2015年 · 第95卷第10期

High-dose therapy/autologous hematopoietic stem cell transplantation (HDT/AHSCT) is an important method in the treatment of malignant solid tumors. In 1978, Appelbaum et al. of the National Cancer Institute of the United States^[1]It is reported for the first time that HDT combined with autologous bone marrow transplantation (ABMT) in the treatment of Burkitt lymphoma can cure some patients with poor efficacy of conventional chemotherapy in the past, thus stimulating the increasing application of HDT/AHSCT in the treatment of malignant solid tumors. Since 1989, the Department of Internal Medicine, Cancer Hospital, Chinese Academy of Medical Sciences, completed the first case of ABMT therapy in the treatment of malignant lymphoma patients in China^[2,3]This technology has gone through a 25-year history in China and has developed into a mature treatment method. The Cancer Hospital of the Chinese Academy of Medical Sciences alone has applied this technology to treat more than 300 patients with various malignant solid tumors. Related research progress has made the indications for treatment clearer, and the safety and effectiveness of treatment have been continuously improved. 2015 marks the 100th anniversary of the founding of Chinese Medical Journal. This article will systematically review the development of AHSCT technology in the treatment of malignant solid tumors in my country in the past 25 years to express congratulations.

multiple myeloma (MM) has become the second most common malignant tumor in the hematological system. Like other malignant tumors, the vast majority of MM patients are still incurable. How to improve the long-term survival of patients, including prolonging the progression-free survival (PFS) time and overall survival (OS) time, has become the treatment goal of MM. MM has many prognostic factors such as ISS stage, renal function, cytogenetics, extramedullary infiltration^[1]et al., closely related to PFS and OS is the quality of response, and sustained complete response (CR) is an important factor in obtaining long-term PFS and OS. The CR/near-complete response (nCR) rate of MM patients who have previously used traditional chemotherapy drugs is only about 5%. The application of high-dose melphalan combined with autologous hematopoietic stem cell transplantation (HDT-ASCT) increased the CR/nCR rate to 10% ~20% in MM patients^[2,3]While also significantly improving the prognosis of patients. Recently, with the application of new drugs such as bortezomib, thalidomide and lenalidomide in MM, the CR/nCR rate of newly diagnosed patients can reach 30% ~40%^[3,4]The CR/nCR rate of relapsed/refractory patients can also reach 10% ~20%. Similarly, these drugs significantly delay the relapse of MM patients and improve OS. Therefore, striving for CR has become one of the goals of MM treatment. However, the study found that even the prognosis of patients with CR is different. Although some patients reach CR, they relapse and progress in a short time. Therefore, even in CR patients, there may be differences in the depth of remission. For example, in chronic myeloid leukemia, in addition to complete hematological remission, there are cytogenetic remission and molecular genetic remission. The deeper the remission, the less likely it is to relapse., the better the prognosis. In MM, as the response rate increases, the sensitivity of disease surveillance means also increases: strictly meaningful CR (sCR) appears in the efficacy judgment criteria of the International Myeloma Working Group (IMWG); MRI assessment of tumor activity in the lesion can also improve the prognosis of CR; Other, more sensitive methods are also used to detect the presence of minimal residual disease (MRD).

The prevalence of obesity hypopnea syndrome (OHS) in adults is about 0.6%^[1]Acute respiratory failure and/or heart failure often caused by respiratory tract infections are admitted to hospital, with critical illness and high prevalence and mortality^[1]。 Non-invasive ventilation is the first choice of treatment for OHS complicated with acute respiratory failure and heart failure, but the failure rate of severe OHS patients is high. Most of the cases reported at home and abroad failed the initial non-invasive ventilation treatment, and finally had to switch to invasive ventilation^[2,3]。 OHS patients are difficult to perform invasive ventilation due to extreme obesity, and there are many complications. Three typical cases successfully treated by non-invasive ventilation in our department are analyzed as follows.

