With the increasing number of people with immune deficiency in recent years, fungal infections become an important factor threatening human health.Likewise, the number of children who are immunosuppressed due to hematological diseases, malignancies, use of immunosuppressants and spectrum antibacterial drugs has increased, leading to a high mortality of fungal infections.Moreover, infections of the non-candida albicans and aspergillu are prevalent, serving as important causes for the death of critically ill children. Therefore, this review aims to introduce and summarize the epidemiological characteristics, diagnosis and treatment of pediatric invasive fungal infections, thus yielding the concern of pediatric invasive fungal infections, reducing the occurrence of pediatric fungal infections and improving the prognosis.

Objective:To investigate the impact of BMI1 expression in OSCC on the recruitment and differentiation of tumor-associat-ed macrophages(TAMs).Methods:BMI1 expression in 519 cases of OSCC tissues and 44 normal controls was analyzed using online datasets of GEPIA 2.0,and validated in 3 cases of OSCC samples and controls by qRT-PCR and western blotting.The function of BMI1/NF-κB axis during OSCC carcinogenesis was investigated by CCK8 assays,wound healing test and transwell assays.Macrophage phenotypes and recruitment were determined using qRT-PCR and western blotting following coculture of the cells with human monocyte cells(THP-1)by OSCC conditioned medium.Moreover,a cell line-derived xenograft(CDX)model was used to detect the effect of BMI1 on tumor growth in vivo.Results:Compared with the normal tissues and cells,the expression level of BMI1 in OSCC tissues and cells was significantly upregulated.BMI1 knockdown impaired the proliferation,migration,and invasion abilities of OSCC cell lines in NF-κB-dependent manner.Furthermore,OSCC cells with high BMI1 expression inhibited the migration of THP-1 cells,promoted M2-like macrophage polarization through NF-κB pathway in vitro.Xenograft experiments further confirmed the inhibitory effect of BMI1 knockdown on the tumorigenesis ability of OSCC cells in vivo.Conclusion:BMI1 promotes M2-like polarization by regulating NF-κB and may be used as a potential therapeutic target for antitumor immunity.

BACKGROUND:Increasing evidence suggests that N6-methyladenosine(m6A)regulators are closely associated with osteoarthritis and are considered to be a new direction in the prevention and treatment of osteoarthritis,but their specific mechanism of action is unknown. OBJECTIVE:To conduct a bioinformatics analysis of the osteoarthritis gene microarray dataset in order to explore the role of m6A in osteoarthritis and analyze the pathogenesis of osteoarthritis. METHODS:The m6A regulators associated with osteoarthritis and their expression were first extracted from the GSE1919 dataset in the GEO database using R software,and then the results were analyzed by gene difference analysis and GO and KEGG enrichment analyses.Subsequently,the results of protein-protein interaction network topology analysis and machine learning results were intersected to obtain the m6A Hub regulators,which were validated by in vitro cellular experiments. RESULTS AND CONCLUSION:A total of 16 osteoarthritis-related m6A regulators were extracted and 11 m6A differential regulators,including ZC3H13,YTHDC1,YTHDF3 and HNRNPC,were obtained by differential analysis.GO enrichment analysis showed that osteoarthritis-related m6A differential regulators played a role in the biological processes such as mRNA transport,RNA catabolism,and regulation of insulin-like growth factor receptor signaling pathway.(3)KEGG enrichment analysis showed that the differential regulators were mainly involved in the p53,interleukin-17 and AMPK signaling pathways.The combined protein-protein interaction network topology analysis and machine learning results obtained the m6A Hub regulator-YTHDC1.(5)The results of in vitro cellular experiments showed that there was a significant difference in the expression of m6A key regulator between the control and experimental groups(P<0.05).To conclude,YTHDC1 is closely related to the development of osteoarthritis,which is expected to be a molecular target of m6A for the treatment of osteoarthritis.

