2016年 · 第55卷第02期

With the progress of China's aging society and the continuous progress of myeloma diagnosis and treatment in the world, the diagnosis and treatment of multiple myeloma (MM) has attracted more and more attention of hematologists, even orthopedists and nephrologists, and has become a hot field. In recent years, a large number of research results have emerged in this field. Followed by the update of international MM diagnostic criteria and efficacy evaluation criteria, more refined prognosis stratification, the continuous emergence of new drugs and the continuous improvement of efficacy, will eventually make MM patients benefit. Since the first edition of the Guidelines for the Diagnosis and Treatment of Multiple Myeloma in China was published in our journal in 2008, the Guidelines have been revised to the fourth edition-Guidelines for the Diagnosis and Treatment of Multiple Myeloma in China (Revised in 2015), which has been published in the 12th issue of this journal in 2015. The formulation and every revision of this guideline have played a promoting role in popularizing myeloma-related knowledge, clarifying concepts, and standardizing diagnosis and treatment. In this issue of our journal, Professor Huang Xiaojun wrote a monograph "Realizing Clinical Practice with Chinese Characteristics with International Standards", and invited domestic experts in this field to write relevant special written talks to conduct an in-depth interpretation of the guide. Welcome to read! Relevant content has also been published simultaneously on the WeChat platform of our journal (WeChat signal: zhnkzz).

With the progress of China's aging society and the continuous progress in the field of myeloma treatment in the world, the diagnosis and treatment of multiple myeloma (MM) has undoubtedly attracted more and more attention of hematologists, even orthopedists and nephrologists in recent years, and has become a hot field. There are many changes in this field, including constantly updated diagnosis and efficacy evaluation criteria, prognostic stratification system, etc. The efficacy of various new drug regimens continues to improve, but the cost remains expensive. Therefore, the Hematologist Branch of Chinese Medical Doctors Association and the Hematology Branch of Chinese Medical Association revised the "Guidelines for the Diagnosis and Treatment of Multiple Myeloma in China" for the fourth time, which was published in the 12th issue of Chinese Journal of Internal Medicine, 2015 (hereinafter referred to as the new edition of the Guidelines)^[1]。 The diagnostic criteria and efficacy evaluation criteria in the new version of the guidelines basically adopt international standards; However, in terms of treatment suggestions, according to the characteristics of China (there are few types of new drugs, few combinations of new drugs, new drugs are basically not covered by medical insurance, and the prevalence of some special groups such as hepatitis B is higher than the international average, etc.), it is recommended to reflect clinical practice with Chinese characteristics. How to adopt international diagnosis and evaluation standards to achieve clinical practice with Chinese characteristics under the reality of China, and influence the formulation of international standards in the future, is a huge challenge for Chinese doctors at present.

Guidelines for Diagnosis and Treatment of Multiple Myeloma in China (Revised in 2015)^[1](hereinafter referred to as the new edition of the guide) meet with you again. Compared to the last two editions, it has a larger revision in the diagnostic section. The addition of new biological markers on the basis of traditional diagnostic criteria enables some high-risk smoldering multiple myeloma (SMM) patients to intervene in advance, in order to improve the overall efficacy and survival of multiple myeloma (MM) patients. In terms of prognostic staging, it is suggested that qualified units can adopt the newly introduced revised International Staging System (R-ISS), in order to better stratify the prognosis of patients. Therefore, the new version of the guide not only keeps up with the forefront of international disciplines, but also is based on the reality of China. It is comprehensive and specific, concise and clear in diagnosis and prognosis staging. It is specifically embodied in the following three aspects.

