Objective To investigate the effects of polybutylene terephthalate(PBT)grafted with various monomers,such as acrylic acid(AA),acrylamide(AM),sodium styrene sulfonate(SSS),AA+AM and AA+SSS on platelet adhesion and function.Methods The AA,AM,SSS,AA+AM,and AA+SSS were grafted onto the surface of PBT by γ-ray irradia-tion,and the grafted PBT was characterized by fourier transform infrared spectrometry(FTIR)and wetting time.Platelet ac-tivation and aggregation of different monomers grafted with PBT were observed by scanning electron microscopy(SEM).Platelet concentration,maximum aggregation ability,positive expression rate of CD62p and hypotonic shock rate(HSR)of PBT grafted with different monomers were tested to study their effect on platelet adhesion and function.Results The char-acteristic absorption peaks of AA,AM and SSS appeared in FTIR,and the hydrophilicity of the grafted material was im-proved obviously,indicating that the monomer was grafted successfully.The results of SEM showed that the degree of platelet activation and aggregation caused by the original PBT was significantly higher than that of modified ones.Compared with the original platelets,the platelet concentration of PBT was(533.00±4.58 vs 672.00±3.61)×109/L,the maximum platelet ag-gregation rate was(48.80±0.96 vs 58.60±1.37)%,the positive expression rate of CD62p was(45.35±0.58 vs 39.90±0.52)%,and the platelet HSR was(48.74±0.46 vs 51.86±0.93)%(P<0.05).Compared with the original PBT,the platelet loss and platelet function damage caused by PBT grafted with different monomers decreased significantly(P<0.05).PBT-(AA+AM)had the least comprehensive effect on platelets[platelet concentration(637.00±2.65)×109/L,maximum plate-let aggregation rate(62.45±0.61)%,positive expression rate of CD62p(37.39±0.42)%,platelet HSR(53.51±0.58)%].Conclusion The comprehensive effect of PBT grafted with AA+AM on platelet adhesion and function is significantly lower than that of PBT grafted with other monomers,so it is anticipated to apply filtering and removing leukocytes in platelet prep-arations.

Objective By comparing the changes in cerebral blood flow,neuronal morphology in brain tissue,and the levels of serum oxidation and inflammatory factors in models of cerebral hypoperfusion,three experimental rat models were assessed for their suitability as subjects of studies on the mechanisms and therapeutic drugs of cerebrovascular diseases and neurodegenerative diseases.Methods A total of 88 male SD rats were randomly divided into a sham operation group(n=16),classic bilateral common carotid artery occlusion group(classic 2-VO group,n=24),modified 2-VO group(n=24),and intraluminal thread technique group(n=24).Bilateral common carotid artery ligation was performed on the classic 2-VO group,while blood was drawn from the common carotid artery before ligation in the modified 2-VO group(1 mL/100 g).Middle cerebral artery occlusion was performed on the intraluminal thread technique group.In the sham operation groups of the first two models,the common carotid artery was separated but not ligated,while the proximal end of the common carotid artery and the external carotid artery were ligated;in addition,the bolt thread was not inserted in the sham group of the intraluminal thread technique group.Cerebral blood flow,infarct volume,serum inflammatory factor levels,hematoxylin and eosin-stained morphology,and ultrastructure of the hippocampal tissue were assessed at 1,3,and 7 days after the operations.Results Laser speckle interferometry showed a decrease in cerebral blood flow of the modified 2-VO group that was more obvious than that of the other two groups.On day 7,only the modified 2-VO group still had significant differences in cerebral blood flow compared with the sham group,and it remained in a state of hypoperfusion(cerebral blood flow decreased by 30％compared with that before the operation).TTC staining showed that infarcts in the striata of the three groups gradually increased with time after the operation;4 rats(about 26.7％)in the modified 2-VO group and 10 rats(about 66.7％)in the intraluminal thread technique group had infarcts in both the cortex and striatum.ELISA showed that the levels of inflammatory factors,such as TNF-α,IL-1 β,and hs-CRP,in the three groups were increased after the operations,and levels of the pro-oxidation factor ROS were also increased.In contrast,levels of the antioxidant factor SOD decreased.On postoperative day 7,there was no significant difference in the hs-CRP of the classic 2-VO and intraluminal thread technique groups compared with that of the sham group.However,the modified 2-VO group still exhibited significant differences in all the above indicators compared with the sham group.Hematoxylin and eosin staining showed that the modified 2-VO group had more severe damage to the hippocampal CA1 and CA3 regions compared with the other groups.Transmission electron microscopy demonstrated that the modified 2-VO group showed more severe damage to the mitochondrial and endoplasmic reticulum in the hippocampal region compared with the other groups.Conclusions A cerebral hypoperfusion model was successfully established.Compared with the classic 2-VO and intraluminal thread techniques,the modified 2-VO method can induce more complete cerebral hypoperfusion and more severe neural damage within the same time frame,resembling the pathological state of human cerebral hypoperfusion more closely.

