1.Expression changes of insulin-like growth factor-1 and its receptor as well as extracellular signal regulated kinase 1/2 in the vestibular epithelium of guinea pigs following gentamycin toxicity
Hongshen SHENG ; Yue HE ; Guang XU ; Jingyu SUN ; Jinling WANG
Chinese Journal of Tissue Engineering Research 2007;11(36):7302-7305
BACKGROUND:Insulin-like growth factor-1 (IGF-1) is an important mitogen and an indispensable regulator during normal hair cell development. Extracellular signal regulated kinase 1/2 (ERK1/2) is also expressed in mammalian vestibular organs.OBJECTIVE: To investigate the changes of the expression and the distribution of IGF-1, IGF-1 receptor (IGF-1R) and ERK1/2 in guinea pig's vestibular epithelium following gentamycin injury.DESIGN: A randomly controlled study.SETTING: Department of Otorhinolaryngology, General Hospital of Chengdu Military Area Command of Chinese PLA.MATERIALS: Twenty healthy and adult guinea pigs, weighing 300 to 350 g, provided by the Experimental Animal Center,Fourth Military Medical University of Chinese PLA, were randomly divided into four experimental groups and a control group with 4 in each group.METHODS: The experiment was performed at Department of Otorhinolaryngology Research Laboratory of Xijing Hospital,Fourth Military Medical University of Chinese PLA from January 2002 to May 2002. In the experimental groups,gentamycin was intraperitoneally administered daily (80 mg/kg) for 10 consecutive days. For the control group, 1 mL of 0.9% sterile saline was administered in the same way. The guinea pigs, in which unsteady gait or nystagmus appeared,could be involved in the further experiments. Before being sacrificed, the animals' gait, nystagmus and the amount of food-intake were observed every day. The animals were anesthetized deeply with 50 mg/kg pentobarbital 1, 7, 14 or 21days after the last gentamycin administration and then decapitated. Bilateral otic vesicles were harvested and immersed in 4% paraformaldehyde. Then the specimens were decalcified in 10% ethylenediamine tetraacetic acid (EDTA),thereafter embedded in OCT gel and serially sectioned at a thickness of 10 μm in the cryostat. The behavioral changes of guinea pigs were observed. The morphological changes of vestibular epithelium were examined by hematoxylin and eosin (HE) staining. The expression and distribution changes of IGF-1/1R and ERK1/2 were investigated immunohistochemically. MAIN OUTCOME MEASURES: The behavioral, morphological, expression and distribution changes of IGF-1/1R and ERK1/2 of guinea pigs in each group.RESULTS: Twenty involved guinea pigs entered the stage of final analysis. ① All the guinea pigs' vestibular functions were impaired after gentamycin treatment, then partially restored without any pharmaceutical treatment. ②Morphological injury was obvious after gentamycin treatment, and improved 1 week later. ③The expression of IGF-1/1R was low in the control group, and in the 1-day group it increased significantly to its maximum. After that, its expression decreased gradually, but was still higher in the 21-day group than that in the control group. There were significant differences in the expression of IGF-1/1R among different groups (F =51.8,45.7,P < 0.05). The expression changes of IGF-1 and its receptor were similar. ④The expression of ERK1/2 was low in the control group, and increased gradually after gentamycin toxicity. In the 7-day group, the immunoreactivity reached its maximum. Then the levels of ERK1/2 decreased gradually, but were still higher in the 21-day group than that in the control group. There were significant differences in the expression of ERK1/2 among different groups (F =103.7,106.4, P < 0.01), but no significant differences existed in the expression between ERK1 and ERK2 among different groups (P > 0.05).CONCLUSION: The expression of IGF-1/1R and ERK1/2 in vestibular epithelium increased after gentamycin treatment,and IGF-1 may play an important role as an endogenous mitogen through a paracrine or autocrine manner in the early stage of hair cell self-repair of guinea pigs. ERK1/2 may play an important role in signal transduction during vestibular hair cell self-repair after gentamycin toxicity in guinea pigs.