Guidelines for Diagnosis and Treatment of Multiple Myeloma in China (Revised in 2015)^[1](hereinafter referred to as the new version of the guidelines) Compared with the 2013 version, the overall strategy of its initial treatment is still composed of induction therapy, high-dose chemotherapy combined with autologous hematopoietic stem cell transplantation (ASCT), and consolidation and maintenance (continuous) therapy. Among them, the strategies and protocols recommended for consolidation and maintenance (continuous) treatment are basically similar to the 2013 version of the guidelines. The main modifications or supplements of the new guidelines to the initial treatment of multiple myeloma (MM) are as follows: (1) Based on the biological heterogeneity of smoking (asymptomatic) MM (SMM), clinical management strategies for high-risk SMM are clearly recommended; (2) For active (symptomatic) MM, emphasize the comprehensive consideration of the patient's age and clinical status (based on the assessment of physical fitness and coexisting diseases), and finally decide the selection of its induction therapy regimen and the eligibility of ASCT conditions; (3) The new version of the guidelines affirms the value and status of lenalidomide-related regimens in the initial treatment of MM (especially elderly MM).

With the widespread application of therapeutic strategies such as proteasome inhibitors, immunomodulators and hematopoietic stem cell transplantation in newly diagnosed multiple myeloma (MM), the remission time and survival time of MM patients are gradually prolonged, but patients will eventually relapse and progress. 2015 edition of Chinese guidelines for diagnosis and treatment of multiple myeloma^[1]The treatment of relapsed/refractory MM has been elaborated in principle, but how to better treat patients with relapsed/refractory MM in combination with the guidelines is still the focus of discussion. Now the content of this part will be interpreted.

Looking back at the development history of efficacy standards for multiple myeloma (MM), every efficacy standard is formulated or updated with the emergence of new treatment methods or methods. The purpose of updating the efficacy standards is to match the therapeutic effect brought by the new treatment methods. From 1980s to 1990s, due to the application of autologous hematopoietic stem cell transplantation (ASCT) in MM, the therapeutic effect has made progress, and the original efficacy standard of MM can no longer meet the requirements of efficacy judgment in the era of transplantation therapy. Therefore, the International Bone Marrow Transplant Registry (IBMTR), the European Bone Marrow Transplant Collaborative Group (EMBT) and the American Bone Marrow Transplant Registry (ABMTR) developed criteria for judging the efficacy of MM, the famous EBMT or Blade criteria (1998). The standard has been applied internationally for a considerable time without revision or update. Until new drugs such as thalidomide (1999), bortezomib (2004), and lenalidomide (2005) were widely used in clinical practice, sequential or non-sequential ASCT, the efficacy of MM was significantly improved. In order to adapt to this significant improvement in efficacy, the International Myeloma Working Group (IMWG) developed the IMWG standard in 2006^[1]。 With the increase of methods or treatments such as sequential or non-sequential transplantation of various new drugs, the highest efficacy level in 2006 and before-complete response (CR) or strict complete response (sCR) is far from meeting the evaluation of MM treatment effect. Therefore, the IMWG in 2011 respectively^[2]2014^[3]New efficacy evaluation criteria were published. Compared with the two IMWG efficacy criteria published, there was no change except for the addition of one item in the 2014 version, "If the baseline M protein level is ≥50 g/L, then M protein only needs to be increased by 10 g/L to be judged as PD". Compared with the efficacy criteria before 2006, the new efficacy criteria of IMWG in 2011 and 2014 proposed the use of flow cytometry and molecular methods to detect minimal residual disease (MRD), and specified the methods used to meet these criteria. Immunophenotypic CR (ICR) and molecular CR (MCR) can be used to judge the efficacy more sensitively and deeply. Guidelines for Diagnosis and Treatment of Multiple Myeloma in China (Revised in 2015)^[4]The efficacy criteria (hereinafter referred to as the new version of the guidelines) are based on the 2014 version of the IMWG consensus, aimed at adapting to the increasingly advanced treatment of MM and the significant efficacy that comes with it, and have a common "language" with the international community.

