Plant natural products have a wide range of pharmacological properties, not only can they be used as plant dietary supplements to meet the nutritional needs of the human body in the accelerated pace of life, but also occupy an important position in the research and development of therapeutic drugs for the treatment of tumors, inflammation and other diseases, and have been widely accepted by the public due to their good safety. However, despite the above advantages of plant natural products, limiting factors such as low solubility, poor stability, lack of targeting, high toxicity and side effects, and unacceptable odor have greatly impeded their conversion to clinical applications. Therefore, the development of new avenues for the application of new natural products has become an urgent problem to be solved at present. In recent years, with the continuous development of research, various strategies have been developed to improve the bioavailability of natural products. Among them, nanocarrier delivery system is one of the most attractive strategies at present. In past studies, a large number of nanomaterials (organic, inorganic, etc.) have been developed to encapsulate plant-derived natural products for their efficient delivery to specific organs and cells. Up to now, nanotechnology has not only been limited to pharmaceutical applications, but is also competing in the fields of nanofood processing technology and nanoemulsions. Among the various nanocarriers, liposomes are the largest nanocarriers with the largest market share at present. Liposomes are bilayer nanovesicles synthesized from amphiphilic substances, which have advantages such as high drug loading capacity and stability. Attractively, the flexible surface of liposomes can be modified with various functional elements. Functionalized modification of liposomes with different functional elements such as antibodies, nucleic acids, peptides, and stimuli-responsive moieties can bring out the excellent drug delivery function of liposomes to a greater extent. For example, the modification of functional elements with targeting function such as nucleic acids and antibodies on the surface of liposomes can deliver natural products to the target location and improve the bioavailability of drugs; the modification of stimulus-responsive groups such as photosensitizers, magnetic nanoparticles, pH-responsive groups, and temperature sensitizers on the surface of liposomes can achieve controlled release of drugs, localized targeting, and synergistic thermotherapy. In addition to the above properties, by using functionalized liposomes to encapsulate natural products with irritating properties can also effectively mask the irritating properties of natural products, improve public acceptance, and increase the possibility of application of irritating natural products. There are various strategies for modifying liposomes with functional elements, and the properties of functionalized liposomes constructed by different construction strategies differ. The commonly used construction strategies for functionalized liposomes include covalent modification and non-covalent modification. These two types of construction strategies have their own advantages and disadvantages. Covalent modification has better stability than non-covalent modification, but its operation is cumbersome. With the above background, this review focuses on the three typical problems faced by plant natural products at present, and summarizes the specific applications of functionalized liposomes in them. In addition, this paper summarizes the construction strategies for building different types of functionalized liposomes. Finally, this paper will also review the opportunities and challenges faced by functionalized liposomes to enter clinical therapy, and explore the opportunities to overcome these problems, with a view to better realizing the precise control of plant nanomedicines, and providing ideas and inspirations for researchers in related fields as well as relevant industrial staff.

Objective:To establish a graded method to avoid mean fluorescence intensity(MFI)threshold of HLA Class I antibodies corresponding antigen,and the HLAMatchmaker program has been used to select the minimum mismatch value of donor-patient epitopes.Evaluate the application value of combining both methods in selecting HLA compatible platelets(PTL)for patients with immune platelet transfusion failure(IPTR)in improving platelet the corrected count increment(CCI).Methods:A total 7 807 PLT cross-matching compatible were performed by the solid-phase red cell adherence(SPRCA)method for 51 IPTR patients.The Luminex single antigen flow cytometry was used to detect HLA Class I antibodies in patients,and detected the MFI value for different specificity antigens of HLA Class I antibodies,was graded into strong positive group(MFI＞4 000,level 1),medium positive group(1 000＜MFI 4 000,2),weak positive group(500＜MFI≤1 000,3),and one negative control group(MFI≤500).The results of 7 807 SPRCA their negative/positive reaction wells were enrolled and statistically analyzed in different grades and the four groups,the statistical differences between the four groups were compared.Multiple applications for the select HLA Class I compatible donor events were made for patients in two cases,and HLAMatchmaker program was used to calculate the number of HLA Class I epitopes mismatches between the donors and patients.The donor with the minimum number of epitopes mismatches was selected,while avoiding the corresponding antigens of HLA Class I antibodies in levels 1 and 2,the provision of HLA compatible platelets for IPTR.After the transfusions,the CCI value of the platelet transfusion efficacy evaluation index was calculated,and the clinical evaluation of the transfusion effect was obtained through statistical analysis.Results:There were statistically significant differences in the positive results of SPRCA immunoassay among the strong positive group,medium positive group,and weak positive group of 51 IPTR patients with different specific of HLA-I class antibodies and corresponding antigens(all P＜0.001).The positive results showed a range from high to low,with strong positive group＞medium positive group＞weak positive group.There were a statistical difference among between the strongly positive or moderately positive groups and the negative control group(P＜0.001).There was no statistical difference between the weakly positive group and the negative control group(P＞0.05).The strong positive group was set as the corresponding specific HLA Class I site corresponding antigen grade 1 avoidance threshold,the medium positive group as the grade 2 avoidance thresholds,and the weak positive group as the grade 3 avoidance threshold.In the case of donor platelet shortage,it is not necessary to avoid the weak positive group.Avoiding the strategy of donor antigens and HLAMatchmaker program scores≤7 corresponding to HLA Class I antibodies of levels 1 and 2,with CCI values＞4.5 × 109/L within 24 hours,can obtain effective clinical platelet transfusion conclusions.Conclusion:When selecting HLA Class I compatible donors for IPTR patients,the grading avoids HLA Class I antibodies corresponding to donor antigens,and the donor selection strategy with the minimum scores of HLAMatchmaker program is comprehensively selected.The negative result confirmed by platelet cross-matching experiments has certain practical application value for improving platelet count in IPTR patients.

