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.

The promise of regeneration therapy for restoration of damaged myocardium after cardiac ischemic injury relies on targeted delivery of proliferative molecules into cardiomyocytes whose healing benefits are still limited owing to severe immune microenvironment due to local high concentration of proinflammatory cytokines. Optimal therapeutic strategies are therefore in urgent need to both modulate local immunity and deliver proliferative molecules. Here, we addressed this unmet need by developing neutrophil-mimic nanoparticles NM@miR, fabricated by coating hybrid neutrophil membranes with artificial lipids onto mesoporous silica nanoparticles (MSNs) loaded with microRNA-10b. The hybrid membrane could endow nanoparticles with strong capacity to migrate into inflammatory sites and neutralize proinflammatory cytokines and increase the delivery efficiency of microRNA-10b into adult mammalian cardiomyocytes (CMs) by fusing with cell membranes and leading to the release of MSNs-miR into cytosol. Upon NM@miR administration, this nanoparticle could home to the injured myocardium, restore the local immunity, and efficiently deliver microRNA-10b to cardiomyocytes, which could reduce the activation of Hippo-YAP pathway mediated by excessive cytokines and exert the best proliferative effect of miR-10b. This combination therapy could finally improve cardiac function and mitigate ventricular remodeling. Consequently, this work offers a combination strategy of immunity modulation and proliferative molecule delivery to boost cardiac regeneration after injury.

Objective:Human leukocyte antigen(HLA)B27 is a susceptibility allele of ankylosing spondylitis(AS),and HLA-B27 antigen typing is an important indicator for clinical diagnosis of AS,but current typing methods such as sequence specific primer polymerase chain reaction(PCR-SSP)still possess limitation.Therefore,this study aims to analyze the correlation between B27 subtypes and susceptibility to AS in Hunan Province by applying high-resolution polymerase chain reaction-sequence-based typing(PCR-SBT). Methods:Peripheral blood of 116 patients with suspected AS(suspected AS group)and 121 healthy volunteers(control group)admitted to the Second Xiangya Hospital from January 2020 to December 2020 were collected for HLA-B genotyping by PCR-SBT.Among the patients in the suspected AS group,23 patients were finally diagnosed with AS(confirmed AS group),and the remaining 93 undiagnosed patients served as the non-confirmed AS group.PCR-SBT and PCR-SSP were used to detect HLA-B27 typing in 116 patients with suspected AS,and the results of the 2 methods were compared. Results:The HLA-B27 allele frequency in the suspected AS group was significantly higher than that in the control group[11.63%vs 2.48%;P<0.001,odds ratio(OR)=5.18,95%confidence interval(CI)2.097 to 12.795].B*27:04,B*27:05,B*27:06,and B*27:07 were detected in the suspected AS group and the control group.The frequency of the B*27:04 allele in the suspected AS group was significantly higher than that in the control group(9.48%vs 1.24%;P<0.001,OR=8.346,95%CI 2.463 to 28.282).The positive rate of B27 in the suspected AS group and the confirmed AS group(B27+/+ and B27+/-)was significantly higher than that in the control group(χ2=16.579,P<0.001;χ2=94.582,P<0.001,respectively).Among the confirmed AS group,21 were HLA-B27 carriers,and the B27 positive rate in the confirmed AS group was 91.3%.PCR-SBT could achieve high resolution typing of the HLA-B gene locus,with higher sensitivity,specificity,positive predictive value,negative predictive value,and accuracy than PCR-SSP. Conclusion:PCR-SBT typing analysis shows a strong correlation between HLA-B * 27:04 and AS in Hunan province.The PCR-SBT method can be used as the preferred option for the auxiliary diagnosis of clinical AS.

