ABSTRACT
Purpose: This study aimed to evaluate 5-year outcomes and the late toxicity profile of chrono-chemotherapy with different infusion rates in patients with locally advanced nasopharyngeal carcinoma (NPC). Methods and materials: Our retrospective analysis included 70 patients with locally advanced NPC stages III and IVB (according to the 2010 American Joint Committee on Cancer staging system). Patients were treated with two cycles of induction chemotherapy (IC) before concurrent chemoradiotherapy (CCRT) at Guizhou Cancer Hospital. The IC with docetaxel, cisplatin (DDP) and fluorouracil regimen. Patients were divided into two groups during CCRT. Using a "MELODIE" multi-channel programmed pump, DDP (100 mg/m2) was administered for 12 hours from 10:00 am to 10:00 pm and repeated every 3 weeks for 2-3 cycles. DDP was administered at the peak period of 4:00 pm in the sinusoidal chrono-modulated infusion group (Arm A, n=35). The patients in Arm B received a constant rate of infusion. Both arms received radiotherapy through the same technique and dose fraction. The long-term survival and disease progression were observed. Results: After a median follow-up of 82.8 months, the 5-year progression-free survival rate was 81.3% in Arm A and 79.6% in Arm B (P = 0.85). The 5-year overall survival rate was not significantly different between Arm A and Arm B (79.6% vs 85.3%, P = 0.79). The 5-year distant metastasis-free survival rate was 83.6% in Arm A and 84.6% in Arm B (P = 0.75). The 5-year local recurrence-free survival rate was 88.2% in Arm A and 85.3% in Arm B (P = 0.16). There were no late toxicities of grade 3-4 in either group. Both groups had grade 1-2 late toxicities. Dry mouth was the most common late toxic side effect, followed by hearing loss and difficulty in swallowing. There was no statistically significant difference between Arm A and Arm B in terms of side effects. Conclusion: Long-term analysis confirmed that in CCRT, cisplatin administration with sinusoidal chrono-modulated infusion was not superior to the constant infusion rate in terms of long-term toxicity and prognosis.
ABSTRACT
[Objective]To summarize the academic experience of Professor ZENG Qingqi in the use of classical prescription in the diagnosis and treatment of insomnia combined with reproductive system diseases.[Methods]Through clinical follow-up studying,reading ancient books,Professor ZENG's clinical experience in treating insomnia and reproductive system diseases was analyzed from the aspects of the treatment of insomnia with classical prescription,the treatment ideas of reproductive system diseases with classical prescription,and the concept of homotherapy for heteropathy in Chinese medicine for insomnia combined with reproductive system diseases,which was supported by medical cases.[Results]Professor ZENG's treatment of insomnia combined with reproductive system diseases follows the concept of homotherapy for heteropathy in Chinese medicine,advocating the use of the"five differentiation"diagnostic and treatment mode based on Chinese medicine viewpoint,such as body differentiation,disease differentiation,syndrome differentiation,local differentiation and micro differentiation,and paying attention to promoting medication according to the situation,combining warming and clearing,dredging and tonifying.It is believed that the key to the effectiveness of classical prescription in treating insomnia combined with reproductive system diseases lies in dealing with the problems of"suppressing hyperactivity"and"releasing",emphasizing the reconciliation between the relationship of heart(brain),heart and kidney,and not only dredging to treat the symptoms,but also cultivating and replenishing to treat the root cause.The patient in case one was of insomnia combined with impotence,identified as liver depression and Qi stagnation,spleen and kidney deficiency syndrome,modified Sini Powder and Shenqi Pills was used in treatment.Case two was of insomnia combined with menstruation,identified as disconnection of the heart and kidney,deficiency cold of Chong Ren and blood stasis blocking the uterus,treated with Huanglian Ejiao Decoction and Zhizishi Decoction combined with Wenjing Decoction.Both used classical prescriptions and achieved good results.[Conclusion]Professor ZENG specializes in the treatment of insomnia combined with reproductive system diseases with the use of meridian prescription,flexible identification,and appropriate prescription,with precise efficacy,its rich clinical experience is worth clinical learning and further promotion.
