Objective To analyze the genomic alterations of papillary thyroid carcinoma(PTC) by nextgeneration sequencing(NGS),and to explore the relationship between mutation frequency and clinicopathological features. Methods  The tissue samples and clinical data from 34 PTC patients were collected in our hospital from May 2015 to May 2021.The 70 gene sequencing instrument was used for the detection of gene variations.Then we analyzed the relationship between BRAF mutation frequency and clinicopathological characteristics. Results  A total of 5 genes and 7 variant sites were identified in 34 PTC patients,among which BRAF V600E was the most common(80.77%).BRAF V600E and NCOA4-RET were present in both primary and recurrent lesions.BRAF mutation frequency ranged from 1.14% to 34.24% in the primary focus,subjects with high-frequency mutation(> 15%) mostly were a single larger tumor(>2 cm),but ones with low-frequency mutation(≤15%) was multiple smaller lesions(≤2 cm). Conclusion NGS is helpful to reveal the multigenic variation of PTC.BRAF mutation frequency,may contribute to diverse clinical biological features.

Objective To investigate the diagnosis,treatment and prognosis of multiple endocrine neoplasia syndrome type 1(MEN1). Methods There were 2 MEN1 patients, whose clinical manifestations were mainly hyperparathyroidism, 1 underwent radical thyroidectomy + subtotal parathyroidectomy, and the other underwent subtotal parathyroidectomy. Results Elevated parathyroid hormone(PTH) and blood calcium were found in both patients.Ultrasound and MIBI showed parathyroid adenoma.Gene detection confirmed MEN1 gene mutation.The two patients were both treated by resection of 3.5 parathyroids,and the PTH and blood calcium had returned to the normal range after operation. Conclusion MEN1 is a rare autosomal dominant inherited disorder,which is easy to be missed and misdiagnosed.Comprehensive analysis of clinical data,rational use of gene detection combined with surgery and other appropriate intervention measures are of great significance to the diagnosis,treatment and prognosis of MEN1.

Objective To investigate the risk factors of cervical lymph node metastasis of medullary thyroid carcinoma(MTC),and to investigate the value of serum calcitonin(Ctn) in predicting cervical lymph node metastasis. Methods The clinicopathological data of 47 patients with postoperative pathological diagnosis of MTC were retrospectively analyzed,and divided into two groups according to whether or not there were cervical lymph node metastasis.The risk factors of cervical lymph node metastasis were analyzed by univariate analysis and Logistic regression analysis.The sensitivity and specificity of Ctn value in predicting cervical lymph node metastasis were studied by ROC curve. Result Univariate analysis showed that the lateral cervical metastasis group had larger MTC diameter( P = 0.004 ),higher serum Ctn( P =0.000) and CEA( P =0.003),multiple lesions rate(55.56% vs 13.79%, P = 0.004)  and higher central lymph node metastasis rate(77.78% vs 37.93%, P =0.015).Regression analysis showed that increased serum Ctn( P =0.036) and central lymph node metastasis( P =0.017) were independent risk factors for lateral cervical metastasis.When the Ctn cut-off point was 300.9 ng/L),the sensitivity,specificity and area under ROC curve(AUC) for predicting lateral cervical lymph node metastasis were 94.4%,62.1% and 0.808 respectively.  Conclusion  Elevated serum Ctn and central lymph node metastasis are independent risk factors for cervical lymph node metastasis of MTC,and Ctn can be used as a sensitivity index for predicting cervical lymph node metastasis.