Eosinophilic granulomatous vasculitis (EGPA) is a systemic necrotizing vasculitis involving middle and small arteries and veins, characterized by bronchial asthma (hereinafter referred to as asthma), peripheral blood eosinophilia and extravascular eosinophilic granuloma formation. It is often misdiagnosed as refractory asthma and idiopathic eosinophilia syndrome (IHES). In this study, the clinical data of 14 cases involving pulmonary EGPA were retrospectively analyzed, aiming to improve the diagnostic level of clinicians.

Primary hyperparathyroidism (PHPT) is due to the excessive synthesis and secretion of parathyroid hormone (PTH) caused by lesions (tumors or hyperplasia) of the parathyroid gland itself. Through its effects on bones and kidneys, blood calcium is increased and blood phosphorus is decreased. The clinical manifestations are recurrent kidney stones, peptic ulcer, mental changes and extensive bone resorption. Hyperparathyroidism (hereinafter referred to as hyperparathyroidism) crisis is one of the rare but seriously life-threatening acute and severe diseases in clinic, with high mortality rate. Foreign reports show that the mortality rate of hyperparathyroidism crisis was 93% in the 1950s. Recent reports show that the mortality rate has decreased significantly, but it is still 14%. The incidence rate of hypercalcium crisis in hyperparathyroidism patients is 1.6% ~6%^[1]。 Four cases of hyperparathyroidism crisis complicated with multiple organ function impairment were reported. After effective treatment such as active surgery, anti-shock and multiple organ support, the prognosis was good, which provided experience and reference for differentiating hyperparathyroidism crisis, avoiding misdiagnosis and misdiagnosis and giving correct and timely treatment.

Different from infectious disease specialist hospitals, the infectious disease department of general hospitals not only treats patients with infectious diseases, but also treats patients with various infectious diseases other than national legal infectious diseases, and guides etiological diagnosis and rational application of anti-infectious drugs. Consultation related to the diagnosis and treatment of infectious diseases is its important business scope. This study analyzed the consultation situation of our department to relevant departments of our hospital in 2012, and attempted to understand the influence of the consultation opinions of infectious diseases physicians on the disease management of relevant departments.

The patient was a 40-year-old male. He was admitted to our hospital on October 13, 2013 due to "intermittent fever, epistaxis for 10 days, and ineffective anti-infective treatment". Admission physical examination: mild anemia, no bleeding and yellowing staining of skin and mucosa; Obvious sternal tenderness, slightly thick breathing sounds in both lungs, and no dry and wet rales were heard; Heart rate 85 beats/min, homogeneous rhythm; Soft abdomen, no tenderness, rebound pain and abdominal muscle tension, untouched under liver, spleen and costs; There was no edema in both lower limbs. Blood routine: WBC 52.41×10⁹/L, Hb 85 g/L, PLT 51×10⁹/L; Bone marrow image: active hyperplasia, primordial granule 0.305, peroxidase (POX) positive; Immunophenotype: Abnormal cell population accounted for 12.8%, co-expressing CD₃₃CD₃₄HLA-DR, CD₁₃, partially expressing CD₁₁₇, intracellular myeloperoxidase (cMPO) is weakly expressed and does not express CD₇CD₁₀CD₁₉CD₂₀cCD_79aCD₁₄CD₅₆； Chromosome: 46, XY [20]; Acute myeloid leukemia (AML) fusion gene AML-ETO and BCR/ABL190 and BCR/ABL210 were all negative; c-kit, FLT3-TKD and NPM were all negative; FLT3-ITD positive. Clinical diagnosis: pulmonary infection; AML-M2a with FLT3-ITD positive. After admission, anti-infective therapy was given and DA regimen (daunorubicin 60 mg/d, days 1 to 3; cytarabine 200 mg/d, days 1 to 7) was given on 15 October. Bone marrow image on November 3rd: hyperplasia was obviously active, with primitive granules accounting for 0.105. Regimen IA (normethoxydaunorubicin 15 mg/d, days 1-3; cytarabine 200 mg/d, once/12 h, days 1-5) was administered on November 7. Bone marrow image on Nov. 13: active hyperplasia, original granule 0.155, so CHG regimen was added [homoharringtonine 2 mg/d, days 1 to 9; cytarabine 25 mg/time, once/12 h, subcutaneous injection, days 1 to 9; granulocyte colony stimulating factor (G-CSF) 150 μ G/d, days 1 to 9]. On December 2nd, the bone marrow image showed active hyperplasia, and the original granule was 0.135. On December 16th, the bone marrow image increased to 0.465. Sorafenib in combination with CHAG was given on 21 December (sorafenib 400 mg/dose, twice/d orally; arubicin 20 mg/d, days 1-4; homoharringtonine 2 mg/d, days 1-6; cytarabine 25 mg/dose, once/12 h, subcutaneously, days 1-14; G-CSF 150 μ G/d, days 1-14). On January 10, 2014, the bone marrow image was re-examined: the hyperplasia was active, and the original granule was 0.01. Later, sorafenib combined with chemotherapy was consolidated, and sibling homogeneous allogeneic hematopoietic stem cell transplantation was performed in early April 2014, but recurrence occurred more than 4 months after transplantation.