ABSTRACT
Based on the theory of spleen-stomach in The Inner Canon of Yellow Emperor （《黄帝内经》）， the theory of "middle jiao deficiency causes seminal changes" focuses on the ways in which the spleen-stomach deficiency affect male seminal disorders， as well as the ideas and methods of treating seminal disorders from the perspective of the spleen and stomach. Based on the discussion of spleen and stomach in The Inner Canon of Yellow Emperor， the theoretical connotations of “middle jiao deficiency causes seminal changes” are clarified in terms of the scope of the disease， the etiology of the spleen deficiency， the pathogenesis changes， and the treatment of the disease. It is believed that the connotation of "semen" includes the semen itself and the semen chamber as a whole， and that the core pathogenesis of "seminal changes" is the deficiency of spleen and stomach， which also involves kidney deficiency. Taking the theory of "middle jiao deficiency causes seminal changes" as a guide， the treatment idea of "regulating middle jiao and rectifying essence" was established， with the key of tonifying the middle jiao and regulating transportation and transformation of spleen and stomach， and the aim of regulating essence chamber and promoting the metabolism of turbid substances and the production of essence. It is divided into three methods， including tonifying， transporting， and clearing the middle jiao to rectify semen， so as to providing new ideas for the treatment of male seminal disorders from the spleen and stomach.
ABSTRACT
Objective:To establish and assess the precision of pre-surgical condyle position planning using mandibular movement trajectory data for orthognathic surgery.Methods:Skull data from large-field cone beam computed tomography(CBCT)and dental oral scan data were imported into IVSPlan 1.0.25 software for 3D reconstruction and fusion,creating 3D models of the maxilla and mandible.Trajectory da-ta of mandibular movement were collected using a mandibular motion recorder,and the data were inte-grated with the jaw models within the software.Subsequently,three-dimensional trajectories of the con-dyle were obtained through matrix transformations,rendering them visually accessible.A senior oral and maxillofacial surgeon with experience in both diagnosis and treatment of temporomandibular joint disease and orthognathic surgery selected the appropriate condyle position using the condyle movement trajectory interface.During surgical design,the mobile mandibular proximal segment was positioned accordingly.Routine orthognathic surgical planning was completed by determining the location of the mandibular distal segment,which was based on occlusal relationships with maxilla and facial aesthetics.A virtual mandible model was created by integrating data from the proximal and distal segment bone.Subsequently,a solid model was generated through rapid prototyping.The titanium plate was pre-shaped on the mandibular model,and the screw hole positions were determined to design a condylar positioning guide device.In accordance with the surgical plan,orthognathic surgery was performed,involving mandibular bilateral sagittal split ramus osteotomy(SSRO).The distal segment of the mandible was correctly aligned inter-maxillary,while the proximal bone segment was positioned using the condylar positioning guide device and the pre-shaped titanium plate.The accuracy of this procedure was assessed in a study involving 10 patients with skeletal class Ⅱ malocclusion.Preoperative condyle location planning and intraoperative po-sitioning were executed using the aforementioned techniques.CBCT data were collected both before the surgery and 2 weeks after the procedure,and the root mean square(RMS)distance between the preope-rative design position and the actual postoperative condyle position was analyzed.Results:The RMS of the condyle surface distance measured was(1.59±0.36)mm(95％CI:1.35-1.70 mm).This value was found to be significantly less than 2 mm threshold recommended by the expert consensus(P＜0.05).Conclusion:The mandibular trajectory may play a guiding role in determining the position of the mandibular proximal segment including the condyle in the orthognathic surgery.Through the use of a con-dylar positioning guide device and pre-shaped titanium plates,the condyle positioning can be personalized and customized with clinically acceptable accuracy.