Objective To explore the risk factors associated with parathyroid injury after thyroidectomy by Meta-analysis. Methods To retrieve the related literature of hypocalcemia and hypoparathyroidism after thyroidectomy in domestic and foreign literature databases(as of April 2021).Literature retrieval，screening，evaluation and data extraction were performed by two investigators.Feeding data into the software(Revman 5.3) for Meta-analysis. Results A total of 809 literatures were retrieved.The final 9 papers(English:1，Chinese:8)were finally included after screening by two investigators，A total of 2324 subjects were studied.After the software analysis of the study data，the results of the study were obtained:gender [OR=0.66，95%CI(0.47，0.92)， P =0.01]；surgery number of procedures [ OR= 0.50，95%CI(0.34，0.73)， P <0.0004]； Surgical method[OR=4.12，95%CI(2.18，7.77)， P < 0.0001]；Central Lymph Node Dissection(CLND) [OR=0.32，95%CI(0.24，0.44)， P <0.00001]； combined Hashimoto`s Thyroiditis  [OR=0.17，95%CI(0.09，0.25)，P<0.0001]；tumour invasion of the envelope [OR=1.65，95%CI(1.18，2.32)，P=0.004]；Inadvertent Parathyroidectomy(IP) [OR=3.00，95%CI(1.40，6.42)，P=0.005]；type of pathology[OR=4.31，95%CI(1.98，9.35)，P=0.0002]were risk factors for parathyroid injury after surgery.Conclusions There are many factors leading to parathyroid gland injury. Various methods should be taken to protect the parathyroid gland during operation to avoid or reduce parathyroid gland injury. If misincision occurs, parathyroid gland implantation is a remedy method.

Objective To systematically evaluate the application value of the combination of indocyanine green(ICG) and methylene blue(MB) in sentinel lymph node biopsy(SLNB) of early-stage breast carcinoma(EBC). Methods A literature search was performed using CBM,CNKI,WanFang databases,VIP,PubMed,Embase,Web of Science and Cochrane Library to identify papers published from January 1,2000 to May 15,2021 to research the application value of the combination of ICG and MB in SLNB of EBC.The literature was screened according to inclusion and exclusion criteria.Relevant data were extracted,and a quality assessment was conducted.The meta-analysis was used to disclose the differences in identification rate(IR) of patients,the false negative rate(FNR),specificity and accuracy between the above methods.Egger test was used to evaluate the publication bias. Results A total of 21 studies with 4813 patients were included in this Meta-analysis.The results showed that the IR of patients(OR=7.19,CI=5.23-9.87, P ＜0.001),specificity(OR=4.18,95%CI=1.78-9.83, P ＜0.001),accuracy(OR=4.60,95%CI=2.10-10.11, P ＜0.001) was obviously increased and the FNR(OR= 0.22, 95%CI=0.13-0.37, P ＜0.001) was significantly decreased by using ICG plus MB compared with MB alone. Conclusion Compared with MB alone,ICG with MB enjoys a significant advantage.It expects to offer innovative approaches in SLNB of EBC.

Objective To study the expression significance of cancer gene Gankyrin in invasive ductal carcinoma(IDC) and precancerous lesions of the breast. Methods A total of 105 cases of IDC and precancerous tissue paraffin specimens resected during January 2016 to June 2018 were selected as research objects,including 65 cases of IDC tissue paraffin specimens and 40 cases of precancerous tissue paraffin specimens,and another 25 cases of normal breast tissue paraffin specimens with nontumor lesions resected during the same period were taken as controls.Compared the expression of Gankyrin in different histopathological specimens,and explore the relationship between Gankyrin expression in IDC histopathological specimens and disease characteristics and patient prognosis. Results The expression of Gankyrin in IDC was significantly higher than that in precancerous lesions and normal breast tissue( P <0.05),and the expression of Gankyrin in precancerous lesions was significantly higher than that in normal breast tissue( P <0.05).Among IDC patients,the positive rate of Gankyrin expression in patients with lymph node metastasis was 94.1%,which was significantly higher than that of patients without lymph node metastasis(67.7%)( P <0.05);the positive rate of Gankyrin expression in patients with intravascular tumor thrombus was 91.7%,significantly higher than those without intravascular tumor thrombus( 69.0 %)( P <0.05).The 3-year DFS of Gankyrin positive expression was 24.49%,and the 3-year DFS of negative expression was 60.00%.There was a statistically significant difference in the 3-year DFS curve between Gankyrin positive expression and negative expression( P <0.05).Cox regression analysis showed that clinical stage,degree of differentiation,lymph node metastasis,and Gankyrin positive expression were independent prognostic factors affecting progression-free survival(DFS)( P <0.05). Conclusion The cancer gene Gankyrin is highly expressed in IDC and precancerous tissues.Gankyrin expression is related to the prognosis of IDC disease.

