Objective To investigate the distribution characteristics of pathogens causing infections within 90 days after liver transplantation and the influencing factors of infection. Methods Clinical data of 176 recipients who underwent liver transplantation at the Liver Transplant Center of Beijing Friendship Hospital Affiliated to Capital Medical University from September 2021 to August 2024 were retrospectively analyzed. Patients were divided into the infection group (n=124) and the non-infection group (n=52) based on whether they developed infection within 90 days after transplantation. The distribution characteristics of pathogens in infected patients were analyzed. Univariate and multivariate logistic regression analyses were used to explore the influencing factors of infection. Results Among the 176 liver transplant recipients, 124 cases developed 243 episodes of 518 bacterial, fungal, viral or mycoplasma infections within 90 days after transplantation, with an overall infection rate of 70.5% (124/176). The composition of pathogens was mainly Gram-negative bacteria (38.6%, 200/518), followed by Gram-positive bacteria (32.2%, 167/518) and viruses (15.4%, 80/518), and fungi accounted for 13.1% (68/518). Among Gram-negative bacteria, the main pathogen was Klebsiella pneumoniae (6.8%, 35/518), and among Gram-positive bacteria, the main pathogen was Enterococcus faecalis (8.5%, 44/518). Viruses included Epstein-Barr virus (3.7%, 19/518) and cytomegalovirus (3.7%, 19/518), and fungi were mainly Candida albicans (6.8%, 35/518). The most common infection site among the 243 episodes was pulmonary infection (42.0%, 102/243), followed by abdominal infection (22.6%, 55/243) and bloodstream infection (18.1%, 44/243). The infections mainly occurred within 2 weeks after transplantation (60.9%, 148/243). Multivariate logistic regression analysis indicated that preoperative infection within 2 weeks, a high preoperative model for end-stage liver disease (MELD) score, and preoperative sarcopenia were independent risk factors for infection within 90 days after liver transplantation (all odds ratio>1, P<0.05). After multivariate correction, the levels of CD4⁺T cells and CD8⁺T cells within 90 days after surgery were independently associated with the occurrence of infection. Low levels of CD4⁺T cells and CD8⁺T cells might be related to an increased risk of infection. Conclusions The infection rate after liver transplantation is high, and the pathogens are mainly Gram-negative bacteria. The lungs are the most common infection site. Preoperative MELD score, preoperative sarcopenia and preoperative infection within 2 weeks are independent risk factors for infection within 90 days after liver transplantation. Regular monitoring of immune indicators CD4⁺T cells and CD8⁺T cells levels after transplantation is helpful to reduce the occurrence of post-transplantation infection.

ObjectiveThis study aims to compare the modeling effects of submaxillary gland antigen and salivary gland antigen in the establishment of Sjögren syndrome (SS) mouse models, and to characterize the phenotypic and immunological features of these models in comparison with spontaneous SS-prone non-obese diabetic (NOD)/LtJ mice. MethodsAdult C57BL/6J mice (equal numbers of males and females) were immunized with submaxillary gland antigen or salivary gland antigen, respectively, combined with Freund's adjuvant to induce SS models. Mice immunized with phosphate-buffered saline (PBS) combined with Freund's adjuvant served as the control group. Immunization was induced via multiple subcutaneous injections in the back with antigen combined with Freund's complete adjuvant (FCA) on Days 1 and 7. A booster immunization was administered via multiple subcutaneous injections in the back with antigen combined with Freund's incomplete adjuvant (FIA) on Day 14. Female NOD/LtJ mice were used as the spontaneous SS model group, with ICR mice as the corresponding control strain for comparative analysis. Body weight, water intake, and salivary flow rate of mice were dynamically monitored for 4 weeks. At the end of the experiment, tissue and serum samples were collected, the weights of submaxillary glands, thymus, and spleen were measured, and organ indices (organ-to-body weight ratios) were calculated. Pathological morphological analysis of the submaxillary gland and spleen was performed with hematoxylin and eosin (HE) staining. Serum interleukin-17 (IL-17) level was detected using enzyme-linked immunosorbent assay (ELISA). Real-time quantitative polymerase chain reaction was used to detect the mRNA expression levels of SS type A (SSA) and SS type B (SSB) in submaxillary gland tissues. ResultsFemale mice in the submaxillary gland antigen group exhibited significantly increased water intake (P<0.05) and reduced salivary flow