Immune evasion has made ovarian cancer notorious for its refractory features, making the development of immunotherapy highly appealing to ovarian cancer treatment. The immune-stimulating cytokine IL-12 exhibits excellent antitumor activities. However, IL-12 can induce IFN-γ release and subsequently upregulate PDL-1 expression on tumor cells. Therefore, the tumor-targeting folate-modified delivery system F-DPC is constructed for concurrent delivery of IL-12 encoding gene and small molecular PDL-1 inhibitor (iPDL-1) to reduce immune escape and boost anti-tumor immunity. The physicochemical characteristics, gene transfection efficiency of the F-DPC nanoparticles in ovarian cancer cells are analyzed. The immune-modulation effects of combination therapy on different immune cells are also studied. Results show that compared with non-folate-modified vector, folate-modified F-DPC can improve the targeting of ovarian cancer and enhance the transfection efficiency of pIL-12. The underlying anti-tumor mechanisms include the regulation of T cells proliferation and activation, NK activation, macrophage polarization and DC maturation. The F-DPC/pIL-12/iPDL-1 complexes have shown outstanding antitumor effects and low toxicity in peritoneal model of ovarian cancer in mice. Taken together, our work provides new insights into ovarian cancer immunotherapy. Novel F-DPC/pIL-12/iPDL-1 complexes are revealed to exert prominent anti-tumor effect by modulating tumor immune microenvironment and preventing immune escape and might be a promising treatment option for ovarian cancer treatment.

Objective:To investigate whether prophylactic use of metal clips is necessary after cold snare polypectomy (CSP) of colorectal polyps of 6-10 mm.Methods:A total of 200 patients with 6-10 mm polyps that met the criteria of cold snare resection in Chengdu Third People's Hospital from 15 February 2022 to 30 May 2022 were randomly divided into two groups: a group that received preventive metal clip treatment and an observation group. Age, gender, body mass index (BMI), Boston score, endoscopy entry time, wound size, operation time, intraoperative bleeding time, postoperative delayed bleeding rate and cost between the two groups were compared and analyzed.Results:Ninety-eight patients in the metal clip group had 122 polyps removed, and 97 patients in the observation group had 119 polyps removed. There was no significant difference in the age, gender, BMI, Boston score, endoscopy entry time or wound size between the two groups. There were significant differences in the operation time (171.03±90.78 s VS 69.81±43.26 s, t=2.266， P=0.010), intraoperative bleeding time (19.98±17.37 s VS 29.16±17.56 s, t=-2.875， P=0.006) and surgery cost (571.63±110.92 yuan VS 366.32±13.2 yuan, t=18.102， P<0.001) between the metal clip group and the observation group. There was no significant difference in the delayed bleeding incidence［0.0%（0/98）VS 1.0%（1/97）， P=0.497］between the two groups. Conclusion:For patients with continuous bleeding time <60 seconds after CSP of 6-10 mm colonic polyps, the prophylactic use of metal clips may reduce the bleeding time, but may increase the operation time and cost. Metal clips have little effect on preventing postoperative complications.

Objective By analyzing the prevalence pattern and drug resistance of carbapenem-resistant enterobacteriaceae(CRE)infections in our hospital,we aim to provide the basis and suggestions for infection prevention and control as well as clinical management in large general hospitals.Methods A retrospective method was used to select 609 CRE strains isolated from hospitalized patients in our hospital from 2019 to 2022,and analyze their specimen sources,distribution of pathogenic bacteria,departmental distribution and drug resistance.Results A total of 6656 strains of Enterobacteriaceae and 609 strains of CRE were detected in the four years,with Klebsiella pneumoniae predominating(354 strains,58.13％),followed by Enterobacter inguinale(82 strains,13.46％)and Escherichia coli(77 strains,12.65％),and the department with the most detected CREs was the intensive care unit(ICU)(44.50％),followed by the Department of Burn Repair(13.79％),Department of Cardiac and Major Vascular Surgery(8.87％)and Department of Oncology(6.4％),and the sources of specimens were sputum(46.96％),secretions(15.60％),urine(13.30％),and blood(8.7％)in that order.The drug sensitivity results showed that the CRE strains had resistance rates＞50％to the rest of the clinically used antimicrobial drugs,except for tigecycline,polymyxin and minocycline,which were sensitive(1.31％,0.56％and 7.22％),and amikacin,fosfomycin,as well as cotrimoxazole,which had a lower resistance rate(23.65％,35.14％and 35.96％).Conclusion The overall trend of CRE detection rate in this hospital from 2019-2022 was increasing,and most of them showed multiple resistance to clinically used antibiotics,attention should be paid to strengthen the rational use of antimicrobial drugs and increase the supervision of bacterial resistance to curb the wide spread of CRE.

