Immune checkpoint inhibitors induced pituitary immune-related adverse events: diagnosis and management / 中华肿瘤杂志

Immune checkpoint inhibitors (ICIs) have been used in treating a wide variety of cancers, but they challenge clinicians with a series of special immune related adverse events (irAEs) resulting from activated immune system. Since June 2018, when the first programmed cell death 1 (PD-1) inhibitor, nivolumab, was approved by the National Medical Products Administration (NMPA), abundant experience has been accumulated in coping with irAEs from PD-1 and PD-1 ligand 1 (PD-L1) blockade therapies. In October 2021, the first CTLA-4 inhibitor, ipilimumab, which has a different spectrum of irAEs was also approved by NMPA. The discrepancy in clinical features of pituitary irAEs is obvious between these two types of ICIs. Pituitary irAEs include hypophysitis and hypopituitarism. In this review of latest literature, we have summarized the incidence, possible mechanisms, time of onset, clinical presentations, hormone test, pituitary imaging, treatment strategies and recovery patterns of pituitary irAEs. By referring to domestic and foreign clinical guidelines, we have proposed practical suggestions for screening, diagnosing and treating pituitary irAEs.

Pituitary immune-related adverse events induced by programmed cell death protein 1 inhibitors in advanced lung cancer patients: A report of 3 cases / 北京大学学报(医学版)

Pituitary immune-related adverse events induced by programmed cell death protein 1 inhibitors in advanced lung cancer patients: A report of 3 cases SUMMARY Programmed cell death protein 1 (PD-1) and its ligand 1 (PD-L1) have been widely used in lung cancer treatment, but their immune-related adverse events (irAEs) require intensive attention. Pituitary irAEs, including hypophysitis and hypopituitarism, are commonly induced by cytotoxic T lymphocyte antigen 4 inhibitors, but rarely by PD-1/PD-L1 inhibitors. Isolated adrenocorticotropic hormone(ACTH) deficiency (IAD) is a special subtype of pituitary irAEs, without any other pituitary hormone dysfunction, and with no enlargement of pituitary gland, either. Here, we described three patients with advanced lung cancer who developed IAD and other irAEs, after PD-1 inhibitor treatment. Case 1 was a 68-year-old male diagnosed with metastatic lung adenocarcinoma with high expression of PD-L1. He was treated with pembrolizumab monotherapy, and developed immune-related hepatitis, which was cured by high-dose methylprednisolone [0.5-1.0 mg/(kg·d)]. Eleven months later, the patient was diagnosed with primary gastric adenocarcinoma, and was treated with apatinib, in addition to pembrolizumab. After 17 doses of pembrolizumab, he developed severe nausea and asthenia, when methylprednisolone had been stopped for 10 months. His blood tests showed severe hyponatremia (121 mmol/L, reference 137-147 mmol/L, the same below), low levels of 8:00 a.m. cortisol (< 1 μg/dL, reference 5-25 μg/dL, the same below) and ACTH (2.2 ng/L, reference 7.2-63.3 ng/L, the same below), and normal thyroid function, sex hormone and prolactin. Meanwhile, both his lung cancer and gastric cancer remained under good control. Case 2 was a 66-year-old male with metastatic lung adenocarcinoma, who was treated with a new PD-1 inhibitor, HX008, combined with chemotherapy (clinical trial number: CTR20202387). After 5 months of treatment (7 doses in total), his cancer exhibited partial response, but his nausea and vomiting suddenly exacerbated, with mild dyspnea and weakness in his lower limbs. His blood tests showed mild hyponatremia (135 mmol/L), low levels of 8:00 a.m. cortisol (4.3 μg/dL) and ACTH (1.5 ng/L), and normal thyroid function. His thoracic computed tomography revealed moderate immune-related pneumonitis simultaneously. Case 3 was a 63-year-old male with locally advanced squamous cell carcinoma. He was treated with first-line sintilimab combined with chemotherapy, which resulted in partial response, with mild immune-related rash. His cancer progressed after 5 cycles of treatment, and sintilimab was discontinued. Six months later, he developed asymptomatic hypoadrenocorticism, with low level of cortisol (1.5 μg/dL) at 8:00 a.m. and unresponsive ACTH (8.0 ng/L). After being rechallenged with another PD-1 inhibitor, teslelizumab, combined with chemotherapy, he had pulmonary infection, persistent low-grade fever, moderate asthenia, and severe hyponatremia (116 mmol/L). Meanwhile, his blood levels of 8:00 a.m. cortisol and ACTH were 3.1 μg/dL and 7.2 ng/L, respectively, with normal thyroid function, sex hormone and prolactin. All of the three patients had no headache or visual disturbance. Their pituitary magnetic resonance image showed no pituitary enlargement or stalk thickening, and no dynamic changes. They were all on hormone replacement therapy (HRT) with prednisone (2.5-5.0 mg/d), and resumed the PD-1 inhibitor treatment when symptoms relieved. In particular, Case 2 started with high-dose prednisone [1 mg/(kg·d)] because of simultaneous immune-related pneumonitis, and then tapered it to the HRT dose. His cortisol and ACTH levels returned to and stayed normal. However, the other two patients' hypopituitarism did not recover. In summary, these cases demonstrated that the pituitary irAEs induced by PD-1 inhibitors could present as IAD, with a large time span of onset, non-specific clinical presentation, and different recovery patterns. Clinicians should monitor patients' pituitary hormone regularly, during and at least 6 months after PD-1 inhibitor treatment, especially in patients with good oncological response to the treatment.

