1.Downregulation of MUC1 Inhibits Proliferation and Promotes Apoptosis by Inactivating NF-κB Signaling Pathway in Human Nasopharyngeal Carcinoma
Shou-Wu WU ; Shao-Kun LIN ; Zhong-Zhu NIAN ; Xin-Wen WANG ; Wei-Nian LIN ; Li-Ming ZHUANG ; Zhi-Sheng WU ; Zhi-Wei HUANG ; A-Min WANG ; Ni-Li GAO ; Jia-Wen CHEN ; Wen-Ting YUAN ; Kai-Xian LU ; Jun LIAO
Progress in Biochemistry and Biophysics 2024;51(9):2182-2193
ObjectiveTo investigate the effect of mucin 1 (MUC1) on the proliferation and apoptosis of nasopharyngeal carcinoma (NPC) and its regulatory mechanism. MethodsThe 60 NPC and paired para-cancer normal tissues were collected from October 2020 to July 2021 in Quanzhou First Hospital. The expression of MUC1 was measured by real-time quantitative PCR (qPCR) in the patients with PNC. The 5-8F and HNE1 cells were transfected with siRNA control (si-control) or siRNA targeting MUC1 (si-MUC1). Cell proliferation was analyzed by cell counting kit-8 and colony formation assay, and apoptosis was analyzed by flow cytometry analysis in the 5-8F and HNE1 cells. The qPCR and ELISA were executed to analyze the levels of TNF-α and IL-6. Western blot was performed to measure the expression of MUC1, NF-кB and apoptosis-related proteins (Bax and Bcl-2). ResultsThe expression of MUC1 was up-regulated in the NPC tissues, and NPC patients with the high MUC1 expression were inclined to EBV infection, growth and metastasis of NPC. Loss of MUC1 restrained malignant features, including the proliferation and apoptosis, downregulated the expression of p-IкB、p-P65 and Bcl-2 and upregulated the expression of Bax in the NPC cells. ConclusionDownregulation of MUC1 restrained biological characteristics of malignancy, including cell proliferation and apoptosis, by inactivating NF-κB signaling pathway in NPC.
2.Role of mitochondrial autophagy and the curative effect of rehmannia glutinosa leaves total glycoside capsules on nucleos(t)ide drug-induced renal injury
Kai ZHONG ; Manman ZHANG ; Zixin ZHU ; Xin LIAO ; Baofang ZHANG ; Mingliang CHENG
Chinese Journal of Hepatology 2024;32(2):125-132
Objective:To study the curative effect of rehmannia glutinosa leaves total glycoside capsules and the role of mitochondrial autophagy on nucleos(t)ide drug-induced renal injury.Methods:Adefovir dipivoxil (ADV) was used to construct a hepatitis B virus (HBV) transgenic mouse model for renal injury. Renal function was measured in each group at one and two weeks of modeling. Mitochondrial autophagy indicators were measured at two weeks of modeling in renal tissue. Transmission electron microscopy was used to detect mitochondrial autophagy phenomena in renal tissue. The model was established for two weeks. Mouse with renal injury were treated with rehmannia glutinosa leaves total glycoside capsules or isotonic saline for eight weeks by intragastric administration. Renal function was measured. Renal tissue morphology was observed. Mitochondrial autophagy indicators were detected in renal tissue. The protective effect of different concentrations of verbascoside (the main active ingredient of rehmannia glutinosa capsule) was observed on HK-2 cell damage induced by ADV. HK-2 cells were divided into control, ADV, and ADV plus verbascoside groups. The effects of verbascoside at different times and concentrations were observed on the HK-2 mitochondrial autophagy indicators. Fifty patients with chronic hepatitis B were collected who presented with renal injury after treatment with nucleos(t)ide analogs. The random number method was used to divide 29 cases into a control group that received conventional treatment. The treatment group of 21 cases was treated with rehmannia glutinosa leaves total glycoside capsules on the basis of the control group. Serum creatinine (Scr) and urinary protein were detected at eight weeks.The χ2 test or t-test was used for statistical analysis. Results:Compared with the control group, two weeks of modeling in the ADV group induced renal function injury in HBV mice. The expression of autophagy indicators was higher in the renal tissue of the ADV group than that of the control group. Transmission electron microscopy had revealed mitochondrial autophagy in the renal tissue of the ADV group. Compared with the control group, the renal function of HBV mice treated with rehmannia glutinosa leaves total glycoside capsules improved for two months, and the expressions of autophagy indicators were down-regulated.Verbascoside promoted proliferation in ADV-damaged HK-2 cells, and the expression of autophagy indicators was down-regulated compared with the ADV alone group. In 50 patients with renal function injury, the urinary protein improvement was significantly superior in the treatment group than that in the control group, with eighteen and three cases being effective and ineffective in the treatment group and 12 and 17 cases being effective and ineffective in the control group, with a statistically significant difference ( χ2 ?=?9.975 0, P ?=?0.001 6). Serum creatinine was decreased in the treatment group compared with the control group, with 11 and 10 cases being effective and ineffective in the treatment group and 12 and 17 cases being effective and ineffective in the control group, with no statistically significant difference ( χ2 ?= 0.593 5, P ?=?0.441 1). Conclusion:Rehmannia glutinosa leaves total glycoside capsule can improve the nucleos(t)ide drug-induced renal function injury in chronic hepatitis B, possibly playing a role via inhibiting PINK1/Parkin-mediated mitochondrial autophagy.
