Clinical Analysis of Colistin Sulfate in the Treatment of Hematonosis Infected by Multidrug-Resistant Gram-Negative Bacteria / 中国实验血液学杂志

OBJECTIVE@#To investigate the efficacy and safety of colistin sulfate in the treatment of hematonosis patients infected by multidrug-resistant (MDR) gram-negative bacteria (GNB), and discuss the possible factors that affect the efficacy of colistin sulfate.@*METHODS@#The clinical data of 85 hematologic patients infected with MDR GNB in the Soochow Hopes Hematonosis Hospital from April 2022 to November 2022 were collected and divided into clinically effective group with 71 cases and ineffective group with 14 cases according to the therapeutic efficacy of colistin sulfate. The age, gender, type of hematologic disease, status of hematopoietic stem cell transplantation, infection sites, type of pathogen, timing of administration, daily dose and duration of colistin sulfate, and combination with other antibacterial agents of patients in two groups were compared. Logistic regression was used to analyze on the meaningful variables to study the influencing factors of colistin sulfate. The adverse reactions of colistin sulfate were also evaluated.@*RESULTS@#There were no significant differences in age, gender, type of hematologic disease, hematopoietic stem cell transplantation status, infection sites and pathogen type between the effective group and the ineffective group (P>0.05). Compared with the medication time more than 7 days, meropenem used within 7 days in the clinical effective group, and timely replacement with colistin sulfate could obtain better efficacy, the difference was statistically significant (P=0.018). The duration of tigacycline before colistin sulfate did not affect the efficacy, and there was no significant difference in efficacy between the effective and ineffective groups. The therapeutic effect of colistin sulfate at daily dose of 500 000 U q8h was better than that of 500 000 U q12h, the difference was statistically significant (P=0.035). The time of colistin sulfate use in the clinically effective group was longer than that in the ineffective group, which had a statistical difference (P=0.003). Compared with the clinical ineffective group, the efficacy of combination regimens with colistin sulfate was better than that of colistin sulfate monotherapy, and the difference was statistically significant (P=0.013). Multivariate logistic regression analysis was performed on the indicators with statistical differences in the two groups of patients, which suggested that the use time of colistin sulfate (B: 2.358; OR: 10.573; CI: 1.567-71.361; P=0.015) and the combination of colistin sulfate (B: 1.720; OR: 5.586; CI: 1.210-25.787; P=0.028) were influential factors in the efficacy of colistin sulfate. During the treatment, the incidence of nephrotoxicity, hepatotoxicity and peripheral neurotoxicity were 5.9%, 1.2% and 1.2%, respectively.@*CONCLUSION@#The use of colistin sulfate improves the clinical efficacy of MDR GNB infections in hematological patients, and the timing of colistin sulfate administration and the combination of drugs are independent factors affecting its clinical efficacy, and the safety during treatment is high.

Humanized anti-CD25 monoclonal antibody as a salvage therapy for steroid-refractory acute graft-versus-host disease after hematopoietic stem cell transplantation / 中华血液学杂志

Objective: To investigate the efficacy of humanized anti-CD25 monoclonal antibody for steroid-refractory acute graft-versus-host disease (SR-aGVHD) in allogeneic hematopoietic stem cell transplantation (allo-HSCT) recipients. Methods: A total of 64 patients with SR-aGVHD between June 2019 and October 2020 in Suchow Hopes Hematology Hospital were enrolled in this study. Humanized anti-CD25 monoclonal antibodies 1 mg·kg(-1)·d(-1) were administered on days 1, 3, and 8, and then once per week according to the disease progression. Efficacy was assessed at days 7, 14, and 28 after humanized anti-CD 25 treatment. Results: Of the 64 patients with a median age of 31 (15-63) years, 38 (59.4%) were male and 26 (40.6%) were female. The overall response (OR) rate of the humanized CD25 monoclonal antibody in 64 patients with SR-aGVHD on days 7, 14, and 28 were 48.4% (31/64), 53.1% (34/64), and 79.7% (51/64), respectively. Liver involvement is an independent risk factor for poor efficacy of humanized CD25 monoclonal antibody for SR-aGVHD at day 28 (OR=9.588, 95% CI 0.004-0.291, P=0.002). The median follow-up time for all patients was 17.1 (0.2-50.8) months from the start of humanized CD25 monoclonal antibody therapy. The 1- and 2-year OS rates were 63.2% (95% CI 57.1% -69.3%) and 52.6% (95% CI 46.1% -59.1%), respectively. The 1- and 2-year DFS rates were 58.4% (95% CI 52.1% -64.7%) and 49.8% (95% CI 43.4% -56.2%), respectively. The 1- and 2-year NRM rates were 28.8% (95% CI 23.1% -34.5%) and 32.9% (95% CI 26.8% -39.0%), respectively. The results of the multifactorial analysis showed that liver involvement (OR=0.308, 95% CI 0.108-0.876, P=0.027) and GVHD grade Ⅲ/Ⅳ (OR=9.438, 95% CI 1.211-73.577, P=0.032) were independent risk factors for OS. Conclusion: Humanized CD25 monoclonal antibody has good efficacy and safety for SR-aGVHD. This study shows that SR-aGVHD with pretreatment grade Ⅲ/Ⅳ GVHD and GVHD involving the liver has poor efficacy and prognosis and requires early intervention.