ABSTRACT
This paper summarized Professor PENG Peichu's experience in the differentiation and treatment of prostate cancer in three phases and four stages. It is considered that prostatic cancer is categorized into root deficiency and branch excess， with depletion of healthy qi as the root， and the accumulation of cancer toxin as the minifestation. Clinical diagnosis and treatment of prostatic cancer can be divided into three phases and four stages according to the exuberance and decline of pathogenic and healthy qi and the changes of deficiency and excess of yin and yang. In the initial accumulation phase of cancer toxin （yang excess stage）， the key pathogenesis is the accumulation of dampness， heat and static blood， and internal generation of cancer toxin， and the treatment should be resolving toxins， fighting cancer and dispelling yang excess. In the phase of healthy qi deficiency and toxin accumulation （yin deficiency stage）， with the lung and kidney yin deficiency， dampness， heat and static toxin accumulation as the key pathogenesis， the treatment should be centered on mutual generation between metal and water to nourish kidney yin， supplemented with the method of clearing heat and draining dampness， activating blood and resolving toxins， for which self-made Nanbei Formula（南北方）is usually used. In the phase of yang deficiency and cold stagnation （yang deficiency stage and yin excess stage）， with the spleen and kidney yang deficiency， cold dampness stagnation， static heat and toxin accumulation as the key pathogenesis， the treatment should be warming and tonifying spleen and kidney to dissipate cold accumulation； for deficiency of both yin and yang， and excess pathogen obstruction， modified Yanghe Decoction（阳和汤） is recommended， while for yang deficiency， cold congealing and blood stasis， self-made Wenshen Sanjie Formula（温肾散结方） can be used， and for cold dampness binding with cancer toxin， and cold complex with heat， self-made Quanan Formula （泉安方） is advised.
ABSTRACT
Objective To explore the relationship between the expression of M2 pyruvate kinase(PKM2)and E-cad-herin(E-cadherin)in tumor tissues and the clinicopathology and prognosis of breast cancer patients.Methods 447 patients with breast cancer admitted from February 2020 to February 2022 were selected as the objects of this study.Breast cancer tissues and adjacent tissues of patients were taken,and patients were divided into good prognosis group(261 cases)and poor prognosis group(186 cases)according to the prognosis of patients.Immunohistochemistry was used to determine the expression of PKM2 and E-cadherin in the tissues of the patients,and the patients were followed up for 6 months.The patients were divided into groups according to whether the patients had recurrence and metastasis,and the relationship between the expression of PKM2 and E-cadherin in the breast cancer tissues of the patients and the clinicopathology was explored.The expression of PKM2 and E-cad-herin protein between breast cancer tissue and adjacent tissue,and between good prognosis group and poor prognosis group were compared,and the correlation between PKM2 and E-cadherin protein expression and poor prognosis of patients was explored.Results There were no differences in the expression of PKM2 and E-cadherin in breast cancer patients with different ages,tumor sites and tumor sizes(P＞0.05).The positive rate of PKM2 protein expression was higher and the positive rate of E-cadherin protein expression was lower in postmenopausal,middle and highly differentiated,stage I to II and no lymph node metastasis(P＜0.05).The positive rate of PKM2 in patients with poor prognosis was 94.62%,higher than 81.23%in patients with good prognosis;The positive rate of E-cadherin in patients with poor prognosis was 30.65%,which was lower than 46.36%in patients with good prognosis(P＜0.05).By Spearman correlation coefficient analysis,poor prognosis was positively correlated with the positive rate of PKM2 in breast cancer tissues(r=0.195,P＜0.001),and negatively correlated with the positive rate of E-cad-herin protein(r=-0.158,P=0.001).Conclusion PKM2 and E-cadherin protein expression in tumor tissues of breast canc-er patients has some link with the clinicopathology of patients,and there is some correlation with patient prognosis.
ABSTRACT
Objective:To explore the safety and effectiveness of medium-frequency electrotherapy for increasing the volume of the latissimus dorsi muscle.Methods:Fifteen adult New Zealand white rabbits were randomly divided into three groups, namely group A, group B, and group C, with 5 rabbits in each group. This was a self-control study, with the right latissimus dorsi muscle as the experimental group and the left latissimus dorsi muscle as the control group. The three groups corresponded to three different current intensity levels: 7.062 mA for group A (6th gear), 10.593 mA for group B (9th gear), and 14.124 mA for group C (12th gear). After the 12th, 24th, and 36th sessions of the experiment, ultrasonography was used to collect the thickness of the latissimus dorsi muscle. After the 36th electrostimulation, the latissimus dorsi muscle samples were collected to measure their in vivo muscle thickness and wet weight and were then sent for HE and MASSON staining.Results:After the 12th, 24th, and 36th electrostimulation sessions, ultrasonographic sampling in groups A and B showed an increase in the thickness of the right latissimus dorsi muscle compared to the left; for example, the thickness on the right of group B increased by 37.8%. The wet weight data collected after the 36th electrostimulation in groups A and B showed an increase in the right latissimus dorsi muscle compared to the left; for example, the wet weight on the right of group B increased by 5.04%.Conclusions:Different electrostimulation modes of medium-frequency therapy technology can induce muscle fiber thickening or atrophy. In this experiment, the 9th gear (10.593 mA) of medium-frequency therapy technology may be a suitable choice for inducing muscle fiber thickening, and the 12th gear (14.124 mA) may be a suitable choice for inducing skeletal muscle thinning.
