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1.
Article in Chinese | WPRIM | ID: wpr-862724

ABSTRACT

Objective To investigate the pollution levels of six indicator polychlorinated biphenyls (PCBs) in animal-derived foods in Hebei Province. Methods A total of 96 food samples (including beltfish, snakehead, egg, pork liver, pork and beef meat) were collected from Hebei Province in 2019. The contents of six indicator PCBs (PCB 28, PCB 52, PCB 101, PCB 138, PCB 153 and PCB180) in different food samples were determined using isotope dilution-high resolution gas chromatography-high resolution mass spectrometry (HRGC-HRMS). Results The contents of indicative PCBs in fish samples ranged from 0.12 to 0.32 ngg-1 fresh weight, while the content of PCBs in other samples ranged from 0.11 to 1.10 ng g-1 fat. PCB 138 and PCB 153 were the main compounds detected in fish samples, while PCB 28 and PCB 52 were the main compounds detected in other samples. The average estimated daily dietary intake of PCBs for residents in Hebei Province was 0.14 ng kg-1·bw-1·d-1, and the highest contribution rate was beltfish (61.52%). Conclusion The pollution levels of indicator PCBs in animal-derived foods in Hebei Province are relatively low, and the residents has lower health risks through dietary intake of indicator PCBs.

2.
Cancer Research and Clinic ; (6): 168-173, 2021.
Article in Chinese | WPRIM | ID: wpr-886028

ABSTRACT

Objective:To explore the expressions of miRNA-17-92 (miR-17-92) cluster and mitofusin 2 (MFN2) protein in endometrial cancer (EC) and their clinical significances.Methods:A total of 72 EC tissues, 36 endometrial lesions of patients with endometrial atypical hyperplasia, and 22 normal endometrial tissues from total hysterectomy for grade Ⅲ cervical intraepithelial neoplasia in the Second Affiliated Hospital of Shandong First Medical University from January 2008 to December 2014 were collected; at the same time, all patients' paraffin-embedded tissues were collected. Real-time quantitative polymerase chain reaction was used to detect the expression level of miR-17-92 in each tissue. Immunohistochemical SP method was used to detect the localization and expression level of MFN2 protein in each paraffin-embedded tissue. The correlation of miR-17-92 and MFN2 protein with clinicopathological features of EC patients was analyzed. Kaplan-Meier method was used to draw survival curve of patients with different miR-17-92 and MFN2 levels, and log-rank test was made; Cox proportional hazard regression model was used for multivariate survival analysis.Results:The relative expression of miR-17-92 in EC, atypical hyperplasia and normal endometrial tissues were 1.49±0.46, 1.01±0.30 and 0.69±0.20, respectively. The expression of miR-17-92 in EC tissues was higher than that in the other endometrial tissues, and the differences were statistically significant (both P < 0.01). The high-expression rates of MFN2 protein in EC, atypical hyperplasia and normal endometrial tissues were 20.8% (15/72), 39.4% (13/33) and 85.0% (17/20); the high-expression rate of MFN2 protein in EC tissue was lower than that in the other endometrial tissues, and the differences were statistically significant (both P < 0.012 5). In EC patients, the relative expression of miR-17-92 in patients with histological type Ⅱ was higher than that in patients with histological type Ⅰ ( P < 0.05); the relative expression of miR-17-92 in patients with myometrial invasion depth ≥1/2 were higher than that in patients with myometrial invasion depth <1/2 ( P < 0.05). The high-expression rate of MFN2 protein in patients with histological type Ⅰ was higher than that in patients with histological type Ⅱ ( P < 0.05); the high-expression rate of MFN2 protein in patients with International Federation of Gynecology and Obstetrics (FIGO) grade Ⅰ was higher than that in patients with FIGO grade Ⅱ and Ⅲ ( P < 0.05). When the EC patients were grouped according to the median relative expression of miR-17-92 (1.421), Kaplan-Meier survival analysis showed that the median overall survival (OS) time of the miR-17-92 low-expression group (36 cases) was not reached, and the high-expression group (36 cases) was 36 months (95% CI 32-42 months), and the difference in OS between the two groups was statistically significant ( P = 0.049); the median OS time of the MFN2 high-expression group (15 cases) was not reached, and the low-expression group (57 cases) was 38 months (95% CI 33-41 months), and the difference in OS between the two groups was statistically significant ( P = 0.046). Multivariate Cox regression analysis showed that the expression levels of miR-17-92 and MFN2 were independent influencing factors for the survival of EC patients ( HR = 3.10, 95% CI 1.36-7.07, P = 0.007; HR = 0.30, 95% CI 0.09-0.99, P = 0.048). Conclusion:The high-expression of miR-17-92 and low-expression of MFN2 protein in EC tissues may be involved in the occurrence and development of EC, and they can be used as indicators for judging the prognosis of EC patients.