Establishment of contralateral arteriovenous fistula by using the waste vein on the side of central venous lesion: a case report / 中华肝脏病杂志

Central venous lesion is a difficult problem in the vascular access complications of hemodialysis, which can cause serious clinical symptoms and affect the quality of hemodialysis and life of patients. We established arteriovenous fistula of the contralateral graft blood vessel with the used vein on the diseased side of the central vein of the patient. The arteriovenous fistula of the graft blood vessel was successfully punctured and hemodialysis was performed 2 weeks later. In this way, we not only solved the problem of venous hypertension and subsequent vascular access in the patient, but also reserved more vascular resources.

Clinical observation on deep needling at Xiaguan (ST 7) with round sharp needle combined with plum-blossom needle for trigeminal neuralgia of wind and heat / 中国针灸

OBJECTIVE@#To compare the clinical therapeutic effect between deep needling at Xiaguan (ST 7) with round sharp needle combined with plum-blossom needle and conventional acupuncture in patients with trigeminal neuralgia (TN) of wind and heat, and explore its mechanism.@*METHODS@#A total of 60 patients with TN of wind and heat were randomized into an observation group (30 cases) and a control group (30 cases). In the observation group, deep needling with round sharp needle was applied at Xiaguan (ST 7), and tapping with plum-blossom needle was applied at Yangbai (GB 14), Quanliao (SI 18), Dicang (ST 4), Sibai (ST 2), etc. of affected side. In the control group, conventional acupuncture was applied at the same acupoints selected in the observation group. The treatment was given once a day, 5 times a week for 4 weeks in the both groups. Before and after treatment, the scores of short-form McGill pain questionnaire (SF-MPQ), TCM syndrome, patient global impression of change (PGIC) and comprehensive symptom were observed, the serum levels of interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), vasoactive intestinal peptide (VIP) and β-endorphin (β-EP) were detected, and the adverse reaction was observed in the both groups.@*RESULTS@#After treatment, the scores of PRI, PPI, VAS, TCM syndrome, PGIC and comprehensive symptom and the serum levels of IL-6, TNF-α and VIP were decreased compared before treatment in the both groups (@*CONCLUSION@#Deep needling at Xiaguan (ST 7) with round sharp needle combined with plum-blossom needle can effectively treat the trigeminal neuralgia of wind and heat and relieve pain, its therapeutic effect is superior to conventional acupuncture. The mechanism may be related to the regulation of serum IL-6, TNF-α, VIP and β-EP.

Oxidative Damage of Bone Marrow Stromal Cells Caused by Chemotherapy Drugs / 中国实验血液学杂志

OBJECTIVE@#To explore the oxidative damage of OP9 cells induced by daunorubicin (DNR) treatment.@*METHODS@#The TMRM probe was used to detect mitochondrial membrane potential by flow cytometry; the reactive oxygen species (ROS) was determined by flow cytometry DCFDA probe; the real-time PCR was used to detect the molecular expression of antioxidant enzyme，glutathione peroxidase (GPX) in OP9 cells; the expression of γ-H2AX was determined by flow cytometry.@*RESULTS@#Compared with normal OP9 cells, the positive rate of TMRM in DNR-treated OP9 cells decreased by 56.7% (P＜0.05); the positive rate of DCFDA in DNR-treated OP9 cells increased by 3.52 times (P＜0.01). Compared with normal OP9 cells, DNR-treated OP9 cells showed a decrease in the expression of GPX4 by 44.22% (P＜0.001); the expression of GPX7 decreased by 65.7% (P＜0.001); the expression of GPX8 decreased by 24.7% (P＜0.001); the positive rate of γ-H2AX in DNR-treated OP9 cells increased (P＜0.05).@*CONCLUSION@#After DNR treatment, mitochondrial membrane potential of OP9 cells decreases; the level of reactive oxygen species increases; the expression of glutathione peroxidase (GPX) molecules decreases significantly; genomic instability increases obviously; the oxidative damage of cells increased.