Objective To investigate the clinical effect of surgical treatment for moyamoya disease complicated with intracranial aneurysm. Methods A retrospective analysis was performed on 264 patients with moyamoya disease treated by surgery in Department of Neurosurgery,Renmin Hospital of Wuhan University from January 2015 to June 2021,including 233 patients in the non aneurysmal group(patients with moyamoya disease treated with intracranial and extracranial artery bypass) and 31 patients in the aneurysmal group(patients with moyamoya disease complicated with intracranial aneurysm underwent bypass and intracranial aneurysm interventional embolization or craniotomy clipping).DSA or CTA follow-up was performed and mRS scores were recorded. Results Among 237 patients with complete follow-up data,209 patients had good prognosis(mRS<3),including 191 patients(191/212,90.1%) in the non aneurysmal group and 18 patients(18/25,72.0%) in the aneurysmal group( P <0.05).157 patients with early Suzuki stage had good prognosis.Among them,there were 144 cases(144/233, 61.8 %) in the non aneurysmal group and 13 cases(13/31,41.9%) in the aneurysmal group( P < 0.05 ). Conclusion Compared to patients with MMD alone,the Suzuki stage of patients with MMD complicated with intracranial aneurysm is higher,which will increase the incidence of postoperative complications and make the prognosis  poor.

Objective To investigate the relationship between trimethylamine N-oxide(TMAO),short-chain fatty acids(SCFAs) and serum of intestinal flora metabolites in patients with traumatic brain injury(TBI) Correlation of metabolic marker levels. Methods Among 99 TBI patients admitted from September 2018 to December 2020,33 healthy subjects were selected as the control group.Detect intestinal TMAO,SCFAs levels,serum total cholesterol(TC),triglyceride(TG),and high-density lipoprotein cholesterol by high-performance liquid chromatography,gas chromatography,and automatic biochemical analyzer.(High-density lipoprotein cholesterol,HDL-C),low-density lipoprotein cholesterol(LDL-C),glycosylated hemoglobin(HbA1c) and fasting blood glucose levels. Results The intestinal TMAO levels,serum TC,TG,LDL-C,HbA1c,and fasting blood glucose levels in TBI patients were higher than those in the control group,and gradually increased with the severity of the disease(P< 0.05) ;intestinal butyric acid and serum HDL-C levels were lower than the control group,and gradually decreased with the worsening of the disease( P <0.05).Pearson correlation analysis showed that TMAO was positively correlated with HbA1c and TC,and negatively correlated with TG and LDL-C.Butyric acid was positively correlated with TG and LDL-C,and was negatively correlated with TC and fasting blood glucose.Multivariate logistic regression analysis showed that TC,LDL-C,HbA1c and fasting blood glucose levels were the risk factors for the intestinal TMAO and butyric acid levels to affect the prognosis of TBI patients. Conclusion Intestinal TMAO and butyric acid levels are closely related to serum metabolic marker levels,and are related to the progression of TBI patients.They provide possible new targets for the prevention and treatment of TBI,but their mechanisms need to be further studied.

Objective To compare the surgical parameters,complications and prognosis of patients with esophageal squamous cell carcinoma treated by thoracoscopic modified recurrent laryngeal nerve lymph node dissection and traditional lymph node dissection. Methods The data of 162 patients who underwent thoracoscopic esophageal carcinoma resection in our hospital from March 2015 to August 2019 were retrospectively analyzed.Among them,73 patients underwent traditional lymph node dissection and 89 patients underwent modified recurrent laryngeal nerve lymph node dissection.Operation-related indicators(duration of operation,intraoperative blood loss,duration of postoperative drainage tube indwells and length of stay),lymph node dissection,postoperative complications and Disease free survival(DFS) were compared between the two groups.Finally,independent prognostic factors affecting DFS were screened by COX univariate and multivariate analysis. Results In the modified group, the operative time was (125.65±23.85) min, the intraoperative blood loss was (215.69±26.37)ml, the postoperative drainage tube indwelling time was (7.04±1.31) days, and the hospital stay was (11.51±2.43) days,while in the traditional group they were (123.76±25.05) minutes, (211.29±20.21)ml, (7.11± 1.62 )days, (11.72±2.71)days,respectively.no statistically significant difference were observed in the two groups (all  P ＞0.05).The time of RLNLN dissection in the modified group was less than that in the traditional group,and the number of left and right RLNLN dissection was more than that in the traditional group,the incidence of recurrent laryngeal nerve injury in the modified group(2.2%) was significantly lower than that in the traditional group(11.0%)(all  P <0.05).COX multivariate analysis showed that modified recurrent laryngeal nerve lymph node dissection,tumor stage and tumor differentiation were independent prognostic factors for DFS( P =0.022,0.037,0.026). Conclusion Improved recurrent laryngeal nerve lymph node dissection has certain advantages over traditional lymph node dissection,and is associated with better prognosis of patients.

