Objective: To investigate the expression and functional role of FK506 binding protein 10 (FKBP10) in oral squamous cell carcinoma (OSCC), and to provide a research basis for the estimated prognosis and targeted therapy of OSCC. Methods: A total of 284 OSCC samples and 19 normal samples were selected from the Cancer Genome Atlas (TCGA) database, and diagnostic analysis was performed to determine mRNA expression. Survival analysis for FKBP10 and OSCC was conducted on a gene expression profile interaction analysis website. Real-time fluorescence quantitative PCR and Western Blot were used to detect the mRNA and protein expression of FKBP10 in four OSCC cell lines and SAS and SCC9 cells transfected with siRNA. The cell proliferation ability of FKBP10-silenced cells was detected using the CCK8 method, and the cell cycle distribution and apoptosis were detected by flow cytometry. Cell migration and invasion ability were detected through wound healing and invasion experiments. The expression changes of total protein and phosphatidylinositol 3-kinase (PI3K)-serine/threonine kinase (AKT) after FKBP10 silencing were analyzed by proteomics and Western Blot. Results: According to the analysis of gene expression levels, the mRNA expression level of FKBP10 in OSCC was significantly higher than that in normal tissues (P < 0.001). In terms of diagnosis, the expression level of FKBP10 has unique diagnostic value for OSCC (P < 0.05). The survival analysis of FKBP10 and OSCC showed that a high expression of FKBP10 led to a decrease in patient survival and poor prognosis (P < 0.05). The expression of FKBP10 mRNA and protein in OSCC cell lines was higher than that in normal oral keratinocytes (P < 0.001). Silencing FKBP10 can reduce the proliferation, invasion, and migration ability of SAS and SCC9 (P < 0.001), and also block their cell cycle in the G0/G1 phase (P < 0.001), with a significant increase in apoptosis (P < 0.05). Protein mass spectrometry and Western blot analysis revealed that FKBP10 silencing significantly downregulated the expression of multiple proteins in the RAP1 signaling pathway, mainly RAP guanine nucleotide exchange factor 1 (RAPGEF1) (P < 0.05) and the phosphorylation of PI3K-AKT proteins (P < 0.05). Conclusion FKBP10 is highly expressed in OSCC, leading to poor prognosis for patients. Downregulated FKBP10 expression can inhibit the proliferation, migration, and invasion ability of OSCC cells, hinder cell cycle progression, and promote apoptosis via the RAP1-PI3K-AKT axis. FKBP10 is a potential therapeutic target and prognostic biomarker for OSCC.

Objective To monitor the susceptibility of clinical isolates to antimicrobial agents in tertiary hospitals in major regions of China in 2022.Methods Clinical isolates from 58 hospitals in China were tested for antimicrobial susceptibility using a unified protocol based on disc diffusion method or automated testing systems.Results were interpreted using the 2022 Clinical &Laboratory Standards Institute(CLSI)breakpoints.Results A total of 318 013 clinical isolates were collected from January 1,2022 to December 31,2022,of which 29.5％were gram-positive and 70.5％were gram-negative.The prevalence of methicillin-resistant strains in Staphylococcus aureus,Staphylococcus epidermidis and other coagulase-negative Staphylococcus species(excluding Staphylococcus pseudintermedius and Staphylococcus schleiferi)was 28.3％,76.7％and 77.9％,respectively.Overall,94.0％of MRSA strains were susceptible to trimethoprim-sulfamethoxazole and 90.8％of MRSE strains were susceptible to rifampicin.No vancomycin-resistant strains were found.Enterococcus faecalis showed significantly lower resistance rates to most antimicrobial agents tested than Enterococcus faecium.A few vancomycin-resistant strains were identified in both E.faecalis and E.faecium.The prevalence of penicillin-susceptible Streptococcus pneumoniae was 94.2％in the isolates from children and 95.7％in the isolates from adults.The resistance rate to carbapenems was lower than 13.1％in most Enterobacterales species except for Klebsiella,21.7％-23.1％of which were resistant to carbapenems.Most Enterobacterales isolates were highly susceptible to tigecycline,colistin and polymyxin B,with resistance rates ranging from 0.1％to 13.3％.The prevalence of meropenem-resistant strains decreased from 23.5％in 2019 to 18.0％in 2022 in Pseudomonas aeruginosa,and decreased from 79.0％in 2019 to 72.5％in 2022 in Acinetobacter baumannii.Conclusions The resistance of clinical isolates to the commonly used antimicrobial agents is still increasing in tertiary hospitals.However,the prevalence of important carbapenem-resistant organisms such as carbapenem-resistant K.pneumoniae,P.aeruginosa,and A.baumannii showed a downward trend in recent years.This finding suggests that the strategy of combining antimicrobial resistance surveillance with multidisciplinary concerted action works well in curbing the spread of resistant bacteria.