Efficacy and Safety of the Induction Therapy with Different Doses of Anthracyclines for Patients with Newly Diagnosed Acute Promyelocytic Leukemia / 中国实验血液学杂志

@#]Objective:To investigate the efficacy and safety of induction regimens containing arsenite, allo-transretinoic acid (ATRA) and anthracyclines of different doses as induction chemotherapy for acute promyelocytic leukemia (APL).@*METHODS@#The clinical data of 129 consecutive hospitalized newly diagnosed APL patients from January 2011 to December 2017 were collected and retrospectively analyzed. Sixty-six patients received arsenite, ATRA and anthracyclines of low doses (low dose group), while other 63 patients received arsenite, ATRA and anthracyclines of standard doses (standard dose group), the efficacy and safety were compared and analyzed in 2 groups.@*RESULTS@#There were no statistically significant differences in terms of age, sex, routine blood indexes,LDH level, bone marrow promyelocyte count,prognostic stratification between patients in two groups (P>0.05). During the treatment, WBC count peak and its time point were not significantly different between two groups (P>0.05). Both induction regimens showed good efficacy, the PML-RARα gene conversion rate from positive into negative, the 2-year overall survival rate and disease-free survival rate in the low-dose group were similar to those in the standard dose group(P＞0.05). The recovery time of neutrophils and platelets in the low-dose group was 0 d and 11 d, respectively, which were statistically  significantly shorter than those in the standard dose group (3 d,15 d) (both P=0.000). The median value of platelet and erythrocyte transfusion in the low-dose group was 6.9 U and 4.2 U, respectively, which were statistically significantly lower than that in the standard dose group (8.4 U,6.8 U) (P=0.037，0.000). And the inpatient time in the low and the standard dose groups were 30.98 and 30.71 days, respectively (P=0.770).@*CONCLUSION@#For newly diagnosed patients with APL, the efficacy was similar between induction therapy containing arsenite,ATRA and low dose anthracyclines and the induction therapy containing arsenite, ATRA and standard dose anthracyclines, however, the former appears even safer.

Effect of hyperglycemia at admission in patients with acute ischemic stroke on endovascular treatment outcome / 中国脑血管病杂志

Objective To investigate the effect of hyperglycemia at admission in patients with acute ischemic stroke on endovascular treatment outcome.Methods From May 2012 to December 2016,200 consecutive patients with acute ischemic stroke (excluding patients with diabetes mellitus) underwent endovascular mechanical thrombectomy at the Department of Neurosurgery,the First People's Hospital of Changzhou were enrolled retrospectively.They were divided into either a hyperglycemia group (hyperglycemia was defined as glucose ＞7.8 nmol/L at admission,n =57) or a non-hyperglycemia group (n =143) according to the blood glucose levels at admission.The neurological function of the patients was evaluated by the National Institutes of Health Stroke Scale (NIHSS) at admission and discharge.The modified thrombolysis in cerebral infarction (mTICI) grade was used to evaluate the degree of recanalization.The modified Rankin scale (mRS) was used to evaluate the prognosis of the patients at 90 d after procedure.The general information of the patients were analyzed,including sex,age,past history,hospitalization time,onset to recanalization time (ORT),TOAST classification of cerebral infarction,and recanalization.The endovascular treatment outcomes of both groups were compared.Results (1) There were no significant differences in TOAST classification,age,hypertension history,atrial fibrillation history,stroke history,coronary heart disease history,ORT,NIHSS at admission between the patients of the two groups (all P ＞ 0.05).(2) There were no significant differences in days of hospitalization,mTICI grade,and number of thrombectomy between the patients of the two groups (P ＞0.05).(3) The discharge mortality and incidence of in-hospital neurological deterioration in the patients of the hyperglycemia group were 28.1％ (16/57) and 31.6％ (18/57) respectively,while those in the non-hyperglycemia group were 14.7％ (21/143) and 18.2％ (26/143) respectively.There were significant differences between the two groups (P =0.028 and 0.039 respectively).Conclusion Hyperglycemia at admission may have adverse effects on the prognosis in patients after receiving mechanical thrombectomy.