3.
Article in Chinese | WPRIM | ID: wpr-885978

ABSTRACT

Objective: To observe the clinical efficacy of ginger-partitioned moxibustion plus pediatric massage (tuina) in treating infantile diarrhea due to spleen deficiency. Methods: Ninety infants were randomly divided into a massage plus moxibustion group, a massage group and a drug group by the random number table method, with 30 cases in each group. The intervention was conducted for two consecutive courses. The infants in the massage plus moxibustion group were treated with pediatric massage and ginger-partitioned moxibustion at Shenque (CV 8). The infants in the massage group were treated with pediatric massage alone, while those in the drug group were treated with smecta. The primary and secondary symptom scales were assessed before and after treatment and at the follow-ups, and the total effective rate was evaluated after treatment. Results: The total effective rate in the massage plus moxibustion group was significantly different from that in the massage group and drug group (both P<0.05). After treatment, the scores of primary and secondary symptoms decreased in all three groups, with statistically significant intra-group differences (all P<0.05); the scores of primary symptoms were significantly different between the massage plus moxibustion group and the drug group (P<0.05); the scores of secondary symptoms in the massage plus moxibustion group and the massage group were significantly different from that in the drug group (both P<0.05). The differences in the time to recover normal bowel movement frequency among the three groups were not statistically significant (P>0.05). Conclusion: Ginger-partitioned moxibustion plus pediatric massage compared with pediatric massage or smecta monotherapy shows superior clinical efficacy in treating infantile diarrhea due to spleen deficiency, and has the advantages of appetite improvement, physique strengthening and short course.

4.
Article in Chinese | WPRIM | ID: wpr-884572

ABSTRACT

Objective:To preliminarily investigate the efficacy and safety of bevacizumab plus neoadjuvant chemotherapy combined with concurrent chemoradiotherapy in the treatment of locally advanced giant cervical cancer (LACC).Methods:Twenty-four patients with LACC who were treated with bevacizumab combined with neoadjuvant chemotherapy were assigned into the study group, and 30 patients receiving neoadjuvant chemotherapy in phase Ⅱ clinical trial (ChiCTR-TRC-11001832) were allocated in the control group. The survival rate was calculated by the Kaplan- Meier method, and the significance of differences between the variables was determined by the log-rank test. Results:The tumor volumes were (1.64±23.15) cm 3 and (12.83±15.08)( P=0.037), and the complete remission (CR) rates were calculated as 45.8% and 13.3%( P=0.004) in the study and control groups after neoadjuvant chemotherapy. The tumor volumes were (0±1.5) cm 3 and (1.00±10.63) cm 3( P=0.022) and the CR rates were 70% and 50%( P=0.009) in the study and control groups before afterloading treatment. The median follow-up was 24.6(9.3-101.7) months. The 1-and 2-year overall survival rates were 96%, 96% and 90%, 71%( P=0.110), the recurrence-free survival rates was 96%, 96% and 97%, 89%( P=0.512), and the distant metastasis-free survival rates were 96%, 88% and 83%, 80%( P=0.297) in the study and control groups, respectively. Adverse reactions were acceptable in both groups. Conclusion:Bevacizumab combined with neoadjuvant chemotherapy can significantly reduce the tumor volume, improve the tumor CR rate and yield tolerable adverse reactions.

5.
Article in Chinese | WPRIM | ID: wpr-884348

ABSTRACT

Objective:To evaluate the efficacy and safety of dienogest (DNG) in the treatment of refractory endometriosis-associated pain (REAP).Methods:In this study, REAP was defined according to the following criteria: (1) the pain duration was ≥12 months and visual analogue scale (VAS)≥60 mm; (2) the previous treatments with over two medicines like oral contraceptives and levonorgestrel-releasing intrauterine system failed to achieve satisfactory relief of pain, with VAS reduction less than 50%; with gonadotropin-releasing hormone agonist or mifepristone, the pain could be controlled temporarily, but it recurred after discontinuation of medicines; (3) the pain could not be relieved by surgery or even repeated surgeries. In the present study, 48 patients with REAP were treated with DNG 2 mg/day orally and the clinical outcomes were retrospectively analyzed. The VAS scores, levels of CA 125, estradiol, FSH, LH and changes in the size of endometriotic lesions before and after treatment were compared respectively. The side effects were also analyzed. Results:The average duration of DNG treatment was (20.1±12.8) months. After 3 months of medication, the VAS score was significantly reduced from (77.9±15.8) mm to (20.8±10.7) mm ( P<0.01), and CA 125 level was significantly reduced from (95±139) kU/L to (38±45) kU/L ( P<0.05). The effects were maintained with continuation of DNG treatment. Endometriotic lesions tended to shrink, after 12 months of DNG treatment, the size of ovarian endometriomas was reduced significantly from (3.1±1.0) cm to (1.9±1.2) cm ( P<0.05). The mean level of estradiol was maintained at 124.82-221.04 pmol/L and levels of FSH and LH did not change significantly during the treatment. The major side effect was irregular bleeding (75%, 36/48). Conclusions:DNG could effectively relieve REAP and is a well-tolerated therapy. It may supply an alternative option for patients with REAP.

