1.Research progress on the application of membrane biomimetic nanocarriers in targeted therapy of lung diseases
Wen-jing BAI ; Rong GUO ; Lin XIONG ; Leng-jing ZHU ; Jia-xin LI ; Ya-shi WANG ; Man LI ; Qin HE
Acta Pharmaceutica Sinica 2024;59(10):2730-2740
Pulmonary disease is one of the major threats to human health. However, the current clinical treatment drugs for lung diseases generally have problems such as low lung delivery efficiency, fast clearance rate and obvious toxic side effects. Recently, membrane biomimetic nanocarriers have attracted more and more attention. Due to their advantages of high targeting, long cycle time, good biocompatibility and strong immune escape ability, membrane biomimetic nanocarriers have become a major research hotspot in targeted therapy of lung diseases. In this review, we discuss the main preparation methods of membrane biomimetic nanoparticles, the characteristics of membrane biomimetic nanocarriers from different cell sources and their application in the targeted therapy of lung diseases. At the same time, according to the characteristics of different membranes, the shortcomings, current technical limitations and future prospects are discussed. This review is expected to provide references for the design of membrane biomimetic nanocarriers and their potential applications in the treatment of lung diseases.
2.Value of SHOX2 and RASSF1A Gene Methylation in Alveolar Lavage Fluid in Patients with Pulmonary Nodules or Masses in the Diagnosis of Lung Cancer
Dongping ZHU ; Haifeng LI ; Junfei FENG ; Qiuheng TANG ; Jing LENG
Journal of Kunming Medical University 2024;45(3):106-111
Objective The diagnostic efficacy of the two gene methylation indexes was verified by lung biopsy or postoperative disease examination results.Methods A prospective study was conducted to collect 99 patients diagnosed with pulmonary nodules and masses in the Third People's Hospital of Yunnan Province from March 2019 to March 2020.After bronchoscopy and BALF samples were collected,regular follow-up,lung puncture biopsy and post-operative disease examination were performed.Results Ninety-nine patients with pulmonary nodules and masses were divided into lung cancer group(n = 50)and benign lung disease group(n = 49)after pathological diagnosis.The age of patients in the lung cancer group was(62.64±9.71)years,and that of the benign lung disease group was(60.48±13.69)years,and there was a statistical difference between the two groups(P = 0.032).In the diagnosis of lung cancer,the sensitivity and specificity of SHOX2 and RASSF1A genes alone were found to be 72%and 58%,respectively,and 92.3%and 95.9%,respectively.The combined test of the two genes showed a higher sensitivity in the diagnosis of lung cancer,0.84,compared to 0.102 in the benign disease group(P<0.001).ROC curve analysis showed that the sensitivity of the two genes could be increased to 84%when methylation was combined.Conclusion The methylation test of SHOX2 and RASS1A gene in alveolar lavage fluid has a good value in the diagnosis of lung cancer patients with pulmonary nodules and masses and SHOX2 combined with RASSF1A can be an important supplementary tool for early diagnosis of lung cancer when imaging and histological diagnosis are unclear.
3.P450-mediated dehydrotyrosine formation during WS9326 biosynthesis proceeds via dehydrogenation of a specific acylated dipeptide substrate.
Songya ZHANG ; Lin ZHANG ; Anja GREULE ; Julien TAILHADES ; Edward MARSCHALL ; Panward PRASONGPHOLCHAI ; Daniel J LENG ; Jingfan ZHANG ; Jing ZHU ; Joe A KACZMARSKI ; Ralf B SCHITTENHELM ; Oliver EINSLE ; Colin J JACKSON ; Fabrizio ALBERTI ; Andreas BECHTHOLD ; Youming ZHANG ; Manuela TOSIN ; Tong SI ; Max J CRYLE
Acta Pharmaceutica Sinica B 2023;13(8):3561-3574
WS9326A is a peptide antibiotic containing a highly unusual N-methyl-E-2-3-dehydrotyrosine (NMet-Dht) residue that is incorporated during peptide assembly on a non-ribosomal peptide synthetase (NRPS). The cytochrome P450 encoded by sas16 (P450Sas) has been shown to be essential for the formation of the alkene moiety in NMet-Dht, but the timing and mechanism of the P450Sas-mediated α,β-dehydrogenation of Dht remained unclear. Here, we show that the substrate of P450Sas is the NRPS-associated peptidyl carrier protein (PCP)-bound dipeptide intermediate (Z)-2-pent-1'-enyl-cinnamoyl-Thr-N-Me-Tyr. We demonstrate that P450Sas-mediated incorporation of the double bond follows N-methylation of the Tyr by the N-methyl transferase domain found within the NRPS, and further that P450Sas appears to be specific for substrates containing the (Z)-2-pent-1'-enyl-cinnamoyl group. A crystal structure of P450Sas reveals differences between P450Sas and other P450s involved in the modification of NRPS-associated substrates, including the substitution of the canonical active site alcohol residue with a phenylalanine (F250), which in turn is critical to P450Sas activity and WS9326A biosynthesis. Together, our results suggest that P450Sas catalyses the direct dehydrogenation of the NRPS-bound dipeptide substrate, thus expanding the repertoire of P450 enzymes that can be used to produce biologically active peptides.
