Objective:To prepare a 177Lu labeled human epidermal growth factor receptor 2 (HER2) affibody 177Lu-1, 4, 7-triazacyclononane-1, 4, 7-triacetic acid (NOTA)-maleimide (Mal)-cysteine (Cys)-ZHER 2: 342 ( 177Lu-NOTA-MZHER2 for short), and investigate its labeling process and anti-tumor properties. Methods:Two kinds of buffer systems (sodium acetate buffer system and sodium ascorbate buffer system) were investigated. The effects of pH value, precursor mass and reaction temperature on 177Lu labeling NOTA-MZHER2 were compared to obtain optimal labeling conditions. The radiochemical purity of labeled product was determined by instant thin-layer chromatography (ITLC), and its stabilities in PBS and plasma were observed. Human ovarian cancer cell line SKOV-3 was selected for cell internalization and cytotoxicity test to evaluate cell uptake and killing effect of 177Lu-NOTA-MZHER2. SKOV-3 tumor-bearing mice( n=3) were injected with 177Lu-NOTA-MZHER2, and microSPECT/CT imaging was performed. Another 40 tumor-bearing mice were divided into 22.2 MBq group (tail vein injection with probe of 22.2 MBq), control group (tail vein injection with PBS), low-dose group (tumor injection with probe of 3.7 MBq) and high-dose group (tumor injection with probe of 7.4 MBq). Tumor volume and mass of tumor-bearing mice were monitored after injection, and the anti-tumor effect and toxicity of probe were evaluated. Repeated measurement analysis of variance (Bonferroni method) was used to analyze the data. Results:The optimal labeling condition was 70-80 ℃ for 30 min in the system of sodium acetate buffer solution with pH=4 and precursor mass of 50 μg. Under these conditions, the labeling rate of 177Lu-NOTA-MZHER2 was (99.3±0.4)% and radiochemical purity was >99%. After 12 d in PBS and plasma, the radiochemical purities were (95.0±1.5)% and (95.0±2.1)%. Results of cell experiment showed that the internalization of 177Lu-NOTA-MZHER2 accounted for (29.02±3.50)% of the total uptake, and the survival rate of SKOV-3 cells was (48±6)% with the probe concerntration of 6×10 -3 Bq/L. SPECT imaging showed that 177Lu-NOTA-MZHER2 was still concentrated at the tumor site 96 h after injection with a dose of 18.5 MBq. Relative tumor volume (RTV) of tumor-bearing mice in 22.2 MBq group, high-dose group and low-dose group was significantly different from that in control group ( F=21.75, P<0.001). Twenty days after injection, RTV and relative body mass of the tumor-bearing mice in high-dose group were (140±7)% and (80±9)%, respectively. Compared with control group, high-dose group had obvious anti-tumor effect (both P<0.001). Conclusion:177Lu-NOTA-MZHER2 is successfully prepared, which is simple and efficient, and the probe has good anti-tumor effect.

Objective:To radiolabel hyperbranched polymer (HG)-modified liquid metal nanodroplet (LMND)@HG with 177Lu, and explore the radiotherapy sensitization effect on anti-breast cancer therapy. Methods:The ultrasonication method was used to prepare LMND@HG, and then 177LuCl 3 was mixed with LMND@HG to label 177Lu by alloying reactions. The labeling rate, plasma stability and cytotoxicity of 177Lu-LMND@HG were detected. Xenograft mouse model of breast cancer was constructed, and the tumor inhibition test was performed by an intratumoral injection. The tumor progression was monitored by in vivo imaging system. The mechanism of tumor inhibition was verified by immunohistochemistry and immunofluorescence assays. One-way analysis of variance, repeated measures analysis of variance, and the least significant difference t test were used to analyze the data. Results:177Lu was successfully labeled to LMND@HG with a high labeling efficiency >95%. The product did not require further purification and the plasma radiochemical purity was still higher than 95% after 5 d. The cytotoxicity test showed that a dose of 888 kBq (40 mg/L) 177Lu-LMND@HG had obvious toxicity to 4T1 cells, which was significantly lower than 177LuCl 3 (cell viabilities: (16.48±7.81)% vs (85.77±8.87)%; F=77.81, t=11.73, P<0.001) and LMND@HG ((46.53±5.75)%; t=6.20, P<0.001). The biological distribution results showed that 177Lu-LMND@HG was mainly distributed in tumor tissue 5 d after intratumoral injection. The results of the tumor inhibition experiment showed that 1.48 MBq 177Lu-LMND@HG could significantly inhibit the tumor growth compared with the 177LuCl 3 (tumor volume: (222.66±97.70) vs (789.13±245.04) mm 3;F=18.55, t=4.29, P=0.005). In vivo optical imaging of small animals showed that 1.48 MBq and 3.70 MBq 177Lu-LMND@HG both significantly inhibited the tumor growth. Immunofluorescence and immunohistochemical results showed that 177Lu-LMND@HG caused double-stranded DNA break, and suppressed the tumor growth by inhibiting cell proliferation and angiogenesis. Conclusions:A novel 177Lu-liquid metal-based reactive oxygen species (ROS) radiation sensitizer is successfully prepared in this study. The preparation method is efficient and convenient, and the product has high stability. 177Lu-LMND@HG shows an obvious radiotherapy sensitization effect on breast tumor-bearing mice.

