A phosphine-mediated domino sequence of salicylaldehyde with but-3-yn-2-one: rapid access to chromanone.

Chromanone is a privileged structure with a wide range of unique biological activities. A phosphine-promoted, three-component domino sequence of salicylaldehyde with but-3-yn-2-one was well designed for the construction of the chromanone skeleton under mild conditions. As a consequence, a series of novel chromanone analogues bearing an all-carbon quaternary center were facilely assembled from commercially available starting materials with moderate to good yields, which hold promising applications in pharmacological studies. Mechanistic experiments were conducted to confirm the proposed mechanism.

Phosphine-Mediated MBH-Type/Umpolung Addition Domino Sequence: Divergent Construction of Coumarins.

We herein report a phosphine-mediated domino process of MBH-type reaction/umpolung γ-addition through the rational integration of the privileged reactivities of alkynoate. Simply by manipulating the nucleophilic reagent, the developed protocol offers a facile, diversity-oriented construction of a wide range of three-substituted coumarins.

Visible-Light-Driven, Photoredox-Catalyzed Cascade of ortho-Hydroxycinnamic Esters To Access 3-Fluoroalkylated Coumarins.

A general and straightforward protocol for di-/perfluoroalkylation of ortho-hydroxycinnamic esters via a photoredox-catalyzed cascade was developed to access a variety of 3-fluoroalkylated coumarins. This method was characterized by all-in-one synthetic design, simplified operation, mild reaction conditions, and broad substrate scope. Moreover, a sequential one-pot procedure starting from commercially available salicylaldehyde was also successfully realized to synthesize 3-fluoroalkylated coumarins.

Organocatalytic, Enantioselective, Polarity-Matched Ring-Reorganization Domino Sequence Based on the 3-Oxindole Scaffold.

A one-pot squaramide-catalyzed enantioselective ring-reorganization domino sequence (Michael addition/intramolecular ring-opening/lactamization) of 3-hydroxyoxindole and methyleneindolinone, which can be readily derived from 3-oxindole, has been established in this work. As a result, novel polycyclic quinolinone-spirooxindoles bearing three contiguous chiral centers were efficiently and step-economically assembled under mild conditions in high yields (up to 97%) with excellent enantioselectivities (up to >99% ee) and moderate to good diastereoselectivities (up to >95:5 dr).

Intramolecular hydrogen-bonding-assisted phosphine-catalysed [3 + 2] cyclisation of ynones with o-hydroxy/amino benzaldehydes.

A new strategy for the synthesis of functionalized tetrahydrofuran derivatives was developed via a phosphine-catalysed [3 + 2] cyclization reaction of aromatic aldehydes with 4-phenylbut-3-yn-2-one. This is the first example of intermolecular cyclization of ynones with benzaldehydes, which essentially benefited from the intramolecular hydrogen bonding. This new protocol features a broad substrate scope, mild reaction conditions, operational simplicity and easy scale-up.

Construction of Bispirooxindole Heterocycles via Palladium-Catalyzed Ring-Opening Formal [3 + 2]-Cycloaddition of Spirovinylcyclopropyl Oxindole and 3-Oxindole Derivatives.

A palladium-catalyzed ring-opening oxo-formal [3 + 2]-cycloaddition reaction of novel donor-acceptor spirovinylcyclopropyl oxindole with 3-oxindole is described. The developed protocol provides facile access to oxo-bispirooxindole derivatives in good yields (up to 82% yield) with excellent diastereoselectivities (up to 20:1 dr).

Unraveling and Manipulating the Stereospecific Retro-Aldol Reaction in the Organocatalytic Asymmetric Aldol Reaction of Isatin and Cyclohexanone.

An l-pyroglutamic acid-derived bifunctional organocatalyst was designed and applied in an organocatalytic asymmetric direct aldol reaction between isatins and cyclohexanone, in which an erosion of enantiomeric excess of aldol adduct was unexpectedly observed. Through closely monitoring the reaction and performing extensive control experiments, it was determined that the erosion of ee was attributed to a rare stereospecific retro-aldol process. Moreover, effective manipulation of the retro-aldol process by tuning the use of starting materials was ultimately accomplished, leading to evidently upgraded enantioselectivity and functional group tolerance. This study demonstrates the impact of the hidden reaction pathway on the enantioselectivity in asymmetric transformation.

