Volume 99 ·  Issue 18 ·  2019

Islet autoantibody detection is an important cornerstone of diagnosis and morbidity prediction of autoimmune diabetes, and radioligand method is the "gold standard" of islet autoantibody detection at present. Recently, enzyme-linked immunosorbent (ELISA) kit and electrochemiluminescence method using biotin-streptavidin bridging sandwich method have good sensitivity. In the face of the current situation of many detection methods and uneven quality of commercial kits, this paper proposes that we should not only learn from the valuable experience of developed countries in Europe and America, but also establish a detection quality evaluation system suitable for ourselves gradually based on the actual national conditions of developing countries along the "the belt and road initiative", so as to improve the diagnostic level of autoimmune diabetes.

Autoimmune type 1 diabetes mellitus (T1D) arises from immune-mediated islet beta cell destruction induced by genetic and environmental factors. Existing studies have shown that T1D is a continuous spectrum state from onset to clinical symptoms. Autoimmune pre-T1D includes stages 1 and 2 in the new T1D staging method, which refers to the period from the onset of islet autoimmune markers to the onset of dominant diabetes. It belongs to the pre-symptomatic stage, and its main diagnostic basis is the appearance of two or more islet autoantibodies in the circulation without hyperglycemia symptoms.

To describe the clinical characteristics and classification diagnosis of newly diagnosed diabetes onset with ketosis or ketoacidosis in adult patients.

Medical records of newly diagnosed diabetes onset with ketosis or ketoacidosis in the Third Affiliated Hospital of Sun Yat-sen University between January 2011 and August 2016 were reviewed. Patients aged 18 years or older were included, while other diseases that may cause urinary ketoacidosis and special types of diabetes were excluded. Patients were classified as type 1 diabetes mellitus (T1DM) or type 2 diabetes mellitus (T2DM) or diabetes mellitus untyped based on discharged diagnosis, and groups were compared for differences in clinical profiles. Then the patient′s medication, final diagnosis and outcome within 2 years of discharge were tracked through the inpatient and the outpatient medical record systems. Receiver operating characteristics (ROC) curves were analyzed to check the ability of clinical indicators such as onset age, body mass index (BMI) and C-peptide to discriminate T1DM from T2DM, and to find the best diagnostic cut-off points.

A total of 123 patients (88 males) were enrolled [with a mean age of (41.1±13.6) years old], with 37 patients (30.1%) diagnosed as T1DM, 60 patients (48.8%) diagnosed as T2DM and 26 patients (21.1%) diagnosed as Untyped. There was a statistically significant difference in onset age, BMI, blood pressure, blood gas pH and bicarbonate, blood lipids, fasting, 0.5 h and 2 h C-peptide level, any diabetic antibody and anti-glutamic acid decarboxylase antibody (GADA) positive rate, combined fatty liver ratio and family history among the three groups (all P<0.05). ROC curve analysis was performed on patients diagnosed with T1DM (n=36) and T2DM (n=87) after 2 years follow-up, and the area under the curve (AUC) of onset age, BMI, fasting C-peptide, 0.5 h and 2 h C-peptide was 0.735, 0.813, 0.855, 0.898, and 0.882, respectively.

The ROC curve analysis indicates that C-peptide, onset age and BMI can provide effective diagnostic value, and the diagnostic value of C peptide is better than BMI and onset age.

To evaluate the effect of peripheral hyperinsulinemia on assessment of pharmacokinetics (PK) and pharmacodynamics (PD) of insulin preparations in euglycemic clamp.

A total of 40 healthy male volunteers aged 18-45 years old in West China Hospital between 2015 and 2017 were divided into euglycemic-hyperinsulinaemic clamp (A) group and euglycemic clamp (B) group. Humulin R (0.2 U/kg) was given subcutaneously at steady state of clamp after infusion of short-acting insulin in A group while in B group Humulin R was given subcutaneously without establishment of artificial hyperinsulinemia. The blood glucose was maintained within target range during the whole clamp.

