1.Changes of gastrointestinal hormones before and after hepatic ischemia reperfusion and the role of salvia miltiorrhiza pretreatment
Zhiyong ZHANG ; Qiping LU ; Xiaoping CHEN
Chinese Journal of Digestive Surgery 2014;13(3):213-217
Objective To study the changes of gastrointestinal hormones before and after hepatic ischemia reperfusion and the role of salvia miltiorrhiza pretreatment.Methods The clinical data of 32 patients with hepatic diseases who were admitted to the Wuhan General Hospital of Guangzhou Military Area of PLA from May 2010 to May 2012 were prospectively analyzed.Thirty-two patients with hepatic inflow occlusion were randomly divided into the ischemia reperfusion group (IR group,15 patients) and salvia miltiorrhiza pretreatment group (SM group,17 patients).Patients in the IR group and SM group received partial hepatectomy with hepatic inflow occlusion by Pringle maneuver for 15-20 minutes.Patients in the IR group and SM group were injected with normal saline and salvia miltiorrhiza (30 mL/d) by intravenous drip for 3 days before operation,respectively.Twelve patients with hepatic diseases who received open surgery without block of hepatic inflow occlusion were enrolled in the negative control group (SO group) and 5 healthy volunteers were enrolled in the normal control group (CO group).The changes of the motilin,cholecystokinin,vasoactive intestinal peptide and secretin of the 4 groups were recorded.All data were analyzed using the analysis of variance or LSD-t test.Results The level of motilin of the CO group was (347 ± 14)μg/L.The levels of motilin of the SO group,IR group,and SM group at postoperative 24,48 and 72 hours were (324 ± 13) μg/L,(345 ± 12)μg/L,(345 ± 13)μg/L,(307 ± 10)μg/L,(316 ±9)μg/L,(338 ±13) μg/L,(313 ± 7) μg/L,(337 ± 12) μg/L and (345 ± 12) μg/L,respectively.The level of motilin of the SO group at postoperative 24 hours was significantly lower than that of the CO group (t =5.25,P < 0.05) ; the levels of motilin of the IR group at postoperative 24,48 and 72 hours were significantly lower than those of the SO group (t =10.05,8.09,2.07,P <0.05) ; the levels of motilin of the SM group at postoperative 24 and 48 hours were significantly lower than those of the SO group (t =9.83,2.28,P < 0.05),while there was no significant difference in the level of motilin between the SM group and the SO group at postoperative 72 hours (t =0.36,P >0.05) ;the levels of motilin of the SM group at postoperative 24,48 and 72 hours were significantly higher than those of the IR group (t =3.80,7.10,2.35,P<0.05).The levels of cholecystokinin of the CO group was (2.53±0.06)μg/L.The levels of cholecystokinin of the SO group,IR group and SM group at postoperative 24 hours were (3.28 ±0.09) μg/L,(2.52 ±0.09) μg/L,(2.54 ±0.16)μg/L,(4.34 ±0.21) μg/L,(3.63 ±0.31)μg/L,(3.25 ± 0.09) μg/L,(3.71 ±0.28)μg/L,(3.28±0.11)μg/L and (2.53 ±0.09)μg/L,respectively.The level of cholecystokinin of the SO group at postoperative 24 hours was significantly higher than that of the CO group (t =4.33,P < 0.05) ; the levels of cholecystokinin of the IR group at postoperative 24,48and 72 hours were significantly higher than those of the SO group (t =9.32,5.37,2.16,P<0.05) ; the levels of cholecystokinin of the SM group at postoperative 24 and 48 hours were significantly higher than those of the SO group (t =7.21,3.42,P < 0.05),while there was no significant difference in the level of cholecystokinin between the SM group and the SO group at postoperative 72 hours (t =0.29,P > 0.05) ; the levels of cholecystokinin of the SM group at postoperative 24,48 and 72 hours were significantly higher than those of the IR group (t =5.62,4.63,3.57,P < 0.05).The level of vasoactive intestinal peptide of the CO group was (11.8 ±1.6) tμg/L.The levels of vasoactive intestinal peptide of the SO group,IR group,and SM group at postoperative 24,48 and 72 hours were (21.5 ± 3.8) μg/L,(12.2 ± 1.6) μg/L,(11.9 ± 1.7) μg,/L,(29.7 ± 4.1) μg/L,(22.9±4.2)μg/L,(18.8±2.8)μg/L,(22.4 ±4.1)μg/L,(16.4±2.3)μg/L and (12.1 ±1.6)μg/L,respectively.The level of vasoactive intestinal peptide of the SO group at postoperative 24 hours was significantly higher than that of the CO group (t =3.59,P < 0.05) ; the levels of vasoactive intestinal peptide of the IR group at postoperative 24,48 and 72 hours were significantly higher than those of the SO group (t =6.35,3.22,2.36,P < 0.05) ; the levels of vasoactive intestinal peptide of the SM group at postoperative 24 and 48 hours were significantly higher than those of the SO group (t =5.04,2.33,P < 0.05),while there was no significant difference in the level of vasoactive intestinal peptide between the SM group and the SO group at postoperative 72 hours (t =0.18,P > 0.05) ;the levels of vasoactive intestinal peptide of the SM group at postoperative 24,48and 72 hours were significantly lower than those of the IR group (t =4.27,3.87,2.45,P < 0.05).The level of secretin of the CO group was (75 ± 5) μg/L.The levels of secretin of the SO group,IR group and SM group at postoperative 24,48 and 72 hours were (98 ± 6) μg/L,(76 ± 4) μg/L,(76 ± 4) μg/L,(129 ± 6) μg/L,(102 ±8) μg/L,(89 ± 6) μg/L,(104 ± 8) μg/L,(90 ± 6) μg/L and (74 ± 4) μg/L,respectively.The level of secretin of the SO group at postoperative 24 hours was significantly higher than that of the CO group (t =3.27,P < 0.05) ;the levels of secretin of the IR group at postoperative 24,48 and 72 hours were significantly higher than those of the SO group (t =5.20,2.94,1.77,P < 0.05) ; the level of secretin of SM group at postoperative 24 and 48 hours were significantly higher than those of the SO group (t =4.16,2.54,P<0.05),while there was no significant difference in the level of secretin between the SM group and the SO group at postoperative 72 hours (t =0.23,P > 0.05) ; the levels of secretin of the SM group at postoperative 24,48 and 72 hours were significantly lower than those of the IR group (t =5.13,4.32,2.87,P < 0.05).Conclusions Gastrointestinal congestion caused by hepatic blocking leads to the decline of the expression of motilin,but the increase of the expression of cholecystokinin,vasoactive intestinal peptide,secretin.Salvia miltiorrhiza may improve micro-circulation,abate gastrointestinal adema,and influence the gastrointestinal hormone expression in an indirect way.
2.MTL and SEC expression in hepatic ischemia-reperfusion intestinal congestion and effects of Salvia Miltiorrhiza pretreatment on it
Zhiyong ZHANG ; Xiaoping CHEN ; Qiping LU
Chinese Journal of Hepatobiliary Surgery 2010;16(7):527-530
Objective To study the excitability gastrointestinal hormone MTL and inhibitory gastrointestinal hormone SEC expression in the intestinal congestion and the effects of Salvia miltior-rhiza pretreatment at different time limits in 45min of rat hepatic ischemia-reperfusion to explore its possible mechanism and significance. Methods 80 rats were randomly divided into 4 groups: normal control group(CO group), sham-operated group(SO group), injury group(IR group), salvia miltior-rhiza pretreatment group(SM group). Non-invasive artery clamp was used to clip then slacken the he-patic pedicle to produce animal model of ischemia-reperfusion. The clamp time was 45 min. The rats in Salvia miltiorrhiza pretreatment group were injected 40 ml/kg saline with 6 g/kg Salvia Miltiorrhiza from caudal vein 30 min before clamping hepatic pedicle. While in the sham-operated group, the porta hepatis was dissected after laparotomy and hepatic pedicle not clamped. The upper jejunums at differ-ent reperfusion time phases (0 h, 3 h, 12 h, 24 h, 72 h) were made into specimens respectively, and then MTL and SEC immunohistochemical measurement were conducted. Results At 0 min of hepatic ischemia-reperfusion digestive tract congestion, the MTL expression of upper jejunum went down,SEC expression of upper jejunum went up. With the reperfusion time extending, the MTL expression also descended to minimum at 24 h, but SEC expression increased to reach the peak at 24 h. The ex-pression of these 2 hormones gradually returned to normal at 72h. The MTL expression of Salvia milt-iorrhiza pretreatment group was higher, SEC expression of SM group were lower than the IR group in each time phase of reperfusion. Conclusion The intestinal congestive injury caused by liver ischemia can down-regulate the excitability of gastrointestinal hormone MTL and up-regulate the gastrointesti-nal inhibitory gastrointestinal hormone SEC expression at reperfusion to inhibit gastrointestinal motili-ty. Salvia miltiorrhiza preconditioning can partly weaken the descending of jejunal MTL and increasing of the jejunal SEC expression, which may contribute to the early recovery of gastrointestinal motility.
