Volume 97  ·  Issue 08  ·  2017

Fulminant type 1 diabetes mellitus (FT1D) is a new subtype of type 1 diabetes mellitus (T1DM) proposed by Japanese scholars in 2000^[1]。 The disease has a sudden onset, critical condition and dangerous prognosis. It is an acute and critical metabolic disease that often involves internal medicine, pediatrics, obstetrics and gynecology, dermatology, emergency department and other clinical disciplines. The etiology and pathogenesis of FT1D are still unclear. Initially, it was considered that its islet autoantibody was negative, and no isletitis was found in pancreatic pathological examination. It is a new subtype different from classical T1DM, so it was classified as idiopathic T1DM. The main clinical features are acute fulminant onset, severe ketoacidosis, high blood glucose and relatively low glycosylated hemoglobin levels, and acute β cell function failure. Drug allergy syndrome, viral infection and pregnancy may be susceptible factors to FT1D. Subsequent studies have found that autoimmune diseases and human leukocyte antigen (HLA) genes may be related to FT1D. In this paper, the genetic characteristics of FT1D from HLA genes and non-HLA genes are described as follows, so as to provide reference for peers.

multiple endocrine neoplasia type 2 (MEN2) is a cancer syndrome characterized by tumor or hyperplasia of neuroendocrine cells such as thyroid, adrenal medulla and parathyroid glands. It is autosomal dominant inheritance, high penetrance rate and early onset age. MEN2 includes 2 subtypes: MEN2A and MEN2B^[1]。 The incidence rate is approximately 1 in 30 000^[1,2,3]。

Treatment of short bowel syndrome (SBS) includes parenteral/enteral nutritional support therapy, medical therapy to improve symptoms and promote intestinal adaptation, increasing the effective absorption area of the intestine and surgical treatment for SBS complications, and small bowel transplantation in case of severe parenteral nutritional support complications. Faced with SBS patients with huge individual differences, clinicians often have a lot of confusion about how to formulate reasonable and effective individualized treatment plans. In order to make every SBS patient get standardized diagnosis and treatment, the China Short Bowel Syndrome Treatment Collaborative Group was established in Nanjing on November 27, 2015. According to the progress of SBS treatment at home and abroad, the Short Bowel Syndrome Treatment Center of Nanjing General Hospital of Nanjing Military Region drafted and wrote the consensus on the diagnosis and treatment of short bowel syndrome in China, which was reviewed, discussed and revised by all members of the China Short Bowel Syndrome Treatment Collaborative Group. At the same time, it is suggested that Xinhua Hospital affiliated to Shanghai Jiaotong University should add parts related to the diagnosis and treatment of children's SBS for the reference of clinicians in decision-making.

To analyze the insulin dose of type 1 diabetic patients who treated with insulin pump therapy during pregnancy in order to explore the features of these patients' insulin requirement during gestation.

A total of 12 well-controlled type 1 diabetic women patients who were treated with insulin pump therapy before and during gestation without any adverse pregnancy outcomes from June 2011 to December 2014 were selected from Guangdong Type 1 Diabetes Translational Medicine Study and included in the study. Demographic data, hemoglobin A1c (HbA1c) before pregnancy and before delivery, insulin dose, hypoglycemia episodes and pregnancy outcomes were collected to analyze the insulin dose of preconception, the 1^st, the 2^nd and the 3^rd trimester to analyze the requirement of insulin before and throughout pregnancy.