ABSTRACT
Objective:To explore the pathological differences of surgically resected specimens of advanced esophageal squamous cell carcinoma (ESCC) to different neoadjuvant therapies (neoadjuvant radiochemotherapy and toripalimab combined with neoadjuvant radiochemotherapy).Methods:Thirty patients diagnosed with advanced ESCC who underwent surgical operation after neoadjuvant therapy in Jiangsu Cancer Hospital from October 2020 to September 2021 were included. Among them, 15 patients received neoadjuvant radiochemotherapy (radiochemotherapy group) and 15 patients were treated with toripalimab combined with radiochemotherapy (immunotherapy combined with radiochemotherapy group). Surgically resected specimens were collected. The histopathological features of primary esophageal lesions and the responses of involved lymph nodes were analyzed and compared between two groups.Results:The major pathological response (MPR) rate in the radiochemotherapy group was 10/15, and 14/15 in the immunotherapy combined with radiochemotherapy group ( P=0.17). The pathological complete response (pCR) rate of the primary lesions in the radiochemotherapy group was 7/15, and 10/15 in the immunotherapy combined with radiochemotherapy group ( P=0.46). In the radiochemotherapy group, the incidence rate of tertiary lymphoid structure (TLS) was 7/15, and 12/15 in the immunotherapy combined with radiochemotherapy group ( P=0.02). The incidence rate of necrosis in the radiochemotherapy group was 6/15, and 1/15 in the immunotherapy combined with radiochemotherapy group ( P=0.03). In addition, the incidence rate of foam cell infiltration in the radiochemotherapy group was 6/15, and 13/15 in the immunotherapy combined with radiochemotherapy group ( P=0.01). Furthermore, the pCR rate of involved lymph nodes in the radiochemotherapy group was 7/33, and 11/12 in the immunotherapy combined with radiochemotherapy group ( P<0.001). Conclusion:Compared with the radiochemotherapy group, the incidence of TLS and foam cell infiltration is higher, the incidence of necrosis is lower and clinical efficacy of involved lymph nodes is higher in the immunotherapy combined with radiochemotherapy group, prompting that toripalimab combined with neoadjuvant radiochemotherapy exert higher synergistic immune effect.
ABSTRACT
Objective:To study the composition and distribution of human papillomavirus(HPV)in female genital tract of Zhuang and Han nationality in Guangxi.Methods:The composition and distribution of cervical human papillomavirus(HPV)infection in Han and Zhuang women visiting Department of Gynecology and Obstetrics of the First Affiliated Hospital of Guangxi Medical University from August 2012 to October 2020 were retrospectively analyzed to provide the basic data for prevention and treatment of HPV infection.A total of 20 736 cases were divided into Han nationality group(n=16 390 cases)and Zhuang nationality group(n=4 346 cases). Polymerase chain reaction(PCR)was used to detect HPV type 21 and analyze the epidemiological characteristics of cervical HPV in women of different ethnic groups in this area.Results:In the 20, 736 cases, the proportion of positive HPV was 27.0%(5 591/20, 736). Among them, positive HPV accounted for 27.7%(4 536)in the Han group, and 24.3%(1 055)in Zhuang group, which were statistically significant( χ2=20.17, P<0.01). Peak age of infection in Zhuang women was more than 65 years.The most common HPV genotypes in both ethnics groups in Guangxi were HPV 16, 52, 58, 18, and 53.In women with positive HPV, the constituent ratio of HPV16 and HPV 52 rose with age ageing, while constituent ratio of HPV 6 and 11 presented the opposite trend. Conclusions:The HPV and HR(high-risk)-HPV positive composition ratio is lower in Zhuang women than in Han women in Guangxi.Among Han and Zhuang females, HPV 16, 52, 58, 18 and 53 have the highest positive composition ratio.HPV genotyping shows an age-increasing change.