[Changes in prostatic stromal composition and benign prostatic hyperplasia].

OBJECTIVE: To investigate whether there are different stromal compositions in the prostate tissue of patients with benign prostatic hyperplasia (BPH) and evaluate their significance in the course of the disease. METHODS: Forty-three surgical or bioptic prostatic specimens of BPH and 5 autoptic normal prostatic specimens were stained by the Masson method to display the elements of the muscle fiber and collagen. The relationship of the changes in the prostatic stromal composition was analyzed with the degree of bladder outlet obstruction (BOO) , IPSS and medication results. RESULTS: The mean ratio of muscle fiber to collagen in the normal prostate tissue was (3.2 +/- 0.2):1, significantly higher than that of the BPH patients (1: [4.7 +/- 3.1] ) (P < 0.01); that in the BPH patients with BOO was 1: (5.4 +/- 3.7) markedly lower than in those without BOO (1: [2.5 +/- 1.1] ) (P = 0.02); that in the BPH patients with severe prostatic symptoms was 1: (9.1 +/- 2.9), remarkably lower than in those with moderate (1: [5.3 +/- 3.4]) and mild prostatic symptoms (1: [2.8 +/- 1.7]) (P < 0.01); and that in the BPH patients with satisfactory medicinal therapeutic results was 1:(2.3 +/- 1.9), significantly higher than in those with poor therapeutic results (1: [7.6 +/- 4.3]) (P < 0.01). CONCLUSION: The stromal composition in the prostatic tissue of BPH patients undergoes different degrees of changes. More obvious BPH symptoms and poorer therapeutic results are associated with a bigger proportion of collagens and a smaller proportion of muscle fibers in the prostatic tissue. These changes may play an important role in the development and progression of BPH.

[Effect of ischemia on the structure of bladder in rabbits with partial bladder outlet obstruction].

OBJECTIVE: To compare the structures and functions of rabbit bladder after partial bladder outlet obstruction versus without ischemia so as to explore the effects of ischemia on bladder pathogenesis in rabbits with partial bladder outlet obstruction. METHODS: A total of 64 mature male rabbits were divided into 4 groups (n = 16 each). Four of each group underwent operation to establish an ischemic animal model (ischemia group), another 4 underwent operation to establish a partial bladder outlet obstruction animal model (obstruct group), the other 4 underwent operation to establish an ischemic and partial bladder outlet obstruction animal model (combination group) and the remaining 4 underwent a sham operation as control. The rabbits in 4 groups were evaluated at Week 1, 2, 4 and 8 post-operation respectively. The weight of bladder, the thickness of mucosal, submucosa, muscular layer and placenta percreta and the activities of sarco/endoplasmic reticulum Ca(2+) ATPase citrate synthase of cystic smooth muscle were detected respectively. MASSON staining was used to observe the smooth muscle and collagen in stroma of bladder and S-100 staining for observing the neurons in bladder. RESULTS: In obstruct and combination groups, the weights of bladder at week 1 were (5.10 ± 0.29) g and (4.80 ± 0.37) g respectively. They were both significantly higher than control group [(1.93 ± 0.17) g, all P < 0.05]. The weights of bladder in obstruct and combination groups peaked at Week 4 and they were (18.48 ± 2.03) g and (12.35 ± 0.39) g respectively. The weight of bladder in obstruct group was significantly heavier than combination group in the same terms. And they were both significantly heavier than control and ischemia groups (all P < 0.05). Muscular tissue vicariously thickened during the first 4 weeks, and collagen and stroma increased at Week 4 in obstruct group. Muscular tissue, collagen and stroma all increased initially. But at Week 2 only collagen and stroma increased in combination group. Compare with control group, the other groups all have deletion of neurons, especially in combination group. The activities of sarco/endoplasmic reticulum Ca(2+) ATPase and citrate synthase of cystic smooth muscle of obstruct group peaked at Week 4. In combination group, the activities of sarco/endoplasmic reticulum Ca(2+) ATPase and citrate synthase of cystic smooth muscle were decreased over 2 - 8 weeks. In the same terms, the activities of sarco/endoplasmic reticulum Ca(2+) ATPase and citrate synthase of cystic smooth muscle in control group were significantly higher than those in obstruct and combination groups (all P < 0.05). CONCLUSION: Ischemia can reduce the tolerance of bladder and aggravate the impairment of bladder to partial outlet obstruction.