Subjects were (26.9±2.6) years old, with a diabetes duration of (6.6±4.4) years. HbA1c were (5.8±0.5)% before conception. The preconception total daily insulin dose, basal rate, bolus and bolus proportion were (0.60±0.18)U/kg, (0.28±0.10)U/kg, (0.32±0.13)U/kg and (54.8±12.9)%, respectively. Both of the insulin dose indexes mentioned above changed significantly in different trimesters compared with that in preconception (P value was <0.001, 0.034, <0.001 and <0.001, respectively). The total daily insulin dose, bolus and bolus proportion kept increasing during pregnancy. In the 1 ^st, the 2^nd and the 3^rd trimester, the total daily insulin dose rose by 0.2%, 45.4% and 72.7%, respectively, the bolus rose by 8.0%, 72.2% and 106.8%, respectively, and the bolus proportion rose by 8.0%, 16.8% and 19.0%, respectively. While the basal rate decreased by 9.0% in the 1^st trimester and rose by 14.1% and 32.9% in the 2^nd and 3^rd trimester, respectively.

In well-controlled pregnant women with type 1 diabetes mellitus, insulin requirement increased throughout pregnancy. Most of the increased insulin requirement was attributed to the bolus instead of the basal rate. When titrating the dose of insulin for the pregnant women complicated with type 1 diabetes mellitus, the physicians should consider their features of insulin requirement so as to optimize the glycemic control.

To identify human leukocyte antigen (HLA)-DRB1, DQA1 and DQB1 susceptible alleles and genotypes in latent autoimmune diabetes in adults (LADA) patients of Chinese Han nationality.

All subjects including 652 LADA patients and 1 181 healthy controls from 1999 to 2015 in Han nationality region of Hunan province were genotyped with high resolution at HLA-DRB1, DQA1 and DQB1 locus by PCR-sequence based typing (PCR-SBT). Frequencies of genotypes between patients and controls were compared by chi square test.

The DQA1 susceptible allele was DQA1*03 (OR=1.23, P_c=0.028); the DQB1 susceptible alleles were DQB1*0201 (OR=2.24, P_c<0.001), DQB1*0303 (OR=1.30, P_c=0.030), DQB1*0304 (OR=10.23, P_c=0.004) and DQB1*0401(OR=1.94, P_c<0.001); and the DRB1 susceptible alleles were DRB1*0301 (OR=2.10, P_c<0.001), DRB1*0405(OR=1.89, P_c<0.001) and DRB1*0901(OR=1.36, P_c=0.008), respectively in Chinese Han nationality LADA patients. The HLA-Ⅱ susceptible genotypes were DQA1*03/05 (OR=1.81, P_c=0.007), DQB1*0201/0201(OR=5.74, P_c<0.001), DQB1*0201/0303 (OR=2.58, P_c=0.010), DRB1*0301/0901(OR=3.43, P_c=0.028) and DRB1*0901/0901 (OR=1.82, P_c=0.021), respectively in LADA patients. DQB1*0201 and DRB1*0301 were shared susceptible alleles for Chinese Han and Caucasian LADA patients, while DQA1*03, DQB1*0303, DQB1*0304, DQB1*0401, DRB1*0405 and DRB1*0901 were specific susceptible alleles for Chinese Han LADA patients. Interestingly, the DQB1*0303 allele was susceptible in Chinese while protective in Caucasian (OR: 1.30 vs 0.29).

Susceptible alleles are DQA1*03, DQB1*0201, DQB1*0303, DQB1*0304, DQB1*0401, DRB1*0301, DRB1*0405 and DRB1*0901, and susceptible genotypes are DQA1*03/05, DQB1*0201/0201, DQB1*0201/0303, DRB1*0301/0901 and DRB1*0901/0901 in Chinese LADA patients.

To describe the insulin regimens and their associations with glycemic control and to explore factors associated with intensive insulin therapy.

Patients with type 1 diabetes (T1DM) were recruited from Guangdong Type 1 Diabetes Mellitus Translational Medicine Study which was conducted in 16 centers in Guangdong province. The demographic and clinical data were collected. Patients were grouped according to different insulin regimens: insulin pump (R1), basal insulin plus regular insulin or short-acting insulin (R2), insulin injection 1-3 times per day (R3). Distribution of insulin regimens and the relationships between insulin regimens and hemoglobin A1c (HbA1c) were described. Multivariate logistic regression was used to identify factors associated with intensive insulin therapy.