rate (P<0.05) compared with the female control group. No statistically significant differences were observed in the submaxillary gland index, thymus index and spleen index (P>0.05). Focal lymphocytic infiltration was observed in the submaxillary glands, and the splenic marginal zone was enlarged. Serum IL-17 levels were significantly increased (P<0.05). There was no significant difference in submaxillary gland SSA/SSB expression levels (P>0.05). Compared with the female control group, female mice in the salivary gland antigen group showed no statistically significant differences in water intake, salivary flow rate, submaxillary gland index, and spleen index (P>0.05), whereas the thymus index was significantly reduced (P<0.01). Mild inflammatory cell infiltration and glandular atrophy were observed in the submaxillary glands, and the splenic white pulp and marginal zone were slightly enlarged. Serum IL-17 levels and submaxillary gland SSB mRNA expression levels were significantly increased (P<0.01), whereas no significant change was observed in submaxillary gland SSA expression levels (P>0.05). Compared with the male control group, mild submaxillary gland atrophy was observed in male mice in the submaxillary gland antigen group, whereas no obvious changes were found in other modeling-related indicators (P>0.05). Compared with the ICR control group, NOD/LtJ model mice exhibited elevated water intake (P<0.05), significantly reduced salivary flow rate (P<0.01), no significant differences in the submaxillary gland index or spleen index (P>0.05), but a significantly increased thymus index (P<0.05). Marked focal infiltration was observed in the submaxillary glands, the splenic marginal zone was obviously enlarged, and serum IL-17 concentrations as well as submaxillary gland SSA/SSB expression levels were significantly increased (P<0.05). ConclusionSubmaxillary gland antigen and salivary gland antigen can induce SS-related features in female C57BL/6J mice. The SS-related phenotype is more pronounced in the submaxillary gland antigen group than in the salivary gland antigen group, but weaker than that in spontaneously SS-prone female NOD/LtJ mice. Immunization of male C57BL/6J mice with submaxillary or salivary gland antigens fails to induce an obvious SS phenotype.

ObjectiveTo investigate the effect of solute carrier family 7 member 5 (SLC7A5) inhibitor JPH203 on renal fibrosis induced by unilateral ureteral obstruction in mice. MethodsSixteen SPF male C57BL/6 mice were randomly divided into the control group and the experimental group, with 8 mice in each group. The mouse model of renal fibrosis was established by unilateral ureteral obstruction. From the third day after surgery, the mice in the control group were intraperitoneally injected with phosphate-buffered saline (PBS) for 11 consecutive days, and the injection dose was 200 μL/d. Mice in the experimental group received intraperitoneal injection of JPH203 (50 mg/kg) every day for 11 days. On day 14, the mice were euthanized, then the kidney tissues were obtained. Hematoxylin and eosin (HE) staining was used to assess renal tissue damage, Masson staining was used to evaluate collagen fiber deposition in the extracellular matrix, and immunohistochemistry was used to detect the levels of fibroblast activation markers α-smooth muscle actin (α-SMA) and collagen type Ⅰ (COL-Ⅰ) in kidney tissues. Western blotting was further performed to measure the expression levels of SLC7A5 and transforming growth factor-β1 (TGF-β1), as well as the phosphorylation levels of mammalian target of rapamycin complex 1 (mTORC1) signaling pathway-related molecules. Real-time quantitative PCR was used to verify changes in the mRNA levels of SLC7A5, α-SMA, and COL-Ⅰ in kidney tissues. ResultsCompared with the control group, the experimental group showed reduced destruction of renal tissue structure and a significantly lower pathological injury score (P<0.05). Additionally, collagen deposition in the extracellular matrix was decreased, and the percentage of collagen fiber area was significantly reduced (P<0.001) in the experimental group. The levels of fibroblast activation markers α-SMA and COL-Ⅰ were significantly lower in the experimental group (both P<0.001). The expression levels of SLC7A5 and TGF-β1 were also significantly decreased (P<0.001), and the phosphorylation levels of mTORC1 signaling pathway-related proteins 4E-BP1 and mTORC1 were significantly reduced (P<0.001). Real-time quantitative PCR confirmed that the mRNA levels of SLC7A5, α- SMA, and COL-Ⅰ in kidney tissues were significantly lower in the experimental group (P<0.001). ConclusionJPH203 may inhibit the progression of renal fibrosis in mice by suppressing SLC7A5 expression, regulating the mTORC1 signaling pathway, and altering fibroblast activation status.