ABSTRACT
Objective:To investigate the effect of BMAL1 gene on the proliferation, migration and invasion ability of radiation-resistant nasopharyngeal carcinoma cell line (5-8FR) and the molecular mechanism. Methods:A multi-target click model was constructed for radiation-resistant nasopharyngeal carcinoma cell line 5-8FR by low-dose fractionated irradiation, and the results of clone formation assay were used to fit the multi-target click model and calculate the sensitization ratio of radiotherapy. The expression levels of PI3K/Akt/MMP-2/9 signaling pathway-related proteins in 5-8FR and control 5-8F cell lines were detected by Western blot. The overexpression and knockdown vectors of BMAL1 gene were constructed and transfected with 5-8F and 5-8F cell lines, respectively. The BMAL1 gene overexpression (pcDNA-BMAL1) and its control (pcDNA) and interference (BMAL1-shRNA) and control (con-shRNA) cell lines were stably transfected with nasopharyngeal carcinoma cell line 5-8F and radiation-resistant cell line 5-8FR, respectively. Western blot was performed to verify the infection efficiency and detect the changes of PI3K/Akt/MMP-2/9 signaling pathway-related proteins after overexpression or interference of BMAL1 gene in both groups of cells. CCK-8 assay, cell scratch test and Transwell chamber test were conducted to investigate the proliferation, migration and invasion capabilities of 5-8FR cell line after overexpression or interference of BMAL1 gene. Results:BMAL1 gene expression was down-regulated, and those of PI3K/Akt pathway proteins and downstream related molecules of MMP-2 and MMP-9 were up-regulated, and TIMP-2 and TIMP-1 expression was down-regulated in nasopharyngeal carcinoma radiation-resistant cell lines. Overexpression of BMAL1 gene inhibited the expression of PI3K/Akt pathway proteins and downstream related molecules of MMP-2 and MMP-9, promoted the expression of TIMP-2 and TIMP-1, and inhibited the proliferation, migration and invasion capabilities of radiation-resistant nasopharyngeal carcinoma cells, while interference with BMAL1 gene yielded the opposite results. Conclusions:BMAL1 gene can reverse the expression of PI3K/Akt/MMP-2/9 signaling pathway-related proteins in radiation-resistant nasopharyngeal carcinoma cell lines and inhibit the proliferation, migration and invasion capabilities of radiation-resistant nasopharyngeal carcinoma cell lines.
ABSTRACT
Background@#Xylazole (Xyl) is a veterinary anesthetic that is structurally and functionally similar to xylazine. However, the effects of Xyl in vitro remain unknown. @*Objectives@#This study aimed to investigate the anesthetic mechanism of Xyl using fetal rat nerve cells treated with Xyl. @*Methods@#Fetal rat nerve cells cultured for seven days were treated with 10, 20, 30, and 40 μg/ mL Xyl for 0, 5, 10, 15, 20, 25, 30, 45, 60, 90, and 120 min. Variations of amino acid neurotransmitters (AANTs), Nitric oxide-Cyclic GMP (NO-cGMP) signaling pathway, and ATPase were evaluated. @*Results@#Xyl decreased the levels of cGMP and NO in nerve cells. Furthermore, Xyl affected the AANT content and Na+ -K+ -ATPase and Ca2+ -Mg2+ -ATPase activity in nerve cells. These findings suggested that Xyl inhibited the NO-cGMP signaling pathway in nerve cells in vitro. @*Conclusions@#This study provided new evidence that the anesthetic and analgesic effects of Xyl are related to the inhibition of the NO-cGMP signaling pathway.
ABSTRACT
At present, the etiology and pathogenesis of Premature ovarian insufficiency have not been fully elucidated, and no effective medical treatment options are found.This article reviews the research progress of the etiology of POI, in order to provide theoretical basis for clinical identification of high-risk groups and early prevention and treatment.
