Objective:To evaluate the safety and clinical efficacy of enteral nutrition (EN) initiated within 24 h after heart transplantation in pediatric patients.Methods:A retrospective cohort study was conducted. Clinical data from 16 pediatric heart transplant recipients at the Seventh Medical Center of the Chinese People′s Liberation Army General Hospital between October 2022 and October 2024 were collected, including demographics, anthropometric measurements, biochemical markers, cytokine levels, and clinical outcomes. Based on the timing of EN initiation, the patients were divided into EN-initiated within 24 h and EN-initiated after 24 h 2 groups. Demographic data, preoperative extracorporeal membrane oxygenation (ECMO) support, physical examination indicators, laboratory parameters, and cytokine levels were compared between groups using independent samples t-test, Mann-Whitney U test, Fisher′s exact probability test. Results:The cohort comprised 16 patients (10 males and 6 females) with an age of (12.5±1.9) years. The EN-initiated within 24 h group comprised 6 cases, and the EN-initiated after 24 h group comprised 10 cases. No significant difference was observed between the two groups in age, preoperative body mass index Z-score, preoperative ECMO support, physical examination indicators, laboratory parameters (total protein, albumin, hemoglobin), or cytokine levels (all P>0.05). Compared to the EN-initiated after 24 h group, the EN-initiated within 24 h group exhibited a shorter intensive care unit stay ( t=2.65, P<0.05) and shorter mechanical ventilation duration ( t=2.23, P<0.05) than EN-initiated after 24 h group. Total hospitalization length had no significant difference ( P>0.05). At 72 h post-transplant, the EN-initiated within 24 h group had a lower interleukin-12 P70 ( t=2.46, P<0.05) and interferon-γ levels ( t=2.55, P<0.05) than EN-initiated after 24 h group. Prior to discharge, the EN-initiated within 24 h group has a lower mean skinfold thickness ( t=2.49, P<0.05) and lower mid-upper arm circumference ( t=2.36, P<0.05) compared with the EN-initiated after 24 h group. Conclusions:Initiating EN within 24 h postoperatively is safe and feasible in pediatric heart transplant recipients. Early EN may shorten the length of intensive care unit stay and mechanical ventilation while attenuating postoperative release of inflammatory cytokine.

Objective:To evaluate the safety and clinical efficacy of enteral nutrition (EN) initiated within 24 h after heart transplantation in pediatric patients.Methods:A retrospective cohort study was conducted. Clinical data from 16 pediatric heart transplant recipients at the Seventh Medical Center of the Chinese People′s Liberation Army General Hospital between October 2022 and October 2024 were collected, including demographics, anthropometric measurements, biochemical markers, cytokine levels, and clinical outcomes. Based on the timing of EN initiation, the patients were divided into EN-initiated within 24 h and EN-initiated after 24 h 2 groups. Demographic data, preoperative extracorporeal membrane oxygenation (ECMO) support, physical examination indicators, laboratory parameters, and cytokine levels were compared between groups using independent samples t-test, Mann-Whitney U test, Fisher′s exact probability test. Results:The cohort comprised 16 patients (10 males and 6 females) with an age of (12.5±1.9) years. The EN-initiated within 24 h group comprised 6 cases, and the EN-initiated after 24 h group comprised 10 cases. No significant difference was observed between the two groups in age, preoperative body mass index Z-score, preoperative ECMO support, physical examination indicators, laboratory parameters (total protein, albumin, hemoglobin), or cytokine levels (all P>0.05). Compared to the EN-initiated after 24 h group, the EN-initiated within 24 h group exhibited a shorter intensive care unit stay ( t=2.65, P<0.05) and shorter mechanical ventilation duration ( t=2.23, P<0.05) than EN-initiated after 24 h group. Total hospitalization length had no significant difference ( P>0.05). At 72 h post-transplant, the EN-initiated within 24 h group had a lower interleukin-12 P70 ( t=2.46, P<0.05) and interferon-γ levels ( t=2.55, P<0.05) than EN-initiated after 24 h group. Prior to discharge, the EN-initiated within 24 h group has a lower mean skinfold thickness ( t=2.49, P<0.05) and lower mid-upper arm circumference ( t=2.36, P<0.05) compared with the EN-initiated after 24 h group. Conclusions:Initiating EN within 24 h postoperatively is safe and feasible in pediatric heart transplant recipients. Early EN may shorten the length of intensive care unit stay and mechanical ventilation while attenuating postoperative release of inflammatory cytokine.

