Acute lung injury (ALI) is a kind of lung disease mainly caused by excessive inflammatory reaction. At present, there is a lack of effective therapeutic drugs in clinic. The aim of this study was to investigate the improvement effect of Panax notoginseng saponins (PNS) on ALI and its potential mechanism. The model of wild-type C57BL/6J mice was established by intratracheal instillation of 50 μL 25 mg·mL^-1 lipopolysaccharide (LPS). 24 h later, 200 and 400 mg·kg^-1 PNS was given intragastric, respectively. 24 h after administration, the improvement effect of PNS on ALI mice was evaluated by lung function, wet-to-dry weight ratio (W/D), total protein, interleukin 6 (IL6) and tumor necrosis factor α (TNFα) concentration of bronchoalveolar lavage fluid (BALF), expression levels of IL6 and TNFα in lung tissues, pathological changes of lung tissues and expression of inflammatory cells in BALF. The protein expression levels of NF-κB and its upstream kinases in Raw264.7 cells and ALI mice lung tissues were further detected to evaluate the potential mechanism of PNS improving ALI mice. The experimental scheme was approved by the Animal Experiment Ethics Committee of Shanghai University of Traditional Chinese Medicine. It was found that 400 mg·kg^-1 PNS could significantly improve the lung function of ALI mice, reduce the contents of W/D, BALF total protein, IL6 and TNFα, neutrophils expression in BALF and the infiltration of inflammatory cells in lung tissue. In Raw264.7 cells and ALI mice lung tissue, PNS significantly reduced the expression of NF-κB, reduced the protein expression and phosphorylation of NF-κB, promoted the expression of IκBα, and inhibited the inflammatory response. This study showed that PNS can improve ALI by inhibiting the activity of NF-κB, inhibiting the release of inflammatory factors and inflammatory cells infiltration, alleviating lung inflammation.

Objective: To examine the clinical feasibility of mixed reality navigation (MRN) technology based on multimodal imaging for the resection of intracranial eloquent lesions. Methods: Fifteen patients with intracranial eloquent lesions admitted to the Department of Neurosurgery, the First Medical Center, People's Liberation Army General Hospital from September 2020 to September 2021 were retrospectively enrolled. There were 7 males and 8 females, aged (50±16) years (range: 16 to 70 years). Postoperative pathological diagnosis included meningioma (n=7), metastatic carcinoma (n=3), cavernous hemangioma, glioma, ependymoma, aneurysmal changes and lymphoma (n=1, respectively). The open-source software was used to perform the three-dimensional visualization of preoperative images, and the self-developed MRN system was used to perform the fusion and interaction of multimodal images, so as to formulate the surgical plan and avoid damaging the eloquent white matter fiber tracts. Traditional navigation, intraoperative ultrasound and fluorescein sodium angiography were used to determine the extent of lesion resection. The intraoperative conditions of MRN-assisted surgery were analyzed, and the setup time and localization error of MRN system were measured. The changes of postoperative neurological function were recorded. Results: MRN based on multimodal imaging was achieved in all patients. The MRN system setup time (M(IQR)) was 36 (12) minutes (range: 20 to 44 minutes), and the localization error was 3.2 (2.0) mm (range: 2.6 to 6.7 mm). The reliability of eloquent white matter fiber tracts localization based on MRN was rated as "excellent" in 11 cases, "medium" in 3 cases, and "poor" in 1 case. There were no perioperative death and no new impairment in motor, language, or visual functions after operation. Transient limb numbness occurred in 1 patient after operation, and recovered to the preoperative state in 2 weeks after operation. Conclusion: The MRN system based on multimodal imaging can improve the surgical accuracy and safety, and reduce the incidence of iatrogenic neurological dysfunction.
Humans ; Augmented Reality ; Reproducibility of Results ; Retrospective Studies ; Multimodal Imaging