BACKGROUND:Current studies have confirmed that Ganoderma lucidum polysaccharides can promote nerve regeneration in neurodegeneration-related diseases.The occurrence of neurodegenerative diseases is closely related to mitochondrial dysfunction,but the role of Ganoderma lucidum polysaccharides on the regulation of apoptosis and mitochondrial function in neurodegenerative diseases is not yet clarified. OBJECTIVE:To explore the regulatory effects and mechanisms of Ganoderma lucidum polysaccharides on apoptosis and mitochondrial dysfunction in H2O2-induced SH-SY5Y cells. METHODS:SH-SY5Y cells were divided into three groups:control group,H2O2 group,and Ganoderma lucidum polysaccharides group.Cells in the control group were normally cultured.Cells in the H2O2 group were treated with 300 μmol/L H2O2 for 24 hours.In the Ganoderma lucidum polysaccharides group,the intervention with 300 μg/L Ganoderma lucidum polysaccharides was conducted first for 1-2 hours,followed by the addition of 300 μmol/L H2O2 for 24 hours.The mitochondrial membrane potential was detected by JC-1 kit.Apoptosis was detected by TUNEL staining kit.The activities of malondialdehyde and superoxide dismutase were detected by malondialdehyde test kit and superoxide dismutase test kit,respectively.The apoptosis and expression of mitochondrial dynamics-related proteins were detected by immunofluorescence staining and western blot assay. RESULTS AND CONCLUSION:(1)Compared with the control group,the mitochondrial membrane potential and superoxide dismutase activity were significantly reduced,as well as apoptotic rate and malondialdehyde levels were significantly increased in the H2O2 group(P<0.05).After treatment with Ganoderma lucidum polysaccharides,the membrane potential and superoxide dismutase activities were significantly increased,and apoptotic rate and malondialdehyde levels were significantly reduced compared with the H2O2 group(P<0.05).(2)The expression levels of pro-apoptotic proteins Bax and Caspase-3 were significantly increased,but the expression of anti-apoptotic protein Bcl-2 was significantly decreased in the H2O2 group compared with the control group(P<0.05).Compared with the H2O2 group,the levels of Bax and Caspase-3 were significantly decreased,but the expression of anti-apoptotic protein Bcl-2 was significantly increased in the Ganoderma lucidum polysaccharides group(P<0.05).(3)Compared with the control group,the expression of mitochondrial splitting proteins Fis1 and p-Drp1 was significantly increased,but the expression of mitochondrial fusion proteins OPA1,Mfn1,and Mfn2 was decreased in the H2O2 group(P<0.05).Compared with the H2O2 group,Fis1 and p-Drp1 expression was significantly reduced,but the expression levels of OPA1,Mfn1,and Mfn2 were significantly increased in the Ganoderma lucidum polysaccharides group(P<0.05).(4)The above results confirm that Ganoderma lucidum polysaccharides can attenuate H2O2-induced oxidative stress damage and apoptosis in SH-SY5Y cells by ameliorating mitochondrial dysfunction.

Objective: To compare the effects of 12week maximum fat oxidation (FATmax) intensity exercise combined with dietary restriction and FATmax intensity exercise alone on body composition, blood lipid metabolism and ferroptosis in obese college students with nonalcoholic fatty liver disease(NAFLD),so as to provide a exercise prescription reference for rehabilitation treatment of obese NAFLD college students. Methods: In August 2023,a total of 45 obese NAFLD college students were divided into maximum fat oxidation intensity exercise combined with dietary restriction group (FATmax+DR, n=22) and FATmax group (n=23) by random number table method,who were recruited through online notifications and physical examinations at the Physical Examination Center of Fenyang College of Shanxi Medical University. FATmax group received FATmax intensity exercise with 3 times a week for 12 weeks (FATmax:0.51 g/min, exercise intensity:50.14% VO2max and the heart rate:136.78 times/min). FATmax+DR group underwent 12 weeks of FATmax intensity exercise combined with dietary restriction, and daily dietary energy intake was determined according to resting energy consumption. Body composition, four items of blood lipids and the indicators of oxidative stress and ferroptosis were measured before and after the intervention.The differences of indicators among each group were analyzed by using independent sample t test and paired sample t test. Results: Before the intervention, there were no significant differences in body composition,four items of blood lipid, oxidative stress and iron death between FATmax+DR group and FATmax group (P>0.05). After 12 weeks of intervention, body weight , body mass index(BMI), body fat mass, trunk fat mass, visceral fat area and serum low density lipoprotein(LDL) and malondialdehyde(MDA) levels in FATmax+DR group were significantly lower than those in FATmax group, while serum high density lipoprotein(HDL) and glutathione(GSH) levels were higher than those in FATmax group (t=-2.30，-3.23,-3.97,-5.85,-3.44,-3.06,-2.03,-2.09; 2.73, 2.42, P<0.05). There were no significant differences in serum levels of total cholesterol(TC), triglyceride(TG), superoxide dismutase(SOD) and glutathion peroxidase 4(GPX4) between the two groups (t=1.49, 1.00, -0.01, 0.59, P>0.05). Conclusion Twelveweek FATmax intensity exercise combined with dietary restriction could significantly improve body composition and dyslipidemia, prevent the occurrence of ferroptosis and liver oxidative damage in obese NAFLD college students,which could serve as a timely promotion and application of intervention for obese college students with NAFLD.