Essential oils (EOs) are natural, volatile substances derived from aromatic plants. They exhibit multiple pharmacological effects, including antibacterial, anticancer, anti-inflammatory, and antioxidant properties, with broad application prospects in health care, food, and agriculture. However, the instability of volatile components, which are susceptible to deterioration under light, heat, and oxygen exposure, as well as limited water solubility, have significantly impeded the development and application of EOs. Porous nanoclays are natural clay minerals with a layered structure. They possess unique structural characteristics such as large pore size, regular distribution, and tunable particle size, which are extensively utilized in drug delivery, adsorption separation, reaction catalysis, and other fields. Natural-derived porous nanoclays have garnered considerable attention for the encapsulation and delivery of EOs. This review comprehensively summarizes the structure, types, and properties of natural-derived porous nanoclays, focusing on the structural characteristics of porous nanoclays such as montmorillonite, palygorskite, halloysite, kaolinite, vermiculite, and natural zeolite. It also examines research advances in their delivery of EOs and explores engineering strategies to enhance the delivery of EOs by natural-derived porous nanoclays. Finally, various applications of natural-derived porous nanoclays for EOs in antibacterial, food preservation, repellent, and insecticide aspects are presented, providing a reference for the development and application of EOs.
Humans ; Nanoparticles/chemistry* ; Oils, Volatile/administration & dosage* ; Porosity ; Nanoparticle Drug Delivery System/chemistry*

OBJECTIVE To study the nephrotoxicity of the extracts from different parts o f Miao medicine Wikstroemia indica in healthy rats ，and to provide reference for the study of its toxicity mechanism and clinical drug use. METHODS Using 70％ ethanol as solvent ，total ethanol extract of W. indica was extracted with diacolation method. After dispersing the above extract with water，the fractions of corresponding fractions were obtained with petroleum ether ，ethyl acetate and n-butanol，and the rest was the extract of water fraction. SD rats were randomly divided into total ethanol extract group ，petroleum ether fraction group ，ethyl acetate fraction group ，n-butanol fraction group ，water fraction group and blank group ，with 12 rats in each group （half male and half female ）. The rats in the administration groups were given the corresponding dose of drug solution intragastrically （total ethanol extract 317.520 mg/kg，petroleum ether fraction 7.875 mg/kg，ethyl acetate fraction 78.435 mg/kg，n-butanol fraction 53.865 mg/kg and water fraction 76.545 mg/kg），once a day ，for conse- cutive 2 weeks，and then stopped taking drug for 2 weeks； rats in the blank group were given equal volume of 1.0％ . sodium carboxymethyl cellulose solution intragastrically. Duringthe experiment ，the general conditions of rats were observed. The samples of urine （on the 14th and 28th day ），serum and bilateral renal tissues （on the 15th and 29th day ）were taken respectively，the renal index was calculated ，the levels of @qq.com renal function indexes in serum and urine were detected ，and the pathomorphological changes of renal tissues were observed. RESULTS During administration ，compared with blank group ，the rats in the total ethanol extract group and ethyl acetate fraction group showed poisoning behavior and activity characteristics such as mental depression ，decreased activity and diet ，thin stool and decreased body mass. The mental state of the rats in the petroleum ether fraction group ，n-butanol fraction group and water fraction group were slightly worse than that in blank group，and slightly decreased activity and diet as well as thin stool ，and slowly increased body mass were found ；however，there was no significant difference in anal temperature in each group. After 2 weeks of administration ，the renal index in total ethanol extract group ，the serum levels of N-acetylglucosaminidase（NAG），urea nitrogen （BUN）and creatinine （Cr）in total ethanol extract group and ethyl acetate fraction group ，serum level of NAG in n-butanol fraction group and serum level of Cr in water fraction group ，as while as NAG levels in urine of rats in total ethanol extract group and petroleum ether fraction group ，NAG and urinary protein levels in urine of rats in ethyl acetate fraction group were increased significantly （P＜0.05 or P＜0.01）. In the pathomorphological observation ，renal tubules showed different degrees of unclear structure ，cell swelling and a few cell necrosis in the total ethanol extract group ，petroleum ether fraction group and ethyl acetate fraction group ，accompanying by glomerular pyknosis，renal tubular sclerosis and inflammatory cell infiltration ，compared with blank group. After drug withdrawal ，the mental state of rats in the administration groups were significantly improved ，the amount of activity and diet increased ，and the stool tended to be normal. Two weeks after drug withdrawal and recovery ，the levels of above indexes in serum and urine of rats in administration groups returned to be close to that in blank group （P＞0.05）；the glomerular structure of rats in each administration group gradually recovered clearly ，and cell swelling and inflammatory cell infiltration were rare in total ethanol extract group ， petroleum ether fraction group and ethyl acetate fraction group. CONCLUSIONS The total ethanol extract ，petroleum ether fraction and ethyl acetate fraction of Miao medicine W. indica have certain nephrotoxicity and reversibility. The toxic component may