Endovascular treatment of central venous stenosis and obstruction in hemodialysis patients / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Central venous stenosis and obstruction (CVD) is a serious and prevalent challenge to both resolve the venous hypertension symptoms and maintain the pantency of the ipsilateral hemodialysis access in hemodialysis patients. This study aimed to summarize our experience of the endovascular management of the central venous stenosis or obstruction in hemodialysis patients.</p><p><b>METHODS</b>Twenty-four haemodialysis cases of central vein stenosis or obstruction with ipsilateral functional vascular access in our hospital between July 2006 and February 2012 were treated by interventional therapy and the data were analyzed retrospectively.</p><p><b>RESULTS</b>Eighteen males and six females with mean age of (66.4 ± 13.8) years and manifesting with arm swelling and venous hypertension were enrolled; 62.5% of them had a history of catheterization. Venography showed stenotic lesion in 10 cases including eight cases of brachiocephalic vein stenosis and two cases of subclavian vein stenosis and 14 cases of obstruction lesions including seven cases of short brachiocephalic obstruction and seven cases of long segment obstruction. Interventional therapy was performed and the technique success rate was 83.3%. Percutaneous transluminal angioplasty (PTA) was performed in nine cases and stent was performed in 11 cases firstly. The symptoms of venous hypertension were resolved after intervention in all the cases. There was no major complication and death perioperatively. During follow-up, reintervention was done, the primary patency rates were (88.9 ± 10.5)%, (64.8 ± 10.5)% and (48.6 ± 18.7)% at 3 months, 6 months and 1 year after treatment in the PTA group; (90.0 ± 9.5)% and (77.1 ± 14.4)% at 6 months and 1 year after treatment in the stent group, respectively. The secondary patency rates were (48.6 ± 18.7)% in the PTA group and (83.3 ± 15.2)% in the stent group 1 year after treatment, respectively. There was no significant difference between the two groups (primary patency, P = 0.20; secondary patency, P = 0.10).</p><p><b>CONCLUSIONS</b>The endovascular intervention is a safe and effective method for CVD in short term; enhanced follow-up and repeated interventions are required to maintain patency for long term. The prevention is most important. Avoiding and minimizing the placement of the central venous catheter may be the key point for the prevention.</p>

Retrograde tibial approach for endovascular recanalization of popliteal and tibioperoneal artery occlusion / 中华外科杂志

<p><b>OBJECTIVES</b>To describe a procedure of the retrograde approach for endovascular treatment of complex popliteal and/or infrapopliteal occlusions and to determine its safety and efficacy in minimizing failure rates.</p><p><b>METHODS</b>Between January 2010 and March 2012, 28 patients (16 male and 12 female patients) received retrograde tibial approach after failure of antegrade intervention. There were 3 patients with severe claudication (Rutherford category 3) and 25 patients with critical limb ischemia (Rutherford category 4 to 6). From this group, two techniques were employed. Twenty-four patients were treated via a retrograde transpedal access site and 4 patients via a transcollateral loop technique. The clinical and follow-up data of these patients were analyzed retrospectively.</p><p><b>RESULTS</b>The technique success rates were 92.8% (26/28). No major complications and 3 (10.7%) minor sequelaes were documented in this study. Twenty-three patients were followed up for 3 to 29 months, with a mean of (14 ± 9) months. Overall patency was 73.9% (17/23) and 47.8% (11/23) at 6 and 12 months. Overall survival and limb salvage was 95.7% (22/23), ulcer were healed in 9/10 patients.</p><p><b>CONCLUSION</b>The use of retrograde tibial or pedal approach seems feasible and safety in case of failure in antegrade revascularization of popliteal and/or infrapopliteal occlusions.</p>

