Volume 95  ·  Issue 10  ·  2015

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).

To evaluate the impact of cytogenetic grouping and autologous stem cell transplantation on the prognosis of patients with multiple myeloma (MM) induced by PAD (velcade + epirubicin + dexamethasone) and TAD (thalidomide + epirubicin + dexamethasone).

A total of 191 patients with a definite diagnosis of MM were enrolled from May 2008 to December 2013 into this prospective study. They were non–randomly induced by PAD (n=132) or TAD (n=59) plus autologous stem cell transplantation or chemotherapy. Response and survival rates were also analyzed between two groups.

The overall response rates of PAD and TAD groups were 84.4% (108/128) and 69.5% (41/59) (P=0.011) respectively. The very good partial remission(VGPR) rates were 70.3% (90/128)and 32.2% (19/59) (P<0.001) and near complete remission/complete remission (nCR/CR) rates 68.0% (87/128) and 25.4% (15/59) respectively (P<0.001). Both progression–free survival (PFS) and overall survival (OS) showed no significant inter–group difference (P=0.223, 0.989). The survival analysis of PAD group showed that FISH high–risk group had shorter PFS and OS than FISH low–risk group (15.2 vs 19.1 months for PFS, P=0.098; 41.2 months vs non–attaining for OS, P=0.017). In FISH high–risk group, patients consolidated with autologous stem cell transplantation showed longer PFS than those with chemotherapy (17.8 vs 14.6 months, P=0.029) while the OS showed no difference(P=0.840). In FISH low–risk group, no difference were observed in PFS and OS between patients with consolidation therapies alone (P=0.131, 0.294).

The response rates are higher in patients induced by PAD than by TAD. After PAD induction, cytogenetic grouping may further distinguish the prognosis of MM patients. For FISH high–risk patients, their PFS is prolonged by autologous stem cell transplantation.

To explore the clinical characteristics of multiple myeloma (MM) patients with overall survival (OS) less than 24 months so as to stratify high–risk population.

A total of 177 newly diagnosed MM inpatients were recruited from July 2008 to July 2012. Clinical parameters at diagnosis of international staging system (ISS), lactic dehydrogenase (LDH), serum calcium, extramedullary involvement and amyloidosis were collected and cytogenetic abnormalities were detected by fluorescence in situ hybridization (FISH). Response and death were recorded as endpoints. Otherwise the follow–up period was over 24 months.

And 73 patients dying within 24 months were classified into high–risk group while another 104 survivors for over 24 months into control group. Age and gender at baseline were comparable. However, OS of high–risk group was only 8 months while it was not attained during a median follow up of 38 months in control group (P<0.001). The most common cause of death was progressive disease in both groups. The pre–treatment percentages of the following parameters were significantly higher in high–risk group, including ISS stage Ⅲ (76.71% (56/73) vs 50.00% (52/104),P=0.002), renal dysfunction (47.95% (35/73) vs 31.73% (33/104), P=0.029), elevated LDH (20.55% (15/73) vs 7.69% (8/104), P=0.015)and plasma cell leukemia (PCL, 5.48% (4/73) vs 0(0/104), P=0.016). Conversely, extramedullary involvement, plasmacytoma, amyloidosis and hypercalcemia were similar. Despite comparable chemotherapeutic regimens, the rate of deep response, including complete response (CR) and very good partial response (VGPR), was significant lower in high–risk group than that in control group (12.33% (9/73) vs 53.85% (56/104), P<0.001). Overall response rates (ORR, i. e. CR + VGPR + partial response (PR))were markedly different (38.36% (28/73)vs 86.54% (90/104),P<0.001). Univariate analysis of cytogenetic abnormalities indicated a higher proportion of 1q21 amplification in high–risk group(35.62% (26/73)vs 25.15% (22/104),P=0.033). Multivariate Logistic regression revealed that ISS, LDH and primary response worse than PR independently affected early death(P=0.046, 0.005, <0.001).

MM patients with OS less than 24 months have distinct clinical characteristics. And aggressive regimens are needed to improve the outcomes of high–risk population.

To explore the clinical features and prognostic factors of newly diagnosed multiple myeloma patients with renal insufficiency (MM-RI).