Objective: To study the influence of steroid withdrawal protection strategy on height growth in pediatric patients after kidney transplantation. Methods: The prospective cohort study enrolled 40 stage 5 chronic kidney disease children receiving kidney transplantation from July 2017 to September 2022 at Guangzhou Women and Children's Medical Center. Based on the primary preoperative disease, patients with immune abnormality-associated glomerular diseases or unknown causes were assigned to the steroid maintenance group, in which patients received steroid tapering within 3 months after surgery to a maintenance dose of 2.5 to 5.0 mg/d. While patients with hereditary kidney disease or congenital urinary malformations were assigned to the steroid withdrawal group, in which patients had steroids tapered off within 3 months. The characteristics of height catch-up growth and clinical data were compared between the 2 groups at baseline, 6, 12, 18 and 24 months after kidney transplantation. T-test, repeated measurement of variance analysis, Mann-Whitney U test, and Fisher exact test were used for the comparison between the 2 groups. Results: Among the 40 children, 17 were males, 23 were females, 25 were in the steroid withdraw group ((7.8±2.8) years old when receiving kidney transplantation) and 15 cases were in the steroid maintenance group ((7.6±3.5) years old when receiving kidney transplantation). The study population was followed up for (26±12) months. The total dose per unit body weight of steroids in the steroid withdrawal group was lower than that in the steroid maintenance group ((0.13±0.06) vs. (0.36±0.19) mg/(kg·d), t=5.83, P<0.001). The height catch-up rate (ΔHtSDS) in the first year after kidney transplantation in the steroid withdraw and steroid maintenance groups was 1.0 (0.7, 1.4) and 0.4 (0.1, 1.0), respectively; in the second year, the ΔHtSDS in the steroid withdraw group was significantly higher than that in the steroid maintenance group (1.1 (0.2, 1.7) vs. 0.3 (0, 0.8), U=28.00, P=0.039). The HtSDS in the steroid withdrawal group at the five follow-up time points was -2.5±0.8, -2.0±0.8, -1.5±0.8, -1.3±0.9 and -0.5±0.3, respectively, while in the steroid maintenance was -2.4±1.3, -2.2±1.1, -2.0±1.0, -1.8±1.0 and -1.6±1.0, respectively. There were statistically significant differences in HtSDS at different follow-up time points in both 2 groups (F=19.81, P<0.01), but no statistical differences in overall impact between the 2 groups (F=1.13, P=0.204). The steroid treatment was interaction with the increase of follow-up time (F=3.62, P=0.009). At the 24^th month after transplantation, the HtSDS in the steroid withdrawal group was significantly higher than that in the steroid maintenance group (P=0.047). Six patients in the steroid withdrawal group experienced antibody-mediated immune rejection (AMR), while 3 did in the steroid maintenance group. Moreover, there was no significant difference in AMR between the two groups (χ²=0.06, P=0.814). Conclusion: The steroid withdrawal protection strategy favors the height catch-up growth in pediatric patients after kidney transplantation and does not increase the risk of postoperative antibody-mediated immune rejection.
Male ; Humans ; Child ; Female ; Child, Preschool ; Kidney Transplantation ; Prospective Studies ; Steroids/therapeutic use* ; Antibodies ; Body Weight