ObjectiveTo elucidate the effects of autonomic neuromodulators [calcium chloride (CaCl₂)-acetylcholine (ACh)] on atrial electrical remodeling and histopathological changes in rats, thereby providing evidence for further investigation into the pathological mechanisms by which autonomic imbalance induces atrial fibrillation (AF). MethodsTen 8-week-old male Sprague-Dawley (SD) rats were randomly divided into experimental and control groups, with 5 rats in each group. The experimental group received daily tail vein injections of a CaCl₂-ACh mixed solution for 28 days, while the control group received an equal volume of saline. Surface electrocardiograms were recorded before and after daily administration. On day 28 of administration, under isoflurane inhalation anesthesia, echocardiography was performed, and then the rats were euthanized by exsanguination under isoflurane anesthesia for tissue collection. Body weight and heart weight of rats were measured, and electrophysiological parameters including AF inducibility, conduction velocity, and conduction dispersion in isolated rat hearts were monitored using the MappingLab multichannel electrophysiological mapping system. HE staining was performed to evaluate atrial tissue architecture and inflammatory cell infiltration. The expression levels of matrix metalloproteinase 9 (MMP-9) and interleukin-1 beta (IL-1β) were analyzed by Western blotting. Masson staining was used to quantitatively analyze the proportional distribution of collagen fibers and myocardial fibers, and to calculate the area of collagen deposition, thereby evaluating the degree of myocardial fibrosis. Wheat germ agglutinin (WGA) staining was used to evaluate morphological changes of cardiomyocytes. Dihydroethidium (DHE) staining was used to detect the level of oxidative stress in atrial myocytes. Terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) staining was used to detect atrial cell apoptosis. ResultsCompared with the control group, the experimental group showed obvious arrhythmias on electrocardiograms. Echocardiography after 28 days of administration revealed significant structural remodeling in the experimental group, with a marked increase in left atrial anteroposterior diameter (P < 0.05), and also showed cardiac dysfunction, with significant decreases in left ventricular ejection fraction and left ventricular fractional shortening (P < 0.01). Compared with the control group, the experimental group showed a significantly increased heart weight-to-body weight ratio (P < 0.05), a markedly higher AF inducibility (P < 0.001), a significantly slowed atrial conduction velocity (P < 0.05), an uneven isochronal map with irregular directions, and a significantly increased conduction dispersion (P < 0.01). HE staining showed that atrial myocytes in the experimental group were disorganized, with slight inflammatory cell infiltration. Western blotting showed that the expression levels of MMP-9 and IL-1β in the atrial tissue of the experimental group were significantly upregulated (P < 0.05). Masson staining showed a significant increase in collagen deposition and a significant increase in fibrosis area in the atrial tissue of the experimental group (P < 0.001). WGA staining showed that cardiomyocytes in the experimental group were significantly hypertrophied compared with the control group (P < 0.05). DHE staining and TUNEL staining revealed that the level of oxidative stress in atrial myocytes (P < 0.001) and the apoptotic rate (P < 0.01) were both significantly increased. Conclusion Daily tail vein injections of the autonomic neuromodulator CaCl₂-ACh mixed solution for 28 days can successfully induce AF in rats, accompanied by significant atrial structural remodeling, electrical remodeling, and oxidative stress.

