BACKGROUND:Radiotherapy for head and neck tumors is very likely to cause radiation-induced oral mucositis,which seriously affects the health of patients and the treatment plan of tumors.Mesenchymal stem cells have shown therapeutic potential in many diseases,and exosomes are one of the important factors for their function.At present,there is no application of adipose mesenchymal stem cell-derived exosomes in the study of radiation-induced oral mucositis. OBJECTIVE:To investigate the role of adipose mesenchymal stem cell-derived exosomes in radiation-induced oral mucositis. METHODS:Adipose mesenchymal stem cells and adipose mesenchymal stem cell-derived exosomes were extracted and identified.In vitro model of radiation-induced oral mucositis was induced by radiating oral mucosal epithelial cells with 3 Gy X-ray.Adipose mesenchymal stem cells or adipose mesenchymal stem cell-derived exosomes were pretreated for 48 hours before modeling.The proliferation capacity of oral mucosal epithelial cells was detected by EdU assay and clonal formation assay.A mouse model of radiation-induced oral mucositis was constructed through 3 Gy X-ray radiation.Adipose mesenchymal stem cells and adipose mesenchymal stem cell-derived exosomes were injected into the tail vein of radiation-induced oral mucositis mice.Hematoxylin-eosin staining and immunohistochemistry were used to evaluate the inflammatory changes of oral mucosal epithelial tissue. RESULTS AND CONCLUSION:(1)Compared with the control group,both adipose mesenchymal stem cells and adipose mesenchymal stem cell-derived exosomes promoted the formation of oral epithelial cell clones and increased the positive rate of EdU in oral epithelial cells.(2)Both adipose mesenchymal stem cells and adipose mesenchymal stem cell-derived exosomes alleviated the inflammation of oral mucosal epithelium of irradiated mice;CD45 positive cells decreased and PCNA positive cells increased in oral mucosal epithelium.It is concluded that adipose mesenchymal stem cell-derived exosomes promote the proliferation of oral mucosal epithelial cells and release oral mucosal inflammation in mice with radiation-induced oral mucositis.

Objective To investigate the seroprevalence of antibody against Toxoplasma gondii among patients with hematological malignancies, and compare it with that among health individuals, so as to provide insights into unraveling the pathogenesis of hematological malignancies. Methods A total of 225 patients with hematological malignancies in Department of Hematology, Xuzhou Central Hospital and 300 healthy individuals in the same hospital were enrolled from 2017 to 2024. Blood samples were collected from all subjects, and the serum IgG and IgM antibodies against T. gondii were detected using chemiluminescent immunoassay. Demographic and clinical features were collected from patients with hematological malignancies, including gender, age, contact with cats, consumption of raw or undercooked meat, type of malignancy, clinical symptoms, blood transfusion and treatment, and the seroprevalence of anti-T. gondii antibody was compared among patients with different characteristics. Results The age (t = 0.72, P > 0.05) and gender (χ² = 0.93, P > 0.05) were compared between patients with hematological malignancies and healthy individuals. The seroprevalence of T. gondii infection was 20.89% among patients with hematological malignancies and 4.33% among healthy individuals (χ² = 34.81, P < 0.01), and the seroprevalence of anti-T. gondii IgG antibody was 20.89% among patients with hematological malignancies and 4.33% among healthy individuals (χ² = 34.81, P < 0.01), while there was no significant difference in the seroprevalence of anti-T. gondii IgM antibody between patients with hematological malignancies and healthy individuals (1.33% vs. 0; corrected χ² = 2.02, P > 0.05). The seroprevalence of T. gondii infection was 23.08% among patients with leukemia, 16.67% among patients with lymphoma, 19.23% among patients with multiple myeloma, 24.00% among patients with myeloproliferative neoplasm, and 26.09% among patients with myelodysplastic syndrome (χ² = 1.44, P > 0.05), and was all higher than among healthy individuals (corrected χ² = 23.92, 10.74, 13.76, 12.84 and 14.54; all P values < 0.01). In addition, there were no significant differences in the detection of anti-T. gondii antibody among patients with hematological malignancies in terms of gender, age, contact with cats, consumption of raw or undercooked meat, chemotherapy or blood transfusion (χ² = 0.76, 1.97, 0, 2.81, 2.38 and 0.66; all P values > 0.05). Conclusions There is a high risk of T. gondii infection among patients with hematological malignancies, and intensified surveillance of T. gondii infection is recommended among patients with hematological malignancies.