6.
Article in Chinese | WPRIM | ID: wpr-884240

ABSTRACT

Objective:To investigate the safety of early hip fracture surgery for elderly patients on clopidogrel.Methods:This retrospective study included 242 consecutive elderly patients (≥65 years) with acute hip fracture who had undergone surgery at Department of Orthopaedic Trauma, Beijing Jishuitan Hospital between November 2016 and April 2017. Of them, 20 were assigned into the study group who had taken clopidogrel before injury but discontinued its use within 4 days before surgery. They were 6 males and 14 females, with a median age of 80 years (77, 81). Their operation procedures for hip fracture included internal fixation with cannulated screws for femoral neck fracture in 2 cases, hemiarthroplasty for displaced femoral neck fracture in 11 cases, and internal fixation for intertrochanteric fracture in 7 cases. The control group included 222 patients who had undergone the same operative procedures but not taken any antiplatelet or anticoagulant drugs. The 2 groups were compared in terms of time between admission and operation, operation duration, intraoperative blood loss, perioperative transfusion and complications related to bleeding to analyze the safety of early surgery.Results:There was no significant difference in the preoperative general data between the 2 groups, showing comparability ( P>0.05). There was no significant difference between the 2 groups in the time between admission and operation [42.5 (36.3, 48.0) h for the study group versus 43.0 (28.0, 61.0) h for the control group] ( P=0.870). The median time between the last use of clopidogrel and operation was 55.0 (30.5, 71.0) h. There were no significant differences between the 2 groups in preoperative hemoglobin, operation duration, intraoperative blood loss, rate or amount of perioperative blood transfusion, or rate or amount of wound drainage ( P>0.05). The rate of general anesthesia was significantly higher for the study group (45.0%, 9/20) than for the control group (18.5%,41/222) ( P=0.012). No complications related to spinal hematoma occurred in the patients receiving spinal anesthesia from the study group. Wound hematoma and subsequent infection occurred in 2 patients from the control group. Conclusion:Early hip fracture surgery is safe for elderly patients on clopidogrel.

7.
Article in Chinese | WPRIM | ID: wpr-883022

ABSTRACT

Objective:To study the changes of food characters in early swallowing recovery in patients with different laryngeal function preservation surgery.Methods:Collected patients with laryngeal cancer hypopharyngeal cancer who underwent laryngeal function preservation surgery in Lihuili Hospital of Ningbo Medical Center from January 2019 to March 2020. By fiberoptic endoscopic evaluation of swallowing (FEES) combined with Penetration and Aspiration Scale (PAS), prospectively observed the aspiration and invasion of solid, paste, fluid and other food in the early stage of trial feeding in patients with laryngeal hypopharyngeal cancer undergoing open laryngeal function preservation.Results:Among the 69 patients, 21 had vertical partial laryngectomy and 19 had partial pharyngeal partial laryngectomy. 15 days after the operation, 2 groups of patients after solid and paste food adaptability scored (1.14±0.36), (1.29±0.56) and (2.53±2.04), (2.84±2.31) points, Friedman Mtest for comparison difference had statistical significance ( Mvalues were 23.463 and 22.227, P<0.01); the liquid food for adaptability scored (2.10±1.09), (4.42±2.24) points, the pairwise comparison of liquid, solid and paste showed statistically significant differences ( tvalues were-0.976 to 1.105, P<0.05). The pairwise comparison of the adaptability of the two groups on 20 days after surgery showed no statistically significant difference ( P>0.05).Throat on the cricoid cartilage resection-ring hyoid epiglottis anastomosis (SLCP-CHEP) was 17 cases, laryngeal glottis level partial resection was 12 cases; postoperative 15 days the adaptability on the behavior of three kinds of food grade 2 groups of patients (4.65±1.90), (5.59±1.46), (6.53±1.13) points and (6.67±1.07), (4.50±2.07), (6.92±0.79) points, respectively; Minspection differences were statistically significant ( Mvalues were 29.525, 22.136, P<0.01).The pairwise comparison of solid and paste food in the two groups 20 days after the operation showed no statistically significant difference ( P>0.05), while the difference of liquid and paste was statistically significant ( tvalues were-1.375 to-0.853, P<0.05). Conclusion:In the early recovery of patients undergoing laryngeal function preservation surgery, the vertical group and the partial pharyngeal partial laryngectomy group has better adaptability to solid and paste food. The horizontal group has better adaptability to paste, the CHEP group has better adaptability to solid, and the four groups has the worst adaptability to convection, the recovery time of convective mass between the CHEP group and the horizontal group was longer. To understand the adaptability of patients with different surgical methods to food traits at the early stage of trial feeding can help to implement targeted rehabilitation programs, carry out progressive diet training, and reduce the complications of misinvasion, aspiration, aspiration pneumonia and other complications in the recovery cycle.