Objective:To evaluate the feasibility of delineating subvolume target in radiotherapy for brain tumors using Gd-based contrast clearance difference.Methods:Twenty-six patients with malignant brain tumors were scanned with MRI. The first and second acquisitions of standard T 2-weighted images (T 2WI) and T 1-weighted images (T 1WI) were performed at 5 min and 60 min after injection of contrast agent. Delayed contrast extravasation (DCEM) MRI computed by Brainlab comprised regions of contrast agent clearance representing active tumors and regions of contrast accumulation representing non-tumor tissues. Based on T 2WI images, 14 patients with liquefaction necrosis were divided into group A, and 12 patients without liquefaction necrosis into group B, respectively. Then, gross target volume (GTV) was delineated on T 1WI images. Based on the GTV, active tumor (GTV tumor) and non-tumor regions (GTV non-tumor) were delineated on T 1WI-DCEM fusion images, while liquefaction necrosis (GTV liquefaction) and non-liquefaction (GTV non-liquefaction) were delineated on T 1-T 2WI fusion images. Finally, the differences between different subvolumes were compared by paired t-test. Results:In group A, the GTV non-liquefaction and GTV liquefaction were (13.65±18.15) cm 3 and (6.30±7.57) cm 3. The GTV tumor was (10.40±13.52) cm 3 and the GTV non-tumor was (9.55±14.57) cm 3. The GTV non-liquefaction was significantly increased by 16.3% on average compared with the GTV tumor ( P<0.05). The GTV non-tumor was significantly increased by 16.3% on average compared with the GTV liquefaction ( P<0.05). In group B, The GTV non-tumor was significantly reduced by 68.8% on average compared with the GTV tumor ( P<0.05). Conclusions:Compared with T 2WI, DCEM has advantages in identifying the liquefaction area and can clearly differentiate the subvolume of active tumors from non-liquefaction necrosis. DCEM provides evidence for guiding the delineation of subvolume in primary and metastatic brain tumors.