Objective: To explore the micro associations and key bridge nodes between physical fitness indicators and anxiety/depressive symptoms among college students using network analysis, so as to provide a theoretical foundation for promoting physical and mental health of college students. Methods: From September to October 2025, a combination of purposive sampling and cluster sampling was employed to select 2 158 college students from three universities in Xuzhou City. Seven physical fitness indicators were measured and standardized according to the National Student Physical Health Standard. The Generalized Anxiety Disorder Scale-7 (GAD-7) and the Patient Health Questionnaire-9 (PHQ-9) were used to assess anxiety and depressive symptoms. Independent samples t-test was used for intergroup comparisons of physical fitness indicators and psychological symptom scores. A gaussian graphical model (GGM) was constructed to calculate node and bridge strength, followed by stability analyses. Results: The detection rates of anxiety and depressive symptoms among college students were 21.3% and 24.5%, respectively. Male participants demonstrated superior performance in physical fitness indicators such as vital capacity, 50 meter sprint, and standing long jump compared to female participants, whereas females exhibited better results in the sit and reach test ( t =48.35, -44.82 , 70.21, -16.51, all P <0.01). Regarding psychological indicators, female participants showed higher scores of anxiety and depressive symptoms than males ( t =-4.15, -4.46, both P <0.01). Physical fitness and psychological symptoms were predominantly negatively correlated. "feeling tired" and "not being able to stop or control worrying" were the symptoms with the highest centrality in the network of physical fitness and phychological symptoms among college students (standardized strengths were 2.15 and 1.98, respectively). Among the bridge indicators, the "1 000 m (male)/800 m (female) run" exhibited the highest strength (0.85), outperforming "vital capacity" (0.35); it was linked to the symptom cluster primarily by negatively predicting "feeling tired" (edge weight=-0.38). The network stability was excellent of physical fitness and phychological symptoms among college students (correlation stability coefficient= 0.60 ). Conclusions Endurance capacity serves as the most critical bridge connecting physical and mental health, and its decline is closely related to intensified feelings of fatigue. Colleges should prioritize endurance training as a core target for promoting college students mental health.

OBJECTIVE: To explore the spectrum of genetic variants and phenotypes of Phenylalanine hydroxylase deficiency (PAHD) in Lianyungang area and the correlation between genotype and phenotypes among the patients. METHODS: Eighty children with Hyperphenylalaninemia (HPA) diagnosed at the Lianyungang Branch of Jiangsu Provincial Newborn Screening Center between January 2015 and December 2022 were enrolled. Peripheral blood samples were collected for genetic analysis using next generation sequencing (NGS), Sanger sequencing, and multiplex ligation-dependent probe amplification (MLPA) to identify the variants of PAH gene. Clinical and phenotypic data were concurrently analyzed to investigate the correlation between the types of PAH gene variant and phenotypes. This study was approved by the Medical Ethics Committee of Lianyungang Maternal and Child Health Care Hospital (Ethics No.: XM2022041). RESULTS: PAH gene variants were identified in 93.75% (75/80) of the children, classified as PAHD cases, while 6.25% (5/80) harbored PTS gene variants. Of the 150 PAH alleles from 75 PAHD children, a total of 152 variants (55 distinct types) were detected, with a detection rate of 100%. 80.26% (122/152) of the variants were located in exons, with the main types being missense variants (67.11%, 102/152). 53.29% (81/152) of coding sequence variants have occurred in the PAH gene's catalytic center region, while 19.74% (30/152) of the variants involved non-coding sequences. The phenotypes of the 75 PAHD children were evenly distributed. The re-screened Phe concentrations and Phe/Tyr ratios of classic-phenylketonuria (CPKU) and mild-phenylketonuria (MPKU) patients were markedly higher than initial screening values (P < 0.001, P < 0.001; P = 0.004, P = 0.016). The genotypes of the PAHD patients mostly occurred as compound heterozygotes, and different mutation positions and variant types have significantly affected the phenotypes (P = 0.042, P = 0.045). APV/GPV genotype-phenotype analysis of 61 patients showed high consistency between predicted and actual phenotypes (κ = 0.755, P < 0.001). CONCLUSION PAH gene variants were detected in most HPA children from Lianyungang area. The location and type of PAH gene variants has correlated with the severity of the phenotype, and the non-coding sequence variants and non-missense variants may aggravate the phenotype, and the APV/GPV model has predicted the phenotype with high consistency with the actual phenotype.
