1.Pulmonary endothelium-targeted nanoassembly of indomethacin and superoxide dismutase relieves lung inflammation.
Yi YANG ; Makhloufi ZOULIKHA ; Qingqing XIAO ; Feifei HUANG ; Qi JIANG ; Xiaotong LI ; Zhenfeng WU ; Wei HE
Acta Pharmaceutica Sinica B 2023;13(11):4607-4620
Lung inflammation is an essential inducer of various diseases and is closely related to pulmonary-endothelium dysfunction. Herein, we propose a pulmonary endothelium-targeted codelivery system of anti-inflammatory indomethacin (IND) and antioxidant superoxide dismutase (SOD) by assembling the biopharmaceutical SOD onto the "vector" of rod-like pure IND crystals, followed by coating with anti-ICAM-1 antibody (Ab) for targeting endothelial cells. The codelivery system has a 237 nm diameter in length and extremely high drug loading of 39% IND and 2.3% SOD. Pharmacokinetics and biodistribution studies demonstrate the extended blood circulation and the strong pulmonary accumulation of the system after intravenous injection in the lipopolysaccharide (LPS)-induced inflammatory murine model. Particularly, the system allows a robust capacity to target pulmonary endothelium mostly due to the rod-shape and Ab coating effect. In vitro, the preparation shows the synergistic anti-inflammatory and antioxidant effects in LPS-activated endothelial cells. In vivo, the preparation exhibits superior pharmacodynamic efficacy revealed by significantly downregulating the inflammatory/oxidative stress markers, such as TNF-α, IL-6, COX-2, and reactive oxygen species (ROS), in the lungs. In conclusion, the codelivery system based on rod-like pure crystals could well target the pulmonary endothelium and effectively alleviate lung inflammation. The study offers a promising approach to combat pulmonary endothelium-associated diseases.
2.Long-read sequencing revealed alterations of microbial relationship between tongue coating and gastric mucosa in patients with gastric intestinal metaplasia
WU Jianping ; LI Meifeng ; HUA Zhaolai ; LU Bin ; XIANG Jiao ; WU Zhenfeng ; ZHANG Junfeng
Digital Chinese Medicine 2023;6(4):438-450
Objective:
To explore the microbial correlation between oral tongue coating (TC) and gastric mucosa (GM) in patients with gastric intestinal metaplasia (GIM).
Methods:
The present study recruited 1360 volunteers for upper gastrointestinal cancer screening. The microbiota in TC and GM were profiled by long-read sequencing of full-length 16S rRNA gene. The microbial diversity, community structure, and linear discriminant analysis effect size (LEfSe) were analyzed by the software Visual Genomics. SparCC correlation analysis was used to construct the commensal network and the graphical display was conducted by R software.
Results:
The population included 44 patients with precancerous GIM, and 28 matched controls with negative rapid urease test (RUT) and non-symptomatic chronic superficial gastritis (CSG). No significant difference in diversity was observed between GIM patients and controls in TC or GM microbiota (P > 0.05). Patients had a higher percentage of 41 – 60 co-occurring operational taxonomic units (OTUs) between TC and GM than controls (34.1% vs. 25.0%) (P < 0.05). The LEfSe showed that TC Prevotella melaninogenica and three gastric Helicobacter species (i.e., Helicobacter pylori, Helicobacter pylori XZ274, and Helicobacter pylori 83) were enriched in patients with GIM. Furthermore, GIM patients with positive RUT had a lower percentage of co-occurring OTUs over 20 (P < 0.05), and lower abundances of gastric Veillonella, Pseudonocardia, and Mesorhizobium than those with negative RUT (P < 0.05). The commensal network between TC and GM was more complex in GIM patients than in controls. GIM patients with positive RUT demonstrated more bacterial correlations between TC and GM than those with negative RUT. Finally, the serum ratio of PG-I/II was negatively correlated with three gastric Helicobacter species (Helicobacter pylori, Helicobacter pylori XZ274, and Helicobacter pylori 83) in patients with negative RUT (P < 0.05), and negatively correlated with two TC species (Fusobacterium nucleatum subsp. nucleatum and Campylobacter showae) in patients with positive RUT (P < 0.05).
Conclusion
The development of GIM potentiated the commensal network between oral TC and GM, providing microbial evidence of the correlation between TC and the stomach.