Diversity-oriented synthesis is aimed to increase the chemical diversity of target natural products for extensive biological activity evaluation. Indole ring is an important functional group in a large number of drugs and other biologically active agents, and indole-containing natural products have been frequently isolated from marine sources in recent years. In this paper, a series of indole-containing marine natural hyrtioreticulin derivatives, including 19 new ones, were designed, synthesized through a key Pictet-Spengler reaction, and evaluated for their inflammation related activity. Compound 13b displayed the most promising activity by inhibiting TNF-α cytokine release with an inhibitory rate of 92% at a concentration of 20 μmol·L^-1. A preliminary structure-activity relationship analysis was also discussed. This research may throw light on the discovery of marine indole alkaloid derived anti-inflammatory drug leads.
Animals ; Anti-Inflammatory Agents/pharmacology* ; Biological Products/pharmacology* ; Indole Alkaloids/pharmacology* ; Porifera ; Structure-Activity Relationship

OBJECTIVE: To analyze the detection rate of the inferior pyloric artery (IPA) in patients with gastric cancer by computed tomography arteriography (CTA). MATERIALS AND METHODS: Fifty-four patients (48 males and 6 females; mean age, 59.0 ± 1.5 years) who had undergone radical gastrectomy for gastric cancer from September 2016 to July 2017 at our institution were recruited prospectively. Patients underwent abdominal contrast-enhanced CT scans and CTA imaging reconstruction before the operation. The origin of the IPA in all cases was determined by a radiologist based on CTA images and verified by the surgeon. The accuracy of CTA in diagnosing the origin of the IPA was calculated. Dominant vessels of the origin were analyzed. RESULTS: IPAs were detected by CTA in 51 patients (94.4%). Among these, IPAs originated from the right gastroepiploic artery (RGEA) (24 cases), the gastroduodenal artery (GDA) (4 cases), and the anterior superior pancreaticoduodenal artery (ASPDA) (20 cases). In the remaining 3 cases, the IPAs contained two branches originating from the RGEA and ASPDA, respectively. During surgery, in 2 (3.7%) of the 54 cases of gastric cancer, IPAs could not be detected; the IPAs originated from the RGEA (22 cases), GDA (5 cases), and ASPDA (24 cases). One case had an IPA originating from both the RGEA and the GDA. Finally, the accuracy of CTA in diagnosing the origin artery of the IPA was 85.2% (46/54). CONCLUSION: CTA can detect the origin of the IPA accurately, which can aid surgeons while performing pylorus-preserving operations.
Angiography ; Arteries ; Female ; Gastrectomy ; Gastroepiploic Artery ; Humans ; Male ; Prospective Studies ; Stomach Neoplasms ; Surgeons ; Tomography, X-Ray Computed

OBJECTIVEOver the last few decades, diabetic cardiomyopathy has been identified as a significant contributor in cardiac morbidity. However, the mechanisms of diabetic cardiomyopathy have not been clarified.

METHODSIn the present study, a diabetic rat model was induced by the intraperitoneal injection of streptozotocin. The myocardial CD147 expression and extent of glycosylation, as well as thematrixmetalloproteinases(MMPs) expression and activity, were observed in the diabetic and synchronous rats.

RESULTSThe results showed that CD147 located on sarcolemma of cardiomyocytes. The myocardial CD147 expression and glycosylation were significantly increased in the diabetic rats as compared with the control. Expression of MMP-2 protein, MMP-2 and MMP-9 activity were also increased in left ventricular myocardium in the diabetic rats. Tamoxifen only inhibited the enhanced expression of myocardial CD147 in the diabetic rats, but not in synchronous control rats. Tamoxifen inhibited glycosylation of myocardial CD147 in both diabetic and control rats. The inhibition of tamoxifen on CD147 glycosylation was stronger than on the expression in the myocardium. The extent of myocardial CD147glycosylation was positively related toMMP-2 and MMP-9 activity. Tamoxifen induced an inhibition of myocardial MMP-2 and MMP-9 activity in the control and diabetic rats.

CONCLUSIONThese results indicate that myocardial CD147 expression, especially the extent of glycosylation, regulates MMP-2 and MMP-9 activity, then accelerates cardiac pathological remodeling inducing diabetic cardiomyopathy. Tamoxifen inhibits myocardial CD147 glycosylation and further depress the activity of MMPs. Therefore, tamoxifen may protect the diabetic rats against diabetic myocardium.