4.Efficacy and safety of enhanced recovery after surgery in the perioperative period of pancreaticoduodenectomy: A systematic review and Meta-analysis
Lin ZHU ; Xiaoli YANG ; Li LIU ; Lanting XU ; Yuanhong LENG ; Jing CHEN
Journal of Clinical Hepatology 2022;38(6):1356-1363
Objective To investigate the efficacy and safety of enhanced recovery after surgery (ERAS) in the perioperative period of pancreaticoduodenectomy (PD). Methods Chinese and English databases were searched for controlled clinical trials on the application of ERAS in PD published from 2000 to 2021. Screening, quality assessment, and data extraction were performed for the articles, and RevMan5.3 software was used for meta-analysis. This study was registered on PROSPERO with a registration number of CRD42021287931. Results A total of 22 controlled clinical trials were included, with 3531 patients in total. The results showed that the implementation of ERAS in the perioperative period of PD reduced the incidence rates of total complications (odds ratio [ OR ]=0.63, 95% confidence interval [ CI ]: 0.48-0.83, P =0.001), abdominal infection ( OR =0.65, 95% CI : 0.47-0.88, P =0.005), pulmonary complications ( OR =0.57, 95% CI : 0.42-0.78, P =0.000 5), pancreatic leakage ( OR =0.80, 95% CI : 0.67-0.97, P =0.02), and delayed gastric emptying ( OR =0.58, 95% CI : 0.48-0.71, P < 0.001) and effectively shortened the length of postoperative hospital stay (mean difference=-2.76, 95% CI : -3.36 to -2.16, P < 0.001). However, there were no significant differences between the two groups in mortality rate, incision infection, postoperative bleeding rate, reoperation, and rehospitalization (all P > 0.05). Conclusion ERAS has good efficacy and safety in the perioperative period of PD and can significantly reduce the incidence rates of postoperative complications and shorten the length of postoperative hospital stay. Therefore, it holds promise for clinical application.
5.Pathogenetic gene changes of eutopic endometrium in patients with ovarian endometriosis.
Ling LI ; Qian CHEN ; Qing-Bo FAN ; Shu WANG ; Hong-Hui SHI ; Lan ZHU ; Da-Wei SUN ; Jin-Hua LENG ; Jing-He LANG
Chinese Medical Journal 2019;132(9):1107-1109
Antigens, Neoplasm
;
genetics
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Apoprotein(a)
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genetics
;
Carrier Proteins
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genetics
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Endometriosis
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metabolism
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pathology
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Endometrium
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metabolism
;
pathology
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Female
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Humans
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Intracellular Signaling Peptides and Proteins
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genetics
;
Membrane Proteins
;
genetics
;
Mutation, Missense
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genetics
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Nuclear Proteins
;
genetics
;
Ovarian Neoplasms
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metabolism
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pathology
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Proprotein Convertase 5
;
genetics
;
Salivary Cystatins
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genetics
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Ubiquitin-Protein Ligases
;
genetics
;
Whole Exome Sequencing
6.Clinical Manifestations of Adenomyosis Patients with or without Coexisting Endometriosis.
Yun-Wei LI ; Yu-Ting LIU ; Shu WANG ; Hong-Hui SHI ; Qing-Bo FAN ; Lan ZHU ; Jin-Hua LENG ; Da-Wei SUN ; Jian SUN ; Jing-He LANG
Chinese Medical Journal 2018;131(20):2495-2498
7.Risk Factors for Recurrence of Ovarian Endometriosis in Chinese Patients Aged 45 and Over.
Zheng-Xing HE ; Ting-Ting SUN ; Shu WANG ; Hong-Hui SHI ; Qing-Bo FAN ; Lan ZHU ; Jin-Hua LENG ; Da-Wei SUN ; Jian SUN ; Jing-He LANG
Chinese Medical Journal 2018;131(11):1308-1313
BackgroundWhen considering the issue of recurrence, perimenopausal women may have more dilemma during management comparing with young women, for example, whether to retain the uterus and ovary during surgery, whether it is necessary to add adjuvant medicine treatment after operation, and there is no evidence for reference about using of gonadotropin-releasing hormone agonist. This study aimed to study the risk factors for the recurrence of ovarian endometriosis (EM) in patients aged 45 and over.