【Objective】 To investigate the expressions of containing CKLF like MARVEL transmembrane domain gene 6 (CMTM6) and ras protein activator like 2 (RASAL2) in prostate cancer tissues, and to analyze the relationships between the above factors and the clinicopathological characteristics and prognosis of prostate cancer patients. 【Methods】 The prostate cancer tissues and adjacent tissues of 80 prostate cancer patients admitted to Zhumadian City Center Hospital during Feb.2018 and Feb.2020 were collected.Expressions of CMTM6 and RASAL2 were detected with immunohistochemical method.The relationship between the expressions of CMTM6 and RASAL2 and the clinical pathological characteristics of prostate cancer were analyzed.The survival curve was plotted with Kaplan-Meier method.The prognostic factors were analyzed with multivariate Cox regression. 【Results】 The positive expression rate of CMTM6 in prostate cancer tissues was 67.50%, which was obviously higher than 38.75% in adjacent tissues (χ²=13.277, P<0.001).The positive expression rate of RASAL2 in prostate cancer tissues was 47.50%, which was obviously lower than 73.75% in adjacent tissues (χ²=11.546, P=0.001).The expressions of CMTM6 and RASAL2 were not related to patients’ age, tumor size and tissue differentiation (P>0.05), but to TNM staging, Gleason score, lymph node metastasis and preoperative PSA level (P<0.05).Survival curve showed that the 3-year survival rate of positive CMTM6 expression patients was 61.11% (33/54), which was obviously lower than that of negative patients, which was 88.46% (23/26) (χ²=5.940, P=0.015).The 3-year survival rate of positive RASAL2 expression patients was 81.85% (31/38), which was obviously higher than that of negative patients, which was 59.52% (25/42) (χ²=4.887, P=0.027).Cox multivariate regression showed that Gleason score, lymph node metastasis, preoperative PSA level, CMTM6, and RASAL2 were independent influencing factors of prognosis (P<0.05). 【Conclusion】 The positive expression rate of CMTM6 in prostate cancer tissues is significantly higher than that in paracancer tissues, while the positive expression rate of RASAL2 in prostate cancer tissues is significantly lower than that in paracancer tissues. Both CMTM6 and RASAL2 are closely related to the clinical pathological characteristics and prognosis of prostate cancer patients, and may provide reference for the prognosis.

Polymyxins, a class of cyclic peptide antibiotics, have become the last line of defense against gram-negative bacterial infections as the number of multidrug-resistant bacteria continues to rise. Heteroresistance refers to the presence of subpopulations within the same strain with varying sensitivities to antibiotics, which cannot be detected by standard clinical tests and may result in treatment failure. In several common gram-negative bacteria, mutations in the PhoPQ and PmrAB two-component systems are key contributors to polymyxin heteroresistance. This review aims to summarize recent research on the mechanisms of polymyxin heteroresistance in gram-negative bacteria, so as to provide insights for developing rapid detection methods and improving clinical treatment strategies.

OBJECTIVE To investigate the bleeding site,clinical features,treatment methods and curative effect of difficult-to-control epistaxis. METHODS The clinical data of 127 patients with difficult-to-control epistaxis admitted for treatment were retrospectively analyzed to investigate the common bleeding sites,clinical features,and curative effect. RESULTS There were statistically significant differences in the bleeding sites among patients of different age groups(P=0.000),whether they were combined with hypertension 2,3 grades(P=0.030),and whether patients taking long-term anticoagulants(P=0.000). Among the enrolled patients,14 patients were successful in the secondary hemostasis. Among the patients with two successful bleeding stops,the one-time cure rate of patients with hypertension 2,3 grades was significantly different from that of patients with hypertension 1 grade and non-hypertension(P=0.000). CONCLUSION Male patients with difficult-to-control epistaxis are more than female patients. The common bleeding sites are related to age,hypertension 2,3 grades,and long-term use of anticoagulants. Nasal endoscopic electrocoagulation is the preferred treatment method. The cure rate of electrocoagulation is related to blood pressure,and blood pressure control is necessary for patients with poor blood pressure control.