Animals ; Basigin ; metabolism ; Diabetes Mellitus, Experimental ; complications ; Diabetic Cardiomyopathies ; drug therapy ; Glycosylation ; Heart ; drug effects ; Matrix Metalloproteinase 2 ; metabolism ; Matrix Metalloproteinase 9 ; metabolism ; Myocardium ; metabolism ; Myocytes, Cardiac ; cytology ; Rats ; Sarcolemma ; metabolism ; Tamoxifen ; pharmacology

OBJECTIVETo explore the risk factors and prevention strategies of post-operative complications in elderly patients with colorectal cancer.

METHODSData of 107 elderly patients (≥75 years) undergoing surgery for colorectal cancer were collected from January 2006 to December 2009 in the Department of Gastrointestinal Surgery, Peking University People's Hospital. POSSUM and E-POSSUM scoring systems were used to predict post-operative complications. ROC curve and observe/expect(O/E) were used to assess the validity of scoring systems. Logistic regression was used to evaluate the independent risk factors associated with post-operative complications of elderly patients with colorectal cancer.

RESULTSThe predictive complication rates of E-POSSUM and POSSUM in elderly patients with colorectal cancer were 13.9%-86.6%(average, 32.7%) and 19.1%-99.1% (average, 55.5%). The predictive validity of E-POSSUM was better than POSSUM(AUC of ROC: 0.862 vs. 0.576, O/E: 0.771 vs. 0.454), the former was closer to the actual complication rate(25.2%, 27/107). Concurrent diabetes mellitus(P=0.019) and rectal lesion(P=0.005) were independent risk factors associated with surgery-related post-operative complications. Anastomotic leakage was the most common surgery-related post-operative complications. Chronic obstructive pulmonary disease(P=0.026), ASA score(P=0.025), intestinal obstruction(P=0.037) and perforation(P=0.001) were independent risk factors associated with non-surgery-related post-operative complications. Pulmonary infection was the most common non-surgery-related post-operative complication.

CONCLUSIONSThe application of E-POSSUM scoring system can provide more accurate prediction of post-operative complications in elderly patients undergoing surgery for colorectal cancer. Positive interventions should be taken for high-risk patients to prevent post-operative complications.

Aged ; Colorectal Neoplasms ; surgery ; Female ; Humans ; Male ; Postoperative Complications ; etiology ; prevention & control ; Risk Factors

OBJECTIVETo study the effects of iptakalim (IPT) on pressure-overload induced cardiac remodeling in rats, and investigate correlation between this protection effects and plasma PGI2 content.

METHODThe pressure-overload induced cardiac remodeling model was induced by abdominal aorta constriction for 6 weeks, and the rats were divided into 5 groups repectively: (1) sham group, (2) control group, (3) IPT 3 mg/kg group (IPT 3), (4) indomethacin 2 mg/kg group (Indo 2), (5) indomethacin 2 mg/kg + IPT 3 mg/kg group (Indo 2 + IPT 3). RM6000 eight channel physiological recorder was used to record haemodynamics index, heart weight was weighed and the cardiac remodeling index was calculated, HE stain and Masson's stain were employed to perform histological analysis, colorimetric method was used to detect the hydroxyproline content in cardiac tissue, radioimmunological method was used to measure the plasma PGI2 content.

RESULTSAfter 42 days of aortic banding, the hyperdynamic circulation state, cardiac remodeling and decreased plasma PGI2 content were observed in the model group compared with those in the sham group, which were effectively reserved by treatment with IPT 3 mg/kg. Single-use indomethacin led to further deterioration of this pathophysiological changes, however, combination administration of IPT 3 mg/kg prevented these from worsening characteristic by ameliorating hyperdynamic circulation state and cardiac remodeling, augmnent plasma PGI2 content.

CONCLUSIONIPT can significantly reverse abdominal aorta binding/pressure-overload induced cardiac remodeling, its mechanism may contribute to binding K(ATP) channel in endothelial cells, ameliorating endothelium cells function, augmenting PGI2 synthesis and secretion.

Animals ; Aorta, Abdominal ; surgery ; Constriction ; Endothelium, Vascular ; metabolism ; physiology ; Epoprostenol ; blood ; Hypertension ; blood ; physiopathology ; KATP Channels ; drug effects ; Male ; Propylamines ; pharmacology ; Rats ; Ventricular Remodeling ; drug effects