Objective:To evaluate the efficacy and safety of oral anisodine hydrobromide tablets in the treatment of nonarteritic anterior ischemic optic neuropathy (NAION).Methods:A multicenter nonrandomized controlled trial was conducted.A total of 282 acute NAION patients (282 eyes) were recruited from 16 hospitals in China from July 2020 to May 2021.Patients were divided into two groups according to treatment methods, which were control group (124 cases, 124 eyes) receiving regular treatment including citicoline sodium plus Ginkgo biloba leaf liquid extract or Ginkgo biloba leaf extract tablets plus mecobalamin, and experimental group (158 cases, 158 eyes) receiving treatment in control group plus oral anisodine hydrobromide tablets 1 mg, twice daily for 2 to 3 months.Best corrected visual acuity (BCVA), visual field index (VFI), peripapillary retinal nerve fiber layer (pRNFL) and radial peripapillary capillary vessel density (RPC) were assessed at 1, 2, 3, and 6 months after enrollment using the standard decimal visual acuity chart, 750i Humphery visual field analyzer, Cirrus HD-OCT 4000/Cirrus HD-OCT 5000, RTVue-XR optical coherence tomography respectively.The primary outcomes were BCVA and VFI, and the secondary outcomes were pRNFL, RPC, and the side effects during the follow-up.The study adhered to the Declaration of Helsinki.All patients were fully informed about the treatment and purpose of this study and voluntarily signed the informed consent form.The study protocol was approved by Chinese PLA General Hospital (No.S2020-021-01). Results:In all, 242 patients (242 eyes) completed the follow-up of BCVA, and 98 patients (98 eyes) completed the VFI follow-up.In terms of visual function, BCVA and VFI improved significantly over time in the two groups, and BCVA and VFI were better in experimental group than in control group at various follow-up time points (all at P<0.05). In terms of structure, pRNFL gradually decreased in both groups with the extension of treatment, and pRNFL was significanthy thinner in experimental group than in control group at various follow-up time points (all at P<0.05). There was no significant difference in RPC between the two groups at the last follow-up ( P>0.05). There were two cases with side effects and one case was discontinued due to side effects 25 days after enrollment. Conclusions:Oral anisodine hydrobromide can improve visual acuity and visual field in NAION and accelerate the regression of optic disc edema, with good safety.

Biapenem is a carbapenem antibiotic， and can be used for the treatment of sepsis， pneumonia， lung abscess， chronic respiratory lesions secondary infection， complex urinary tract infection and pyelonephritis， etc. This article reviewed the studies on the pharmacokinetics， pharmacodynamics and therapeutic drug monitoring （TDM） of biapenem. The pharmacokinetic parameters of biapenem are not significantly different in healthy subjects， and there is no accumulation after multiple doses of biapenem. However， there are large differences in pharmacokinetic parameters in patients with severe disease and patients with abnormal renal function compared with healthy subjects， which leads to conventional treatment regimens not achieving the desired outcome. In terms of pharmacodynamics， biapenem can improve the rate of reaching the target value by increasing the frequency of administration and prolonging the infusion time. For patients with anuria in end-stage renal disease， dosing intervals can be extended to avoid drug accumulation. However, for patients with severe infection, a daily dose of 1.2 g still can not control infections caused by Acinetobacter baumannii or Pseudomonas aeruginosa, which limits its use in patients with severe disease. It is recommended to implement TDM in severe patients and patients with abnormal renal function， and explore the best dosing regimen for biapenem in combination with pharmacokinetic models to ensure that the time that the free blood concentration of biapenem remains above minimum inhibitory concentration as a percentage of the time between doses （%fT＞MIC） is within the effective range，so that biapenem can exert a greater efficacy in severe patients and patients with abnormal renal function. For medical institutions that cannot carry out TDM， the efficacy of biapenem can be maximized by increasing the frequency of administration and prolonging the infusion time. For infections caused by P. aeruginosa， A. baumannii and Serratia marcescens with high drug resistance rates， it is recommended to combine or replace other antibiotics.

