Volume 99 ·  Issue 34 ·  2019

With the progress of science and technology, new technologies for blood glucose monitoring and treatment of type 1 diabetes are constantly emerging. New insulin analogs, intelligent insulin pumps, continuous glucose monitoring (CGM) systems and closed-loop insulin infusion systems help to improve the management level of patients with type 1 diabetes. The combination of artificial intelligence and new technologies may further boost the individualized blood sugar control of patients with type 1 diabetes and improve the quality of life of patients.

For a long time, there has been a lack of unified diagnostic criteria for gestational diabetes mellitus (GDM) in the world, until the hyperglycemia and adverse outcomes of pregnancy (HAPO) study was announced in 2008, and the diagnostic criteria of the International Consensus Group on Pregnancy Complicated with Diabetes (IADPSG) were born in 2010. It was adopted by more and more countries and academic institutions, which basically ended this situation. In 2019, with the successive publication of the HAPO Follow-up Study (HAPO FUS), the industry has developed a deeper understanding of the postpartum outcome of GDM and the far-reaching impact of mild hyperglycemia during pregnancy on both mothers and infants. This article will explain from HAPO research to HAPO FUS to understand the implications of these landmark studies.

Islet endothelial cells and beta cells are important components of pancreatic islets, and there is a close relationship between them in cell function and survival. At the same time, pancreatic islet endothelial cells play a certain role in the pathogenesis and therapy of diabetes. Therefore, in-depth exploration of the molecules and signaling pathways involved in the dialogue between islet endothelial cells and β cells will be beneficial to understand the regulatory mechanism of islet function and may provide new targets for diabetes treatment.

To investigate the awareness of preconception care among women of child-bearing age with type 1 diabetes (T1DM) and their self-management status, in order to provide evidence for establishment of management pathway for women with T1DM in pregnancy in China.

This cross-sectional survey recruited female participants of child-bearing age from the cohort of Guangdong Type 1 Diabetes Translational Medicine Study conducted between June 2011 and December 2017. The participants were asked to fill out a questionnaire on the awareness of preconception care, their frequency of self-monitoring of blood glucose (SMBG) and other related variables. Chi-squared test or chi-squared test for trend was used in comparisons of categorical variables, and logistic regression analysis was performed to assess associated factors.

Totally, 441 women of child-bearing age with T1DM were investigated. The results show that their awareness of preconception care was poor (15.42%, 68/441). Higher educational level (χ^2trend=3.990, P=0.046), experience of post-diabetes education evaluation (P<0.001), and better coverage of different modules in diabetes education (survival skills: χ ²=7.525, P=0.004; basic knowledge: χ ²=8.598, P=0.002; advanced knowledge: P<0.001) were associated with better awareness of preconception care. The average frequency of SMBG in these participants was 0.29 (0.14, 2.00) times per day, and only 8.5% (37/435) of them reached the frequency (≥4 times per day) recommended by guidelines. Moreover, 21.1% (92/435) of them hardly ever performed SMBG.

Child-bearing age women with T1DM in Gunangdong had poor awareness of preconception care, with a much lower SMBG frequency than recommendation.

To investigate the changes of circulating proteinase 3 (PR3) in latent autoimmune diabetes mellitus in adults (LADA) patients, type 2 diabetes mellitus (T2DM) patients, obese patients without diabetes and healthy controls, and explore the value of serum PR3 in differentiating LADA and T2DM.

Forty LADA patients, 29 T2DM patients, 26 obesity patients without diabetes, and 76 healthy controls were enrolled in Department of Metabolism & Endocrinology, the Second Xiangya Hospital, Central South University. Serum PR3 was detected by enzyme-linked immunosorbent assay (ELISA). The differences of serum PR3 among the four groups were compared. The correlation between serum PR3 and other metabolic indexes was analyzed. The value of serum PR3 in the differential diagnosis between LADA and T2DM was evaluated.

