[Feasibility of a three-sided encapsulation procedure based on fascia anatomy in laparoscopic lateral lymph node dissection for middle and low rectal cancer].

Objective: To explore the feasibility and value of performing a three-sided encapsulation procedure based on fascia anatomy in laparoscopic lateral lymph node dissection (LLND) for middle and low rectal cancer. Methods: This was a retrospective review. The study cohort comprised patients who met the diagnostic criteria for rectal cancer according to the Chinese Guidelines for the Diagnosis and Treatment of Colorectal Cancer, had a short lymph node diameter of >5 mm on the lateral side within the 15 days before surgery, were evaluated as feasible candidates for laparoscopic total mesorectal excision+LLND surgery, had been diagnosed with low or intermediate level rectal cancer, and whose tumor was less than 8 cm away from the anal verge according to pathological examination of the operative specimen. Patients with a history of other malignant tumors of the abdomen or with incomplete follow-up data were excluded. Forty-two patients with middle and low rectal cancer who had undergone lateral lymph node dissection in diagnosis and treatment center of Gastrointestinal Cancer of Guangdong Hospital of Chinese Medicine from Jan.2018 to Dec.2022 were enrolled. There were 24 men (57.1%) and 18 women (42.9%) aged 58.4±11.8 years and the median BMI was 22.5 (19.3-24.1) kg/m2. The main point of the three-sided encapsulation procedure is to expand the external side medial to the external iliac artery and vein, narrowing the range of exterior side dissection. The anterior-medial side is designed to expand the vesical fascia to define the range of anterior-medial side extension. The internal side is fully extended to the ureterohypogastric nerve fascia; the distal point of the caudal extension reaches the level of the Alcock canal and the bottom reaches the piriformis, enabling dissection of the obturator nerve and No.283 lymph nodes. No.263D lymph nodes are dissected by exposing the internal iliac artery and its branches, dissecting the group No.263P lymph nodes, and severing the inferior vesical artery. Finally, the lateral lymphatic tissue is completely resected. Relevant variables were recorded, including the number of lateral lymph nodes detected, the rate of lymph node metastasis, operation duration, intraoperative blood loss, postoperative complications, postoperative hospital stay, and 3-year overall survival rate. Results: Laparoscopic surgery was successfully completed in all patients with no conversions to open surgery and no intraoperative complications. Twenty-seven (64.3%) of the study patients underwent left-sided LLND, 10 (23.8%) right-sided LLND, and five (11.9%) bilateral LLND, with lymph nodes cleared on both sides. All patients' lymph nodes were examined pathologically. A median of 17.0 (11.7, 26.0) lymph nodes was detected, the median of lateral lymph nodes being 5.0 (2.0, 10.2). The median operation time was 254.5 (199.0, 325.2) minutes. The median intra-operative blood loss was 50.0 (30.0, 100.0) mL. All patients were diagnosed with adenocarcinoma by pathological examination of the operative specimen. Two patients developed postoperative intestinal obstruction, one lymphatic leakage, and one a perineal incision infection. There were no cases of anastomotic leakage. The median postoperative hospital stay was 6.0 (5.0, 7.0) days and the median follow-up time 23.5 (9.0, 36.7) months. During follow-up, three patients (7.1%) died of tumor recurrence and metastasis. Two (4.8%) experienced mild urinary dysfunction, and one (2.4%) had moderate postoperative erectile dysfunction. One patient (2.4%) was found to have prostate and lung metastases 3 month after surgery. The 3-year overall survival rate was 74.4%. Conclusions: Three sided encapsulation is a safe and feasible procedure for LLND, achieving accurate and complete clearance of lateral lymphatic tissue.

[A clinical observational study on the preliminary effect of dupilumab in the treatment of severe asthma].