Maximum insulin concentration [(667±141) pmol/L vs (267±68) pmol/L, P<0.01] and area under curve (AUC) of insulin concentration [(152±32) nmol·L^-1·min vs (57±7) nmol·L^-1·min, P<0.01] in A group were higher while maximum glucose infusion rate (GIR) [(3.70±0.70) mg·kg^-1·min^-1 vs (7.66±2.11) mg·kg^-1·min^-1, P<0.01] and AUC of GIR [(931±272) mg/kg vs (1 920±452) mg/kg, P<0.01] were lower compared to B group. The serum C-peptide levels were lower in both groups after administration of insulin compared with baseline.

It is not necessary applying euglycemic-hyperinsulinaemic clamp to evaluate the PK/PD of insulin preparations, which may overestimate the PKparameters and underestimate the PD parameters of insulin preparations.

To explore the effect of adiponectin (APN) on islet injury induced by chronic intermittent hypoxia (CIH).

Thirty-six SD rats were randomly divided into three groups: Normal control (NC), CIH, and CIH + APN groups. The rats in the CIH and CIH+APN groups received an intermittent hypoxia exposure while the rats in NC group received the room air only. The rats in CIH+APN group received the intravenous injection of APN. The intermittent hypoxia events persisted 8 hours a day and last for 35 days. The fasting blood glucose and fasting insulin were detected at the time of 0, 7, 14, 21, 28, and 35 day. After 35 days, the level of serum adiponectin, and adenosine triphosphate (ATP) level, superoxide dismutase (SOD), malondialdehyde (MDA), the mRNA levels of mitochondrial oxidative phosphorylation function and mitochondrial synthesis gene, and the protein level of mitochondrial and cytoplasmic cytochrome C of pancreatic islet were detected.

The glucose and insulin level had no statistically differences among three groups at different time points (all P>0.05). However, compared with NC and CIH+APN groups, CIH reduced the serum adiponectin [(7 265±2 209) ng/ml, (6 536±1 678) ng/ml vs (4 923±1 742) ng/ml, both P<0.05], ATP levels [(30.92±1.12) nmol/mg, (26.55±0.72) nmol/mg vs (20.22±1.47) nmol/mg, both P<0.05], mRNA levels of mitochondria oxidative phosphorylation function and mitochondrial synthesis gene, the activity of SOD, and the rate of mitochondrial/cytoplasmic cytochrome C protein level while increased the MDA level in pancreatic islet. Compared with NC group, the MDA level increased (P<0.05) and the APN level had no statistically difference, while the level of other indicators decreased in CIH+APN group (all P<0.05).

APN ameliorates the pancreatic islet injury induced by CIH through inhibition of oxidative stress.

To explore quality of spirometry in Hunan province and the impact of education on it.

Cross-sectional study and a prospective randomized cohort study. (1) A total of 460 public hospitals in Hunan province were investigated. Research assistants collected 20 consecutive reports of pulmonary ventilation test reports (PVTRs) and basal information of those hospitals which owned spirometry. (2) To measure the effect of education, 28 randomly selected 2^nd level hospitals which owned spirometry were randomized to intervention and control group (1∶1). The intervention group received a short-time training which included face-to-face lectures and a hand-by-hand operation training course, while the control group received usual care. PVTRs were investigated 3 months after the intervention. All PVTRs were classified to grade A, B, C, D and E according to the Chinese pulmonary ventilation test (PVT) guidelines.

The recovery rate was 100%. The spirometry-equipped ratio was 1.6% (2/129) at 1^st level hospitals, 39.0% (105/269) at 2^nd level hospitals, 100% (62/62) at 3^rd level hospitals in Hunan province. There were 100% (2/2), 91.4% (96/105) and 93.5% (58/62) utilization rate at 1^st, 2^nd and 3^rd level hospitals. Common reasons for not owning a spirometer were equipment cost and insufficient insurance. Lack of knowledge about spirometry and inadequate benefits were the top two reasons for low utilization rate. There were 3 120 PVTRs from 156 hospitals which used spirometry, a total of 50.4% (1 574/3 120) PVTRs got grade A, a total of 14.8% (462/3 120) PVTRs were judged as unreliable (grade D, E). There were 560 PVTRs and 28 questionnaires, respectively, before and after intervention. The technicians′ knowledge improved after education compared to before (9.8±0.6 vs 8.6±1.1) (P<0.05). And 75.0% (210/280) PVTRs got A grade in the intervention group, which was significantly higher than those in the control group (75.0% vs 37.9%, P<0.05). While none of PVTRs was unreliable, which was lower than that in the control group (0 vs 14.6%, P<0.05).