Objective To develop a 3D visualization endoscopic navigation system based on CT portal angiography (CTPA) and explore its clinical value in assisting precise treatment of esophageal and gastric varices (EGV). Methods Patients with EGV needing treatment in the Department of Gastroenterology of Zhongshan Hospital, Fudan University from September 2021 to April 2023 were collected. Preoperative examinations including CTPA and hematological examinations were performed, and a 3D visualization endoscopic navigation system was developed to assist endoscopic treatment. Real time comparison was made between the endoscopic 3D portal vein system image reconstructed by intelligent imaging and the actual endoscopic observation of the vascular morphology inside the cavity. The responsible blood vessels that are prone to bleeding were embolized using a sandwich injection method of “lauromacrogol+tissue adhesive+lauromacrogol”. For patients with portal shunting, ultrasound-guided coil insertion was performed. Postoperative endoscopic ultrasound or CTPA was used reexamination to evaluate vascular embolism and complications. Results A total of 13 patients successfully underwent endoscopic ultrasound-guided variceal embolization. The average maximum inner diameter of target veins was (3.3\begin{document}$ \pm $\end{document}1.3) cm; on average, implanted coil number was 1(0,2) in each patient, with median dosages of lauromacrogol and tissue adhesive were 9.5(7.8,10.0) mL and 1.5(1.0,2.1) mL respectively. Postoperatively, endoscopic ultrasound detecting confirmed complete occlusion of all target veins. At 8 weeks after treatment, none of the patients experienced rebleeding. At 24 weeks after treatment, rebleeding occurred in 3 patients, on postoperative days 107, 126 and 147, respectively. Conclusion The 3D visualization endoscopic navigation system based on CTPA can effectively and safely assist preoperative diagnosis and intraoperative localization of target blood vessels, which is beneficial for the precise treatment of EGV patients.

Portal vein thrombosis (PVT) is a common complication in patients with liver cirrhosis, impacting the efficacy of endoscopic treatment for esophagogastric varices (EGV) by exacerbating portal hypertension and altering hemodynamics and coagulation function. This paper systematically reviews the pathogenesis of PVT, and its impact on the efficacy of endoscopic therapy for EGV. PVT is closely associated with early hemostatic failure post-endoscopic treatment, elevated rebleeding rate, and elevated long-term mortality. Although anticoagulation therapy facilitates partial thrombus recanalization and reduces portal pressure, its combination with endoscopic treatment requires careful consideration of the bleeding risk. Current clinical practice necessitates optimization of combined therapeutic strategies integrating anticoagulation and endoscopic treatment, complemented by personalized treatment approaches, to improve clinical outcomes.