Objective: To investigate the effect and safety of dupilumab in the treatment of patients with severe asthma in a preliminary clinical observational study. Methods: This study retrospectively analyzed the clinical data of 20 patients with severe asthma who received dupilumab for 4-12 months between 2019 and 2022 at the First Hospital of Guangzhou Medical University, comparing pre-and post-treatment laboratory data, oral glucocorticoid dose (OCS), asthma control test (ACT) and adverse effects. The median age of the 20 patients was 48.5 (41.0-52.8) years, including 14 males and 6 females. The clinical data of 10 patients treated with other biologic agents were further analyzed to determine the reasons for switching to biologic drug treatment and the efficacy of dupilumab in these patients. Paired t-tests or Wilcoxon signed-rank tests were used for comparisons. Mann-Whitney analysis was used for inter-group comparison, and chi-square test or Fisher test was used for inter-group comparisons of count data. Results: A total of 20 patients were included in this study. All 20 severe asthma phenotypes were type 2 (T2)-high and completed at least the first 4 months of treatment, including 17 patients who completed 12 months of treatment. Among patients who completed 4 months of treatment, the asthma exacerbation score decreased from 1.0(0.3-1.0) episodes/4 months to 0.0(0.0-1.0) episodes/4 months, P<0.001, and FEV1/FVC increased from 58.4% (50.5%-69.0%) to 66.9% (59.6%-77.7%), P<0.01. The number of patients requiring OCS maintenance therapy decreased from 15 (75%) to 9 (45%), P<0.05. Among patients who completed 12 months of treatment, the asthma exacerbation score decreased from 1.0(0.5-1.0) episodes/4 months to 0.0 (0.0-0.0) episodes/4 months, P<0.01, and FEV1/FVC increased from 57.9% (49.6%-67.8%) to 72.7% (64.6%-78.7%), P<0.01. The number of patients requiring OCS maintenance therapy decreased from 13 (76%) to 6 (35%), P<0.01. In 10 patients with a history of previous biologic therapy, the most common reasons for switching to a biologic were a poor response to previous monoclonal antibodies (40%) and loss of control of asthma symptom control after discontinuation of monoclonal antibodies (30%). The remaining reasons were patients' uncontrolled symptoms of chronic rhinosinusitis (20%) and irregular or underdosed use of previous biologics (10%). After 4 months of switching to dupilumab, 10 patients experienced varying degrees of improvement in asthma control. Conclusions: The application of dupilumab for the treatment of T2-high severe asthma showed good efficacy and few adverse effects. Biologically targeted therapy is an important treatment approach to achieving better control of severe asthma.

[Efficacy of omalizumab in the treatment of eosinophilic granulomatous polyangiitis with asthma as the first symptom].

Objective: To investigate the efficacy, and safety of omalizumab in the treatment of eosinophilic granulomatous with polyangiitis (EGPA) with asthma as the first symptom. Method: The clinical characteristics of 22 EGPA patients with asthma as the first symptom treated with omalizumab in the First Affiliated Hospital of Guangzhou Medical University from March 2018 to December 2020 were retrospectively analyzed. The asthma control test (ACT) score, the frequency of asthma exacerbation (AE), the Birmingham Vasculitis Activity Score (BVAS), the variation rate of peak expiratory flow (PEF), the percentage of PEF to predicted value of PEF (PEFpred%), the percentage of forced expiratory volume in first second (FEV1) to predicted value of FEV1 (FEV1pred%), the dosage of oral corticosteroid (OCS) and other clinical data [M(Q1, Q3)] were collected before and after treatment, to observe the efficacy and adverse reactions of omalizumab. Results: There were 22 subjects recruited in this study. The median age was 42 (22-70) years. Eleven of the patients were males. After treated with omalizumab for 4 months, there were 68.2%(15/21) of patients who responded to the treatment. In the response group (n=15), the patients' ACT score increased from 19.0 (16.5, 21.0) to 23.0 (21.5, 24.0) (P=0.001). The frequency of AE decreased from 0.7 (0.3, 1.0) to 0 (0, 0.7) per four mouths (P<0.001). The BVAS decreased from 4.0 (2.0, 6.0) to 2.0 (2.0, 4.0) (P=0.007). The variation rate of PEF decreased from 18.8% (14.0%, 27.7%) to 9.2% (6.8%, 11.9%) (P=0.007). The PEFpred% increased from 80.8% (73.5%, 90.7%) to 100.5% (79.4%, 114.0%) (P=0.005). The maintenance dosage of OCS reduced from 15.0 (10.0, 20.0) mg/d to 8.8 (5.0, 10.0) mg/d (P=0.005). The level of baseline eosinophil in peripheral blood of patients in non-response group was higher than that in response group [11.4% (9.2%, 22.6%) vs 3.4% (1.1%, 6.5%), P<0.05]. A total of 190 injections were performed in 22 patients, and only 4 patients (2.1%) had adverse reactions after a single injection of omalizumab, such as dizziness, swelling of injection site and pruritus. The adverse reactions were tolerable. Conclusions: Omalizumab has certain curative effect on EGPA, can reduce asthmatic symptoms and OCS maintenance dosage, and has a good safety profile. The rate of response to the treatment is higher in patients with mild eosinophilic inflammation.

