Objective To investigate the expression changes of iron autophagy-mitochondrial ferric ion transport protein families(SFXNs)in acute kidney injury(AKI)and chronic kidney disease(CKD)mouse models induced by cisplatin(Cis)and ischemia reperfusion(IR).Methods C57BL/6 mice were randomly divided into control group(control),Cis-AKI group,Cis-CKD group,sham-operated group(sham),IR-AKI group,and IR-CKD group.Serum and kidney tissue samples were collected from mice.Serum creatinine(Cr)and blood urea nitrogen(BUN)levels were detected.Pathological changes in renal tissues were observed by HE staining.Western blot was used to detect the expression of renal SFXNs and kidney injury related proteins.Results Compared with the control or sham group,the levels of BUN and Cr in the serum of the model group were significantly increased(P＜0.05),the renal tissue showed significant pathological damage,with the kidney injury molecule-1(KIM-1),neutrophil gelatinase-associated lipocalin(NGAL),and pro-apoptotic protein Bax significantly upregulated(P＜0.05),while the anti-apoptotic protein Bcl-2 was significantly downregulated(P＜0.05).Compared to the control or sham group,the Cis-AKI group showed a significant downregulation of SFXN4(P＜0.05);The SFXN4 and SFXN5 subtypes were significantly downregulated in the IR-AKI group and Cis-CKD group(P＜0.05);All five subtypes of SFXN in the IR-CKD group were significantly downregulated(P＜0.05).Conclusions Cis or IR in-duces renal tissue damage and tubular mitochondrial injury in mice and affects the expression of SFXN family pro-teins,suggesting their potential role in renal injury of animal models.

Objective:Postoperative neurosurgical bacterial meningitis (PNBM) has been frequently reported, but fewer studies have focused on the contemporaneous comparison of clinical features of PNBM caused by different pathogenic bacteria. This study aimed to simultaneously investigate the clinical characteristics and outcomes of PNBM by Gram-positive bacterial(GPB) or Gram-negative bacterial (GNB) infection.Methods:Inpatients with PNBM at our institution were recruited between February 2013 and October 2023. These PNBM patients were categorized into two groups: GPB infection and GNB infection. Data from electronic medical records were collected and analyzed.Results:A total of 401 patients with PNBM were finally included, with 78 (19.5%) having GPB infections and 323 (80.5%)having GNB infection. The average age of the patients was 56 years, and 55.1% were male. Compared to the GPB group, PNBM patients with GNB infection had significantly higher SOFA and APACHE Ⅱ scores, higher proportions of hyperthermia (body temperature>39°C) and altered consciousness, increased ratios of postoperative cerebral hemorrhage or intracranial aneurysm, as well as greater needs for ICU treatment and mechanical ventilation (all P <0.05). The proportions of inflammatory indicators such as blood CRP and PCT≥2 ng/mL, alanine aminotransferase (ALT), aspartate aminotransferase (AST), and total bilirubin (TBIL) were significantly higher in the GNB group (all P<0.05). In contrast, The concentrations of hemoglobin and albumin were substantially lower in this group(both P <0.05). Additionally, the cerebrospinal fluid in the GNB group showed significantly higher nucleated cell counts, protein concentration, and adenosine deaminase concentration, and but lower glucose level (all P <0.001). A total of 426 bacterial strains were isolated, with 343 strains (80.5%) being GNB and 83 strains (19.5%) being GPB. Among these, 25 (6.2%) patients had 2 or more gram-positive or gram-negative bacterial infections. The proportions of multidrug-resistant (MDR) bacteria and intrathecal treatment were higher in the GNB group (80.5% vs. 68.7%, 36.5% vs. 2.6%, respectively), while the ratio of correct empirical antibiotic treatment was significantly lower (30.3% vs. 80.0%) (all P <0.05). In terms of outcomes, the length of stay in the ICU was significantly longer in the GNB group [(median (interquartile range, IQR): 11.5 (5.25,22.75) vs. 17.0 (9.0,30.0), P <0.01)], and the rate of septic shock (9.3% vs. 2.6%), poor prognosis (GCS≤8 at discharge) (65.9% vs. 32.1%), and 28-day hospital mortality rate (34.4% vs. 10.3%) were significantly higher compared to the GPB group (all P <0.05). However, there were no differences in 7-day hospital mortality and total hospitalization time. Conclusions:Gram-negative bacterial infections are more prevalent than Gram-positive bacterial infections in PNBM, and they are also associated with more severe symptoms, abnormal cerebrospinal fluid findings, higher severity, and more treatment difficulty. Despite comparable short-term (7-day) mortality rates between Gram-positive and Gram-negative bacterial infections, Gram-negative bacterial infections result in higher medium- to long-term (14-day and 28-day) case-fatality rates among patients with post-neurosurgical bacterial meningitis and are associated with overall poorer prognosis, warranting greater attention from clinicians.