Short-term efficacy and perioperative safety of catheter-based intervention for pulmonary vein stenosis caused by fibrosing mediastinitis / 中华心血管病杂志

Objective: To evaluate the short-term efficacy and perioperative safety of catheter-based intervention in patients with pulmonary vein stenosis caused by fibrosing mediastinitis (FM). Methods: It was a case series study. Consecutive patients with pulmonary vein stenosis caused by FM, who underwent percutaneous pulmonary vein angioplasty in Gansu Provincial Hospital from January 2018 to June 2020, were retrospective enrolled. The baseline characteristics, comorbidities, exercise capacity and hemodynamic data before and after treatment were compared, and the procedural related complications were evaluated. Results: A total of 30 patients ((64.3±7.1) years, 15 males) were included. Sixty-three pulmonary vein stenosis were treated by 32 percutaneous pulmonary vein angioplasty procedures. Forty-four stents were implanted in 41 pulmonary veins after balloon angioplasty, and the diameter of implanted stents was (8.3±1.2)mm. Balloon angioplasty was performed on 22 pulmonary vein stenosis, the mean balloon diameter was (4.2±2.1)mm. The pulmonary vein diameter increased from (2.6±1.3) to (6.6±2.6) mm (P<0.001) and the pressure gradient across the pulmonary vein stenotic segment reduced from 19 (12, 29) to 2 (0, 4) mmHg (1 mmHg=0.133 kPa) (P<0.001) immediately post procedure. The pulmonary vein flow grade was significantly improved compared with baseline (P<0.001). The most common operation related complications were lung injury (44.0% (11/25)) and hemoptysis (18.8% (6/32)), which did not need special treatment. During the 2.0 (1.3, 3.2) months follow-up, the WHO functional class was significantly improved (P<0.05), the 6-minute walking distance increased from (254.8±114.5) m to (342.8±72.4)m (P<0.05), the mean pulmonary arterial pressure decreased from (40.9±8.3) mmHg to (35.4±7.7) mmHg (P<0.01), 17 out of 19 patients with refractory pleural effusion experienced total remission during the follow-up period (P<0.001). CT pulmonary venography was repeated in 17 patients. The incidence of in-stent restenosis of pulmonary vein was 24.0% (6/25). Conclusions: Percutaneous pulmonary vein angioplasty is effective for the treatment of pulmonary vein stenosis caused by fibrosing mediastinitis. However, it's not so safe, procedural related complication should be paid attention to and the rate of in-stent restenosis is relative high during the short-term follow-up.

Chinese Herbal Prescription Against Esophageal Cancer： A Review / 中国实验方剂学杂志

Esophageal cancer is a type of upper gastrointestinal malignant tumor with a high degree of malignancy， strong invasion ability， and poor prognosis， which belongs to the category of "dysphagia" in traditional Chinese medicine （TCM）. In addition to tumor resistance， Chinese herbal prescription plays a role in sensitization. In light of information in literature， the syndrome elements of esophageal cancer include Qi stagnation， phlegm， Qi deficiency， blood stasis， and Yin deficiency. After clinical differentiation， the syndromes of esophageal cancer are divided into phlegm and Qi obstruction， Qi and Yin deficiency， fluid deficiency and heat accumulation， Qi deficiency and phlegm dampness， combined phlegm and heat， combined phlegm and stasis， combined heat toxin and stasis， healthy Qi deficiency and toxin accumulation， et al. Dabanxiatang， Qigesan， Xuanfu Daizhetang， Liujunzitang， Shashen Maidongtang， and Tongyoutang are the common clinical prescriptions， where Qigesan， Liu Junzitang， and Tongyoutang have been proved by in vitro and in vivo experiments to exert anti-esophageal cancer effect by directly inhibiting tumor cell proliferation， promoting apoptosis， affecting tumor microenvironment， regulating cell energy metabolism， and inhibiting angiogenesis. In addition， an increasing number of studies have been conducted on anti-esophageal cancer effect of Chinese herbal prescription by targeting non-coding single-stranded microRNA. The specific mechanisms of Da Banxiatang， Shenzhe Peiqitang， Xiao Xianxiongtang， Renshen Banxiatang， and Liushenwan have been scarcely reported despite good clinical efficacy. Wuzhuyu Tang and Tongguansan recorded in ancient books have been rarely applied in modern times. Therefore， the present study reviewed the special drugs and prescriptions mentioned in ancient TCM classics， the commonly used Chinese herbal prescriptions in modern clinical practice， and experimental research progress， to promote treatment methods of Chinese herbal prescriptions against esophageal cancer.