In recent years, the development of host-acting antibacterial compounds has gradually become a hotspot in the field of anti-infection. Through research on the interaction mechanism between hosts and pathogenic bacteria, it has been found that the immune system is one of the key targets of host-acting antibacterial compounds. There is a communication system called the quorum sensing system in microorganisms, which mainly adjusts the structure of multi-microbial community and coordinates the group behavior. When the quorum sensing molecules secreted by microorganisms reach a threshold concentration, the quorum sensing system is activated and the overall gene expression of the microorganism is changed. In addition to regulating the density of microorganisms, quorum sensing molecules can also act as a link between pathogenic microorganisms and hosts, entering the host immune system and playing a role in affecting the morphological structure of immune cells, secreting cytokines, and inducing apoptosis, leading to host immune injury and causing host immune dysfunction.The key mechanism of 3-oxo-C12-HSL and other acyl-homoserine lactone (AHL) molecules in the innate immune system has been extensively studied. The lipid solubility allows AHLs to pass through the plasma membrane of host immune cells easily and induce dissolution of lipid domains. Then, it acts through signaling pathways such as p38MAPK and JAK-STAT, further influencing the immune cell’s defense response to bacteria and potentially leading to cell apoptosis. Additionally, the human lactonase paraoxonase 2, which can degrade3-oxo-C12-HSL, has been found in macrophage. It acts as an immune regulator that promotes macrophage phagocytosis of pathogens and is hypothesized to have the ability to reduce bacterial resistance. The mechanism of quorum sensing molecules in the adaptive immune system is less studied, the current results suggest that 3-oxo-C12-HSL is closely related to the mitochondrial pathway in host immune cells. For example, 3-oxo-C12-HSL induces apoptosis of Jurkat cells by inhibiting the expression of three mitochondrial electron transport chain proteins; it can also trigger mitochondrial dysfunction and induce mast cell apoptosis through Ca²⁺ signaling.Among the quorum sensing molecules, the AHLs have the greatest impact on plant immune system. The different effects on plant resistance depends on the chain lengths of acyl groups in bacterial-produced AHLs. Short-chain AHLs (C4-HSL and C8-HSL) induce plant resistance to pathogenic bacteria mainly through the auxin pathway and jasmonic acid pathway. Long-chain AHL (3-oxo-C14-HSL) is commonly used in hosts against fungal pathogens by inducing stomata defense responses, and the reaction process is related to salicylic acid. Diffusible signal factor molecules also interfere with the stomatal immunity caused by pathogens. It may act through the formin nanoclustering-mediated actin assembly and MPK3 pathway to inhibit the innate immunity of Arabidopsis. In summary, AHLs induced different plant pathways and affects the plant-bacteria interactions to trigger plant immunity. As a quorum sensing molecule of fungi, farnesol has similar effects on host immunity as AHLs, such as stimulating cytokine secretion and activating an inflammatory response. It also plays a unique role on dendritic cell differentiation and maturation. In addition, studies have found that farnesol has a protective effect on autoimmune encephalomyelitis, which may be related to its effect on the composition of intestinal microorganisms of the host.Therefore, targeting the host immune system and quorum sensing molecules to develop antibacterial compounds can effectively inhibit the invasion of pathogens and subserve the host to resist the influence of pathogenic bacteria. This article will review the mechanism of host immune responses triggered by important quorum sensing molecules, aiming to explore the targets of host-acting antibacterial compounds and provide new directions for the prevention or treatment of causative infectious sources and the development of related drugs.