Objective:To investigate the effect of ethephon exposure on sperm quality of adolescent male SD rats and the influence mechanism.Methods:A total of 40 45-day-old male SD rats were divided into control group and low, middle and high experimental groups according to the random number table method, 10 rats in each group.The said 4 groups were given 9 g/L normal saline, 100 mg/kg, 200 mg/kg, and 400 mg/kg ethephon aqueous solution for 28 days, respectively.One epididymal tail was taken to prepare sperm suspension, the sperm concentration and motility were detected.The testis and epididymis tissues were stained with HE, and their pathological changes were observed under light microscope.The activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px), and the malondialdehyde (MDA) content in the testis were detected.Enzyme linked immunosorbent assay kit was used to mea-sure the epididymal α-glucosidase activity, L-carnitine (LC) content, nuclear factor erythroid 2-related factor 2 (Nrf2) and organic cation transporter 2 (OCTN2) expression levels.Then the oxidative damage caused by ethephon to epididymis was evaluated.SPSS 26.0 software was used for data analysis.Data were compared by One- way ANOVA among groups and LSD method between 2 groups. Results:The sperm concentration of the control group, low, medium and high dose groups were (40.21±1.94)×10 9/L, (35.23±2.53)×10 9/L, (23.61±2.62)×10 9 /L, and (18.86±2.16)×10 9 /L, respectively.The sperm activity rate were (70.98±3.01)%, (57.96±3.75)%, (45.71±2.41)%, and (31.23±2.26)%, respectively.The concentration and vitality of epididymal sperms in the experimental group were significantly lower than those in the control group (all P<0.01). In the control group, low, medium and high dose groups, the SOD activity were (46.48±2.21) U/mg prot, (38.49±2.56)U/mg prot, (33.80±1.73) U/mg prot, and (27.65±2.05) U/mg prot, respectively.The GSH-Px activity in said 4 groups were (21.41±1.95) U/mg prot, (17.32±1.28) U/mg prot, (15.09±0.94) U/mg prot, and (14.08±1.23) U/mg prot, respectively.The MDA content in said 4 groups were (1.41±0.09) nmol/mg prot, (1.59±0.09) nmol/mg prot, (1.81±0.09) nmol/mg prot, and (2.16±0.14) nmol/mg prot, respectively.Compared to the control group, the experimental groups had significantly lower SOD and GSH-Px activities and significantly higher MDA content (all P<0.05). α-glucosidase levels in the control group, low, middle and high experimental groups were (15.46±0.71) U/mL prot, (12.95±0.72) U/mL prot, (11.34±0.65) U/mL prot, and (8.76±0.60) U/mL prot, respectively.LC levels in the control group, low, middle and high dose groups were(6.21±0.31) μg/L, (5.89±0.13) μg/L, (5.02±0.12) μg/L, (4.38±0.07) μg/L, respectively, compared with those of the control group, the concentration of α-glucosidase and LC in experimental groups decreased significantly (all P<0.01). The expression levels of Nrf2 in epididymis of the control group, low, middle and high dose groups were (1.34±0.05) ng/L, (1.25±0.04) ng/L, (1.08±0.06) ng/L, (0.92±0.04) ng/L, respectively; the expression levels of OCTN2 in epididymis of the control group, low, middle and high dose groups were (4.55±0.12) ng/L, (4.23±0.11) ng/L, (3.20±0.24) ng/L, (2.59±0.05) ng/L, respectively, compared with those of the control group, the expression levels of Nrf2 and OCTN2 in experimental groups decreased significantly (all P<0.01). Conclusions:Ethephon exposure leads to excessive generation of reactive oxygen and oxidative stress in reproductive organs.Ethephon exposure may activate the Keap1-Nrf2/ARE signal pathway, resulting in a decrease in the number, vitality and quality of sperms, and impaired fertility.