Dermatitis herpetiformis / 中华皮肤科杂志

Dermatitis herpetiformis is an autoimmune bullous disease associated with celiac disease, which occurs mostly in Caucasians carrying HLA-DQ2 or HLA-DQ8 alleles. Studies have shown a variety of antibodies against transglutaminase and other antigens in the serum of patients with dermatitis herpetiformis, and epidermal transglutaminase is an autoantigen. The occurrence of dermatitis herpetiformis not only is associated with genetics and gluten sensitivity, but also may be related to the imbalance of intestinal microbiome. Gluten-free diet and dapsone are still the main therapies for dermatitis herpetiformis. This review summarizes epidemiological features, pathogenesis, clinical manifestations, laboratory features, diagnosis and treatment of dermatitis herpetiformis.

Effect of Yinxing Mihuan Oral Solutionon P2RX7/NLRP3 Signaling Pathway in Depression Model Rats Induced by Isolation Combined with Chronic Unpredictable Mild Stress / 中国实验方剂学杂志

Objective:To explore the antidepressant mechanism of Yinxing Mihuan oral solution （YMO） by investigating its effect on depression model rats. Method:The depression rats were induced by isolation combined with chronic unpredictable mild stress （CUMS） and then randomly divided into model group， fluoxetine group （10 mg·kg^-1） and high-dose （618 mg·kg^-1） and low-dose （309 mg·kg^-1） YMO groups. A blank control group was also set up and ten rats were included in each group. Modeling lasted for 21 consecutive days， and rats were administered the 8th day after stimulation at a dose of 10 mL·kg^-1 for 14 days， except those in the blank control and model groups which were given distilled water. Afterward， the sucrose preference test， open field test， tail suspension test were carried out. The pathological changes of hippocampus in depression rats were observed after hematoxylin-eosin （HE） staining. The content of interleukin-1<italic>β </italic>（IL-1<italic>β</italic>）， interleukin-6 （IL-6） and tumor necrosis factor-<italic>α </italic>（TNF-<italic>α</italic>） in the hippocampus of rats in each group and the expression of NOD-like receptor 3 （NLRP3） and other proteins in its related activation signaling pathways were detected with multi-factor detection （Luminex） and Western blot. Result:After 14 days of continuous administration， compared with the blank control group， the model group witnessed significantly reduced sugar water consumption rate and the times of rearing and significantly prolonged cumulative time of immobility during tail suspension （<italic>P</italic><0.05， <italic>P</italic><0.01）. Compared with the model group， the fluoxetine group and the high-dose YMO group saw increases in the times of rearing， times of crossing and sugar water consumption rate and a significant decrease in the cumulative time of immobility during tail suspension （<italic>P</italic><0.05， <italic>P</italic><0.01）. The results of HE staining showed that the neurons in the hippocampus of rats in the high-dose YMO group were arranged in order and slightly loosened， without obvious microglia infiltration observed. The levels of IL-1<italic>β</italic>， IL-6 and TNF-<italic>α</italic> in the hippocampus of the model group increased significantly as compared with the blank control group （<italic>P</italic><0.05， <italic>P</italic><0.01）， and their content in the high-dose YMO group was significantly lowered in the comparison with the model group （<italic>P</italic><0.05， <italic>P</italic><0.01）. Molecular biology experiments demonstrated that compared with the results of blank group， the expression of purinergic receptor P2X7 （P2RX7）， NLRP3， apoptosis-associated speck-like protein （ASC）， Caspase-1 and IL-1<italic>β</italic> remarkably increased in the model group （<italic>P</italic><0.05， <italic>P</italic><0.01）. Additionally， the expression of P2RX7， NLRP3， ASC， Caspase-1 and IL-1<italic>β </italic>was significantly inhibited in the fluoxetine group and the high-dose YMO group compared with the model group （<italic>P</italic><0.05， <italic>P</italic><0.01）. Conclusion:YMO can improve the depression-like behaviors of rats induced by isolation combined with CUMS， and its mechanism of action is related to the regulation of the P2RX7/NLRP3 signaling pathway.