ABSTRACT
Objective:To evaluate the efficacy of intravitreal ranibizumab (IVR) injection and/or laser photocoagulation on diabetic macular edema (DME) of different morphologic patterns based on optical coherence tomography (OCT).Methods:A non-randomized controlled clinical trial was conducted.A total of 79 diabetic patients (108 eyes) who were diagnosed as DME in Affiliated Hospital of Nanjing University of Chinese Medicine from March 2017 to February 2018 were enrolled.The subjects were divided into diffuse macular edema (DRT) group (41 eyes), cystoid macular edema (CME) group (37 eyes) and serous retinal detachment (SRD) group (30 eyes) according to the morphological characteristics of OCT, and received intravitreal injection of 0.05 ml (0.5 mg) ranibizumab and/or laser photocoagulation according to treatment guidelines.Best corrected visual acuity (BCVA), central macular thickness (CMT) of the subjects were recorded before treatment and 1 month, 3, 6 and 12 months after treatment.The morphologic changes of macular edema and complications were recorded.This study protocol adhered to the Declaration of Helsinki and was approved by an Ethics Committee of Affiliated Hospital of Nanjing University of Chinese Medicine (No.2017NL-13-03). Written informed consent was obtained from each patient before any medical examination and treatment.Results:The 1-, 3-, 6- and 12-month post-treatment average BCVA (LogMAR) of the DRT, CME and SRD groups were improved in comparison with before treatment, and the average CMT of the three groups at various time points after treatment was reduced than that before treatment (all at P<0.05). For the 39 eyes who received IVR treatment, the 12-month post-treatment average BCVA (LogMAR) of the DRT group was 0.41±0.40, which was significantly better than 0.60±0.40 of the CME group ( P=0.039). The 12-month post-treatment CMT of the DRT group was (286.05±109.56) μm, which was significantly thinner than (338.30±101.87)μm of the SRD group ( P=0.045). For the 69 eyes who received IVR combined with laser photocoagulation treatment, the 6- and 12-month post-treatment average BCVA (LogMAR) of the DRT group were significantly better than those of the CME group ( P=0.048, 0.043), and the average CMT at 12 months after treatment in the DRT group was (304.59±106.66)μm, which was significantly smaller than (369.34±107.80)μm in the SRD group, showing a statistical significance ( P=0.041). During the follow-up, 5 eyes with SRD turned to DRT, and 3 SRD eyes turned to CME.No eye changing from DRT and CME to SRD was found. Conclusions:Intravitreal ranibizumab injection and/or laser photocoagulation can significantly improve BCVA and reduce CMT of DME patients, and the efficacy is better in eyes with DRT than eyes with SRD or CME.
ABSTRACT
Type 1 diabetes mellitus (T1DM) is a chronic autoimmune disease with an increasing prevalence and affects quality of life.Daily insulin replacement therapy is not a radical treatment.With the progress of the disease course,it is often accompanied by a variety of complications and has a high rate of disability and mortality.Many breakthroughs have been made in the prevention and treatment of type 1 diabetes through immune intervention,but clinical trials that have always failed to achieve the desired results have led scientists to rethink where immunotherapy should go in the future.
ABSTRACT
Objective@#To investigate the expression discordances of estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor2 (HER-2) and Ki-67 in primary and metastatic breast cancer specimens and explore the clinical significances.@*Methods@#Biopsies of metastatic lesions were performed in 203 patients with breast cancer recurrence and metastasis indicated by physical examination and/or imaging examination. We confirmed pathological properties and assessed the expressions of ER, PR, HER-2 and Ki-67 in primary and metastatic lesions, their relationships with prognosis were also analyzed.@*Results@#Biopsy failed in 3 patients, the pathology and immunohistochemitry results of metastatic lesions were not obtained. One person was diagnosed as tuberculosis and another was primary lung cancer. Among the 198 cases of primary and metastatic lesions, the discordance rates of ER, PR, HER-2 and Ki-67 were 27.3%, 34.3%, 11.8% and 15.1%, respectively.The expressions of ER, HER-2 and Ki-67 were not significantly different between the primary and metastatic lesions, however, the expressions of PR were more likely to turn negative in the metastases (P<0.001). The disease-free survival (DFS) of patients with ER, PR positive, HER-2 negative and low expression of Ki-67 in metastatic lesion was much longer (P<0.05).@*Conclusions@#The expressions of ER, PR, HER-2 and Ki-67 in metastatic lesions are associated with the prognosis of breast cancer patients.Their expression discordances between primary and metastatic lesions can guide the treatment and evaluate the risks of recurrence and prognosis.