A total of 1 421 patients with the age of 27.8 (19.4, 38.3) years and a duration of T1DM of 3.3 (0.5, 7.1) years were recruited. There was 12.3% of patients in R1 (n=175), 35.5% in R2 (n=504), and 52.2% in R3 (n=742), respectively. HbA1c was 8.0 (6.8, 9.3)%, 8.9 (7.1, 11.8)%, and 9.2 (7.5, 11.4)% in R1, R2, R3, respectively, and it was associated with insulin regimens (P<0.001). HbA1c target rate was 32.3%, 21.1%, 17.8% in R1, R2, R3, respectively (P=0.002). Older age (OR=1.01, P=0.027), higher education level (college or above) (OR=1.56, P=0.003), and higher household income (>30 000 yuan per year per person)(OR=1.45, P=0.009) were associated with intensive insulin therapy in adult patients.

The study suggested that insulin therapy need to be optimized in patients with T1DM. The optimization of insulin regimens and diabetes education may be helpful for improvement of glycemic control.

To investigate the clinical characteristics and prognosis of multiple myeloma (MM) patients undergoing hemodialysis (HD).

All MM patients initiating HD between Jan 1 st, 2008 and Oct 31 st, 2015 at Kidney Disease Center of the First Affiliated Hospital of Zhejiang University with complete data (n=96) were enrolled. Age, initiating HD time and vascular access matched non-MM patients receiving HD were selected as the control group, and the ratio was 1∶2 (n=192). Chi-squared analysis was used for unadjusted comparisons and logistic regression was used for adjusted comparisons between patients with and without MM. Kaplan-Meier analysis and log-rank test were applied to compare survival of patients. Cox proportional hazards regression was used to analyze prognostic factors for patients with MM after HD.

Compared to the control group, MM patients had higher percentage of coronary heart disease, pulmonary infection, and serum calcium, lower percentage of diabetes, lower hemoglobin and platelet (P<0.05). The median follow-up time was 488 (212-1 064) days. At the end of the study, 68.8% (66/96) patients in the MM group died, 26.0% (25/96) patients survived, and no patients (0/96) switched to transplantation; in the non-MM group, the above-mentioned percentage was 16.7% (32/192), 70.8% (136/192), 6.3% (12/192), respectively. Kaplan-Meier analysis showed that MM patients had significantly lower survival rate (P<0.01). In the MM group, the median total survival time was 205 days, and the median survival time for patients with hematologic complete remission (CR), partial remission (PR) and below PR (three subgroups) was 1 115, 417, 124 days, respectively. Kaplan-Meier analysis showed that the difference of cumulative survival rate of three subgroup was statistically significant (P<0.01). Four factors were found to be correlated with survival rate of MM patients required HD using Cox multivariate regression model: age≥70 years (HR=1.98, P=0.03), use of catheter (HR=3.24, P=0.02), low albumin (HR=2.31, P=0.04), and below PR (HR=2.80, P<0.01).

MM patients undergoing HD had higher percentage of coronary heart disease, pulmonary infection, and serum calcium, lower percentage of diabetes, lower hemoglobin and platelet. The survival of MM patients required HD was poor, with high risk of mortality. Age, vascular access of HD, albumin and hematological response were correlated with survival of patients.

To identify the clinicopathological features of extramammary Paget's disease(EMPD) and investigate the clinical and histopathological significance of acantholysis in EMPD.

From June, 2010 to October, 2016, a total of 56 patients were diagnosed as EMPD in the Department of Dermatology, Peking Union Medical College Hospital. Clinical and histopathological data were retrieved from these patients' medical records and analyzed respectively. The cases were divided into two subgroups according to the histopathological pattern (with or without acantholysis): the acantholytic EMPD (AEMPD) group and the non-acantholytic EMPD (N-AEMPD) group. The clinicopathological data were compared and statistically analyzed between the two groups.