Objective: To explore the effect of Feng-liao-chang-wei-kang (FLCWK) on acute and chronic gastroenteritis, synergistic effect on the growth inhibitory effect with 5-fluorouracil (5-FU) on colorectal cancer and its underlying mechanisms. Methods: In the in vitro study, HT-29 cells were divided into 5-FU alone, FLCWK alone and coadministration groups. The MTT assay was used to analyze the proliferation of HT-29 cells at 24 h. Flow cytometry was used to observe the apoptosis, cycle of colorectal cancer HT-29 cells at 24 h. In the in vivo experiment, The subcutaneous transplantation tumor model of colorectal cancer HT-29-Luc was established with nude mice. All mice were randomly divided into 5-FU alone, FLCWK alone and coadministration groups according to body weight. During administration, the Interactive Video Information System small animal live imaging system was used to monitor the growth of subcutaneous transplantation in nude mice. The model of colitis-associated colorectal cancer (CACC) was established with BALB/c mice. BALB/c mice were randomly divided into the normal control group, the model control group, and the FLCWK group. At the end of the administration, the pathological status was detected by HE staining. Cell apoptosis of tumor tissue tumor and colon tissues were observed by TUNEL staining and TUNEL green fluorescence. The protein expression of Caspase 3, p-STAT3, Bcl-2, Bax and P-gp in tumor tissues tumor and colon tissues were tested by using immunohistochemical assay. Results: FLCWK and 5-FU coadministration suppressed HT-29 cell viability and induced S phase arrest and apoptosis compared to treatment with 5-FU alone. Furthermore, compared to treatment with 5-FU alone, coadministration of FLCWK and 5-FU obviously reduced tumor volume and weight and induced apoptosis through decreasing p-STAT3 and P-gp and increasing Caspase 3 protein expression in a murine xenograft tumor model. Moreover, the result revealed decreased number and size of tumors following FLCWK protective administration, downregulated p-STAT3 and Bcl-2 levels and upregulated Bax and Caspase 3 expression in mice with CACC. Conclusions: FLCWK has synergistic effects with 5-FU on colorectal cancer by suppressing the STAT3 pathway and downregulating P-gp expression. Furthermore, FLCWK administration suppresses CACC tumorigenesis by inhibiting the STAT3 pathway.

This study aims to prepare lipid bilayer-coated calcium phosphate core-shell nanoparticles (LCAPNs), which can dissolve in an acidic environment to improve the tumor cell toxicity of antitumor drug. Paclitaxel (PTX) loaded lipid coated calcium phosphate nanoparticles (PTX-LCAPNs) were prepared by thin-film dispersion method. The morphology, particle size and in vitro release behavior were characterized. Meanwhile, the intracellular uptake, intracellular dissolution, cell toxicity of PTX-LCAPNs and intracellular accumulation of PTX were evaluated in human HCC cell line (Huh-7). The results suggested that the mean diameter of the spherical LCAPNs was 124.73±6.41 nm. The PTX-LCAPNs demonstrated little drug leakage in simulated normal physiological conditions, while a rapid release was observed in simulated intracellular condition in vitro. Moreover, the PTX-LCAPNs achieved 1.7 fold improvement in the intracellular PTX concentration leading to 5-fold reduction in half maximal inhibitory concentration (IC₅₀) values of PTX compared with calcium phosphate nanoparticles loaded with PTX (PTX-CAPNs), demonstrating a stronger cancer cell lethality.