Sepsis is characterized by a severe and life-threatening host immune response to polymicrobial infection accompanied by organ dysfunction.Studies on the therapeutic effect and mechanism of immunomod-ulatory drugs on the sepsis-induced hyperinflammatory or immunosuppression states of various im-mune cells remain limited.This study aimed to investigate the protective effects and underlying mechanism of artesunate(ART)on the splenic microenvironment of cecal ligation and puncture-induced sepsis model mice using single-cell RNA sequencing(scRNA-seq)and experimental validations.The scRNA-seq analysis revealed that ART inhibited the activation of pro-inflammatory macrophages recruited during sepsis.ART could restore neutrophils'chemotaxis and immune function in the septic spleen.It inhibited the activation of T regulatory cells but promoted the cytotoxic function of natural killer cells during sepsis.ART also promoted the differentiation and activity of splenic B cells in mice with sepsis.These results indicated that ART could alleviate the inflammatory and/or immunosuppressive states of various immune cells involved in sepsis to balance the immune homeostasis within the host.Overall,this study provided a comprehensive investigation of the regulatory effect of ART on the splenic microenvironment in sepsis,thus contributing to the application of ART as adjunctive therapy for the clinical treatment of sepsis.

Objective:To analyze the research hotspots and frontiers of hospital research management research from 1981 to 2022.Methods:The relevant literature in the field of hospital scientific research management was retrieved from the CNKI database to explore the trends of publications in this research field. A scientific knowledge graph was drawn and a visualization analysis of the information of authors, issuing units, and research institutions were conducted by Cite Space.5.8.R3.Research hotspots were discussed based on keyword emergence, cluster analysis, and keyword time zone graph.Results:The publication trend in this field was generally policy-oriented, but the cooperation among authors and institutions was relatively loose, and the research hotspots were gradually shifting from scientific research funding management to discipline construction, talent training, translational medicine, and informatization. Cluster analysis found that the main content of hospital scientific research management was scientific research funding and clinical scientific research management and the main management objects were the medical and nursing staff.Conclusions:Hospital scientific research managers must adhere to the policy-oriented approach, strengthen the cooperation and exchanges in scientific research management, innovate the scientific research management mode around the research hotspots and development trends, and promote the quality and efficiency of scientific research management.