[Arteriosclerotic risk factors and benign prostatic hyperplasia].

OBJECTIVE: To evaluate the correlation between arteriosclerotic risk factors and the severity of benign prostatic hyperplasia (BPH). METHODS: A total of 877 patients with diagnosed BPH were selected according to the inclusion criteria. The weight of the prostate was estimated by transrectal ultrasonography, the degree of bladder outlet obstruction determined by urodynamic examination, and the symptoms quantified by the International Prostate Symptom Score (IPSS). Arteriosclerotic risk factors included age, hypertension, dyslipidemia, type 2 diabetes mellitus, and smoking. Comparative studies were made on the data obtained by univariate and multivariate analyses. RESULTS: The severity of BPH was increased with the increase in the severity of the risk factors and the incidence of the disease. The logistic regression analysis showed that type 2 diabetes mellitus was a prominent predictor of the prostate volume, IPSS and degree of bladder outlet obstruction (OR = 3.179, 3.862 and 2.847, P < 0.001), while the level of serum triglyceride was not (P > 0.05). Age, hypertension, high LDL, low HDL and smoking were all prominent predictors of the severity of BPH. CONCLUSION: Arteriosclerotic risk factors are obviously correlated with the development and severity of BPH, among which type 2 diabetes mellitus is the most important.

[Effectiveness and significance of prostatic ischemia in rabbit].

OBJECTIVE: To evaluate the effect of prostatic ischemia in rabbit and approach the significance of ischemia in the development of benign prostatic hyperplasia. METHODS: Male rabbits underwent surgical prostatic ischemia for durations of 1, 2, 4, 8 and 12 weeks and sham-operated rabbits served as controls. The weight of prostate was examined and a histological examination conducted. Ki67 immunohistochemical stain for the generation of prostatic cells and TUNEL test for the apoptosis of prostatic cells were used. RESULTS: In sham-operated rabbits, the mean (SD) weight of prostate were 0.831(0.127) g, the mean (SD) positive Ki67 staining prostatic epithelial cells 2.1(0.8) in 100 prostatic epithelial cells and stromal cells 2.6(1.1) in 100, mean (SD) positive TUNEL test prostatic epithelial cells 2.0(1.0) in 100 and stromal cells 2.5(0.7) in 100. In operated rabbits, the generation of prostatic stromal cells increased and the apoptosis of prostatic stromal cells decreased over 1 - 12 weeks. The generation of prostatic epithelial cells increased and the apoptosis of prostatic epithelial cells decreased over 2 - 12 weeks, but in the first week, there were no significantly difference between operated and sham-operated rabbits in the generation and apoptosis of prostatic epithelial cells. The weight of prostate in operated animals increased at Weeks 4, 8 and 12, were significantly heavier than sham-operated rabbits, 1 week post-op and 2 weeks post-op rabbits, there were no significantly difference between the latter 3 groups. CONCLUSION: Ischemia can induce the gain of prostatic weight by improving the generation and inhibiting the apoptosis of prostatic cells. And the effect of ischemia to prostate is correlated with ischemic time. Ischemia may play an important role in the development of benign prostatic hyperplasia. The first response to ischemia is the change of prostatic stromal cells.

[Half-dose Zenapax for acute rejection prevention after renal transplantation].