There was no significant difference in age among LADA patients, T2DM patients, obesity patients without diabetes and healthy controls [(50±13) years, (49±6) years, (49±6) years vs (47±7) years, P=0.254], while there was significant difference in gender among the four groups (χ²=18.28, P<0.001). Serum PR3 was significantly increased in LADA patients compared to the other three groups [195.4 (127.6, 288.1) μg/L vs 43.4 (30.9, 53.7) μg/L, 36.0 (29.2, 46.4) μg/L, 41.2 (30.2, 52.8) μg/L, all P<0.01], whereas there was no significant differences among the other three groups. After adjustment for age, gender and body mass index (BMI), serum PR3 remained higher in LADA patients compared to the other three groups. Correlation analysis indicated that PR3 correlated positively with fasting and 2-hour postprandial blood glucose (r=0.346, r=0.357, both P<0.001). Receiver operating characteristic (ROC) curve showed that the cut-off value of PR3 (71.7 μg/L) for differentiating LADA and T2DM had a sensitivity of 97.5% and specificity of 89.7% and rendered an area under the curve of 0.955 (95% CI: 0.894~1.000, compared to 0.5, P<0.01).

Serum PR3 significantly elevated in LADA patients, and may serve as a biomarker for differentiating LADA and T2DM patients.

To investigate the relationship between insulin resistance (IR) and dyslipidemia in adults with type 1 diabetes (T1DM) and provide more insights on diabetes-related cardiovascular disease management.

A cross-sectional study recruiting patients from Guangdong T1DM Translational Study cohort was conducted between 2011 and 2017. The patients aged ≥18 years, with a diabetes duration of ≥1 year were enrolled in the study. Plasma lipid profile data of eligible patients, including total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C) and high-density lipoprotein cholesterol (HDL-C) were collected and their relationships with insulin resistance were analyzed. IR in these adults with T1DM was estimated by glucose disposal rate (eGDR) calculated by a model published previously. Patients with eGDR lower than 25 percentiles were grouped as severe IR, otherwise non-severe IR.

In total, 499 eligible patients were studied, among which 274 were women (54.9%). The level of eGDR was 8.43 (6.11, 10.63) mg kg^-1 min^-1 and the overall incidence of lipid disorders was 65.3% (326/499) in the study population. The result showed that eGDR was correlated with TC, TG, HDL-C and LDL-C (r=-0.163, -0.303, 0.170 and -0.150, respectively, all P<0.05). After adjusting for gender, age and diabetes duration, eGDR was still associated with TG, TC and LDL-C (all P<0.05). Stepwise multiple linear regression analysis showed that gender (female), elevated TC and declined HDL-C were independent factors associated with the severity of IR (t=5.651, 5.823 and 2.908, respectively, all P<0.05).

IR is associated with dyslipidemiain in adults with T1DM. Elevated TC and decreased HDL-C are independent associated factors for insulin resistance.

To investigate the expression and interaction of VHL/HIF-α pathways including HIF-1α, HIF-2α as well as VHL in erythroid progenitor cells of bone marrow from chronic mountain sickness (CMS) patients.

A total of 25 patients with CMS and 21 healthy controls were recruited for this study. The CD71⁺CD235a⁺ cells in bone marrow mononuclear cells, marked as erythroid progenitor cells, were isolated using MACS separation technology. The expression levels of HIF-1α, HIF-2α and VHL in erythroid progenitor cells were detected by Western blotting and real-time fluorescence quantitative PCR.

The mRNA levels of HIF-2α were higher in erythroid progenitor cells of CMS than in healthy controls [1.68 (0.81, 2.22) vs 0.98 (0.60, 1.19),P<0.05], while HIF-1α and VHL mRNA levels were similar between the two groups (P>0.05). Spearman analyses indicated that HIF-2α mRNA was positively associated with hemoglobin (Hb) levels in the erythroid progenitor cells of CMS (ρ=0.504, P<0.05). Furthermore, the mRNA level of HIF-2α was correlated with the mRNA level of VHL in the erythroid progenitor cells of CMS (ρ=0.647, P<0.05).The protein levels of HIF-2α in the erythroid progenitor cells of CMS were higher than that of healthy controls [0.94(0.68, 3.30) vs 0.59(0.30, 0.88),P<0.05], but the protein levels of HIF-1α and VHL were similar between the two groups (P>0.05).