The function of the ACE2/Ang(1-7)/Mas receptor axis of the renin-angiotensin system in myocardial ischemia reperfusion injury.

OBJECTIVE: Angiotensin-converting enzyme 2(ACE2) is a critical element of the renin-angiotensin system (RAS), which can convert angiotensin (Ang)II to Ang(1-7), followed by binding Mas receptor (MasR) and subsequently produces cardioprotective effects through various signal transduction pathways. It has been discovered in research that activation of the RAS contributes a crucial influence during the myocardial ischemia reperfusion injury (MIRI) development. The features of ACE2, Ang(1-7), and MasR, as well as the function of the ACE2/Ang(1-7)/MasR axis in MIRI, are discussed in our review, with the therapeutic potential of this axis as a new treatment option for MIRI patients shown. MATERIALS AND METHODS: To retrieve a thorough collection of studies, we performed a search in PubMed using the following combination of keywords: (ACE2) or (Ang1-7) or (Mas receptor) and (Myocardial Ischemia reperfusion injury). The time limits used for the search were 1986 to 2021. RESULTS: In total, 367 articles were included. Titles and abstracts of articles were screened for relevance, and all relevant articles published in English were included. CONCLUSIONS: ACE2, a prominent member of the RAS, performs a crucial regulatory function in the cardiovascular system. ACE2 regulates the RAS inversely mainly by hydrolyzing the harmful AngII to the beneficial Ang(1-7). Increasing or activating ACE2 or Ang(1-7) may help prevent and treat MIRI. However, additional research into the specific processes behind the ACE2/Ang(1-7)/MasR axis in MIRI is necessary, as well as the performance of additional in-depth studies to go from basic research to clinical translation.

[Preliminary clinical observation of omalizumab therapy for moderate to severe asthma].

Objective: To observe the effectiveness, safety and management of omalizumab therapy for moderate to severe asthma in real-world clinical practice in China. Methods: This retrospective analysis involved 79 patients with moderate to severe asthma who received omalizumab therapy for at least 4 months in the First Affiliated Hospital of Guangzhou Medical University from March 2018 to April 2020. All participants were between 14 to 76 years old(median 50 years),including 30 males and 49 females. Data regarding the patients' clinical manifestations, eosinophil count, fractional exhaled nitric oxide (FeNO), lung function, oral corticosteroid dosage, and adverse reactions were collected before and after treatment. Paired t-test or non-parametric paired Wilcoxon analysis was used for pairwise comparison, Mann Whitney analysis for inter-group comparison, and Chi square test or Fisher test for inter-group comparison of count data. Results: The following changes were noted after 4 months of omalizumab thearpy. The patients' Asthma Control Test (ACT) scores increased from 17.0 (13.0-19.0) to 20.0 (18.0-24.0) points (P<0.001). The frequency of acute exacerbations(AE) decreased from 1.0 (0-1.0) to 0 (0-1.0) episodes every 4 months (P<0.001). The variation rate of the peak expiratory flow (PEF) decreased from 16.5 (13.8-27.3)% to 10.4 (6.0-16.2)% (P<0.001). The percent predicted value of PEF (PEFpred%) increased from 71.7 (51.4-91.6)% to 87.5 (65.2-105.5)% (P<0.001). The percent predicted value of the forced expiratory volume in 1 second(FEV1%pred) increased from 73.6 (53.9-90.8)% to 80.6 (68.7-91.8)% (P=0.007). The maintenance dose of oral corticosteroids (OCS) decreased from 12.0 (10.0-20.0) to 5.0 (0-17.5) mg/day (P=0.001). After 4 months of treatment, the response rate of the 79 patients with asthma was 74.7%. The response rate of patients with allergic asthma (77.3%) was higher than that of patients with non-allergic asthma (25.0%) (P=0.019). Among 5 patients who completed 1 year of treatment, the ACT score, frequency of AE, PEFpred%, variation rate of PEF and OCS maintenance dose were still improved after 1 year of treatment. Adverse reactions occurred in 3 patients (3.8%), for a total of 3 (0.6%) times. Stratified analysis showed that after 4 months of treatment, the improvement in the ACT score and the decrease in the PEF variation rate among patients who reached the recommended treatment dose (full dose) [3.0 (1.0-8.0) points, 6.5 (3.5-15.8) %] were significantly higher than those among patients who did not reach the recommended treatment dose (insufficient dose) [1.0 (-0.3-3.0) points, 2.9 (1.5-5.0) %] (P<0.05). Additionally, the treatment response rate in patients with a sufficient dose (80.0%) was higher than that in patients with an insufficient dose (50.0%) (P=0.019).The main factors associated with stopping treatment within 1 year despite a response to omalizumab was economic burden (70.3%), followed by satisfactory improvement by self-evaluation (21.9%) and less improvement in symptoms than expected (7.8%). Conclusion: Omalizumab was an effective treatment for moderate to severe allergic asthma with few adverse effects. The response rate was higher when the recommended injection dose was achieved. Financial difficulty was the main reason for stopping treatment within 1 year despite a good therapeutic response.

