2018年 · 第57卷第05期

Hematopoietic stem cell transplantation is an emerging field in the development of clinical medicine, with a history of only about half a century. However, in the past 10 years, the development of this transplantation technology has spread all over the world, and it has become an effective method for radically curing malignant hematological tumors, bone marrow failure diseases and other refractory diseases. The clinical application of allogeneic hematopoietic stem cell transplantation (allo-HSCT) in China is later than that in developed countries, and began in the early 1980s. In the past 10 years or so, China's allo-HSCT has developed by leaps and bounds after solving the problem of lack of donor sources. It has led the trend of international transplantation development in the field of human leukocyte antigen (HLA) hemiconsistent hematopoietic stem cell transplantation, and has become the most important at home and abroad. One of the most important HLA hemiconsistent transplantation methods. In this issue, Professor Ren Hanyun of the First Hospital of Peking University was invited to write an article "The characteristic development of hematopoietic stem cell transplantation in China", reviewing the difficult entrepreneurial history of allo-HSCT in China for more than 30 years. I believe that its continuous innovation and breakthrough of allo-HSCT key technical difficulties one by one will also have certain reference significance for other clinical disciplines in China to build a treatment system with Chinese characteristics.

Hematopoietic stem cell transplantation is an emerging field in the development of clinical medicine, with a history of only about half a century. However, in the past 10 years, the development of this transplantation technology has spread all over the world, and it has become an effective method for radically curing malignant hematological tumors, bone marrow failure diseases and other refractory diseases. China's isogenic and autologous hematopoietic stem cell transplantation is in synchronization with the international community, but its development is relatively slow. The clinical application of allogeneic hematopoietic stem cell transplantation (allo-HSCT) in China is later than that in developed countries, and began in the early 1980s. In the past 10 years or so, China's allo-HSCT has developed by leaps and bounds after solving the problem of lack of donor sources. It has led the trend of international transplantation development in the field of human leukocyte antigen (HLA) hemiconsistent hematopoietic stem cell transplantation, and has become the most important at home and abroad. One of the most important HLA hemiconsistent transplantation methods. Looking back on the development history of allo-HSCT in China for more than 30 years, it can be divided into initial stage, development stage and leading stage.

By activating traditional technology and using new thinking methods, critical ultrasound gives critical care doctors a pair of "perspective" eyes, interprets critical care medicine from a new angle, and integrates its own characteristics into the diagnosis, monitoring and treatment of critical illness. With the widespread application of critical ultrasound, critical care doctors are facing new problems. How to correctly operate and obtain parameters? How to correctly interpret and apply it reasonably? How to further develop critical ultrasound and so on^[1]。

Cryptococcal meningitis is a common and refractory central nervous system infection, with high rates of mortality and disability. The experts of the Society of Infectious Diseases of Chinese Medical Association have reached this consensus after a thorough discussion. Based on the current situation of cryptococcal meningitis in China, the management of cryptococcal meningitis includes 6 aspects: introduction, microorganism identification, clinical manifestations and diagnosis, principles of antifungal therapy, treatment of refractory and recurrent meningitis, treatment of intracranial hypertension. There is not a separate consensus on human immunodeficiency virus (HIV) infection in patients with cryptococcal meningitis. This article focuses on different antifungal regimens and reducing intracranial pressure by reference to Infectious Disease Society of America (IDSA) guidelines. The importance of early diagnosis, combined long-term antifungal therapy, control of intracranial hypertension are emphasized.

