1.The effect of insulin intensive therapy on serum level of oxidative stress in patients with first diagnosed type 2 diabetes mellitus
Jing ZHAO ; Xiaofeng Lü ; Xingguang ZHANG
Chinese Journal of Postgraduates of Medicine 2013;36(22):1-4
Objective To observe the difference in serum level of oxidative stress between first diagnosed type 2 diabetes mellitus (T2DM) patients and healthy person with normal glucose,compare the difference in serum level of oxidative stress between T2DM patients with continuous subcutaneous insulin injection (CSII) and multiple subcutaneous insulin injection (MSII),and further explore the possible mechanism of CSII superior to MSII.Methods Sixty patients with first diagnosed T2DM were divided into CSII group and MSII group by random digits table,with 30 patients in each group and given 14 days treatment of CSII and MSII respectively.Thirty healthy person were selected with age and sex matched in same period as control group,then fasting plasma glucose (FPG),2-hour postprandial blood glucose (2 h PG),glycosylated serum protein (GA),fasting insulin (FINS),superoxide dismutase (SOD),reduced glutathione (rGSH) and malondialdehyde (MDA) before and after treatment was measured and analyzed.Results The FPG,2 h PG,GA,HOMA model of insulin resistance (HOMA-IR) and MDA before treatment in CSII group and MSII group was higher than that in control group [FPG:(13.81 ± 3.14),(13.58 ±2.10) mmol/L vs.(5.21±0.42) mmol/L; 2 h PG:(21.72 ±4.43),(22.07 ±3.86) mmol/L vs.(6.19 ± 0.47) mmol/L;GA:(28.74 ± 4.40),(28.83 ± 5.01) mmol/L vs.(13.24± 1.26) mmol/L;HOMA-IR:0.45 ±0.13,0.43 ±0.12 vs.0.20 ±0.15;MDA:(4.37 ± 1.13),(4.44 ± 1.07) mmol/L vs.(2.37 ±0.58) mmol/L] (P < 0.01),and the HOMA model 3 cell function index (HOMA-β),SOD and rGSH was lower than that in control group [HOMA-β:0.98 ±0.17,0.96 ±0.12 vs.1.91 ±0.19;SOD:(29.63 ±9.29),(28.07 ±9.62) mU/L vs.(41.00 ± 12.89) mU/L;rGSH:(157.03 ±46.58),(165.23 ±45.66) ng/L vs.(212.00 ± 61.67) ng/L] (P < 0.01).There was no significant difference between CSII group and MSII group (P > 0.05).The FPG,HOMA-β,SOD and MDA after treatment in CSII group was no significant difference compared with that in control group (P > 0.05).But the FPG and MDA after treatment in MSII group was higher than that in control group(P< 0.01 or < 0.05),and the HOMA-β and SOD was lower than that in control group (P < 0.01).The FPG,2 h PG,GA and MDA after treatment in CSII group was lower than that in MSII group (P < 0.01 or < 0.05).The HOMA-β was higher than that in MSII group (P < 0.01).Multi-factor analysis results showed that the HOMA-β and FPG (r =-0.919,P < 0.01),2 h PG (r =-0.904,P < 0.01),GA (r =-0.830,P < 0.01) and MDA (r =-0.653,P < 0.01) was negatively correlated,and SOD (r =0.454,P < 0.01) and rGSH (r =0.394,P < 0.01) was positively correlated.Conclusions Oxidative stress level of first diagnosed T2DM is significantly higher than that of healthy people.Two intensive insulin treatment for first diagnosed T2DM can reduce blood glucose level,oxidative stress levels and improve insulin resistance and β cell function.CSII can effectively reduce blood glucose,reduce the level of lipid peroxidation and improve β-cell function compared with MSII.