[Three dimensional nephrometry system for partial nephrectomy: Our initial exploration].

OBJECTIVE: To construct a preoperative evaluation system for partial nephrectomy using CT three-dimensional visualization technology and to explore its practical value. METHODS: The clinical data of the patients who underwent partial nephrectomy for renal tumors in Department of Urology, Peking University First Hospital were collected retrospectively. At the same time, the homogenized standard data of patients who underwent partial nephrectomy for renal tumors were collected in 16 clinical centers in China. The CT three-dimensional visualization system was applied (IPS system, Yorktal) to evaluate tumor anatomy, blood supply, perirenal fat and other information. The parameters were summarized to build a three-dimensional nephrometry system, on the basis of which virtual surgery design and intraoperative navigation were completed. RESULTS: A three-dimensional visualization image was established based on the enhanced CT urography. The nephrometry system included the longest diameter and volume of the tumor, proportion volume of tumor invading the parenchyma, maximum depth of the tumor invading the parenchyma, contact surface area, flatness of the tumor surface, renal segment where the tumor was located, vascular variation, and perirenal fat. The average two-dimensional diameter of the tumor was (2.78±1.43) cm, the average three-dimensional maximum diameter was (3.09±1.35) cm, and the average postoperative pathological size was (3.01±1.38) cm. The maximum tumor diameter in the three-dimensional image was significantly related to the prolonged renal artery clamping time and intra-operative blood loss (r=0.502, P=0.020; r=0.403, P=0.046). The three-dimensional and pathological tumor volume were (25.7±48.4) cm3 and (33.0±36.4) cm3, respectively (P=0.229). The tumor volume was significantly related to the intraoperative blood loss (r=0.660, P < 0.001). The proportion volume of the tumor invading into renal parenchyma was significantly related to the prolongation of renal artery clamping and the occurrence of postoperative complications (r=0.410, P=0.041; r=0.587, P=0.005). The tumor contact surface area and the presence of vascular variation did not show correlation with the perioperative data and postoperative complications. While the preoperative evaluation was completed, the reconstructed three-dimensional image could be zoomed, rotated, combined display, color adjustment, transparency, and simulated cutting on the Touch Viewer system. The process generally consisted of showing or hiding the tissue, adjusting the transparency of the interested area, rotating and zooming the image to match the position of the surgical patient. Together, these functions met the requirements of preoperative virtual surgery plan and intraoperative auxiliary navigation. CONCLUSION: Three-dimensional images can provide a more intuitive anatomical structure. The CT three-dimensional visua-lization system clearly displays tumor anatomical parameters, blood supply and perirenal fat. The three-dimensional nephrometry system for renal tumors can help predict the difficulty of partial nephrectomy and perioperative complications. Importing the reconstructed three-dimensional visualization image into the specified program or robot operating system can complete virtual surgery and intraoperative navigation, helping the surgeon to better grasp the surgical process. The indexes included in the nephrometry system and the score weights of each index need to be confirmed and perfected by multi-center study with large samples.

[Study on purification effect of formaldehyde in cleanroom by new return air device].