OBJECTIVE: To investigate the efficacy and safety of half-dose Zenapax for prevention of acute rejection after renal transplantation. METHODS: According to the immunosuppressive regimen and renal function after transplantation, patients were divided into 4 groups, namely groups A, B, C, and D of 90, 73, 11 and 13 patients, respectively. Blood creatinine measured 1 week after operation was <176.6 micromol/L in groups A and B, and was >353 micromol/L in groups C and D. Patients in groups A and C were given 25 mg Zenapax (0.5 mg/kg) and MMF 0.75 g before operation, and those in groups B and D had only MMF of 0.75 g. All patients were given Pred, CsA and MMF after operation, and the rejection episodes, the time of acute rejection onset, the rate of rejection reversal and complications were analyzed in the time period of 6 months after operation. RESULTS: After the operation, 13 patients (14.4%) developed acute rejection in group A, 18 (24.6%) in group B, 6 (54.5%) in group C and 7 (53.8%) in group D (P<0.01). The incidence of acute rejection in group B was significantly lower than that in groups C and D groups (P<0.01), and the latter two groups had similar incidence. The time of acute rejection onset ranged from 3 to 9 days postoperatively (mean 6.2-/+3.2 days) in group A, significantly delayed as compared with that in group B (range 2-8 days, mean 4.7-/+3.1 days), group C (range 2-7 days, mean 4.3-/+4.2 days) and group D group (range 2-9 days, mean 3.9-/+3.5 days), but the time was similar between groups B, C, and D (P>0.05). All acute rejection cases in group A was reversed, and the rate of reversal was 88.9% (16/18) in group B, 83.3% in group C, and 71.4% in group D. No significant differences were noted in such complications as infection, vascular injuries or gastrointestinal reactions between the 4 groups (P>0.05). CONCLUSION: Zenapax at the dose of 25 mg can safely decrease the risk of acute rejection in patients with good postoperative renal function recovery, but dose not seem effective in patients with delayed graft function recovery.

[Management of urinary obstruction following renal transplantation: report of 16 cases].

OBJECTIVE: To explore the diagnosis and treatment of urinary obstruction involving the transplanted kidney. METHODS: A retrospective analysis was performed in 16 cases of urinary obstruction involving the transplanted kidney, including 5 cases of ureteral calculi, 6 vesicoureteral anastomotic stricture, 2 pyeloureteral junction stricture after transplantation, 1 ureter necrosis due to graft rejection, and 2 infection surrounding the renal graft and ureter end necrosis. RESULTS: Only one patient had the renal graft removed due to massive hemorrhage in an open surgery for correction of urinary obstruction, and the renal function of the graft was preserved in all the other cases after endoscopic or open surgeries. In the follow-up for 0.5 to 3 years after the second surgery, serum creatinine of the patients were maintained within the range of 90-150 micromol/L, without further renal enlargement or exacerbation of renal retention shown by B-mode ultrasonography. CONCLUSION: Urinary obstruction after renal transplantation is a difficult surgical complication, which can be managed by endoscopic or open surgeries depending on the causes of the obstruction.

[Surgical techniques for the ureterointestinal anastomosis in continent urinary diversion].

OBJECTIVE: To compare the complications of direct and antirefluxing techniques of ureterointestinal anastomosis in continent urinary diversion. METHODS: Sixty-three patients underwent continent urinary diversion. Twenty-four patients were treated by the direct ureteroenteric anastomosis and the others treated by the antirefluxing technique. The follow up studies included following-up the information of ureteric stricture, ureteric reflux, renal function and acute urinary infection. It was assessed for 3 months to 6 years with a mean follow up of 26 months after operation. RESULTS: Of 78 ureters reimplanted using antirefluxing technique. A total of 12 ureters had anastomotic stricture formation postoperatively. Only one of 48 ureters reimplanted using direct anastomoses had anastomotic stricture. The difference between the direct and antirefluxing technique groups was remarkable (chi2 = 4.375, P < 0.05). Furthermore, there was no significant difference between the direct and antirefluxing technique groups in regard to ureteric reflux, renal function and acute urinary infection. CONCLUSIONS: Antirefluxing anastomoses resulted in obviously higher rate of ureterointestinal anastomotic stricture in comparison with the direct anastomosis. The direct ureteroenteric anastomosis may be the suitable choice for patients undergoing continent urinary diversion.

[Application of multihole U-shaped drainage stent in complex posterior urethra surgery].

OBJECTIVE: To study a method for using a new drainage stent following complex posterior urethral operation. METHODS: Fifty-five patients,15 of whom had complex posterior urethrorectal fistula, 35 had complex posterior stricture or atresia, and 5 had bladder exstrophy, received surgical treatment, after which multihole U-shaped drainage stent was applied. RESULTS: All the patients were normal in micturition and no complications occurred during the follow-up period lasting for 1 to 10 years. CONCLUSION: Multihole U-shaped drainage stent performs the functions of both stenting and drainage, and is applicable in complex posterior urethral surgery.