Objective To explore the efficacy and safety of recombinant human anti-severe acute respiratory syn-drome coronavirus 2(anti-SARS-CoV-2)monoclonal antibody injection(F61 injection)in the treatment of patients with coronavirus disease 2019(COVID-19)combined with renal damage.Methods Patients with COVID-19 and renal damage who visited the PLA General Hospital from January to February 2023 were selected.Subjects were randomly divided into two groups.Control group was treated with conventional anti-COVID-19 therapy,while trial group was treated with conventional anti-COVID-19 therapy combined with F61 injection.A 15-day follow-up was conducted after drug administration.Clinical symptoms,laboratory tests,electrocardiogram,and chest CT of pa-tients were performed to analyze the efficacy and safety of F61 injection.Results Twelve subjects(7 in trial group and 5 in control group)were included in study.Neither group had any clinical progression or death cases.The ave-rage time for negative conversion of nucleic acid of SARS-CoV-2 in control group and trial group were 3.2 days and 1.57 days(P=0.046),respectively.The scores of COVID-19 related target symptom in the trial group on the 3rd and 5th day after medication were both lower than those of the control group(both P＜0.05).According to the clinical staging and World Health Organization 10-point graded disease progression scale,both groups of subjects improved but didn't show statistical differences(P＞0.05).For safety,trial group didn't present any infusion-re-lated adverse event.Subjects in both groups demonstrated varying degrees of elevated blood glucose,elevated urine glucose,elevated urobilinogen,positive urine casts,and cardiac arrhythmia,but the differences were not statistica-lly significant(all P＞0.05).Conclusion F61 injection has initially demonstrated safety and clinical benefit in trea-ting patients with COVID-19 combined with renal damage.As the domestically produced drug,it has good clinical accessibility and may provide more options for clinical practice.

Objective To investigate the changes of brain networks function in patients with primary dysmenorrhea(PDM)during menstruation based on topological attributes of brain network.Methods Brain resting-state functional MRI of 57 PDM patients(PDM group)and 50 healthy women(health control[HC]group)were prospectively collected within the first or the second day of menstruation.Clinical scores were obtained and compared between groups.Results Visual analogue scale,cox menstrual symptom scale,self-rating anxiety scale and self-rating depression scale scores in PDM group were all higher than those in HC group(all P＜0.05).At the sparsity of 0.04-0.50,brain networks in both groups conformed to the small world attribute characteristics,and no significant difference of global attributes of brain network was found between groups(all P＞0.05).The node efficiency(Ne)and node degree(Dc)of bilateral posterior cingulate gyrus(PCG),as well as De and node betweenness(Bc)of left middle frontal gyrus(MFG)in PDM group were all higher than those in HC group,while Ne and De of left inferior temporal gyrus in PDM group were lower than those in HC group(all P＜0.01).Compared with HC group,the functional connections between left PCG and right calcarine fissure and surrounding cortex,right lingual gyrus and left MFG,as well as between right PCG and right dorsolateral superior frontal gyrus and left MFG,between right insula and left middle occipital gyrus enhanced in PDM group(all P＜0.001).Conclusion In PDM patients,local brain networks function such as default mode network,central executive network and salience network were over-activated during menstruation,yet the overall brain network still had good coordination and organization.

Objective:To explore the impacts of thermotherapy combined with gemcitabine on the biological behavior of tongue squamous cell carcinoma cells.Methods:Human tongue squamous cell carcinoma Tca8113 cells were divided into the control group (blank control), gemcitabine group, thermotherapy group (heated in an incubator at 43℃ for 1 h and then incubated at 37℃ for 24 h) and thermotherapy + gemcitabine group. The proliferation ability of Tca8113 cells was assessed by EdU staining and CCK-8 assay. Cell apoptosis and cell cycle of Tca8113 cells were detected by flow cytometry. The invasion of Tca8113 cells was determined by Transwell chamber assay. The expression levels of cyclin D1 (CyclinD1), Bcl-2-associated X protein (Bax), matrix metalloproteinase (MMP)-9, phosphorylated histone H2AX (γH2AX) and Nijmegen breakage syndrome 1 (NBS1) proteins in Tca8113 cells were measured by Western blot. The changes of tumor mass and volume were detected by xenograft tumor in vivo test in nude mice. Multi-group comparison was performed by one-way ANOVA. Two group comparison was conducted by SNK- q test. Results:Compared with the control group, EdU positive cell percentage, OD 450 value, invasive cell number, CyclinD1, MMP-9 and NBS1 protein expression of Tca8113 cells were decreased, whereas the apoptosis rate, the expression of Bax and γH2AX proteins were increased in the gemcitabine, thermotherapy and thermotherapy + gemcitabine groups ( q=4.45-72.06, all P<0.001). Compared with the control group, the proportion of G 0/G 1 phase cells was decreased, whereas the proportion of S and G 2/M phase cells was increased in the gemcitabine and thermotherapy + gemcitabine groups, the proportion of G 0/G 1 phase cells was decreased and the proportion of G 2/M phase cells was increased in the hyperthermia group ( q=10.36-61.09, all P<0.001). Compared with the gemcitabine and thermotherapy groups, EdU positive cell percentage, OD 450 value, G 0/G 1 phase cell proportion, invasive cell number, CyclinD1, MMP-9 and NBS1 protein expression of Tca8113 cells were decreased, whereas apoptosis rate, S, G 2/M phase cell proportion, Bax and γH2AX protein expression were increased in the thermotherapy + gemcitabine group ( q=4.45-28.73, all P<0.001). Xenograft tumor in vivo test in nude mice showed that the tumor volume and mass of nude mice in the gemcitabine, thermotherapy, and thermotherapy + gemcitabine groups were decreased compared with those in the control group ( q=5.58-73.02, all P<0.001). Compared with the gemcitabine and thermotherapy groups, the tumor volume and mass in the thermotherapy + gemcitabine group were decreased ( q=5.58-21.45, all P<0.001). Conclusion:The combination of thermotherapy and gemcitabine can inhibit the proliferation and invasion, block the cell cycle, and induce cell apoptosis of Tca8113 cells.

