Allergic asthma is a chronic obstructive disease of the airways characterized by airway hyperresponsiveness,inflammation and remodeling.Exhaled nitric oxide (eNO) level is highly correlated with eosinophilic airway inflammation.Since the advantage of noninvasion,convenience,and specificity of eNO measurement,it has been widely used as a biomarker.In this article eNO metabolism and its effects on airway physiology and pathophysiology are described.The usefulness of eNO in asthma diagnosis and management is discussed in detail.

This study plans to prepare lipid bilayer-coated mesoporous silica nanoparticles (LMSNs) which are pH sensitive with core-shell structure to improve the tumor cell lethality of antitumor drug. The lipid coated mesoporous silica nanoparticles loaded with irinotecan (CPT-11) (CPT-11-LMSNs) were prepared by hot water-film hydration method, and the characterized its morphology, particle size and release in vitro. Meanwhile, the intracellular uptake and cell toxicity of CPT-11-LMSNs and intracellular accumulation of CPT-11 were evaluated on human breast carcinoma cell line (MCF-7). The results indicated that the mean diameter of the spherical LMSNs was (120.27 +/- 5.91) nm. The slow release in simulated normal physiological conditions and a rapid release under simulated intracellular condition demonstrated the pH sensitivity of CPT-11-MSNs in vitro. Moreover, the CPT-11-LMSN could improve the intracellular CPT-11 cumulant 2.1 times and reduce half maximal inhibitory concentration (IC50) values of CPT-11 1.4 times compared with CPT-11-MSNs, demonstrating a stronger cell lethality.

In this work, we developed PEO-PPO-PEO micelles loaded with irinotecan hydrochloride (CPT-11) using breast cancer resistance protein (BCRP) inhibitory material PEO20-PPO70-PEO20, and studied its mechanism of decreasing CPT-11 induced delayed diarrhea and intestinal toxicity. BCRP-overexpressing MDCKII (MDCKII/BCRP) cells were used to evaluate the effect of PEO20-PPO70-PEO20 and PEO-PPO-PEO micelles on transmembrane transport of CPT-11 in vitro. The biliary excretion, delayed diarrhea and intestinal damage of CPT-11 loaded PEO-PPO-PEO micelles of rats were investigated. The results showed that the obtained micelles could decrease the biliary excretion of CPT-11, ameliorate delayed diarrhea and intestinal toxicity of rats through inhibiting BCRP-mediated CPT-11 efflux. PEO-PPO-PEO micelles were promising carriers to reduce intestinal toxicity of CPTs.

The purpose of this study is to prepare galactosyl modified lipid bilayer-coated mesoporous silica nanoparticles (GPEM) to enhance the antitumor efficacy against hepatocellular carcinoma cells. The irinotecan (CPT-11) loaded mesoporous silica nanoparticles (MSNs) was coated with the Gal-P123 modified functional lipid bilayer by thin-film dispersion method. Nanoparticles were characterized with particle size, zeta potential, morphology and drug release in vitro. Afterwards, the cell uptake, intracellular concentration of CPT-11, cell apoptosis rate and cytotoxicity were evaluated on human hepatocellular carcinoma cell line Huh-7. The results showed that MSNs were coated with intact lipid bilayers and the nanoparticles had clear core-shell structure. GPEM is stable with the mean particle size of (78.01 +/- 2.04) nm. The low leakage rate in normal physiological conditions in vitro is contributed to the protection of stable lipid bilayer, and the fast drug release in acid environment due to the destruction of the lipid bilayer. On the cell level, the vector could improve the intracellular CPT-11 concentration by 4 times because of the functional lipid bilayer. The high CPT-11 concentration led to the increasement of apoptosis rate by 48.6%, and the reduction of half maximal inhibitory concentration (IC50) values of CPT-11 by 2 times, indicating stronger cell cytotoxicity.