8.
Article in Chinese | WPRIM | ID: wpr-882768

ABSTRACT

Objective:To investigate the proper choice and improve the survival rate in neonates suffering from giant omphalocele (GO)with liver protrusion by analyzing the clinical characteristics, different treatments and outcomes.Methods:Neonates with GO admitted in Department of Neonatal Surgery in Wuhan Children′s Hospital were retrospected from January 2009 to May 2019.The treatment methods include: (1) repaired with similar silo-bag by staged operation; (2) one-stage repair with patch or not; (3) delayed repair by conservative treatment for some time (from 2 to 8 weeks) firstly.Data included gestational age, gender, birth weight, average diameter of omphalocele, contents of omphalocele, associated malformation, treatment method, duration of ventilator use and clinical outcome.These neonates were divided into 2 groups according to the contents of protrusion: group with liver protrusion and group with liver and other organs protrusion.Clinical data were summarized and compared between different groups.Results:Sixteen cases were collected, including 9 males and 7 females.The average age was (1.25±0.45) d (1-2 days), the average birth weight was (2.48±0.37) kg, and pregnant week was (36.23±1.17) weeks.The average diameter of the omphalocele was (9.88±3.30) cm, ranging from 5 cm to 15 cm.Seven cases were belonged to the group with liver protrusion, cases undergone one-stage repair, delayed repair were 6 cases and 1 case, respectively.There were 9 cases in group with liver and other organs protrusion, and the protruded organs included liver, intestine, colon or spleen.Among them, cases needed one-stage repair, delayed repair and silo-bag repair were 3 cases, 3 cases, 3 cases, respectively.Cases needed respiratory machine were 3 cases (42.8%) and 8 cases (88.89%) in group with liver protrusion and group with liver and other organs protrusion, respectively.Neonates had a longer time of needing respiratory machine in group with liver protrusion, comparing with the neonates in group with liver and other organs protrusion[(30.67±19.0) h vs.(106.25±69.36) h, P=0.021], and the risk rate to use respiratory machine was 5.143(95% CI: 0.727-36.368). There were no dead cases in group with liver protrusion.Three cases were dead in group with liver and other organs protrusion.All the patients were followed from 3 months to 4 years, and hernia in abdominal wall was found in 5 cases, including 1 case in group with liver protrusion and 4 cases in group with liver and other organs protrusion.If the dead cases had been excluded, the rate of hernia was 66.7% (4/6 cases) in group with liver and other organs protrusion. Conclusions:Individual treatment should be emphasized in neonates suffering from GO with liver protrusion.Neonates with single liver protrusion have a better prognosis than those with liver and other organs protrusion.One-stage repair is recommended in the former, and the delayed repair is highly recommended in the latter.The accessory liver should be considered when GO neonates presenting liver protrusion.

9.
Article in Chinese | WPRIM | ID: wpr-878944

ABSTRACT

By preparing 15 batches of lyophilized powder samples of substance benchmark in Houpo Wenzhong Decoction,the fingerprint,index component content and extract rate were determined,and the characteristic peaks,the range of similarity with the reference map,the content range and transfer rate range of magnolol,hesperidin,glycyrrhizic acid and pinocembrin,the extract rate range and the change range were clarified. The results showed that the similarity between the fingerprint of substance benchmark and the reference map R generated from the 15 batches of substance benchmark samples was higher than 0. 90. The assignment of the characteristic peaks in the full prescription's fingerprint of the herbs except Poria cocos was clarified. Nineteen characteristic peaks were assigned,and 12 characteristic peaks were assigned by the reference substance,of which 4 were from Magnolia ocinalis Cortex,5 from Exocarpium Citri Rubrum,2 from Radix aucklandiae,3 from Glycyrrhiza Radix et Rhizoma,4 from Semen Alpiniae Katsumadai,and one from Rhizoma Zingiberis and Zingiber officinale Roscoe. The index component content range and transfer rate range were 0. 80%-1. 14% and 20. 25%-39. 61% for hesperidin,0. 49%-0. 79% and 23. 09%-33. 87%for glycyrrhizic acid,0. 03%-0. 07% and 3. 55%-10. 09% for pinocembrin,0. 15%-0. 38% and 8. 08%-24. 35% for magnolol. The extract rate range and the change range were22. 60%-25. 57% and 12. 67%-23. 68% respectively. In this study,we introduced the concepts of index component content,fingerprint,extract rate,explored the transfer relation of quality value transmitting of substance benchmark in Houpo Wenzhong Decoction,and initially established the quality standard of Houpo Wenzhong Decoction,all of which would provide ideas for the development and research of similar prescriptions.


