Acta Academiae Medicinae Sinica

Objective To construct certain chimeric E3s expression plasmids targetting oncoprotein Ras by harnessing the theory of protein knockdown. Methods We chose the binding domain of Raf-1, PI3K, RalGDS, and the function domain of F-Box as well as the U-Box to construct the plasmids. Then used the double enzyme, PCR, and sequence to test the validity and integrity of the cloned nucleotide fragments. The expression efficiency of the plasmids in eukaryotic cells was detected by Western blot analysis. Results Five of 6 plasmids in this study expressed the corresponding fusion proteins in HEK293T cells, and (RBD+CRD)^Raf-1- U-Box-pcDNA3.1 can knocked down the protein level of Ras in PANC-1 cells. Conclusions We successfully constructed the chimeric E3 expression plasmids, which provides a solid basis for further research on protein knockdown.

Objective To study the effect of LY294002 on the adriamycin- induced epithelial-mesenchymal transition in human breast carcinoma cells. Methods Human breast carcinoma cells MCF-7 was cultured in vitro and then exposed to adriamycin with or without LY294002. The protein expression levels of Akt, phosphorylated-Akt (p-Akt), Snail, and E-cadherin was detected by Western blot analysis. The mRNA expressions of Snail and E-cadherin were determined by RT-PCR. Results Adriamycin significantly increased the protein expression of Snail and depressed the protein expression of E-cadherin (P<0.05). The pre-treatment with LY294002 significantly reversed the changes of activities and levels of the above proteins (P<0.05). Conclusion LY294002 could reverse the adriamycin-induced epithelial-mesenchymal transition in human breast carcinoma cells by regulating the expressions of Snail and E-cadherin through suppressing PI3K/Akt signaling pathway.

Objective To explore the effects of propofol and dizocilpine maleate (MK-801) on the cognitive abilities the hyperphosphorylation of Tau protein of rats after the electroconvulsive therapy. Methods Two intervention factors including electroconvulsive shock therapy (ECT) (two levels: not applied and one treatment course) and drug intervention (three levels: intravenous saline,intravenous MK-801, and intravenous propofol). The morris water maze test started within 1 day after ECT to evaluate the learning-memory. The glutamate level in the hippocampus of rats was determined by high-performance liquid chromatography. The Tau protein that includes Tau5 (total Tau protein), PHF-1 (pSer^396/404), AT8 (pSer^199/202), and 12E8 (pSer²⁶²) in the hippocampus of rats was determined using Western blotting. Results Propofol, MK-801, and ECT could induce the impairment of learning-memory in depressed rats. The electroconvulsive shock significantly up-regulated the glutamate level, which was reduces by the propofol. The ECT up-regulated the hyperphosphorylation of Tau protein in the hippocampus of depressed rats, which was reduced by propofol and MK-801. Conclusion Both propofol and MK-801 could protect against the impairment of learning-memory and reduce the hyperphosphorylation of Tau protein induced by ECT in depressed rats.

Objective To observe the effect and mechanism of zoledronate on prevention of collapse in an animal model of osteonecrosis. Methods Ischemic osteonecrosis was surgically induced in 16 SD rats (which were further divided into zoledronate group and placebo group); another 8 rats were used as sham surgery group (n=8). The animals were killed 5 weeks after surgery. Radiographic, Micro-CT，histological, and immunohistochemical assessments were performed. Results Radiographic assessment showed better preservation of the femoral head shape in the zoledronate group than in the placebo group but not significantly different from the sham surgery group. Micro-CT assessment showed higher totol volume, bone volume, and total mineralized content in the zoledronate group（all P0.05). Compared with the placebo group, the zoledronate group had reduced osteoclast and osteoblast activity, as confirmed by histological examinations. Conclusion Zoledronate can decrease the femoral head deformity by reducing the osteoclast activity while suppressing new bone and vessels formation in a rat model of traumatic osteonecrosis, and therefore may delay the collapse of femoral head.

Objective To explore the efficacy of homemade hemostatics of injected gelatin matrix (HIGM) for immediately treating blunt hepatic trauma in canine model without additional pressure. Methods A total of 27 commercial hybrid dogs underwent celiotomy to establish hepatic trauma model after general anesthesia. The dogs were prospectively randomized into 3 groups: the treatment group (n=9, with the direct application of homemade hemostat), the positive control group (n=9, with thrombin solution), and the negative control group (n=9, with 0.9% normal saline). Time to hemostasis and intra-abdominal blood loss were recorded, and heart rate (HR), mean arterial pressure (MAP), and hematological parameters were compared among these three groups. Gross examinations were performed 30 minutes after surgery. Results Significantly shorter time to hemostasis [(1.20±0.33) min] and less blood loss [(47.22±8.61) ml] were observed in the treatment group than in control groups (P 0.05). No cases of bleeding occurred in any animals in the treatment group, and no signs of infection and adhesion formation were evident due to exposure to HIGM. Two cases in the positive control group (22.22%) were found to have rebleeding. All animals in the negative control group experienced visible bleeding. Conclusion HIGM is effective for controlling bleeding after hepatic trauma without the additional compression, and therefore may be valuable in field surgery.