The patient was a 72-year-old male. He complained of fever after being cold on January 29, 2017, and his self-measured body temperature was as high as 39.6℃, accompanied by chills and cough. On February 2, 2017, the patient developed blood in sputum and shortness of breath. On the morning of February 3, the patient went to the fever clinic of our hospital for blood test routine: white blood cells 2.7×10⁹/L, neutrophils 1.71×10⁹/L, lymphocytes 0.87×10⁹/L, hemoglobin 112 g/L, platelets 26×10⁹/L, high-sensitivity C-reactive protein 88.0 mg/L; Chest CT showed patchy, punctate density-increased shadows of the right upper middle lung, constituting a grid-like interstitial lesion with small patchy consolidation shadows (Figure 1）。 The patient denied a history of contact with poultry, and considered the need to further rule out the possibility of hematological diseases complicated with infection, and admitted the patient to the hematology department. The patient was previously in good health. Physical examination: body temperature 39.3℃, pulse 97 beats/min, blood pressure 119/55 mmHg (1 mmHg =0.133 kPa), blood oxygen saturation 94%, clear consciousness, poor spirit, no cyanosis of the lips, no yellowing staining of the skin and sclera of the whole body, no palpable swelling of superficial lymph nodes, slightly thick breathing sounds in both lungs, no obvious dry and wet rales, uniform heart rhythm, no obvious murmur in each valve area, soft abdomen, no swelling of the liver and spleen under the costs, no tenderness in the whole abdomen, no swelling of both lower limbs, bilateral Babinsky sign (-). Re-examination of blood routine on the afternoon of February 3rd: white blood cells 2.0×10⁹/L, neutrophils 1.50×10⁹/L, lymphocytes 0.40×10⁹/L, hemoglobin 104 g/L, platelets 15×10⁹/L, high-sensitivity C-reactive protein 67.0 mg/L. Bone marrow puncture was performed, and the smear showed decreased nucleated cell proliferation, increased proportion of mature monocytes and mature plasma cells, moderate number of megakaryocytes, and phagocytic reticulocytes (Figure 2）。 After admission, the patient's fever persisted. On February 3, the patient was tested by flow cytometry of cell inflammatory factor spectrum when he had chills. The results showed that IL-2 was 5.3 ng/L (reference value: 1.1~9.8 ng/L), IL-4 was 4.8 ng/L (reference value: 0.1~3.0 ng/L), IL-6 was 157.5 ng/L (reference value: 1.7~16.6 ng/L), IL-10 was 307.5 ng/L (reference value: 2.6~4.9 ng/L), tumor necrosis factor α was 43.1 ng/L (reference value: 0.1~5.2 ng/L), and gamma interferon was 231.6 ng/L (reference value: 1.6~17.3 ng/L). Serum soluble IL-2 receptor (sCD₂₅) 3678 U/ml (reference value: 223-710 U/ml); Serum ferritin 6 057.5 μ g/L (reference: 21.8-374.0 μ g/L). Cefoperazone sodium/sulbactam sodium injection 0.2 g once/8 h, moxifloxacin injection 0.4 g once/d combined with voriconazole tablets 0.2 g once/12 h were administered to fight infection. From February 4 to February 5, the patient's condition deteriorated rapidly, mainly manifested by uncontrollable fever and shortness of breath, the oxygen saturation level dropped to 78%, and blood gas analysis suggested type I respiratory failure. After methylprednisolone injection (40 mg once/8 h), the patient's fever and shortness of breath did not improve, and the oxygen saturation level increased to about 90% after non-invasive ventilator-assisted ventilation.