The AEMPD group included 22 cases (39.3%), while the N-AEMPD group included 34 cases (60.7%). The male: female ratio, the age of onset, and the median duration of the disease were 10∶1 vs 10.3∶1, (64±8)vs (64±10)years, and 42(4-240)months vs 48(3-120) months in the AEMPD and N-AEMPD groups, respectively, with no significant difference (all P>0.05). There was no significant difference in the severe dermal inflammation (27.3% vs 17.6%,P=0.600 ) and cytologic anaplasia(13.6% vs17.6%, P=0.979)between the AEMPD and N-AEMPD groups.Adnexal involvement or dermal invasion (72.7%) was significantly more common in cases with AEMPD, compared to cases with N-AEMPD (23.5%, P<0.001). And 17 cases in the AEMPD group (77.3%) were Hailey-Hailey-disease-like subtype. The recurrence rate after surgical management (29 cases) showed no significant difference between the two groups (1/12 vs 4/17,P=0.370).

Acantholysis is common in EMPD. It is not associated with sex, the age of onset, and the duration of the disease. Acantholysis may indicate invasive growth of Paget's cells. Its occurrence has no association with severe dermal inflammation or cytologic anaplasia. Hailey-Hailey-disease-like subtype is the most common subtype in AEMPD, requiring careful consideration to avoid misdiagnosis. Postoperative recurrence is not associated with acantholysis in EMPD.

To explore the effects of microRNA (miR)-373 on proliferation and invasion of breast cancer cells and its mechanisms.

Breast carcinoma tissues and its corresponding normal tissues (80 cases) were obtained from the First Affiliated Hospital of Zhengzhou University from 2010 to 2014. Quantitative real-time (RT)-PCR was used to detect the expression of miR-373 of breast carcinoma tissues and its corresponding normal tissues. The cellula experiment was divided into three groups: the normal control group, the miR-373 mimic group and the miR-373 inhibitor group. The proliferation was detected by Cell Counting Kit.8 (CCK-8) method and the invasion and migration were detected by Transwell method. Effect of miR-373 on cell apoptosis was determined by Flow Cytometry.

Expression of miR-373 in breast cancer tissue was significant lower than the normal breast tissues (0.21±0.09 vs 0.98±0.23, P<0.001); expression of miR-373 contributed to the inhibition of Bcl-6 expression. The apoptosis rate in miR-373 was higher than normal control group (18.29%±0.29% vs 4.91%±0.31%), cell proliferation, cell invasion and cell migration were lower than normal control group [(0.69±0.11) vs (1.25±0.12) (the fifth day), (30.50±0.20) vs (66.50±0.42), (29.50±0.21) vs (48.50±0.31), allP<0.05].

miR-373 plays a suppressive role in proliferation and invasion of breast carcinoma, and the downregulation of miR-373 promotes the invasion of breast cancer which may mediate by the increased expression of Bcl-6.

Prostate cancer is commonly diagnosed among old men while younger men are rarely diagnosed with prostate cancer. In this study we identify clinical and pathological features of 154 patients with prostate cancer younger than 55 years old and to assist intreatment decisions.

The medical records of 154 prostate cancer patients younger than 55 years old in Peking University First Hospital from Feb 1953 to Jun 2016 were reviewed, retrospectively. Data was collected including symptoms, digital rectal examination (DRE), prostate-specific antigen (PSA), Gleason score, tumor stage, treatment strategies.

The mean age was 50.9±4.5, and 25.3% patients were between 40-50 years. Fifty-six (36.4%) patients initially presented with lower urinary tract symptoms. A solid mass could be found by digital rectal examination in 48(31.2%) patients. All patients were diagnosed by pathology of biopsy or surgery. The median Gleason score was 8. Gleason 2-6, 3+ 4, 4+ 3, 8, 9-10 were 15 cases(9.7%), 28 cases(18.2%), 21 cases(13.6%), 15 cases(9.7%), 51 cases(33.1%), respectively. Based on 2009 AJCC TNM Classification criteria the distribution of tumor stage was T1, T2, T3, and T4 in 2(1.3%), 54 (35.1%), 60 (39.0%), and 37 (24.0%) patients. Forty patients (25.9%) were found with bone metastasis and four (2.5%) suffered from visceral metastasis. Fifty-three(34.4%)underwent hormonal therapy and 79(51.3%) underwent radical prostatectomy.