Regardless of the underlying etiology, renal fibrosis is the final histological outcome of progressive kidney disease. Unilateral ureteral obstruction (UUO) is an ideal and reproducible experimental rodent model of renal fibrosis, which is characterized by tubulointerstitial inflammatory responses, accumulation of extracellular matrix, tubular dilatation and atrophy, and fibrosis. The magnitude of UUO-induced renal fibrosis is experimentally manipulated by the species chosen, animal age, and the severity and duration of the obstruction, while relief of the obstruction allows the animal to recover from fibrosis. The pathogenesis of renal fibrosis is complex and multifactorial and is orchestrated by activation of renin-angiotensin system (RAS), oxidative stress, inflammatory response, transforming growth factor beta 1-Smad pathway, activated myofibroblasts, cell death (apoptosis, autophagy, ferroptosis, and necroptosis), destruction of intracellular organelles, and signaling pathway. The current therapeutic approaches have limited efficacy. Inhibition of RAS and use of antioxidants and antidiabetic drugs, such as inhibitors of sodium-glucose cotransporter 2 and dipeptidyl peptidase-4, have recently gained attention as therapeutic strategies to prevent renal scarring. This literature review highlights the state of the art regarding the molecular mechanisms relevant to the management of renal fibrosis caused by UUO.

Objective:To observe the expression levels of related cytokines in the vitreous humor of eyes with rhegmatogenous retinal detachment (RRD) associated with lattice degeneration (LD).Methods:A clinical observational study. From May 2022 to February 2023, 43 patients of 43 eyes diagnosed with RRD, with or without accompanying LD, who underwent their first pars plana vitrectomy (PPV) at Zhongda Hospital Southeast University and The Affiliated Eye Hospital of Nanjing Medical University were included in the study. The patients were divided into two groups: RRD with LD (LD group), consisting of 27 patients with 27 eyes, and RRD without LD (Non-LD group), consisting of 16 patients with 16 eyes. Additionally, 6 patients (6 eyes) with idiopathic macular holes and 4 patients (4 eyes) with idiopathic epiretinal membranes during the same period were selected as the control group. Before initiating PPV and without intraocular perfusion, a 0.5 ml sample of undiluted vitreous fluid from the central portion was excised and aspirated. The concentrations of monocyte chemoattractant protein-1 (MCP-1), macrophage inflammatory protein-1 alpha (MIP)-1α, MIP-1β, interferon-γ-inducible protein 10 (IP-10), interleukin-6 (IL-6), IL-8, macrophage migration inhibitory factor (MIF), tumor necrosis factor-alpha-α, interferon-γ, intercellular adhesion molecule 1 (ICAM-1), vascular cell adhesion molecule-1, platelet endothelial cell adhesion molecule 1 (PECAM-1), placental growth factor (PLGF) and vascular endothelial growth factor (VEGF) in the vitreous fluid were quantitatively measured using the Luminex high-throughput multiplex assay technology. The comparison of cytokine expression levels between groups was performed using the Kruskal-Wallis rank sum test, with significance levels for post-hoc pairwise comparisons adjusted by DSCF methods.Results:The eyes of the patients in the LD group, Non-LD group, and control group showed statistically significant differences ( P<0.05) in the concentrations of IL-6 ( H=14.400), IL-8 ( H=13.610), MCP-1 ( H=12.050), VEGF ( H=9.920), MIP-1α ( H=6.620), IP-10 ( H=7.780), MIF ( H=12.920), PECAM-1 ( H=9.990), ICAM-1 ( H=8.070), and PLGF ( H=16.850). Upon pairwise comparison between groups, the vitreous fluid concentrations of IL-6, IL-8, and PLGF in the LD group were found to be significantly higher than those in the Non-LD group ( P<0.05). Conclusion:The expression levels of IL-6, IL-8, and PLGF are elevated in the vitreous fluid of eyes with RRD accompanied by LD.