The equipment ratio and the utilization rate of spirometry are still low and imbalanced among three levels hospitals in Hunan. The short-time training is helpful to improve quality of spirometry.

To determine the association of serum fibroblast growth factor-23 concentrations with age-related cardiac diastolic function subclinical state and whether this association differs by sex.

Seven hundred sixteen healthy subjects (aged 35-89 years, 68.4% female) were selected from National Basic Research Program of China (973 Program-China Medical University subsection) between January 2014 and February 2015 and assigned into 4 groups according to sex and age:< 60 years old male and female group, ≥ 60 years old male and female group. Blood biochemical indicators and general clinical data of the subjects were measured. The glomerular filtration rate (eGFR) were estimated using the Modified Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI-ASIA) equation. The fibroblast factor 23 (FGF-23), C-reactive protein (CRP) and interleukin-6 (IL-6) were measured by enzyme-linked immunosorbent assay (ELISA). Cardiac structure and function parameters including left atrial diameter (LAD), inter-ventricular septum thickness (IVST), left ventricle posterior wall thickness (LVPWT), left ventricle mass index (LVMI),left atrial mass index (LAVI) and the ratio of peak velocity of early filling to the septal early peak diastolic mitral annulus velocity(E/e′) were measured by echocardiography. Association between serum FGF-23 and aging-related diastolic function subclinical status was analyzed by binary Logistic regression analysis.

(1) Serum log-transformed FGF-23 levels were significantly higher in males than in females [(2.0±0.3) ng/L vs (1.9±0.4) ng/L, P<0.05]. (2) Cardiac diastolic function gradually decreased with age, and age related cardiac diastolic function decline of female was significantly higher than males[E/e′:<60 years old male group (7.6±2.6), ≥ 60 years old male group (8.6±2.7),P<0.01;<60 years old female group (8.3±2.3), ≥ 60 years old female group (9.5±3.1),P<0.01; LAVI:<60 years old female group (14±5) ml/m², ≥ 60 years old female group (16±5) ml/m², P<0.01]. (3) Serum FGF-23 was significantly positively correlated with age (r=0.089, P<0.05) and LAVI (r=0.084, P<0.05) in total study population while with E/e′ (r=0.149, P<0.05) only in males. There was no significant correlation between serum FGF-23 and cardiac diastolic function parameters in females. (4) Binary Logistic regression analysis showed that median and high FGF-23 were independently associated with age-related cardiac diastolic function decline (OR=2.831, 95% CI: 1.144-7.009, P=0.024; OR=2.548, 95% CI: 1.053-6.163, P=0.038) in males.

Serum FGF-23 concentrations are associated with age-related cardiac diastolic function subclinical state in a healthy Chinese population. High levels of FGF-23 are independently associated with age-related cardiac diastolic function decline in males.

To study the clinical and imaging characteristics of cerebral amyloid angiopathy characterized by cortical superficial siderosis and improve clinicians′ understanding of the disease.

Retrospective analysis was performed on 16 patients with cerebral amyloid angiopathy characterized by cortical superficial siderosis from June 2013 to August 2016 in Beijing Hospital, and the information including epidemiological data, clinical features, cranial MRI and electroencephalogram (EEG) results were analyzed.

The ratio of male to female in 16 patients was 1.67∶1, and the average age of onset was 73 (69-79) years. The most common clinical symptoms were transient focal neurological episodes (TFNEs)(12/16). Cranial MRI showed localized (9/16) and diffuse type cortical superficial siderosis (7/16); few of them were associated with different degrees of cerebral microbleeds. Most of the EEG findings were normal (6/9) and a few showed focal slow waves (3/9). During a mean follow-up of 17 (17±11) months, 5 patients developed repeated TFNE, of which 1 had cerebral hemorrhage.

Cerebral amyloid angiopathy characterized by cortical superficial siderosis occurs predominantly in the elderly. TFNE is the most common clinical manifestation. Cranial MRI is the most important diagnostic method, and antithrombotic therapy should be avoided as much as possible.