Objective: To effectively reduce the concentration of poisons in cleanroom, protect the health of workers, realize the optimization and automatic control of the new return air device. And the influence of initial concentration, air volume, temperature and relative humidity of formaldehyde on the purification effect of the new return air device was explored. Methods: The purification effect of the new return air device installed with the activated carbon and the photocatalyst purification net or ordinary activated carbon purification network was tested in a 60 m(3) simulated cleanroom. The concentration of formaldehyde was determined by solution absorption-phenol reagent spectrophotometry. Based on the single factor experiment to determine the combination of two purification nets. The effects of air volume, initial formaldehyde concentration, temperature and relative humidity on the purification effect of the new return air device were investigated by orthogonal test. Then, the performance parameters of the return air device to purify formaldehyde were determined. Results: The formaldehyde purification efficiency of the two types of purification nets in the new return air device was higher than that of the ordinary activated carbon purification network (P<0.05) . The combination of activated carbon and photocatalyst purification net has no effect on the formaldehyde purification efficiency of the return air device (P>0.05) . According to the direct analysis and variance analysis, air volume was the most sensitive factor (F value is 18.894, P<0.05) , followed by initial concentration (F value is 16.128, P<0.05) , while temperature and relative humidity have little effect (F value is 0.041 and 0.599, respectively, P>0.05) . LSD analysis showed that there was no significant difference in the purification efficiency of formaldehyde between 475 m(3)/h and 626 m(3)/h (P>0.05) . From the perspective of formaldehyde purification efficiency and energy saving, when the air volume is set to 475 m(3)/h, the new return air device has higher purification efficiency for high concentration of formaldehyde. Conclusion: The new return air device consisting of activated carbon and photocatalyst purification net can play a good purification role in cleanroom with different temperatures and different humidity. Its formaldehyde purification efficiency is affected by air volume and initial concentration.

[Study on the effect of activated carbon on formaldehyde in clean workshop].

Objective: To study the effect of activated carbon on the purification of formaldehyde in the clean workshop return air purification device and its influencing factors. Methods: From May to June 2018, choosed 4 different commercial activated carbons (bamboo charcoal, 1-3 mm, 3-5 mm; coconut shell charcoal, 6-12 mesh, 8-16 mesh) to make 5 types of activated carbon purification net. In the simulated clean plant laboratory, the detection of occupational disease hazards was used to test the purification effect of different types of activated carbon purification nets on formaldehyde. Results: The purification effect of different types of activated carbon increased with the prolongation of purification time, and the difference was statistically significant (P<0.05) . Compared with other types of activated carbon, coconut shell charcoal (8-16 mesh, double layer) had the best purification effect, 15 min and 30 min purification efficiency was 58.72% and 85.20% respectively, and the difference was statistically significant (P<0.05) . The purification effect of double-layer coconut shell charcoal was better than single layer (P<0.05) . The purification effect of double-layer coconut shell charcoal (8-16 mesh) was better than double-layer coconut shell charcoal (6-12 mesh) , the difference was statistically significant (P<0.05) . Coconut shell charcoal (8-16 mesh, double layer) had better purification effect than bamboo charcoal (P<0.05) . Conclusion: Different specific surface area, particle size, and thickness of activated carbon have a certain effect on the purification effect of formaldehyde, and its selection has a certain significance in improving the occupational health protection level in the clean plant, solving the safe use of return air and reducing energy consumption.

[Clinical analysis of 3 cases of eosinophilic granulomatosis with polyangiitis].

Objective: To improve the clinical recognition of eosinophilic granulomatosis with polyangiitis(EGPA) in clinical manifestations, diagnosis and treatment. Methods: The clinical manifestations, pathological characteristic, imaging manifestations, diagnosis and the therapy of three patients with EGPA were presented. Results: These 3 patients had asthma-like symptoms and extrapulmonary manifestations of systemic vasculitis. They were 20, 40 and 44 years old. All of them were female.They denied exposure or contact. Chest radiographic examination showed that the most common features were nodule shadow and tree-in-bud in the lung. The pathological manifestation was characterized by hypereosinophilia, high total IgE(over 300 KU/L) and high CRP(over 14.1mg/L). The FeNO of 2 patients was over 100ppb. The ANCA of these 3 patients was negative. The pulmonary pathology was observed had eosinophil infiltration in the alveolar, interstitial and vessel for 3 cases. The clinical manifestations were nonspecific. All patients were treated by glucocorticoid and immune-inhibitor(alkylating agents or purine synthesis inhibitors) therapy. Because patients were complicated with other organs involved, they needed long-time treatment. Conclusions: This disease is diverse and complex, with a lack of pathognomonic symptoms. We should highly suspect eosinophilic granulomatosis with polyangiitis, when the patients present severe asthma and eosinophilia. Early detection, early treatment, and the prognosis could be better.

[Review on the associations of signal transducer and activators of transcription 3 with hepatocellular carcinoma].

Hepatocellular carcinoma (HCC) is one of the most common malignancies with high fatality rate in China. To investigate the related risk factors and therapeutic targets, and actively carry out the prevention and early treatment is of great public health value. Signal transducer and activators of transcription 3 (STAT3) is the key molecule of multiple inflammation-associated signaling pathways. Recent studies have found that HCC patients have high expressing levels of STAT3 in tumor tissues, and aberrant activation of STAT3 is closely associated with the occurrence, development, invasion, metastasis, and prognosis of HCC. In this paper, we reviewed the researches on the associations of STAT3 with the occurrence and prognosis of HCC and prospected on the issues of causal prophylaxis and targeted therapy for HCC which could offer reference for the protection strategy of HCC.

