Volume 94  ·   Issue 12  ·  2014

Research misconduct is a global problem. In 2013, Hiroaki Matsuhara, a former professor at Kyoto Prefectural Medical University in Japan, artificially manipulated and changed the news of clinical trial data in a clinical research paper on the prevention of stroke by the antihypertensive drug valsartan, and GlaxoSmithKline's experimental compound for the treatment of multiple sclerosis. The data fraud storm once again triggered extensive discussions in the medical community about scientific integrity and scientific research misconduct^[1]。 It is not an isolated incident to artificially alter the data in papers and manipulate the research results of clinical trials. In recent years, with the repeated exposure of many cases of forgery, tampering and plagiarism in the scientific community, scholars with different research qualifications in the medical field have paid widespread attention to and thought about scientific research misconduct in clinical medical research in China.

To explore the clinical characteristics, diagnosis, treatment and outcomes of renal angiomyolipoma(RAML)associated with tuberous sclerosis complex (TSC).

The clinical data were analyzed for 10 cases of renal angiomyolipomas associated with tuberous sclerosis. There were 4 males and 6 females with a mean age of 23.5 (9-44) years. Five patients were admitted for flank pain or hematuria. RAML was found by TSC associated imaging examinations for those with extra renal organ involvement.

Bilateral multiple renal angiomyolipomas were all confirmed on imaging tests and consistent with clinical TSC. The maximal diameter of RAMLs was from 2 to 15(7.3±3.5) cm. Six patients of tumor hemorrhage had an average maximal diameter of 9.2 cm. Selective arterial embolization (SAE) (n=4) and homeostasis, antiinflamation and immobilization therapy (n=2) were performed. Four asymptomatic cases accepted close observation. During a follow-up period of 9-116 months, one of 4 SAE cases underwent secondary SAE due to rebleeding 12 months later while there was no recurrence of flank pain in other 3 cases. The mean enlargement of maximal diameter was 1.5 cm/year and serum creatinine elevated by 3.1 μmol/L/year. Six cases on conservative medical therapy or under observation had a mean enlargement of maximal diameter of 0.7 cm/year and serum creatinine elevated by 2.2 μmol/L/year. Three cases remained asymptomatic, one died of respiratory failure from TSC-associated pulmonary lymphangioleiomyomatosis, two had flank pain at 16 and 40 months respectively, one underwent secondary SAE and another received rapamysin with marked tumor regression.

Bilateral multiple RAMLs occur in most TSC patients. After excluding malignancy, SAE becomes an important choice for its mini-invasiveness, efficacy and chances of re-embolization. And rapamysin provides ameliorative treatment for TSC patients.

To assess the mid-long-term efficacies of orthotopic urinary diversion in women.

From February 2003 to August 2012, 28 female patients with bladder cancer underwent radical cystectomy and orthotopic ileal neobladder. Open (n=18) and laparoscopic (n=9) procedures were performed. Ileal neobladder included 17 T-pouch and 11 modified Studer pouch reconstruction. The continence status, urodynamics, serum electrolyte and renal function were followed up.

The mean follow-up period was 55 (8-114) months. Excellent continence was achieved during day-time in 82.1%, 92.3% and 90.5% cases at 6, 12 and 24 months postoperatively and in 53.6%, 88.5% and 90.5% cases at night respectively. The mean capacity of pouch was 282±87, 345±72 and 357±75 ml at 6, 12 and 24 months postoperatively respectively. The mean filling pressure of pouch was 10.8±3.2, 6.7±2.6 and 6.2±2.1 cmH₂O postoperatively respectively. One case of neobladder-vaginal fistula was cured by surgical repair. Another case of urethral stenosis responded well after regular dilation for 6 months. Renal function and electrolyte metabolism were stable in all cases. There was no instance of tumor recurrence or metastasis.

Orthotopic urinary diversion in females has excellent long-term results with fewer complications so that it is highly recommended.

To detect Treponema pallidum(T.pallidum) DNA with polymerase chain reaction (PCR) in whole blood samples of syphilis patients and analyze their features of sub-genotypes.

The clinical data of patients were collected from July 2012 to February 2013. And polA gene of syphilis was detected by PCR. The arp and tpr genes of polA gene-positive samples were analyzed by the established genotyping system. Statistical analyses were performed to compare different clinical courses and features to examine their correlations.