The patient was a 72-year-old female. He was admitted to the hospital on April 17, 2013 for the main reason of "abdominal pain, diarrhea, fever with intermittent disorder of consciousness for 4 days". Previous history of type 2 diabetes, oral metformin therapy, ideal glycemic control. On April 13, 2013, the patient developed abdominal pain and diarrhea 5 times after eating unclean at night, which was yellow loose stools with mucus and no pus and blood. Nausea and vomiting 3 times, which were non-jetting, and the vomit was stomach content; Chills, chills, high fever, body temperature 39.0℃, confusion and delirium the next day. The local hospital gave anti-inflammatory treatment without improvement, and he was transferred to the emergency department of our hospital on the evening of April 14th. Emergency physical examination: body temperature 39.4℃, shallow coma, bilateral pupils of equal size and round size, no yellowing, petechiae, ecchymosis on the skin and mucosa of the whole body, no palpable swelling of superficial lymph nodes, soft neck without resistance, no tenderness in sternum, wet rales can be heard at the floor of both lungs, heart rate 152 beats/min, uniform rhythm, slightly tight abdominal muscles, positive tenderness in the whole abdomen, insignificant rebound pain, weak intestinal sound, no edema in both lower limbs, bilateral Babinsky sign (+). Emergency laboratory test: Routine blood WBC 9.65×10 on April 14⁹/L, Hb 126 g/L, PLT 78.0×10⁹/L; Reviewed on 15 Apr, WBC 8.71×10⁹/L, Hb 118 g/L, PLT 43.0×10⁹/L; Coagulation function test showed that PT was prolonged for 3 s, and APTT, fibrinogen and D-dimer were all normal; Blood biochemistry, blood urea nitrogen (BUN) 17 mmol/L, serum creatinine (SCr) 147.0 μ mol/L, blood glucose 20.0 mmol/L, lactate dehydrogenase (LDH) 391 U/L, creatine kinase (CK) 1 228 U/L, total bilirubin (TBil) 38.70 μ mol/L, indirect bilirubin (IBil) 28.40 μ mol/L; Urine routine showed occult blood and protein (+ +), ketone body (-); The routine stool showed brown and mushy stool, occult blood (+), and 0~2 white blood cells/high-power field; Blood gas analysis, pH 7.42, blood oxygen partial pressure 64 mmHg (1 mmHg =0.133 kPa), blood carbon dioxide partial pressure 24 mmHg; reticulocytes 0.002; There were no red blood cell debris and young red blood cells in the peripheral blood smear. No abnormalities were found in emergency head CT; Chest CT showed inflammation of both lungs.