Conventional tumor culture models include two-dimensional tumor cell cultures and xenograft models. The former has disadvantages including lack of tumor heterogeneity and poor clinical relevance, while the latter are limited by the slow growth, low engraftment successful rate, and high cost. In recent years, in vitro three-dimensional (3D) tumor models have emerged as the tool to better recapitulate the spatial structure and the in vivo environment of tumors. In addition, they preserve the pathological and genetic features of tumor cells and reflect the complex intracellular and extracellular interactions of tumors, which have become a powerful tool for investigating the tumor mechanism, drug screening, and personalized cancer treatment. 3D tumor model technologies such as spheroids, organoids, and microfluidic devices are maturing. Application of new technologies such as co-culture, 3D bioprinting, and air-liquid interface has further improved the clinical relevance of the models. Some models recapitulate the tumor microenvironment, and some can even reconstitute endogenous immune components and microvasculature. In recent years, some scholars have combined xenograft models with organoid technology to develop matched in vivo/in vitro model biobanks, giving full play to the advantages of the two technologies, and providing an ideal research platform for individualized precision therapy for specific molecular targets in certain subtypes of tumors. So far, the above technologies have been widely applied in the field of colorectal cancer research. Our research team is currently studying upon the application of patient-derived tumor cell-like clusters, a self-assembly 3D tumor model, in guiding the selection of postoperative chemotherapy regimens for colorectal cancer. A high modeling success rate and satisfactory results in the drug screening experiments have been achieved. There is no doubt that with the advancement of related technologies, 3D tumor models will play an increasingly important role in the research and clinical practice of colorectal cancer.
Humans ; Organoids/pathology* ; Cell Culture Techniques ; Colorectal Neoplasms/pathology* ; Tumor Microenvironment

Objective: To investigate the clinical characteristics and maternal and fetal prognosis of pregnant women with acute fatty liver of pregnancy (AFLP). Methods: The clinical data of 86 AFLP pregnant women admitted to the Third Affiliated Hospital of Guangzhou Medical University from September 2017 to August 2022 were collected, and their general data, clinical characteristics, laboratory tests and maternal and fetal outcomes were retrospectively analyzed. Results: (1) General information: the age of the 86 pregnant women with AFLP was (30.8±5.4) years, and the body mass index was (21.0±2.5) kg/m². There were 50 primiparas (58.1%, 50/86) and 36 multiparas (41.9%, 36/86). There were 64 singleton pregnancies (74.4%, 64/86) and 22 twin pregnancies (25.6%, 22/86). (2) Clinical characteristics: the main complaints of AFLP pregnant women were gastrointestinal symptoms, including epigastric pain (68.6%, 59/86), nausea (47.7%, 41/86), anorexia (46.5%, 40/86), vomiting (39.5%, 34/86). The main non-gastrointestinal symptoms were jaundice of skin and/or scleral (54.7%, 47/86), edema (38.4%, 33/86), fatigue (19.8%, 17/86), bleeding tendency (16.3%, 14/86), polydipsia or polyuria (14.0%, 12/86), skin itching (8.1%, 7/86), and 17.4% (15/86) AFLP pregnant women had no obvious symptoms. (3) Laboratory tests: the incidence of liver and kidney dysfunction and abnormal coagulation function in AFLP pregnant women was high, and the levels of blood ammonia, lactate dehydrogenase and lactic acid were increased, and the levels of hemoglobin, platelet and albumin decreased. However, only 24 cases (27.9%, 24/86) of AFLP pregnant women showed fatty liver by imageology examination. (4) Pregnancy outcomes: ① AFLP pregnant women had a high incidence of pregnancy complications, mainly including renal insufficiency (95.3%, 82/86), preterm birth (46.5%, 40/86), hypertensive disorders in pregnancy (30.2%, 26/86), gestational diabetes mellitus (36.0%, 31/86), fetal distress (24.4%, 21/86), pulmonary infection (23.3%, 20/86), disseminated intravascular coagulation (16.3%, 14/86), multiple organ dysfunction syndrome (16.3%, 14/86), hepatic encephalopathy (9.3%, 8/86), and intrauterine fetal death (2.3%, 2/86). ② Treatment and outcome of AFLP pregnant women: the intensive care unit transfer rate of AFLP pregnant women was 66.3% (57/86). 82 cases were improved and discharged after treatment, 2 cases were transferred to other hospitals for follow-up treatment, and 2 cases (2.3%, 2/86) died. ③ Neonatal outcomes: except for 2 cases of intrauterine death, a total of 106 neonates were delivered, including 39 cases (36.8%, 39/106) of neonatal asphyxia, 63 cases (59.4%, 63/106) of neonatal intensive care unit admission, and 3 cases (2.8%, 3/106) of neonatal death. Conclusions: AFLP is a severe obstetric complication, which is harmful to mother and fetus. In the process of clinical diagnosis and treatment, attention should be paid to the clinical manifestations and laboratory tests of pregnant women, early diagnosis and active treatment, so as to improve maternal and fetal outcomes.
Pregnancy ; Infant, Newborn ; Female ; Humans ; Adult ; Retrospective Studies ; Premature Birth/epidemiology* ; Pregnancy Complications/diagnosis* ; Fatty Liver/diagnosis* ; Fetal Death ; Stillbirth