Clinical data of 15 primary central nervous system lymphoma (PCNSL) children aged ≤18 years admitted to our hospital between May 2013 to May 2023 were retrospectively analyzed. Our goal was to summarize the clinical features of children and investigate the therapeutic effect of a high-dose methotrexate (HD-MTX) based chemotherapy regimen on this disease. The male-to-female ratio was 2.7∶1, and the median age was 7.2 (2.3-16.4) years at diagnosis. The initial clinical symptoms were primarily cranial hypertension, with imaging findings revealing multiple lesions. Pediatric PCNSL with normal immune function has a favorable prognosis with HD-MTX-based chemotherapy. Patients with a stable disease can be treated with minimal or no maintenance. HD-MTX-based chemotherapy remains effective when the disease progresses or recurs after an initial course of non-HD-MTX-based chemotherapy.

Regardless of the underlying etiology, renal fibrosis is the final histological outcome of progressive kidney disease. Unilateral ureteral obstruction (UUO) is an ideal and reproducible experimental rodent model of renal fibrosis, which is characterized by tubulointerstitial inflammatory responses, accumulation of extracellular matrix, tubular dilatation and atrophy, and fibrosis. The magnitude of UUO-induced renal fibrosis is experimentally manipulated by the species chosen, animal age, and the severity and duration of the obstruction, while relief of the obstruction allows the animal to recover from fibrosis. The pathogenesis of renal fibrosis is complex and multifactorial and is orchestrated by activation of renin-angiotensin system (RAS), oxidative stress, inflammatory response, transforming growth factor beta 1-Smad pathway, activated myofibroblasts, cell death (apoptosis, autophagy, ferroptosis, and necroptosis), destruction of intracellular organelles, and signaling pathway. The current therapeutic approaches have limited efficacy. Inhibition of RAS and use of antioxidants and antidiabetic drugs, such as inhibitors of sodium-glucose cotransporter 2 and dipeptidyl peptidase-4, have recently gained attention as therapeutic strategies to prevent renal scarring. This literature review highlights the state of the art regarding the molecular mechanisms relevant to the management of renal fibrosis caused by UUO.

Objective:To summarize the clinical manifestations and prognostic factors of patients with hepatic amyloidosis in a single center.Methods:The clinical data of 28 primary systemic light chain amyloidosis cases with liver involvement in our center from October 2012 to January 2023 were retrospectively analyzed. The main clinical manifestations and prognostic factors were studied. Statistical analysis were performed using the χ 2 test, Fisher's exact test, Wilcoxon rank test, or Kaplan-Meier survival curve log-rank test according to the different data. Results:The main clinical manifestations of patients with liver involvement were abdominal distension, hepatomegaly, and edema. CD56 and chemokine receptor 4 protein expression accounted for 52% (13/25) and 56% (14/25). 64.3% (9/14) patients were combined with t (11,14), and 21.4% (3/14) patients were positive for 1q21 (+), and no patients were detected with del(17p). Univariate analysis showed that Mayo 2004 and 2012 stages and total bilirubin (TBil) ≥34.2 μmol/L were associated with progression-free survival and overall survival. The median progression-free survival and overall survival were significantly inferior in patients with TBil≥34.2μmol/L group (0.178 years, 0.195 years) than with the TBil<34.2μmol/L group (0.750 years, 3.586 years) ( P ?