Objective To study the status of diabetic foot and its related factors in Hanzhong area in recent years, and to provide a scientific basis for the prevention and management of diabetic foot complicated by type 2 diabetes. Methods A stratified sampling method was used to select 528 patients with type 2 diabetes among permanent residents in Hanzhong from April 2016 to April 2022. Relevant medical history and laboratory examination data were collected, and the incidence of diabetic foot was calculated. The influence of related factors on the risk of diabetic foot was analyzed by regression model. Results Among 528 subjects in this study, the disease course and body type of T2DM showed that male patients had significantly longer disease, and the proportion of overweight and obesity was higher, P<0.05. The incidence of diabetic foot was 16.29% (86 cases). The proportion of male patients and female patients was 24.66% and 5.93%（χ²=27.516，P<0.05）. The proportion of male patients complicated with diabetic foot was higher than that of female patients (P<0.05). At the same time, the incidence of Wagner Grade I was higher in males than in females (P<0.05). The effects of potential factors on the risk of diabetic foot were discussed by gender. Univariate analysis and multivariate logistic regression analysis indicated that the risk factors of diabetic foot in male T2DM patients included: Increased course of disease, increased age, poor blood glucose control, increased total cholesterol level, increased BMI level and increased platelet to lymphocyte ratio . Potential risk factors in women include increased course of disease, age, poor blood sugar control (increased glycosylated hemoglobin levels) and increased platelet to lymphocyte ratios in all cases（P<0.05）. Conclusion The current prevalence rate of type 2 diabetes patients complicated with diabetes foot in Hanzhong area is 16.29%, which is still high , and the prevalence rate of men is significantly higher than that of women. Older age, long duration of T2DM, poor blood glucose control, increased total cholesterol level, increased blood uric acid level, decreased urine pH value, and increased platelet lymphocyte ratio are potential risk factors for diabetes foot. Male patients should also pay attention to the occurrence of overweight and obesity tendency to reduce the risk of diabetes foot.

OBJECTIVE To prepare and evalu ate doxorubicin-loaded red blood cell membrane chitosan-targeted nanoparticles of targeting tumor cell folate acid （FA）receptor（FA-RBC-DOX-CS-NPs）. METHODS Doxorubicin-loaded chitosan nanoparticles （DOX-CS-NPs） were prepared by ion cross-linking method. FA and amino polyethylene glycol phospholithin （NH2- PEG2000-DSPE）were covalently linked to modify the red blood cell membrane to construct FA-RBC-DOX-CS-NPS. FA-RBC- DOX-CS-NPs were characterized and investigated on in vitro drug release characteristics ，antitumor activity and endocytosis ability （investigation with human breast cancer MCF- 7 cells）. RESULTS Average particle size of FA-RBC-DOX-CS-NPs was （254.200± 2.651）nm，and polydispersity index was 0.199±0.031；Zeta potential was （－10.100±0.213）mV. FA-RBC-DOX-CS-NPs released fast in the tumor microenvironment （pH6.5）. Cellular experiments showed that ，the nanoparticles could inhibit the activity of MCF- 7 cell proliferation and improve the efficiency of endocytosis. CONCLUSIONS FA-RBC-DOX-CS-NPs are prepared successfully. The nanoparticles have good tumor cell targeting and endocytosis ability ，and can realize the enrichment of drugs in tumor cells.