Humans ; Phenylalanine Hydroxylase/genetics* ; Female ; Phenylketonurias/enzymology* ; Male ; Phenotype ; Genotype ; Child ; Infant ; Infant, Newborn ; Child, Preschool ; China ; Mutation ; Alleles

AIM To analyze the dynamic change patterns of aflatoxin B1,aflatoxin B2,aflatoxin G1,aflatoxin G2,T-2 toxin and deoxynivalenol contents during the fermentation of Massa Medicata Fermentata.METHODS The analysis was performed on a 40 ℃ thermostatic Waters ACQUITY UPLC HSS T3 column(100 mm×2.1 mm,1.8 μm),with the mobile phase comprising of 0.01％formic acid-[acetonitrile-methanol(1∶1)]flowing at 0.3 mL/min,and electron spray ionization source was adopted in positive ion scanning with multiple reaction monitoring mode.RESULTS Six mycotoxins showed good linear relationships within their own ranges(R2＞0.998 0),whose average recoveries were 76.1％-119.3％with the RSDs of 0.49％-9.27％,and except for deoxynivalenol,their contents demonstrated the trends of growing out of nothing and gradually increasing.CONCLUSION The risk of mycotoxin infection exists in the fermentation of Massa Medicata Fermentata.This simple,efficient,rapid and sensitive method can provide a reference for whole-process monitoring the fermentation process for Massa Medicata Fermentata.

OBJECTIVE Melatonin(MEL),a natural hormone with broad-spectrum anticancer effects,has been shown to potentiate the therapeutic outcomes of conventional chemotherapy.This study aims to investigate the combined effects of Doxorubicin(DOX)and MEL on head and neck squamous cell carcinoma(HNSCC)cell lines.METHODS The effects of MEL and DOX on cell proliferation in HNSCC cell lines TU686 and CAL-27 were assessed using the MTT assay.The effects of MEL and DOX on reactive oxygen species(ROS)expression levels in HNSCC cell lines were detected using DCFH-DA fluorescent probe.The effects of MEL and DOX on 8-hydroxy-2′-deoxyguanosine(8-oxodG)levels in HNSCC cell lines were measured by enzyme-linked immunosorbent assay(ELISA).The effects of MEL and DOX on γ-H2AX protein levels in HNSCC cell lines were analyzed via Western blot.The effects of MEL and DOX on antioxidant enzymes levels in HNSCC cell lines were evaluated based on spectrophotometry.The effects of MEL and DOX on cell apoptosis in HNSCC cell lines were detected using an ELISA cell death detection kit.RESULTS The MTT assay revealed that MEL significantly enhanced the cytotoxic effects of DOX in HNSCC cell lines(tTU686=13.51,tCAL-27=17.580,all P<0.05).The combination of MEL and DOX markedly increased intracellular ROS levels(FTU686=89.984,FCAL-27=102.853,all P<0.05),while the expression of antioxidant enzymes was significantly reduced(TU686:the F values of CAT,GPx,GR,GST and SOD are 176.035,34.662,20.260,120.105 and 184.254,all P<0.05;CAL-27:the F values are 96.801,177.398,97.849,102.750 and 186.608 respectively,all P<0.05).Furthermore,this combination treatment significantly elevated the expression levels of 8-oxodG(FTU686=200.078,FCAL-27=663.982,all P<0.05)and γ-H2AX(FTU686=192.500,FCAL-27=285.700,all P<0.01)in HNSCC cell lines.Additionally,compared to single-agent treatment,MEL significantly enhanced DOX-induced apoptosis in HNSCC cell lines(FTU686=2718.253,FCAL-27=5185.334,all P<0.01).CONCLUSION The combination of MEL and DOX can enhance cytotoxic effects on HNSCC cell lines,increase intracellular ROS levels,induce DNA oxidative damage,and impair cellular antioxidant defense capacity,thereby effectively promoting HNSCC cell apoptosis.This combination may represent a novel therapeutic approach to improve clinical outcomes in HNSCC.

