 100 mg·kg~(-1), ig + 50 mg·kg~(-1), ip). The treatment groups received the corresponding medications once daily for 14 consecutive days. On the day after the last administration, cardiac functions were evaluated, and serum and cardiac tissue samples were collected. These samples were analyzed for serum aspartate aminotransferase(AST), lactate dehydrogenase(LDH), creatine kinase-MB(CK-MB), cardiac troponin I(cTnI), reactive oxygen species(ROS), interleukin(IL)-1β, IL-4, IL-6, IL-10, IL-18, and tumor necrosis factor-α(TNF-α) levels, as well as cardiac tissue catalase(CAT), glutathione(GSH), malondialdehyde(MDA), myeloperoxidase(MPO), superoxide dismutase(SOD), total antioxidant capacity(T-AOC) activities, and cytochrome C levels in mitochondria and cytoplasm. Hematoxylin-eosin, Masson, uranium acetate and lead citrate staining were used to observe morphological and mitochondrial ultrastructural changes in the cardiac tissues, and myocardial injury area and collagen volume fraction were calculated. Flow cytometry was applied to detect the relative content and M1/M2 polarization of cardiac macrophages. The mRNA expression levels of macrophage polarization markers [CD86, CD206, arginase 1(Arg-1), inducible nitric oxide synthase(iNOS)], CF markers [type Ⅰ collagen(Coll Ⅰ), Coll Ⅲ, α-smooth muscle actin(α-SMA)], and cytokines(IL-1β, IL-4, IL-6, IL-10, IL-18, TNF-α) in cardiac tissues were determined by quantitative real-time PCR. Western blot was used to detect the protein expression levels of Coll Ⅰ, Coll Ⅲ, α-SMA, Drp1, p-Drp1, voltage-dependent anion channel(VDAC), hexokinase 1(HK1), NOD-like receptor protein 3(NLRP3), apoptosis-associated speck-like protein(ASC), caspase-1, cleaved-caspase-1, gasdermin D(GSDMD), cleaved N-terminal gasdermin D(GSDMD-N), IL-1β, IL-18, B-cell lymphoma-2(Bcl-2), B-cell lymphoma-xl(Bcl-xl), Bcl-2-associated death promoter(Bad), Bcl-2-associated X protein(Bax), apoptotic protease activating factor-1(Apaf-1), pro-caspase-3, cleaved-caspase-3, pro-caspase-9, cleaved-caspase-9, poly(ADP-ribose) polymerase-1(PARP-1), and cleaved-PARP-1 in cardiac tissues. The results showed that VA significantly improved cardiac function in mice with CF, reduced myocardial injury area and cardiac index, and decreased serum levels of AST, CK-MB, cTnI, LDH, ROS, IL-1β, IL-6, IL-18, and TNF-α. VA also lowered MDA and MPO levels, mRNA expressions of IL-1β, IL-6, IL-18, and TNF-α, and mRNA and protein expressions of Coll Ⅰ, Coll Ⅲ, and α-SMA in cardiac tissues, and increased serum levels of IL-4 and IL-10, cardiac tissue levels of CAT, GSH, SOD, and T-AOC, and mRNA expressions of IL-4 and IL-10. Additionally, VA ameliorated cardiac pathological damage, inhibited myocardial cell apoptosis, inflammatory infiltration, and collagen fiber deposition, reduced collagen volume fraction, and alleviated mitochondrial damage. VA decreased the ratio of F4/80~+CD86~+ M1 cells and the mRNA expressions of CD86 and iNOS in cardiac tissue, and increased the ratio of F4/80~+CD206~+ M2 cells and the mRNA expressions of CD206 and Arg-1. VA also reduced protein expressions of p-Drp1, VDAC, NLRP3, ASC, caspase-1, cleaved-caspase-1, GSDMD, GSDMD-N, IL-1β, IL-18, Bad, Bax, Apaf-1, cleaved-caspase-3, cleaved-caspase-9, cleaved-PARP-1, and cytoplasmic cytochrome C, and increased the expressions of HK1, Bcl-2, Bcl-xl, pro-caspase-3, pro-caspase-9 proteins, as well as the Bcl-2/Bax and Bcl-xl/Bad ratios and mitochondrial cytochrome C content. These results indicate that VA has a significant ameliorative effect on ISO-induced CF in mice, alleviates ISO-induced oxidative damage and inflammatory response, and its mechanism may be closely related to the inhibition of Drp1/HK1/NLRP3 and mitochondrial apoptosis signaling pathways, suppression of myocardial cell inflammatory infiltration and collagen fiber deposition, reduction of collagen volume fraction and CollⅠ, Coll Ⅲ, and α-SMA expressions, thus mitigating CF.
Animals ; Isoproterenol/adverse effects* ; Male ; Mice ; Signal Transduction/drug effects* ; Vanillic Acid/administration & dosage* ; Dynamins/genetics* ; Mice, Inbred C57BL ; Fibrosis/genetics* ; Apoptosis/drug effects* ; Mitochondria/metabolism* ; NLR Family, Pyrin Domain-Containing 3 Protein/genetics* ; Myocardium/metabolism* ; Humans