Objective This study aimed to investigate the antimicrobial resistance profiles of bacterial strains isolated from pediatric intensive care units(PICU)in China for better antimicrobial therapy.Methods Clinical isolates were collected from 17 institutions,including tertiary care children's hospitals and pediatric department of tertiary general hospitals in China from January 1,2020 to December 31,2022.Antimicrobial susceptibility testing was carried out according to a unified protocol using Kirby-Bauer method or automated systems.Results were interpreted according to the breakpoints released by the Clinical and Laboratory Standards Institute(CLSI)in 2020.Results A total of 10 688 isolates were collected,including gram-positive organisms(39.2％)and gram-negative organisms(60.8％).The top three organisms were S.aureus(13.6％,1 453/10 688),A.baumannii(10.0％,1 067/10 688),and coagulase-negative Staphylococcus(9.9％,1 058/10 688).Multi-drug resistant organisms(MDROs)were very common in children.The prevalence of methicillin-resistant Staphylococcus aureus(MRSA),carbapenem-resistant Enterobacterales(CRE),carbapenem-resistant E.coli,carbapenem-resistant K.pneumoniae(CRKP),carbapenem-resistant A.baumannii(CRAB),and carbapenem-resistant P.aeruginosa(CRPA)was 41.1％,19.4％,8.8％,30.9％,67.4％,and 28.8％,respectively.Overall,more than 50％of Enterobacteriales isolates were resistant to cephalosporins,while nearly 25％of Enterobacteriales isolates were resistant to carbapenems.MDROs were highly resistant to commonly used antibiotics.More than 80％of CRE and CRAB strains were resistant to all beta-lactam antibiotics.CRE and CRAB showed low resistance rates to tigecycline and polymyxin.CRPA showed lower resistance rates to piperacillin,beta-lactamase inhibitor combinations than the resistance rates to third and fourth generation cephalosporins.All of the Staphylococcus and Enterococcus isolates were susceptible to vancomycin and tigecycline.None of PRSP strains isolated from meningitis and nonmeningitis samples were resistant to rifampicin,vancomycin,or linezolid.The prevalence of β-lactamase-negative ampicillin-resistant(BLNAR)strains was 43.3％in Haemophilus influenzae.Conclusions MDROs were prevalent in PICU.It is necessary to establish an effective multidisciplinary team(MDT)to control the antimicrobial resistance.

Background and Aims:Gastroesophageal reflux disease(GERD)is a common complication following sleeve gastrectomy(SG),particularly in patients with concomitant hiatal hernia,where symptoms tend to be more persistent and refractory,significantly impairing postoperative quality of life.This study aimed to evaluate the efficacy of laparoscopic hiatal hernia repair combined with gastroesophageal fixation in SG patients with severe GERD and hiatal hernia,providing clinical reference for revisional surgical strategies.Methods:The clinical data of 9 patients with severe GERD after SG who underwent laparoscopic hiatal hernia repair and gastroesophageal fixation at Huashan Hospital,Fudan University,between January 2023 and June 2024 were retrospectively analyzed.GerdQ scores,proportion of endoscopically confirmed reflux esophagitis,and proton pump inhibitor(PPI)usage were compared before and after surgery.Surgical parameters and follow-up outcomes were also recorded.Results:All patients successfully completed the surgery without major intraoperative complications,and the mean postoperative hospital stay was 5.22 d.After a mean follow-up period of 15.27 months,the GerdQ score significantly decreased from 11.67±2.00 to 7.22±1.48.The proportion of patients with GerdQ score≥8 decreased from 100.00％to 44.44％,and the rate of endoscopically confirmed GERD dropped from 88.89％to 11.11％;PPI use also significantly declined,with all differences reaching statistical significance(all P＜0.05).Conclusion:Laparoscopic hiatal hernia repair combined with gastroesophageal fixation can effectively alleviate reflux symptoms in SG patients with coexisting hiatal hernia,demonstrating favorable short-term efficacy and high safety.This approach may be a preferable surgical option for selected patients.