The patient was a 70-year-old female. He was admitted to hospital on February 11, 2014. Eight months before admission, he had intermittent cough and a small amount of white phlegm without trigger, accompanied by swelling and pain of symmetrical proximal interphalangeal joints and metacarpophalangeal joints of both hands, which was obvious in the morning. Within 8 months, he was intermittently treated with cefaclor and ibuprofen sustained-release capsules, and the symptoms could be alleviated. He was admitted for further diagnosis and treatment. Previous history of hypertension for more than 40 years, with the highest blood pressure 190/110 mmHg (1 mmHg =0.133 kPa). Old myocardial infarction for 2 years, long-term oral administration of isosorbide mononitrate tablets (60 mg, once a day, 2 years) and atorvastatin tablets (1 mg, once a day, 2 years). Physical examination: body temperature 36 ℃, pulse 81 beats/min, breathing 21 beats/min, blood pressure 150/80 mmHg. The breathing sounds of both lungs were thick, scattered wet rales could be heard, and the symmetrical proximal interphalangeal joints and metacarpophalangeal joints of both hands were swollen and tender, but no abnormalities were observed. Auxiliary examination: arterial blood gas analysis: oxygen concentration 21%, PaO₂88 mmHg, PaCO₂38 mmHg. Blood routine: WBC 9.76×10⁹/L, percentage neutrophils 58.8%, absolute eosinophils 1.47×10⁹/L, % eosinophils 15.11%, PLT 352×10⁹/L. C-reactive protein (CRP) 70 mg/L. ESR 44 mm/1h. Rheumatoid factor 1 000 IU/ml, anti-cyclic citrulline antibody (CCP) positive. Exhaled nitric oxide 132.8 ppb. Chest CT: Lobular dense shadow in right lung (Figure 1)。 In order to further clarify the nature of lung lesions, bronchoalveolar lavage examination was performed, and routine examination of bronchoalveolar lavage fluid (BALF): neutrophil percentage 5%, eosinophil percentage 24%, macrophage percentage 71%. The patient was orally administered nifedipine extended-release tablets (30 mg, once a day, 10 years) and isosorbide mononitrate tablets (60 mg, once a day, 2 years). Parasite antigen, anti-neutrophil cytoplasmic antibody (ANCA), bone marrow puncture and blood smear were found no abnormalities after admission, further excluding parasites, ANCA-related vasculitis and hematological diseases. Diagnosis: rheumatoid arthritis (RA) with eosinophilic lung disease. Treatment: Methylprednisolone (40 mg, once/d), inhaled budesonide (2 ml/time, three times/d) anti-inflammatory, cyclophosphamide (100 mg, once/d), celecoxib (0.2 g, twice/d), montelukast sodium (10 mg, once/night) and other treatments, the patients' symptoms gradually alleviated after 7 days, CRP, peripheral blood eosinophils (0.09×10⁹/L) and exhaled nitric oxide (10.2 ppb) returned to normal. Methylprednisolone was sequentially administered orally (24 mg, once/d) and then discharged. After outpatient follow-up, chest CT showed that patchy shadows mainly in the right lung were gradually absorbed (Figure 2、Figure 3)。