3.Observation and imaging analysis of signs of ankylosing spondylitis in spinal specimens
Wei-Xing ZHONG ; Zhi-Hong WANG ; Jun-Hua LI ; Li-Qing LIAO ; Zu-Jiang CHEN ; Yi-Kai LI
Acta Anatomica Sinica 2024;55(3):329-333
Objective To provide anatomical,radiological,and clinical diagnostic and therapeutic references for ankylosing spondylitis and spinal surgical operations.Methods Non-measurement spinal observations,X-ray examinations,and measurements were performed on two spinal specimens,along with digital image acquisition and processing.Results The first specimen included thoracic vertebra 7(T7)to lumbar vertebra 3(L3),with an average total length of 29.7 cm;the second specimen ranged from cervical vertebra 7(C7)to lumbar vertebra 2(L2),with an average total length of 38.3 cm.The specimens showed partial or complete calcification of ligaments,ossification of the small joints and intervertebral discs,and osteoporosis;The anterior-posterior diameter(width)of the vertebral foramen was narrower than that of a normal adult,while most of the superior-inferior diameter(height)was wider.Radiographically,the anterior longitudinal ligament calcification appeared as dot-like or striated,but it was actually flaky in the actual specimens.The specimens provided views of the facet joints,costovertebral joints,and intervertebral foramina that was difficult to demonstrate on two-dimensional X-ray images.Conclusion As ankylosing spondylitis progresses,the range of motion in spinal bending and rotation decreases,as does the extent of thoracic expansion,thereby affecting respiration and complicating procedures such as intraspinal anesthesia and sacral canal injections.In terms of diagnosis,bone specimens and X-ray films allow us to understand the development process and severity of ankylosing spondylitis more directly and accurately.
4.Clinical efficacy between modified Overlap anastomosis and traditional auxiliary incision anastomosis in laparoscopic total gastrectomy
Chuying WU ; Kai YE ; Jianhua XU ; Jian′an LIN ; Wenjin ZHONG ; Wengui KANG ; Zhengrong LIAO ; Jintian WANG ; Jiabin DU ; Junxing CHEN ; Weinan LIU ; Pengcheng WANG
Chinese Journal of Digestive Surgery 2020;19(9):988-994
Objective:To intestigate the clinical efficacy between modified Overlap anastomosis and traditional auxiliary incision anastomosis in laparoscopic total gastrectomy.Methods:The retrospective cohort study was conducted. The clinicopathological data of 115 patients with gastric cancer who were admitted to the Second Affiliated Hospital of Fujian Medical University from January 2016 to December 2018 were collected. There were 62 males and 53 females, aged from 27 to 83 years, with a median age of 62 years. Of 115 patients, 51 patients undergoing totally laparoscopic total gastrectomy with modified Overlap anastomosis using linear stapler were divided into modified Overlap group and 64 patients undergoing laparoscopic assisted total gastrectomy with traditional auxiliary incision anastomosis using circular stapler were divided into traditional assisted group. Observation indicators: (1) surgical situations; (2) postoperative situations; (3) anastomotic complications; (4) follow-up. Follow-up using outpatient examination or telephone interview was conducted to detected tumor recurrence and survival of patients up to December 2019. Measurement data with normal distribution were represented as Mean± SD, and comparison between groups was analyzed using the t test. Count data were represented as absolute numbers or percentages, and comparison between groups was analyzed using the chi-square test or Fisher exact probability. Comparison of ranked data was analyzed using the rank sum test. Results:(1) Surgical situations: the operation time, time of esophagojejunostomy, volume of intraoperative blood loss, the number of lymph node dissected, length of proximal incisional margin and length of auxiliary incision of the modified Overlap group were (234.0±11.0)minutes, (29.4±2.1)minutes, (53±14)mL, 42±13, (2.0±0.3)cm and (5.1±0.4)cm, respectively. The above indicators of the traditional assisted group were (231.0±11.0)minutes, (29.2±2.2)minutes, (50±13)mL, 40±10, (2.2±0.4)cm and (8.2±0.4)cm, respectively. There was significant difference in the length of auxiliary incision between the two groups ( t=-43.098, P<0.05), and there was no significant difference in the operation time, time of esophagojejunostomy, volume of intraoperative blood loss, the number of lymph node dissected, length of proximal incisional margin between the two groups ( t=1.168, 0.460, 0.990, 1.127, -1.926, P>0.05). (2) Postoperative situations: cases with mild, moderate, severe pain (postoperative pain degree), time to first flatus, time to initial fluid diet intake, duration of postoperative hospital stay of the modified Overlap group were 40, 9, 2, (2.9±1.0)days, (4.8±2.2)days, (11.7±2.8)days, respectively. The above indicators of the traditional assisted group were 31, 27, 6, (3.9±1.4)days, (6.5±2.5)days, (13.0±3.1)days, respectively. There were significant differences in the above indicators between the two groups ( Z=-3.217, t= -4.344, -3.888, -2.261, P<0.05). (3) Anastomotic complications: cases with anastomotic leakage, cases with anastomotic bleeding, cases with anastomotic stenosis of the modified Overlap group were 1, 1, 0, respectively. The above indicators of the traditional assisted group were all 1. There was no significant difference in the above indicators between the two groups ( P>0.05). Cases with anastomotic leakage were cured after the treatment of enteral nutritional support through nasogastric catheterization, which were confirmed by gastroenterography. Cases with anastomotic bleeding were improved by active hemostatic therapy. Cases with anastomotic stenosis were improved after the symptomatic treatment of anti-inflammatory and anti-swelling. (4) Follow-up: 109 of the 115 patients were followed up. Forty-eight of 51 patients in the modified Overlap group were followed up for 15.0-45.0 months, with a median follow-up time of 33.5 months. Sixty-one of 64 patients in the traditional assisted group were followed up for 16.0-46.0 months, with a median follow-up time of 27.0 months. There was no tumor recurrence in the modified Overlap group. One patient in the traditional assisted group had tumor recurrence with liver metastasis and survived with tumor. There was no significant difference in tumor recurrence rate between the two groups ( P>0.05). There was no patient died during the follow-up. Conclusion:Compared with traditional auxiliary incision anastomosis, patients undergoing total laparoscopic total gastrectomy with modified Overlap anastomosis have small incision, good postoperative recovery.
5.Antegrade Knuckle technique assisting reverse controlled antegrade and retrograde subintimal tracking technique for caleified or tortuous chronic total occlusion recanalization
Jing-Ye LIN ; Zhi-An ZHONG ; Bin ZHANG ; Ze-Han HUANG ; Kai-Ze WU ; Hong-Tao LIAO
Chinese Journal of Interventional Cardiology 2018;26(6):316-319
Objective To demonstrate the efficiency and safety of the modified reverse controlled antegrade and retrograde subintimal tracking(CART)technique for chronic total occlusion(CTO)recanalization.Methods Thirteen patients with CTO underwent this modified reverse CART technique.Based on the traditional reverse CART,the technology advocated the use of antegrade guidewire Knuckle technology to promote access to the subintimal space.With the use of a strong penetrating and well controllable retrograde guidewire,balloon was inflated in the CTO lesion in favor of advancing the retrograde guidewire through the lesion to reach the proximal true lumen.Results The occlusion site was located in the RCA in 10 patients and in the LAD in 3 patients.Among the 13 lesions,2 had J-CTO score = 1,4 had J-CTO score = 2,6 had J-CTO score = 3,and 1 had J-CTO score=4.Nine cases were considered as the Werner`s Collateral Connection grade 1 and other 4 cases were grade 2.All 13 cases had achieved technical success.1 case needed pericardiocentesis due to collateral branch perforation.Conclusions CTO lesions can be efficiently and safely recanalized using this modified reverse CART technique.