Current research situation of the characteristics of recurrent optic neuritis and the pathogenesis of optic neuritis / 中华眼底病杂志

Optic neuritis (ON) is one of the symptom of a central nervous system demyelinating,systemic or infectious disease.The pathogenetic mechanism of ON is still not completely clear,and its core is inflammation and immune that occurred in the optic nerve axons,and apoptosis of RGC was induced.Few patients experience recurrent episodes after treatment,presenting a remission-recurrence course of polyphasic disease,named recurrent ON (RON).Two forms of RON have been assigned:recurrent isolated optic neuritis,which is a chronic corticosteroid-dependent optic neuropathy with intermittent acute relapses,and recurrent isolated optic neuritis,which is a non-progressive relapsing ON without steroid dependence.Recurrence of ON causes cumulative damage to the optic nerve lesions and impaired visual signal transmission,thus causing irreversible damage to vision.Therefore,it is very important to have a deep understanding of the pathogenesis of ON and the clinical characteristics of RON,so as to better conduct clinical treatment.

The Lymphatic Drainage Pattern of Internal Mammary Sentinel Lymph Node Identified by Small Particle Radiotracer ((99m)Tc-Dextran 40) in Breast / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: The purpose of this study was to detect the lymphatic drainage pattern of internal mammary area and verify the concept of internal mammary sentinel lymph node (IM-SLN) in breast. MATERIALS AND METHODS: A small particle radiotracer ((99m)Tc-Dextran 40) was prepared and tested. (99m)Tc-Dextran 40 was injected into intraparenchyma at the sound breast by a modified radiotracer injection technique. Subsequently, dynamic single-photon emission computed tomography (SPECT), computed tomography (CT), and SPECT/CT combination images were performed to identify the radioactive lymph vessels and internal mammary lymph nodes (IMLNs). The direction of lymph drainage and the location of the IMLNs were identified in the SPECT/CT imaging. RESULTS: The radiochemical purity of (99m)Tc-Dextran 40 was > 95%. (99m)Tc-Dextran 40 could drainage into first, second, and third lymph node and the radioactive lymph node could be detected by the γ detector in the animal experiment. After (99m)Tc-Dextran 40 injecting into intraparenchyma, 50.0% cases (15/30) were identified the drainage lymphatic vessels and radioactive IMLNs by SPECT. The drainage lymphatic vessel was found from injection point to the first IMLN (IM-SLN) after 10.5±0.35 minutes radiotracer injection, and then (99m)Tc-Dextran 40 was accumulated into the IM-SLN. The combination imaging of SPECT/CT showed the second IMLN received the lymph drainage from the IM-SLN. The lymphatic drainage was step by step in the internal mammary area. CONCLUSION: The lymph was identified to drain from different regions of the breast to IM-SLN, and then outward from IM-SLN to other IMLN consecutively. It demonstrated the concept of the IM-SLN and provided more evidences for the application of internal mammary sentinel lymph node biopsy.

Comparison of the curative effects of laparoscopic surgery and traditional open surgery in the treatment of patients with stage Ⅰendometrial cancer and the influence on prognosis and quality of life / 中国基层医药

Objective To compare the curative effect of laparoscopic surgery and traditional open surgery in the treatment of patients with stage Ⅰ endometrial cancer and the influence on prognosis and quality of life . Methods 90 patients with stageⅠ endometrial cancer in the First People's Hospital of Xiangshan County from January 2010 to May 2011 were selected.According to the surgical method ,the patients were divided into study group and control group ,with 45 cases in each group .The patients in the study group were treated with laparoscopic surgery . The patients in the control group were treated with traditional open surgery .The surgery -related indicators , the prognosis and quality of life of the endometrial cancer patients in the two groups were compared and analyzed . Results Compared with the control group, the blood loss, operative time, flatus time, postoperative independent ambulation time,indwelling catheter time , and the average length of hospital stay of the study group were reduced significantly(t=97.58,17.06,9.51,8.24,12.16,8.09,all P<0.01).The incidence rate of complication in the study group was 13.33％,which was significantly lower than 31.11％ in the control group(χ2 =4.11,P<0.05). There were no statistically significant differences in the 5-year survival rate and local recurrence rate between the two groups (77.78％ vs.88.89％,35.55％ vs.26.67％,χ2 =2.00,0.58,all P>0.05).Compared with the control group,the scores of quality of life,included physiology,physiological functions,physical illness,general health, energy,social function,role emotional,and mental health in the study group were increased significantly (t=15.85, 11.17,13.86,22.47,15.20,11.32,10.78,20.67,all P<0.01).Conclusion Compared with traditional open surgery,laparoscopic surgery has a positive role in improving prognosis and quality of life of patients with stage Ⅰendometrial cancer .