Objective:To evaluate the relationship between long-term learning and memory impairment induced by sevoflurane anesthesia and postsynaptic density protein-95 (PSD-95)/Kalirin-7/Ras-related C3 botulinum toxin substrate 1 (Rac1) signaling pathway in neonatal rats.Methods:Sixty SPF male Wistar rats, aged 7 days, weighing 12-18 g, were divided into 5 groups ( n=12 each) using a random number table method: control group (group C), 1% sevoflurane anesthesia for 2 h group (group S 1), 1% sevoflurane anesthesia for 4 h group (group S 2), 2% sevoflurane anesthesia for 2 h group (group S 3) and 2% sevoflurane anesthesia for 4 h group (group S 4). Morris water maze test was performed at 4, 8 and 12 weeks after anesthesia.The rats were sacrificed after the last Morris water maze test, and the hippocampal tissues were obtained for microscopic examination of the pathological changes (using HE staining), neuron apoptosis (by TUNEL staining), and expression of PSD-95, Kalirin-7 and Rac1 protein and mRNA (by Western blot and quantitative real-time polymerase chain reaction). The apoptosis rate was calculated. Results:Compared with group C, the escape latency was significantly prolonged, the number of crossing the original platform was reduced, the time of stay in the target quadrant was shortened, and the apoptosis rate of hippocampal neurons was increased at 4th, 8th and 12th weeks after anesthesia, phosphorylated Rac1/Rac1 ratio was decreased, and the expression of PSD-95 and Kalirin-7 protein and mRNA was down-regulated in S 1, S 2, S 3 and S 4 groups ( P<0.05). Compared with group S 4, the escape latency was significantly shortened, the number of crossing the original platform was increased, the time of stay in the target quadrant was prolonged, and the apoptosis rate of hippocampal neurons was decreased, phosphorylated Rac1/Rac1 ratio was increased, the expression of PSD-95 and Kalirin-7 protein and mRNA was up-regulated, and the histopathological changes of hippocampal tissues were attenuated in S 1, S 2 and S 3 groups ( P<0.05). Conclusions:The mechanism by which sevoflurane anesthesia induces long-term learning and memory impairment may be related to inhibition of activity of PSD-95/Kalirin-7/Rac1 signaling pathway in hippocampi of neonatal rats.

Objective:Intensive physicians have relatively insufficient knowledge and experience in treating patients with decompensated schistosomiasis cirrhosis (DSC) admitted in intensive care unit (ICU), but are relatively familiar with patients with decompensated alcoholic cirrhosis (DAC). For this purpose, the clinical characteristics and prognosis of these patients were compared and analyzed.Methods:A retrospective analysis was performed from January 2013 to May 2019 in our hospital and Quzhou People’s hospital. The demographic data, laboratory examination, liver function, Child-Pugh classification, complications of cirrhosis, ultrasonic imaging gastroscopy manifestations were recorded and analyzed. In addition, the treatments and prognosis were also compared.Results:A total of 30 patients (12 males and 18 females) with DSC (aged 57-88) and 31 patients with DAC (aged 41-75) were collected. Compared with patients with DAC, DSC patients were more likely to have coronary heart disease, lower proportion of hyponatremia and lower need of ventilator support. Although the incidences of jaundice and hepatic encephalopathy were significantly reduced ( P<0.05), but parameters of liver function and coagulation were no significant differences in both groups ( P>0.05). B-mode ultrasound of liver in patients with DSC displayed more proportion of patchy and diffuse echo changes and liver volume reduction ( P<0.05), whereas the manifestations of gastroscope in both groups were similar. No significant difference in main treatment measures like uses of somatostatin and three-chamber and two-capsule tube was observed. After treatment, the stop time of gastrointestinal bleeding was similar between groups of DAC and DSC [1.25 (0.5-4.125) days vs. 1.75 (1-2.375) days] ( P>0.05). In addition, the length of ICU stay in DAC group was similar to DSC group [(4.96±3.58) days vs. (3.82±1.99) days], so did the 28-day mortality [14.29% (2/14) vs. 18.18% (2/11)] (both P>0.05). Conclusions:In genenal, patients with decompensated schistosomiasis cirrhosis have the similar clinical characteristics, major biochemical indicators and accessory examination results like ultrasound and gastroscopic examinations to patients with decompensated alcoholic cirrhosis. After timely treatments, both of these patients could achieve a good prognosis.