The patient was an 80-year-old female. He was admitted to the Department of Infection and Clinical Microbiology of our hospital due to fever for 3 days and diarrhea for 1 day. Physical examination at admission: temperature 38.2℃, pulse 108 beats/min, breathing 20 beats/min, blood pressure 124/68 mmHg (1 mmHg =0.133 kPa). The pharynx is congested, both lungs knock without sound, and scattered fine wet rales can be heard in both lower lungs. Heart rate 100 beats/min, arrhythmia, no pathological murmur was heard in each valve area. Light tenderness in the upper abdomen (+), tenderness point in the right ureter (+). Stool routine: yellow soft stools, red blood cells (-), white blood cells (-), occult blood (-). Urine routine: urine red blood cells (±), bacteria count 85/μ L. Blood routine: white blood cells 19.82×10⁹/L, neutral 0.94, hemoglobin 117 g/L, platelets 156×10⁹/L, procalcitonin (PCT) 50.65 μ g/L and C-reactive protein (CRP) 138 mg/L. After hospitalization, amoxicillin-sulbactam 1.5 g was given intravenously 3 times/d. After 2 days of anti-infective treatment, the maximum body temperature still reached 38.9 ℃. Blood routine: white blood cells 18.47×10⁹/L, neutral 0.93, lymphatic 0.04; Red blood cells 3.61×10¹²/L; Hemoglobin 103 g/L; Platelets 120×10⁹/L; The PCT was 20.93 μ g/L. Considering the patient's systemic severe infection, the antibiotic was adjusted to piperacillin-tazobactam 4.5 g every 8 hours. The patient had a prior history of atrial fibrillation for 30 years, hypertension for 10 years, maximum blood pressure 180/130 mmHg, and diabetes for 10 years. After admission, chest CT showed: bilateral pulmonary cords and ground glass density shadows, considering interstitial changes combined with mild inflammation, bilateral localized pleural thickening and adhesion, and bilateral pleural effusion; Spleen low-density lesions, further abdominal examination is recommended. Enhanced CT of the whole abdomen showed cystic mass occupation in the spleen on the 4th day after admission (FIG. 1A), considering the possibility of splenic abscess. Puncture and drainage of splenic abscess were performed, and about 100 ml of brown turbid liquid was drained. The drainage liquid was routinely: Li Vanta test + +; The total number of cells was 16 243 537/μ L, the number of white blood cells was 963 537/μ L, and the classified mononuclear cells were 5.00%; Drainage fluid biochemistry: total protein 13.20 g/L; Chlorine 98.7 mmol/L; Sugar 14.88 mmol/L; Lactate dehydrogenase 5 314 U/L; Adenosine deaminase 509 U/L. The patient's white blood cell count and PCT showed a downward trend, and the anti-infective treatment with piperacillin-tazobactam continued. On the 7th day after admission, the patient's body temperature returned to normal, the drainage tube was unobstructed, and about 10 ml of yellow-brown pus could be drawn out every day, and the patient's condition improved. On the 11th day of admission, there was no fever, and the PCT 0.30 μ g/L was significantly lower than before. Fourteen days after admission, the cystic space in the spleen was significantly reduced by reexamination of abdominal CT (FIG. 1B)。 After continuing anti-infective therapy for 6 days, the PCT was 0.05 μ g/L, and the patient was discharged in stable condition.

March 2015BloodA study "Rituximab combined with recombinant human thrombopoietin versus rituximab in the treatment of glucocorticoid ineffective or recurrent immune thrombocytopenia" led by Professor Hou Ming of the Department of Hematology, Qilu Hospital, Shandong University and jointly completed by 12 centers in China was published [Zhou H, Xu M, Qin P, et al. A multicenter randomized open-label study of rituximab plus rhTPO vs rituximab in corticosteroid-resistant or relapsed ITP. Blood, 2015, 125 (10): 1541-1547]. This study is the first to compare the efficacy and safety of rituximab in combination with recombinant human thrombopoietin and rituximab monotherapy in patients with glucocorticoid-ineffective or recurrent immune thrombocytopenia (ITP).

November 2015BloodA multi-center clinical study of DEP regimen in the treatment of adult refractory hemophagocytic lymphohistiocytosis led by Professor Wang Zhao of Beijing Friendship Hospital affiliated to Capital Medical University and jointly completed by six centers in China was published [Wang Y, Huang W, Hu L, et al. Multicenter study of combination DEP regimen as a salvage therapy for adult refractory hemophagocytic lymphohistiocytosis. Blood, 2015, 126 (19): 2186-2192]. This study is the first prospective clinical trial in the world on the salvage treatment of refractory hemophagocytic lymphohistiocytosis (HLH) in adults.