Research advances in the association between transient receptor potential cation channel 6 and kidney disease / 中国当代儿科杂志

Transient receptor potential cation channel 6 (TRPC6) is a member of the transient receptor superfamily encoded by the TRPC6 gene and is widely expressed in tissues and organs of the human body, especially in the glomerular podocytes. TRPC6 interacts with various slit diaphragm (SD) proteins including podocin, nephrin, ACTN4, and CD2AP to maintain the normal structure and function of glomerular podocytes. Foot process fusion caused by podocyte damage due to various factors is the most important morphological change in kidney disease. This article reviews the biological function of TRPC6 and its effect on kidney disease.

Clinical, endoscopic, pathologic and prognostic factors of primary gastric lymphoma / 中华消化杂志

Objective To explore the clinical,endoscopic,pathologic and prognostic characteristics of primary gastric lymphoma (PGL) and to improve the level of diagnosis and treatment.Methods Sixtythree patients who were confirmed as PGL with operation and endoscopic biopsy pathology during January 2001 to December 2010 were retrospectively analyzed with respects of clinical,endoscopic and pathologic features.Survival analysis and prognosis were evaluated by kaplan-Meier and Cox proportional hazard model,respectively.Results In 63 PGL patients,the numbers of male and female were 40 and 23,respectively,and the average age was (59.8±13.3)years.The major symptoms were abdominal pain,abdominal distension,and gastrointestinal hemorrhage,accounting for 47.6 ％ (30/63),17.5 ％ (11/63),and 17.5 ％ (11/63),respectively.There were 39 (61.9 ％) PGL patients with endoscopic performance for ulcers,34 (54.0 ％) cases involved the gastric stomach antrum.The most immunohistochemistry analyses were diffuse large B-cell lymphoma (DLBCL) (71.4 ％,45/63),followed by mucosa-associated lymphoid tissue (MALT) lymphoma (22.2％,14/63).The frequency of Helicobacter pylori (H.pylori) positivity was lower in patients with DLBCL than that in patients with MALT lymphoma (37.8％(17/45) vs 10/14,x2 =4.872,P=0.027).The accumulate survival rates of one,three and five years were 74.6％,63.5％,55.6％,respectively,and the average survival time was (41.5±3.0) months (95％ confidence interval (CI) 35.7 to 47.4 months) in PGL patients.There was no difference in the average survival time between DLBCL patients treated with surgery combined chemotherapy and those with surgery or chemotherapy alone (38.33±5.21) months vs (50.17±8.98) months vs (41.39±4.40) months,P＞0.05).The patients diagnosed as DLBCL with H.pylori positive had longer average survival time than those with H.pylori negative ((51.90±4.30) months vs (33.30±4.50) months,t=-4.004,P＜0.01).Conclusions Male patients with PGL are slightly more than female.Abdominal pain is the most frequent symptom.Ulcerative lesions are the most common endoscopic demonstrations mostly at stomach sinus.DLBCL is the most pathologic characteristic.There is no significant difference in the survival rate between patients treated with surgery combined with chemotherapy and those treated with surgery or chemotherapy alone.

Intravascular Ultrasound Classification of Plaque in Angiographic True Bifurcation Lesions of the Left Main Coronary Artery / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Accurately, characterizing plaques is critical for selecting the optimal intervention strategy for the left main coronary artery (LMCA) bifurcation. Coronary angiography cannot precisely assess the location or nature of plaques in bifurcation lesions. Few intravascular ultrasound (IVUS) classification scheme has been reported for angiographic imaging of true bifurcation lesions of the unprotected LMCA thus far. In addition, the plaque composition at the bifurcation has not been elucidated. This study aimed to detect plaque composition at LMCA bifurcation lesions by IVUS.</p><p><b>METHODS</b>Fifty-eight patients were recruited. The location, concentricity or eccentricity, site of maximum thickness, and composition of plaques of the distal LMCA, ostial left anterior descending (LAD) coronary artery and, left circumflex (LCX) coronary artery were assessed using IVUS and described using illustrative diagrams.</p><p><b>RESULTS</b>True bifurcation lesions of the unprotected LMCA were classified into four types: Type A, with continuous involvement from the distal LMCA to the ostial LAD and the ostial LCX with eccentric plaques; Type B, with concentric plaques at the distal LMCA, eccentric plaques at the ostial LAD, and no plaques at the LCX; Type C, with continuous involvement from the distal LMCA to the ostial LCX, with eccentric plaques, and to the ostial LAD, with eccentric plaques; and Type D, with continuous involvement from the distal LMCA to the ostial LAD, with eccentric plaques, and to the ostial LCX, with concentric plaques. The carina was involved in only 3.5% of the plaques. A total of 51.7% of the plaques at the ostium of the LAD were soft, while 44.8% and 44.6% were fibrous in the distal LMCA and in the ostial LCX, respectively.</p><p><b>CONCLUSIONS</b>We classified LMCA true bifurcation lesions into four types. The carina was always free from disease. Plaques at the ostial LAD tended to be soft, whereas those at the ostial LCX and the distal LMCA tended to be fibrous.</p>