Objective:To evaluate the prognostic value of pretreatment systemic immune-inflammation index (SII) and lactate dehydrogenase (LDH) in non-metastatic nasopharyngeal carcinoma (NPC).Methods:We retrospectively collected the data of 839 patients with non-metastatic NPC from National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital and Sun Yat-sen University Cancer Center between January 2007 and October 2015. All patients received intensity modulated radiation based treatment. Optimal cutoff value of SII and LDH were determined by X-title software. The association between SII, LDH and clinical prognosis of non-metastatic NPC patients were analyzed. Kaplan-Meier method was used for survival analysis, and Log rank test was used for comparison of survival rates between groups. Propensity score matching (PSM) analysis was carried out to minimize the effects of confounding factors. The risk stratification model of prognosis by combining N stage, SII and LDH was constructed to compare the prognosis of patients in high risk group, middle risk group and low risk group, and the receiver operating characteristic (ROC) curve analysis was used to evaluate its prognostic value.Results:The optimal cutoff value of SII is 447.2×10 9/L for predicting the 5-year overall survival (OS) of NPC patients, and the best cutoff value of LDH is 198.9 U/L. The proportion of patients with stage T3-4 and stage III-IVB in high SII group was higher than that in low SII group ( P<0.001). Multivariate Cox regression analysis showed that N stage, SII and LDH were independent factors of OS, progression-free survival (PFS) and distant metastasis-free survival (DMFS) of NPC patients (N stage, HR=1.705, 95% CI: 1.247-2.332; HR=1.755, 95% CI: 1.342-2.295; HR=2.161, 95% CI: 1.515-3.082. SII, HR=1.525, 95% CI: 1.097-2.119; HR=1.518, 95% CI: 1.150-2.004; HR=1.837, 95% CI: 1.272-2.653. LDH, HR=2.041, 95% CI: 1.403-2.968; HR=1.725, 95% CI: 1.233-2.414; HR=2.492, 95% CI: 1.690-3.672, respectively). After PSM, SII was still an independent prognostic factor of OS, PFS and DMFS in NPC patients ( HR=1.52, 95% CI: 1.09-2.12; HR=1.52, 95% CI: 1.15-2.00; HR=1.82, 95% CI: 1.26-2.63, respectively). Combined with N 2-3 stage, SII (>447.2×10 9/L), and LDH (>198.9 U/L), patients were divided into high-(3 risk factors), intermediate- (2 risk factors) and low-risk (0-1 risk factors) groups. The 5-year OS rates of patients in low-, intermediate- and high-risk groups were 86.1%, 79.8% and 41.2% respectively, the 5-year PFS rates were 80.7%, 70.2% and 33.9% respectively, and the 5-year DMFS rates were 88.9%, 79.2% and 47.5% respectively. There were significant differences in OS, PFS and DMFS among these three groups ( P<0.001). Distant metastasis was the main failure pattern in low-, intermediate- and high-risk groups, and the highest rate of distant metastasis was 83.3% (15/31) in high-risk group. ROC curve of the risk stratification model for predicting 5-year OS of NPC patients is 0.610, which is higher than TNM stage (0.609), SII (0.574) and LDH (0.558). Conclusions:Pretreatment SII and LDH are significantly correlated with the prognosis of patients with non-metastatic NPC. The combination of SII, LDH and N stage can stratify the prognostic risk of NPC patients. The risk stratification model can enhance the accuracy of prognosis.