3.Propensity score matching method evaluate the clinical efficacy of comprehensive treatment for synchronous pri-mary advanced gastric and esophageal cancer
Peichan ZHANG ; Chunyang LUO ; Wenya WU ; Zhenfeng WU ; Qinhong CAO ; Che CHEN ; Xiaoyu WU ; Xuequan YAO ; Fukun LIU
Journal of Surgery Concepts & Practice 2023;28(6):551-555
Objective To evaluate the clinical efficacy of comprehensive treatment for synchronous primary advanced gastric and esophageal cancer by propensity score matching(PSM).Methods A total of 2 551 patients with advanced gastric cancer admitted to Jiangsu Province Hospital of Chinese Medicine from January 2013 to December 2022 were retrospectively analyzed.Among them,45 patients with synchronous primary esophageal cancer were distributed to the observation group,and 2 506 patients without esophageal cancer were distributed to the control group.Through the PSM method,the control group was matched with the observation group and the equilibrium samples of covariates between two groups were obtained.The overall survival(OS)between the two groups were compared.Results Both observation and control group contained 45 patients in this study.According to the treatment regimen,the patients in the observation group was divided into radical resection treatment subgroup(n=22)and chemoradiotherapy(CRT)subgroup(n=23).In the radical resection subgroup,4 patients underwent the simultaneous surgical resection of gastric and esophageal tumors through proximal gastrectomy with the Ivor Lewis operation.Eighteen patients underwent endoscopic submucosal dissection(ESD)of their esophageal tumors and gastric cancer radical resection.Radical resection of gastric cancer combined with preoperative chemoradiotherapy of esophageal cancer was performed in the CRT subgroup.Survival analysis showed that OS in the observation group was significantly shorter than that in the control group(P=0.042)and there was no significant difference in OS between the radical resection subgroup and the control group(P=0.799).The 1-,3-,and 5-year survival rates of the patients in the CRT subgroup were significantly lower than those of the control group(P=0.003).While the 1-,3-,and 5-year survival rates of the patients in the radical resection subgroup were not statistically significant,compared to those of the CRT subgroup(P=0.071).Conclusions Multidisciplinary and comprehensive treatment can significantly improve the prognosis of patients with synchronous primary advanced gastric and esophageal cancer.Radical resection of gastric cancer combined with ESD of esophageal cancer is an optional treatment for patients with gastric cancer complicated with early esophageal cancer.Radical resection of gastric cancer combined with CRT of esophageal cancer can improve the prognosis of patients with advanced gastric cancer complicated with unresectable esophageal cancer.
4.Clinicopathological and molecular features of biphenotypic sinonasal sarcoma
Nan WU ; Xuan WANG ; Kai CHENG ; Xue WEI ; Rusong ZHANG ; Zhenfeng LU ; Qiu RAO
Chinese Journal of Pathology 2020;49(12):1261-1266
Objective:To study the clinicopathologic features, immunophenotype, molecular genetics and differential diagnosis of biphenotypic sinonasal sarcoma (BSNS), and to evaluate the role of PAX3 and PAX8 immunohistochemical (IHC) antibodies in the diagnosis of BSNS.Methods:Nasal sinus spindle cell tumors surgically treated at the Jinling Hospital from 2000 to 2019 were collected, including three cases of BSNS, 10 cases of acinar rhabdomyosarcoma, eight cases of schwannoma, five cases of hemangiopericytoma, three cases of fibrosarcoma, and one case of triton tumor. The cases were evaluated by histology, IHC by EnVision for PAX3 and PAX 8 (including PAX8 murine monoclonal antibody, clone number OTI6H8, hereinafter referred to as PAX8-OTI6H8 antibody; PAX8 rabbit monoclonal antibody, clone number EP298, hereinafter referred to as PAX8-EP298 antibody) molecular genetic tests.Results:All three BSNS patients were elderly women with clinical manifestations of nasal congestion and bleeding. Imaging showed a soft tissue density shadow of the nasal cavity and sinuses with bone destruction. The boundaries of tumors which were covered with ciliated columnar epithelium were unclear, and mucosal invasion and squamous metaplasia could be seen. Tumor cells were spindle-shaped, arranged in a bundle-like, braided arrangement, with little cellular atypia and occasional atypical mitotic figures. The tumoral interstitial vessels were mostly thin-walled, some showing staghorn-like changes. There was focal striated muscle differentiation in two cases, and bone invasion was seen in two cases. IHC staining showed that all three cases of BSNS expressed PAX3 and PAX8-OTI6H8, but not PAX8-EP298. All eight cases of schwannoma, five cases of hemangiopericytoma, and one case of triton tumor did not express PAX3, PAX8-OTI6H8 or PAX8-EP298. Eight of the ten cases of alveolar rhabdomyosarcoma expressed PAX3 and PAX8-OTI6H8, but not PAX8-EP298. Three cases of fibrosarcoma showed weak PAX3 and PAX8-OTI6H8 expression, but there was no PAX8-EP298 expression. FISH detection showed that PAX3 break apart in the tumor cells from all three patients (four specimens).Conclusions:BSNS is a distinct sinonasal low grade malignancy with dual differentiation which could be readily confused with a variety of spindle cell tumors encountered in the sinonasal cavity. The molecular genetics of PAX3 gene break is the gold standard for diagnosis of this tumor. IHC marker monoclonal PAX3 is 100% expressed in BSNS, while the specificity is limited. PAX8-OTI6H8 is also expressed in BSNS due to the cross reaction with PAX3 antibody, while PAX8-EP298 is all negative for these tumors.