Analysis on Research Status of Integration of the Body and the Spirit Based on Literature / 中国中医药信息杂志

Objective To analyze research literature about integration of the body and the spirit; To understand the research status of this classical theory.Methods Relevant articles about integration of the body and the spirit in CNKI, Wanfang Data, VIP-Chinese Scientific and Technological Journal Data were searched, and bibliometric analysis with NoteExpress3.0, Bicomb2.0 and SPSS19.0 software was used to analyzed the data.ResultsA total of 156 efficient articles were retrieved. The number of published articles increased, but the core author group had not yet been formed. The number of cited articles was low. The study hot spots mainly focused on TCM constitution, the subject of health preservation, TCM basic theories, and psychosomatic medicine.Conclusion Domestic studies on integration of the body and the spirit are still in the initial stage. Research number should be increased, meanwhile, innovation and quality should be emphasized.

MicroRNA-10a expression in FAB different subtype of acute myeloid leukemia and its relationship with drug resistance / 中国实验血液学杂志

<p><b>OBJECTIVE</b>This study was to investigate the expression of miR-10a in the different FAB subtype of acute myeloid leukemia (AML) and its relationship with drug resistance.</p><p><b>METHODS</b>Forty de novo patients with AML, 16 patients with non-malignant hematologic disease and three AML cell lines HL-60, U937 and HL-60/ADR were enrolled in this study, the MiR-10a expression in bone marrow mononuclear cells of above-mentioned patients and 3 AML cell lines was detected by TaqMan RT-PCR. The correlation of miR-10a with clinicopathological factors of AML patients was analyzed.</p><p><b>RESULTS</b>The miR-10a expression level in HL-60 cell line was higher than that in U937 cell line (P = 0.039). And its expression level in de novo AML patients was higher than that in patients with non-malignant hematologic disease (P < 0.01). FAB-AML-M3 patients exhibited higher expression of miR-10a than that in M1, M2 and M4 (P < 0.05); HL-60/ADR cell line showed higher miR-10a expression than that in HL-60 cell line (P < 0.01) . Except M3, the patients without CR (non-CR) after the first cycle of chemotherapy showed a higher level of miR-10a as compared with CR patients (P < 0.01).</p><p><b>CONCLUSION</b>The high expression of miR-10a may be closely related to over-proliferation of promyelocyte and drug resistance of acute myeloid leukemia cells, except M3.</p>

Comparison and analysis of SNV results: detected by transcriptome sequencing technology on initial diagnosis and remission stage of a patient with AML-M2 / 中国实验血液学杂志

This study was aimed to further clarify the pathogenesis of acute myeloid leukemia(AML), and to forecast new somatic mutations related with leukemia. The peripheral blood samples on initial diagnosis and remission stage of a patient with partial differentiated AML(AML-M2) were sequenced by high throughput transcriptome sequencing technology. The single nucleotide variation (SNV) which possibly related with pathogenesis of leukemia was screened through comparison of the expressed genes on initial diagnosis and after remission. The results showed that the Reads distributed uniformly in genome and covered completely, detecting most expression genes. by screening the SNV, a total of 29881 mutations were discovered, including 28113 germline mutations and 752 individual mutations. Among them, 11 acquired mutations (P < 0.05) in coding regions were got, including ZRSR1, MLXIP, TLN1, LAP3, HK3. It is concluded that the high throughput sequencing as an unbiased new method can find new tumor-related mutations. MLXIP may be a new molecular marker of AML-M2.