The patient was a 64-year-old female. He came to the Second People's Hospital of Wuxi City, Jiangsu Province for examination due to conscious fatigue for 2 days. B-mode ultrasound (B-ultrasound) showed hypoechoic occupation in the right lobe of the liver, and he was admitted to hospital on May 15, 2014. Admission diagnosis: "right liver tumor". Admission examination: normal body temperature, no emaciation, no yellowing stain of sclera, and no palpable swelling of superficial lymph nodes throughout the body. Abdominal B-ultrasound showed that the liver was regular in shape, the capsule was smooth, the echoes of the parenchyma were evenly distributed, the vascular texture was clearly displayed, and the movement was normal. A mixed echoic area was visible in the right lobe of the liver, about 54 mm ×48 mm in size, with regular shape and clear boundaries. There seemed to be a hypoechoic halo at the edge, and the internal echoes were not uniform. Color Doppler flow imaging (CDFI): short stripes of blood flow signals were visible inside. After intravenous pellet injection of 2.4 ml of contrast medium Sono Vue, the whole mass was enhanced and developed earlier than the liver parenchyma at 15 s. The intensity of contrast medium reached its peak at 23 s, which was significantly higher than that of the peripheral liver parenchyma. The time of decline of contrast medium in the mass was the same as that in the liver parenchyma. After continuous observation for 4 min, the mass showed hypoechoic area (Figure 1)。 Abdominal CT showed that the shape of the liver was normal and the size was within the normal range. The right lobe of the liver showed a low-density focus with a size of about 4.9 cm ×6.1 cm. The arterial phase of enhanced scan was significantly enhanced, the density of the portal phase and the delayed phase was decreased, the intrahepatic bile duct was not dilated, and the retroperitoneal lymph nodes were not significantly enlarged. There was no sign of effusion in the abdominal cavity. Laboratory tests showed that alpha-fetoprotein (AFP), carbohydrate protein CA-125, CA19-9, CA72-4, CEA and ferritin were normal, and hepatitis B core antibody (HBC-Ab), E antibody (HBE-Ab), E antigen (HBE-Ag) and surface antigen (HBS-Ag) were negative, and hepatitis B surface antibody (HBS-Ab) was positive. Hepatitis C antibody, hepatitis E antibody, HIV antibody, Treponema pallidum antibody, serum anti-Toxoplasma gondii and various virus antibodies were all negative. Blood routine: white blood cell count 10.9×10⁹/L, neutrophils 80%, lymphocytes 12.3%, and erythrocyte sedimentation rate 120 mm/h. Liver and kidney function was normal. Clinical diagnosis: hepatocellular carcinoma of the right lobe of the liver. Right lobe hepatocarcinoma was resected under general anesthesia on May 25. Surgical findings: The liver capsule was smooth, without nodules on the surface, soft in texture, without sclerosis, and a mass could be palpable in the VI segment of the right lobe of the liver. Gross findings: The mass is 6 cm ×5 cm in size, with clear boundaries, no envelope, medium texture, and does not shrink when pressed. The mass is mainly gray-white, and locally gray-yellow. Microscopically, the boundary between the tumor and the surrounding liver tissue was clear, and a large number of mature lymphocytes were seen in the tumor area, accompanied by a large number of plasma cells. Small lymphocytes were seen to aggregate in nodular shape. Immunoenzyme labels: LCA, CD20, CD3, CD43, CD79a, CD5 were partially positive, Lambda (+), Kappa (+) (Figure 2), Ki-67 large cell positive index<10%； Large spindle-shaped cells were seen in some areas, with rich powder staining in serum, unclear cell boundary, nuclear vesicle-like, clear nucleolus, and immunoenzyme label: Vimentin positive; S-100, CD34, HMB-45, ALK, Actin, SMA, CD21, CD35, CD23, Ckpan, EMA, CD15, CD30, EBV-LMP, CK8 were all negative (Figure 3)； Large binuclear cells are scattered, with large nucleoli, resembling R-S-like cells. Pathological diagnosis: (right liver) nodular lymphoid hyperplasia (NLH).

A 43-year-old female came to our hospital in May 2014 due to progressive visual loss in her left eye for more than 2 years. The patient developed Raynaud's phenomenon 11 years ago. Two years later, the skin of his limbs was hardened and the muscles were stiff. He was diagnosed with "systemic scleroderma (SSc)" in the Department of Rheumatology and Immunology, General Hospital of Tianjin Medical University. He has been treated with corticosteroids, immunosuppressants, anticoagulants and vasodilators since then. Finger amputation 3 years ago due to ischemic gangrene of the right index finger. In the same year, he had right lateral facial paralysis, and found that the black shadow in front of his right eye was occluded, which was not treated. Family history: Two sisters of the patient died of systemic lupus erythematosus and renal failure, respectively. Admission physical examination: blood pressure: 130/80 mmHg (1 mmHg =0.133 kPa), chest radiograph showed no abnormalities in cardiopulmonary diaphragm, electrocardiogram showed left ventricular hypertrophy, complete right bundle branch block, left anterior branch block; Extensive skin pigmentation, poor elasticity, mask face (Figure 1The shooting and publication have obtained the consent of the patient), the right nasolabial fold becomes shallow, the corner of the mouth rises, the tongue is extended to the right, and the taste in the front 2/3 of the right half of the tongue is reduced; The mobility of body joints is acceptable, there are multiple subcutaneous nodules in both hands, and the mobility of finger joints is limited (Figure 2)。 Ophthalmological examination: visual acuity of right eye 0.01, intraocular pressure 12 mmHg, transparent cornea, mild opacity of lens cortex and nucleus, obvious opacity under posterior capsule, blurred fundus, only optic disc and a large amount of fibroproliferative membrane; The visual acuity of the left eye was 0.06, the intraocular pressure was 14 mmHg, the cornea was transparent, the lens cortex and nucleus were mildly opacified, and the posterior subcapsular opacity was obvious (Figure 3), the fundus is blurred, the optic disc boundary is clear and colorful, and the posterior pole is suspected of microangioma. Auxiliary examination: B-ultrasound of the eye showed: vitreous opacity of the right eye, traction retinal detachment (Figure 4)； Vitreous opacity in the left eye. Optical coherence tomography (OCT) showed mild edema in the macular area of the left eye (Figure 5)。 Clinical diagnosis: Complicated cataract in both eyes; retinopathy of left eye (nature to be determined); Retinal detachment by traction in the right eye. All ophthalmic examinations were completed after admission, and phacoemulsification and intraocular lens implantation were performed in the left eye under topical anesthesia. The postoperative distance visual acuity was 0.6. Fundus fluorescence angiography (FFA) performed 1 week after operation showed that the retinal structure of the right eye was unclear, large areas of fluorescence were obscured, strong fluorescence leakage around the optic disc, and the blood vessels around the optic disc of the left eye were distended and leaked obviously (Figure 6，Figure 7)。