The abnormal increased expression of HIF-2α in the erythroid progenitor cells of CMS patients leads to the abnormal expression of hypoxia sensitive genes downstream, participating in the occurrence and development of CMS.

To assess the effectiveness and safety of sacral neuromodulation (SNM) therapy for men with idiopathic dysuria.

From January 2012 to December 2016, a total of 26 patients treated with SNM therapy from multi-center across the country were retrospectively studied. The age ranged from 19 to 86 years with an average age of 45.2 years. Patients suffered from one or multiple urinary symptoms such as frequency of urination, urgency, urinary retention, etc. All patients had received more than two types of conservative therapy including oral and behavioral therapy, but had poor or no improvement. The voiding diary, urgency score and the quality of life score before implantation, in stageⅠ after implantation and stage Ⅱ after permanent implantation were recorded and compared.

A total of 22 patients chose to receive IPG at the end of stageⅠ therapy while 4 patients refused further stage Ⅱ therapy because of dissatisfactory effect. The conversion rate of stage Ⅰ to stage Ⅱ was 84.6% (22/26). The average follow-up time was 19.2 months, ranging from 3 to 63 months. The baseline of residual urine, voiding frequency and average voiding amount and those after stage Ⅰ therapy were [5 (0, 137.5) ] ml vs [0 (0, 40) ] ml, 14.6±6.1 vs 9.1±2.8, [100 (80, 135) ] ml vs [190 (150, 210) ] ml, respectively. The differences were statistically significant(allP<0.05).However, no significant differences were found in urination volume and quality of life (QoL) before and after implantation(P>0.05). During an average follow-up time of 19.2 months after the permanent implantation, over 80% patients had an improvement of residual urine volume by more than 50% after permanent implantation while the improvement was 55.6% after stage Ⅰ therapy, suggesting that the improvement of residual urine volume might be positively correlated with the duration of regulation. No significant differences were found in other parameters between stage Ⅰ and Ⅱ therapy. No adverse events like wound infection and electrode dislocation happened during our study.

SNM is an effective and safety procedure for male patients with idiopathic dysuria, with a relatively high transfer rate. The medium-term curative effect is stable. The duration of regulation may be positively correlated with the improvement of residual urine.

To investigate the phenomenon of small airway epithelial-mesenchymal transition (EMT) in patients with normal pulmonary function and chronic obstructive pulmonary disease (COPD) who received surgical treatment for lung tumors.

In this study, 52 patients undergoing surgical treatment for lung tumors admitted to the General Hospital of Ningxia Medical University were included from January 2018 to January 2019. According to the preoperative pulmonary function and smoking history, patients were divided into group A (non-smoking with normal pulmonary function group, 15 patients), group B (smoking with normal pulmonary function group, 21 patients), group C (COPD stable phase group, 16 patients). HE staining was performed to observe the pathological changes in small airway and lung tissue. Immunohistochemistry was used to detect the localization and expression of E-cadherin, α-smooth muscle actin (α-SMA) and Vimentin in small airway. Western blot was used to detect the levels of E-cadherin, α-SMA and Vimentin.