Gout is a group of diseases in which blood uric acid increases due to disorders of purine metabolism and/or decreased uric acid excretion, resulting in tissue damage. Gout is divided into two main categories: primary and secondary. Primary gout has certain family heredity, and environmental factors are involved in the pathogenesis. Secondary gout is caused by other diseases, such as kidney disease, blood disease, or by taking certain drugs, tumor radiotherapy and chemotherapy, etc. Primary gout is more common in men, with a male-to-female ratio of 9:1. Gout is often associated with central obesity, hyperlipidemia, diabetes, hypertension and cardiovascular and cerebrovascular diseases.

For a long time, the relationship between postprandial blood glucose and the occurrence and development of diabetes has been a hot topic in the field of diabetes treatment. As early as the onset of diabetes, postprandial blood glucose has increased significantly^[1]。 Epidemiological survey data show that postprandial blood sugar increases are the main patients with type 2 diabetes in China^[2]。 Postprandial blood glucose or an independent risk factor for cardiovascular disease (CVD)^[3,4]。 Therefore, the International Diabetes Federation (IDF) has repeatedly updated the guidelines for postprandial glucose management to emphasize the importance of postprandial glucose management^[5,6]。 The following briefly describes the management of postprandial blood glucose in combination with evidence-based evidence at home and abroad.

Osteoarthritis is the most common chronic joint disease, most frequently involving the knee joint clinically^[1]。 With the aging of the social population, the incidence of this disease is increasing day by day. It has been reported in foreign literature that more than 60% of the elderly over 60 years old have degeneration of articular cartilage. Its main pathophysiological changes are cartilage loss, subchondral bone remodeling, osteophyte formation and inflammatory response of synovial fluid^[2]。 In the early stage, the main manifestations are swelling, pain and stiffness of the joint and its surrounding tissues. With the progression of the disease, it gradually leads to partial or even complete loss of joint function. According to a survey, the global disability rate of osteoarthritis was 2.2% in 2010, and the number of disabled people in the same year exceeded 1.7 million^[3,4]It has brought serious harm to society, families and individuals, so how to effectively treat osteoarthritis has become an increasingly urgent need of society. With further exploration and research, it has been found that hyaluronic acid in synovial fluid of osteoarthritis patients depolymerizes and is cleared at a higher clearance rate than that of healthy people, and these changes reduce the viscoelasticity of synovial fluid. Therefore, viscoelastic supplementary therapy for osteoarthritis came into being. After years of clinical practice and research comparison, there are still many controversies and uncertainties. Now, the research progress of hyaluronic acid in the treatment of knee osteoarthritis is comprehensively expounded.

acute nonvariceal upper gastrointestinal bleeding (ANVUGIB) is one of the most common critical emergencies in clinic. In 2009, Chinese Journal of Internal Medicine, Chinese Journal of Digestion and Chinese Journal of Digestive Endoscopy organized many special discussions with experts from gastroenterology, digestive endoscopy, general surgery and critical medicine in Hangzhou, and jointly formulated and promulgated the Guidelines for Diagnosis and Treatment of acute Non-variceal upper gastrointestinal bleeding (2009, Hangzhou)^[1]This guideline has played a very good guiding role in the clinical diagnosis and treatment of ANVUGIB in my country. In the past five years, with the rapid development of technology in various disciplines, new research progress has been made on the diagnosis and treatment of ANVUGIB. The guidelines issued in 2009 can no longer fully meet the needs of current clinical practice. Therefore, in November 2015, Chinese Journal of Internal Medicine, Chinese Journal of Medicine, Chinese Journal of Digestion and Chinese Journal of Digestive Endoscopy organized experts in related fields again, and revised the guidelines promulgated in 2009 as follows in combination with evidence-based medicine at home and abroad in recent years and reference to updated foreign guidelines.

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