Objective To evaluate the effect of central obesity on the clinical efficacy of laparoscopic D2 radical gastrectomy for distal gastric cancer. Methods The clinical and pathological data of 168 patients with distal gastric cancer who underwent laparoscopic D2 radical gastrectomy in Beijing Chaoyang Hospital Affiliated to Capital Medical University from April 2013 to January 2021 were collected.The male waist circumference ≥85 cm and female waist circumference ≥80 cm were divided into two groups.There were 64 cases in obesity group and 104 cases in non-obesity group.Propensity score matching method was used to balance the clinical baseline characteristics of the two groups except BMI and waist circumference.The operation related indexes,postoperative complications indexes,postoperative pathological indexes and prognostic survival indexes were compared between the two groups after matching. Results Before matching,there were significant differences in age and anesthesia risk score between obese group and non-obese group(except BMI and waist circumference)( P <0.05).After matching,61 cases in obesity group and 61 cases in non-obesity group were matched successfully.There was no significant difference in basic data(except BMI and waist circumference) between the two groups( P >0.05).The operation related indexes of the two groups were compared,the operation time,intraoperative blood loss and postoperative hospital stay were(219.8±33.6)min,(156.6±55.1) ml and(14.6±2.3) days in obese group and(198.2±24.7) min,(122.1±44.3) ml and(13.4±2.7) days in non-obese group,the difference was statistically significant( P <0.05).The recovery time of gastrointestinal function was(3.0±0.8) days in the obese group and(2.8±0.9) days in the non-obese group,the difference was not statistically significant(P >0.05).Comparison of postoperative complications between the two groups,there were 15 patients with 22 complications in the obese group and 13 patients with 18 complications in the non-obese group,the difference was not statistically significant( P >0.05).Comparison of postoperative pathological indexes between the two groups,the number of lymph nodes in obese group was(21.9±4.2),the rate of lymph node metastasis was 77.0%,the number of positive lymph nodes was(3.3±2.4),the number of pTNM stage Ⅰ/Ⅱ/Ⅲ was 17/23/21,and the numbers of non-obese group were(22.4±5.6),70.5%,(3.1±2.4) and 19/23/19,the difference was not statistically significant( P >0.05).Comparison of prognosis and survival indexes between the two groups,there were 16 patients died of tumor recurrence and metastasis in obese group and 14 patients died of tumor recurrence and metastasis in non-obese group.There was no significant difference in overall survival between the two groups The difference was not statistically significant( P >0.05). Conclusion Central obesity increases the difficulty of laparoscopic D2 radical gastrectomy for distal gastric cancer.The recovery of patients with central obesity is slower,but the prognosis is not affected.

Objective To investigate the treatment strategies of pancreatic leak in bladder-drained simultaneous pancreas and kidney transplantation(SPK) recipients. Methods Retrospective,three cases of SPK recipients with pancreatic leakage,all medical history,clinical data,and treatment strategies were recorded and analyzed. Results All the three SPK recipients had bladder-drained pancreatic grafts.Pancreatic leakage occurred in two patients during the perioperative period of SPK and in one recipient at one-year post-transplantation.Bladder decompression,full drainage and transplanted duodenum fistula repair were the main strategies,in addition to symptomatic supportive treatments including antibiotic treatment,inhibition of pancreatic exocrine secretion,maintenance of homeostasis and nutritional support.Eventually,all the 3 patients were successfully cured without any graft loss or patient death. Conclusion Severe pancreatic leakage in SPK patients can lead to serious consequences,which can be effectively treated by drainage and transplanted duodenum fistula repair.