The team led by Professor Tang Xiangdong of the Sleep Medicine Center of West China Hospital cooperated with the team of Professor Vgontzas of Pennsylvania State University School of Medicine. Through the study of 219 patients with chronic insomnia and 96 healthy controls in West China Hospital, it was found that some patients with physiological high wakefulness The risk of hypertension in chronic insomnia patients exceeds that of the control group by 300% ~400%. The study primarily used results known as multiple sleep incubation period measurements as an indicator of physiological high arousal. The method of multiple sleep incubation period measurement is to allow the subject to sleep for 20 minutes at 9: 00, 11: 00, 13: 00 and 15: 00 during the day, respectively, and use the objective average time of falling asleep four times judged by electroencephalogram as an index to examine the difficulty of falling asleep. The shorter the time, the easier it is to fall asleep. At the same time, the prolonged incubation period of falling asleep also reflects physiological high arousal. The study found that if people with chronic insomnia fell asleep in incubation period for>14 minutes, the probability of developing hypertension was 300% that of the control group; >17 min, up to 400% of the control group; While<There was no statistically significant difference compared with the control group at 14 min. This shows that if insomnia patients have physiological high arousal, that is, it is difficult to fall asleep during the day (judged by electroencephalogram, rather than their own subjective feelings), the risk of hypertension will be significantly increased.

Irritable bowel syndrome (IBS) is a functional intestinal disease characterized by recurrent abdominal pain or abdominal discomfort, accompanied by changes in stool characteristics and defecation habits. It is one of the most common functional gastrointestinal diseases in clinic. Its prevalence rate is 5% ~25% worldwide, and the prevalence rate of Chinese population is 5% ~8%^[1,2]。 IBS is a multi-factor related disease. Previous studies suggest that abnormal gastrointestinal motility, visceral hypersensitivity, psychological stress, intestinal infection, small intestinal bacterial overgrowth, brain-intestinal axis dysfunction, immune and endocrine system disorders are all related to the occurrence and development of IBS. With the progress of intestinal microbial research, the role of intestinal microbiology in the occurrence and development of IBS has gradually been paid attention to, and it has become a new therapeutic target. There is more and more evidence of probiotics and antibiotics for the treatment of IBS.

Cytogenetic abnormalities are the most important prognostic factors in patients with multiple myeloma (MM). International Myeloma Working Group^[1]And Mayo Medical Center^[2]It is recommended that the risk of MM patients be stratified by cytomolecular genetic indexes, such as Del (17p) and t (4; 14) as high-risk genetic indexes; And t (11; 14) is the standard risk index. Among them, the poor prognosis of t (4; 14) can be overcome by bortezomib-based therapy, and its risk grade is reduced from high risk to medium risk, which becomes a model of stratified therapy for MM. Future research hotspots will also focus on improving new prognostic indicators and evaluating the prognostic significance of various genetic indicators under different new drug backgrounds.

As reported in the literature^[1]More than half of the patients diagnosed with type 2 diabetes have hypertriglyceridemia accompanied by the deposition of visceral fat, and insulin resistance (IR) can be significantly improved after lipid-lowering therapy. It can be seen that lipid metabolism disorders are involved in the development of type 2 diabetes, which is called lipotoxicity.

Venous thromboembolism (VTE), including deep vein thrombosis (DVT) and pulmonary embolism (PE), is the third most common cardiovascular disease after ischemic heart disease and stroke^[1]。 In the United States, the incidence of VTE increased by 33.1% from 317 cases per 100 000 in 2002 to 422 cases per 100 000 in 2006^[2]； There is no systematic epidemiological data of VTE in China, but the awareness and concern about the disease are gradually increasing^[3]。 According to statistics, the annual incidence of DVT among people over 65 years old in China is 81.1/100 000 people^[4], similar to Europe and America.