(1) There were no significant differences in age, gender, and the ratio of disease composition among the three groups (P>0.05), but forced expiratory volume in one second (FEV₁) as percentage of predicted value (FEV₁%pred) and FEV₁/forced vital capacity (FEV₁/FVC) in group C were lower than those in groups A and B (all P<0.01), while there was no significant difference between group A and group B (P>0.05); (2) the bronchial wall thickness in group B and group C were higher than that of group A [(32.4±2.4) and (54.6±4.9) vs (22.4±2.2) μm], and group C was significantly higher than group B ( P=0.003); (3) the expression levels of E-cadherin in the epithelial cells of small airway in group B and group C were lower than those in group A (0.021±0.008 and 0.018±0.007 vs 0.062±0.010) (all P<0.05), while the levels of mesenchymal cell markers such as α-SMA and Vimentin in group B and group C were higher than group A, and group C was higher than group B (α-SMA: 0.641±0.113, 0.780±0.133 vs 0.404±0.123; Vimentin: 0.064±0.033, 0.083±0.022 vs 0.030±0.021) ( P=0.002 and P=0.003).

In patients undergoing surgical treatment of lung tumors, there is EMT in the small airways of patients with COPD, and EMT has occurred in the small airways of smokers with normal pulmonary function.

To explore the relationship between blood pressure load and sleep stability in hypertensive patients by cardiopulmonary coupling monitoring (CPC) and 24-hour ambulatory blood pressure monitoring.

One hundred and fifty-five patients with essential hypertension were divided into high load group and low load group according to whether the blood pressure load was higher than 50%. The relationship between sleep stability and systolic blood pressure load was analyzed by logistic regression.

After adjusting for sex, age and body mass index (BMI), logistic regression analysis showed that stable sleep was the protective factor (OR=0.736,P=0.047) for the decrease of nocturnal blood pressure load, and unstable sleep was the risk factor for increasing day time blood pressure load (OR=1.336, P=0.037) in patients with hypertension.

The effect of sleep stability on blood pressure load is different between day and night. Stable sleep is the protective factor of nocturnal systolic blood pressure load decrease, and unstable sleep is the harmful factor of daytime systolic blood pressure load increase. Increasing sleep stability helps to reduce systolic blood pressure load.

To investigate the clinical features of patients with atrial fibrillation (AF) and occult pulmonary embolism (PE).

Clinical data of 67 AF patients complicated with PE (AP group) admitted to the Tianjin Chest hospital from January 2014 to July 2018 were analyzed. A total of 70 AF patients without PE served as the control group (AF group). The AP group was divided into 2 subgroups: AF with occult PE (OPE subgroup) and symptomatic PE (SPE subgroup). The clinical features of OPE subgroup were analyzed.

The levels of leukocyte counts, C-reactive protein, D-dimer and N-terminal pro-brain natriuretic peptide in the AP group were (7.4±2.7)×10⁹/L, 18.0 (5.9, 65.7) mg/L, 2.61 (1.63, 3.72) mg/L and 1 657 (600, 3 172)ng/L, which were higher than those in the AF group (P=0.008, P<0.001, P<0.001 and P=0.002, respectively); Arterial oxygen pressure in the AP group was (74±13) mmHg (1 mmHg=0.133 kPa), lower than the AF group (P<0.001); and pulmonary artery systolic pressure was (46±16) mmHg, higher than the AF group (P<0.001). In the OPE subgroup, 12 cases (66.7%) were complicated with localized pulmonary embolism, more than those in the SPE subgroup (P=0.008), and pulmonary artery systolic pressure was (39±11) mmHg, which was lower than the SPE subgroup (P<0.001); the levels of leukocyte counts, C-reactive protein and D-dimer in the OPE subgroup were (7.6±2.3)×10⁹/L, 18.3 (3.7, 67.3) mg/L and 2.31 (1.27, 3.61) mg/L, higher than the AF group (all P<0.05); arterial oxygen pressure in the OPE subgroup was (75±12) mmHg, lower than the AF group (P<0.05).

Occult pulmonary embolism is not uncommon in patients with atrial fibrillation. Comparing with AF group, the OPE subgroup was associated with increased levels of inflammatory markers and D-dimer and hypoxemia.

To investigate the clinical features of lung natural killer (NK)/T cell lymphoma.