Subject(s)
Benchmarking , Chromatography, High Pressure Liquid , Drugs, Chinese Herbal , Glycyrrhiza , Quality Control
10.
Article in English | WPRIM | ID: wpr-878406

ABSTRACT

OBJECTIVES@#A study was conducted to explore the expression pattern and function of ferritin heavy polypeptide gene (fth1b) in zebrafish pharyngeal teeth development and lay the foundation for subsequent research on teeth development and mineralization.@*METHODS@#The zebrafish embryos were harvested at 56, 72, 96, and 120 h after fertilization. The expression of fth1b in zebrafish pharyngeal teeth development was detected by whole embryo @*RESULTS@#The expression pattern of fth1b gene was very similar to that of the known zebrafish pharyngeal teeth marker dlx2b and was specifically expressed in the zebrafish pharyngeal teeth during development. After the specific knockout of the gene fth1b, the earliest gene that can be detect in zebrafish pharyngeal teeth-pitx2 was expressed normally during early development. The dlx2b expression was not significantly different from that of wild type zebrafish, but the mineralization of pharyngeal teeth in the mutant was weaker than that of wild type zebrafish.@*CONCLUSIONS@#The gene fth1b is specifically expressed in zebrafish pharyngeal teeth and acts on their early mineralization.


Subject(s)
Animals , In Situ Hybridization , Odontogenesis , Pharynx , Tooth , Zebrafish/genetics
11.
Article in English | WPRIM | ID: wpr-878332

ABSTRACT

Objective@#Testicular germ cell tumors (TGCT) are the most common cancer among men aged 15 to 39 years. Previous studies have considered factors related to TGCT survival rate and race/ethnicity, but histological type of the diagnosed cancer has not yet been thoroughly assessed.@*Methods@#The data came from 42,854 eligible patients from 1992 to 2015 in the Surveillance Epidemiology and End Results 18. Frequencies and column percent by seminoma and nonseminoma subtypes were determined for each covariates. We used Cox proportional hazard regression to assess the impact of multiple factors on post-diagnostic mortality of TGCT.@*Results@#Black males were diagnosed at a later stage, more commonly with local or distant metastases. The incidence of TGCT in black non-seminoma tumors increased most significantly. The difference in survival rates between different ethnic and histological subtypes, overall survival (OS) in patients with non-seminoma was significantly worse than in patients with seminoma. The most important quantitative predictor of death was the stage at the time of diagnosis, and older diagnostic age is also important factor affecting mortality.@*Conclusion@#Histological type of testicular germ cell tumor is an important factor in determining the prognosis of testicular cancer in males of different ethnic groups.


Subject(s)
Adult , Health Status Disparities , Humans , Male , Neoplasms, Germ Cell and Embryonal/pathology , Prognosis , Risk Factors , SEER Program/statistics & numerical data , Seminoma/pathology , Survival Rate/trends , Testicular Neoplasms/pathology , United States/ethnology
12.
Article in Chinese | WPRIM | ID: wpr-877085

ABSTRACT

Objective To analyze the epidemiological characteristics of food poisoning in Shenzhen from 2009 to 2018, and to provide a scientific basis for formulating control strategies of food poisoning. Methods The data of food poisoning events in Shenzhen from 2009 to 2018 was analyzed with descriptive epidemiological methods. Results There were 182 reported food poisoning events, resulting in 1786 cases and 3 death. The incidence of food poisoning events had a seasonal peak during May to September, and a total of 119 reported food poisoning events (65.39%, 119/182) occurred in that period of time with 1156 cases (64.73%, 1156/1786). There were 77 food poisoning events (42.31%) occurring in collective canteens with 927 cases (51.91%), making them the most frequent locations for food poisoning. The main pathogenic factors were bacteria, poisonous plants and chemicals. Incidents of bacterial food poisoning were mainly caused by Vibro parahemolyticus (51.73%, 60/116), Salmonella (26.73%, 30/116), and Staphylococcus aureus enterotoxin (11.21%, 13/116), etc. Hyacinth bean toxin and mushroom were responsible for 33.33% of the incidents caused by poisonous plants. Incidents of chemical food poisoning were mainly caused by nitrite (8.33%). Conclusion The prevention and control of food poisoning in Shenzhen should be focused on reducing bacterial food poisoning such as Salmonella and Vibrio parahaemolyticus, and supervision of food safety of catering units and collective canteens should be strengthened. Additionally, health education on prevention and control of food poisoning should be targeted at the high-risk population to reduce the risk of food poisoning.

13.
Acta Pharmaceutica Sinica ; (12): 855-864, 2021.
Article in Chinese | WPRIM | ID: wpr-876517

ABSTRACT

Compared with crystalline drugs, their amorphous forms present long-range disordered molecular arrangements, and often exhibit higher apparent solubility and dissolution. However, several small molecule amorphous drugs may exhibit gelation phenomenon during the dissolution process, and show abnormal dissolution behavior with significantly lower dissolution than crystalline drugs. The current study aims to discover the relationship between the gelation of amorphous drugs and their abnormal dissolution, and further explore the internal gelation mechanism. Amorphous simvastatin (SIM), carvedilol (CAR), and irbesartan (IRB) were prepared by melt cooling method and characterized via X-ray powder diffraction (XRPD), differential scanning calorimetry (DSC), and Fourier transform infrared spectroscopy (FT-IR). Gel formation causes the dissolution of these three amorphous drugs to be significantly lower than their crystalline state. The formed gels were characterized as three-dimensional dense network structures by scanning electron microscope (SEM). Furthermore, amorphous SIM, CAR and IRB showed the critical gel temperature at 8-15 ℃, 25-30 ℃ and 45-50 ℃, and amorphous CAR and IRB showed the critical gel pH at 1 and 0.25. The mechanism of gel formation was proposed to be closely related to the transformation of amorphous drugs into the supercooled liquid state (as the important driving force) and the protonation induced self-assembling under acidic conditions. In addition, the wettability and properties of amorphous drugs also affect the formation of gelation.