Objective To evaluate the efficacy of cardiac output ( CO ) and corrected flow time ( FTc) monitored by ultrasonic cardiac output monitor ( USCOM) in guiding volume therapy in patients un-dergoing laparoscopic colorectal surgery. Methods Eighty American Society of Anesthesiology physical sta-tus Ⅰ or Ⅱ patients, aged 18-60 yr, with body mass index of 18-25 kg∕m2 , undergoing laparoscopic colorectal surgery, were divided into 2 groups ( n=40 each) using a random number table method: control group ( group C ) and USCOM-guided fluid therapy group ( group U ) . Mean arterial pressure was main-tained at 60-100 mmHg, central venous pressure at 5-10 cmH2 O and urine volume>0. 5 ml·kg-1 ·h-1 u-sing conventional fluid therapy in group C. In group U, goal-directed fluid therapy was performed under the monitoring of USCOM, FTc was maintained at 326-400 ms and CO at 4. 2-5. 9 L∕min. The volume of crys-talloid and colloid solution, total volume of fluid infused, blood loss, urine volume and requirement for va-soactive agents during surgery and time of surgery were recorded. Blood samples were collected from the left radial artery for determination of the blood lactate concentration immediately after anesthesia induction, at the end of the operation and at 1 and 2 days after surgery. The time of passing the first flatus after surgery, adverse cardiovascular events ( hypertension, hypotension, cardiac insufficiency ) , pulmonary complica-tions ( pulmonary edema, pulmonary atelectasis) , and oliguria and anuria within 24 h after surgery, and length of hospital stay were recorded. Results Compared with group C, the volume of crystalloid, total volume of fluid infused and urine volume were significantly decreased during surgery, the volume of colloid solution was increased during surgery, the blood lactate concentration was decreased at the end of surgery, the incidence of postoperative cardiovascular and pulmonary complications was decreased, and the time of passing the first flatus after surgery and length of hospital stay were shortened in group U ( P<0. 05) . Con-clusion USCOM-monitored CO and FTc produces better efficacy in guiding volume therapy and is helpful for improving recovery in patients undergoing laparoscopic colorectal surgery.

Objective To examine the protein expression of the nucleotide excision repair gene (ERCC-1) in patients with locally advanced cervical cancer and its relationship with the efficacy of radiotherapy and chemotherapy.Methods The expression of ERCC-1 protein in 88 patients with locally advanced cervical cancer treated in our hospital between 2007-2011 was measured using immunohistochemistry (IHC).The patients were divided into high-expression group (n=48) and low-expression group (n=40) based on the fluorescence intensity on the IHC staining.All patients received cisplatin (40 mg/m2 per week) during radiotherapy.The relationship between ERCC-1 protein expression and the clinicopathological factors of cervical cancer was analyzed using the chi-square test.Survival was calculated using the Kaplan-Meier method and compared by the log-rank test.Multivariate prognostic analysis was performed using the Cox model.Results The overall response rate (CR+PR) was 81%(39/48) in the high-ERCC-1 expression group and 85%(34/40) in the low-ERCC-1 expression group (P=0.641).ERCC-1 protein expression was associated with recurrence and metastasis (P=0.043,0.043).The 5-year survival rate was significantly higher in the low-ERCC-1 expression group than in the high-ERCC-1 expression group (65% vs.42%, P=0.029).Conclusions Patients with high ERCC-1 protein expression are more likely to have local recurrence and distant metastasis than those with low ERCC-1 protein expression.ERCC-1 protein expression may be a clinically significant biomarker for predicting the prognosis of cervical cancer patients.

OBJECTIVETo determine the effect of intermittent hypoxia on lipid metabolism in liver cells and to explore the possible molecular pathways involved in this process.

METHODSAn intermittent hypoxia cell model system was established by incubating the human hepatic cell lines L02 and HepG2 in an atmosphere of 2% O₂, 5% CO₂ and 93% N₂ for 8 hours per day over a period of 1, 2, 3, 4 or 5 days. Cells cultured in normoxia conditions (21% O₂) served as controls. Changes in intracellular lipid droplets and triglyceride (TG) levels were assessed by biochemical assays and oil red staining. Changes in intracellular reactive oxygen species (ROS) were assessed by inverted fluorescence microscopy and flow cytometry. Changes in expression of hypoxia-inducible factor (HIF)-1a and HIF-2a proteins, and the downstream ADFP, SREBP-1c and FAS proteins, were detected by western blotting.