2.Assessment of the accuracy of real-time continuous glucose monitoring system and its correlated factors
Pei LUO ; Qianpeng CHENG ; Jinxiao WU ; Mingyang ZHANG ; Xiaofeng Lü
Chinese Journal of Endocrinology and Metabolism 2013;29(11):954-958
Objective To assess the factors that influence the accuracy of real-time continuous glucose monitoring system (RT-CGM).Methods A total of 79 diabetic patients wore RT-CGM for three days continuously while calibrating by interphalangeal glucose values 4-8 times a day.We counted matching rate of interphalangeal glucose values and RT-CGM probe value,and analyzed correlation of the matching rate with MAGE,SDBG,MBG,AUC10,AUC3.9,and NGE by Pearson correlation analysis and multiple linear regression analysis.Then we grouped corresponding match rate by MAGE and MBG,compared the difference among groups.Furthermore,we analyzed correlation of RT-CGM probe values of all-day,fasting-postprandial,and nighttime and the corresponding interphalangeal glucose values by Pearson correlation analysis.Results Pearson correlation analysis showed that the matching rate was negatively correlated with the MAGE,SDBG,MBG,and AUC10.MAGE,MBG,and NGE were in the regression equation.MAGE <3.9 mmol/L,matching rate was 81%,3.9 ≤ MAGE<7 mmol/L,matching rate was 67%,MAGE≥7 mmol/L,the matching rate was 52%,the difference among 3 groups was statistically significant (P<0.01).MBG<7.8 mmol/L,matching rate was 78%,7.8 ≤ MBG< 10 mmol/L,matching rate was 68%,MBG ≥10 mmol/L,the matching rate was 57%,the difference among 3 groups was statistically significant (P < 0.01).When Youden index was 0.409 and MAGE was less than 3.745 mmol/L,the match rate was more than 75%.When Youden index was 0.369 and MBG was less than 8.38 mmol/L,the matching rate was more than 75%.The correlation coefficients of all day,fasting,postprandial and nighttime probe values and the corresponding interphalangeal glucose values were 0.958,0.963,0.944,and 0.965 (all P<0.01).Conclusions The probe values show good consistency with the interphalangeal glucose values,are able to be used for blood glucose assessment.Blood glucose fluctuations influences accuracy of RT-CGM,the smaller the blood glucose fluctuations,the smaller the mean glucose concentration,the smaller the effective blood glucose fluctuations in frequency,the higher would be the accuracy.It seems to be more effective to do calibration during fasting and nighttime.
3.Relationship between menstrual disorder and ovarian morphology of adolescent women
Li WANG ; Xiaofeng YANG ; Wenjun MAO ; Shulan Lü
Journal of Xi'an Jiaotong University(Medical Sciences) 2017;38(4):579-583
Objective To study the relationship between menstrual disorder and ovarian morphology of adolescent women in order to provide basis for diagnosis of adolescent polycystic ovary syndrome (PCOS).Methods We analyzed the clinical data of 212 patients with adolescent menstrual disorders 2 years after menstruation collected from the Department of Gynecology and Women's Health of First Affiliated Hospital of Xi'an Jiaotong University between September 2014 and September 2015.Results ① Oligomenorrhea was the most common in the 212 adolescent women (33.96 %),followed by amenorrhea (16.51%).There was a significant difference in F-G score and acne score among patients with different types of menstrual disorder (F=1.39,1.77,all P<0.05),the highest in those with oligomenorrhea.② The volume of the ovary,number of sinusoidal follicles,maximum area of the ovary in women with oligomenorrhea were significantly higher than those in non-oligomenorrhea women (t =2.89,5.76,6.23,all P< 0.05).③ Clinical manifestations differed significantly among normal ovarian group,MFO group and PCO group (x2=43.25,P<0.05).Incidence rate of oligomenorrhea ranked the top in polycystic ovary group (49.30%),followed by multiple ovarian follicles group (42.59%),and there were significant differences in blood LH,T,and LH/FSH (F=3.45,2.43,2.76,all P<0.05) was found in PCO group.There was significant difference in diagnosis of puberty PCOS (x2=26.58,P<0.05).④ Among these 212 adolescent women,45 ones had puberty PCOS (21.23%).The ovary volume,number of sinus follicles,and the largest area in the obese patients were significantly higher than those in non-obese group (t =3.42,7.89,4.02,all P<0.05);HOMA IR was also significantly higher than that in non-obese group (t =8.89,10.62,all P < 0.05).Conclusion Oligomenorrhea is the most common menstrual disorder in adolescent women.Ovarian morphological abnormalities occur in most women with oligomenorrhea and obesity,who should be followed up regularly.