Younger prostate caner patients usually presented with LUTS symptoms and were featured for higher tumor stage and aggressiveness. More optimal and personalized risk-based therapy options are required.

To investigate the effects of miR-382 on cell migration, invasion and proliferation of gastric cancer cell lines MGC-803.

The level of miR-382 expression was detected by real-time RT-PCR in 50 paired gastric cancer tissues and their adjacent normal tissues. miR-382 overexpression was achieved by transfection of construct pcDNA-miR-382 into MGC-803 cells. The migration, invasion and proliferation of MGC-803 cells were detected by the scratch wound assay, Transwell and CCK-8, respectively.

miR-382 was decreased in 41 cases (82%) of gastric cancer tissues compared to their control. Furthermore, overexpression of miR-382 effectively inhibited the migration, invasion and proliferation of MGC-803 cells(P<0.05).

Down-regulation of miR-382 has a correlation with the progression of gastric cancer. Up-regulation of miR-382 can inhibit the migration, invasion and proliferation of MGC-803 cells.

To develop and validate an autoverification system for biochemistry and immunology test results for application in routine work.

Algorithms was designed and translated into the laboratory information system. Parameters including verify limit, delta check, logic relation between tests was set up in the system. Verification rate of every test and the causes of fails were analyzed, according to which the system and parameters were modified. The autoverified reports were evaluated by chief technicians. Only when all of the autoverified results pass the evaluation, the system applied for routine work of releasing the results. Autoverification rate and turnaround time(TAT) were calculated for evaluation of the efficiency of the system.

A brand new autoverification system was developed and applied for routine work. The autoverification rate for each single test was 91.1%-96.6%. The autoverification rate for reports was 74%. With the autoverification system, the media of TAT reduced from 111.6(53.9-270.7) min to 87.2(45.4-202.4) min, whereas the time from instrument finishing analysis to releasing the reports reduced from 18.6(1.0-99.3) min to 0.1(0-58.3)min. The number of staff specified for results validation reduced from three to one.

The newly developed system can be used for autoverification of biochemistry and immunology test results. The autoverification system can greatly reduce TAT and raise working efficiency. It's essential to employ carefully designed algorithm, appropriate parameters and comprehensive evaluation when developing a new autoverification system.

Left heart disease-associated pulmonary hypertension (PH-LHD) is a common type of pulmonary hypertension, which can be accompanied by various left heart diseases, such as valvular heart disease, heart failure, congenital or acquired left ventricular inflow or outflow tract obstruction, and hereditary cardiomyopathy^[1]。 The prevalence of PH-LHD accounts for about 1/3 of pulmonary hypertension. Up to 80% of patients with heart failure can develop PH-LHD, including heart failure with preserved or reduced ejection fraction. Once combined with pulmonary hypertension, it can lead to aggravation of symptoms and poor prognosis^[2,3]。

Acute lymphocytic leukemia (ALL) is the most common malignant tumor in children. With the improvement of diagnostic classification technology and the application of combined chemotherapy in recent years, the long-term survival rate has reached 90%^[1]However, relapsed and refractory B-line acute lymphocytic leukemia (B-ALL) remains an important cause of childhood leukemia-related mortality^[2,3]。 Adult ALL has a low incidence but poor prognosis, with an overall 5-year survival rate of less than 40%^[4]The average survival time of relapsed patients was only 6 months^[5]。 Tumor-targeted immunotherapy represented by T cells modified by chimeric antigen receptor (CAR) has shown good targeting, killing and durability in vitro and clinical trials, demonstrating great application potential and development prospects. Among them, the great success of CAR-T cells targeting CD19 molecules (CD19 CAR-T) in the treatment of relapsed and refractory B-ALL is a milestone in this field^[6]。 After many achievements, its existing problems have gradually surfaced. In recent years, there have been endless reports of recurrence after treatment, and even cases of CD19 turning negative after treatment have appeared. This paper discusses the recurrence mechanism of this emerging immunotherapy.