RESULTSFor both L02 and HepG2 cell lines, the cells grown under hypoxic conditions showed significantly higher lipid droplet accumulation and TG content than the cells grown under normoxic conditions (F(L02) =61.83, FHepG2 =104.19, P less than 0.01). Both oxygen concentration and time appeared to be correlated with these lipid-related changes (F(L02) =39.60, FHepG2 =76.39, P less than 0.01). The ROS fluorescence index was significantly increased after 2 days of intermittent hypoxia L02: 0.703 ± 0.129 vs. 3.310 ± 0.198, t =22.0637 and HepG2:0.617 ± 0.156 vs. 2.33 ± 0.42, t =7.2003, P < 0.05); in addition, increasing trends were observed in the ROS content and intensity of green fluorescence in conjunction with increased time of exposure to intermittent hypoxia (F(L02) =1021.84, FHepG2 =49.89, P less than 0.01). Compared with their respective control groups, the L02 and HepG2 cells both showed significantly upregulated expression of HIF-1a ADFP, SREBP-1c and FAS (L02:FHIF-1a =371.19, FsREBP-1c =204.49, FFAS =38.20, FADFP =154.31, P less than 0.05 and HepG2:FHF-1a =150.84, FSRERBP-1c =107.35, FFAs =279.71, FADFP =352.06, P less than 0.01). In contrast, the HIF-2a level was markedly decreased in the cells after 4 and 5 days of exposure to intermittent hypoxia (F(L02) =125.29, FHcpG2 =10.68, P less than 0.05).

CONCLUSIONUnder intermittent hypoxic conditions, ROS may regulate the expression of hypoxia-inducible factors and the adipose differentiation-related protein,as well as influence fatty acid metabolism via a HIF-1 a-SREBP-1 c-FAS signal and upregulation of the ADFP protein, in liver cells.

Objective To report the clinical features and treatment outcomes of 27 patients with fungal endophthalmitis (27 eyes)over a five year period.Methods The authors retrospectively reviewed the etiology,direct smear examination,fungal cul-ture and treatments of 27 patients with culture-proven fungal endophthalmitis at the affiliated Hospital of Medical College Qing-dao University from 2007 to 2012.Results Exogenous infection was defined in 21 patients (77.8%),including 20 associated with penetrating wound,and 1 following cataract surgery.Endogenous infection was found in 6 patients (22.2%),including 3 associated with recent use of high-dose steroids,1 after abortion,1 following pelvic fracture,and 1 with long-term use of im-munosuppressive agents.Fungal hyphae were found in 17 smears of 27 samples (63.0%)by direct microscopic examination. The fungal strains cultured from 27 samples belonged to 8 genus and 12 species.The most common isolates were Aspergillus , Fusarium and Candida species.A.flavus (22.2%)and A.fumigatus (18.5%)were the predominant Aspergillus species. F .moniliforme (14.8%)and F .oxysporum (11 .1 %)were the most predominant Fusarium species.Two eyes were eviscer-ated immediately due to the serious condition.Among the other 25 eyes,22 (88.0%)got improvement after at least one of such treatments as intravitreal injection of antifungal agent,vitrectomy or penetrating keratoplasty (PK).Conclusions Exoge-nous fungal endophthalmitis is the most common type of fungal endophthalmitis in this hospital.Penetrating wound is the main cause of such infections.Microscopic examination of hyphae and fungal culture were effective for the diagnosis of fungal endophthalmitis.Aspergillus is the predominant pathogens, followed by Fusarium.Intravitreal injection of antifungal a-gent combined with vitrectomy is an effective treatment of fungal endophthalmitis.