Objective:To report the clinical and genetic characteristics of autosomal recessive spastic ataxia of Charlevoix-Saguenay (ARSACS) induced by a new homozygous mutation in the SACS gene, and to improve the clinicians′ recognition of the disease. Methods:Detailed nervous system physical examination was performed on the patient and his parents from a consanguineous family admitted to the Genetics and Metabolism Clinic of the Department of Neurology, the First Affiliated Hospital of Kunming Medical University in March 2022. The peripheral blood DNA of the patient and his parents was extracted, and whole exon sequencing (WES) was performed on the patient and his parents using second-generation sequencing technology. The mutation sites were verified by Sanger sequencing, and the mutation sites were analyzed by software.Results:The 18-year-old Han ethnic male patient developed a progressive stiffness of his bilateral lower limbs and gait unsteadiness since the age of 3. He had pyramidal tract sign in his bilateral lower limbs, cerebellar ataxia, pes cavus and hammer toes. Brain magnetic resonance imaging (MRI) showed symmetrical low signal of bilateral pons, cerebellar atrophy and thinning of corpus callosum in T 2WI and T 2 fluid attenuated inversion recovery (FLAIR) sequences. Neuroelectrophysiological examination showed sensory motor peripheral neuropathy. Ophthalmic examination revealed concomitant exotropia and ametropia in both eyes. WES revealed a homozygous variant of c.6958T>C (p.Tyr2320His) in exon 10 of the SACS gene of the patient, and his parents were heterozygous variant carriers confirmed by Sanger sequencing. The variant was classified as possibly pathogenic (PM1+PM2+PP3+PP4) according to the American Society for Medical Genetics and Genomics. The patient was clearly diagnosed as ARSACS caused by homozygous mutation of c.6958T>C in the SACS gene. Conclusions:A novel pathogenic variant (c.6958T>C) in the SACS gene identified in this study leads to the manifestation of ARSACS. The primary clinical manifestations include cerebellar ataxia, pyramidal tract signs, and sensorimotor peripheral neuropathy. Head MRI examination of T 2WI and T 2FLAIR sequences with symmetrical low signal on both sides of the pons helps to narrow down the scope of differential diagnosis.

Objective:To compare the patient-reported outcomes and short-term clinical outcomes between robotic-assisted and laparoscopic-assisted radical gastrectomy for locally advanced gastric cancer.Methods:This single-center prospective randomized controlled trial was conducted in the Department of Gastrointestinal Surgery, Affiliated Hospital of Qingdao University from October 2020 to August 2022. Patients with locally advanced gastric cancer who were to undergo radical gastrectomy were selected and randomly divided into two groups according to 1∶1, and received robotic surgery and laparoscopic surgery, respectively. Patient-reported outcomes and short-term clinical outcomes (including postoperative complications, surgical quality and postoperative short-term recovery) were compared between the two groups by independent sample t test, Mann-Whitney U test, repeated ANOVA, generalized estimating equation, χ2 test and Fisher′s exact test. Results:A total of 237 patients were enrolled for modified intention-to-treat analysis (120 patients in the robotic group, 117 patients in the laparoscopic group). There were 180 males and 59 females, aged (63.0±10.2) years (range: 30 to 85 years). The incidence of postoperative complications was similar between the robotic group and laparoscopic group (16.7% (20/120) vs. 15.4% (18/117), χ2=0.072, P=0.788). The robotic group had higher patient-reported outcomes scores in general health status, emotional, and social domains compared to the laparoscopic group, differences in time effect, intervention effect, and interaction effect were statistically significant (general health status: χ2 value were 275.68, 3.91, 6.38, P value were <0.01, 0.048, 0.041; emotional: χ2 value were 77.79, 6.04, 6.15, P value were <0.01, 0.014, 0.046; social: χ2 value were 148.00, 7.57, 5.98, P value were <0.01, 0.006, 0.048). However, the financial burden of the robotic group was higher, the differences in time effect, intervention effect and interaction effect were statistically significant ( χ2 value were 156.24, 4.08, 36.56, P value were <0.01, 0.043,<0.01). Conclusion:Compared to the laparoscopic group, the robotic group could more effectively relieve postoperative negative emotions and improve recovery of social function in patients.