Polymyxin E shows effective treatment of the infection induced by resistant gramnegative bacteria, but its nephrotoxicity severely limits the clinical application of this drug. In this work, methoxypolyethylene glycols 2000 (mPEG2K)-polymyxin E (PME) was synthesized via chemical grafting reaction and had been characterized. The antimicrobial activity and cytotoxicity of mPEG2K-PME in vitro were investigated on Escherichia coli and HK-2 cells, separately. Intra-abdominal infection model was further established in order to study the therapeutic effect and the toxic effect on kidney of mice. The results showed that mPEG2K-PME exhibited significant inhibitory effect on Escherichia coli and had a lower toxicity on HK-2 cells in vitro. At the same time, mPEG2K-PME had a good efficacy in the treatment of Escherichia coli infected mice in vivo. Moreover, nephrotoxicity caused by mPEG2K-PME was significantly reduced compared to free PME. mPEG2K-PME is promising in development of new preparations with high efficiency and low toxicity.

Primary seminal vesicle adenocarcinoma is a rare malignant tumor of reproductive system. A 21-year-old patient with primary seminal vesicle adenocarcinoma was treated in our hospital in August 2014. Without surgical treatment, the patient survived for 4.5 years after 6 cycles of chemotherapy and pelvic radiotherapy. Local recurrence was found in February 2019 and laparoscopic radical prostatectomy was performed. There was no local recurrence and metastasis after follow-up for 10 months.

Objective:To analyze the correlation between R. E.N.A.L., PADUA, C-index, DAP scoring system and the efficacy and safety of nephron-sparing surgery (NSS) for T 1b renal tumors, and to construct a nomogram model to predict the efficacy and safety of surgery by combining multiple parameters. Methods:The data of 80 patients with stage T 1b renal tumor who received NSS from March 2020 to July 2021 in Changhai Hospital of Naval Military Medical University were retrospectively analyzed. There were 59 males and 21 females, aged (56.9±10.2) years old. The tumor diameter was (4.7±0.9) cm, with 40 cases on the left and 40 on the right sides. Tumors were located in the upper/lower pole in 46 cases and in the middle in 34 cases. The tumors were located in 59 cases laterally, 21 cases medially, and 74 cases were bulging, 16 cases endogenous. There were 53 round tumors, 18 lobular tumors, and 9 irregular tumors. One case underwent open surgery, 43 cases underwent laparoscopic surgery, and 36 cases underwent robotic surgery.42 cases underwent transperitoneal approach, and 38 cases underwent retroperitoneal approach. The composite outcome (MIC) achieved by all three indicators, including negative surgical margins, warm ischemia time <20 min, and no serious complications, was used as the main indicator to evaluate the efficacy and safety of surgery. Secondary indicators were operation time, intraoperative blood loss, postoperative hospital stay, postoperative creatinine changes and hemoglobin changes. Relevant risk factors were analyzed by logistic regression, and a nomogram model for predicting surgical efficacy and safety was constructed. Receiver operating characteristic(ROC) curves were used to compare the predictive power of the nomogram model with other scoring systems. Results:Univariate logistic regression analysis showed that PADUA and R. E.N.A.L. scores were risk factors for MIC achievement( OR=1.419, P=0.038; OR=1.358, P=0.038). However, C-index and DAP were not risk factors for MIC achievement( P>0.05). The results of correlation analysis showed that R. E.N.A.L. score was significantly correlated with postoperative hemoglobin decrease(R 2=0.197). PADUA score was significantly correlated with postoperative hospital stay(R 2=0.186). C-index was significantly correlated with postoperative creatinine increase(R 2=-0.221). DAP was significantly associated with operation time (R 2=0.192). The results of univariate logistic regression analysis showed that body mass index ( OR=1.257, P=0.025), tumor morphology ( OR=18.741, P=0.005), longitudinal location of tumor ( OR=1.992, P=0.038), the relationship between tumor and collection system ( OR=4.886, P=0.002) were risk factors for MIC attainment. A nomogram prediction model was constructed by combining these indicators with the Mayo adhesive probability (MAP) index. The ROC curve showed that the area under the curve (AUC) of the nomogram model and R. E.N.A.L. score, PADUA score, C-index, and DAP were 0.834, 0.645, 0.643, 0.526, and 0.593, respectively. The nomogram model had the highest predictive power for T 1b renal tumors achieving MIC. Conclusions:In the renal tumor scoring system, PADUA and R. E.N.A.L. scores can predict whether the MIC of T 1b renal tumor NSS is achieved or not. The nomogram model composed of patient body mass index, tumor shape, longitudinal position of tumor, relationship between tumor and collecting system and MAP can better predict whether the MIC of T 1b renal tumor NSS is achieved or not.