Objective:To evaluate the feasibility of magnetic resonance (MR) perfusion imaging for sub-region segmentation of brain metastases (BMs), and to provide reference for individualized radiotherapy based on blood flow perfusion heterogeneity in BMs patients.Methods:96 BMs patients were selected, including 55 patients with necrosis and 41 without necrosis. Each patient was scanned with CT simulation and MR simulation before radiotherapy. MIM Maestro 6.8.8 software was used to delineate the gross tumor volume (GTV) and necrosis GTV (GTV N) from enhanced T 1W images and T 2 Propeller images, respectively, and the solid GTV (GTV S) was obtained by the subtraction of the two. Then, the cerebral blood flow map of three dimensional arterial spin labeling (3D-ASL) was employed to determine the high perfused GTV (GTV H) and low perfused GTV (GTV L). The volume and proportion of sub-regions were counted and compared between two groups and the correlation of each sub-region was analyzed. Results:The volume of GTV in the necrosis and non-necrosis groups was 19.56 and 7.34 cm 3, respectively. Besides, the AUC of the ROC between GTV volume and necrosis was 0.749. In the necrosis group, the ratio of GTV N, GTV S, GTV H and GTV L to GTV was 20.47%, 79.53%, 33.03% and 46.50%, respectively (all P<0.05). Among them, the r value between GTV S and GTV was 0.963, 0.849 for GTV L and GTV, and 0.840 for GTV L and GTV S, significantly higher than 0.683 for GTV H and GTV and 0.764 for GTV H and GTV S (all P<0.05). In the non-necrosis group, the ratio of GTV H to GTV was higher than that in the necrosis group (58.95% vs. 33.03%, P<0.05). In addition, the ratio of GTV L to GTV was slightly lower than that in the necrosis group (41.05% vs. 46.50%, P>0.05). The r value between GTV H and GTV was 0.776, significantly higher than 0.574 between GTV L and GTV ( P<0.05). Conclusion:MR-3D-ASL can quantitatively analyze the heterogeneous blood perfusion of BMs, which could guide the sub-region segmentation and local dose escalation of tumors.

Objective To evaluate the clinical effect after laparoscopic sacral colpopexy (LSC) of combined transabdominal-transvaginal approach on stage Ⅳpelvic organs prolapse (POP). Methods The clinical data of 65 patients undergoing LSC of combined transabdominal-transvaginal approach from January 1st, 2010 to July 30th, 2017 due to POP stage Ⅳ in First Affiliated Hospital of Guangzhou Medical University were retrospectively analyzed. Objective outcome was assessed by comparing preoperative and postoperative pelvic organ prolapse quantification (POP-Q) systems. Subjective effects were assessed by comparing pelvic floor distress inventory-short form 20 (PFDI-20), pelvic floor impact questionnaire short form (PFIQ-7), pelvic organ prolapse/urinary incontinence sexual questionnaire-12 (PISQ-12) and patient global impression of improvement (PGI-I). Results All 65 patients were successfully performed without any intraoperative complications. Fifty-three patients were followed in the clinic department and 12 were followed up by telephone. The follow-up duration was 6.1-80.3 months and the median follow-up duration was 24.5 months. The bleeding loss was 20-250 ml. Postoperative urethral catheter residence day was (2.5± 1.1) days, length of postoperative stay was (6.2±1.7) days. The postoperative POP-Q scores were compared with preoperative scores which had significantly improved except pb (all P<0.01). The objective cure rates of vaginal anterior wall, apical and posterior wall prolapse stageⅣwere 90% (47/52), 100% (23/23) and 95% (20/21).About PGI-I, except for 1 patient who chose"improvement", the other 64 patients (98%, 64/65) all chose"significant improvement". Furthermore, preoperative and postoperative PFDI-20, PFIQ-7, and PISQ-12 scores were all statistically significant (all P<0.01). Subjective efficacy was significant. Three cases (5%, 3/65) of postoperative fever occurred. Two cases (4%, 2/53) had mesh exposure. Six patients (11%, 6/53) had recurrence of postoperative prolapse. Five cases had recurrence of vaginal anterior wall prolapse and no reoperation was performed; 1 case was recurrence of posterior vaginal wall prolapse who diagnosed as vaginal posterior wall prolapse stage Ⅲ; no recurrence of apical prolapse. The rate of reoperation (including exposed-mesh removal and pelvic floor reconstruction surgery) was 5% (3/65). Conclusions The LSC of combined transabdominal-transvaginal approach has a high subjective efficacy rate. The objective cure rate in the case of apical prolapse stage Ⅳ is one hundred percent.The LSC of combined transabdominal-transvaginal approach has low mesh exposure, low postoperative infection and the reoperation rate, which is one of optional pelvic floor reconstruction surgery. However, there is still a risk of recurrence in patients with POP stageⅣwith severe bladder bulging.

OBJECTIVETo judge whether algesia sensitization of some acupoints is existed and whether the acupoint algesia sensitization area is expanded in the patients of intestinal cancer.