3.Characteristics and prognosis of visual field of G11778A mutation Leber hereditary optic neuropathy
Yanting XIA ; Liang LIAO ; Taotao ZHANG ; Jian ZHOU ; Qiping WEI
Chinese Journal of Ocular Fundus Diseases 2021;37(3):180-188
Objective:To analyze the characteristics and prognosis of visual field of Leber hereditary optic neuropathy (LHON) with G11778A mutation.Methods:A retrospective clinical study. Twenty-two (44 eyes) of LHON patients diagnosed with G11778A site mutation by mt-DNA examination from May 2008 to February 2018 in Ophthalmology Department of Dongfang Hospital of Beijing University of Chinese Medicine, were enrolled in this study. All patients underwent best corrected visual acuity (BCVA), visual field and optical coherence tomography (OCT). The BCVA examination was performed using the international standard visual acuity chart, which was converted into logarithm of the minimum angle of resolution (logMAR) BCVA for record. The thickness of the retinal nerve fiber layer (RNFL) in the 200μm×200μm annular region 1.73 mm outside the optic disc was measured by OCT. At least 7 visual field examinations were performed within one month before and after 2, 4, 8, 12, 18, 24 and 30 months of the course of disease by using Octopus 101 perimetry. Among 44 eyes, 27 eyes were detected with G2 procedure (G2 group) and 17 eyes were detected with LVC procedure (LVC group). The mean field defect (MD) and mean optical sensitivity (MS) were used as the main outcome indexes. According to the onset age, the patients were further divided into the ≤14 years old group and>14 years old group. There was a significant difference in initial logMAR BCVA between the G2 group and LVC group ( t=4.994, P=0.000), but there was no significant difference in gender ( χ2=1.896, P=0.169) and age ( t=0.337, P=0.708) between the two groups. Independent sample t test was used for comparison between groups, paired t test was used for comparison within groups, and one-way analysis of variance was used for comparison between groups. The statistical data were compared by χ2 test. Results:In the G2 group, the MD value of the subgroup of children (≤14 years old) decreased gradually during the follow-up period, and the MD value since 18 months after onset was significantly lower than the value of 2 months after onset ( t=3.813, 4.590, 5.033; P=0.002, 0.001, 0.000). No obvious visual field index changes were seen in other subgroups ( P>0.05). The central scotoma was the most common type of visual field defect in the early stage, and the diffuse defect was the most common type of visual field defect in the late stage. There was a significant difference in the types of visual field distribution between the early and late stage in G2 group ( χ2=17.414, P=0.015). There was no significant difference in the type of visual field distribution between the early and late stage in LVC group ( χ2=4.541, P=0.474). The MD value in the G2 group remained stable within 8 months after onset, but significantly improved after 18 months after onset ( t=2.100, 3.217, 3.566; P=0.046, 0.003, 0.001). The MS in the LVC group did not significantly improve during follow-up ( P>0.05). The average visual acuity of the G2 group was significantly improved from 12 months ( t=3.039, 3.678, 4.264, 5.078; P=0.008, 0.002, 0.001, 0.000). The visual acuity of the eyes in the G2 group was better than that of the LVC group during all follow-up periods ( P≤0.05). The RNFL thickness of all patients continued to decrease after onset, but the RNFL thickness was significantly higher at 4, 8, 18, 24, 30 months in the G2 group than those in the LVC group ( t=2.471, 2.269, 2.474, 2.509, 2.782; P=0.018, 0.028, 0.017, 0.016, 0.008). Conclusions:The main types of visual field defect of LHON with G11778A mutation are the central scotoma in the early stage, while the diffuse defect and central scotoma are both very common in the later stage. The visual field of LHON patients examined by G2 procedure is significantly improved during the follow-up, as well as the visual acuity improved significantly, and the visual field improvement in younger cases (≤14 years old) is better than that of older cases (>14 years old), but the visual field of the LVC procedure cases did not improve during follow-up.