To explore the classification, clinical features, the short-term efficacy of intravenous immunoglobulin (IVIg) for Guillain-Barré syndrome(GBS) and look for predictors of acute motor axonal neuropathy (AMAN) during pregnancy.

The clinical data of 45 hospitalized pregnant patients with GBS recruited from October 2008 to October 2017 at the Tianjin Medical University general hospital, Handan City First Hospital and Nankai University Affiliated Tianjin Fourth Central Hospital, were collected and analyzed retrospectively, and patients were divided into the acute inflammatory demyelinating polyneuropathies (AIDP) group and the AMAN group. The clinical features and efficacy of IVIg were compared between the two groups. Logistic regression analysis was used to analyze the predictors of AMAN.

There were 25 cases in the AIDP group and 20 cases in the AMAN group. AIDP usually started with distal limb weakness (P=0.001), and AMAN often started with limb weakness (P=0.001) and mostly accompanied by dyspnea (P=0.042). AIDP was often associated with paresthesia (P=0.001) and autonomic dysfunction (P=0.007). The response days of active treatment in the AIDP group and the AMAN group were (1.6±0.5)d and (2.3±0.8)d (P=0.022), the improvement days were (3.6±0.8)d and (5.9±1.0)d (P=0.000), the basic cure days were (7.7±1.3)d and (9.0±0.8)d (P=0.002), the cure days were (12.3±1.1)d and (12.8±0.9)d (P=0.148). Multivariate Logistic regression analysis revealed that preceding diarrhea (OR=13.750; 95% CI 1.386-136.387), limb weakness(OR=12.000;95% CI 2.359-61.048) and limb weakness with dyspnea (OR=10.000; 95% CI 1.048-95.457) were significantly associated with the AMAN-type GBS.

AIDP and AMAN are the main types of pregnancy complicating GBS. Most patients present with a single and benign course of disease. IVIg is generally safe and effective. Preceding diarrhea, limb weakness and limb weakness with dyspnea are the predictors of AMAN-type pregnancy complicating GBS.

To explore the expression of long non-coding RNA-LINC01410 in the pancreatic cancer tissues, corresponding paracancerous tissues, human pancreatic cancer cell lines and normal pancreatic ductal epithelial cell line, and analyze the effect of LINC01410 on pancreatic cancer cell proliferation and migration.

Real-time fluorescent quantitative PCR (RT-qPCR) was used to detect the expression level of LINC01410 in 16 cases of pancreatic cancer tissue and its adjacent tissues. RT-qPCR was performed to analyze LINC01410 expression in the pancreatic cancer cell lines AsPC-1, CAPAN-1, SW1990, BxPC-3 and CFPAC-1, and human normal pancreatic ductal epithelial cell line HPDE6-C7. Transfection of interference plasmid (shRNA) in the pancreatic cancer cell line with the highest expression level of LINC01410 were used to knock-down the expression of LINC01410. CCK-8 assay, colony formation assay, and transwell chamber assay were performed to detect the proliferation and migration of pancreatic cancer cells. The complementary paired miRNAs and downstream genes of LINC01410 were predicted by bioinformatics. The expression of miRNA and downstream genes was detected by RT-qPCR, and the protein expression of downstream genes was determined by Western blot.

The expression of LINC01410 in the pancreatic cancer tissues was significantly higher than that in the adjacent tissues [(3.46±0.32) vs (0.65±0.08), P<0.01]. The expression levels of LINC01410 in the pancreatic cancer cell lines were significantly higher than that in the normal human pancreatic ductal epithelial cells (P<0.05). The expression of LINC01410 was highest in BxPC-3 cells (P<0.01). After knock-down of the LINC01410 expression in the pancreatic cancer cell line BxPC-3, the cell proliferation was significantly inhibited (P<0.05), and the cell migration ability was decreased (P<0.05). LINC01410 complementarily paired with miR-497-5p, and miR-497-5p complementarily paired with IFITM3. After inhibiting the expression of LINC01410, the expression of miR-497-5p was increased [(1.04±0.17) vs (5.79±0.43), P<0.01], the mRNA expression of IFITM3 was decreased [(0.39±0.05) vs (1.00±0.03), P<0.01], and the protein expression of IFITM3, CDK6, Cyclin D2, PCNA, Vimentin, and N-cadherin was decreased.