The common treponemal gene target (polA) of 35 samples were detected in whole blood by PCR in 181 samples. A total of 24 cases (35.8%) were positive in 67 patients with newly diagnosed non-latent syphilis untreated patients; 26 cases of latent syphilis were negative; 7 cases (9.7%) were positive in 72 subsequent visit patients; 4 cases (25.0%) were positive in 16 patients with sero-resistant. There were 4 subtypes of 14a (n=7), 14b (n=10), 13c (n=4) and 14d (n=14). Among those positive samples, there were 4 sero-resistant samples of 3 subtypes 14d and 1 subtype 14b.

The feasibility of peripheral blood is confirmed. Although the positive rate of whole blood detection of T. pallidum gene is low, the method is both simple and reliable for patients with sero-resistant syphilis.

To explore the clinical characteristics of adrenocorticotropic hormone (ACTH) independent macronodular adrenal hyperplasia (AIMAH).

A total of 30 AIMAH patients from January 2001 to December 2011 at our hospital were reviewed retrospectively and their clinical data collected.

AIMAH was equally distributed between genders. Their mean age was 44±9 years and median course of disease 5 years. Hypertension was the most common clinical manifestation. Circadian rhythm of plasma cortisol disappeared in all patients, and the level of 24 hour urinary free cortisol (24 hUFC) was normal only in 4(13.3%) patients. Both low and high dose dexamethasone suppression tests were not suppressed in 30(100.0%) and 28(93.3%) patients respectively. The stimulation tests for detecting aberrant expression of hormone receptors were performed in 14 patients. At least one aberrant cortisol response was identified in 12 patients. Twenty-five patients underwent adrenalectomy. Among 7 patients of bilateral adrenalectomy, 6 achieved remission while 8 patients did so among 14 patients of unilateral adrenalectomy.

AIMAH should be considered in patients with massively enlarged bilateral adrenal glands. Treatment modalities should be decided according to clinical manifestations and cortisol level so as to relieve symptoms and improve prognosis.

To detect serum Chlamydia pneumoniae(C.pneumonia)antibodies and analyze the epidemiologic data.

Micro-immunofluorescence(MIF)was used to detect IgG and IgM antibodies against C. pneumoniae in 7 802 serum specimens from May 2008 to September 2013.C.pneumoniae past or recent infections were determined based on specific IgG and IgM antibodies and their titers. The analysis of relationship between age, gender and other clinical factors associated with antibody titers was performed.

The positive rate of C. pneumonia IgG antibodies(≥ 1∶16 and <1∶512)was 87.5% (6 827/7 802). And the lowest rate of 50.6%(78/154)was shown in patients of 2-4 years age group while the highest rate of 98.7%(1 277/1 294)in those above 70 years old. The average geometric mean titer (GMT) of C. pneumonia IgG antibodies was 43.9. GMT in males was significantly higher than that in females (45.8 vs 41.9, P=0.000 1). And 282 (3.6%) patients were diagnosed with recent C. pneumoniae infection(IgG≥1∶512 or IgM≥1∶16 or acute and convalescent serum antibody titers turned to positive or four times and more elevated). The lowest rate of 0.5%(2/417)was detected in < 2-year-old patients while the highest rate of 6.7%(24/357)in 10-14-year-old group patients. The miss ratio was as high as 68.1%(192/282)if C. pneumoniae IgM antibody was used as an only criteria for C. pneumoniae recent infection. The recent infection rates in patients with autoimmune diseases (7.1%(24/336)) and those with pneumonia/chest radiological shadow findings (4.7% (69/1 467)) were statistically higher than the average rate (3.6%) of total population(P=0.000 4, 0.014 0).

The positive rate of C. pneumonia IgG antibody is quite high in the population. And the GMT of C. pneumoniae IgG antibody in males is significantly high than that in females. Recent C. pneumonia infection is to be missed if IgM antibody is used as a sole criterion.

To explore the relationship between metabolic diseases and death from all causes, cardiovascular diseases (CVD) in an elderly male population.

A cohort of 1 447 elderly males was followed up for 15 years from 1996 to 2011. All of them received annual check-ups at our hospital. The Cox proportional hazard model was applied to multivariate survival analysis for all-cause and CVD mortality. And the cumulative survival rates were calculated by Kaplan-Meier method and log-rank test was used to compare the survival rates.