Objective:To observe the activation of cerebral regions during swallowing by magnetoencephalography (MEG), and discuss the temporal and spatial characteristics of neural circuit.Methods:Ten healthy subjects were selected, and the magnetic signals of their brains were recorded using 148 channel full head type MEG system in the magnetic shielding room.Data were analyzed using CURRY8 analysis software and the localization algorithm was based on minimum modulus low resolution electromagnetic imaging method (LORETA). Every 300 ms data were set as an independent analysis stage and made the highest position of the cerebral cortex F-distribution values (F-distributed) as the activation area.The activation areas were analyzed during swallowing through time and space location.Results:Paracentral lobule, anterior central gyrus, medulla oblata, posterior central gyrus, inferior frontal gyrus, parietal lobules, angular gyrus, corpus callosum, middle frontal gyrus, cingulate gyrus, orbital gyrus, thalamus, bottom of third ventricle, corona radiata, precuneus, frontal insula, cerebellopontine angle, superior frontal gyrus and basal ganglia area were activated during swallowing, in which the top eight brain regions were paracentral lobule, anterior central gyrus, corpus callosum, posterior central gyrus, superior parietal lobule, middle frontal gyrus, cingulate gyrus, and basal ganglia.When the 10 subjects performed the deglutition, MEG signals of 8 subjects were mainly activated by the left cerebral hemisphere at 0-300 ms, the bilateral cerebral hemisphere or intermediate region at 301-600 ms, and the right cerebral hemisphere at 601-900 ms.MEG signal of 1 subject was activated by the right cerebral hemisphere at 0-300 ms, and the left cerebral hemisphere at 301-600 ms and 601-900 ms.MEG signal of 1 subject was mainly activated by the right cerebral hemisphere at 0-300 ms and 601-900 ms, and in the intermediate region at 301-600 ms.Conclusion:During swallowing the MEG signals appeared left laterality in the early stage and right laterality in the later stage, and showed a close correlation with time.There may be a swallowing neural circuit composed by the central region, corpus callosum, superior parietal lobule, middle frontal gyrus, cingulate gyrus and basal ganglia, in which the central region is the core.

Among all gynecological tumors, ovarian cancer is the third most common cancer but the most lethal one. Currently, the standard first-line treatment for ovarian cancer is cytoreductive surgery combined with platinum and paclitaxel chemotherapy. Although the patients with ovarian cancer respond to the standard therapeutic approach and gain a high remission rate, the most patients relapse after about 2 years of complete remission, the recurrence rate is as high as 80%. The patients with recurrent epithelial ovarian cancer are resistant to almost all chemotherapy drugs due to the acquired resistance. Multidrug resistance to chemotherapy is a major cause of treatment failure. Therefore, it is an urgent problem to reveal the molecular mechanism of ovarian cancer resistance. In recent years, tumor microenvironment as an emerge concept has provided a new perspective for the study of tumorigenesis, progression and drug-resistance. Ovarian cancer is characterized by a unique tumor microenvironment that impairs immune surveillance and mediates therapy resistance. Explaining the mechanism of chemotherapy resistance from the perspective of ovarian cancer microenvironment is helpful to find effective targets reversing the drug resistance of ovarian cancer. This review first introduces the general situation of drug resistance and microenvironment of ovarian cancer, and then focuses on the research progress in the relationship of various components of ovarian cancer microenvironment with drug resistance, in order to explain the occurrence mechanisms of ovarian cancer resistance and find effective targets in the microenvironment to solve the problem of clinical drug resistance. In the end, the forward research directions in this field are prospected in this review.