This study aims to synthesize new phospholipids, 1,3-dipalmaminophospholipid(Pad-PC-Pad), and prepare shear-stress sensitive liposomes(SSSL). ¹H NMR and MS indicated that Pad-PC-Pad were fully synthesized successfully. SSSL were prepared by filming-rehydration method with Pad-PC-Pad, which loaded calcein with aggregation-caused quenching(ACQ)characteristics to evaluate shear-stress sensitivity of liposomes and release behavior of liposomes in vitro. The results showed that the particle size of liposomes was 106.91 ± 1.24 nm and liposomes had lenticular morphology under transmission electron microscope. The release of calcein was increased with ultrasonic power, which suggests that the liposomes is shear-stress sensitive. Moreover, the liposomes exhibited a releasing effect for obstructed region under high shear-stress in a model system. Therefore, we synthesized quick functional phospholipid Pad-PC-Pad and the liposomes made from Pad-PC-Pad was shear-stress sensitive, which may be used for treatment of thrombosis.

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.
Animals ; Cell Line ; Colistin ; pharmacology ; toxicity ; Escherichia coli ; drug effects ; Escherichia coli Infections ; drug therapy ; Humans ; Kidney ; cytology ; drug effects ; Mice ; Polyethylene Glycols ; chemistry

To study the protective effect and the mechanism of asiatic acid (AA) from Potentilla chinensis on alcohol hepatic injury in rats. Male Wistar rats were randomly divided into six groups: the normal control group, the AA control group (8 mg · kg(-1) AA), the model group (5.0-9.0 g · kg(-1) alcohol) and high, medium and low-dose AA-treated groups (alcohol + 8, 4, 2 mg · kg(-1) AA). Each group was orally administered with the corresponding drugs once a day for 24 weeks. Approximately 1. 5 hours after the final administration, all rats were killed, and their blood samples and hepatic tissues were collected. The AST and ALT in rat serum and the contents of MPO, TNF-α, IL-1β, SOD, GSH-Px, GSH-Rd and MDA in hepatic tissues were detected. The expressions of NF-κB, TLR4, CD14, MyD88, TRIF and protein expression in hepatic tissues were measured by western blot. The pathological changes in liver tissues were observed by histological examination. The results showed that compared with the model group, the AA-treated groups showed significant decreases in serum ALT, AST and MDA and increases in the activities of SOD, GSH-Px, GSH-Rd and MPO. Moreover, AA markedly inhibited the expressions of TNF-α, IL-1β, TLR4, CD14, MyD88 and NF-κB. The histological examination showed alleviated hepatic issue ijury to varying degrees. In short, asiatic acid (AA) from P. chinensis could protect alcohol-induced hepatic injury in rats. Its mechanism may be related to the inhibition of NF-κB inactivation and the reduction of inflammatory response.
Animals ; Liver ; drug effects ; pathology ; Liver Diseases, Alcoholic ; prevention & control ; Male ; NF-kappa B ; physiology ; Pentacyclic Triterpenes ; pharmacology ; Potentilla ; chemistry ; Protective Agents ; pharmacology ; Rats ; Rats, Wistar ; Toll-Like Receptor 4 ; antagonists & inhibitors

Objective To observe the clinical efficacy of infrared laser combined with alpha-zinc sulfate for the treatment of diabetic peripheral neuropathy ( DNP).Methods A total of 106 patients with DPN were randomly divided into observation group ( n =53 ) and control group (n=53).Besides base hypoglycemic drug therapy, patients in the control group received alpha-zinc sulfate injection 0.6 g once a day.The patients in observation group were given the above treatment plus anodyne therapeutic apparatus treatment.The treatment period lasted for 12 days.The data of clinical symptoms, temperature, and nerve conduc-tion velocity of two groups were observed before and after treatment.Results The effective rate and total effective rate were 52.83% and 90.57%in the observation group, significantly better than 41.51%and 86.66%in control group ( P<0.05 ).The data of peroneal nerve and sural nerve conduction velocity in observation group were much signifi-cantly improved than before treatment(P <0.05).No significant adverse effect was observed.Conclusion Infrared laser combined with alpha-zinc sulfate is effective on the treatment of diabetic peripheral neuropathy.

OBJECTIVETo assess the value of preoperative coronary computed tomographic angiography (CCTA) in the detection of coronary artery disease (CAD) in patients planned to undergo non-cardiac surgery at intermediate or high risk to avoid unnecessary invasive coronary angiography (ICA).