During a 15-year follow-up, 639 subjects died, including 186 deaths from cardiovascular causes. Multivariate Cox regression analysis showed that age [relative risk (RR)=1.131, 95% confidence interval (CI) 1.114-1.148], impaired glucose metabolism (RR=1.344, 95%CI 1.139-1.585), hypertension(RR=1.241, 95%CI 1.055-1.460), elevated fasting glucose level(RR=1.101, 95%CI 1.031-1.177)and lower body mass index(BMI)(RR=0.968, 95%CI 0.943-0.993)increased the risks of all-cause mortality while age(RR=1.119, 95%CI 1.086-1.153), impaired glucose metabolism(RR=1.856, 95%CI 1.386-2.458)and hypertension(RR=1.699, 95%CI 1.242-2.324)elevated the risks of CVD mortality. The cumulative survival rates from all-cause and CVD mortality in impaired glucose regulation and diabetes group were significantly lower than those in normal glucose tolerance group(P<0.01). However, no difference existed between impaired glucose regulation (IGR) and diabetes groups. The cumulative survival rates from all-cause and CVD mortality significantly decreased in cases of impaired glucose metabolism and hypertension (P<0.01). The cumulative survival rates from all-cause mortality in low BMI group were significantly lower than those in normal and high BMI groups(P<0.05). A substantially higher risk of all-cause and CVD mortality was present in those with 2 or more metabolic disorders versus those with 0-1 metabolic disorder (P<0.01).

Malignant tumor and CVD are the main cause of death for Chinese elderly male population. Advanced age, impaired glucose metabolism, hypertension and 2 or more concurrent metabolic disorders are risk factors of all-cause and CVD mortality. And underweight is associated with an increased risk of death in elders.

To explore the gender and age difference of abdominal fat distribution in Chinese older adults and examine the effects of metabolic syndrome (MS) on abdominal fat distribution by computed tomography (CT).

Chinese elders (aged ≥65 years old) undergoing abdominal CT scanning at our hospital from January 2009 to December 2010 were collected through retrospective analysis. A total of 52 healthy normal-weight subjects and gender-specific body mass index (BMI)-matched middle-aged adults were selected (28 males, 24 females) to compare the difference of abdominal fat during the same period. Visceral fat area (VFA) and subcutaneous fat area (SFA) were measured at the cross-sections of L4 and L5 intervertebral space.

A total of 390 subjects were enrolled. There were 252 males and 138 females. Total abdominal fat (TAF) was not significantly different in both genders [female (323±122 cm²) vs male (303±141 cm²), P=0.146]. However, females had higher TAF than males after height correction(128±49 vs 105±49 cm²/m², P=0.000). VFA and SFA were higher with higher BMI values across lean, normal weight, overweight and obese groups in both genders. VFA and SFA were not significantly different in both genders among 3 different age groups (>65-75, >75-85, >85 years;P>0.05). Compared with healthy normal weight elders and BMI-matched middle-aged adults, VFA and SFA increased with more components of MS except in only one component group. When the patients were excluded suffering from 2 or more components of MS, VFA was not significantly different between normal weight elders and those with only one component of MS (diabetes/hyperlipidemia/hypertension). Logistic regression analysis showed VFA was a risk factor for elders with MS(male:OR=1.03, 95%CI: 1.012-1.047; female: OR=1.06, 95%CI: 1.026-1.088). However, SFA and age were not.

The elder females have more TAF than the elder males while abdominal fat does not increase with age in elders. TAF, VFA and SFA have a highly positively correlation with BMI. Visceral fat, not subcutaneous fat, is a risk factor for elders with MS and it increases with an increment of more than 2 components of MS.

To compare the performance of 7 prognostic staging systems in predicting the survival of surgical patients with hepatocellular carcinoma(HCC).

A total of 908 surgical HCC patients were recruited from January, 1999 to December, 2010 at our hospital. They were assigned retrospectively into different stages according to the classification criteria of 7 different staging systems. That is, Tumor-Node-Metastasis classification system(TNM7th), Barcelona Clinic Liver Cancer staging system(BCLC), Tokyo score, Japan Integrated Staging score(JIS), model for the Chinese University Prognostic Index grade(CUPI), Cancer of the Liver Italian Program score(CLIP) and Okuda staging. Kaplan-Meier survival estimations were performed and P values assessed with Log-rank test.