6.Guideline for diagnosis and treatment of ALK positive non-small cell lung cancer in China.
Xuchao ZHANG ; Shun LU ; Li ZHANG ; Meilin LIAO ; Changli WANG ; Ying CHENG ; Gandi LI ; Mok TONY ; Cheng HUANG ; Xiaoqing LIU ; Jie WANG ; Mengzhao WANG ; Yiping ZHANG ; Jianying ZHOU ; Xiaojun ZHOU ; Xiaoyan ZHOU ; Dongmei LIN ; Jinji YANG ; Yong SONG ; Kai WANG ; Yong HE ; Hui LI ; Wenzhao ZHONG ; Yilong WU
Chinese Journal of Pathology 2015;44(10):696-703
7.In utero exposure to di-n-butyl phthalate induces testicular cell apoptosis and vacuolization in the pubertal male rat offspring.
Hua SHEN ; Kai LIAO ; Hong-fei WU ; Hong-chao LU ; Zhong LI ; Wei ZHANG
National Journal of Andrology 2015;21(12):1064-1070
OBJECTIVETo investigate the impact of in utero exposure to di-n-butyl phthalate (DBP) on the apoptosis of testicular cells in the pubertal male rat offspring.
METHODSTen pregnant SD rats were randomly divided into a control and an experimental group to be treated intragastrically with olive oil (1 ml per day) and DBP (500 mg per kg of body weight per day) respectively between gestation days 12 and 19. At the pubertal age (postnatal day 45, PND 45), the testes of the male rat offspring were removed for observation of the cell structure under the transmission electron microscope and the development of different spermatogenetic cells by HE staining. The apoptosis of testicular cells was detected by the TUNEL method, the expressions of the apoptosis-regulating proteins Bcl-2, Bcl-XL, Bax and p53 were determined by immunohistochemistry and Western blot, and the data obtained were compared between the two groups by t-test.
RESULTSTransmission electron microscopy revealed increased apoptosis and vacuolization of testicular cells in the PND-45 rat offspring, HE staining showed markedly decreased numbers of different spermatogenetic cells, TUNEL manifested significantly increased apoptosis of testicular cells in the experimental group as compared with the control (12.00 ± 5. 22 vs 3.17 ± 1.47, P < 0.01), and immunohistochemistry and Western blot exhibited remarkably higher expressions of Bax and p53 in the former than in the latter group (P < 0.05).
CONCLUSIONIn utero exposure to DBP can increase the apoptosis of germ cells and Sertoli cells, induce the vacuolization of testicular cells, and significantly elevate the expressions of the apoptosis-promoting proteins Bax and p53 in the pubertal male rat offspring.
Animals ; Apoptosis ; Body Weight ; Dibutyl Phthalate ; adverse effects ; Female ; Immunohistochemistry ; In Situ Nick-End Labeling ; Male ; Pregnancy ; Prenatal Exposure Delayed Effects ; Rats ; Rats, Sprague-Dawley ; Sertoli Cells ; cytology ; pathology ; Spermatogenesis ; Testis ; cytology ; pathology ; Tumor Suppressor Protein p53 ; metabolism ; bcl-2-Associated X Protein ; metabolism
8.Morphological changes of bone in the progress of rat chronic fluorosis
Shu-ling, FAN ; Sheng-bin, BAI ; Wen, QIN ; Ya-lou NG ZHA ; Jin-jie, ZHONG ; Rong, CHEN ; Tian, LI ; Shu-mei, FENG ; Kai-tai, LIU ; Xue-gang, LUO ; Long, CHEN ; Li-bin, LIAO
Chinese Journal of Endemiology 2012;31(2):151-155
ObjectiveTo observe the morphological changes of bone in the progress of chronic fluorosis.MethodsWistar rats were randomly divided into three groups,30 rats in each group:normal control group,experimental group Ⅰ and experimental group Ⅱ according to body weight.Rats in normal control group drank distilled water freely.Experimental group Ⅰ and group Ⅱ drunk distilled water with sodium fluoride preparation of fluorine containing ion 100,150 mg/L solution for six months,respectively.Bone mineral density was detected by X-ray,bone morphological changes were observed under light microscope and bone histomorphometric parameters were calculated using image analysis software.ResultsThe bone mineral density values were different statistically between the three groups after feeding for 2 and 4 months(F =19.79,3.28,all P < 0.05).However no significant difference was found after feeding for 6 months(F =1.80,P > 0.05).The bone mineral density of experimental group Ⅰ (0.20 ± 0.03,0.21 ± 