Addition of clopidogrel to aspirin in 45,852 patients with acute myocardial infarction: randomised placebo-controlled trial.

BACKGROUND: Despite improvements in the emergency treatment of myocardial infarction (MI), early mortality and morbidity remain high. The antiplatelet agent clopidogrel adds to the benefit of aspirin in acute coronary syndromes without ST-segment elevation, but its effects in patients with ST-elevation MI were unclear. METHODS: 45,852 patients admitted to 1250 hospitals within 24 h of suspected acute MI onset were randomly allocated clopidogrel 75 mg daily (n=22,961) or matching placebo (n=22,891) in addition to aspirin 162 mg daily. 93% had ST-segment elevation or bundle branch block, and 7% had ST-segment depression. Treatment was to continue until discharge or up to 4 weeks in hospital (mean 15 days in survivors) and 93% of patients completed it. The two prespecified co-primary outcomes were: (1) the composite of death, reinfarction, or stroke; and (2) death from any cause during the scheduled treatment period. Comparisons were by intention to treat, and used the log-rank method. This trial is registered with ClinicalTrials.gov, number NCT00222573. FINDINGS: Allocation to clopidogrel produced a highly significant 9% (95% CI 3-14) proportional reduction in death, reinfarction, or stroke (2121 [9.2%] clopidogrel vs 2310 [10.1%] placebo; p=0.002), corresponding to nine (SE 3) fewer events per 1000 patients treated for about 2 weeks. There was also a significant 7% (1-13) proportional reduction in any death (1726 [7.5%] vs 1845 [8.1%]; p=0.03). These effects on death, reinfarction, and stroke seemed consistent across a wide range of patients and independent of other treatments being used. Considering all fatal, transfused, or cerebral bleeds together, no significant excess risk was noted with clopidogrel, either overall (134 [0.58%] vs 125 [0.55%]; p=0.59), or in patients aged older than 70 years or in those given fibrinolytic therapy. INTERPRETATION: In a wide range of patients with acute MI, adding clopidogrel 75 mg daily to aspirin and other standard treatments (such as fibrinolytic therapy) safely reduces mortality and major vascular events in hospital, and should be considered routinely.

Early intravenous then oral metoprolol in 45,852 patients with acute myocardial infarction: randomised placebo-controlled trial.

BACKGROUND: Despite previous randomised trials of early beta-blocker therapy in the emergency treatment of myocardial infarction (MI), uncertainty has persisted about the value of adding it to current standard interventions (eg, aspirin and fibrinolytic therapy), and the balance of potential benefits and hazards is still unclear in high-risk patients. METHODS: 45,852 patients admitted to 1250 hospitals within 24 h of suspected acute MI onset were randomly allocated metoprolol (up to 15 mg intravenous then 200 mg oral daily; n=22,929) or matching placebo (n=22,923). 93% had ST-segment elevation or bundle branch block, and 7% had ST-segment depression. Treatment was to continue until discharge or up to 4 weeks in hospital (mean 15 days in survivors) and 89% completed it. The two prespecified co-primary outcomes were: (1) composite of death, reinfarction, or cardiac arrest; and (2) death from any cause during the scheduled treatment period. Comparisons were by intention to treat, and used the log-rank method. This study is registered with ClinicalTrials.gov, number NCT 00222573. FINDINGS: Neither of the co-primary outcomes was significantly reduced by allocation to metoprolol. For death, reinfarction, or cardiac arrest, 2166 (9.4%) patients allocated metoprolol had at least one such event compared with 2261 (9.9%) allocated placebo (odds ratio [OR] 0.96, 95% CI 0.90-1.01; p=0.1). For death alone, there were 1774 (7.7%) deaths in the metoprolol group versus 1797 (7.8%) in the placebo group (OR 0.99, 0.92-1.05; p=0.69). Allocation to metoprolol was associated with five fewer people having reinfarction (464 [2.0%] metoprolol vs 568 [2.5%] placebo; OR 0.82, 0.72-0.92; p=0.001) and five fewer having ventricular fibrillation (581 [2.5%] vs 698 [3.0%]; OR 0.83, 0.75-0.93; p=0.001) per 1000 treated. Overall, these reductions were counterbalanced by 11 more per 1000 developing cardiogenic shock (1141 [5.0%] vs 885 [3.9%]; OR 1.30, 1.19-1.41; p<0.00001). This excess of cardiogenic shock was mainly during days 0-1 after admission, whereas the reductions in reinfarction and ventricular fibrillation emerged more gradually. Consequently, the overall effect on death, reinfarction, arrest, or shock was significantly adverse during days 0-1 and significantly beneficial thereafter. There was substantial net hazard in haemodynamically unstable patients, and moderate net benefit in those who were relatively stable (particularly after days 0-1). INTERPRETATION: The use of early beta-blocker therapy in acute MI reduces the risks of reinfarction and ventricular fibrillation, but increases the risk of cardiogenic shock, especially during the first day or so after admission. Consequently, it might generally be prudent to consider starting beta-blocker therapy in hospital only when the haemodynamic condition after MI has stabilised.