Objective To investigate the incidence rate,clinical characteristics,and prognosis of neonatal stroke in Shenzhen,China.Methods Led by Shenzhen Children's Hospital,the Shenzhen Neonatal Data Collaboration Network organized 21 institutions to collect 36 cases of neonatal stroke from January 2020 to December 2022.The incidence,clinical characteristics,treatment,and prognosis of neonatal stroke in Shenzhen were analyzed.Results The incidence rate of neonatal stroke in 21 hospitals from 2020 to 2022 was 1/15 137,1/6 060,and 1/7 704,respectively.Ischemic stroke accounted for 75％(27/36);boys accounted for 64％(23/36).Among the 36 neonates,31(86％)had disease onset within 3 days after birth,and 19(53％)had convulsion as the initial presentation.Cerebral MRI showed that 22 neonates(61％)had left cerebral infarction and 13(36％)had basal ganglia infarction.Magnetic resonance angiography was performed for 12 neonates,among whom 9(75％)had involvement of the middle cerebral artery.Electroencephalography was performed for 29 neonates,with sharp waves in 21 neonates(72％)and seizures in 10 neonates(34％).Symptomatic/supportive treatment varied across different hospitals.Neonatal Behavioral Neurological Assessment was performed for 12 neonates(33％,12/36),with a mean score of(32±4)points.The prognosis of 27 neonates was followed up to around 12 months of age,with 44％(12/27)of the neonates having a good prognosis.Conclusions Ischemic stroke is the main type of neonatal stroke,often with convulsions as the initial presentation,involvement of the middle cerebral artery,sharp waves on electroencephalography,and a relatively low neurodevelopment score.Symptomatic/supportive treatment is the main treatment method,and some neonates tend to have a poor prognosis.

Objective To explore the inhibitory effect of Guiqi Yiyuan Ointment combined with cisplatin on Lewis lung cancer mice and its mechanism based on the lncRNA H19/miR-19b3p/FTH1 axis.Methods Totally 60 SPF grade male C57BL/6 mice were randomly selected as blank group,and Lewis lung cancer mouse model was replicated in the remaining 50 mice.The modeled mice were randomly divided into model group,cisplatin group,and TCM low-,medium-and high-dosage combined with cisplatin group,with 10 mice in each group.The cisplatin group was given intraperitoneal injection of cisplatin 5 mg/kg,while the TCM low-,medium-and high-dosage combined with cisplatin group were given Guiqi Yiyuan Ointment 1.75,3.5,7.0 g/kg by gavage combined with intraperitoneal injection of cisplatin 5 mg/kg,the blank group and model group were given equal volume of normal saline by gavage for 14 consecutive days.The general condition of mice was observed,the tumor mass of mice was measured,and the tumor inhibition rate,spleen index,and thymus index were calculated,HE staining was used to observe the pathological changes of tumor tissue,and the contents of malondialdehyde(MDA),reduced glutathione(GSH),hydrogen peroxide(H2O2),and ferrous ions(Fe2+)were detected in the tumor tissue,immunohistochemistry and Western blot were used to detect the expression of nuclear factor E2 related factor 2(Nrf2),glutathione peroxidase 4(GPX4),ferritin heavy chain 1(FTH1)and solute carrier family 7 member 11(SLC7A11)protein in tumor tissue,real time fluorescence quantitative PCR was used to detect the expression of lncRNA H19 and miR-19b3p mRNA in tumor tissue.Results Compared with the blank group,the body mass,spleen index and thymus index of mice in the model group were decreased(P<0.05).Compared with the model group,the mental state and tumor histopathological morphology of mice in each administration group were improved to different degrees,the tumor mass of mice was reduced(P<0.05),the spleen index and the thymus index of mice increased(P<0.05),tumor cell lysis,rupture,and decrease in quantity,the contents of MDA,H2O2,Fe2+in tumor tissue increased(P<0.05),while GSH content decreased(P<0.05),the expression of Nrf2,GPX4,FTH1,SLC7A11 protein in tumor tissue decreased(P<0.05),the lncRNA H19 mRNA expression decreased(P<0.05),miR-19b3p mRNA expression increased(P<0.05).Compared with the cisplatin group,the tumor mass of mice in TCM high-dosage combined with cisplatin group reduced(P<0.05),the body mass,spleen index and thymus index increased(P<0.05),the contents of MDA,H2O2,Fe2+in tumor tissue of mice increased(P<0.05),the content of GSH decreased(P<0.05),the expression of Nrf2,FTH1,SLC7A11,GPX4 protein expression decreased(P<0.05),lncRNA H19 mRNA expression decreased(P<0.05),miR-19b3p mRNA expression increased(P<0.05).Conclusion Guiqi Yiyuan Ointment combined with cisplatin can significantly inhibit the tumor of Lewis lung cancer mice,and its mechanism may be related to regulating the expression of ferroptosis molecules related to the lncRNA H19/miR-19b3p/FTH1 axis.

