Objective To analyze the risk factors of nosocomial infection among the patients in neuro-surgical ICU,and to construct the risk prediction model to provide reference for the prediction of nosocomial infection in neurosurgical ICU patients.Methods The clinical data of 280 patients admitted and treated in the neurosurgery ICU of this hospital from January 2021 to December 2022 were retrospectively analyzed.The pa-tients were divided into the infection group and non-infection group based on whether or not nosocomial infec-tion occurring,140 cases in each group.A total of 196 patients were extracted as the training set by a ratio of 7︰3 for constructing the model,while the remaining 84 patients served as the validation set for conducting the internal verification.The logistic regression was used to analyze the risk factors of nosocomial infection in the neurosurgery ICU patients,and a predictive model was established.The receiver operating characteristic (ROC) curve was drawn to evaluate the predictive effect of the model.Results The multivariate logistic re-gression analysis indicated that old age,long surgery time,catheter use and glucocorticoids use were screened as the main risk factors of nosocomial infection occurrence in neurosurgery ICU patients.The nomogram mod-el was constructed based on the results of multivariate analysis,the area under the curve of training set and validation set were 0.796 and 0.875,respectively.The correcting model reflected good consistency between actual diagnosis and predictive diagnosis.Conclusion The model constructed in this study has the high predic-tive value for the nosocomial infection occurrence risk in the patients of the neurosurgery ICU.

Objective　To shorten the detection time of Staphylococcus aureus (SA), this study established a rapid detection method for the thermostable nuclease nuc gene and mecA resistance gene of SA based on recombinase aided amplification (RAA) combined with lateral flow strips (LFS). Methods Efficient RAA primers and probes were designed and screened based on the conserved sequences of the nuc gene in the SA genome and the mecA gene on the staphylococcal SCCmec removable genetic element, and then, the reaction temperature and for the simultaneous detection of nuc and mecA genes by time of RAA-LFS were verified. Sensitivity, specificity, and comparison with quantitative real-time PCR (qPCR) were also assessed. A prospective evaluation was conducted using 52 vials of non-repeat positive blood cultures from two tertiary hospitals. Results The RAA-LFS was able to amplify both nuc and mecA genes under the reaction conditions of 20-45 °C for 15-30 minutes, with a detection limit of 10² CFU/mL. A total of 50 clinically isolated non-SA strains were validated with 100% specificity for both nuc and mecA genes. Of the 30 methicillin-resistant Staphylococcus aureus (MRSA) and 30 methicillin-susceptible Staphylococcus aureus (MSSA) strains preserved in our laboratory, all were positive for the nuc gene, and 30 strains were positive for the mecA gene. The positive and negative concordance rates with qPCR were both 100%, with a consistency test Kappa value of 1. In a prospective analysis of the 52 vials of positive blood cultures, the identification and antibiotic susceptibility test results of 16 strains of MSSA and 6 strains of MRSA showed a 100% concordance rate with the results obtained using the Mérieux VITEK-2 compact microbiological detection system. Conclusions We combined nucleic acid release agents, RAA, and lateral flow strips to develop a simple, rapid, and highly sensitive assay applicable for SA and mecA resistance gene detection in colonies or positive blood culture bottles.

Metabolic-associated fatty liver disease (MAFLD), which is previously known as non-alcoholic fatty liver disease (NAFLD), represents a major health concern worldwide with limited therapy. Here, we provide evidence that ferroptosis, a novel form of regulated cell death characterized by iron-driven lipid peroxidation, was comprehensively activated in liver tissues from MAFLD patients. The canonical-GPX4 (cGPX4), which is the most important negative controller of ferroptosis, is downregulated at protein but not mRNA level. Interestingly, a non-canonical GPX4 transcript-variant is induced (inducible-GPX4, iGPX4) in MAFLD condition. The high fat-fructose/sucrose diet (HFFD) and methionine/choline-deficient diet (MCD)-induced MAFLD pathologies, including hepatocellular ballooning, steatohepatitis and fibrosis, were attenuated and aggravated, respectively, in cGPX4-and iGPX4-knockin mice. cGPX4 and iGPX4 isoforms also displayed opposing effects on oxidative stress and ferroptosis in hepatocytes. Knockdown of iGPX4 by siRNA alleviated lipid stress, ferroptosis and cell injury. Mechanistically, the triggered iGPX4 interacts with cGPX4 to facilitate the transformation of cGPX4 from enzymatic-active monomer to enzymatic-inactive oligomers upon lipid stress, and thus promotes ferroptosis. Co-immunoprecipitation and nano LC-MS/MS analyses confirmed the interaction between iGPX4 and cGPX4. Our results reveal a detrimental role of non-canonical GPX4 isoform in ferroptosis, and indicate selectively targeting iGPX4 may be a promising therapeutic strategy for MAFLD.