Significant survival difference was found across all groups of these staging systems(P<0.05) except for comparison between TNM7th Stage Ⅳ versus Ⅲ(P=0.538), Tokyo score 4 versus 3(P=0.290) and 1 versus 0(P=0.398), CLIP score 4 versus 3(P=0.073) and 3 versus 2(P=0.805) and Okuda stage Ⅱ versus stage Ⅰ(P=0.872). For neutralizing potential bias in comparing prognostic scores with different numbers of stages, Akaike information criterion(AIC) was calculated by the results of Cox′s regression. Therefore TNM7th had the lowest AIC result(AIC=3 719.39).

TNM7th staging system is a better staging model for HCC of Chinese population among seven currently applied staging systems.

To explore the association of Jab1 (c-Jun activation domain binding protein 1) expression during carcinogenesis and clinicopathological characteristics of colorectal carcinoma(CRC).

Tissue specimens were obtained from 80 cases of CRC from January 2007 to December 2008. And the expression of Jab1 protein for each specimen was detected by immunohistochemistry (EnVision). Six representative paired samples of cancerous and paired adjacent normal tissues were collected for Western blot. The relationships between the expression level of Jab1 protein and the clinicopathological characteristics of primary CRC were retrospectively analyzed.

A high-level expression of Jab1 was present in cancerous tissues but not in paired adjacent normal tissues. The positive expression rate of Jab1 protein was as high as 96.3%(77/80). And its high expression rate was 82.5%(66/80), low expression rate 17.5%(14/80)and 8.8%(7/80)in cancerous and paired adjacent normal tissues respectively(P<0.05). Its expression was correlated with differentiation, invasion depth, TNM stage and lymph node metastasis(allP<0.05). Jab1 was significantly correlated with Ki-67(r=0.548, P<0.01)and inversely with p27^kip1(r=-0.461, P<0.01).

An over-expression of Jab1 protein might play an important role in the pathogenesis of CRC. Thus it may become a novel diagnostic marker and a therapeutic target in patients with CRC.

To explore the effects of cigarette smoke extract (CSE) on phagocytosizing function of monocyte-derived macrophages (MDMs) in patients with chronic obstructive pulmonary disease (COPD).

From January 2012 to March 2013, peripheral blood monocytes were isolated from 32 stable COPD patients and 32 healthy controls at First Hospital, Lanzhou University. MDM was induced and cultured from monocytes in vitro. The MDMs from COPD patients and healthy controls were divided into 4 groups of COPD non-CSE (conventional culture), COPD CSE (4% CSE treatment for 6 h), healthy non-CSE (conventional culture) and healthy CSE (4% CSE treatment for 6 h). Flow cytometry (mean fluorescence intensity, MFI) and laser scanning confocal microscopy (fluorescence grey level) were applied to detect the ability of MDM phagocytosed fluorescein-labeled Escherichia coli (FITC-E.coli). Total antioxidative capacity (TAC) was measured by o-phenanthroline colorimetry. Malondialdehyde (MDA) was measured by thiobarbituricacid colorimetry and glutathione peroxidase (GSH-PX) by 5, 5′-dithiobis-2-nitrobenzoic acid (DTNB) method.

MFI and fluorescence grey level in COPD non-CSE group (20.2±2.2, 51.5±5.8) significantly decreased than those in healthy non-CSE group (56.9±6.7, 87.3±7.3). And in COPD CSE (7.6±0.7, 14.1±3.4) and healthy CSE groups (48.0±5.4, 69.7±6.0) decreased more than those in COPD non-CSE and healthy non-CSE groups (all P<0.01). The levels of TAC and GSH-PX in COPD non-CSE group ((4.1±0.5), (47.1±4.1) U/ml) were lower than those in healthy non-CSE group ((5.1±0.6), (88.4±2.3) U/ml). And in COPD CSE and healthy CSE groups ((3.1±0.4), (26.8±6.2) U/ml) and (4.5±0.4), (72.3±5.1) U/ml) were respectively lower than those in COPD non-CSE and healthy non-CSE groups (allP<0.01). The content of MDA in COPD non-CSE group was higher than that in healthy non-CSE group [(4.8±0.5) vs (2.1±0.4) μmol/L)]. And in COPD CSE and healthy CSE groups ((7.7±0.9), (3.0±0.6)μmol/L) were higher than those in COPD non-CSE and healthy non-CSE groups (allP<0.01). At basic status, positive correlations existed between MFI and TAC, GSH-PX (r=0.523, 0.818, P=0.038, 0.001) while negative correlations between MFI and MDA (r=-0.501, P=0.048) in COPD patients and after CSE treatment, the above relationships still existed (r=0.704, 0.716, -0.522, P=0.002, 0.002, 0.038).