The clinical data of patients with lung NK/T-cell lymphoma confirmed by pathology who were hospitalized due to lung shadow and initially treated as pneumonia from the First Affiliated Hospital of Zhengzhou University was collected from June 2013 to January 2019. The clinical manifestations, laboratory tests, chest CT findings, treatment procedures, outcomes, and misdiagnosis were retrospectively analyzed.

Among the 15 enrolled patients with lung NK/T-cell lymphoma, 5 were primary and the other 10 were secondary. There were 8 males and 7 females, aged 20-76 years. Fever presented in 14 cases, dyspnea was observed in 4 cases and 2 cases had cough. A total of 12 cases had leukopenia, 10 cases had mononuclear cell increase, 10 cases had liver dysfunction, 13 cases had elevated serum lactate dehydrogenase (LDH), and 2 cases of primary lung NK/T-cell lymphoma had increased pleural LDH and adenosine deaminase. Five cases of primary lung NK/T-cell lymphoma had multiple lung lesions, with diffuse multiple solid shadows, ground glass and patchy shadows, some with nodules; 10 cases of secondary lung NK/T-cell lymphoma showed nodular masses, some were accompanied by patchy shadows, and most patients had multiple lesions scattering in the lung. All the fifteen patients were misdiagnosed as pneumonia in the early stage, and then were diagnosed by percutaneous lung biopsy or transbronchial biopsy. Six patients underwent chemotherapy, of which 1 achieved complete response, 4 were in follow-up and 1 died of respiratory failure; 5 patients died of respiratory failure after diagnosis and 4 patients discharged and died within half a year.

The lung NK/T-cell lymphoma are rare. The clinical manifestations and pulmonary imaging findings are indistinguishable from pulmonary inflammatory lesions. They are easily misdiagnosed as pneumonia. Early CT-guided percutaneous lung biopsy or transbronchial biopsy can improve the diagnostic accuracy.

To established Apc^loxp/loxp+Kras^LSL-G12D/-+Smad4^loxp/loxp transgenic mouse model that mimick the occurrence and development of human sporadic colorectal cancer(CRC) and its liver metastasis.

C57BL/6-Apc^tm1Tyj/J(Apc^loxP), B6.129S4-Kras^tm4Tyj/J(Kras^LSL-G12D), 129S6-Smad4^tm2.1Cxd/J(Smad4^loxP) and C57BL/6J mice were crossed, and genotype with Apc^loxP/loxP+Kras^LSL-G12D/-and Apc^loxP/loxP+Kras^LSL-G12D/-+Smad4^loxP/loxPwere generated. Genotypes of the mice were identified by PCR and real-time quantitative PCR. The mice were divided into Apc^loxP/loxP+Kras^LSL-G12D/-+Smad4^loxP/loxP group (n=20) and Apc^loxP/loxP+Kras^LSL-G12D/-group(n=24). Lentivirus expressing Cre enzyme and IRES-luciferase were injected into the submucosa of colon or rectum of the transgenic mice under colonoscopy. Intraabdominal injection of D-luciferase into mice every 4 weeks, imaging with small animal in vivo imaging system(IVIS). The tumor size, tumorigenesis rate and metastasis ratio were analyzed. At the end of the 20th week, the colorectal lesions and metastatic tissues of mice were stained with hematoxylin-eosin(HE) and the pathological changes were observed under microscope.

Apc^loxp/loxp+Kras^LSL-G12D/-+Smad4^loxp/loxp and Apc^loxp/loxp+Kras^LSL-G12D/-transgenic mice were successfully bred. The colorectal stem cells of the transgenic mouse mutated leading tumor lesion and liver metastatic under the induction of Lentivirus^{Cre-IRES-luciferase}. The primary and metastatic foci of colorectal carcinoma and liver metastasis in mice were proved to be adenocarcinoma and liver metastatic carcinoma by histopathological examination. The primary tumor size inApc^loxP/loxP+Kras^LSL-G12D/-+Smad4^loxP/loxP group and Apc^loxP/loxP+Kras^LSL-G12D/-group was(3.52±0.26) and(3.45±0.20)mm, respectively,without significant difference(t=0.872, P=0.388).The tumorigenesis rate was 70.0% and 50.0% respectively, and there was no significant difference between the two groups(χ²=0.440, P=0.507). The metastasis rate of two groups were 58.3% and 8.3%respectively(Fisher′s exact test, P=0.027).