Tumor microenvironment possesses immunosuppression characteristics via the mechanism of inducing tumor cell immune escape. The interaction between tumor cells and tumor microenvironment is an important factor affecting tumor genesis and development. As an important part of tumor microenvironment, cancer-associated fibroblasts interact directly or indirectly with tumor cells and produce various cytokines to regulate tumor immune microenvironment. In recent years, hyperthermia has become an auxiliary means of anti-tumor therapy. With the development of research on tumor hyperthermia and tumor microenvironment, a large number of studies have found that hyperthermia can regulate cancer-associated fibroblasts in tumor microenvironment. In this article, recent research progresses of the effects of hyperthermia on cancer-associated fibroblasts and related cells and cytokines in tumor microenvironment were reviewed, providing a new way for clinical application of hyperthermia combined with immune or targeted therapy.

Objective: To investigate the association of the levels of high sensitivity C-reactive protein (hs-CRP) with frailty and its components among the elderly over 65 years old in 9 longevity areas of China. Methods: Cross-sectional data from the Health Ageing and Biomarkers Cohort Study (HABCS, 2017-2018) were used and the elderly over 65 years old were included in this study. Through questionnaire interview and physical examination, the information including demographic characteristics, behavior, diet, daily activity, cognitive function, and health status was collected. The association between hs-CRP and frailty and its components in the participants was analyzed by multivariate logistic regression model and restrictive cubic spline. Results: A total of 2 453 participants were finally included, the age was (84.8±19.8) years old. The median hs-CRP level was 1.13 mg/L and the prevalence of frailty was 24.4%. Compared with the low-level group (hs-CRP<1.0 mg/L), the OR (95%CI) value of the high-level group (hs-CRP>3.0 mg/L) was 1.79 (1.35-2.36) mg/L. As for the components, the hs-CRP level was also positively associated with ADL disability, IADL disability, functional limitation and multimorbidity. After adjusting for confounding factors, compared with the low-level group, the OR (95%CI) values of the high-level group for the four components were 1.68 (1.25-2.27), 1.88 (1.42-2.50), 1.68 (1.31-2.14) and 1.39 (1.12-1.72), respectively. Conclusion: There is a positive association between the levels of hs-CRP and the risk of frailty among the elderly over 65 years old in 9 longevity areas of China. The higher hs-CRP level may increase the risk of frailty by elevating the risk of four physical functional disabilities, namely ADL disability, IADL disability, functional limitation and multimorbidity.
Humans ; Aged ; Aged, 80 and over ; C-Reactive Protein/analysis* ; Frailty/epidemiology* ; Cohort Studies ; Cross-Sectional Studies ; China/epidemiology*