Objective To explore the clinical value of pulse indicates continuous cardiac output (PICCO) in fluid resuscitation of patients with ARDS complicated with septic shock caused by severe pneumonia. Methods Thirty-nine ARDS patients complicated with septic shock caused by severe pneumonia were divided into two groups, namely PICCO group and control group. The data of demographics and clinical findings of both groups were collected. At the same time, the data of serum lactic acid, Pa02/Fi02, MAP, the volume of fluid input, the amount of vasoactive agent, APACHE Ⅱ Scores of both groups at 6 hours and 24 hours after admission were collected, and the data of EVLWI, PVPI, CI, SVRI, GEDVI in PICCO group were documented at admission and 24 hours later, as well as the duration of mechanical ventilation, length of stay in the respiratory ICU and 30-day mortality were recorded. SPSS software of version 21.0 was used to statistically analyze the data. Results ① There were no statistically significant differences in in age, gender, APACHEII score and other relevant physiological parameters between two groups.② Compared with control group at 6 h and 24 h, the PICCO-guided treatment significantly reduced the level of Lac, elevated the MAP value and decreased the volume of fluid input (all P＜0.05) At the same time, this approach improved 24 h-Pa02/ Fi02(P=0.001).More importantly, the PICCO-guided treatment significantly reduced the duration of mechanical ventilation[(8.83 ± 3.57) vs (13.54 ± 4.06)d, P=0.000],shortened the stay in the respiratory ICU[(10.12 ± 4.46) vs (14.10 ± 5.65)d,P=0.020]and decreased the 30d mortality 15.79％ vs 50％,p=0.041. ③ In PICCO group, EVLWI and PVPI were significantly decreased[(12.27 ± 4.42) vs (16.11 ± 5.99) mL/ kg,P=0.028; (3.66 ± 1.71) vs (6.88 ± 2.93) mL/m2, P=0.000]; respectively and SVRI and GEDVI were significantly increased[(1212.70 ± 304.10) vs (958.50 ± 192.40)kPa·s/(min·m2),P=0.004; (676.57 ± 77.86) vs (616.33 ± 57.49)mL/(min · M2),P=0.010]; respectively at 24h compared those at admission. Conclusions Compared with conventional fluid resuscitation, PICCO-oriented treatment can quickly improve the relevant physiological parameters, direct the fluid resuscitation more accurately, shorten the duration of mechanical ventilation as well as the stay in ICU, and decrease the 30d mortality in patients with ARDS complicated with septic shock caused by severe pneumonia. Therefore, PICCO-oriented fluid resuscitation has noticeable clinical value, and be worthy of further clinical application especially in this kind of patients.

To reflect specialty teaching characteristics and levels in clinical standardized training of medical professional degree postgraduates and highlight the thinking of evidence-based medicine culture,in urology rotation training practice,we conducted clinical pathway teaching according to picot principle (PICOT-CP teaching).According to the requirements of the teaching syllabus,the six kinds of major diseases were brought into PICOT-CP teaching.After the screening of pre teacher training,teaching tools and teaching cases,and based on the form of PICOT-CP,we standardized the implementation of clinical teaching of Urology,fully used subject website platform to discuss the interaction between teachers and students,and assessed the effect in combination with the departmental rotation examination and the teaching questionnaire survey of the students and the training teachers.Preliminary practice shows that PICOT-CP teaching helps to stimulate students' interest in learning,improve their overall quality,expand their clinical thinking,and establish their concept of evidence-based medicine.In addition,PICOT-CP teaching is beneficial to the teaching norms of teachers' teaching and can improve teaching level.