Background The diagnosis of central serous chorioretinopathy (CSC) is mainly dependent onfluorescine fundus angiography (FFA). However, the combination of optical coherence topography (OCT) with FFA offers a new approach to the research of the pathogenesis of CSC. Objective This clinical study was designed to study the combined application of the FFA and OCT for the research of the pathogenesis of central serous chorioretinopathy (CSC). Methods Forty-four eyes of 44 patients with CSC were included in this study with 36 cases of males and 8 cases of female. The patients were aged 39.3 ± 5.3 years and the visual acuity was 0. 64 ±0. 27. FFA and OCT examinations were performed in all patients and the FFA images were imported into the Topcon 3D OCT 1000 device to locate the conformity of OCT lesions with the leakages of FFA. The neuroepithelial layer thickness at the fovea and the height of the neuroepithelial layer detachment were measured using 3-D OCT. Results OCT showed serous REP detachment in 34 eyes (77.3%) and rough surfaces of RPE in 10 eyes (22. 7% ). In thirtyfour eyes with RPE detachment, the OCT lesions and FFA leakage spots conformed to the same locations in 31 eyes, but the other three eyes did not. The mean foveal neuroepithelial thickness was (138.5±19.4) μm in CSC eyes and that of normal eyes was ( 131.35±5. 01 ) μm ,showing a significant difference between them( t=0. 39 ,P＞0. 05 ). The mean height of neuroepithelial detachment was (263.3 ± 126.7 ) μm in CSC eyes. Conclusion RPE detachment occurs in CSC eyes and further induces macular neuroepithelial detachment. Leakage lesion of fluorescine corresponds to RPE detachment. CSC without RPE detachment may be related to the increase in RPE permeability. OCT can accurately measure the thickness of the macular neuroepithelial layer and the height of the neuroepithelial detachment.

OBJECTIVETo evaluate the long-term effect of sodium glycididazole (CMNa) as a hypoxic radiosensitizer on the radiotherapy for nasopharyngeal carcinoma.

METHODSBetween May 1999 and May 2002, 211 patients with pathologically confirmed nasopharyngeal carcinoma were randomized into group-A treated by radiotherapy plus CMNa or group-B by radiotherapy alone. The staging was determined according to 92' Fuzhou staging systerm. The type, procession and dosage of radiotherapy were identical in both groups. The early adverse effect grade was assessed based on the CTC2.0 criteria and the late adverse effects were evaluated according to the RTOG/EORTC criteria. The median follow-up time was 52 months. All the data was analyzed by the SPSS 13.0 software. Characteristics and adverse events of these patients were compared between the two groups using t-test and the Wilcoxin rank sum test. Time-to-event curves were estimated using the Kaplan-Meier method. The prognostic parameters were analyzed using univariate analysis and the Cox multivariate regression analysis.

RESULTSThe clinical data of the two groups were comparable. The 3-year survival was 88.4% in group-A, while 75.2% in group-B, with a statistically significant difference between two groups (P = 0.010). Univariate analysis showed that the 3-year survival was statistically correlated with N-staging ((N0-1, 86.9%, N2-3 73.8%, P < 0.001), T-staging (T1-2 85.6%, T3-4 79.3%, P = 0.014), TNM staging (P = 0.039), and whether using CMNa or not during rediotherapy (Group-A 88.4%, Group-B 75.2%, P = 0.010). The 5-year recurrence-free survival, 5-year metastasis-free survival and 5-year overall survival were 75.8%, 74.9% and 77.7% in Group-A, while 63.0%, 63.0% and 62.4% in Group-B with a statistically significant difference between two groups (0.013, 0.022 and 0.010, respectively). If stratified in the subgroups, the overall survival of stage III - IV patients was statistically different between group A and B (P = 0.009), however, not of stage I - II patients (P = 0.502). Cox multivariate regression analysis showed that the independent prognostic parameters for survival were N-stage (RR = 3.288) , T-stage (RR = 2.147) and use of CMNa during rediotherapy (RR = 0.407). However, there was no statistically significant difference between two groups in acute or late adverse effects on nervous system or heart, which suggested that use of CMNa during radiotherapy would not aggravate the toxicity caused by radiotherapy.

CONCLUSIONSodium glycididazole is well tolerable effective as a hypoxic radiosensitizer, which can improve the efficacy of radiotherapy and the long-term result of nasopharyngeal carcinom a patients, especially for the stage III - IV patients.

Adolescent ; Adult ; Aged ; Female ; Follow-Up Studies ; Humans ; Kaplan-Meier Estimate ; Male ; Metronidazole ; adverse effects ; analogs & derivatives ; therapeutic use ; Middle Aged ; Multivariate Analysis ; Nasopharyngeal Neoplasms ; pathology ; radiotherapy ; Neoplasm Staging ; statistics & numerical data ; Prognosis ; Proportional Hazards Models ; Radiation-Sensitizing Agents ; adverse effects ; therapeutic use ; Time Factors ; Treatment Outcome ; Vomiting ; chemically induced