14.
Acta Pharmaceutica Sinica ; (12): 487-495, 2021.
Article in Chinese | WPRIM | ID: wpr-873772

ABSTRACT

Nanoparticles have better applicability in the detection, treatment of cancer and various difficult diseases, but mononuclear phagocytosis system can seriously shorten the time of nanoparticles in vivo circulation, reduce the drug efficacy. The protein crown formed on the surface of the nanoparticle after entering the body can change its surface properties, interfere with the recognition of phagocytes, and thus affect its circulation time in vivo. This article outlines the general composition and formation process of protein crowns. It also summarizes the influence of the physical and chemical properties of nanoparticles, such as particle size, surface charge, hydrophilicity and surface materials on the formation of protein crowns. The protein crown affects the circulation of nanoparticles in vivo, mainly because the adsorbed opsonic protein promotes cell phagocytosis. Therefore, we also introduce the method of using protein crowns to promote the long circulation of nanoparticles in vivo. By designing appropriate physical and chemical properties, surface modification, and directed design of protein crowns, the adsorption of proteins on the surface of nanoparticles can be reduced. Therefore, it can reduce the clearance of nanoparticles in the mononuclear phagocytic system (mainly the phagocytes of the liver and spleen), and achieve the goal of long circulation of nanoparticles in the body.

15.
Acta Pharmaceutica Sinica ; (12): 538-544, 2021.
Article in Chinese | WPRIM | ID: wpr-873758

ABSTRACT

M701 is a bispecific CD3/EpCAM T-cell engager antibody for the treatment of malignant ascites. We developed a population pharmacokinetic/pharmacodynamic (PK/PD) model to quantitatively describe and predict the antitumor effect of M701 in human colorectal cancer xenograft mice. We developed the M701 PK model based on plasma concentration data after i.v. administration. A tumor growth model for human colorectal cancer xenograft was developed to evaluate the antitumor effect of M701. We additionally simulated the inhibitory effect of M701 on tumor volume under different dose regimens based on a PK/PD model. A two-compartment model was developed to predict the PK in human colorectal cancer xenograft mice. The relationship between the M701 concentration and tumor growth inhibition was characterized by a combined Simeoni tumor growth/transit compartment model. The estimated pharmacodynamic parameters were related to the tumor growth characteristics λ0 (0.212 d-1) and λ1 (0.044 7 cm3·d-1), to the drug potency k2 (0.071 5 mL·ng-1·d-1), and to the kinetics of tumor cell death k1 (2×10-5 d-1). A model visual predictive check showed that both the PK model and the tumor growth model closely fit the observed data. Simulated tumor growth after administration of M701 (0.5 mg·kg-1 every 6 days and 0.25 mg·kg-1 every 3 days) could be effectively inhibited. This population PK/PD model of M701 provides insight into the antitumor effect of M701 and supports the further therapeutic development of M701.

16.
Article in Chinese | WPRIM | ID: wpr-873346

ABSTRACT

Objective:To study the effect of Zuoguiwan on the differentiation of CD4-CD8-T cells in thymus during the development of kidney-deficient fetal rats and the application value of kidney and essence-tonifying method, in order to explore the theoretical connotation of "kidney being the origin of congenital constitution". Method:Male and female rats were paired at a ratio of 2∶1, and three stress methods were combined to construct the kidney-deficient model. Pregnant rats were divided into control group, model group, thymosin group (0.003 g·kg-1), and low-dose Zuoguiwan group and high-dose Zuoguiwan group (2,8 g·kg-1). Normal saline was given to the control group, model group was used for modeling and given normal saline by gavage, thymosin group was given thymosin capsule solution by gavage, and low-dose Zuoguiwan group and high-dose Zuoguiwan group were given Zuoguiwan suspension by gavage. Embryos that were 16 days, 19 days and born on the first day (E16, E19, P1) were selected to calculate fetal rat thymus index. Electron microscope was used to observe thymic epithelial cell ultrastructure of fetal rats. Enzyme-linked immunosorbent assay (ELISA) method was used to detect thymus thymosinβ4 (TMSβ4) and thymosinα1 (Tα1) content, fluid cytology detection of fetal rats on the surface of CD4, CD8, CD25, CD44 expression for identifying T cell type. Result:The morphology of thymus epithelial cells in the model group was irregular, the nucleus was deformed, and the chromatin of the nucleus was significantly increased. The results of ELISA showed that the content of TMSβ4 and Tα1 in thymus increased in the model group and the low-dose and high-dose Zuoguiwan groups. Flow cytometry showed that, compared with the control group, CD4-CD8-T cells were significantly increased in the model group at E16, E19 and P1 stages (P<0.05), suggesting that T cells were blocked during the development from DN to DP. CD4-CD8-CD25-CD44-T (DN4) was significantly increased (P<0.05), suggesting that T cell development was inhibited during DN4-DP transition. Compared with the model group, CD4-CD8-T cells were significantly reduced in low and high-dose groups (P<0.05) at E16, E19 and P1 stages. At the same time, DN4 was significantly reduced (P<0.05), suggesting that Zuoguiwan could promote the development of T cells from DN4 stage to DP stage as thymosin. Conclusion:Zuoguiwan can improve the structure of thymus epithelial cells in rats with kidney deficiency, and induce the differentiation of T cells in thymus from DN4 stage to DP stage by increasing the secretion of TMSβ4 and Tα1 in thymus of embryonic rats, indicating that Zuoguiwan can promote the development and maturation of T cells and regulate the immune status of fetal rats with kidney deficiency by tonifying kidney and spermatogenesis.