Objective We reported and analyzed a case with multiple complications after cervical spine surgery to provide some experience for clinical front-line workers. Methods To retrospectively analyze a patient with cervical spondylosis admitted to Wuhan First Hospital in 2017,who underwent anterior cervical subtotal vertebral decompression and implant fusion (ACCF).Epidural hematoma and esophageal fistula occurred after surgery,which healed after emergency surgery and two repairs.The causes,clinical manifestations,treatment and prevention of postoperative epidural hematoma and esophageal fistula were analyzed through literature review. Results Early epidural hematoma should be surgically removed in time to avoid serious neurological dysfunction;esophageal fistula mostly manifests as dysphagia,it will lead to serious consequences if not detected in time.Surgical repair of esophageal fistula is mostly unavoidable,which is the way to achieve good results. Conclusion Multiple postoperative complications after cervical spine are rare.Strengthening perioperative management and preventing complications are important for patients.Early detection,diagnosis and treatment will avoid risk factors，which are great significance for the quality of surgery and the prognosis of patients.

Objective To observe the effect of direct anterior approach and minimally invasive SuperPath approach on THA of traumatic femoral neck fracture. Methods 240 patients with traumatic fracture diagnosed from January 2017 to October 2019 were selected as the research objects.According to the random number table method, they were divided into observation group and control groupp,with 120 cases in each group.The observation group was treated with minimally invasive technology superpath,and the control group was treated with direct approach.The operation time and intraoperative bleeding rate of the two groups were observed Blood volume,postoperative bed rest time,fracture healing time,Harris score,standing walking time,single leg standing test time,6min walking test distance and quality of life. Result There was no significant difference in operation time and intraoperative bleeding volume( between the two groups（ P ＞0.05）.The postoperative bed rest time of the observation group was significantly lower than that of the control group（ P ＜0.05）.The Harris scores of patients at 7 days,1 month and 12 months were significantly higher than those of the control group（ P ＜0.05）.After treatment,the standing walking time of patients in the observation group was significantly lower than that in the control group,and the single leg standing test time and 6min walking test distance were significantly higher than those in the control group（ P ＜0.05）.The physical pain,social function,mental health and overall health of the observation group were significantly higher than those of the control group（ P ＜ 0.05 ）. Conclusion Minimally invasive THA surgery through superpath approach is adopted in patients with traumatic femoral neck fracture.The protective effect of joint capsule is good and the curative effect is remarkable.

Objective The neoadjuvant immunotherapy of immune combined chemotherapy can coordinate and kill tumor cells. However, the immune imbalance in the process of immune activation can lead to immune-related adverse events (IRAEs). It has obvious clinical significance to explore how to develop an effective treatment plan for IRAEs through case analysis. Methods 2 cases bladder cancer patients who received neoadjuvant therapy of teriprizumab, gemcitabine and carbamazepine (GC regimen).  Result 2 patients got remission after trtatment, but got immune-related bladder inflammation. After treatment of steroids, patients immune-related bladder inflammation symptoms had improved. Robot-assisted laparoscopy laparoscopic radical cystectomy and ileal bladder replacement was performed. 2 patients were followed up, their prognosis were good. 

Objective To investigate the expression of Dickkopf-related protein 2(DKK2) in cancer tissues of patients with bladder cancer and its relationship with prognosis. Methods Eighty-six patients with bladder cancer who were treated in our hospital from May 2016 to June 2018 were selected for surgical treatment of bladder cancer,and bladder cancer tissue specimens and adjacent tissues(≥5 cm from the cancer tissue) were collected.Compare the expression of DKK2 in cancerous tissues and adjacent tissues.Analyze the relationship between DKK2 expression in cancer tissues and clinicopathological characteristics.Cox regression analysis of multiple factors affecting the prognosis of bladder cancer patients.To analyze the relationship between the expression of DKK2 in cancer tissues and the prognosis of bladder cancer patients. Results The negative expression rate of DKK2 in bladder cancer tissue was higher than that in adjacent tissues( P <0.05).There was no significant difference in the negative expression rate of DKK2 in cancer tissues of bladder cancer patients with different gender,age,BMI,smoking,drinking,and the number of tumors( P >0.05).The maximum diameter of the tumor was ≥3 cm,the clinical stage Ⅲ to Ⅳ,there was The negative expression rate of DKK2 in the cancer tissues of patients with lymph node metastasis,poorly differentiated,and vascular invasion of bladder cancer is higher than that in patients with tumors with a maximum diameter of <3 cm,clinical stages Ⅰ to Ⅱ,no lymph node metastasis,moderate/well differentiated,and no vascular invasion.The difference was statistically significant( P <0.05).86 patients with bladder cancer were followed up for 3 years,and 5 cases were lost to follow-up.Of the remaining 81 patients,19 died,with a mortality rate of 23.46%.Cox regression analysis showed that clinical stage,lymph node metastasis,degree of differentiation,and negative expression rate of DKK2 were independent factors affecting the prognosis of bladder cancer patients(OR=3.018,2.267,3.184,4.645, P <0.05).By the end of the follow-up,the survival rates of patients with DKK2-positive and DKK2-negative bladder cancer were 94.44% and 71.43%,respectively.The survival curve of patients with positive expression of DKK2 and patients with negative expression of DKK2 were compared,and the difference was statistically significant( P <0.05). Conclusion The negative expression rate of DKK2 in cyst carcinoma tissues is relatively high.The expression of DKK2 has a certain correlation with tumor diameter,clinical stage,lymph node metastasis,degree of differentiation,vascular invasion and prognosis in patients with bladder cancer.Monitoring its expression is beneficial to patients with bladder cancer Prognosis evaluation has important reference value.