In this study, the colorectal carcinogenesis and its spontaneously metastasis to the liver of CRC were induced by Lentivirus^{Cre-IRES-luciferase} in our established transgenic mice,which successfully simulated the occurrence and development of human sporadic CRC and its liver metastasis.

To observe the biomechanical characteristics of bridge-link type combined internal fixation system (BCFS) with mixed-rod in the treatment of long segmental comminuted fracture of femoral shaft.

A total of 16 models of long comminuted segment fracture of femoral shaft with mixed-rod and double-rod were made (8 each structure), and divided into the mixed-rod group and the double-rod group. The axial compression experiment and the radial torsion experiment were carried out on each of the mixed rod group and the double rod group. Four models were randomly selected from the two groups for axial compression experiment and radial torsion experiment, respectively. The changes of axial compression yield load and displacement, and also radial torsional yield load and angle were observed in two groups. At the same time, the maximum load was recorded when the curve had a break point or in a horizontal state, and then calculated the yield load. The data of normal distribution were compared with one-sample t test.

When the two groups were compressed axially at the same speed, as the axial compression yield load increased gradually, the longitudinal compression displacement of the mixed-rod group was obviously smaller than that in the double-rod group; and the maximum axial compression yield load of the mixed-rod group was greater than that in the double-rod group ((7 517±4)N vs (2 290±4) N, t=1 848.071, P=0.000). When the two groups were twisted radially at the same speed,as radial torsional yield load increased gradually, the radial torsion angle of the mixed-rod group was smaller than that in the double-rod group; and the maximum radial torsional yield load of the mixed-rod group was greater than that in the double-rod group ((61.3±2.0) Nm vs (24.4±2.2)Nm, t=25.201, P=0.000).

For the long segment comminuted fracture of femoral shaft, the mixed-rod of BCFS can fix fracture more strongly than double-rod in longitudinal direction and maintain the stability of fracture end. The transverse torsion resistance is better than that of the double-rod, and the fatigue resistance is strong.

This article reports the case of a 59-year-old female admitted for 1 week with intermittent left upper abdominal pain. Physical examination found that the spleen was abnormally enlarged; Abdominal CT showed that the spleen was obviously enlarged, and there was a circular mass shadow, about 12.2 cm ×9.4 cm in size, with uneven lesion density and patchy lower density shadow. Surgical resection was followed by pathological diagnosis of splenic epithelioid hemangioendothelioma with hemorrhage and necrosis.

In the transplant neighborhood, transplant rejection and toxicity of immunosuppressive agents have been the main reasons affecting the long-term survival of patients. It is the common goal of transplantation direction to induce patients' immune tolerance to transplantation and detach from immunosuppressant dependence. Regulatory macrophages are an independent macrophage subtype with immunosuppressive function. In recent years, there have been many studies on cell therapy based on immunosuppressive cells for inducing immune tolerance in transplantation. Regulatory macrophages combined with commonly used immunosuppressive agents have important application prospects in clinical organ transplantation.

Immune checkpoint inhibitors have become one of the most popular tumor immunotherapy methods by reactivating systemic immunity, enhancing anti-tumor immune response, and improving the objective remission rate and survival rate of patients with advanced tumors. At present, they have been used in a variety of solid and hematological system tumors. With the wide application of drugs, the immune-related adverse events caused by them have attracted more and more attention. Among them, endocrine dysfunction is hidden and non-specific. If delayed diagnosis is fatal, early treatment has a good prognosis. This kind of drug has been on the market in China for a short time, and there are few literature reports on drug-related endocrine dysfunction at present. This article reviews the relevant literature to improve the early diagnosis and treatment rate and improve the prognosis of such patients.