Cigarette smoke can reduce the phagocytosizing ability of MDM in COPD patients. And it may be related with oxidative stress.

The fifteenth World Cancer Day is celebrated on February 4, 2014, and the theme of this year's Cancer Day is "Eliminating misconceptions about cancer". Globally, the following four points are the main misconceptions about cancer: (1) We don't need to talk about cancer; (2) For people who have or are about to suffer from cancer, there are no signs and signals that can predict it; (3) There is nothing we can do about cancer; (4) It is useless to use various lifestyles to prevent cancer. The World Health Organization (WHO) and the International Agency for Research on Cancer (IARC) strongly support the International Alliance Against Cancer (UICC) to use various methods to reduce the global burden of cancer, accelerate the progress in cancer research, prevention and treatment, and benefit mankind. Preventing cancer and improving the quality of life of cancer patients are recurring themes on World Cancer Day.

An 81-year-old male patient underwent esophagography in an external hospital on August 6, 2013 due to "eating obstruction for 6 months and aggravation for 1 week". It showed that a 4 cm long oval filling defect was seen in the middle esophagus, which was considered to be cancer of the middle esophagus. On August 8th, I was admitted to the 105th Hospital of the People's Liberation Army. Chest CT showed that the local wall of the middle and lower esophagus was obviously unevenly thickened, and the local wall was mass-shaped and concave into the lumen, and the lumen of the lesion area was narrow. The initial diagnosis was middle and lower esophageal cancer. On August 12th, gastroscopy showed that the esophageal mucosa was 25-30 cm away from the incisors, which was considered esophageal cancer. Immunohistochemical results of esophageal lesions on August 19 showed: tumor cells S-100+, Melan-A +, HMB45+, 34 β E12-, 35 β H11-or +, LCA-, CD34-, CD117 partially weak +, CK5/6-, P63-, esophageal biopsy impression: malignant melanoma; There were no obvious abnormalities in blood, biochemistry, urine, fecal routine and abdominal B-ultrasound. The patient consumed alcohol occasionally and had no history of smoking. Physical examination: Multiple superficial lymph nodes were palpable in the right neck and bilateral axillaries, with the largest size of 1 cm ×1 cm; There were no obvious abnormalities in the rest. Therapeutically, three-dimensional conformal radiotherapy and interferon biological therapy were given. After 3 months of follow-up, reexamination of chest CT showed that the extent of esophageal lesion was significantly reduced, and semi-liquid was now available.

To explore the effects of lipopolysaccharide (LPS) pretreatment on endotoxin tolerance of human umbilical cord mesenchymal stem cells (hUCMSCs) and its possible mechanism.

hUCMSCs (1×10⁴ cells/well) were exposed to 0, 0.1, 1.0, 10.0, 20.0, 30.0, 40.0, 50.0 μg/ml LPS for 24 h respectively. And the cell viability of hUCMSCs was detected by 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT). 1 μg/ml and 50.0 μg/ml LPS were used as pretreatment and apoptosis induction concentrations respectively. Pyrrolidine dithiocarbamate (PDTC) (20 μmol/L, pretreatment for 20 min) was used as a specific inhibitor of nuclear transcription factor NF-κB. hUCMSCs were randomly divided by Stata software into 7 groups: control (A), LPS induction (B), pretreatment + LPS induction (C), PDTC (D), PDTC+ pretreatment + LPS induction (E), pretreatment (F) and PDTC + pretreatment (G). The apoptosis of hUCMSCs was measured by Hoechst 33258 staining and flow cytometry (FCM). The expressions of NF-κB p65 and cellular FLICE-inhibitory protein (c-FLIP) were measured by Western blot.