Objective To establish a new culture method to induce the differentiation of embryonic pancreatic cells into mature endocrine cells. Methods Mouse embryos at day 12.5 were used and embryonic pancreata were isolated. The isolated embryonic pancreata were cultured on the filter for 7 days, which floated in the dish containing medium. During culture, the expression of pancreas duodenum homeobox-1 (PDX-1), a pancreatic stem cell marker, was examined at day 1. The expression of neurogenin 3 (Ngn3), a pancreatic progenitor cell marker, was examined at day 3. The expressions of endocrine and exocrine markers, insulin, glucagon, and carboxypeptidase (CPA) were examined at day 7 by immunohistochemistry. The kinetics of pancreatic marker expression during culture was assayed by real-time PCR. Results Many pancreatic stem cells still existed in embryonic pancreata cultured for 1 day; meanwhile, these pancreatic stem cells proliferated in high rate. A large amount of pancreatic progenitor cells were found in embryonic pancreata cultured for 3 days.Pancreatic stem/progenitor cells differentiated into mature endocrine and exocrine cells in embryonic pancreata after having been cultured for 7 days. Furthermore, the expression pattern of pancreatic marker is consistent with that in vivo. Conclusion We successfully established a new culture method, with which embryonic pancreatic cells can efficiently differentiate into mature endocrine cell.

Objective To study the effect of adenovirus-mediated basic fibroblast growth factor(FGF-2) gene transfer in vivo on oligodendrocyte cell numbers throughout ventrolateral white matter following spinal cord injury in rats. Methods Thirty-two adult female Sprague Dawley rats were injured with the Infinite Horizon Impactor, and then were randomly assigned to four groups: FGF-2-Adts high-titer group (1.27x10⁷ pfu/rat), FGF-2-Adts intermediate-titre group (6.37x10⁶ pfu/rat), FGF-2-Adts low-titer group (3.18 x 10⁶ pfu/rat), and green fluorescent protein (GFP)-Adts group (5.9x10⁷ pfu/rat). The transgenic expression in vivo was detected with fluorescence microscopy. The locomotor function of the hindlimbs of rats was evaluated using Rivlin plate. Slides mounted with tissue sections were processed for immunohistochemical detection and quantification of oligodendrocytes (CC1⁺) in the ventral lateral funiculi (VLF) of injured spinal cords. Results One week after spinal cord injury, GFP showed that many cells had expressed objective gene in vivo and the angles of the occlusal plane of rats in FGF-2 groups were significantly higher than in GFP-Adts group. Also, there was a significant difference among the FGF-2-Adts treatment groups for the volume of gray matter sparing. However, there were no significant differences for total white matter sparing. Stereological quantification of total CC1⁺ cell numbers in the spared VLF showed a significant reduction in numbers with GFP controls compared to all other groups 4 weeks after injury. In contrast, the FGF-2 Adts intermediate-titer group had significantly more CC1⁺ cells when compared to both the FGF-2-Adts high- and low-titer groups. Conclusion Adenovirus-mediated FGF-2 gene transfer can promote the functional recovery of the injured spinal cord by enhancing the proliferation and/or differentiation of oligodendrocytes.

Objective To investigated the effect of 50-Hz 3.6-mT sinusoidal electromagnetic fields (SEMFs) on the proliferation and differentiation of osteoblasts in vitro. Methods The newborn rat calvarial osteoblasts were isolated by enzyme digestion and randomly divided into 6 groups after one passage. The treatment groups under 50-Hz 3.6-mT SEMFs and controls without SEMFs treatment. The cells were exposed in the SEMFs for 0.5 h, 1.0 h, 1.5 h, 2.0 h, and 2.5 h. They were observed under the contrast phase microscope each day. The calcified nodules were stained by alizarin red. The SEMFs were arranged in spiral appearance after 3 to 5 days. Results The SEMFs showed characteristic distribution 3 to 5 days after SEMFs treatment. On the 9^th day after treatment, the activity of alkaline phosphatase (ALP) significantly increased in the 0.5-h group, whereas the ALP histochemical straining results and the area of calcified nodules were consistent with ALP activity. In the 48-h and 96-h groups, the genetic expression levels of osteoprotegerin and collagen-Ⅰ were significantly higher than that in the control group; particularly, the mRNA expression increased in the 0.5-h group. Conclusion The SEMFs at 50-Hz 3.6-mT could suppress the proliferation of osteoblasts maturation but stimulate the differentiation and maturation of osteoblasts in vitro.