4.The auxiliary diagnosis value of enzyme-linked immunosorbent spot assay and flow cytometry in detection of IFN-γ in tuberculous pleurisy
Fengjiao DU ; Qiping GE ; Panjian WEI ; Hongyan JIA ; Shuxiang GU ; Zongde ZHANG
Chinese Journal of Laboratory Medicine 2011;34(7):617-622
Objective To explore the value of IFN-γ produced or secreted by CD+4 T Lymphocytes from pleural effusion mononuclear cells for the diagnosis of tuberculous pleurisy(plTB).Methods The PEMCs of 40 patients with tuberculous pleural effusion and 30 patients with malignancy pleural effusion were selected as the tuberculosis and disease control groups, then co-cultured with the early secretory antigenic target 6 (ESAT-6) and culture filtered protein 10 (CFP-10) fusion protein (E/C).The numbers of spot forming cells(SFC) secreting IFN-γ were enumerated by ELISpot and the ratios of cells producing IFN-γ were detected by flow cytometry and intracellular cytokine staining.Moreover, the two indicators were compared between tuberculosis and disease control groups to evaluate the 2 methods detecting IFN-γ in the diagnosis of plTB.Results After E/C stimulation, the numbers of SFC were 205(125-450)SFC/5×104 PEMC in tuberculosis group and 5(2-18)SFC/5×104 PEMC in disease control group by ELISpot.The difference between two groups was statistically significant (U= 20.00, P<0.01).The proportion of IFN-γ-secreting CD+4 T lymphocytes was 3.27% (1.81%-7.34%) in tuberculosis group and 0.12% (0.06%-0.46%) in control group detected by FCM. The difference between the two groups was statistically significant (U=45.00, P<0.01).The indicators of ELISpot in detection of IFN-γ which was secreted by PEMC after co-cultured with E/C were as follows: sensitivity 92.5% (37/40), specificity 80.0% (24/30), positive predictive value 0.86, negative predictive value 0.89, positive likelihood ratio 4.63, negative likelihood ratio 0.09 and accuracy 87.1%;and for FCM, they were 87.5% (35/40), 90.0% (27/30), 0.92, 0.84, 8.75 and 0.14, respectively and accuracy 88.6%.Conclusion After E/C stimulation, the assay for IFN-γ-secreting CD+4 T lymphocytes by FCM and ELISpot is highly sensitive and specific for diagnosis of plTB as an auxiliary method.
5.FK506 promoting proliferation of Schwann cells in vitro and NGF of Schwann cells secreted highly by itself
Chunhua LI ; Jun YANG ; Lei WU ; Jianwen LIAO ; Zehua CHEN ; Qiping WANG ; Zhenwei ZHANG ; Jianqiang QIN
Chinese Journal of Microsurgery 2008;31(6):428-431,illust 4
Objective To explore on FK506 promoting proliferation of Schwann cells in vitro and NGF of Schwaun cells secreted highly by itself. Methods Purified Schwann cells divide into six groups:group A (control group) DMEM/F12 contained 10% calf bloodserum; group B contained 0.1 ng/ml FK506; group C contained 0.5 ng/ml FK506; group D contained FK506:1.0 ng/ml;group E contained FK506:5.0 ng/ml; group F contained FK506:10 ng/ml. Morphology of Schwann cells were oboyrved by invert microscope and evaluated Schwann cells in immunocytochemistry staining with anti-S-100. The best concentration of FK506 who promoted proliferation of Schwann cells by MTT. Cell cycle of Sehwarm cells were determined by flow cytometry. The level of NGF in the conditioned media was determined by an enzyme-linked immunoadsordcnt assay after 72 h. Results Group C was the best concentration which promoting proliferation of Schwann cells among 5 groups, when the concentration 1.0 ng/ml FKS06 to promote Schwann cell proliferation gradually weakened. Detected by flow cytometry showed that: containing 10% fetal DMEM/F12 bovine serum for 24 h,72 h and 48 h after Schwann cells in S phase percentage were 27.8%,39.3% and 58.4% in the 0.5 ng / ml FK506 for 24 h,72 h and 48 h after Schwann cells S percentage period were 54.2% ,60.3% and 94.6%. S phase of the latter than the former in 24 h,72 h and 48 h, respectively higher: 26.4% and 21% and 36.2%. FK506 detected by ELISA promote Schwann cell proliferation after the expression of NGF in the experimental study found: 0.5 ng/ml FK506 for 72 h after the Schwann cells secreted by the NGF as high as 0.188 ng/ml, rcspectiveIy. Conclusion FKS06 can promote proliferation of Schwann cells at early time in vitro and Schwann cells' good situation is highly kept to secrete NGF.