Objective To observe the anti-tumor effect and mechanism of Guiqi Yiyuan Ointment combined with cisplatin in Lewis lung cancer bearing mice based on AMPK/ULK1 signaling pathway.Methods The mice were inoculated with Lewis lung cancer cells to establish a subcutaneous tumor model in the right axillary subcutaneous area,and were randomly divided into blank group,model group,cisplatin group and Guiqi Yiyuan Ointment high-,medium-and low-dosage+cisplatin groups,with 10 mice in each group.The cisplatin group received intraperitoneal injection of 5 mg/kg(once every 7 days)cisplatin,while the Guiqi Yiyuan Ointment high-,medium-and low-dosage+cisplatin groups received gavage of 7.0,3.5 and 1.75 g/kg Guiqi Yiyuan Ointment on the basis of cisplatin group,once a day,for 14 consecutive days.HE staining was used to observe the morphology of tumor tissue,immunohistochemical method was used to detect the protein expression of p-AMPK and p-ULK1 in tumor tissue,transmission electron microscopy was used to observe the number of autophagosomes,RT-PCR was used to detect the expression of p62,Beclin-1,Atg5 and LC3 mRNA in tumor tissue,Western blot was used to detect the expression of Beclin-1,p62,Atg5,LC3 and AMPK/ULK1 signaling pathway proteins in tumor tissue.Results Compared with the model group,the tumor mass of mice in all administration groups decreased significantly(P<0.05);the tumor tissue showed patchy necrotic areas and an increase in the number of autophagosomes,the mRNA expressions of Beclin-1,Atg5,and LC3 increased,the protein expressions of Beclin-1,Atg5,LC3 Ⅱ/Ⅰ,AMPK,p-AMPK,ULK1 and p-ULK1 increased,and the expression of p62 mRNA and protein decreased(P<0.05).Compared with the cisplatin group,the tumor mass of mice in Guiqi Yiyuan Ointment high-,medium-dosage+cisplatin groups decreased(P<0.05),the tumor inhibition rate increased;the expressions of ULK1 protein and Atg5 mRNA in tumor tissue of Guiqi Yiyuan Ointment high-,medium-and low-dosage+cisplatin groups significantly increased(P<0.05),the expressions of Beclin-1 and LC3 mRNA in Guiqi Yiyuan Ointment high-,medium-dosage+cisplatin groups significantly increased(P<0.05),the expressions of Atg5,LC3 Ⅱ/Ⅰ,AMPK,p-AMPK and p-ULK1 protein significantly increased(P<0.05),and the expression of p62 protein significantly decreased(P<0.05),the expression of p62 mRNA in Guiqi Yiyuan Ointment high-dosage+cisplatin group significantly decreased(P<0.05),the expression of Beclin-1 protein significantly increased(P<0.05).Conclusion Guiqi Yiyuan Ointment combined with cisplatin may activate autophagy and inhibit subcutaneous tumor growth in Lewis lung cancer bearing mice through the AMPK/ULK1 signaling pathway.