Objective To explore the podocyte injury in patients with diabetic nephropathy (DN) and analyze its relationship with glucose regulated protein 78 (GRP78) and proteinuria. Methods The clinical data of 48 patients diagnosed as DN by renal biopsy were reviewed. All patients were divided into two groups according to proteinuria (>3.5 g/d, n=31 and 3.5 g/d group was significantly lower than that of urine protein>3.5 g/d group urine protein<3.5 g/d group（P=0.003), and it was negatively correlated with proteinuria (P=0.005). The expressions of synaptopodin and GRP78 in podocytes were also negatively correlated with proteinuria (P=0.004 and P=0.001). Conclusion The podocyte injury is aggravated with increased proteinuria in DN patients, along with the decrease of the adaptive ability of endoplasmic reticulum to stress.

Objective To investigate the role of contrast-enhanced ultrasound in the differential diagnosis of high- and low-grade urothelial carcinoma. Methods The radiological data of 96 patients with urothelial carcinomas who had undergone gray-scale contrast-enhanced ultrasound from August 2010 to April 2011 were analyzed retrospectively. Pathological examination demonstrated that the tumors were high-grade in 55 cases (high-grade group) and low-grade in 41 cases (low-grade group). The dynamic images were analyzed by time-intensity curve, and the arrival time (AT), peak intensity (PI), time to peak (TTP), and washout time (WT) were measured. The enhancement patterns of different urothelial carcinomas were analyzed. Results Both PI (P=0.005) and WT (P=0.002) were significantly higher in high-grade group than in low-grade group, whereas AT (P=0.374) and TTP (P=0.386) showed no significant difference between these two groups. In the high-grade group, 47 cases (85.5%) were identified as fast wash-in and slow wash-out; in the low-grade group, 35 (85.4%) were identified as fast wash-in and fast wash-out. When the enhancement pattern was used as a diagnostic indicator for differentiating urothelial carcinomas, the sensitivity, specificity, accuracy, positive predictive value, and negative predictive value were 85.5%, 90.2%, 87.5%, 92.2%, and 82.2% for high-grade tumor and 85.4%, 90.9%, 88.5%, 87.5%, and 89.3% for low-grade tumor. Conclusions Different grade urothelial carcinomas show different enhancement finding on contrast-enhanced ultrasound. The enhancement pattern can serve as an important diagnostic indictor.

Objective To investigate the prognostic value of ultra-sensitive pregnancy associated plasma protein-A (PAPP-A) level in the early phase of acute coronary syndrome (ACS) attack. Methods Patients diagnosed as ACS were enrolled and the level of circulatory PAPP-A was measured within 12 hours after ACS attack. The patients were followed at the time of 1st, 6th, and 12th months post-ACS attack in order to observe the incidence of the cardiovascular adverse events. According to the highest quintile, the patients were devided into 2 groups: high level (≥26.08 μg/L) group and low level (<26.08 μg/L) group, to evaluate the association between the level of PAPP-A and the incidence of the cardiovascular events. Results Compared with the low level group, the incidence of the composite outcome is significantly increased in the high level group, and the values of OR are 4.76, 4.38, 3.75 for 1st, 6th, 12th months respectively (P=0.000). For myocardial infarction (MI) + cardiac death (CD) the values of OR were 9.81, 6.08, 4.12 (P<0.01). Multivariate logistic regression analysis demonstrates that PAPP-A was an independent risk factor for the cardiovascular adverse events in the early, median, and late phase of ACS (P<0.05). Conclusion In the early phase of ACS attack, the elevation of PAPP-A is an independent risk factor for the occurrence of cardiovascular adverse events.

Objective To investigate the effectiveness of pimecrolimus cream 1% for sensitive skin in adult women and its underlying mechanisms. Methods The changes of subjective symptoms and signs were evaluated before and after the application of pimecrolimus cream 1% based on the severity of pruritus (SP) and severity of burning sensation (SB) scores, and on a basic syntax and molecular substrate (molecular psychophysics) of nociception and pruriception established by temperature-sensitive transient receptor potential (TRP) channels. Results The SP and SB scores were significantly decreased in 32 patients with sensitive skin after using topical pimecrolimus cream 1% (P<0.05). Twenty (62.5%) patients showed positive capsaicin-like response (i.e. burning with consequent rapid amelioration of pruritus or burning sensation) and 6 (18.8%) showed positive camphor-like response (i.e. warming with consequent rapid amelioration of pruritus) on application sites after using the topical pimecrolimus cream 1%, and 6 (18.8%) showed negative capsaicin-like response and/or negative camphor-like response. Conclusions Pimecrolimus may rapidly inhibit or alleviate itch or burning sensation of patients with sensitive skin. The therapeutic effect of pimecrolimus is relevant to the mechanisms that activate or sensitize transient receptor potential vanilloid 1 (TRPV1) and desensitizes TRPV1 in the skin sensory afferents.