6.Narrative medical enlightenment on medical humanities quality education in China
Qiong YANG ; Xinhua ZHANG ; Qiping HUANG ; Gebo WEN ; Zhihan TANG ; Juan PENG
Chinese Journal of Medical Education Research 2016;15(9):943-946
Narrative medicine has brought new ideas to medical humanities education, and its con-notation is suitable to Undergraduate Medical Education Standards-Clinical Medicine (Trial). By analyz-ing the proposal and development of narrative medicine, its foundation and core, its programs and methods, as well as its forms and values, the author deepened the understanding of narrative medicine. And through the following four pathways including strengthening the renewal of ideas and concepts on medical humanities quality education, promoting the diversification of teaching ways and methods of medical humanities educa-tion, enhancing the effect of early exposure to clinical medical students, opening the path of integration narrative medicine and evidence-based medicine, the author analyzed narrative medical enlightenment on medical humanities quality education in China.
7.Value of methylated Septin 9 detection in screening colorectal cancer in elderly people
Qingqing DING ; Hao ZHANG ; Haichen XU ; Xiaolin LI ; Yun SHAO ; Qiping XUE ; Weihao SUN
Chinese Journal of Geriatrics 2015;34(12):1348-1350
Objective To investigate the value of detecting methylated SEPT9 gene (mSEPT9) in serum and stool in screening colorectal cancer in elderly people.Methods Subjects were divided into three groups, the colorectal cancer group (n=82), the colorectal polyps group (n=80) and the healthy control group (n=100).Real-time quantitative polymerase chain reaction (PCR) was used to detect mSEPT9 in peripheral blood and feces.The relationship between mSEPT9 and clinical and pathological characteristics of colorectal cancer was analyzed.The agreement between serum and stool results was analyzed.Results The positive rate of serum mSEPT9 was 73.2% in the colorectal cancer group, 6.3% in the colorectal polyps group and 4.0% in the healthy control group, with statistical significance between the colorectal cancer group and the other two groups (P<0.01).The sensitivity and specificity for plasma mSEPT9 detection in screening colorectal cancer were 73.2 % and 95.6%, respectively.The positive rate was higher in patients with tumor maximum diameter over 3.0 cm, invasion of the entire serosa layer, lower differentiation or advanced clinical staging (P<0.05).The detection results of plasma mSEPT9 were in complete agreement with those of stool mSEPT9 from the same patients.Conclusions The expression of mSEPT9 is high in elderly patients with colorectal cancer and has a high sensitivity and specificity for PCR detection.Complete agreement can be seen in results from plasma and feces.Detecting mSEPT9 can be a valuable approach to screening colorectal cancer in the elderly.
8.Impact of collateral circulation on neurological function and prognosis outcome of patients with acute cerebral infarction
Qiping ZHANG ; Yingdao CHEN ; Yuying LI ; Haining LI ; Bingsong LIANG ; Jian LI
The Journal of Practical Medicine 2016;32(7):1040-1043
Objective To investigate the impact of collateral circulation on neurological function and prognosis outcome of patients with acute cerebral infarction. Methods Assessed the collateral circulation of 274 patients with acute cerebral infarction from June 2012 to April 2015 in the department of neurology in Worker′s Hospital of Wuzhou using DSA, analyzed patients′ neurological function and prognosis outcome concerning their collateral circulation. Results (1) Impairment of neurological function were different between collateral circulation group and non-collateral circulation group ( P < 0 . 05 ) , but there was no significant difference in neurological impairment between the primary collateral circulation and secondary collateral circulation (P > 0.05). (2)14 and 90 days after treatment, symptoms of neurological impairment in posterior communicating artery, before pial artery, after pial artery and combination artery were significantly improved as with their NIHSS scores (P<0.05). However, symptoms of neurological impairment in anterior communicating artery, arteria ophthalmica and non-collateral circulation did not significantly improved at 14 and 90 days after treatment, with no significantly different NIHSS score (P > 0.05). Conclusions (1) Neurological function of patients with collateral circulation was better without collateral circulation. Grading of collateral circulation had did not relate to neurological function. (2) Prognosis of patients with collateral circulation was improved significantly than the patients without collateral circulation. The types of collateral circulation affect the prognosis of the patients with acute cerebral infarction.