ABSTRACT
Background The fibrosis of filtering area caused by proliferation of human Tenon fibroblasts (HTFs) is one of failure causes following glaucoma surgery.Researches revealed that hydroxycamptothecin can induce the apoptosis of HTFs,but its influence on autophagy of HTFs is unclear.Objective This study attempted to investigate whether hydroxycamptothecin can cause an alteration of autophagic activity in HTFs.Methods Human Tenon capsular tissue was obtained from 3 patients during strabismus correction surgery under the informed consent of patients and their parents for the primary culture and passaged of HTFs in DMEM containing 10％ fetal bovine serum.The generation 3 to 6 cells then were incubated with 0.0,0.5,1.0,4.0,10.0 mg/L hydroxycamptothecin for 24 hours,respectively.A cell counting kit-8 (CCK-8) was used to detect the cell viability in different treated groups.The autophagic activity of HTFs was evaluated by a Cyto-ID autophagy detection kit,and then the autophagic flux was evaluated by counting the Cyto-ID positive cells under a fluorescence microscope,and the green fluorescence intensity was determined by flow cytometry.Quantitative reverse transcriptase PCR (qRT-PCR) and Western blot analysis were employed to assay the relative expressions of autophagic-associated genes and their proteins in HTFs,including Beclin-1,autophagy related gene 5 (ATG-5) and light chain 3 (LC-3).Results The cell viability of HTFs in the 0.0,0.5,1.0,4.0 and 10.0 mg/L hydroxycamptothecin groups were (100.00 ± 6.44) ％,(91.70 ± 6.36) ％,(81.47 ± 6.00) ％,(68.43 ± 6.69) ％ and (59.97 ± 6.98) ％ respectively,showing a gradually declining trend with the increase of hydroxycamptothecin doses,with a significant difference among them (F=19.040,P＜0.001),and the viability of HTFs in the 1.0,4.0 and 10.0 mg/L hydroxycamptothecin groups were significantly decreased than the control group (P＜0.05,P＜0.01,P＜0.01).qRT-PCR analysis revealed that the relative expression levels of Beclin-1 mRNA,ATG-5 mRNA and LC-3 mRNA in 4.0 mg/L hydroxycamptothecin group were (3.225 ±0.346),(2.839 ±0.418) and (3.761±0.224) folds higher than those of the control group.The expressions of Beclin-1 and ATG-5 proteins were significantly increased in the 4.0 mg/L hydroxycamptothecin group in comparison with the control group,and the expression intensity ratio of LC-3-Ⅱ/Ⅰ was 0.965±0.159 in the hydroxycamptothecin group,which was significantly higher than 0.275 ±0.860 of the control group (P =0.003).Cyto-ID staining showed that the percentage of autophagic cells increased dramatically from (11.333±4.010) ％ to (55.000±9.013) ％ upon the exposure of HTFs to 4.0 mg/L hydroxycamptothecin (P=0.002).Flow cytometry analysis showed that the green fluorescence intensity in the 4.0 mg/L hydroxycamptothecin group was (3.037 ±0.513) fold relative to that in the control group,showing a significant difference between the two groups (P =0.003).Conclusions Hydroxycamptothecin can induce autophagy in HTFs in vitro.
ABSTRACT
Objective To investigate the effects of propofol anesthesia on cognitive function of aged rats. Methods Ninety-six male aged SD rats (16 months) were collected and given propofol anesthesia via tail vein catheter. At 7, 30, and 90 d after anesthesia, fear conditioning experiment was performed to test long-term memory of the aged rats (12 rats at each time point, total 36 rats). At 1, 2, 3, 4, and 5 d after anesthesia, spontaneous alternation in Y-maze experiment was performed to test spatial working memory of the aged rats (12 rats at each time point, total 60 rats). Results There were no statistical differences in long-term memory at 7, 30, and 90 d after anesthesia between the propofol group and control group (P>0.05). While spatial working memory of aged rats in propofol group was impaired at 1 and 2 d after anesthesia (P0.05). Conclusions These results indicate that clinical dose propofol anesthesia will not induce long-term memory impairment of aged rats, although it impairs spatial working memory of aged rats within 48 h after anesthesia.