Objective: To investigate the epidemiological characteristics of malaria in Hangzhou City from 2004 to 2021, so as to provide the evidence for formulating the post-elimination control strategy for malaria in Hangzhou City. Methods: The epidemic situation of malaria in Hangzhou City from 2004 to 2021 were collected from the National Information System for Disease Control and Prevention in China, and the temporal, spatial and human distributions of malaria cases and the source of malaria infections were analyzed in Hangzhou City during the pre-elimination stage (2004 to 2009), the elimination stage (2010 to 2015) and the post-elimination stage (2016 to 2021). Results: Totally 602 malaria cases were reported in Hangzhou City from 2004 to 2021,and the annual mean incidence of malaria was 0.22/105, 0.20/105 and 0.18/105 during the pre-elimination, elimination and post-elimination stages, appearing a tendency towards a decline. Men accounted for 63.96%, 85.07% and 93.75% of all malaria cases and there were 67.86%, 82.84% and 80.00% of cases at ages of 18 to 50 years during the pre-elimination, elimination and post-elimination stages, both appearing a tendency towards a decline (χ2trend=56.748, P<0.001; χ2trend=39.971, P<0.001). The predominant occupation of malaria cases shifted from farmers or migrant workers to multiple occupations, and the proportion of commercial servants increased from 4.87% during the pre-elimination stage to 24.38% during the post-elimination stage (χ2trend=73.308, P<0.001). The proportion of Plasmodium vivax malaria cases reduced from 96.43% during the pre-elimination stage to 7.50% during the post-elimination stage, and the proportion of P. falciparum malaria cases increased from 3.57% to 71.25%, while P. ovale, P. malariae and mixed infections were identified since 2010. There was a significant season-specific incidence of P. vivax malaria during the pre-elimination stage, and the period between May and October was an epidemic season; however, there was no season-specific incidence of P. vivax malaria during the elimination and post-elimination stages. The regional distribution of malaria cases presented a tendency towards a shift from suburb and rural areas to urban areas (χ2trend=74.229, P<0.001). No local cases were detected in Hangzhou City since 2010, and 94.22% of malaria cases were overseas imported cases after malaria elimination, including 90.61% from Africa. Conclusions oung and middle-aged men were high-risk populations for malaria in Hangzhou City from 2004 to 2021, and overseas commercial servants gradually became the predominant source of malaria infections, with malaria parasite species tending to be diverse. Improving the management of overseas imported cases and timely identification and treatment of cases are major interventions to consolidate malaria elimination achievements in Hangzhou City.

Objective:To learn about the knowledge and practice of iodine deficiency disorders (IDD) prevention and control among main caregivers of pregnant women in trimester and its related influencing factors, so as to provide a scientific basis for effectively improving the iodine nutrition level of pregnant women.Methods:In April 2020, using the stratified sampling method, 2 districts and counties were selected in the urban, suburban and rural areas of Hangzhou City, respectively, and 5 maternal and child health care institutions were selected as the survey sites in each district and county according to the five directions of East, West, South, North and Middle. A face-to-face questionnaire investigation was used to investigate the knowledge and practice of IDD prevention and control among main caregivers of pregnant women.Results:Totally 601 caregivers of pregnant women were investigated. Among them, 68.9% (414/601) knew that eating iodized salt was the best way to prevent IDD. However, 15.0% (90/601) thought that eating seafood was the best way to prevent IDD. And 41.9% (252/601) caregivers of pregnant women would actively purchase iodine-rich food for cooking, and 63.6% (382/601) would choose iodized salt. There were statistically significant differences in the knowledge and practice of IDD prevention and control among caregivers of pregnant women in urban, suburban and rural areas ( P < 0.05). And 50.3% (87/173) male caregivers would actively purchase iodine-rich food for cooking, which was higher than that of female caregivers [38.6% (165/428)], the difference was statistically significant (χ 2 = 6.97, P = 0.008). There was a statistically significant difference between the caregivers of pregnant women of different ages in actively purchasing iodine-rich food for cooking (χ 2 = 12.61, P = 0.013). And there were statistically significant differences between the caregivers of pregnant women with different educational levels in actively purchasing iodine-rich food for cooking and choosing iodized salt (χ 2 = 29.34, 39.42, P < 0.001). Conclusions:The awareness of knowledge about IDD prevention and control and the formation of prevention and control behavior among caregivers of pregnant women in Hangzhou City are poor. Active education of caregivers of pregnant women should be strengthened to promote maternal and infant health.