Effects of isatin on rotational behavior and DA levels in caudate putamen in Parkinsonian rats.

Isatin was a potent endogenous monoamine oxidase (MAO) inhibitor that is more active against MAO-B than MAO-A. The acute effects of isatin on apomorphine (APO)-induced rotations were evaluated in Parkinsonian rats induced by 6-hydroxydopamine (6-OHDA) lesion. Furthermore, the effects of isatin on DA release in caudate putamen (CPu) of model and normal rats were monitored using fast cyclic voltammetry (FCV). The contents of monoamine transmitters and their metabolites in CPu of model and normal rats were also analyzed by high performance liquid chromatography with electrochemical detection after administration of isatin. Here we show that isatin (100 mg/kg, i.p.) apparently inhibited APO-induced rotations of Parkinsonian rats to 39.1+/-3.7% of the control (n=12), while it had no apparent effects on electrical stimuli-induced DA release either in normal rats or in model rats. In addition, the content of 5-hydroxytryptamine but not DA was increased in both normal rats and model rats after isatin (100 mg/kg, i.p.) was administered (P<0.01, n=6). The content of 5-hydroxyindole acetic acid was not changed. These results suggest that isatin cannot increase DA levels in rat CPu. Therefore, the effects of isatin on APO-induced rotations of our Parkinsonian rats could not attribute to its inhibition of DA catabolism as a MAO inhibitor.

Effects of growth hormone (rhGH) and glutamine supplemented parenteral nutrition on intestinal adaptation in short bowel rats.

This study was performed to compare the effects of recombinant human growth hormone (rhGH), glutamine (Gln) and simultaneous treatment with rhGH and Gln in rats subjected to 75% intestinal resection and maintained with parenteral nutrition (PN) for 6 days. Morphological changes including mucosal thickness, villus height, crypt depths and villus surface area of the residue jejunum were measured under a light microscope; expression of PCNA as an index of cell proliferation and apoptotic cells were observed using immunohistochemical staining; Ileal IGF-1 mRNA was determined by Northern blot analysis. The morphological parameters of the jejunal mucosa in rats treated with PN alone were only about 52-62% of those in reference group (P<0.01), this atrophy of the jejunal mucosa was accompanied by a 2.5-fold decrease in absolute counts of PCNA and a 10-fold increase in apoptotic index (P<0.01), IGF-1 mRNA transcript in residue ileum was decreased significantly (P<0.01). However, with rhGH or Gln, the mucosal architecture was improved significantly and was further improved when rhGH and Gln were given together, the morphological values in rats treated with Gln+rhGH was 79% higher than those with PN alone, and was associated with a 2-fold increase in PCNA counts and a 4-fold decrease in apoptotic index (P<0.01), IGF-1 mRNA expression was 78% higher than those with PN alone (P<0.01). We conclude that rhGH and Gln have synergistic effects on adaptation of the intestinal remnant in parenterally fed, short-bowel rats. The underlying mechanisms are associated with increased proliferation and decreased apoptosis in the intestinal epithelial cells. Local intestinal production of IGF-1 plays an important role in adaptation of the small intestine. Our findings support the concept that specific gut-trophic nutrients and growth factors may be combined to enhance the intestinal adaptation.

Effect of cholecystokinin-8 microinjection into ventral tegmental area on dopamine release in nucleus accumbens of rats: an in vivo voltammetric study.