The conversion of abundant and low-cost biomass waste into highly efficient two-electron oxygen reduction(ORR)electrocatalyst is an important link in the degradation of pollutants in industrial wastewater through the electro-Fenton process.In this work,porous biocarbon materials doped with manganese and nitrogen(MnNBC)were prepared from corn stalk.The H2O2 selectivity of MnNBC in acidic media was up to 81% @0.6 Vvs RHE,also MnNBC exhibited a long-term stability in a 10-h uninterrupted lifetime test.The ORR activity of MnNBC could be attributed to the synergistic effect of the hierarchical porous structure,improved defect level and heteroatom doping.Moreover,MnNBC as a cathode material for the electro-Fenton system could completely degrade four kinds of common organic dye pollutants,e.g.,Rhodamine B,methyl orange,methylene blue and crystal violet(25 mg/L),respectively,within 40?60 min.The present study provided valuable insights into the transformation of corn stalk waste into efficient cathode materials for the electro-Fenton process.

Progressive pulmonary fibrosis (PPF) is a progressive and lethal condition with few effective treatment options. Improvements in quality of life for patients with PPF remain limited even while receiving treatment with approved antifibrotic drugs. Traditional Chinese medicine (TCM) has the potential to improve cough, dyspnea and fatigue symptoms of patients with PPF. TCM treatments are typically diverse and individualized, requiring urgent development of efficient and precise design strategies to identify effective treatment options. We designed an innovative Bayesian adaptive two-stage trial, hoping to provide new ideas for the rapid evaluation of the effectiveness of TCM in PPF. An open-label, two-stage, adaptive Bayesian randomized controlled trial will be conducted in China. Based on Bayesian methods, the trial will employ response-adaptive randomization to allocate patients to study groups based on data collected over the course of the trial. The adaptive Bayesian trial design will employ a Bayesian hierarchical model with "stopping" and "continuation" criteria once a predetermined posterior probability of superiority or futility and a decision threshold are reached. The trial can be implemented more efficiently by sharing the master protocol and organizational management mechanisms of the sub-trial we have implemented. The primary patient-reported outcome is a change in the Leicester Cough Questionnaire score, reflecting an improvement in cough-specific quality of life. The adaptive Bayesian trial design may be a promising method to facilitate the rapid clinical evaluation of TCM effectiveness for PPF, and will provide an example for how to evaluate TCM effectiveness in rare and refractory diseases. However, due to the complexity of the trial implementation, sufficient simulation analysis by professional statistical analysts is required to construct a Bayesian response-adaptive randomization procedure for timely response. Moreover, detailed standard operating procedures need to be developed to ensure the feasibility of the trial implementation. Please cite this article as: Zhang C, Nie YS, Zhang CT, Yang HJ, Zhang HR, Xiao W, Cui GF, Li J, Li SJ, Huang QS, Yan SY. An adaptive Bayesian randomized controlled trial of traditional Chinese medicine in progressive pulmonary fibrosis: Rationale and study design. J Integr Med. 2025; 23(2): 138-145.
Female ; Humans ; Male ; Bayes Theorem ; Disease Progression ; Drugs, Chinese Herbal/therapeutic use* ; Medicine, Chinese Traditional/methods* ; Pulmonary Fibrosis/therapy* ; Quality of Life ; Randomized Controlled Trials as Topic ; Research Design ; Adaptive Clinical Trials as Topic