The clinical features, survival rates and prognostic factors were retrospectively analyzed for 897 newly diagnosed multiple myeloma (MM) patients at three hospital from January 1, 2010 to June 30, 2012.

Among them, there were 177 cases (19.7%) of MM-RI patients. There were 125 males and 52 females with an average age of 59 years. And 28.2% (50/177) were over 65 years. The types were 17.2% (30/174) of immunoglobulin (Ig) D-λ and 27.6% (48/174) of light chain isotype. And the stages were 94.9% of DS stage Ⅲ(167/176) and ISS stage Ⅲ (166/175). Compared with MM patients with normal renal function (MM-RN), MM-RI group had a higher proportion of patients with IgD-λ and light chain isotype, more patients of DS and ISS stage Ⅲ; elevated bone marrow plasma cells, white blood cells and uric acid; lower hemoglobin and platelet (allP<0.05). After a median follow-up period of 24(2–114) months, the median progression-free survival (PFS) was 28.0 months for MM-RI patients and 29.0 months for MM-RN patients. And the difference was not statistically significant (P=0.457). The estimated median overall survival (OS) was 44.0 months for MM-RI patients and 59.2 months for MM-RN patients. And the difference was statistically significant (P=0.033). Log-rank univariate analysis showed that age, LDH, β2-MG, first-line treatment with or without bortezomib and previous transplantation or not were independent prognostic factors of MM patients.

MM-RI and MM-RN patients have different clinical features. Age, LDH, β2-MG, first-line treatment with or without bortezomib and previous transplantation or not are independent prognostic factors for newly diagnosed MM patients.

To explore the clinical efficacies and toxicities of lenalidomide combination chemotherapy in the treatment of relapsing or refractory multiple myeloma (MM) patients.

A total of 14 MM patients were recruited to receive lenalidomide combination chemotherapy in Beijing Chaoyang hospital from June 2013 to October 2014. Lenalidomide 25 mg was taken orally daily or every alternate day for 21 days and resting for 7 days. The regimens were RD (lenalidomide and dexamethasone, n=6), RCD (lenalidomide, ifosfamide and dexamethasone, n=4), RDD (lenalidomide, liposomal doxorubicinand dexamethasone, n=1), PRD (lenalidomide, velcade and dexamethasone, n=1) and R + DECP (lenalidomide, cisplatin, etoposide, ifosfamide and dexamethasone, n=2).

Among them, two patients died during the first cycle of lenalidomide. Ten patients finished 2 cycles of treatment and 2 patients attained near complete remission or complete remission (nCR/CR), 6 partial remission (PR) and 2 stable disease (SD) with an overall response rate (ORR) of 8/10. Ten patients finished 3 cycles of treatment and 3 attained CR, 5 PR and 2 SD. Nine patients finished 4 cycles of treatment and 3 attained CR, 5 PR and 1 progressive disease (PD). Six patients finished 5 cycles of treatment and 1 attained CR, 3 PR and 2 PD. Three patients finished 6 cycles of treatment and 1 attained CR, 1 PR and 1 PD. And the most common adverse reactions were fatigue, loss of appetite and hypocytosis. Six patients died.

The lenalidomide combination chemotherapy is both efficacious and safe in the treatment of relapsing or refractory MM.

To explore the differential expressions of lysozyme C and lactoferrin in tears of thyroid-associated ophthalmopathy (TAO) patients versus healthy subjects by proteomics.

Tear samples were obtained from patients with active period TAO and age and gender-matched healthy subjects without symptoms of ocular surface. Then they were divided into patient and control groups. Then tear samples of two groups were analyzed. sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) of 15% gel was performed to determine the different protein bands in sample groups. And different labeled protein bands were collected for in-gel tryptic digestion. Mass spectrometry was employed to determine the protein components from different protein bands. Then Scaffold search engine was used for analyzing the results of mass spectrometry and identifying specific proteins.

Based on mass spectrometric analysis of different protein bands, most proteins were down-regulated or became absent in TAO patients. Both lysozyme C and lactoferrin were up-regulated. Identification of protein relative quantitative ratio (patient/control): lysozyme C: 4.88, lactoferrin: 1.61.