Study on early changes of related hormones in different pregnancy outcomes / 中国综合临床

Objective To explore the rules of early pregnancy related hormone changes in different pregnancy outcomes.Methods Three hundred and fourteen women at early pregnancy women were selected as our subjects.And they were followed up until 3 months of gestation.chemiluminescence analysis was used to test serum human chorionic gonadotropin (β-HCG),progesterone,estradiol and testosterone levels all pregnant women.According to the pregnancy outcome,clinical symptom and body mass index,all subjects were divided into normal and abnormal group.Results Among 314 cases of early pregnancy women,the normal pregnancy group was 53.18％ (167/314) and the abnormal pregnancy were 46.82％ (147/314).While in abnormal pregnancy group,women with the threatened abortion and continues pregnancy were 102 cases(69.39％),with inevitable abortion group were 29 cases (19.73％),and with embryos diapauses were 16 cases (10.88％).Serum estradiol level of cases in normal pregnancy group was (3104.6 ± 1507.1) pmol/L,higher than that in threatened abortion and continues pregnancy,threatened abortion group and inevitable abortion group((2 361.0 ±1 057.9) pmol/L,(1 250.0 ±624.5) pmol/L,(1 465.7 ±724.4) pmol/L)),and the differences were statistically significant(P ＜ 0.05).In normal pregnancy group,the level of serum β-HCG,estradiol and testosterone were positively correlated with gestational age (r =0.57,0.62 and 0.24 ; P ＜ 0.05).However,progesterone levels had no correlation with gestational age (r =0.15,P =0.06).Conclusion Dynamic detection of early pregnancy can guide clinicians to colytic therapy.

Effect and safety of butyl phthalide sequential treatment in cerebral infarction of branch sclerosis of arterial congee appearance / 中国综合临床

Objective To value the effect and safety of butyl phthalide sequential treatment in cerebral infarction of branch sclerosis of arterial congee appearance. Methods Sixty patients with acute cerebral infarction were randomly divided into treated group( n = 31)and control group( n = 29). According to the condition of illness,all patients were given aspirin,atorvastatin calcium,and the injection of ozagrel sodium intravenous;controlled the blood pressure,blood sugar,blood lipid,and treated complications posstively;take the early rehabilitation of nerve treatment afte the illness was in stable condition. Butyl phthalide was used in the patients of treated group(100 ml,twice per day,intravenous drip,during 14 days period therapy,and then 0. 2 g oral,third per day),besides the routine therapy. The degree of neural function defect score( NIHSS)and activities of daily living score(BI)between two groups were observed before and after treatment. Corresponding adverse consequences were recorded. Results Compared with pretreatment,the NIHSS of postreatment at the 14th day in treat and control groups were decreased(treated group:(4. 36 ± 3. 11)vs.(11. 42 ± 3. 20);control group:(6. 12 ± 2. 67)vs.(11. 64 ± 3. 43),P < 0. 05,and the treated group was significantly lower than control group(F inner groups = 2. 125,P < 0. 01;F between groups = 18. 63,P < 0. 01;F cross groups = 25. 34,P< 0. 01;P < 0. 05). The BI of postreatment in two group were increased(treated group:(86. 72 ± 8. 44)vs. (26. 54 ± 13. 36);control group:(75. 96 ± 9. 86)vs.(26. 38 ± 13. 02)),and the treated group was significantly lower than control group(F inner groups = 29. 27,P < 0. 01;F between groups = 32. 48,P < 0. 01;F cross groups= 42. 41,P < 0. 01;P < 0. 05). There was no the adverse reactions. Conclusion Butyl phthalide sequential treatment can improve the NIHSS and BI of cerebral infarction of branch sclerosis of arterial congee appearance and have a better therapy effect.

Influence of veneer application on failure behavior and reliability of lithium disilicate glass-ceramic molar crowns / 中华口腔医学杂志