MethodsThis is a retrospective nested case-control study. We reviewed the medical records of patients aged over 45 years who underwent surgical treatments for ovarian EM from 1994 to 2014, in Peking Union Medical College Hospital of Chinese Academy of Medical Sciences. By following up to January 2016, 45 patients were found to have relapses and regarded as the recurrence group. The patients with no recurrence during the same follow-up period were randomly selected by the ratio of 1:4 as the nonrecurrence group (180 patients in total). Stratified Cox regression was used to analyze the risk factors of the recurrence.
ResultsUnivariate analysis showed that there was a significant difference in the postoperative treatment (the percentage of patients who received postoperative treatment in non-recurrence group and recurrence group, 23.9% vs. 40.0%, χ = 4.729, P = 0.030) and ovarian preservation (the percentage of patients who received surgery of ovarian preservation in non-recurrence group and recurrence group, 25.0 % vs. 44.4%, χ = 19.462, P < 0.001) between the nonrecurrence group and the recurrence group. There was no correlation between recurrence and the following factors including patient's age, menarche age, gravidity, parity, CA125 level, ovarian lesions, menopausal status, combined benign gynecological conditions (such as myoma and adenomyoma) and endometrial abnormalities, and surgical approach or surgical staging (all P > 0.05). Multivariate analysis indicated that whether to retain the ovary was the only independent risk factor of recurrence for patients aged 45 years and over with ovarian EM (odds ratio: 5.594, 95% confidence interval: 1.919-16.310, P = 0.002).
ConclusionOvarian preservation might be the only independent risk factor of recurrence for patients aged 45 years and over with ovarian EM.
Case-Control Studies ; Endometriosis ; epidemiology ; etiology ; Female ; Humans ; Male ; Middle Aged ; Neoplasm Recurrence, Local ; Odds Ratio ; Ovarian Neoplasms ; epidemiology ; etiology ; Ovary ; pathology ; Proportional Hazards Models ; Retrospective Studies ; Risk Factors
8.Expression of C3aR and C5aR in trichloroethylene-sensitized mouse liver.
Feng WANG ; Jing LENG ; Wansheng ZHA ; Shulong LI ; Hui WANG ; Tong SHEN ; Qixing ZHU
Chinese Journal of Industrial Hygiene and Occupational Diseases 2015;33(3):171-174
OBJECTIVETo study the expression of C3aR and C5aR in trichloroethylene-sensitized mouse liver injury and discuss the pathogenesis of Dermatitis Medicamentosa-like of TCE (DMLT).
METHODS6∼8 w female BALB/c mouse were randomly divided into blank control group, solvent control group and TCE treatment group. TCE was given to the mouse for sensitization at 1th, 4th, 7th, 10th day and challenge at 17th day and 19th day. Before killing mouse, liver weight and body weight were recorded. The livers were separated at 24 h, 48 h, 72 h and 7 d after challenge. And the liver sections were used for immunofluorescence stain and RT-PCR to detect the expression levels of C3aR and C5aR.
RESULTSMicroscopic examination showed no significant change in liver structure or organization in TCE non-sensitized group, while liver cell oedema, cell necrosis and inflammatory cell infiltration were clearly observed in TCE-sensitized groups. The expression levels of C3aR and C5aR in 24 h, 48 h, 72 h and 7 d TCE-sensitized groups were significant higher than blank control group, solvent control group and related TCE non-sensitized groups (P < 0.05).
CONCLUSIONComplement activation was involved in TCE-induced liver injury and C3aR and C5aR might play essential role in the process.