The expression of LINC01410 was increased in pancreatic cancer tissues and cell lines. Down-regulation of LINC01410 expression inhibits the proliferation and migration of pancreatic cancer BxPC-3 cells, and its mechanism may be closely related to regulating the miR-497-5p and IFITM3 gene expression.

To analyze the correlation between endogenous EPO levels and electrocardiogram scatter plot changes in patients with coronary heart disease and autonomic nerve function injury.

Forty-eight patients who underwent coronary arteriography (CAG) inspection due to chronic coronary heart diseases were selected from July 2015 to October 2015. All of them were evaluated by the Ewing standard autonomic nervous function test, and were divided into Ewing(+) group and Ewing(-) group according to the results of the test. The clinical data of the patients was collected and venous blood was extracted to detect EPO level.

The EPO level of Ewing (+) group ((13±3) mIU/ml) was significantly higher than that of Ewing (-) group ((10±3) mIU/ml). The Lorenz scatter plot comet shapes between the two groups had a significant difference. As for the quantitative indicators of Lorenz scatterplot, length of the Ewing (+) group ((147±22) ms) was shorter than that of the Ewing (-) group ((164±24) ms) and there was no significant differences in the width between the two groups. EPO level was negatively correlated with length in both groups (r=-0.427, P=0.002), but not with width (r=0.091, P=0.539). Binary logistic regression analysis showed that EPO (OR=1.394) and diastolic blood pressure (OR=1.091) were risk factors for autonomic nervous function damage. Length (OR=0.934) was a protective factor for autonomic nervous function. ROC curve analysis showed that the area under the EPO curve was 0.737 and that under the length curve was 0.719.

The endogenous EPO levels are associated with the changes of electrocardiogram scatter plot in patients with coronary heart disease and autonomic nerve function injury. EPO and length of scatter plot have the similar diagnostic value on predicting of autonomic nerve function injury.

To investigate the causes and treatment of severe acute pancreatitis (SAP) with iatrogenic duodenal fistula.

The clinical data of the SAP patients with duodenal fistula treated in the Severe Acute Pancreatitis Center of Sir Run Run Shaw Hospital from May 2015 to May 2018 was analyzed retrospectively.

A total of 11 patients were enrolled, among which 5 cases of duodenal fistula were caused by iatrogenic injury, including 2 cases of puncture injury, 2 cases of nutritional tube injury and 1 case of drainage tube injury. For patients with poor infection control after conservative treatment, laparoscopic assisted debridement through the right retroperitoneal approach was performed. Treatment of two patients failed for liver failure and the remaining patients were cured.

Iatrogenic injury is one of the causes of duodenal fistula in patients with severe pancreatitis. Laparoscopic assisted debridement through the right retroperitoneal approach is an effective treatment for duodenal fistula.

To investigate the impact of different methods of fluid resuscitation on hemorheology during burn shock stage.

Twenty four miniature swines were randomly divided into four groups with 6 in each group (succinylated gelatin group, hydroxyethyl starch group, Parkland group and allogeneic plasma group). Severe burn shock model was established by burning miniature swine with napalm. Two hours after injury, succinylated gelatin, hydroxyethyl starch (130/0.4) and swine allogenic plasma were used as colloid (alternative colloid) in fluid resuscitation according to the burn shock fluid resuscitation formula which is commonly accepted in the field of Burns Surgery. In Parkland group, miniature swines received liquid recovery according to Parkland Formula. The vital signs before and within 48 h after burn were observed by Solar 8000i electrocardiomonitor during the process of transfusion. The infusion speed was adjusted based on the heart rate, blood pressure, urine volume and central venous pressure. The level of hematocrit (HCT), viscosity of plasma (ηp), index of rigidity (IR), red cell assembling index (RCA) and erythrocyte electrophoresis time (EFT) were measured at the time of pre-injury as well as 4, 8, 24 and 48 h post-injury and statistical analysis was performed.