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 explore the effects of different doses of Ethephon on testes of male pups.Methods:Thirty-two 45-day-old healthy female Sprague-Dawley (SD) rats were randomly divided into the control group and the low dose, middle dose and high dose Ethephon groups by the random figure table.The female rats in the low dose, middle dose and high dose Ethephon groups were given 200, 400, and 800 mg/kg Ethephon solution, respectively.The control group was treated with 9 g/L saline.After the birth of the offspring, the mother rats were not administrated with any medications, and the male offspring rats were given Ethephon solution instead.Twelve offspring male rats were randomly selected from each group and killed at the age of 0, 14 and 28 days after birth.Fresh testicular tissues were stained with hematoxylin eosin (HE), and the morphological changes of testicular tissues were observed under light microscope.The apoptotic cells were labeled by terminal dexynucleotidyl transferase (TdT) mediated dUTP nick end labeling (TUNEL) method and the apoptosis index (AI) of spermatogenic cells was detected by fluorescence microscope.Results:(1) Compared with the newborn rats in the middle dose group, low dose group and control group, se-miniferous tubules in the newborn rats of the high dose group were slightly thicker, and seminiferous cells were arranged slightly in disorder.The AI of the newborn rats in high dose group was significantly higher than that in the control group (1.00±0.06 vs.0.41±0.03, P<0.01). The AI of the newborn rats in the middle dose group was not significantly different from that in the control group and the low dose group ( P>0.05). (2) The seminiferous tubules of the 14-day-old rats in the low dose, middle dose and high dose Ethephon groups were significantly thicker and arranged more loosely than those in the control group.Compared with the control group, there were very few seminiferous cells, which were arranged disorderly in the low dose, middle dose and high dose Ethephon groups.The AI of the 14-day-old rats in the low dose, middle dose and high dose Ethephon groups was (2.13±0.10), (2.18±0.10) and (3.90±0.23), respectively, which were significantly higher than that in the control group (1.00±0.02) ( F=2 508.36, P<0.01). There was no significant difference in the AI between the middle dose and low dose groups ( P>0.05). (3) Compared with the control group, the seminiferous tubules of the 28-day-old rats in the low dose, middle dose and high dose groups were significantly thicker and arranged much more loosely, and spermatogenic cells were even less and arranged in a severely disordered way.The AI of 28-day-old rats in the low dose group (5.52±0.13), the middle dose group (9.44±0.07) and the high dose group (14.56±0.27) was significantly higher than that in the control group (3.11±0.13) ( F=10 784.69, P<0.01). Conclusions:Ethephon can thicken the seminiferous tubules of newborn and young rats, cause the germ cells to arrange disorderly, promote the apoptosis of spermatogenic cells and reduce the ability of spermatogenesis.Moreover, a longer exposure of the rats to a higher concentration of Ethephon will result in more serious damage to testicular tissues.

Objective:To evaluate the oncologic outcomes of different laparoscopic radical hysterectomy.Methods:From January 2011 to December 2014, the laparoscopic operation cases of cervical cancer at stage Ⅰb1, Ⅰb2, Ⅱa1 and Ⅱa2, including the histologic subtypes of squamous-cell carcinoma, adenocarcinoma and adenosquamous carcinoma, were collected in five clinical centers. The data were divided into two groups according to the surgical procedures, that is, modified laparoscopic-vaginal radical hysterectomy (mLVRH) and total laparoscopic radical hysterectomy (TLRH). The overall survival rate (OS), disease-free survival rate (DFS) at 5 years were retrospectively analyzed in this study.Results:There were 674 cases in total, including 377 cases of mLVRH, 297 cases of TLRH. (1) The OS at 5 years: the mLVRH was 96.1% and the TLRH was 92.0%, and the mLVRH was higher than that of TLRH （ P=0.010）. Stratify analysis， including stage of disease （Ⅰb1 and Ⅱa1）， histologic subtypes （squamous-cell carcinoma, adenocarcinoma）， lymph node metastasis， revealed that, ① Stage of disease: in stage Ⅰb1, the OS at five years of mLVRH was higher than that in TLRH group （98.6% vs 93.6%, P=0.012）. In stage Ⅱa1, there was significant difference between the two groups, the OS at five years of mLVRH and TLRH were 93.6% and 77.6% （ P=0.007）. ② Histologic subtypes: for the OS at five years of squamous-cell carcinoma, mLVRH and TLRH were 96.1% and 92.3%, and there was significant difference （ P=0.046）； for adenocarcinoma, the OS at five years were 91.0% and 88.6%， and there was no difference between two groups （ P=0.230）. ③ Lymph node metastasis： the mLVRH and TLRH with lymph node metastasis, the OS at five years were 98.6% and 96.4%; the mLVRH and TLRH without lymph node metastasis, the OS at five years were 89.3% and 80.8%. There were no significant differences between the two groups,respectively ( P=0.156， P=0.093）. (2) The DFS at 5 years: there was no significant difference between mLVRH and TLRH (94.1% vs 90.9%, P=0.220). Stratify analysis for stage of disease, the mLVRH group was higher than that in the TLRH group in stage Ⅰb1 (97.0% vs 92.8%, P=0.039). However, for stage Ⅱa1, there was no significant difference between mLVRH and TLRH group （88.2% vs 75.8%, P=0.074）. Conclusions:The results of this retrospective study indicated that different laparoscopy surgical procedures had diverse oncologic outcomes. The OS at 5 years of the mLVRH is superior to the TLRH. The DFS at 5 years in Ⅰb1 stage, the mLVRH is higher than the TLRH. Therefore, the modified laparoscopy is still an alternative surgery for early cervical cancer patients when following the principle of no-tumor-exposure.