Animals ; Chemical and Drug Induced Liver Injury ; Dermatitis, Occupational ; Edema ; Female ; Liver ; physiopathology ; Mice ; Mice, Inbred BALB C ; Receptor, Anaphylatoxin C5a ; metabolism ; Receptors, Complement ; metabolism ; Solvents ; toxicity ; Trichloroethylene ; toxicity
9.Clinical Characteristics of 30 Cases of Laparoscopic Surgery for Ovarian Cysts in Second Trimester
Ping PENG ; Lan ZHU ; Jing-He LANG ; Zhu-Feng LIU ; Da-Wei SUN ; Jin-Hua LENG
Medical Journal of Peking Union Medical College Hospital 2015;(3):202-205
Objective To investigate the characteristics of laparoscopic surgery for ovarian cysts in second trimester .Methods Between April 2002 and December 2013 , 30 patients were treated with laparoscopic surgery for clinically suspected ovarian cyst in second trimester at Department of Obstetrics and Gynecology , Peking Union Medical College Hospital .Clinical data of these patients were reviewed for identification of clinical charac -teristics, and assessment of feasibility and indications of the surgery .Results Of the 30 patients, the mean age was (28.5 ±3.1) years, gestational age was (14.7 ±2.5) weeks, mean operation time was (50 ±20) mi-nutes, and mean length of hospital stay was (4.5 ±0.8 ) days.Between the patients with gestational age ≥16 weeks (11/30, 36.7%) and those with gestational age <16 week (19/30, 63.3%), no difference was noted in operation time (P>0.05).In the 30 patients, only 5 (16.7%) patients had known about the ovarian masses before pregnancy .The mean diameter of the masses was ( 9.0 ±5.4 ) cm.In the 12 patients ( 40%) who had masses with diameter ≥9 cm, the operation time was significantly longer than that in the 18 patients (60%) who had masses <9 cm ( P <0.05 ) .Five patients ( 16.7%) received emergency surgery , including 2 cases (6.7%) receiving simple salpingo-oophorectomy for ovarian necrosis due to adnexal torsion .In the other 28 pa-tients (93.3%) , the ovary cysts were removed .Postoperative pathological examination showed teratoma in 18 cases (60%), serous cyst in 6 cases (20%), corpus luteum cyst in 3 cases (10%), mucinous cystadenoma in 2 cases (6.7%), and foam fibroma in 1 case (3.3%).One patient (3.3%) experienced postoperative con-tractions , which were cured by magnesium sulfate and progestin .No severe complications occurred .Twenty-six (86.7%) patients delivered healthy full-term infants, and the other 4 (13.3%) cases lost to follow-up.Con-clusions Laparoscopic surgery is a safe and feasible procedure for the treatment of ovarian cysts in second tri -mester of pregnancy .For adnexal masses persistent or suspicious for torsion , surgical management is warranted . Close maternal and fetal monitoring is essential during and after the operation .
10.Levels of complement components C3a and C5a in renal injury among trichloroethylene-sensitized BALB/c mice.
Wansheng ZHA ; Jing LENG ; Feng WANG ; Jiaxiang ZHANG ; Shulong LI ; Hui WANG ; Tong SHEN ; Qixing ZHU
Chinese Journal of Industrial Hygiene and Occupational Diseases 2014;32(5):335-339
OBJECTIVETo determine the levels of complement components C3a and C5a in the kidneys of trichloroethylene (TCE)-sensitized BALB/c mice, and to investigate the role of complement components in TCE-induced renal injury among BALB/c mice.
METHODSSixty-two female BALB/c mice were randomly divided into blank control group, vehicle control group, and TCE sensitization group. The mice in TCE sensitization group were sensitized by one intracutaneous injection and one abdominal smear of TCE. At 24 h, 48 h, 72 h, and 7 d after the second sensitization, mice were sacrificed, and the blood and kidneys were collected. An automatic biochemical analyzer was used in the determination of serum blood urea nitrogen (BUN) and creatinine (Cr). The levels of C3a and C5a in the kidneys were determined by immunohistochemistry.
RESULTSThe sensitization rate of TCE sensitization group was 42.0%. Kidney coefficient and serum levels of BUN and Cr were significantly increased in the TCE sensitization group as compared with the vehicle control group at 48 h and 72 h after sensitization (P < 0.05). The kidney coefficients of the TCE sensitization group at 48 h and 72 h were significantly higher than those of the control groups (P < 0.05). In comparison with the vehicle control group, however, no significant change was found in kidney coefficient, serum BUN, or serum Cr at 7 d after TCE sensitization (P > 0.05). Levels of C3a and C5a at 48 h (3.80±0.84 and 4.00±1.00, respectively) and 72 h (4.40 ± 1.14 and 4.40 ± 1.14, respectively) after sensitization were all significantly higher than those of the vehicle control group (P < 0.05), but no significant difference was found in level of C3a (1.80±0.45) or C5a (2.00 ± 0.71) at 7 d (P > 0.05).
CONCLUSIONTCE sensitization can induce renal injury in mice. Levels of complement components C3a and C5a are elevated in the kidneys of sensitized mice, indicating that C3a and C5a may be involved in the renal injury induced by TCE sensitization.
Animals ; Blood Urea Nitrogen ; Complement C3a ; metabolism ; Complement C5a ; metabolism ; Creatinine ; blood ; Female ; Kidney ; metabolism ; pathology ; Mice ; Mice, Inbred BALB C ; Trichloroethylene ; toxicity

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