HCT in hydroxyethyl starch group and Parkland group at 8 h post-injury were significantly higher than pre-injury [(0.395±0.047) vs (0.333±0.042), (0.379±0.026) vs (0.352±0.019)] (both P<0.05). And compared with pre-injury, HCT in hydroxyethyl starch (130/0.4) group at 48 h decreased significantly (0.232±0.021) vs (0.333±0.042) (P<0.05). HCT in Parkland group at 24, 48 h post-injury were lower than pre-injury [(0.277±0.021), (0.241±0.029) vs (0.352±0.019)] (both P<0.05). Compared with pre-injury, the levels of ηp in Parkland group decreased substantially at 4, 8 and 24 h post-injury [(1.61±0.07), (1.55±0.07) and (1.63±0.07) vs (1.73±0.04) mPa·s] (all P<0.05). Compared with allogeneic plasma group, IR decreased in succinylated gelatin group at 24, 48 h post-injury [(1.10±0.05 vs 1.26±0.07), (1.11±0.05 vs 1.32±0.05)](both P<0.05). RCA in succinylated gelatin group was significantly higher (both P<0.05) at 4 h (6.80±0.87) than pre-injury (5.92±0.43). RCA in hydroxyethyl starch group at 8 h post-injury (6.73±0.56) was significantly higher (both P<0.05) than pre-injury (6.03±0.53). Compared with pre-injury (17.3±1.3 s, 16.4±1.5 s), the levels of EFT in hydroxyethyl starch group (15.5±1.4 s) and Parkland group (13.4±1.2 s) decreased substantially at 48 h post-injury (both P<0.05). Compared with allogeneic plasma group, the level of EFT in succinylated gelatin group at 4 h post-injury (19.5±2.3 s) increased and decreased at 24 h post-injury (12.0±5.7 s) (both P<0.05).

During swine burn shock stage, the hemorheological parameters of shock resuscitation with artificial colloid are more stable than those with Parkland formula resuscitation.

An elderly male patient with a complaint of "left kidney mass" was diagnosed as an IgG4-related disease involving both kidney and coronary artery after renal magnetic resonance enhancement and coronary CT angiography. After 10 months of hormone therapy, the renal and coronary artery lesions were significantly reduced after reexamination.

The clinical data of 2 patients with pulmonary endometriosis diagnosed and treated in the First Affiliated Hospital of Suzhou University were retrospectively analyzed. Hemoptysis was the first symptom in both patients. Hemoptysis occurred 1~2 days before menstruation and/or during menstruation, and the hemoptysis symptoms stopped spontaneously after menstruation. Chest CT showed pulmonary patches or ground glass shadows; The symptoms of hemoptysis disappeared after treatment with gonadotropin-releasing hormone analogues.

This paper reports a patient admitted to hospital with "sudden dizziness, slow response and general fatigue for 4 h 50 min". CT of the head: bilateral lacunar infarction in the basal ganglia area; CT and enhancement showed that the pancreas occupied space, considering pancreatic cancer; Multiple low density in the liver, multiple mass shadows in the abdominal cavity and retroperitoneum, and multiple metastases are considered. Final diagnosis: Trousseau syndrome. Trousseau syndrome is a thromboembolic complication caused by a malignant tumor with hypercoagulable blood. Patients with malignant tumors with ischemic stroke as the first symptom in clinic have fewer routine stroke risk factors, and the risk factors of such acute ischemic stroke are usually ignored.

This paper describes the classification and histological characteristics of mixed gonadal neuroendocrine carcinoma (MANEC) and the mechanism of bile duct MANEC. It discusses the metaplasia-dysplasia, the origin of tumor stem cells and the transdifferentiation pathway of adenocarcinoma. The clinicopathological features, Lewin tissue classification, immunohistochemistry and tissue differentiation grades of bile duct MANEC, as well as the clinical manifestations, diagnosis, treatment and prognosis of bile duct MANEC were reviewed.

Venous thromboembolism (VTE) is a disease caused by genetic, environmental, behavioral and other factors. 50% ~60% of the occurrence of VTE can be attributed to genetic factors. The known genetic factors vary greatly between the eastern and western populations. Protein C deficiency, protein S deficiency and antithrombin deficiency are the main types of genetic defects in Asian populations. More and more attention has been paid to the relationship between polymorphisms of PAI-1, MTHFR, TAFI and the risk of VTE in Asian population. This paper reviews the research progress of VTE-related gene polymorphisms in Asian population and their differences with other ethnic groups.