17.
Article in Chinese | WPRIM | ID: wpr-873164

ABSTRACT

Objective:To observe the clinical efficacy of Jiwei Huangqi Guizhi Wuwutang combined with Xingnao Kaiqiao acupuncture on shouder-hand syndrome (SHS), and its effect on neurogenic inflammatory factors and hemorheology. Method:One hundred and forty-eight patients were randomly divided into control group and observation group (74 cases). Both groups' patients got rehabilitation measures, such as diclofenac sodium sustained release tablets for two to four weeks, 75 min/time, 1 time/day, and patients with apparent swelling got prednisone acetate tablets for one to two weeks, 10 min/time, 1 time/day. And patients in control group got Xingnao Kaiqiao acupuncture, 1 time/day, 6 times/week. Control grouporal Naoxintong capsule 4 tablets/time,3 times/day, patients in observation group were added with Jiwei Huangqi Guizhi Wuwutang, 1 dose/day. The courses of treatment were 4 weeks. Before and after treatment, shoulder hand syndrome scale (SHSS), the upperextremities of the Fugl-meyer movement assessment (U-FMA), ability of daily life activities (ADL), Qi deficiency and blood stasis syndrome and clinical efficacy were scored, disappearing time of pain and swelling were recorded, and levels of calcitonin gene related peptide (CGRP), substance P (SP), bradykinin (BK) and hemorheology were detected. Result:The clinical efficacy in observation group was better than that in control group (Z=2.106, P<0.05). And scores of sensory, autonomic, motion according to SHSS scale and the total scale of SHSS were all lower than those in control group (P<0.01). Disappearing time of pain and swelling were shorten than those in control group (P<0.01). After treatment, scores of U-FMA and ADL were higher than those in control group (P<0.01), while score of syndrome of Qi deficiency and blood stasis was lower than that in control group (P<0.01). And level CGRP was higher than that in control group (P<0.01), and levels of SP and BK were lower than those in control group (P<0.01). After treatment, whole blood viscosity (high cut, low cut), plasma viscosity, fibrinogen and platelet aggregation rate were all lower than those in control group (P<0.05). Conclusion:In addition to the conventional western medicine therapy, Jiwei Huangqi Guizhi Wuwutang combined with Xingnao Kaiqiao acupuncture can reduce the severity of SHS and clinical syndromes of traditional Chinese medicine, shorten the course of disease, improve the motor function of upper limbs, inhibit the neurogenic inflammatory reaction, and improve the blood flow, the ability of daily life and the clinical efficacy of patients..

18.
Article in Chinese | WPRIM | ID: wpr-873029

ABSTRACT

Objective:There were 92 kinds of compound preparations containing Ophiopogonis Radix in the 2015 edition of Chinese Pharmacopoeia, but there was no effective method to identify these compound preparations. Because Ophiopogonis Radix and Liriopes Radix are similar in appearance, it is easy to be confused in application. The aim of this study was to set up a thin layer chromatography (TLC) to identify compound preparations containing Ophiopogonis Radix and distinguish Ophiopogonis Radix and Liriopes Radix in the forms of decoction pieces and standard decoction. Method:In this study, decoction pieces of Ophiopogonis Radix and Liriopes Radix were collected and separately prepared as standard decoction. TLC was used to qualitatively identify decoction pieces and standard decoction of Ophiopogonis Radix and Liriopes Radix, and compound preparations containing Ophiopogonis Radix. In the TLC, the lower solution of chloroform-methanol-water (65∶35∶10) was selected as the developing agent and 10% sulfuric acid ethanol solution as the chromogenic agent. Result:The resolution of this TLC was good. Decoction pieces, standard decoction and preparations of Ophiopogonis Radix had the same characteristic strips, which were two bright white fluorescent strips under ultraviolet lamp (365 nm). But these two characteristic strips were not existed in the TLC of decoction pieces and standard decoction of Liriopes Radix. The corresponding components of both of these two strips were identified as mixture containing saponins by LC-MSn, including ophiopogonin Ra, Tb, ophiopogonin D', borneol glycoside, ophiopogonin C and Liriope muscari baily saponins C. Conclusion:The established TLC method, which has significant advantages such as high specificity and sensitivity, can be applied to the characteristic identification of decoction pieces and standard decoction of Ophiopogonis Radix, the identification of compound preparations containing Ophiopogonis Radix, and the distinction of Ophiopogonis Radix and Liriopes Radix, thus serving as an effective method to qualitatively identify Ophiopogonis Radix and its compound preparations.