0.03) was significantly higher than that of the normal control group(0.17 ± 0.03,0.20 ± 0.04) after feeding for 2 and 4 months.The bone mineral density of experimental group Ⅱ (0.21 ± 0.02) was lower than that of normal control group(0.22 ± 0.03) after feeding for 6 months.The bone lamella in experimental group Ⅰ was arranged disorderly,the number of osteocytes increased with their nucleus atrophy and the osteoblasts were more than that of control grouo which arranged in layers observed under light microscooy.In exoerimental group Ⅱ,the bone lamella was bent deformation,the number of osteocytes had decreased with their nucleus shrinking or even disappeared and the number of osteoclasts had increased significantly observed under light microscopy.In experimental group Ⅰ,the mean trabecular density [(0.33 ± 0.03)%] increased and the mean trabecular separation,thickness [( 163.57 ± 1.99),(59.26 ± 7.18 ) μm] decreased compared with that of normal control group [(0.31 ± 0.02)%,(186.60 ± 2.90)μm,(86.42 ± 1.48)μm,all P < 0.05].In experimental group Ⅱ,the mean trabecular density[(0.26 ± 0.02)%] decreased,the mean trabecular thickness[(71.42 ± 10.77)μm] reduced compared with that of normal control group[(0.31 ± 0.02)%,(86.42 ± 1.48)μm].ConclusionsExcess fluoride can damage bone tissue.Low doses of fluoride can stimulate osteoblast activity and enhance osteogenesis.The activity of osteoblasts is great than that of osteoclasts.High doses of fluoride can stimulate both osteoblasts and osteoclasts activity,but mainly the activity of osteoclasts,and bone resorption increases.
9.Detection of fluoride ion concentration in osteoblasts in vitro by nuclear magnetic resonance spectroscopy
Jin-jie, ZHONG ; Jin-yi, ZHONG ; Jing-quan, LIU ; Sheng-bin, BAI ; Shu-ling, FAN ; Ya-lou NG ZHA ; Shu-mei, FENG ; Wen, QIN ; Long, CHEN ; Tian, LI ; Li-bin, LIAO ; Kai-tai, LIU
Chinese Journal of Endemiology 2012;31(2):147-150
ObjectiveTo detect the concentration and distribution of fluoride ions in osteoblasts exposed to fluoride in vitro culture,and to provide basic information for studying the effect of fluoride on osteoblast injury.MethodsIn vitro cultured osteoblasts were exposed to 0,5,10,20,40 mg/L fluoride for 3,10,30 d (n =6),respectively.Concentration and distribution of fluoride ions in the cytoplasm and the nucleus of these osteoblasts were determined by nuclear magnetic resonance spectroscopy.Results(①) After cultured for 3 d,fluoride ion content of the bone cytoplasm exposed to different concentrations of fluoride 0,5,10,20,40 mg/L were (0.83 ±0.65),(0.54 ± 0.23),(0.65 ± 0.77),(0.59 ± 0.87),(3.64 ± 1.21 )mg/L,respectively,and the values of exposed to 40 mg/L fluoride group was significantly higher than that of exposed to 0,5 mg/L groups (all P < 0.05).(②)after cultured for 10 d,the composition of the fluoride ion in cytoplasm of exposed to fluoride 10,20,40 mg/L groups were (4.03 ± 1.23),(3.66 ± 0.98),(6.26 ± 2.10)mg/L,respectively,which were higher than that of exposed to 0,5 mg/L groups [(0.78 ± 0.75),(2.69 ± 0.89)mg/L,respectively,all P < 0.05].Of fluoride 20,40 mg/L groups,the composition of the fluoride ion in nucleus were (1.63 ± 1.19),(2.17 ± 1.21 )mg/L,respectively,which were higher than that of 0,5 mg/L groups[(0.65 ± 0.46),(1.57 ± 0.33) mg/L,all P < 0.05].(③)After cultured for 30 d,of the exposed to fluoride 10,20,40 mg/L groups,the composition of the fluoride ion in cytoplasm were (3.99 ± 0.84),(4.33 ± 1.67),(5.80 ± 1.38)mg/L,respectively,which were higher than that of 0,5 mg/L groups[(0.88 ± 0.44),(2.84 ± 0.43)mg/L,all P < 0.05].The composition of the fluoride ion in nucleus of the fluoride 20,40 mg/Lgroups were (3.33 ± 1.46),(3.53 ± 1.22)mg/L,respectively,which were significantly higher than that of 0,5mg/L groups [(0.70 ± 0.66),(1.99 ± 0.76)mg/L,all P < 0.05].ConclusionsWhen osteoblasts are exposed to fluoride environment,fluoride ions enter into the osteoblasts quickly,and quickly accumulate in the nucleus,showing a special affinity between fluoride and bone tissue.Intracellular fluoride ions increase with the increase of contact time and exposure dose.