1. Effects of microinjection of cholecystokinin-8 (CCK-8) into the rat ventral tegmental area were studied on dopamine (DA) release from nucleus accumbens (Acb), using fast cyclic voltammetry and carbon fibre microelectrode. 2. DA release was evoked by electrical stimulation of the medial forebrain bundle (MFB). DA release from Acb was increased with increasing intensity or frequency of electrical stimulation in a dose-dependent manner and was inhibited by microinjection of CCK-8 (0.5 microg/kg) into the ventral tegmental area. 3. The release of DA was clearly reduced at all the intensities (0.25, 0.5, 0.75 and 1.0 mA) tested following CCK injection into the VTA, which was statistically significant (P<0.05). But the reduced percentage of DA release did not show significant changes between the data obtained with stimuli of different intensities (P>0.05). 4. While no change could be found with the stimuli of 10Hz, the DA release was significantly suppressed by injection of CCK-8 at the other three frequencies tested (50 Hz, 100 Hz and 250 Hz). Furthermore, although the differences in the reduced amounts of DA release obtained at 50 Hz, 100 Hz and 250 Hz were statistically significant, the reduced percentage seemed to be not closely related to the frequency applied (P>0.05). 5. These results indicate that CCK-8 is involved in the regulation of midbrain DA neurotransmission, and thereby implicated in disorders, such as Parkinson's disease, that involve malfunctions of the basal ganglion DA neuronal systems.

Constituents from the roots of Semiaquilegia adoxoides.

The isolation of griffonilide (1), lithospermoside (2) and magnoflorine (3) from the roots of Semiaquilegia adoxoides is reported.

[Effect of estrogen on dopamine release evoked by electric stimulation of central amygdaloid nucleus].

In vivo fast cyclic voltammetry (FCV) was used to investigate dopamine (DA) release from central amygdaloid nucleus (CAN) of ovariectomized (OVX), estrogen-treated and normal female rats. Radioimmunoassay was used to measure the serum concentration of estradiol (E(2)). DA release was significantly higher in OVX rats treated with estradiol benzoate (EB) as compared with controls. The DA release due to electric stimulation is dose-dependent on serum concentration of estradiol, suggesting that estrogen may play an important role in regulating DA release from CAN.

[The expression of p97 on the membrane of the reticulocyte and the role in iron uptake in rabbit].

AIM: To investigate the expression of p97 on the membrane of the reticulocyte and the possible role in non-transferrin bound iron uptake. METHODS: The SDS-PAGE and the radioisotope (59Fe) was used in this investigation. RESULTS: (1) The protein of the supernatant of reticulocytes was separated on SDS-PAGE. There was one band near 97kDa. The same result was obtained with reticulocytes treated with PI-PLC and the Mean OD of the band was higher than that of untreated reticulocytes. But for the mature erythrocytes, there wasn't apparent band near 97kD. (2) No apparent effect of only PI-PLC treatment on iron uptake by reticulocytes (P > 0.05). Reticulocytes, depleted endogenous-transferrin and then treated by PI-PLC, gave a significant decrease in iron uptake in cytosol and in heme (P < 0.05). CONCLUSION: The results support the possibility that p97 might be able to be expressed on the membrane of reticulocytes and plays a role in non-transferrin bound iron uptake by this type of cells in rabbit.

[Relationship between dopamine and iron contents in the brain of parkinsonian rats].

Using fast cyclic voltammetry (FCV), atomic absorption/flame emission spectrophotometry and high performance liquid chromatography for electrochemical detection, we studied the change in iron content in the substantia nigra (SN) of 6-hydroxydopamine (6-OHDA) lesioned Parkinsonian (PD) rats and the toxic effect of intranigral injection of iron on DA neurons. The neuroprotective effect of desferrioxamine mesylate was also observed. The results are as follows. (1) The iron content in SN on the lesioned side of 6-OHDA-lesioned PD rats was about three times as high as that in nonstandard PD rats. (2) The iron content in caudate putamen (CPu) on the lesioned side of PD rats was not different from that on the unlesioned side. (3) DA release as well as the content of DA and its metabolites were significantly decreased on the lesioned side of PD rats. (4) In the rats pretreated with intracerebroventricular desferrioxamine mesylate before 6-OHDA injection, the release and content of DA on the lesioned side were not significantly different from those on the unlesioned side. (5) Intranigral injection of 40 micrograms FeCl3 resulted in a dramatic reduction of both DA release and content in CPu. The above results strongly suggest that 6-OHDA reduces the DA release from CPu, in which iron plays an important role. Elevation of iron content in SN is one of the mechanisms responsible for the reduction of DA content. Desferrioxamine mesylate may exert a protective action on dopaminergic neurons.