Endovascular recanalization of superior vena cava, brachiocephalic, and subclavian venous occlusions caused by nonmalignant lesions / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Endovascular recanalization (EVR) is becoming the primary therapy for patients with central venous (brachiocephalic, subclavian, and superior vena cava) occlusion (CVO) caused by benign etiology. In this study, we retrospectively analyzed our experience in using EVR to treat benign CVO in 10 patients between April 2005 and September 2010.</p><p><b>METHODS</b>The mean age of the patients was 65.3 years, 2/10 cases were female, and the origin of cause of CVO in 7/10 cases was the hemodialysis access in the upper extremity. The patients were treated with primary stent placement and evaluated with immediate technical success rate and post-interventional patency rate after the procedure.</p><p><b>RESULTS</b>Eight patients were treated successfully with stent placement and experienced symptomatic relief immediately. No technical complications were observed during EVR treatment. Patients were followed up by ultrasonography and venography. Median follow-up was 13 months. Three patients required secondary procedures to maintain patency.</p><p><b>CONCLUSIONS</b>EVR is an effective and safe treatment in patients with benign CVO. It provides immediate symptom relief and maintains a continuous access for hemodialysis.</p>

Subintimal arterial flossing with antegrade-retrograde intervention technique to treat long-segment occlusion of peripheral artery / 中华外科杂志

<p><b>OBJECTIVE</b>To discuss the technique details of subintimal arterial flossing with antegrade-retrograde intervention (SAFARI) to improve technical success in the treatment of chronic total occlusions (CTO) diseases in lower extremity when there is failure to reenter the distal true lumen.</p><p><b>METHODS</b>Between May 2009 and Aug 2010, 15 patients underwent endovascular recanalization with SAFARI technique. There were 8 male and 7 female patients with a mean age of 74.9 years. There were 3 patients with severe claudication (Rutherford category 3) and 12 patients with critical limb ischemia (Rutherford category 4 to 6). The clinical and follow-up data of these patients were analyzed retrospectively.</p><p><b>RESULTS</b>Fourteen patients were treated with SAFARI technique successfully. The technique success rates were 93.3%. The mean ankle brachial index increased from 0.39 to 0.83.Symptoms were relieved in 86.6% patients, Ulcer were healed in 93.3%patients.</p><p><b>CONCLUSIONS</b>SAFARI technique is a safe and effective method in treating CTO diseases, when it is failure to renter the distal true lumen with subintimal angioplasty technique.</p>

The analysis of the follow-up results for the crural artery bypass / 中华外科杂志

<p><b>OBJECTIVE</b>To review the follow-up results of the crural artery bypass.</p><p><b>METHODS</b>Sixty-five limbs in 64 patients with long stenosis or occlusion in femoral artery and popliteal artery were performed 65 times femoral-crural artery bypass surgery or femoral-popliteal-crural bypass surgery during April 2001 to July 2007. The ankle-brachial index before bypass surgery was 0.35 +/- 0.20 in anterior tibial artery and 0.38 +/- 0.21 in posterior tibial artery. Critical limb ischemia was 93.8%.</p><p><b>RESULTS</b>The ankle-brachial index after bypass surgery was 0.84 +/- 0.26 in anterior tibial artery and 0.83 +/- 0.22 in posterior tibial artery. The perioperative mortality rate was 1.6%, the perioperative amputation rate was 1.5%. Fifty-four patients 54 limbs were followed up. The average follow-up time was (24.1 +/- 16.6) months. The follow-up limb salvage rate was 85.2%. The follow-up mortality rate was 25.9%. Critical limb ischemia decreased as 13.0%. The follow-up ankle-brachial index was difference with before and after bypass surgery as 0.66 +/- 0.26 in anterior tibial artery and 0.64 +/- 0.25 in posterior tibial artery. It was no difference in cumulative limb salvage rate, cumulative primary and secondary patency rate by comparing autogenous vein with composite vascular as graft and comparing femoral-crural artery bypass surgery with femoral-popliteal-crural bypass surgery as surgical method.</p><p><b>CONCLUSIONS</b>When the patients are failed in endovascular intervention or have long stenosis or occlusion in femoral artery and popliteal artery to face to amputation, the crural artery bypass is a feasible method. It's helpful to improve the secondary patency rate and limb salvage rate by enhancing the follow-up after operation and early intervention.</p>