The cell viability of 0, 0.1, 1.0, 10.0, 20.0, 30.0, 40.0, 50.0 μg/ml LPS groups were 100%, (117.0±8.8)%, (134.7±6.9)%, (105.3±8.3)%, (99.2±8.3)%, (84.2±9.3)%, (66.4±6.6)% and (59.2±8.0)% respectively. In comparison with 0 μg/ml LPS group, the cell viability of 1.0 μg/ml LPS group increased significantly ( P=0.004) while decreased in 40 and 50 μg/ml LPS groups ( P=0.005, 0.002). Hoechst 33258 staining indicated that chromatin of hUCMSCs was distributed evenly in group A; the apoptotic cell in group B dramatically increased; and the apoptotic cell in group C significantly decreased in comparison with that in group B. Apoptotic rates of groups A, B, C, D and E were (2.8±0.8)%, (29.7±3.4)%, (17.8±3.0)%, (2.9±0.4)% and (23.2±2.6)% respectively. Compared with group A, apoptosis rate significantly increased in group B (P<0.001). The apoptotic rate in group C significantly decreased than that in group B (P<0.001) while group E was higher than group C (P=0.015). The levels of NF-κB p65 and c-FLIP in group F (0.851±0.031, 0.534±0.053) was higher than that in group A (0.220±0.021, 0.049±0.009) (bothP<0.001), G (0.418±0.007, 0.299±0.061) (P<0.001,P=0.007).

LPS pretreatment can resist LPS-induced hUCMSCs apoptosis and enhance the ability of endotoxin tolerance. And the mechanism may be related with activating the NF-κB signaling pathway and up-regulating the expression of c-FLIP.

To explore the mechanism of calcium-sensing receptor (CaSR) in hypoxia-induced airway mucous hypersecretion.

Cultured human airway epithelial cells HBE16 by hypoxia incubator (94%N_2,1%O_2,5%CO_2,37 ℃). HBE16 were transfected with CaSR targeted small interfering RNA (CaSR-siRNA), pretreated with a specific activator of CaSR CaCl₂ and preincubated with various inhibitors [Gα_q/11 protein inhibitor YM-254890, phospholipase C (PLC) inhibitor U73122, inositol 1, 4, 5-triphosphate receptors (IP₃R) inhibitor 2-APB and cell-permeable intracellular calcium chelator BAPTA-AM] before hypoxia. The level of MUC5AC mRNA was detected by reverse transcription-polymerase chain reaction (RT-PCR). And the relative content of CaSR protein was detected by Western blot. The relative content of MUC5AC protein was measured by enzyme-linked immunosorbent assay (ELISA). The intracellular calcium concentration ([Ca²⁺]_i) was measured by laser confocal microscopy.

The relative contents of [Ca²⁺]_i and MUC5AC protein were obviously higher in hypoxic group ((154.2±11.4) nmol/L, (0.624±0.063) μg/L) than those in control group ((67.5±2.8) nmol/L, (0.257±0.051) μg/L) (all P<0.01). The relative levels of CaSR protein and MUC5AC mRNA were significantly higher in hypoxic group (0.423±0.028, 0.736±0.045) than those in control group (0.185±0.036, 0.321±0.034) (allP<0.01). CaCl₂ enhanced the effect of hypoxia. And the results had statistical significances (all P<0.01). Transfection with CaSR-siRNA significantly decreased the effect of hypoxia (allP<0.01). Pretreatments with Gα_q/11 protein inhibitor, PLC inhibitor, IP₃R inhibitor or intracellular calcium chelator all significantly attenuated the hypoxia-induced MUC5AC hypersecretion and [Ca²⁺]_i (all P<0.05).

CaSR mediates hypoxia-induced airway mucous hypersecretion through a signaling pathway of Gα_q/11/PLC/inositol 1, 4, 5-triphosphate (IP₃)/[Ca²⁺]_i.

To explore the changes of expression and biological activity of nuclear factor-kappa B (NF-κB) and matrix metalloproteinase-9 (MMP-9) after using intravenous immunoglobulin (IVIG) in a murine model of Kawasaki disease (KD) and elucidate the therapeutic mechanism of IVIG for the treatment of KD.

A total of 72 mice were categorized randomly into IVIG, KD and control groups.Lactobacillus casei cell wall extract (LCWE) was prepared and injected intraperitoneally into C57BL/6 mice to induce KD (0.5 mg single injection). IVIG group received an intraperitoneal injection of IVIG (2 mg/g) while KD model group had an intraperitoneal injection of normal saline. At Days 14, 28 and 56, the diameter of coronary artery was by echocardiography in 8 mice of each group. At the same time, the stains of hematoxylin & eosin and elastic fiber were used to observe the pathological damage of coronary artery. Western blot was used to evaluate the expressions of NF-κB and MMP-9, electrophoretic mobility shift assay (EMSA) was used to measure the activity of NF-κB and Gelatin zymography was used to evaluate the activity of MMP-9 in heart samples of murine model of KD.