Objective To investigate the efficacy of lenalidomide combined with bortezomib and dexamethasone in the treatment of multiple myeloma(MM)and their effects on heat shock protein 90(HSP90)mRNA,miR-28-5p,anti-tartrate acid phosphatase 5b(TRACP-5b)and high mobility group protein B1(HMGB1).Methods Eighty patients with newly diagnosed MM were selected and divided into the two-combination group(40 patients treated with bortezomib and dexamethasone)and the three-combination group(40 patients treated with bortezomib and dexamethasone combined with lenalidomide)according to the treatment modalities.Real-time fluorescence quantitative polymerase chain reaction was used to detect HSP90 mRNA and miR-28-5p levels.Enzyme-linked immunosorbent assay was used to detect TRACP-5b and HMGB1 levels.The clinical efficacy of the 2 groups was compared.Levels of HSP90 mRNA,miR-28-5p,TRACP-5b,HMGB1,the immune cell function,renal function indexes and the incidence of adverse reactions were compared before and after treatment.Results The total effective rate of the three-combination group was higher than that of the two-combination groups(92.50%vs.75.00%,P＜0.05).Compared with the pretreatment,the levels of HSP90 mRNA,TRACP-5b,blood creatinine(SCr),and urea nitrogen(BUN)decreased in the 2 groups after treatment,and which was lower in the three-combination group than that in the two-combination groups.The levels of miR-28-5p,HMGB1,CD4+,CD3+and CD4+/CD8+were elevated in the 2 groups,and the levels were higher in the three-combination group than those in the two-combination group(P＜0.05).There was no significant difference in the incidence of adverse reactions between the two groups.Conclusion Lenalidomide combined with bortezomib and dexamethasone is clinically effective,safe and reliable in the treatment of MM.

Objective:To investigate the association between different types of lung nodules and the risk of lung cancer in a population at high risk of lung cancer and to provide an epidemiologic basis for the comprehensive management of lung nodules.Methods:Using the free lung cancer screening program of low-dose CT (LDCT) in Wenling, Zhejiang Province, we collected baseline and imaging information of high-risk groups for lung cancer who underwent LDCT screening from April 2019 to October 2021 and patients with previous history of lung cancer, tuberculosis, pneumoconiosis, and silicosis were excluded. A total of 28 539 study subjects were included in the analysis, and the follow-up ended on 31 December 2023. Based on the characteristics of the detected pulmonary nodules, the study subjects were classified with no nodules, with solid nodules, with pure ground glass nodules, and with part solid nodules groups. The association between different characteristics of lung nodules and the risk of lung cancer development was analyzed using the Cox proportional hazard regression model with a new diagnosis of lung cancer during the follow-up period as the outcome.Results:The overall detection rate of lung nodules with a mean diameter of ≥3 mm was 76.5%, of which 53.7%, 18.2%, and 4.6% were detected in the solid nodule, pure ground glass nodule, and partially solid nodule groups, respectively. There were statistically significant differences between the different nodule groups in terms of age, gender, BMI, history of toxic exposure education level, smoking status, history of lung disease, and family history of lung cancer (all P<0.05). The median follow-up time of the study population was 3.4 years, and 485 new lung cancer cases were diagnosed during the follow-up period. After adjusting for covariates, the results of multifactorial Cox proportional hazard regression model analysis showed that the risk of lung cancer was higher in pure ground glass nodules and part solid nodules compared with solid nodules, with HR values (95% CI) of 1.89 (1.52-2.35) and 6.49 (5.18-8.14), respectively. The results of subgroup analysis showed that patients in the group of part solid nodules had the highest risk of lung cancer in all strata of the population, followed by patients with pure ground glass nodules. Patients in the solid nodule group who were older or had previous lung disease had a higher risk of lung cancer, and the risk of lung cancer in the part solid nodule group differed between genders. Conclusions:The proportion of lung nodules detected is high in the high-risk group of lung cancer, and among them, patients with pure ground glass and part solid nodules have a higher risk of developing lung cancer. Attention should be paid to the annual follow-up management for patients with solid nodules who are older or who have had lung diseases, as well as for female patients with part solid nodules.