Pulmonary hypertension is a kind of fatal cardiovascular disease, which causes pathophysiological changes of pulmonary vascular resistance and pulmonary artery pressure gradually increase due to the combined action of genetic, environmental factors and various etiologies. Among them, the first major type of pulmonary hypertension is also called arterial pulmonary hypertension (PAH), which can be further subdivided into idiopathic pulmonary hypertension (IPAH), hereditary pulmonary hypertension (HPAH), drug and poison-related pulmonary hypertension and other disease-related pulmonary hypertension^[1]。

Breast cancer is one of the most common malignant tumors in women, accounting for the first mortality rate of female malignant tumors^[1]。 Although the incidence of breast cancer has been increasing, due to the rapid progress in diagnosis and treatment in the past decade, the mortality rate related to breast cancer has been continuously declining^[2]。 Clinical treatment of breast cancer mainly includes surgery, radiotherapy, chemotherapy, targeted therapy and endocrine therapy. However, due to the widespread existence of drug resistance problems and the lack of effective biomarkers, the treatment of breast cancer is still not ideal. In the context of the precision era, tumor immune targeted therapy has gradually entered our field of vision, bringing earth-shaking changes to tumor treatment. The 2016 American Society of Clinical Oncology (ASCO) Annual Meeting rated tumor immunotherapy as the most important progress in tumor treatment, and tumor immunotherapy officially opened the road to the star of tumor treatment. In tumor immunotherapy, the therapeutic research related to programmed death receptor 1 (PD1) /programmed death ligand 1 (PD-L1) is in full swing in the field of tumor, and has become the focus of attention all over the world. The field of treatment of breast cancer has also emerged. In this paper, the application of the immune checkpoint PD1/PD-L1 pathway in breast cancer will be detailed.

Recently, I had the honor to read "Analysis of the efficacy of simultaneous revascularization in the treatment of severe stenosis of carotid and coronary arteries" published in the 24th issue of Chinese Medical Journal in 2015^[1]This article (hereinafter referred to as "this article") has benefited a lot, but I also feel that there are doubts about the Chinese translation and application of Charlson's Comorbidity Index (WIC) in this article, which is worthy of discussion.

The interpretation of comorbidities in modern Chinese dictionaries is indeed consistent with the author's description, but as a clinician, the understanding of "comorbidities" and "complications" is completely different: complications are a complex clinical medical concept. Scholars have the following definitions of complications: (1) Complications refer to the occurrence of another disease or symptom caused by one disease in the process of development, and the latter is the complication of the former. For example, peptic ulcer may have complications such as pyloric obstruction, gastric perforation or massive bleeding. (2) Complications refer to the combination of one disease and another or several diseases related to this disease in the process of diagnosis, treatment and care. Comorbidity refers to the combination of another disease or diseases under a special physiological condition or during the development of a disease, the latter disease is not caused by a special physiological condition or the former disease. Such as pregnancy complicated with essential hypertension, diabetes complicated with hepatitis B, etc. The difference between complications and comorbidities is whether there is a causal relationship between the two diseases before and after. What is causal is a complication, and what is not causal is a comorbidity. Therefore, according to the literal meaning of Charlson's weighted index of comorbidities (WIC), its comorbidities are close to the underlying disease; The specific translation is: Charlson's comorbidity weight index is more accurate. At present, the commonly used in the article is Charlson's comorbidity index or Charlson's index, with the same content and no obvious ambiguity.