The local inflammatory infiltrate, composed predominantly of mononuclear lymphocytes, of coronary artery trunk and branches was observed at Days 14 and 28 while broken elastin was observed at Day 56. And the inflammatory cell infiltrate was less severe and no apparent broken elastin was observed in IVIG and control groups. On echocardiography, the average value of diameter of left coronary artery in KD model group was higher than that in IVIG and control groups (28 d: (0.48±0.07) vs (0.41±0.03) and (0.35±0.02) mm, all P<0.01). Compared with the other two groups, the result of Western blot showed that the expressions of NF-κB and MMP-9 in KD model group were markedly higher than those in IVIG treatment group and that in control group at each time point (28 d: (58±14) vs (25±14) & (19±11) μg/L, (100±41) vs (39±19) & (35±19) μg/L, allP<0.01). The activity of NF-κB by EMSA and the result from KD model group were much higher than those from the control and IVIG groups (28 d: (84 788±2 081) vs (27 220±4 990) & (50 192±1 586) μg/L, allP<0.01]. And it was in accord with the expression of NF-κB. The outcome of gelatin zymography demonstrated that the activity of MMP-9 had similar change with the expression of MMP-9(18 560±7 963) vs (9 112±3 398) & (11 834±4 996) μg/L, allP<0.05).

NF-κB/MMP-9 is overexpressed and over-activated in the heart of KD mouse models. IVIG may inhibit the inflammatory cell infiltration and alleviate coronary artery. And such a therapeutic effect is possibly achieved by a suppression of the overexpression and over-activation of NF-κB/MMP-9 pathway.

Thyroid cancer is the most common malignant tumor of endocrine system, accounting for about 1% of new human malignant tumors, and it is increasing year by year. The classic treatment regimen for papillary thyroid carcinoma (PTC) and follicular thyroid carcinoma (FTC) is total or near total thyroidectomy plus radioactive¹³¹I therapy + thyroid hormone suppression therapy, the 5-year survival rate is about 85%^[1]。 While the other 15% of patients may develop poorly differentiated thyroid cancer or even undifferentiated thyroid cancer (ATC). As a highly malignant tumor, ATC has strong invasiveness and distant metastasis ability, which makes surgery, radiotherapy and chemotherapy have no obvious effect on prolonging the survival time and improving the quality of life of patients. Poorly differentiated thyroid cancer, due to its extremely low iodine uptake capacity, like ATC, has no effective treatment once it metastasizes.

The recurrence peak of early breast cancer (stage Ⅰ ~ ⅢC) is concentrated 2~3 years after surgery (i.e., recent recurrence), but there are differences in the recurrence pattern of different molecular subtypes^[1]Luminal breast cancer is clinically positive for estrogen receptor (ER) and/or progesterone receptor (PR), accounting for about 60% to 80% of all breast cancers. A meta-analysis covering nearly 10,000 patients showed that the prognosis of early Luminal breast cancer was better than that of hormone receptor-negative patients in the first 5 years after surgery, while the prognosis of Luminal breast cancer was relatively poor 5 to 15 years after diagnosis^[2]and nearly 50% of recurrences occurred after the end of 5 years of adjuvant endocrine therapy (i.e. long-term recurrences)^[3,4]Some even appear decades after surgery, and it is of far-reaching significance to correctly understand long-term recurrence. This article will comprehensively explain the latest research progress affecting the long-term recurrence of Luminal breast cancer after adjuvant therapy.

Adaptive immune response is the main immune response of the body to intracellular or extracellular pathogens, in which CD4^＋Helper T cells (also known as Th cells) play an extremely important role. It was previously believed that initial CD4^＋Differentiation of T cells into various types of effector cells is irreversible. Recent studies have found that certain types of differentiated CD4 cells^＋T cell subset, which can transform its own cytokine secretion profile under certain conditions, is called CD4^＋Plasticity of T cells^[1]。 CD4^＋T cells are involved in the occurrence, development and outcome of bronchial asthma^＋The research progress of T cell plasticity in asthma is reviewed below.