9.Effect of left ventricular hypertrophy and deformation on cardiac function in patients with uremia cardiomyopathy by using quantitative speckle tracking technology
Yi ZHENG ; Xiaohong YANG ; Qiping ZHOU ; Yaoyao HUANG ; Fan ZHANG ; Liangyu WANG
Journal of Central South University(Medical Sciences) 2017;42(4):400-405
Objective:To evaluate the effect of left ventricular hypertrophy and deformation on cardiac function in patients with uremic cardiomyopathy (UCM) by using the technology of two dimensional speckle tracking imaging (2D-STI).Methods:A total of 67 UCM patients were randomly divided into the normal cardiac function group (subgroup A,32 cases) and the abnormal cardiac function group (subgroup B,35 cases)according to the New York Heart Association points (NYHA-P).A total of 30 healthy subjetcs served as the control group.Parameters including left ventricular ejection fraction (LVEF),left ventricular mass index (LVMI),left ventricular spherical index (LVSI),left ventricular myocardial mean radial strain (MRS),mean radial strain rate (MRSR),mean longitudinal strain (MLS),local systolic twist angle (STA),and mitral annulus maximum displacement (TMAD) were detected.Results:MLS,MRS,MRSR,LVSI,STA and TMAD in the Group A and Group B were lower than that in the control group (P<0.05),and LVMI in the Group A and Group B was increased than those in the control group (P<0.05);LVEE MLS,MRS,MRSR,LVSI and STAin the Group B was decreased than that in the Group A (P<0.05).MLS in the Group A and B were positively correlated with LVEF and LVSI,but negatively correlated with LVMI.Using the point of 14.10% for MLS to evaluate UCM patients with NYHA-P>4 points,the sensitivity,the specificity and Yuedden index were 90.5%,71% and 0.585,respectively.STA in UCM patients were lower than that in the control (P<0.05).Conclusion:2D-STI possesses a unique advantage in detecting left ventricular strain and strain rate on left ventricular regional function in UCM with left ventricular hypertrophy and ventricular deformation.There is no direct correlation between the left ventricular hypertrophy and ventricular deformation,but the ventricular hypertrophy and deformation are correlated with regional cardiac function and clinical cardiac function.Left ventricular regional dysfunction may occur before cardiac hypertrophy and deformation.
10.Pneumatic Circulation Treatment on Lower Extremity Swelling and Blood Flow Velocity after Hip Replacement
Xiaoliu LI ; Qiping LIU ; Xiaoyang ZHANG ; Xiaofan YIN ; Xiaoyan XING ; Xuemei AN
Chinese Journal of Rehabilitation Theory and Practice 2011;17(2):168-170
ObjectiveTo investigate the effect of pneumatic circulation treatment on lower extremity swelling and blood flow velocity after hip replacement.Methods48 patients after hip replacement were divided into two groups: treatment group (n=24) and control group (n=24). The treatment group received pneumatic circulation treatment and continuous passive motion, while the control group only received continuous passive motion 2 d after operation, all patients wearing elastic stockings. Circumference of the affected leg was measured and Visual Analogue Scale (VAS) was assessed, and Doppler ultrasonography was to check the blood flow velocity of femoral and deep veins in lower limb before, 3 d and 7 d after rehabilitation.ResultsThere was no difference in circumference, VAS, and the lower limb blood flow velocity between the two groups before operation (P>0.05). There was significant difference in circumference and VAS 3 d after treatment (P<0.01), and a significant difference in circumference and blood flow velocity (P<0.01) but no difference in VAS (P>0.05) 7 d after treatment between the two groups.ConclusionPneumatic circulation treatment may facilitate to eliminate lower extremity swelling and prevent deep vein thrombosis after total hip replacement.