2.The effect of initiation factor 4E-binding protein 1 in the cell signaling pathways of breast cancer
Xiaofei WU ; Mingqian CAO ; Dianlong ZHANG ; Gong ZHANG ; Hongshen CHEN ; Tao LIU ; Yuhong GUO ; Bin WU ; Xiaolan WANG
Chinese Journal of General Practitioners 2011;10(5):356-358
The expression of human epidermal growth factor receptor 2 (HER2), serine-threonine kinase (Akt), 4E-binding protein (4EBP1), phophorylated ribosomal protein S6 kinasel (p70S6Kl) and ribosomal protein S6 ( S6) were detected with immunohistochemistry in 48 cases of human breast cancer. Tumors high-expressing HER2 showed higher Akt expression as compared to tumors with negative HER2 (P < 0. 01). Levels of Akt were correlated with the downstream molecules 4EBP1 ( P < 0. 01) and p70S6K ( P < 0. 05 ). 4EBP1 was mainly expressed in poorly differentiated tumors (P <0. 01) and correlated with tumor size ( P < 0. 05) , lymph node metastasis ( P < 0. 01) and locoregional recurrences ( P < 0. 01). Results suggest that 4EBPl may be the main factor in PI-phosphoinositide-3-kinase (PI3K)-Akt-mammalian targot of rapanycin signal transduction pathways, which is associated with grade of malignancy and prognosis of breast cancer.
3.Effect of acupoint sticking therapy along meridians on gastrointestinal function recovery in patients after lumbar internal fixation surgery
Peiqian LAI ; Pei HU ; Hongshen WANG ; Yanhua ZHENG ; Meiyan LAN ; Shaohua CHEN
The Journal of Practical Medicine 2024;40(2):267-271
Objective To observe the effect of acupoint sticking therapy along meridians on gastrointestinal function recovery in patients after lumbar internal fixation surgery.Methods From January 2020 to March 2022,125 patients with lumbar degenerative diseases were admitted to our hospital's Department of Orthopaedics and divided into two groups:control(n = 62)and acupoint sticking therapy(n = 63).The control group received standard postoperative care for lumbar internal fixation,while the experimental group received routine care based on acupoint sticking therapy along meridians.The NVAS scores for postoperative nausea and vomiting,abdominal distension and pain,bowel sound,initial exhaust,and defecation time were compared between the two groups.Results Both groups experienced gastrointestinal problems to varied degrees following surgery.The experimental group had signifi-cantly lower rates of nausea,NVAS score,vomiting grade,abdominal distension,return to normal bowel sounds,and time of first exhaust and bowel movement compared to the control group(P<0.05).However,there were no significant differences in abdominal pain and abdominal circumference(P>0.05).There were no adverse reactions in either group.The incidence of postoperative abdominal distension,nausea and vomiting in the observation group was lower than that in the control group,and the difference was statistically significant(P<0.05).Conclusion Acupoint sticking therapy along meridians could accelerate the recovery of gastrointestinal function of patients after lumbar internal fixation,promote rapid recovery after surgery,and improve quality of life.