4.Changes of tibial morphology due to propranolol medication in ovariectomized rats
Yanling LI ; Xiaofeng Lü ; Xingguang ZHANG ; Qiu ZU
Chinese Journal of Tissue Engineering Research 2005;9(47):187-189
BACKGROUND: Propranolol is a nonselective competitive adrenergic β-receptor blocker capable of suppressing sympathetic nerve excitation. Postmenstrual osteoporosis may be associated with the changes of sympathetic nerve activity.OBJECTIVE: To observe the effect of propranolol on tibial morphology in ovariectomized rats, and compare it with that of estrogen medication.DESIGN: Completely randomized design and controlled experiment.SETTING: End ocrinology Department, General Hospital of Beijing Military Area Command of Chinese PLA.MATERIALS: This experiment was conducted at the animal laboratory of the Institute of Basic Theory Research of Traditional Chinese Medicine between March 2002 and April 2003. Forty female unmated SD rats aged 6 months were included and randomized into 4 groups with 10 rats in each group: sham-operation group, estrogen medication group, propranolol treatment group, and placebo group.METHODS: ① Rats in estrogen group, propranolol treatment group and placebo group were anesthetized before the abdomen was opened and bilateral ovaries were excised. Rats in sham-operation group had their abdominal cavity opened and a piece of ovary surrounding fattytissue excised before closing the abdomen. ② Estrogen medication group: Rats were given hypodermic injection of grain oil dissolved 17 β-estradiol at a dose of 20 μg/(kg·d). Propranolol treatment group: Propranolol was used for gastric infusion at a dose of 18 mg/(kg·d). Placebo group and sham-op-eration group: The same volume of grain oil and/or distilled water was used instead of hypodermic injection or gastric infusion. Two treatment groups were given the same intervention as placebo group and sham-operation group during treatment; medication was carried out from postoperative week 1 for altogether 12 weeks. ③ Leica Qwin imaging analysis system was used for morphological measurement of bone tissues so as to calculate the volume percentage, active-surface formation percentage, mineralization rate, and formation rate of bone trabecula. ④ t-test was used for comparing the differences.MAIN OUTCOME MEASURES: Comparison of rat tibial morphological parameters between groups.RESULTS: Forty rats were divided into four groups with 10 rats in each and all entered the result analysis. ① Left tibial active-surface formation percentage and mineralization rate of bone trabecula: They were obviously lower in sham-operation group and estrogen group than in placebo group (P < 0.01), but obviously higher in propranolol treatment group than placebo group (P < 0.05). ② Formation rate of left tibial trabecula: It was obviously higher in propranolol treatment group than in placebo group (P < 0.05). ③ The volume percentage of left tibial bone trabecula: It was obviously higher in sham-operation group and propranolol treat ment group than in placebo group (P < 0.01), but obviously lower in pro pranolol treatment group than in sham-operation group and estrogen group (P < 0.01). CONCLUSION: Propranolol can increase bone mass, reduce bone loss, and promote bone formation in osteoporotic rats following ovariectomy, thus displaying obvious preventive and therapeutic effects on osteoperesis in rats.
5.Glycemic fluctuation and endothelial function in patients of coronary heart disease complicated with type 2 diabetes mellitus
Xiaofeng Lü ; Dakun ZHAO ; Jian DU ; Yu GAO
Chinese Journal of General Practitioners 2012;11(8):582-586
Objective To investigate the glycemic fluctuation and endothelial function in patients of coronary heart disease complicated with type 2 diabetes mellitus (T2DM).Methods Fifty eight patients with coronary heart disease were enrolled in the study,including 40 cases complicated with T2DM (group A) and 18 cases without T2DM (group B).All subjects underwent continuous glucose monitoring system (CGMS) and high-resolution ultrasound detection on brachial artery for endothelium-dependent flowmediated dilatation (FMD).According to the results of CGMS,patients with 3 times of standard deviation of blood glucose (SDBG) less than a mean blood glucose in group A were classified as low glucose excursion group (group A1 ),others were classified as high glucose excursion group (group A2 ).The association of glucose fluctuation with FMD in group A was analyzed.Results Compared to group B,the levels of mean amplitude of glycemic excursions (MAGE),the largest amplitude of glycemic excursions (LAGE) and mean postprandial glucose excursion (MPPGE) were elevated and the levels of FMD were lower in group A1 and A2 (P <0.05).Compared to group A1 the levels of MAGE,LAGE,MPPGE and absolute means of daily differences were significantly higher [(5.4 ±0.9) vs.(3.7±0.4),(6.3 ± 1.8) vs.(4.6 ±0.8),(4.7±1.0) vs.(3.5±1.2),(2.45 ±0.75) vs.(1.81 ±0.66)mmol/L,respectively]and the FMD levels were lower [ (3.2 ± 1.0) vs.(5.2 ± 1.2) % ]in group A2 ( all P < 0.05 ).All CGMS parameters were significantly correlated with FMD in group A2 (P < 0.05 ).Multiple stepwise regression analysis showed that MAGE,systolic blood pressure were the independent impact factors of FMD.Conclusions Patients of coronary heart disease complicated with T2DM have prominent glycemic fluctuation and decreased FMD and the glycemic fluctuation may be associated with the impairment of FMD.