Interventional therapy for stenosis and aneurysm in renal graft artery: report of 9 cases.

OBJECTIVE: To study the interventional therapy for renal graft artery stenosis and aneurysm patients with renal transplantation to further improve the survival rate of the graft. METHOD: Seven patients with of renal graft artery stenosis received balloon dilatation of the stenotic artery, followed by stent implantation. For renal graft artery aneurysm in another 2 patients, thrombin infusion and stent implantation were respectively performed. RESULTS: The condition was successfully managed in 6 of the 7 patients with renal artery stenosis, whose serum Cr levels dropped to below 106 micromol/L 3 d after the operation. Thrombin infusion in one of the 2 patients with renal artery aneurysm caused thrombus in the renal graft and then aneurysm rupture, resulting in final graft loss. The other aneurysm case was successfully managed with stent implantation. CONCLUSIONS: Interventional therapy as balloon dilatation combined with stent implantation is ideal for treating renal graft artery stenosis, and stent implantation constitutes an important management for artery aneurysm in the renal graft.

[Modified Madigan prostatectomy].

OBJECTIVE: To improve Madigan prostatectomy (MPC) for a much satisfactory effect in open surgery. METHODS: A total of 52 patients with benign prostatic hyperplasia (BPH) were treated using MPC. The MPC procedure was modified by exposing anterior prostatic urethra near the bladder neck and conjunction with cystotomy. This modified procedure preserved prostatic urethra intact and could also deal with intracystic lesions at the same time. RESULTS: The intact of prostatic urethra was kept completely or almost for 48 cases. The hemorrhage amount during modified procedure was a less. The mean operative time was 120 minutes. The 35 patients had been followed up for 1 - 12 months. The average Qmax was 18.9 ml/s. The cystourethrography revealed that the urethra and bladder neck were intact in 8 patients postoperatively. Furthermore, the prostatic urethra was obviously wider after modified MPC. CONCLUSIONS: The modified MPC can reduce the urethra injury and enlarge the MPC indications. The modified technique is easy to perform with little complications and much more satisfactory clinical result. The modified MPC is highly recommended.

[Misdiagnosis of corticomedullary mixed pathological changes in adrenals: report of 4 cases].

Pathological changes usually occur independently in the adrenal cortex and medulla because of their distinct embryonic origins, and changes involving both the cortex and medulla are rare. We report 4 cases of corticomedullary mixed pathological changes adrenal glands. CT scanning of the adrenal glands showed unilateral abnormalities in all the 4 cases, 3 of which were diagnosed as aldosteronism and the other pheochromocytoma before surgery. Unilateral adrenalectomy was performed in the 4 patients 3 being cured and discharged. The other 1 had recurrence 18 months postoperatively with suspected pathological changes on the other side. Subsequent pathological examination confirmed the suspicion in both the cortex and medulla of the other adrenal gland. In cases with clinical presentations as simultaneous onset of aldosteronism and catecholamine responses, pathological changes in both the cortex and medulla of the adrenal glands should be considered. Perioperative management of such cases should be the same as that in cases of catecholamine responses, and the diagnosis relies on histopathological examination.

[Diagnosis and treatment of adrenal medullary hyperplasia (with report of 8 cases)].

OBJECTIVE: To study the diagnosis and treatment of adrenal medullary hyperplasia (AMH). METHODS: An retrospective analysis of the clinical data of 8 patients with AMH admitted in our hospital from May 1998 to May 2002 were conducted with a review of the follow-up study. RESULTS: CT scanning of the adrenal gland showed unilateral abnormal appearance in all 8 cases. Diagnoses of AMH in 4 patients and pheochromocytoma in the other 4 patients were established before surgery. All the patients underwent unilateral adrenalectomy, among whom 7 were cured and 1 suffered recurrence 1 month after operation because of medullar hyperplasia in the contralateral adrenal gland. CONCLUSIONS: AMH should be differentiated from pheochromocytoma, especially from adrenal nodules shown by catecholamin assay. Definite diagnosis depends on pathological examination and surgical removal through abdominal approach is the best choice of treatment, in which both sides of the adrenal glands should be explored.