Objective To evaluate the anesthetic efficacy of etomidate target-controlled infusion (TCI) in combination with remifentanil in patients undergoing gynecological laparoscopy.Methods Sixty ASA physical status Ⅰ or Ⅱ patients,aged 25-56 yr,with body mass index 18-27 kg/m2,undergoing elective gynecological lapa-roscopy,were equally and randomly divided into 2 groups:propofol TCI combined with remifentanil group (group PR) and etomidate TCI combined with remifentanil group (group ER).Anesthesia was induced with iv injection ofmidazolam 0.1 mg/kg,fentanyl 4 μg/kg and cisatracurium 0.15 mg/kg in both groups,and with TCI of propofolwith the target effect-site concentration (Ce) of 2.5 μg/ml in group PR or with TCI of etomidate (Ce 0.8 μg/ml) ingroup ER.The patients were mechanically ventilated after endotracheal intubation.Anesthesia was maintained withTCI of propofol (Ce 2.0-2.5 μg/ml) in group PR or with etomidate (Ce 0.5-0.7 μg/ml) in group ER,and with ivinfusion of remifentanil 0.1-0.2 μg· kg-1 · min-1 and intermittent iv boluses of cisatracurium 5 mg.BIS value was maintained at 40-60.Before anesthesia (baseline,T0),at the end of operation (T1),and at 24 and 48 h after operation (T2-3),venous blood samples were collected for determination of serum cortisol and aldosterone concentrations by radioimmunoassay.The emergence time,extubation time and requirement for vasoactive agents during operation were recorded.The development of injection pain and muscle twitch during induction of anesthesia,intraoperative awareness,and post-operative agitation,nausea and vomiting were also recorded.Results Compared with the baseline value at T0,the serum cortisol concentration was significantly decreased at T1 in group ER (P ＜0.05),while no significant change was found in serum aldosterone concentrations at each time point in the two groups (P ＞ 0.05).Compared with group PR,the requirement for vasoactive agents and incidence of injection pain were significantly decreased,and the incidence of muscle twitch was increased (P ＜ 0.05),and no significant change was found in the emergence time,extubation time,and incidences of post-operative agitation,nausea and vomiting in group ER (P ＞ 0.05).Conclusion Compared with propofol TCI in combination with remifentanil,etomidate TCI combined with remifentanil is helpful in maintaining the hemodynamics stable and exerts transient inhibition of adrenocortical function with less injection pain in patients undergoing gynecological laparoscopy.

Objective To evaluate the impact of positive end-expiratory pressure (PEEP) on hemodynamic variables including central venous pressure (CVP),mean arterial pressure (MAP) and heart rate (HR) in patients with central respiratory failure treated by mechanical ventilation.Methods Thirty two neurosurgical patients with central respiratory failure,male 19,female 13,mean age (58.8 ± 13.9)years,GCS ≤ 8 points,were enrolled in this prospective,self-control study between June 1,2009,and May 31,2011.Patients were excluded in cases of severe cardiopulmonary disorders,pericardial diseases,person machine confrontation,administration of vasoactive drugs,and hypervolemia or hypovolemia.On admission to neurosurgical intensive care unit,all patients were mechanically ventilated in the mode of synchronized intermittent mandatory ventilation.Hemodynamic effects of six randomly set levels of end-expiratory pressures (0,3,6,9,12,15 cm H2O,every 10 min,1cm H2O =0.098 kPa) were studied in all patients.CVP,MAP and HR were recorded at each of the six end-expiratory pressure levels.One-way analysis of variance and simple linear regression model were used for data analysis.Results The levels of central venous pressure were elevated with increase in end-expiratory pressures.CVP levels were positively correlated with the levels of PEEP (R =0.468,P =0.000),with a simple linear regression equation expressed as:CVP (cm H2O) =7.870 +0.344 ×PEEP (cm H2O),The levels of MAP showed no statistically significant changes at different PEEP levels (F =1.390,P =0.227).No linear correlation between MAP,HR and PEEP levels was found (R =0.042 and 0.160,P =0.413 and 0.002).Conclusions CVP values would be overestimated during mechanical ventilation at different PEEP levels in mechanically ventilated patients due to central respiratory failure,positive correlation existed between CVP values and PEEP levels,whereas MAP was unaffected by different PEEP levels.This study could probably offer a quantitative reference for correct assessment of such a hemodynamic variable as CVP for mechanically ventilated patients without discontinuance of PEEP.Further studies are needed to determine whether these findings could be confirmed in a prospective manner.

Objective To investigate the incidence and the relation between pulmonary hypertension (PH) and cardiac output in hemodialysis (HD) patients with PH. Methods The incidence of PH was estimated with Doppler echocardiography in 78 patients receiving HD. Left ventricular ejection fraction, cardiac volume, cardiac output and cardiac index were compared between patients with or without PH. Results PH was found in 20 patients (25.64%), among them15 had mild PH, 4 had moderate PH and 1 had severe PH. There was no statistical difference of ejection fraction, cardiac volume, cardiac output and cardiac index between the two groups. PH was not related to cardiac output. Conclusion HD can lead to PH, but cardiac output can not result in PH. Further investigations about the effect of elevated cardiac output induced by internal arteriovenous fistula and other factors on PH are needed.