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Chinese Journal of Neurology ; (12): 341-347, 2020.
Article in Chinese | WPRIM | ID: wpr-870818

ABSTRACT

Objective:To characterize the digital language markers in Alzheimer′s disease (AD) and mild cognitive impairment (MCI) patients, and to explore the pathological effect and aging effect on these markers.Methods:AD ( n=14) and MCI ( n=16) patients from memory clinic in Peking Union Medical College Hospital, age-matched cognitively normal elderly adults ( n=18) and youthful adults ( n=19) as controls participated in the study. The digital speech data of animal fluency test were collected. Novel language markers such as response time, semantic similarity and word frequency were analyzed in addition to the traditional word production, clustering and switching indicators by trained professionals. Multiple linear regression analysis with multiple comparison was used to test the associations of language markers with the cognitive status, adjusting for education. Results:The results of multiple regression analysis showed that, after adjusting for the years of education, statistically significant differences existed in 11 language markers among the four groups ( P<0.001), except for the effective word production in the last 15 s, cluster size, the first word response time and the average semantic similarity. Compared to other three groups, AD group differed significantly in effective word production, effective rate, repetitive rate, effective word production in the first 15 s, the number of subcategories, single word production time and inter-subcategory switching interval ( P<0.001). In addition, compared to cognitively normal youthful group, AD group had less number of switching and shorter semantic maximum distance ( P=0.001, P<0.001); both AD and MCI groups had longer intra-subcategory switching interval ( P<0.001, P=0.001); AD, MCI and cognitively normal elderly groups had significantly higher word frequency ( P<0.001); MCI group had significantly less number of effective word production and subcategories ( P=0.002, P=0.003); both MCI and cognitively normal elderly groups had significantly longer single word production time ( P<0.001). Conclusions:The performance of AD patients on the semantic fluency test task was affected by both pathological effect and normal aging effect. Pathological indicators included effective word production, effective rate, repetition rate, effective word production in the first 15 s, the number of subcategories, inter-subcategory switching interval and single word production time. These results provide a new approach to identify the specific effects of AD dementia.

20.
Chinese Journal of Neurology ; (12): 25-30, 2020.
Article in Chinese | WPRIM | ID: wpr-870760

ABSTRACT

protein (T-tau),phosphorylated-tau protein (P-tau) in diagnosis and differentiation of sporadic Creutzfeldt-Jakob disease (sCJD).Methods sCJD (according to 2009 Brain criteria,2018 Neurology amended criteria),Alzheimer's disease (AD;the National Institute on Aging at National Institutes of Health and the Alzheimer's Association revised guidelines 2011 criteria) and other patients without cognitive impairment,matched for sex and age,in the Department of Neurology,Peking Union Medical College Hospital from 2018 to 2019 were enrolled.Twelve sCJD patients,49 AD patients and 14 normal controls were enrolled.Cerebrospinal fluid (CSF) specimens were collected through gravity dropping directly,and further stored in-80℃ and disposed according to widely used standards.The levels of T-tau and P-tau were measured by ELISA.The data on electroencephalogram and neuroimaging findings of sCJD patients were recorded.Moreover,specimens of sCJD patients were sent to the Chinese Center for Disease Control and Prevention to test 14-3-3 protein and PRNP genotype.Results Using Mann-Whitney U test,T-tau concentrations were found higher in patients with sCJD (1 211(448,2 227) pg/ml) than in AD patients (549(314,1 078) pg/ml;U=178,P=0.0349),and both groups had higher T-tau than the control group (127(79,192) pg/ml;U=20,73,P<0.01).The level of P-tau was significantly increased in AD patients (72(58,109) pg/ml) compared to the control group (27(15,42) pg/ml;U=82,P<0.01),but not in sCJD patients (32(24,47) pg/ml).The T-tau/P-tau ratio was higher in sCJD patients (29.77(20.01,54.53)) than in AD patients (7.45(4.79,10.43);U=87,P<0.01).Twelve sCJD patients had cotical hyperintensity on diffusion weighted imaging and five had periodic three-phase waves on electroencephalogram.Nine sCJD patients,whose CSF samples were tested in the Chinese Center for Disease Control and Prevention,carried an M/M genotype at codon 129 and E/E at codon 219.Conclusion The CSF tau level and T-tau/P-tau ratio are significantly increased in sCJD,which may promote the diagnosis and differentiation of sCJD in routine clinical setting.

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