Purpose: Temozolomide is used in first-line treatment for glioblastoma. However, chemoresistance to temozolomide is common in glioma patients. In addition, mechanisms for the anti-tumor effects of temozolomide are largely unknown. Ferroptosis is a form of programmed cell death triggered by disturbed redox homeostasis, overloaded iron, and increased lipid peroxidation. The present study was performed to elucidate the involvement of ferroptosis in the anti-tumor mechanisms of temozolomide. Materials and Methods: We utilized the CCK8 assay to evaluate cytotoxicity. Levels of lactate dehydrogenase (LDH), malondialdehyde (MDA), iron, and glutathione (GSH) were measured. Flow cytometry and fluorescence microscope were used to detect the production of reactive oxygen species (ROS). Western blotting, RT-PCR and siRNA transfection were used to investigate molecular mechanisms. Results: Temozolomide increased the levels of LDH, MDA, and iron and reduced GSH levels in TG905 cells. Furthermore, we found that ROS levels and DMT1 expression were elevated in TG905 cells treated with temozolomide and were accompanied by a decrease in the expression of glutathione peroxidase 4, indicating an iron-dependent cell death, ferroptosis. Our results also showed that temozolomide-induced ferroptosis is associated with regulation of the Nrf2/HO-1 pathway. Conversely, DMT1 knockdown by siRNA evidently blocked temozolomide-induced ferroptosis in TG905 cells. Conclusion Taken together, our findings indicate that temozolomide may suppress cell growth partly by inducing ferroptosis by targeting DMT1 expression in glioblastoma cells.

Purpose: Temozolomide is used in first-line treatment for glioblastoma. However, chemoresistance to temozolomide is common in glioma patients. In addition, mechanisms for the anti-tumor effects of temozolomide are largely unknown. Ferroptosis is a form of programmed cell death triggered by disturbed redox homeostasis, overloaded iron, and increased lipid peroxidation. The present study was performed to elucidate the involvement of ferroptosis in the anti-tumor mechanisms of temozolomide. Materials and Methods: We utilized the CCK8 assay to evaluate cytotoxicity. Levels of lactate dehydrogenase (LDH), malondialdehyde (MDA), iron, and glutathione (GSH) were measured. Flow cytometry and fluorescence microscope were used to detect the production of reactive oxygen species (ROS). Western blotting, RT-PCR and siRNA transfection were used to investigate molecular mechanisms. Results: Temozolomide increased the levels of LDH, MDA, and iron and reduced GSH levels in TG905 cells. Furthermore, we found that ROS levels and DMT1 expression were elevated in TG905 cells treated with temozolomide and were accompanied by a decrease in the expression of glutathione peroxidase 4, indicating an iron-dependent cell death, ferroptosis. Our results also showed that temozolomide-induced ferroptosis is associated with regulation of the Nrf2/HO-1 pathway. Conversely, DMT1 knockdown by siRNA evidently blocked temozolomide-induced ferroptosis in TG905 cells. Conclusion Taken together, our findings indicate that temozolomide may suppress cell growth partly by inducing ferroptosis by targeting DMT1 expression in glioblastoma cells.