Reoperations for occluded arterial bypasses in the lower limbs / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>We reviewed the outcomes of reoperations for 29 patients (30 limbs) who had undergone occluded arterial bypass in the lower limbs from May 1996 to September 2005.</p><p><b>METHODS</b>The 30 lower limbs of the 29 patients with arteriosclerotic obstruction received 44 reoperations, including thrombectomy alone (group T, 27) and inflow or outflow reconstruction plus thrombectomy (group C, 17). Among the 17 operations in group C, 17.6% (3/17) were inflow reconstructions involving the axillary-femoral (1), aorta-iliac (1) and aorta-femoral (1) arteries, and 76.4% (13/17) outflow reconstructions involving the femoral-popliteal bypass-tibial (8), femoral-tibial (1), femoral-popliteal bypass-popliteal arteries below the knee (2), and the femoral-popliteal bypass-tibial-peroneal trunk (2). One patient (1 limb) underwent both inflow and outflow reconstructions with an iliac arterial stent and a graft-popliteal anastomosis patch. Polytetrafluoroethylene (PTFE) grafts were used in the inflow or outflow reconstructions above the knee. Autovenous grafts or autovenously combined PTFE grafts were used in the outflow reconstructions below the knee.</p><p><b>RESULTS</b>The percentages of Fontaine stage III and IV before primary operation and reoperation were 60% (18/30) and 86.7% (26/30), respectively (P < 0.05). Four patients died of heart attack (2), stroke (1) and multiple organ failure (1) after reoperations. Among them, only 1 patient underwent occluded bypass, and others, patent bypass. Five patients after patent bypass are still alive. The accumulative patent rate was 28.6% (8/28). The average duration of patency in groups T and C was (4.16 +/- 5.68) (0.13 - 24) months and (7.14 +/- 6.37) (0.26 - 21) months, respectively (P > 0.05). Among 42 reoperations, 19 failed within 1 month in groups T (16) and C (3) (P < 0.01). Nine patients had limb amputated (10/28 limbs, 35.71%) because of graft infection (2 limbs), pseudo aneurysm at anastomosis (1 limb), and gangrene caused by failed grafts (7 limbs). The amputation was performed on 6 limbs within 1 month and on 4 limbs 1 month after reoperation (P > 0.05). The rate of limb salvage was 64.29% (18/28).</p><p><b>CONCLUSIONS</b>The percentages of Fontaine stage III and IV before reoperation may be much higher than those before primary operation. Thrombectomy plus inflow/outflow reconstruction creates patency better than thrombectomy alone for re-occluded bypass.</p>

High performance liquid chromatography-mass spectrometry analysis of radix Angelica sciensis / 药学学报

<p><b>AIM</b>To analyze the chemical components in Danggui (the roots of Angelica sinensis (Oliv.) Diel).</p><p><b>METHODS</b>HPLC-MS/MS was used to identify the main components in Danggui. Furthermore, the MS fragmentation regularity of the phthalides was proposed. The mobile phase of HPLC consisted of 0.5% acetic acid in water and 0.5% acetic acid in acetonitrile, analytical column was Hypersil ODS2 (250 mm x 4.6 mm, 5 microm), flow rate 1.0 mL x min(-1), injected volume 2 microL. The ionization source was ESI in positive ion mode.</p><p><b>RESULTS</b>Ferulic acid, nine known phthalides and one unknown phthalide derivative were tentatively identified in chromatograms based on their MS data and the comparison of their UV spectra with those published in the literatures.</p><p><b>CONCLUSION</b>The structural information of phthalides was obtained via HPLC-MS/MS, which provides an accurate and fast method to identify the phthalides and provides more scientific information for quality control of Danggui.</p>

Osteoporosis and nitric oxide / 中国病理生理杂志

Recent work has shown that nitric oxide (NO) induction by nitric oxide synthase(NOS) is the physiological mediator of bone cell function and demonstrated that it may be possible to exert differential effects on osteoblast (OB) and osteoclast (OC) activity in vivo. The proinflammatory cytokines, such as tumor necrosis factor-? (TNF-?), interleukin-1? (IL-1?), interferon-? (IFN-?), will stimulate bone resorption by NOS-induced low levels of NO. These findings confirm NO as a potentially important osteoblast-osteoclast coupling factor, indicating that cytokine-induced NO was largely responsible for the mechanisms of osteoporosis. Pharmacological modulation of NO may therefore represent a new approach in the treatment of bone diseases characterized by increased bone resorption, such as osteoporosis (OP).