Objective:To evaluate the prognostic value of pretreatment systemic immune-inflammation index (SII) and lactate dehydrogenase (LDH) in non-metastatic nasopharyngeal carcinoma (NPC).Methods:We retrospectively collected the data of 839 patients with non-metastatic NPC from National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital and Sun Yat-sen University Cancer Center between January 2007 and October 2015. All patients received intensity modulated radiation based treatment. Optimal cutoff value of SII and LDH were determined by X-title software. The association between SII, LDH and clinical prognosis of non-metastatic NPC patients were analyzed. Kaplan-Meier method was used for survival analysis, and Log rank test was used for comparison of survival rates between groups. Propensity score matching (PSM) analysis was carried out to minimize the effects of confounding factors. The risk stratification model of prognosis by combining N stage, SII and LDH was constructed to compare the prognosis of patients in high risk group, middle risk group and low risk group, and the receiver operating characteristic (ROC) curve analysis was used to evaluate its prognostic value.Results:The optimal cutoff value of SII is 447.2×10 9/L for predicting the 5-year overall survival (OS) of NPC patients, and the best cutoff value of LDH is 198.9 U/L. The proportion of patients with stage T3-4 and stage III-IVB in high SII group was higher than that in low SII group ( P<0.001). Multivariate Cox regression analysis showed that N stage, SII and LDH were independent factors of OS, progression-free survival (PFS) and distant metastasis-free survival (DMFS) of NPC patients (N stage, HR=1.705, 95% CI: 1.247-2.332; HR=1.755, 95% CI: 1.342-2.295; HR=2.161, 95% CI: 1.515-3.082. SII, HR=1.525, 95% CI: 1.097-2.119; HR=1.518, 95% CI: 1.150-2.004; HR=1.837, 95% CI: 1.272-2.653. LDH, HR=2.041, 95% CI: 1.403-2.968; HR=1.725, 95% CI: 1.233-2.414; HR=2.492, 95% CI: 1.690-3.672, respectively). After PSM, SII was still an independent prognostic factor of OS, PFS and DMFS in NPC patients ( HR=1.52, 95% CI: 1.09-2.12; HR=1.52, 95% CI: 1.15-2.00; HR=1.82, 95% CI: 1.26-2.63, respectively). Combined with N 2-3 stage, SII (>447.2×10 9/L), and LDH (>198.9 U/L), patients were divided into high-(3 risk factors), intermediate- (2 risk factors) and low-risk (0-1 risk factors) groups. The 5-year OS rates of patients in low-, intermediate- and high-risk groups were 86.1%, 79.8% and 41.2% respectively, the 5-year PFS rates were 80.7%, 70.2% and 33.9% respectively, and the 5-year DMFS rates were 88.9%, 79.2% and 47.5% respectively. There were significant differences in OS, PFS and DMFS among these three groups ( P<0.001). Distant metastasis was the main failure pattern in low-, intermediate- and high-risk groups, and the highest rate of distant metastasis was 83.3% (15/31) in high-risk group. ROC curve of the risk stratification model for predicting 5-year OS of NPC patients is 0.610, which is higher than TNM stage (0.609), SII (0.574) and LDH (0.558). Conclusions:Pretreatment SII and LDH are significantly correlated with the prognosis of patients with non-metastatic NPC. The combination of SII, LDH and N stage can stratify the prognostic risk of NPC patients. The risk stratification model can enhance the accuracy of prognosis.

OBJECTIVE: To explore the genetic basis for a Chinese pedigree affected with X-linked retinoschisis. METHODS: Clinical data of the pedigree was collected. Following DNA extraction, PCR and Sanger sequencing were carried out to detect potential variant in the RS1 gene. The result was verified by using PCR and restriction fragment length polymorphism assay. RESULTS: All male patients were found to harbor a c.458T>G (p.Val153Gly) variant of the RS1 gene, for which Their mothers were heterozygous carriers. The same variant was not detected among unaffected members of the pedigree as well as 100 healthy controls. Bioinformatic analysis suggested the variant to be pathogenic. CONCLUSION The c.458T>G (p.Val153Gly) variant of the RS1 gene probably underlay the X-linked retinoschisis in this pedigree.
China ; Eye Proteins/genetics* ; Genes, X-Linked ; Humans ; Male ; Mutation ; Pedigree ; Retinoschisis/pathology*