5. Solitary fibrous tumor/hemangiopericytoma of central nervous system: a clinicopathological analysis of 60 cases
Yu GUAN ; Xuan WANG ; Nan WU ; Zhenfeng LU ; Qunli SHI ; Jinrong WU
Chinese Journal of Pathology 2019;48(1):31-36
Objective:
To investigate the clinical manifestations, imaging features, clinicopathologic features, and differential diagnosis of solitary fibrous tumors/anginoblastomas (SFT/HPCs) originating in the central nervous system.
Methods:
Sixty cases of SFT/HPCs originating in the central nervous system were collected at Nanjing Jinling Hospital, from January 1, 2008 to December 31, 2016. The clinical data, imaging data, histomorphologic changes and immunohistochemical finding were analyzed in the sixty cases.
Results:
The 60 cases included 26 males and 34 females, aged 14 to 85 (median 49) years. The main clinical manifestations were headache, dizziness with nausea and vomiting. Radiologically, the tumors were large, enhancing, solid and cystic masses attached to the dura. Histopathologically, the neoplasms were composed of spindle cells with oval nuclei, inconspicuous nucleoli and moderate amount of eosinophilic cytoplasm arranged in fascicles with areas of hyalinized stroma, myxoid changes and a staghorn vascular pattern. Immunohistochemically, tumor cells of all cases were positive for vimentin (100.0%, 60/60), STAT6 (98.3%, 59/60), CD34 (61.7%, 37/60), and the tumor cells were typically positive for CD99, bcl-2, EMA and SSTR2 as well.Negative for S-100 protein, SOX10, E-cadherin, GFAP. Ki-67 index ranged from 1% to 50%. Forty cases were followed up for 6 to 82 months with average of 40 months, 30 patients were alive and 10 patients died.
Conclusions
Central nervous system SFT/HPCs can be aggressive and relapses may occur several years after diagnosis. STAT6 is highly sensitive and specific for the diagnosis. Complete tumor resection is optional treatment followed by radiotherapy and chemotherapy. There is a correlation between the prognosis and the location of the disease, the histological grade, Ki-67 index, and fusion gene variants.
6. Experimental study of 99Tcm-3PRGD2 imaging on the angiogenesis of rheumatoid arthritis
Yu WU ; Guojian ZHANG ; Xuemei WANG ; Xin′ai WU ; Zhenfeng ZHAO ; Kaixiu ZHANG ; Ridong JIA
Chinese Journal of Nuclear Medicine and Molecular Imaging 2018;38(8):549-553
Objective:
To observe the uptake of 99Tcm-3 polyethylene glycol Arg-Gly-Asp dimer (3PRGD2) in rat models of rheumatoid arthritis (RA), in order to provide theoretical foundation for early diagnosis of RA.
Methods:
The healthy female SD rats were divided into collagen induced arthritis (CIA) group (
7.Ultrasonography in examining the position of gastric tube in patients undergoing gastrectomy
Zhenfeng ZHOU ; Long CHEN ; Da YU ; Lijun HUANG ; Meng WU ; Shuangfei HU
Chinese Journal of General Practitioners 2018;17(5):388-391
Thirty patients with gastric cancer,ASA Ⅱ or Ⅲ,scheduled for selective radical gastrectomy under tracheal intubation general anesthesia in Zhejiang Provincial People's Hospital from November 2016 to February 2017 were enrolled in the study.The gastric tubes were placed by a nurse before operation.The position of gastric tube was judged under gastric ultrasonography by a sonographer and anesthesiologist respectively;and confirmed by the surgeon during the operation.With the position judged by the surgeon as gold standard,the sensitivity,specificity,positive predictive value,negative predictive value of the judgment of ultrasonographer were 96%,80%,96%,50%,respectively with the Kappa value 0.760 of (P <0.001),those of the judgment of anesthesiologist were 92%,40%,92% and 60%,respectively with a Kappa value of 0.280 (P =0.125);those of the judgment of nurse were 92%,0%,100% and 71.4%,with a Kappa value of-0.105 (P =0.513).The results suggest that ultrasound examination is a simple,reliable and sensitive method for confirming correct gastric tube placement.