The patient was a 58-year-old female. He was admitted to hospital for 2 years due to decreased activity tolerance and edema of both lower limbs. In the second half of 2015, the patient experienced a decrease in activity tolerance without obvious trigger, and felt chest tightness and shortness of breath after walking 300 m on the flat ground and up the next floor. After that, symmetrical depressed edema of both lower limbs gradually appeared, and he could lie down at night without paroxysmal dyspnea at night. In 2016, activity tolerance further decreased, and chest tightness and choking occurred after walking 100 m on flat ground. N-terminal pronatriuretic peptide B (NT-proBNP) 2 033~7 566 ng/L and troponin T 0.126~0.187 mg/L were measured in other hospitals; Echocardiography showed biatrial enlargement, mild regurgitation of each valve, mild pulmonary hypertension (44 mmHg, 1 mmHg =0.133 kPa), and normal left ventricular ejection fraction (LVEF); Coronary angiography showed no abnormalities. Weight loss of 7 kg during the course of the disease. Past history: Sjögren's syndrome (SS) was diagnosed 5 months ago due to dry mouth and dry eyes; Hoarseness for 4 years, aggravated in the past 1 year. Physical examination at admission: blood pressure 92/56 mmHg, hoarseness, bilateral jugular dilatation, heart rate 70 beats/min, uniform rhythm, grade 2 systolic murmur in the auscultation area of mitral and tricuspid valves, and mild concave edema of both lower limbs. Serum IgG lambda was positive, urine free lambda was positive, and bone marrow smear and biopsy were roughly normal. Antinuclear antibody (ANA) (+) S1:160, anti-SSA antibody (double diffusion method) 1:4. Heart-related tests: hypersensitivity troponin I 0.15 μ g/L, NT-proBNP 3 797 ng/L; Electrocardiogram showed sinus rhythm, first degree atrioventricular block, complete right bundle branch block, II, III, aVF lead QS wave (Figure 1）； Echocardiography: Enlargement of both atria and right ventricle, uniform thickening of left ventricular wall about 11-12 mm, LVEF 59%, thickening of mitral and tricuspid valves, poor tricuspid alignment, moderate to severe tricuspid regurgitation (Figure 2), pseudonormalization of left ventricular relaxation, pulmonary systolic pressure 49 mmHg, small pericardial effusion; Cardiac magnetic resonance imaging (MRI): slight thickening of the ventricular septum and atrial septum, diffuse strip-like delayed enhancement of the myocardium in the basal segment and middle segment of the left ventricle, partly in the subendocardium and middle layer of the myocardium, thickening and delayed enhancement of the right ventricular wall, atrial septum, mitral and tricuspid valves and aortic valves (Figure 3）。 The rupture time of the tear film in both eyes was 2 s, the saliva flow rate was 0.08 ml/min, and the parotidography showed punctate dilatation of the duct terminal. Electronic laryngoscope: Both vocal cords were not flat and closed with gaps. Because of the high risk of vocal cord biopsy under general anesthesia, it was not performed. Pathology: rectal mucosa Congo red (+), potassium permanganate Congo red (+) (Figure 4）； Local acinar atrophy in the small salivary gland tissue, slight dilatation of some small ducts, focal lymphocyte and plasma cell infiltration in the interstitium and around the ducts, Congo red (±), potassium permanganate Congo red (±). The diagnosis of immunoglobulin light chain type (AL type) amyloidosis, cardiac involvement is definite, and Sjogren's syndrome is combined. Therapeutically, bortezomib, cyclophosphamide and dexamethasone were given chemotherapy to improve heart failure with diuresis, and oral hydroxychloroquine was given to treat SS.

The patient was a 37-year-old male. Due to nausea and vomiting for 2 days, I went to our hospital for treatment. At that time, there was no chest tightness, chest pain, no breathing difficulty, no fear of cold and fever and other discomfort. Electrocardiogram showed changes in sinus rhythm and T wave, and blood routine showed white blood cell count 14.40×10⁹/L, neutrophil count 11.36×10⁹/L, CRP>90 mg/L. Physical examination: temperature 36.6 ℃, pulse 72 beats/min, breathing 18 beats/min, blood pressure 196/112 mmHg (1 mmHg =0.133 kPa). The mind is clear, the skin and mucous membranes are free of yellowing stain. The breathing sounds of both lungs were clear, and no dry and wet rales were heard. The heart rhythm was uniform, the heart sounds were normal, and no pathological murmur was heard in each valve area. The abdomen was flat, there was tenderness in the upper abdomen, no rebound pain, no palpable mass, no palpable subcostal liver and spleen, and negative Murphy's sign. There was no edema in both lower limbs. There were no obvious abnormalities in the nervous system. He was in good health in the past and denied a history of hypertension and coronary heart disease. According to the symptoms, signs and auxiliary examinations of the patient, acute gastroenteritis was first considered for diagnosis, and temporarily observed in the emergency department, and symptomatic and supportive treatments such as gastric protection, antiemetic and fluid rehydration were given in treatment.

August 2017, Top International Journal of HematologyBloodA clinical study "Application of recombinant human thrombopoietin in the management of pregnant patients with immune thrombocytopenia" led by Professor Hou Ming of Qilu Hospital of Shandong University and jointly completed by eight domestic centers was published [Kong Z, Qin P, Xiao S, et al. A novel recombinant human thrombopoietin therapy for the management of immune thrombocytopenia in pregnancy. Blood, 2017, 130 (9): 1097-1103.]. This study is a multicenter, open-label, single-arm study that is the first to evaluate the efficacy and safety of recombinant human thrombopoietin (rhTPO) in pregnant patients with immune thrombocytopenia (ITP).