<p><b>OBJECTIVE</b>To evaluate the influence of veneer application on failure behavior and reliability of lithium disilicate glass-ceramic (LDG) crowns of maxillary first molar, and thus to reveal the failure mechanism of bilayered LDG crowns.</p><p><b>METHODS</b>Twenty-six LDG maxillary first molar crowns were fabricated in a dental laboratory using IPS e. max Press or IPS e. max Press/Ceram. The crowns were randomly assigned into two groups (with or without veneer application) with thirteen in each group. The crowns were cemented on composite resin dies. After storage in water for one week, the sliding-contact fatigue test was performed by sliding the steatite ceramic ball indenter (6 mm in diameter) from central fossa up to the lingual surface of disto-buccal cusp, cyclic loaded 1 200 000 times with a weight of 100 N at 2 Hz with a fatigue chewing simulator. Survived specimens were subjected to single-load-to-fracture testing using a steatite ceramic ball of 6 mm in diameter at a cross-head speed of 0.5 mm/min in a universal testing machine. Fracture load values were recorded and analyzed with t test. Weibull modulus was calculated to evaluate structure reliability. Fractographic analysis was carried out to determine fracture modes of the failed specimens by a stereomicroscope and a scanning electron microscope (SEM).</p><p><b>RESULTS</b>Statistical analysis results indicated a significant difference of the fracture load values between monolithic group [(2071.23 ± 397.05) N] and bilayered group [(1483.41 ± 327.87) N] (P < 0.001). Monolithic and bilayered groups present similar Weibull modulus (95% confidence interval) as 6.15 (5.15 ∼ 7.15) and 5.54 (4.01 ∼ 7.08) respectively, with no significant difference (the confidence bounds overlapped with each other). Bulk fracture initiating from the middle of oblique ridge of the first maxilla molar was the primary failure mode of monolithic/bilayered LDG crowns. Crack propagation initiated from core-veneer interfacial defects was another major failure mode of bilayered all-ceramic crowns.</p><p><b>CONCLUSIONS</b>Veneer application has some influence on fatigue failure of LDG crowns, but shows no effect on structure reliability. Accumulated damage combined with tensile stress concentration on the surface of veneer layer and defects within core-veneer interface lead to initiating of cracks. The mechanical property of veneering materials should be increased, and procedure of veneer application should be standardized and improved in order to reduce the failure rate of LDG molar crowns.</p>

Significance of miR-155, miR-34a and miR-30a expression in diffuse large B-cell lymphoma / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To determine the expressions of miR-155, miR-34a and miR-30a in diffuse large B-cell lymphoma (DLBCL) and to explore their potential correlation with clinicopathological characteristics.</p><p><b>METHODS</b>The expression level of miR-155, miR-34a and miR-30a in 46 DLBCL samples were determined with TaqMan real-time polymerase chain reaction. Interphase fluorescence in situ hybridization (I-FISH) was performed to detect MYC and p53 genes' status, and immunohistochemistry (Envision method) was used to evaluate the expression of CD3, CD10, CD20, BCL-6 and MUM-1 in DLBCL. The DLBCLs were classified into germinal center B cell-like (GCB) and non germinal center B cell-like (non-GCB) subtypes according to Hans' criteria.</p><p><b>RESULTS</b>Compared with normal controls, miR-155 expression level was significantly higher in DLBCL. The expression level of miR-155 in non-GCB type was higher than that in GCB type. It was shown that the patients with MYC rearrangement had lower expression level of miR-155 than the negative controls. Compared with p53 normal group, the expression level of miR-34a was significantly lower in p53 deletion group. It was also shown that the patients with BCL-6 protein expression had lower expression of miR-30a compared with the negative group.</p><p><b>CONCLUSION</b>miR-155 expression level is different in normal controls, DLBCL and patients with subtype DLBCL. It therefore has a diagnosis value for DLBCL. miR-34a is of great prognostic significance. miR-155, miR-34a and miR-30a may be potential therapy targets for DLBCL.</p>

Clinical study on platelet engraftment by thrombopoietin in patients with hematological malignancies after allogeneic hematopoietic stem cell transplantation / 中华血液学杂志

<p><b>OBJECTIVE</b>To evaluate the efficacy and safety of thrombopoietin (TPO) on platelet engraftment in hematological malignancies patients after allogeneic haematopoietic stem cell transplantation (allo-HSCT).</p><p><b>METHODS</b>One hundred and twenty patients were enrolled in a multicenter, open-label, randomized, controlled clinical trial, and were randomized into 4 treatment groups following allo-HSCT. Group A was the control arm without TPO, while group B, C and D were trial arms with received 300 U×kg(-1)×d(-1) of TPO starting from day +1, +4 and +7, respectively. A total of 89 cases were evaluated, of which 22 cases in group A, 23 in group B, 20 in group C and 24 in group D. Efficacy evaluation (the time of platelet engraftment, the number of platelet transfusion) and safety evaluation \[adverse events, routine blood tests, liver and renal function, coagulation function and occurrence of graft-versus-host disease (GVHD)\] were observed.</p><p><b>RESULTS</b>The median platelet engraftment time in experimental groups (groups B, C and D) were on day (13.17 ± 2.89), day (12.15 ± 2.08), day (12.33 ± 1.76), respectively, and that in control group was on day (14.82 ± 5.05). There was statistically significant difference between two groups (P = 0.029), There were no statistically significant difference in the average amount of platelet transfusion, platelet engraftment time, and platelet nadir value among the 3 experimental groups. No significant adverse events were observed in experimental groups.</p><p><b>CONCLUSIONS</b>TPO administration following allo-HSCT for patients with hematologic malignancies appears to shorten platelet engraftment time. TPO given starting from day +7 is effective and safe.</p>