8.Effect of moxibustion on tumor necrosis factor-α and nuclear transcription factor kappa B in ankle joints of rats with rheumatoid arthritis
Hui ZHANG ; Xiaopeng MA ; Huangan WU ; Shengbing WU ; Sanshan SU ; Yangchun HU ; Zhenfeng LI ; Li ZHANG ; Mingyue XIE
Journal of Acupuncture and Tuina Science 2017;15(3):171-176
Objective: To observe the effect of moxibustion on the expressions of tumor necrosis factor-α (TNF-α) and nuclear transcription factor kappa B (NF-κB) proteins in ankle joints of rats with rheumatoid arthritis (RA), and to explore the anti-inflammatory mechanism of moxibustion in the treatment of RA.Methods: Adjuvant arthritis (AA) rat models were induced and used as rat models of RA. Rats were randomly divided into a normal group, a model group, a moxibustion group and a saline group. Rats in the normal and model groups were not treated; rats in the moxibustion group accepted treatment by moxibustion at Zusanli (ST 36) and Shenshu (BL 23) after modeling; rats in the saline group were injected with 0.15 mL saline to the bottom of the left hind paw and had no other treatments. Hematoxylin-eosin (HE) staining was used to observe the histopathological changes of rats' ankle joints under light microscope. Immunohistochemistry was used to observe the expressions of TNF-α and NF-κB in ankle joints of rats.Results: Compared with the normal group, the rats' ankle joints in the model group showed disorganization, joint surface defect, and significantly increased mean optical density (MOD) of TNF-α and NF-κB (allP<0.05). After moxibustion treatment, rats in the moxibustion group showed repaired ankle tissues, smooth joint surface without defects, decreased MOD of TNF-α and NF-κB than those in the model group (allP<0.05). Rats in the saline group had no damage to ankle joints, while TNF-α and NF-κB were significantly different from those in the model group (P<0.05).Conclusion: Moxibustion could down-regulate the expressions of NF-κB and TNF-α protein in ankle joints of RA rats, and produce an anti-inflammatory effect to promote tissue repair.
9.A new form of pathology network management system
Zhenfeng LU ; Jun DU ; Chun XIA ; Honglin YIN ; Bo WU ; Qunli SHI ; Xiaojun ZHOU
Journal of Medical Postgraduates 2017;30(4):418-420
Objective In order to play the role of pathological network management system better in pathological examination, this study explore the present status of new pathology network management system, give an objective evaluation for the operation condition, reveal the effectiveness and the existing problems of this system, and provide reference for its development and improvement.Methods The software of pathological network management system was applied to the pathological specimen reception, patient information and examination status query, pathological diagnosis and technology process, as well as the paraffin block archive, statistical analysis, data recording, and so on.At last, we recorded all the information and made a classification and arrangement.Results Pathological network management system was running normally through the whole process of pathologic examination, including specimen receiving, all examinations, print of pathological applications and spontaneous print of pathological reports in ward, which really achieve one-stop services.But the system has unstable phenomenon occasionally.Conclusion Pathological network management system links each examination process closely, which can improve the work efficiency, and provide scientific basis for pathology quality control.
10.Study on the Chemical Consitituents of Different Parts of Mentha haplocalyx in Jiangxi by GC-MS
Siqi WU ; Zhenfeng WU ; Xiaofei ZHANG
China Pharmacy 2016;27(21):2959-2961
OBJECTIVE:To establish a method for analyzing the volatile constituents of different parts(root,stem and leaf)of Mentha haplocalyx. METHODS:HS-GC-MS was performed. GC conditions:the column was HP-5MS capillary quartz column, carrier gas was He (constant current mode),flow rate was 1.0 ml/min,volume injection was 1.0 μl,inlet was split mode with split ratio of 10∶1,temperature was 250 ℃(temperature programmed). MS conditions:ionization source was electron bombard-ment,energy was 1 905 V,temperature was 230 ℃,quadrupole temperature was 150 ℃,and the scanning range was m/z 30-550. RESULTS:Totally 10,14 and 48 volatile components were identified from the root,stem and leaf,which accounted for 90.03%, 92.79% and 95.93% of the capacity of the total essential oil from each part of it. And totally 51 volatile compounds was identified, including 7 kinds that shared the same chemical components that regard the piperitone oxide as the main ingredient. CONCLU-SIONS:The method is simple,stable and reproducible,and can be used for the analysis of volatile components of different parts of M. haplocalyx. The volatile components in different parts are quite different,and most is in the leaf.

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