Ventilator-associated pneumonia (VAP) refers to pneumonia in patients with tracheal intubation or tracheotomy 48 hours after mechanical ventilation, and pneumonia within 48 hours after withdrawal and removal of tracheal tube remains VAP. VAP is the most common nosocomial infectious disease in ICU. Its incidence varies greatly from region to region (6% to 52%), and the mortality rate is about 14% to 50%. If it is multidrug-resistant bacterial infection, the mortality rate can be as high as 76%. In addition, the length of stay in ICU of VAP patients is prolonged, and the hospitalization cost is significantly increased. Therefore, early recognition of VAP is key to improved prognosis. However, the diagnosis of VAP has always lacked the "gold standard", so various diagnostic methods, including biomarkers and clinical scores, have emerged. Procalcitonin (PCT) is normally produced by thyroid C cells and rapidly cleaves into calcitonin and other products after production. The PCT value of healthy people is very low, generally not more than 0.1 ng/ml, but in the case of bacterial infection, solid cells throughout the body will continue to secrete PCT, and due to the lack of corresponding lyase, PCT increases rapidly. Multiple studies have shown that PCT has some diagnostic value in bacterial infections. clinical pulmonary infection score (CPIS) combines a variety of clinical signs and symptoms, chest X-rays and laboratory indicators to comprehensively assess the presence of pulmonary infection. When the CPIS is ≥6 points, the diagnosis of VAP may be considered clinically. Studies have shown that the combination of PCT and CPIS can significantly improve the specificity of early diagnosis of VAP, effectively exclude false positives in diagnosis, and has certain clinical value for the diagnosis of VAP. Therefore, PCT and CPIS have become the two most common indicators for the diagnosis, treatment monitoring and prognosis evaluation of VAP. However, in specific clinical practice, how to better understand its value and limitations, through the specific application and analysis of two clinical cases, it provides a reference for first-line clinicians to make more reasonable applications.

myeloid sarcoma (MS) is a tumor formed by infiltration of myeloid immature cells in extramedullary tissues. Burns first reported MS in 1811. Because of the oxidation of peroxidase, the fresh section of the tumor can appear green, and named it chloroma. But not all MS was green, and the tumor was found under the microscope to be composed of immature granulocytes and shaped like a sarcoma, so Rappaport named it granulocytic sarcoma in 1966. In 1988 Davey proposed the concept of extramedullary medullary cell tumor (EMT). In 2008, the World Health Organization (WHO) identified MS as one of the subtypes of myeloid tumors and acute leukemia. MS has various clinical manifestations and is easily misdiagnosed as lymphoma, sarcoma and other diseases. Among them, isolated MS is very rare, with an incidence of about 2/1 000 000. Early clinical diagnosis is very challenging^[1]。 When a mass appears in any part of the body, especially with a history of myeloid tumors, it is necessary to be highly alert to the possibility of MS. The latest progress in the definition, classification, diagnosis and treatment of MS is briefly described.

Statins are currently the basic drugs for the treatment of dyslipidemia such as hypercholesterolemia. Following simvastatin, atorvastatin, rosuvastatin, etc., a new generation of fully synthetic competitive hydroxymethylglutarate monoacyl-coenzyme A (HMG-CoA) reductase inhibitor pitavastatin was launched in October 2003 Approved for marketing in Japan, and approved in China and the United States in 2009 and 2010, respectively, for the treatment of primary hypercholesterolemia and familial hypercholesterolemia. There are certain differences in statins among different races, and pitavastatin, which is commonly used in Asian populations, has higher guiding significance for clinical practice in China. Therefore, the clinical evidence of pharmacokinetics, lipid-lowering efficacy, prognostic endpoints and safety of pitavastatin in East Asian populations (Japan, China, South Korea, etc.) is reviewed to help clinicians comprehensively understand and rationally apply pitavastatin.

irritable bowel syndrome (IBS) is a common functional bowel disease. Patients are mainly manifested by abdominal pain and abdominal discomfort, accompanied by changes in defecation frequency and fecal characteristics. IBS is considered to be a disease with lack of evidence of organic changes, and its pathogenesis has not been fully elucidated. Recent studies have found that IBS patients have immune system activation, including the decline of innate immune defense function and the activation of adaptive immune system. The role of immune factors in the pathogenesis of irritable bowel syndrome is reviewed.