10.Sirolimus use in heart transplantation recipients with chronic renal dysfunction
Dong YIN ; Jie HUANG ; Lei FENG ; Zhong-Kai LIAO ; Guang-Xun FENG ; Wei WANG ; Yun-Hu SONG ; Sheng-Shou HU
Chinese Journal of Cardiology 2012;40(2):136-140
Objective To observe the effect of sirolimus-based immunosuppression administered on heart transplant recipients with chronic renal dysfunction.Methods From June 2004 to December 2008,standard calcineurin inhibitors( CNI)-based immunosuppressive regimen was changed to reduced-dose CNI plus sirolimus due to CNI-related chronic renal dysfunction in 20 out of 138 cardiac transplant recipients at Fuwai Hospital. The standard immunosuppressive regimen included steroid, CNI (cyclosporine or tacrolimus),and mycophenolate mofetil or azathioprine. Sirolimus was started at 0.75 - 1.50 mg/d with titration to achieve levels of 5 -15 μg/L,and CNI dose was reduced gradually to 1/2 -2/3 of the baseline level.Patients were followed for changes in renal function,lipid level and clinical side effects related to immunosuppressive therapy.Endomyocardial biopsy (EMB) was performed routinely at 3 weeks,3,6 and 12 months after transplantation.EMB was also performed at 3 months after regimen change within 1 year post-transplantation or when rejections were suspected in patients beyond 1 year post-transplantation.Echocardiography was performed for monitoring purpose.Results The mean follow-up after regimen change was (7.9 ±6.3) months.Final sirolimus dose was (0.89 ± 0.22) mg/d and blood drug level was (7.6 ±3.8 ) μg/L.Cyclosporine dose was reduced from ( 191.7 ± 60.0) mg/d to ( 123.6 ± 34.8 ) mg/d,with blood drug concentation reduced from ( 175.5 ± 58.0) μg/L to ( 111.9 ± 56.0) μg/L in 18 patients ( P < 0.01 ).Tacrolimus average dose was reduced from 4.25 mg/d to 3.00 mg/d,with blood drug concentation reduced from 13.5 μg/L to 10.5 μg/L in 2 patients.Serum creatinine level fell from ( 160.4 ± 25.5 ) μmol/L to ( 134.4 ± 26.8 ) μmol/L ( P < 0.01 ) and urea nitrogen fell from ( 13.8 ± 4.7 ) μmol/L to ( 10.4±3.0 )μmol/L(P <0.01 )at one month after regimen change.Twenty two EMBs were performed in 11 patients within 1 year post-transplant,there were 4 episodes of acute rejecte ( ISHLT grade 2).Twenty patients are all alive and cardiac function was normal.The most common side effect was hyperlipidemia,and triglycerides,total cholesterol and low density lipoprotein levels were significantly increased at 1 month post regimen change(P < 0.05 or P < 0.01 ).Leukocyte,hemoglobin and platelet as well as liver function remained unchanged at 1 month post regimen change ( all P > 0.05).Conclusion Our results show that change from CNI-based immunosuppressive regimen to reduced-dose CNI plus sirolimus is an effective and safe approach for the management of patients with CNI-related chronic renal dysfunction,leading to an improvement in renal function without compromise in anti-rejection efficacy and with tolerable side effects.

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