Lysozyme C and lactoferrin are two important effectors of tear function and metabolism. Both are up-regulated in TAO patients' tears. Thus both are probably involved in inflammatory process of TAO and play synergistic roles in the pathogenesis of disease.

To evaluate the effects of different end–tidal concentrations of sevoflurane on somatosensory evoked potentials, to explore the feasibility of sevoflurane applied in such kind of surgery, so as to provide useful information in making anesthesia plan for spinal cord surgery.

Thirty–two patients scheduled for spinal cord surgery (ASA Ⅰ–Ⅱ, 18–65 years old) were enrolled. After induction of anesthesia, they were assigned to receive sevoflurane anesthesia of increment end–tidal concentration in the sequence of 0.0%, 0.5%, 1.0% and 1.5% respectively, under a background intravenous infusion of propofol and remifentanil. Remifentanil infusion rate was 0.2 μg·kg ^–1·min^–1, while the propofol infusion rate was adjusted to maintain BIS values within the range of 30–50. The amplitude and latency of each SSEPs were recorded and compared.

Sevoflurane inhibited SSEPs in a dose–dependent manner, SSEPs amplitude significantly decreased following increased end–tidal sevoflurane concentration. The amplitudes of the left side were 2.36(0.42–9.87), 2.14(0.52–9.44), 1.94(0.47–9.44), 1.64(0.36–7.46)μV respectively(F=21.66, P<0.01). The amplitudes of the right side were 2.71(0.43–7.1), 2.73(0.43–7.1), 2.34(0.44–6.6), 1.64(0.39–6.15) μV respectively(F=33.94, P<0.01). SSEPs latencies were significantly prolonged, on the left side, the latencies were (41.48±3.45), (42.45±3.60), (43.20±3.42), (44.38±3.78) ms, respectively (F=68.07, P<0.01). On the right side, the latencies were (40.65±4.91), (41.53±4.76), (42.31±4.93), (43.39±4.79)ms, respectively(F=56.52, P<0.01). Yet, as a monitoring modality for dynamic observation, SSEPs still could be monitored successfully under sevoflurane anesthesia in all these 32 patients.

Sevoflurane has depression effects on SSEPs in a dose–dependent manner. It can decrease the amplitudes and prolong the latencies. Considering significant individual difference, the feasibility of sevoflurane in such kind of surgery can be determined by measuring base amplitude of SSEPs under total intravenous anesthesia.

To analyze the clinical value of the detection of serum desgamma carboxy prothrombin (DCP), golgi glycoprotein 73 (GP73), heat–shock protein 70 (HSP70) in primary hepatic carcinoma (PHC) diagnosis.

Enzyme–1inked immunosorbent assay and electrochemiluminescence immunoassay were used to detect the serum DCP, GP73, HSP70 and α–fetoprotein (AFP) levels in 35 PHC patients and 35 healthy controls.

AFP, DCP and GP73 levels in PHC patients were 13.780(1.140–8 487.000)μg/L, 3 213.953(2.510–53 994.602)pg/ml and 76.838(24.500–232.875)ng/ml respectively, significantly higher than those in healthy controls (1.240(0.605–5.310)μg/L, 104.610(0.000–4 138.770)pg/ml and 30.770(16.343–87.453)ng/ml,U value were 134.50, 258.00 and 168.00, all P<0.01); HSP70 could not be detected in any objects. The area under the ROC curve of DCP or GP73 was 0.789, 0.863 respectively. The sensitivity and specificity to PHC diagnosis were 54.3% and 97.1% by DCP (2 939.4 pg/ml as cut–off value), 85.7% and 74.3% by GP73 (41.3 ng/ml as cut–off value), 45.7% and 100% by AFP (20 μg/L as cut–off value). In combined detection the sensitivity, specificity and accuracy were 88.6%, 74.3%, 81.4% by GP73/AFP and 91.4%, 71.4%, 81.4% by GP73/DCP/AFP.

GP73, DCP are new effective markers in the diagnosis of PHC, and the combined detection of GP73, DCP and AFP can improve the diagnosis value of PHC.