Hepatic stellate cells(HSCs)are essential drivers of fibrogenesis.Inducing activated-HSC apoptosis is a promising strategy for treating hepatic fibrosis.18beta-glycyrrhetinic acid(18β-GA)is a natural com-pound that exists widely in herbal medicines,such as Glycyrrhiza uralensis Fisch,which is used for treating multiple liver diseases,especially in Asia.In the present study,we demonstrated that 18β-GA decreased hepatic fibrosis by inducing the apoptosis in activated HSCs.18β-GA inhibited the expression of α-smooth muscle actin and collagen type Ⅰ alpha-1.Using a chemoproteomic approach derived from activity-based protein profiling,together with cellular thermal shift assay and surface plasmon reso-nance,we found that 18β-GA covalently targeted peroxiredoxin 1(PRDX1)and peroxiredoxin 2(PRDX2)proteins via binding to active cysteine residues and thereby inhibited their enzymatic activities.18β-GA induced the elevation of reactive oxygen species(ROS),resulting in the apoptosis of activated HSCs.PRDX1 knockdown also led to ROS-mediated apoptosis in activated HSCs.Collectively,our findings revealed the target proteins and molecular mechanisms of 18β-GA in ameliorating hepatic fibrosis,highlighting the future development of 18β-GA as a novel therapeutic drug for hepatic fibrosis.

Objective:To explore the effects of different temperature settings on patients with acute hypoxic respiratory failure (AHRF) during application of high-flow nasal cannula (HFNC) .Methods:A total of 90 patients with AHRF who were admitted to the Department of Critical Care Medicine of Zhejiang Hospital and underwent HFNC from January 2019 to May 2020 were selected as research objects by the convenient sampling method. The patients were randomly divided into 3 groups by the random number table method, namely, group A (T=31 ℃) , group B (T=34 ℃) and group C (T=37 ℃) , with 30 cases in each group. The VAS and Borg Scale were used to compare the comfort and dyspnea of patients of 3 groups, and to compare the satisfaction of patients of 3 groups.Results:After applying HFNC for 2 h and 12 h, the scores of VAS and Borg Scale in group B were lower than those in groups A and C, and the differences were statistically significant ( P<0.01) . The VAS scores of the three groups after applying HFNC for 12 h were higher than that after applying HFNC for 2 h, and the scores of Borg Scale were lower than that after applying HFNC for 2 h, and the differences were statistically significant ( P<0.05) . The satisfaction of patients in group B was higher than that in group A and C, and the differences were statistically significant ( P< 0.01) . Conclusions:Different temperature settings of HFNC will affect the comfort, dyspnea and satisfaction of AHRF patients. Among them, 34 ℃ is a more suitable temperature. As time progresses, nursing staff should intervene in time to maintain the comfort of patients, reduce the degree of dyspnea and provide guidance for the clinical application of HFNC.

OBJECTIVE： To establish a method for the determination of related substances in rifabutin crude drug and capsules by HPLC. METHODS： HPLC method was adopted. The determination was performed on Agilent XDB-C8 column with mobile phase consisted of acetonitrile-0.1 mol/L potassium dihydrogen phosphate solution （pH 6.5±0.1） （50 ∶ 50， V/V） at the flow rate of 1.0 mL/min. The detection wavelength was set at 254 nm， the column temperature was 30 ℃， and sample size was 20 μL. The mobile phase was used as solvent to prepare the sample solution with a mass concentration of 1.0 mg/mL. The system suitability test was performed by using newly established method and current method （mass concentration of sample solution 0.5 mg/mL， C18 column） stated in quality standard of rifabutin crude drug and capsules. Related substance test was conducted for 6 batches of rifabutin crude drug and capsule （peak area normalization method）. RESULTS： The linear range of rifabutin was 0.8-16 μg/mL（r＝1.000 0）， RSDs of precision， reproducibility and stability tests （12 h） were all lower than 2.0％ （n＝6）； the limits of detection and quantification were 0.025 4， 0.085 2 μg/mL. In system suitability test， by using new method and current method， separation degree of rifabutin peak and pre-degradation product peak were 7.50 and 3.47. When 6 batches of samples were determined， the number of impurities detected by this method was 1-5 more than that by the current method， and the total amount of impurities was 0.19％-0.55％ higher. CONCLUSIONS： Established new method is well-separated and sensitive， and can be used for the determination of related substance in rifabutin crude drug and capsules， which helps the quality control of drugs.