Objective To investigate the effect of erector spinae plane block on postoperative hyperalgesia and injury stress in patients with kidney stones. Methods 102 patients with renal calculi treated in our hospital were prospectively selected as the research object.According to different anesthesia methods,they were divided into control group and study group,with 51 cases in each group.The control group was given general anesthesia,and the study group was given vertical spinal muscle plane block on the basis of general anesthesia.The clinical indexes,pain sensitivity and psychological stress indexes were compared. Results The clinical indexes in the study group were significantly lower than those in the control group( P <0.05);The VAS score of the study group was lower than that of the control group( P <0.05).The psychological stress indexes such as surgical stress index(SSI),brain state pain index(PI),comfort index(CFI),anxiety index(Anxi)and tension index(NVI)in the study group were significantly lower than those in the control group( P <0.05). Conclusion In the treatment of percutaneous nephroscope holmium laser lithotripsy,the effect of vertical spinal muscle plane block combined with general anesthesia is remarkable,which can effectively improve clinical indexes,have good anti pain sensitivity and stress response.

Medullary thyroid carcinoma is a malignant tumor derived from neuroendocrine cells,which can be hereditary or sporadic.Its molecular genetic alterations mainly include RET gene mutation and RAS gene mutation.Surgery is the main treatment modality for early medullary thyroid carcinoma.Targeted therapy is an important therapeutic alternative for recurrent or advanced medullary thyroid carcinoma.Targeted therapeutic agents currently available for relapsed or advanced medullary thyroid carcinoma include Vandetanib,Carbozantinib,Anlotinib,Pralsetinib and Selpercatinib.The molecular genetics alterations of medullary thyroid carcinoma and progress in targeted therapy for recurrent or advanced medullary thyroid carcinoma were mainly reviewed in the paper.

Glioma is one of the most common primary intracranial tumors,and its malignant degree isⅠ-Ⅳ and histological subtypes,including astrocytoma,pleomorphic glioblastoma(GBM),oligodendroglioma and mixed tumor.Glioma is characterized by rapid cell proliferation and angiogenesis.Glioblastoma is highly malignant,poor prognosis,high recurrence and mortality.Therefore,much attention has been paid to the exploration of the precise molecular mechanism and reliable therapeutic targets of gliomas.Recent studies have found that Long non-coding RNA(lncRNA) is significantly differentially expressed in glioma tissues and cell lines,which may play an important role in the occurrence,development and other malignant phenotypes of gliomas.This review summarizes the main functions of lncRNA and its role in gliomas,and discusses the functions and known mechanisms of several representative LncRNA.Finally,the possible problems of LncRNA research are discussed.

Urolithiasis is one of the most common diseases in urology.The  high incidence and recurrence rate of kidney stone is a difficult problem in urology,and its specific pathogenesis is still unclear.Randall’s Plaques theory is the mechanism of stone formation which is generally recognized by scholars at present among many theories.The retention of crystal particles in the renal tubules is a prerequisite for the formation of Randall’s Plaques.The deposited crystal damage the renal tubules through direct attachment or inflammatory immune response to promote the further deposition of the crystal,and ultimately promote the formation of Randall’s Plaques.The process of crystal deposition will cause kidney damage,but its molecular mechanism is still unknown.This article reviews the research progress on the formation of  Randall’s Plaques and the mechanism of renal injury.