Objective:To investigate the clinical features of patients with local recurrence and secondary operation after partial nephrectomy for renal cancer.Methods:The clinical data of 14 patients who underwent secondary operation for local recurrence of renal cancer after partial nephrectomy in the First Affiliated Hospital and the Second Affiliated Hospital of Naval Medical University from January 2000 to January 2022 were retrospectively analyzed. There were 12 males and 2 females. Nine patients had a body mass index ≥24 kg/m 2. At first diagnosis of renal cancer, nine patients’ R. E.N.A.L. score of renal mass were at least 7. Partial nephrectomy was performed in the first operation of each patient, including 4 cases of open surgery, 6 cases of laparoscopic surgery, and 4 cases of robot-assisted laparoscopic surgery. The pathological stage of nine patients was pT 1aN 0M 0 and that of five patients was pT 1bN 0M 0. Twelve cases were clear cell carcinoma, 1 case was sarcomatoid carcinoma and 1 case was chromophobe cell carcinoma. The mean time from the first operation to local recurrence was (29.3±16.8) months. All recurrence lesions were found by abdominal CT or MRI. Thirteen patients had no clinical symptom at the time of tumor recurrence. The location of recurrence was clear. No sign of invasion of peripheral organs and tissues was observed. There was no other suspicious lesion. The tumor was considered to be completely resectable in all patients. All 14 cases underwent secondary operation. Ten patients underwent radical nephrectomy [tumor size was (2.8±0.9) cm]. Partial nephrectomy was performed in 4 cases [tumor size was (1.8±0.9) cm]after full evaluation by surgeons, including 2 cases of anatomic solitary kidney, and 2 cases of recurrent tumor less than 2 cm with clear tumor margin. Results:Eleven of the 14 cases underwent minimally invasive surgery, and no cases were converted to open surgery. The other 3 cases underwent open surgery. Seven patients had severe adhesions in the operation area. The blood loss in the partial nephrectomy group and the radical nephrectomy group was (100.0±70.7) ml and (143.0±81.2) ml, respectively. According to the Clavien-Dindo classification of surgical complications, Grade Ⅰ and Grade Ⅱ complication occurred in 1 patient respectively, and no patient had Grade Ⅲ or above complication. No tumor cell was found at the surgical margin. The pathological type and nuclear grade were the same as those in the first operation. There were 10 cases of pT 1aN 0M 0 stage, 3 cases of pT 3aN 0M 0 stage and 1 case of pT 3aN 1M 0stage. The follow-up time of 13 patients with complete follow-up data was (21.4±14.9) months after local recurrence resection. The tumor recurred in 3 patients and metastasized in 2 patients. The disease-free survival time of the above 5 patients was (13.2±8.8) months. Of the 4 patients who underwent partial nephrectomy, 3 had recurrence or metastasis. Among the 9 patients who underwent radical nephrectomy, 2 had postoperative recurrence or metastasis, and 7 patients survived without tumor until the last follow-up. Conclusions:For patients with local recurrence after partial nephrectomy who are in good condition and the recurrent lesions can be completely resected, the second operation is safe, feasible and effective. Patients with secondary radical nephrectomy have better prognosis. If the patient has a solitary kidney, the recurrent tumor is small and the margin is clear, partial nephrectomy can also be selected for the second operation. But the postoperative follow-up should be emphasized, and the adjuvant drug therapy should be given if necessary.