Objective:To investigate the clinical manifestations, gene mutation characteristics, imaging and video electroencephalogram (VEEG) characteristics of patients with dentatorubral-pallidoluysian atrophy (DRPLA).Methods:The clinical data of 9 patients with genetically diagnosed DRPLA in the Neurology Center, Beijing Tiantan Hospital, Capital Medical University from January 2018 to January 2023 were collected, and the clinical data of DRPLA patients reported in China were retrieved and summarized.Results:A total of 45 cases were included. The clinical characteristics were summarized as follows: (1) The male to female ratio of 45 patients was 1.00∶1.25, and the age of onset was (28.11±14.58) years. (2) The main clinical symptoms of juvenile type, early-onset adult type and late-onset adult type were analyzed, and the results showed that the frequency of seizures in juvenile type (16/17) was higher than that in early-onset adult type (8/21) and late-onset adult type (2/7), with statistically significant difference (χ 2=15.971, P<0.001). In addition, the frequency of cognitive impairment in juvenile type (16/17) was also higher than that in early-onset adult type (15/21) and late-onset adult type (2/7), also with statistically significant difference (χ 2=10.177, P=0.005). Cognitive impairment, language disorder and involuntary movement were common in early-onset adult patients, and about half of the patients had ataxia. Ataxia and language disorder were more common in late-onset adult patients, while seizures and cognitive impairment were rare. (3) In imaging, cerebellum and brainstem atrophy was the most common, followed by cortical atrophy and white matter lesions. (4) The number of trinucleotide (CAG) repeats was 53-79, and there was a significant negative correlation between the number of CAG repeats and the age of onset ( r=-0.765, P<0.001), that means the younger the age of onset, the higher the number of CAG repeats. (5) In terms of electrophysiology, 21 patients provided complete VEEG data, of which slowed activity (52%, 11/21) and generalized discharge (71%, 15/21) were more common, and focal discharge (33%, 7/21) was uncommon. Conclusions:DRPLA patients can present with epilepsy, cerebellar ataxia, and other clinical manifestations. Brainstem and cerebellar atrophy and white matter lesions can be relatively characteristic in imaging. In terms of electrophysiology, slowed activity and generalized discharge are more common. DRPLA patients are easy to be misdiagnosed in clinical practice and genetic confirmation helps confirm the diagnosis.

OBJECTIVE To analyze the correlation of the peak blood concentration （cmax） of compound sulfamethoxazole （TMP/SMZ） and its metabolite N-acetyl sulfamethoxazole （NSMZ） with clinical efficacy and adverse reactions in critically ill patients. METHODS The data of critically ill patients treated with TMP/SMZ in various ICU of Hainan General Hospital from December 2023 to January 2025 were retrospectively collected. The patients were divided into success group and failure group based on the treatment outcome. Simple linear regression and Spearman correlation analysis were used to analyze the correlation of TMP cmax， SMZ cmax， and NSMZ cmax with clinical efficacy and adverse reactions. The receiver operating characteristic curve （ROC） was used to determine the cutoff values of cmax for predicting the occurrence of adverse reactions. RESULTS Among critically ill patients with an acute physiology and chronic health evaluation Ⅱ （APACHE-Ⅱ） ≥15 points 24 h of check-in at ICU， SMZ cmax of success group was significantly higher than failure group （P＜0.05）. The daily total dose of TMP/SMZ was positively correlated with TMP cmax and SMZ cmax（ P＜0.05）. TMP cmax was significantly correlated with hepatotoxicity and nephrotoxicity， SMZ cmax with hepatotoxicity， and NSMZ cmax with nephrotoxicity （P＜0.05）. The cutoff values of TMP cmax for predicting nephrotoxicity and hepatotoxicity were 7.25 μg/mL and 6.63 μg/mL， respectively. The cutoff value of SMZ cmax for predicting hepatotoxicity was 138.00 μg/mL， and that of NSMZ cmax for predicting nephrotoxicity was 60.76 μg/mL. CONCLUSIONS Among critically ill patients with an APACHE-Ⅱ ≥15 points 24 h of check-in at ICU， SMZ cmax is associated with treatment success. Hepatotoxicity risk significantly increases when TMP cmax ≥6.63 μg/mL or SMZ cmax ≥138.00 μg/mL； nephrotoxicity risk significantly increases when TMP cmax ≥7.25 μg/mL or NSMZ cmax ≥60.76 μg/mL.