4.Early recovery status and outcomes after sepsis-associated acute kidney injury in critically ill patients
Xiaoqin LUO ; Ping YAN ; Ningya ZHANG ; Mei WANG ; Yinghao DENG ; Ting WU ; Xi WU ; Qian LIU ; Hongshen WANG ; Lin WANG ; Yixin KANG ; Shaobin DUAN
Journal of Central South University(Medical Sciences) 2022;47(5):535-545
Objective:Acute kidney injury (AKI) is one of the common complications in critically ill septic patients, which is associated with increased risks of death, cardiovascular events, and chronic renal dysfunction. The duration of AKI and the renal function recovery status after AKI onset can affect the patient prognosis. Nevertheless, it remains controversial whether early recovery status after AKI is closely related to the prognosis in patients with sepsis-associated AKI (SA-AKI). In addition, early prediction of renal function recovery after AKI is beneficial to individualized treatment decision-making and prevention of severe complications, thus improving the prognosis. At present, there is limited clinical information on how to identify SA-AKI patients at high risk of unrecovered renal function at an early stage. The study aims to investigate the association between early recovery status after SA-AKI, identify risk factors for unrecovered renal function, and to improve patients ' quality of life.Methods:We retrospectively analyzed clinical data of septic patients who were admitted to the intensive care unit (ICU) and developed AKI within the first 48 hours after ICU admission in the Second Xiangya Hospital and the Third Xiangya Hospital of Central South University from January 2015 to March 2017. Sepsis was defined based on the Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3). AKI was diagnosed and staged according to the 2012 Kidney Disease:Improving Global Outcomes (KDIGO) guideline. SA-AKI patients were assigned into 3 groups including a complete recovery group, a partial recovery group, and an unrecovered group based on recovery status at Day 7 after the diagnosis of AKI. Patients ' baseline characteristics were collected, including demographics, comorbidities, clinical and laboratory examination information at ICU admission, and treatment within the first 24 hours. The primary outcome of the study was the composite of death and chronic dialysis at 90 days, and secondary outcomes included length of stay in the ICU, length of stay in the hospital, and persistent renal dysfunction. Multivariate regression analysis was performed to evaluate the prognostic value of early recovery status after AKI and to determine the risk factors for unrecovered renal function after AKI. Sensitivity analysis was conducted in patients who still stayed in hospital on Day 7 after AKI diagnosis, patients without premorbid chronic kidney disease, and patients with AKI Stage 2 to 3.Results:A total of 553 SA-AKI patients were enrolled, of whom 251 (45.4%), 73 (13.2%), and 229 (41.4%) were categorized as the complete recovery group, the partial recovery group, and the unrecovered group, respectively. Compared with the complete or partial recovery group, the unrecovered group had a higher incidence of 90-day mortality (unrecovered vs partial recovery or complete recovery: 64.2% vs 26.0% or 22.7%; P<0.001) and 90-day composite outcome (unrecovered vs partial recovery or complete recovery:65.1%vs 27.4%or 22.7%;P<0.001). The unrecovered group also had a shorter length of stay in the hospital and a larger proportion of progression into persistent renal dysfunction than the other 2 groups. After adjustment for potential confounders, patients in the unrecovered group were at an increased risk of 90-day mortality (HR=3.50, 95% CI 2.47 to 4.96, P<0.001) and 90-day composite outcome (OR=5.55, 95%CI 3.43 to 8.98, P<0.001) when compared with patients in the complete recovery group, but patients in the partial recovery group had no significant difference (P>0.05). Male sex, congestive heart failure, pneumonia, respiratory rate>20 beats per minute, anemia, hyperbilirubinemia, need for mechanical ventilation, and AKI Stage 3 were identified as independent risk factors for unrecovered renal function after AKI. The sensitivity analysis further supported that unrecovered renal function after AKI remained an independent predictor for 90-day mortality and composite outcome in the subgroups. Conclusion:The early recovery status after AKI is closely associated with poor prognosis in critically ill patients with SA-AKI. Unrecovered renal function within the first 7 days after AKI diagnosis is an independent predictor for 90-day mortality and composite outcome. Male sex, congestive heart failure, pneumonia, tachypnea, anemia, hyperbilirubinemia, respiratory failure, and severe AKI are risk factors for unrecovered renal function after AKI. Therefore, timely assessment for the renal function in the early phase after AKI diagnosis is essential for SA-AKI patients. Furthermore, patients with unrecovered renal function after AKI need additional management in the hospital, including rigorous monitoring, avoidance of nephrotoxin, and continuous assessment for the renal function, and after discharge, including more frequent follow-up, regular outpatient consultation, and prevention of long-term adverse events.