Objective:To examine the short-term outcomes of modified load-sharing rip-stop repair (mLSRS) and suture-bridge repair (SB) for large rotator cuff tear.Methods:The clinical data of patients who underwent shoulder arthroscopy for large rotator cuff repair at Department of Orthopedic, China Academy of Chinese Medical Sciences Wang Jing Hospital from January 2017 to December 2018 were collected. Totally 111 patients (39 in mLSRS group and 72 in SB group) were included in the study. There were 45 males and 66 females, aged (58.0±6.9)years (range: 40 to 72 years).A total of 39 pairs of patients were successfully matched by propensity score matching. The pain of shoulder joint was assessed by visual analogy score (VAS) , the shoulder function was assessed by Constant-Murley score, the abduction strength of bilateral shoulder joint was assessed by 90? force assessment method of upper limb on the plane of scapula, and the healing of rotator cuff on the operative side was assessed by sugaya ultrasonic classification standard. The difference of short-term outcome between the two groups were compared using t test, χ 2 test, Mann-Whitney U test, repeated measures design anova and multivariate analysis of variance. Results:At the 4th week after surgery, the VAS of mLSRS group was significantly lower than SB group(1 (2) vs. 2 (2) , F=5.32, P=0.02). One year after surgery, Constant-Murley score of two groups were significantly higher than those before surgery, but there was no significant difference between two groups(89.1±5.7 vs. 87.6±7.3, t=1.00, P=0.32). Abductor strength of affected limbs were lower than that of the opposite side, but there were no statistically significant differences between two groups(4.28±1.61 vs. 4.54±1.64, t=-0.70, P=0.49). According to the Sugaya classification, 32 cases in mLSRS group were healed while 7 cases were not healed,30 cases in SB group were healed while 9 cases were not healed(χ 2=0.32, P=0.58). Conclusion:The use of mLSRS fixation construct on large rotator cuff tear can reduce pain and the short-term outcome is reliable.

Objective:To examine the short-term outcomes of modified load-sharing rip-stop repair (mLSRS) and suture-bridge repair (SB) for large rotator cuff tear.Methods:The clinical data of patients who underwent shoulder arthroscopy for large rotator cuff repair at Department of Orthopedic, China Academy of Chinese Medical Sciences Wang Jing Hospital from January 2017 to December 2018 were collected. Totally 111 patients (39 in mLSRS group and 72 in SB group) were included in the study. There were 45 males and 66 females, aged (58.0±6.9)years (range: 40 to 72 years).A total of 39 pairs of patients were successfully matched by propensity score matching. The pain of shoulder joint was assessed by visual analogy score (VAS) , the shoulder function was assessed by Constant-Murley score, the abduction strength of bilateral shoulder joint was assessed by 90? force assessment method of upper limb on the plane of scapula, and the healing of rotator cuff on the operative side was assessed by sugaya ultrasonic classification standard. The difference of short-term outcome between the two groups were compared using t test, χ 2 test, Mann-Whitney U test, repeated measures design anova and multivariate analysis of variance. Results:At the 4th week after surgery, the VAS of mLSRS group was significantly lower than SB group(1 (2) vs. 2 (2) , F=5.32, P=0.02). One year after surgery, Constant-Murley score of two groups were significantly higher than those before surgery, but there was no significant difference between two groups(89.1±5.7 vs. 87.6±7.3, t=1.00, P=0.32). Abductor strength of affected limbs were lower than that of the opposite side, but there were no statistically significant differences between two groups(4.28±1.61 vs. 4.54±1.64, t=-0.70, P=0.49). According to the Sugaya classification, 32 cases in mLSRS group were healed while 7 cases were not healed,30 cases in SB group were healed while 9 cases were not healed(χ 2=0.32, P=0.58). Conclusion:The use of mLSRS fixation construct on large rotator cuff tear can reduce pain and the short-term outcome is reliable.

Multiple sequence alignment is one of the basic techniques in bioinformatics, and it plays a vital role in structure modeling, functional site prediction, and phylogenetic analysis. In this paper, we review the methodologies and recent advances in the multiple protein sequence alignment, e.g., speeding up the calculation of distances among sequences and employing the iterative refinement and consistency-based scoring function, with emphasis on the use of additional sequence and structural information for improving alignment quality.
Algorithms ; Proteins ; chemistry ; Sequence Alignment ; methods ; Sequence Analysis, Protein ; methods