ABSTRACT
Objective To investigate the expression of LKB1 and p53 in human gastric tissues and their correlation with clinical pathological factors.Methods The expression of LKB1 and p53 in 115 cases of gastric carcinoma and 20 cases of normal gastric tissues were detected by immunohistochemistry method,and the relation between the expression and the clinicopathological parameter of gastric carcinoma was analyzed.Results The positive rates of LKB1 in gastric carcinoma and normal tissues were 20.9 ％ (24/115) and 95.0 ％ (19/20),respectively (P ＜ 0.01).The positive rates of p53 in gastric carcinoma and normal tissues were 45.2 ％ (52/115) and 5.00 ％ (1/20),respectively (P ＜ 0.05).The analysis revealed that the high expression of LBK1 was associated with tumor lymph node metastasis,stage,Lauren classification and worse survival (P ＜ 0.05).The expression of p53 was associated with tumor lymph node metastasis,stage,distant metastasis and worse survival (P ＜ 0.05).Conclusions LKB1 protein expression may play an important role in the development and progression of gastric cancer.LKB1 may be used to assess the malignant biological behavior and prognosis of gastric cancer.
ABSTRACT
Objective To study the alterations of CD19+CD5+CD1dhigh B, Th1 and Th17 cells in non-obese diabetic ( NOD) mice and the correlation between B10 cells and type 1 diabetes in NOD mice. Methods Flow cytometry ( FCM) was used to measure the levels of CD19+CD5+CD1dhigh B, CD19+IL-10+B, CD4+IFN-γ+Th1, CD4+IL-17+Th17 and CD4+CD25+Foxp3+T cells in NOD mice ( 4 weeks old NOD mice:group A, n=10;8 weeks old NOD mice:group B, n=10; NOD mice with diabetes: group C, n=10) and age-matched C57BL/6 mice ( control group, n=20 ) .Hematoxylin-eosin staining of pancreatic tissues was performed for histopathological assessment of the development of insulitis in NOD mice.Results (1) Histopathological analysis showed that mice from A, B and C groups respectively showed no insulitis, insulitis and obvious insulitis with no intact islets.(2) The highest levels of B10 cells in NOD mice were ob-served in group B, followed by those in group C and group A (P0.05).More B10 cells were detected in pancreatic lymph nodes than in other tissues of 8 weeks old NOD mice, the levels of which were also higher than those in pancreatic lymph nodes of mice form group C ( P0.05).Conclusion The percentages and distribution of B10 cells in NOD mice changed with age and the development of insulitis.The decrease of B10 cells might participate in the development of type 1 diabe-tes in NOD mice.
ABSTRACT
Objective To explore the expression of human epidermal growth factor receptor -3( HER3) in human epidermal growth factor receptor-2(HER2)-positive breast cancer and its relationship with the therapeutic effect of trastuzumab and clinical prognosis .Methods Clinicopathological characteristics of 235 HER2-positive breast cancer patients undergoing surgery in Jiangsu Cancer Hospital from Jan .2007 to Jun.2012 were analyzed retrospectively.The expression of HER3 was detected using immunohistochemisty staining .The expression of HER3 and its correlation with the clinicopathological characteristics were analyzed .All patients were followed-up to find out the impact of HER3 on the disease free survival and the therapeutic effect of trastuzumab .Results The positive rate of HER3 in Luminal B ( HER2 +) and HER2-overexpressing breast cancer was 100/135 (74.1%), and 85/100(85%)respectively.The difference had statistical significance (P<0.05).The histolog-ical grading and the lymph node metastasis were significantly different in Luminal B ( HER2+) breast cancer .The tumor volume , histological grading and lymph node metastasis were significantly different in HER 2-overexpressing breast cancer .The 5-year disease free survival of HER 2-positive breast cancer patients with negative HER 3 was higher than that with positive HER3.The non-relapse survival time was not significantly different between the pos-itive and negative HER 3 expression in Luminal B ( HER2+) breast cancer patients receiving trastuzumab treat-ment , but was significantly different in HER 2-overexpressing breast cancer patients .Conclusions HER3 is cor-related with unfavourable prognosis in HER 2-positive breast cancer .The treatment targeting HER3 may improve the clinical prognosis of both HER 2-positive and HER3-positive breast cancer patients .The HER2-overexpressing breast cancer patients with negative HER 3 may benefit more from trastuzumab treatment .