6.Stem cell transplantation for ischemic femoral head necrosis Analysis in 20 model rabbits and 188 patients
Xiaofeng YANG ; Hongmei WANG ; Yifeng XU ; Yibin ZHANG ; Yanxiang WU ; Xin Lü ; Naiwu Lü ; Hong SHAN ; Shuyan MA
Chinese Journal of Tissue Engineering Research 2008;12(8):1558-1562
BACKGROUND: Ischemic femoral head necrosis is caused by local vascular injury and blood-supply insufficiency. There exists no optimal treatment for the ischemic femoral head necrosis. Thus, the improvement of the blood supply to the femoral head seems to be a key point for the treatment. OBJECTIVE: To verify the curative effects of autologous bone marrow mesenchymal stem cell transplantation induced vascular regeneration on the improvement of ischemic femoral head necrosis via animal experiments and clinical observations. DESIGN: Contrast animal experiment and self-controlled clinical observation.SETTING: Cell Therapy Center, the 463 Hospital of Chinese PLA.MATERIALS AND PARTICIPANTS: ① Animals: Twenty Japanese white rabbits in either gender and weighing 3.0-4.0 kg were purchased from Animal Experimental Center, General Hospital of Shenyang Military Area Command of Chinese PLA. The animal experiments were coincident with the ethical standards. ② Participants: 188 patients with ischemic femoral head necrosis (335 hips) having whole following-up data were selected from Cell Therapy Center, the 463 Hospital of Chinese PLA from July 2004 to July 2007. There were 113 males and 75 females, and their ages ranged from 18 to 72 years. Diagnosis was done by using X-ray photographs, nuclide scanning, MRI and CT examinations. All patients provided the informed consent, and the study was approved by the local research ethics committee. METHODS: ① Animal experiments: The experiment was carried out at the Animal Experiment Center, General Hospital of Shenyang Military Area Command of Chinese PLA from January to June 2004. Ischemic femoral head necrosis models were established at both hindlimbs by using liquid-nitrogen refrigeration. The right side was regarded as transplantation group and the left one as control group. Mononuclear cells extracted from bone marrow were poured in the right femoral artery, while saline was poured in the left femoral artery. ②Clinical observations: Mononuclear cells were separated from autologous bone marrow of patients with ischemic femoral head necrosis after density gradient centrifugation. MAIN OUTCOME MEASURES: ①Four weeks later, angiogenesis at both femoral arteries was observed by arteriography by using digital subtraction anglography (DSA). Moreover, bilateral femoral head samples underwent pathological sections to observe bone regeneration and repair of femoral head 4 and 12 weeks later. ②Items including hip pain, walking distance and gait, abduction and internal rotation function changes of hip joint were observed in 3, 6, 12 and 24 months after stem cell transplantation in media femoral circum flex artery, lateral femoral circum flex artery and obturator artery. In 6 months after stem cell transplantation, angiogenesis and blood supply of femoral head were observed by using arteriography. In 6, 12 and 24 months after stem cell transplantation, morphological and ischemic changes of femoral head were observed by using CT, X-ray and MRI examinations. Harris scores were used to evaluate function of hip joint before and in 3, 6, 12 and 24 months after stem cell transplantation.RESULTS: Animal experiment: Twenty rabbits were involved in the final analysis. ① DSA-arteriography results: In 4 weeks after transplantation, blood-supply arteries in femoral head of right hindlimb in the transplantation group were more than those in the control group. ② Pathological results: In 12 weeks after transplantation, cartilage, lamellar bone and bone trabecula in the left femoral head were repaired remarkably, but left femoral head necrosis was not improved. Clinical observations: 188 patients were involved in the final analysis. ① Improvement of symptoms: Among 188 patients, 164 (87.3%) had remission of hip pain, 147 (78.4%) had function improvement, and 150 (80.0%) had elongation of walking distance. ② Imaging changes: At 6 months after transplantation, DSA-arteriography in 12 patients demonstrated that blood-supply arteries in femoral head were increased and thickened remarkably as compared with those before transplantation, and the blood flow was rapid. At 12-24 months after transplantation, lesion of bone matrix in 24 patients was improved under the X-ray, CT and MRI examinations. ③ Harris scores of hip joint: The scores at 6, 12 and 24 months after transplantation were significantly higher than those before transplantation (t= -3.423, -6.714, -9.039, P < 0.01).CONCLUSION: Autologous bone marrow mesenchymal stem cell transplantation can effectively improve and treat ischemic femoral head necrosis.