METHODSTotally, 30 patients of intestinal cancer and 30 healthy subjects were included. The electronic Von Fray was used to determine the pressure-pain thresholds at 13 acupoints relevant with gastrointestinal disorders and the reference points at the sites 1and 2lateral to those points as well as the sites at the corresponding nerve segments. Compared with the pressure-pain thresholds at the reference points of the different segments, the relative value was calculated. The changes were analyzed in the pressure-pain thresholds at the relevant acupoints on the body surface in the patients of intestinal cancer as compared with the relative pressure-pain thresholds in the healthy volunteers.

RESULTSThe pressure-pain thresholds at Zusanli (ST 36), Shangjuxu (ST 37), Xiajuxu (ST 39), Quchi (LI 11) and Dachangshu (BL 25) in the patients of intestinal cancer were all significantly reduced as compared with those of the healthy subjects (<0.05,<0.01,<0.001). At the non-acupoint sites 1and 2lateral to those acupoints as well as at the sites of the same segments, the pressure-pain thresholds were reduced significantly as compared with the control group (<0.05,<0.01,<0.001). Particularly, the sensitization zone of Yinlingquan (SP 9) focused on the acupoint, the site 1lateral to it as well as the non-acupoint sites of the same segments (<0.01,<0.001).

CONCLUSIONThe acupoint sensitization is displayed at Zusanli (ST 36), Shangjuxu (ST 37), Xiajuxu (ST 39), Quchi (LI 11), Dachangshu (BL 25) and Yinlingquan (SP 9) and the sensitization area is expended in the patients of intestinal cancer.

Objective To investigate the effect of small interfering RNA (siRNA) interference in the expression of epidermal growth factor receptor (EGFR) on the radiosensitivity of esophageal squamous carcinoma (Eca-109) and esophageal adenocarcinoma (OE-19) cell lines.Methods Human Eca-109 and OE-19 cell lines were selected as study subjects.Various EGFR-siRNA and negative siRNA were synthesized chemically through lipofection.Reverse transcription-polymerase chain reaction and Western blot were applied to measure the expression of EGFR before and after transfection,and the CCK8 assay was applied to analyze the influence of transfection on cell proliferation.Blank control groups of Eca-109 and OE-19 cells (O1 and O2 groups),simple irradiation groups (R1 and R2 groups),and EGFR-siRNA irradiation groups (E-R1 and E-R2 groups) were set,and the doses for single irradiation were 0,2,4,6,and 8 Gy.The colony-forming assay was applied to calculate survival fraction (SF) and sensitization enhancement ratio (SERD0 ratio),and flow cytometry was applied to evaluate the influence of EGFR-siRNA combined with radiotherapy on cell cycle distribution and apoptosis rate,and the dose for single irradiation was 6 Gy.Results The expression of EGFR in both cell lines was significantly down-regulated by EGFR-siRNA,and the inhibition rate of cell proliferation by transfection was＜5％ (4.9％ and 4.5％,respectively).The results of colony-forming assay showed that the cells in the E-R1 and E-R2 groups had a lower SF than those in the O1 and O2 groups,with an SERD0ratio of 1.40 and 1.01,respectively.The results from flow cytometry showed that compared with the E-R2 group,the E-R1 group had a higher proportion of cells in G2/M phase and a lower proportion of cells in S phase after irradiation (P=0.016 and 0.028),as well as a higher apoptosis rate (P=0.007).Conclusions Compared with the cell line OE-19,the cell line Eca-109 has a significantly increased radiosensitivity when treated with siRNA interference in EGFR expression.

Objective To understand patient pathway and clinical characteristics of chronic diseases in urban areas of Shanghai. Methods A total of 10 002 residents were enrolled and assigned to the chronic disease group (including hypertension, diabetes, coronary heart disease, myocardial infarction, and ischemic stroke) and the non-chronic disease group. Body mass index,fasting blood glucose, triglyceride,total cholesterol, high-density lipoprotein cholesterol and low-density lipoprotein cholesterol were tested.Difference of patient pathway and clinical characteristics of those chronic diseases was compared. Results Above chronic diseases were observed in 37.7% participants. About 2/3 diseases were confirmed and 80% patients were followed up in healthcare units not far away from home. Patients with coronary heart disease and myocardial infarction showed more outpatient visit to tertiary hospitals (P＜0. 05 ). However, patients with ischemic stroke had health check, rehabilitation and pharmacy done mainly in local healthcare centers (P＜0. 05 ). Diastolic blood pressure of patients visiting local doctors was significantly decreased (P＜0. 05). Conclusion Some differences in patient pathway were found in this study. Communication and cooperation between medical institutions should be intensified for effective chronic disease control.