To evaluate the efficacies of a modified oral appliance (MOA) for residual obstruction after uvulopalatopharyngoplasty (UPPP) in the treatment of moderate–to–severe obstructive sleep apnea hypopnea syndrome (OSAHS).

The patients with residual airway obstruction on polysomnography (PSG) at four weeks post–UPPP were selected from the Sleep Medicine Center, Gansu Provincial People's Hospital from October 2013 to February 2014. As of week 5 post–UPPP, all subjects wore MOA for 4 weeks. Before and 4 weeks after treatment, questionnaires were distributed to evaluated the improvement of subjective and objective sleep. The average apnea hyponea index (AHI) and sleep patterns were examined by PSG. The sagittal diameter in minimal region of retropalatal and retroglossal patency and the volume of orophary were measured by cone beam computed tomography (CBCT) scans. And the correlation between the outcomes of CBCT and AHI were analyzed.

A total of 10 male OSAHS patients were enrolled. The average age was (42.4±9.2) (31–55) years, body mass index (BMI) (25.0±4.8) (22.8–29.4) kg/m² and AHI was (26.0±7.5)(15.8–35.9)/h. After wearing MOA for 4 weeks, the symptoms of snoring, daytime somnolence and suffocated waking during sleep improved as compared with that pre–treatment. All adapted to sleep with MOA. Average AHI decreased from (26.0±7.5)/h to (6.0±0.7)/h (P<0.001). And the lowest average oxygen saturation value (SaO₂) increased from (79.6±3.9)% to (87.6±1.6)% (P<0.001). PSG indicated that the percentage of awakening time and sleep time in nonrapid eye movement (NREM) stage 1 decreased from (11.0±2.3)% and (26.1±4.3)% to (6.8±1.6)% and (11.1±1.5)% respectively in total sleep time (TST). The percentage of NREM stage3 sleep time and rapid eye movement (REM) sleep time in TST increased on average from (10.2±2.2)% and (11.6±1.4)% to (17.7±3.1)% and (21.3±3.1)% respectively (allP<0.001). CBCT measurements showed that the sagittal diameter in minimal region of retropalatal and retroglossal patency increased on average by (0.64±0.04) and (1.51±0.18) mm respectively. The average volume of orophary increased by (2 446±963) mm³ (all P<0.05). Negative correlations existed between AHI and sagittal diameter of minimal region of retroglossal patency, AHI and volume of orophary (allP<0.05).

The application of MOA after UPPP can significantly increase the sagittal diameter of minimal region of retroglossal patency and the volume of orophary and improve effectively hyperpnoea and disordered sleep patterns.

To explore the effects of glutamine, eicosapntemacnioc acid (EPA) and branched–chain amino acids supplements in esophageal cancer patients on concurrent chemoradiotherapy and gastric cancer patients on chemotherapy.

From April 2013 to April 2014, a total of 104 esophageal and gastric carcinoma patients on chemotherapy or concurrent chemoradiotherapy were recruited and randomly divided into experimental and control groups. Both groups received dietary counseling and routine nutritional supports while only experimental group received supplements of glutamine (20 g/d), EPA (3.3 g/d) and branched–chain amino acids (8 g/d). And body compositions, blood indicators, incidence of complications and completion rates of therapy were compared between two groups.

After treatment, free fat mass and muscle weight increased significantly in experiment group while decreased in control group (P<0.05). And albumin, red blood cell count, white blood cell count and blood platelet count remained stable in experiment group while declined significantly in control group. During treatment, compared to control group, the incidences of infection–associated complication were lower (6% vs 19%,P<0.05) and the completion rates of therapy were significantly higher in experiment group (96% vs 83%,P<0.05).

Supplements of glutamine, EPA and branched–chain amino acids can help maintain nutrition status, decrease the complications and improve compliance for esophageal cancer patients on concurrent chemo–radiotherapy and gastric cancer patients on postoperative adjuvant chemotherapy.

To explore the structural and biomechanical properties of acellular dermal matrix (ADM) of human scar tissue.