7.Effects of MEK signaling inhibitor on the growth of human pacreatic cancer cell lines and the expression of cell cyde associated genes
Xia WANG ; Hui WANG ; Nan JIANG ; Sanhong LIANG ; Wen Lü ; Xiao ZHANG ; Xiaofeng ZHANG
Chinese Journal of Pancreatology 2011;11(4):259-262
Objective To examine the effects of the MEK inhibitor on human pancreatic cancer cells, and to explore the molecular mechanisms. Methods Human pancreatic cancer cell lines CFPANC1, PANC1 and MiaPaCa2 were treated with MEK inhibitor PD98059 or DMSO, the sensitivity was analyzed by an MTT assay, and cell cycle distribution was evaluated by flow cytometry( FCM), The transcriptional level and protein expression of tumor suppressor genes were detected by real-time RT-PCR and western blot respectively. DNA methyltransferase (Dnmt)1, 3a and 3b were also assayed by western blot, The methylation status of the promoter of the p16INK4A gene was assayed by methylation-specific PCR (MSP). Results PD98059 inhibited to various degrees the growth of three pancreatic cancer cell lines, accompanied by G0-G1 cell cycle arrest. PD98059 up-regulated the expression of p16INK4a, p21WAF1, p27KIP1 mRNA, demethylated the hypermethylation status of p16INK4a gene promoter, and decreased Dnmtl and Dnmt3b in CFPANC1 and PANC1 cell lines. PD98059 only increased the expression of p27KIP1, while the changes of p16INK4a, p21WAF1 and Dnmt were less marked in MiaPaCa2 cell line. Conclusions MEK inhibitor PD98059 down-regulate the activation of Dnmt and up-regulate tumor supress genes, along with the inhibition of cell proliferation and cell cycle progression.
8.Biliary-pancreatic double stents for pancreatic cancer with obstructive jaundice
Zhen FAN ; Xiaofeng ZHANG ; Xiao ZHANG ; Wen Lü ; Yinghui GUO ; Qingfeng YUAN ; Youan ZHAO
Chinese Journal of Digestive Endoscopy 2013;(4):181-184
Objective To analysis the clinical effects of biliary-pancreatic double stents in pancreatic cancer patients with obstructive jaundice.Methods From July 2008 to October 2011,a total of 60 patients with advanced pancreatic cancer were randomly divided into two groups to receive biliary-pancreatic double stents (n =28) or biliary stent only (n =32) according to the odd and even numbers of their admission date.Changes in liver function,abdominal pain,quality of life scores (QOL) were compared between two groups.Results The stents were placed successfully in 54 patients (90.0%),in which symptoms were relieved or gradually disappeared in all patients after the procedure.One week after stents placement,the serum total bilirubin decreased significantly from 164.32 ±45.16 μmol/L before ERCP to 63.25 ±27.06 μmol/L (P < 0.05),other parameters including ALT,AST,AKP and r-GT were also decreased significantly compared with those of pre-ERCP (P < 0.01),but there was no significant difference between the two groups (P > 0.05).25 cases in double-stents group and 29 cases in single-stent group had varying degrees of pain relief at 7d after ERCP,but the overall pain relief rate and complete pain relief rate in double-stent group were significantly higher than those in single-stent group (92.0% vs.55.2%; 64.0% vs.34.5%,P<0.05).At 7d and 14d after ERCP,Karnofsky QOL score were improved significantly in double-stent group (P < 0.05).It was significantly better than single-stent group at 14d after ERCP (P <0.05).No death or other severe ERCP-related complications were observed.Conclusion Biliary-pancreatic stent placement for pancreatic cancer could significantly improve liver function and relieve obstructive pain.In the ways of alleviating pain and improving quality of life scores,it was better than ERCP biliary stent placement,especially for patients with pancreatic cancer combined obstructive pain.It indicated that biliary-pancreatic stent placement was better than simple biliary stent placement for advanced pancreatic head cancer patients with obstructive pain.