METHODSThe study protocol was approved by our institutional review board and informed consent was given. In this prospective study, 157 consecutive patients who underwent CCTA before undergoing non-cardiac surgery at intermediate or high risk was involved. The non-cardiac surgery included high-risk surgery (17 patients) and intermediate-risk surgery (140 patients). Follow-up was performed in 6-11 months to define cardiac events described as acute coronary syndrome (ACS) or death secondary to ASC, arrhythmias, cardiac revascularization, or cardiac failure. χ(2) test was performed to compare the differences in incidence of cardiac events among patients who had undergone or who had not undergone preoperative ICA.

RESULTSCCTA was of diagnostic value in 145 of 157 patients. Thirty-seven of 145 had no CAD, and 88 of 145 had no significant CAD (<50% stenosis), and non-cardiac surgery was performed in them without preoperative ICA. No patients in those patients had postoperative ischemic events at follow-up; 20 had significant CAD (≥50% stenosis) and underwent surgery after preoperative ICA. CCTA was non-diagnostic in 12 patients who were referred for preoperative ICA, and 4 of 12 underwent surgery after PCI or CABG. There were no differences in cardiac events between patients who had undergone preoperative ICA and those who had not (P=0.45).

CONCLUSIONSIn patients with planned non-cardiac surgery at medium or high risk of cardiovascular events, preoperative CCTA is an effective diagnostic tool for detecting CAD. Preoperative ICA can be safely avoided in patients with normal findings or with stenosis<50% in CCTA.

Adult ; Aged ; Aged, 80 and over ; Coronary Angiography ; methods ; Coronary Artery Disease ; diagnostic imaging ; Female ; Humans ; Male ; Middle Aged ; Perioperative Care ; Prospective Studies ; Tomography, Spiral Computed ; methods

OBJECTIVETo investigate whether myocardial bridging (MB) is independently associated with coronary atherosclerosis proximal to MB in the left anterior descending coronary artery (LAD) identified by computed tomographic coronary angiography (CCTA).

METHODSFrom March 2011 to December 2012, patients (n=9 862) with suspected coronary disease underwent CCTA using dual-source CT scanner. The baseline clinical characteristics (age, gender, smoking history, presence of hypertension, dyslipidemia, diabetes mellitus, family history of heart attack, and body mass index) and the results of CCTA were reviewed. Two radiologists evaluated the coronary artery for MB and coronary atherosclerosis stenosis (CAS) in LAD and made a diagnosis by consensus. Significant independent risk factors for CAS were investigated by multivariate logistic regression analysis.

RESULTSA total of 3 182 (32.3%) cases of MB and 3 359 cases of CAS of LAD were identified. No patient with CAS in the tunneled segment was found. The mean length of bridges and the mean thickness of the overlying myocardium was (17.3±5.2) mm and (1.2±0.9) mm, respectively. There were 1658 MB cases in 3 359 cases of LAD stenosis and 1 524 MB cases in 6 503 cases of no LAD stenosis (χ(2)=681.12, P<0.05). Logistic regression analysis showed that MB in the LAD were significantly associated with CAS in the proximal LAD (OR=3.07, 95%CI=2.81-3.37, P<0.001), and after final adjustment for age, gender, body mass index, family history of heart attack, smoking, hypertension, dyslipidemia, diabetes mellitus, and resting heart rate (OR=2.86, 95% CI=2.60-3.16, P < 0.001).

CONCLUSIONMB in the LAD is independently associated with CAS in the proximal segment to MB.

Adult ; Aged ; Aged, 80 and over ; Coronary Stenosis ; complications ; diagnostic imaging ; Female ; Humans ; Logistic Models ; Male ; Middle Aged ; Myocardial Bridging ; complications ; diagnostic imaging ; Risk Factors ; Tomography, X-Ray Computed