Randomly choose 8 human mature scar tissue, 8 human hypertrophic scar tissue, and 4 normal human tissue as experimental samples respectively. Then 0.5 mm split–thickness skin grafts were obtained by drum–type scalpel, further acellularized by 2.5 g/L trypsin–0.5% TritonX–100. Structural analyses were performed by macroscopic observation, hematoxylin and eosin histological staining and scanning electron microscope. Then human epithelial stem cells were inoculated, cultured on those materials and observe their adhesive properties. Finally the biomechanical properties of ADM were analyzed through the detection of stress–strain relation, stress relaxation, creep and ultimate stress strength to distinguish different origins.

Prepared ADM was milky white in color despite their distinct origins, physiological and mature scar tissue derived ADM was soft and flexible in texture while ADM from hypertrophic scar showed a more tenacious character. Optical microscopic and electron microscopic analyses showed no sign of visible cellular structures. ADM from physiological group had relatively homogeneous and inerratic collagenous fibers, ADM from hypertrophic group presented with fibers of various diameters and arrayed in a compact and disordered manner. ADM from mature scar tissue possessed traits between the other two groups. Adhesion growth could be observed 2 weeks after inoculating human epithelial stem cells on ADM and cells grew in a cohesive fashion on ADM both from normal skin and mature scar tissue and in an adhesive fashion on hypertrophic scar tissue ADM. Stress–strain β value (3.024±0.413, 2.595±0.443, 2.590±0.366), creep slope (0.018±0.003, 0.019±0.009, 0.023±0.010) and ultimate stress strength (8.971±2.434, 11.011±1.492, 15.567±2.931) of ADM showed no significant differences in hypertrophic scar, mature scar and normal skin tissues (all P>0.05). ADM from mature scar and normal skin tissue showed no differences in stress–strain stretch ratio (0.238±0.083 vs 0.291±0.048), relaxation slope (–0.041±0.009 vs–0.047±0.008), total relaxation (0.775±0.194 vs 0.968±0.211) or total creep (0.033±0.022 vs 0.049±0.020) (allP>0.05). However, the above related indices of ADM from hypertrophic scar tissue (0.188±0.036, –0.033±0.006, 0.481±0.058, 0.020±0.005) were significantly lower than those from normal tissue (allP<0.05).

No significant differences exist between mature scar and normal skin tissues derived ADM both in structural and biomechanical properties. However ADM from mature scar appears to be superior in biomechanical properties than hypertrophic scar derived ADM so that it may become a replacement for original dermis in wound repair.

To explore differences in the clinical characteristics, treatment methods and progness of Chinese (Han) and Western populations (Caucasia) aortic dissection (aortic dissection, AD) patients.

According to the requirements of systematic review, We searched MEDLINE (1980–2014), Emabse (1980–2014), CBM (1980–2014) and CNKI (1980–2014) database overall, the meta–analyses were performed through STATA 12.0.

A total of 6 697 Stanford A AD and 3 381 Stanford B AD Caucasian patients and 850 Standford A AD and 4 745 Stanford B AD Chinese Han patients were deemed eligible. It showed that average age of Han patients was lower, the proportion of Han group was 84.5%, while Cuacasian group was 66.9%, the differences were statistically significant(χ²=365.37, P<0.01). Han patients with history of smoking and that of coronarty heart diseases accounted for 53.0%, 13.8% separately, which were higher than those of Caucasian group, the differences were also statistically significant (χ²=264.23, 68.417, P<0.01). Besides these, the proportions of Han Stanford B AD patients who had hypertension, diabetes were also statistically significant higher than Caucasian group(χ²=264.23, 68.417, P<0.01). The Chinese group was more likely to appear nervous system and heart damages before surgery while the Caucasian group mostly appeared kidney and peripheral vascular damages. In the choice of treatment, the number of open surgery patients was significantly higher than that in Caucasian group. Domestic acute AD patients were more likely to accept TEVAR. The 30–day mortality of Chinese Han group in Stanford B was 2.4%, while Caucasians' mortality was 11.2%, the differences were statistically significant(χ²=142.96, P<0.01).

The incidence of Chinese AD patients who are younger with more basic diseases has been increasing gradually, Although the 30–day mortality and complications rates of Chinese patients accepting early surgery intervention are lower than Caucasians, due to the less available data, large sample researches and further long–term follow–up will be needed.

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.