9.Correlation between carotid intima-media thickness and glucose fluctuation in type 2 diabetic patients
Jinxin HUANG ; Xiaofeng Lü ; Pei LUO ; Xingguang ZHANG ; Xumin JIAO ; Dakun ZHAO
Chinese Journal of General Practitioners 2013;12(4):268-271
Objective To investigate the correlation between carotid intima-media thickness (CIMT) and glucose fluctuation in patients with type 2 diabetes mellitus (T2DM).Methods Sixty-eight T2DM patients admitted to Beijing Military General Hospital from March to August 2012 were enrolled in the study,including 32 cases with CIMT thickening (CIMT ≥ 0.9 mm) and 32 cases with normal CIMT (CIMT <0.9 mm).The 72 h continuous blood glucose levels were monitored from the day of admission.Results There were no significant differences in the gender,age,body mass index (BMI),systolic and diastolic blood pressure,HDL-C,LDL-C,CHO,TG,glycosylate hemoglobin (HbA1c),fasting blood glucose(FBG) and postprandial average blood glucose (MPBG) between two groups (P > 0.05).The atherosclerosis (AS) score and mean amplitude of glycemic excursion (MAGE),glucose standard deviation,frequency of glycemic excursion (FGE) and absolute mean of daily differences (MODD) in patients with thickening CIMT were (11 ± 7) years,(6.9 ± 3.0) mmol/L,(2.8 ± 1.2) mmol/L,(3.4 ± 1.5) times/d,(2.8 ± 1.3) mmol/L,(4.5 ± 1.0) score,respectively ; while those in patients with normal CIMT were (8 ±6) years,(4.2 ± 1.1) mmol/L,(1.6 ± 0.5) mmol/L,(2.2 ± 0.8) times/d,(2.0 ± 1.0) mmol/L,(3.3 ±0.6) score,respectively.There were significant differences between two groups (all P < 0.05).Pearson correlation showed that CIMT was positively correlated with MAGE,FGE,MODD,course of disease,diastolic blood pressure,LDL-C,MPBG and AS score (P < 0.05).Multiple stepwise regression analysis showed that MAGE,MBPG were the influencing factors of CIMT.Conclusions The CIMT of patients with T2DM is closely correlated with glucose fluctuation,indicating that reduction of blood glucose fluctuation and MAGE,MPBG levels may delay the occurrence of diabetic macroangiopathy.
10.EUS-guided rendezvous for malignant obstructive jaundice after failured ERCP
Hao ZHANG ; Ping HUANG ; Xiaofeng ZHANG ; Wen Lü ; Zhen FAN ; Haitao HUANG ; Songmei LOU ; Xia WANG
China Journal of Endoscopy 2017;23(7):22-25
Objective To study the therapeutic effect of EUS-guided rendezvous (EUS-RV) when ERCP failed in patients with malignant obstructive jaundice. Methods 12 cases of malignant obstructive jaundice patients were underwent EUS-RV after unsuccessful ERCP. The operation success rate, liver function recovery 1 week and 1 month after operation, complication rates, hospital stay and patient survival were observed. Results All 12 patients were successfully operated and placed stents by endoscopic ultrasound puncture following by ERCP: 8 patients by the stomach, 4 patients by duodenum, the operation success rate was 100.00%; There were significant difference between the liver function recovery of preoperative and postoperative one week or postoperative one week and postoperative one month (P < 0.05). 1 bleeding occurred and were improved after conservative treatment, the complications rate was 8.33%; the hospital stay was (20.68 ± 5.76) d; the average survival time of patients was 224 d. Conclusion EUS-guided rendezvous may be the alternative treatment due to the diminutive trauma and good effect when ERCP failed in patients with malignant obstructive jaundice.