Objective To study the effect of peroxisome proliferator activated receptor γ (PPAR-γ) agonist on the angiotensin converting enzyme 2 (ACE2) mRNA expression in monocyte-derived macrophages of essential hypertensive patients. Methods Totally 57 essential hypertensive patients were randomly divided into three groups: conventional treatment group (n=18), telmisartan group (n=19), and benazepril group (n=20); 20 patients with normal blood pressure were also selected as the control group. Monocyte-derived macrophages were isolated from blood samples of patients in all four groups. The expression of ACE2 mRNA in monocyte-derived macrophages was detected by RT-PCR before treatment and 4 and 12 weeks after treatment. Results Four and 12 weeks after treatment, the systolic pressure and diastolic pressure of telmisartan group and benazepri group were significantly lower than that of the conventional treatment group (all P<0.01), and the systolic pressure and diastolic pressure of telmisartan group were significantly lower than that of the benazepri group(both P<0.01) .The expression of ACE2 mRNA in monocyte-derived macrophages were significantly lower in essential hypertensive patients than that in control group (P<0.01). After having been treated for 4 weeks and 12 weeks, the expression of ACE2 mRNA in monocyte-derived macrophages of hypertensive patients in telmisartan and benazepril groups were significantly higher than that in conventional treatment group (all P<0.01), and the expression of ACE2 mRNA in telmisartan group was significantly higher than that in benazepril group (both P<0.01). Conclusion PPAR-γ agonist could increase the ACE2 mRNA expression in monocyte-derived macrophages of essential hypertensive patients.

Objective To study the expressions of matrix metalloproteinase-9 (MMP-9) and tissue inhibitor of metalloproteinase-1 (TIMP-1) in the airway of bronchiectasis (BE) patients, and evaluate the effect of pseudomonas aeruginosa (PAE) on the expression of TIMP-1 and MMP-9. Methods In this case-control study, subjects were divided into BE group and control group, and the BE group was further divided into PAE group and other bacteria group based on the culture results of bronchoalveolar lavage fluid (BALF). BALF was obtained by bronchoscopy, the expressions of MMP-9 and TIMP-1 were determined by ELISA, then the ratio of TIMP-1/MMP-9 was calculated. Furthermore, the tissue of bronchic endomembrane was obtained by transbronchial biopsy and the expressions of MMP-9 and TIMP-1 were determined using immunohistochemical method. Results The levels of MMP-9 in the BALF of PAE group and other bacteria group were significantly higher than that in control group (P=0.0000 both), and the expressions of MMP-9 in bronchic endomembrane of PAE group and other bacteria group were also significantly higher (P=0.0421 and 0.0003, respectively). The level of TIMP-1 in BALF of PAE group was significantly lower than that in other bacteria group (P=0.0324). The ratio of TIMP-1/MMP-9 in BALF of BE group was significantly lower than that in control group(P=0.0000), and this ratio of PAE group was significantly lower than those in both other bacteria group and control group (P=0.0026 and 0.0000, respectively). Conclusion PAE infection in BE patients can suppress the expression of TIMP-1 and stimulate the expression of MMP-9, and thus make the disease even worse.

Objective To investigate the association of the polymorphisms of aldehyde dehydrogenase-2(ALDH2) and CYP2E1-RsaI genes and alcohol consumption with oral squamous cell carcinoma (OSCC). Methods The genetic polymorphisms of ALDH2 and CYP2E1-RsaI were determined by polymorphism-polymerase chain reaction (PCR) technique in the peripheral blood leukocytes of 320 OSCC patients and 320 non-cancer controls. Results The frequencies of ALDH2 variant genotypes and CYP2E1-RsaI (c2/c2) were 70.94% and 39.06% in the OSCC group and 43.44% and 20.62% in the control group (both P<0.01). The risk of OSCC with ALDH2 variant genotypes was significantly higher than that in control group (OR=3.178, 95% CI=1.917-4.749), whereas the subjects carried with CYP2E1-RsaI (c2/c2) also had a high risk of OSCC (OR=2.467, 95%CI=1.783-4.045). Combined analysis of the polymorphisms showed that percentage of ALDH2 variant genotypes/CYP2E1-RsaI (c2/c2) in OSCC group and control group was 32.19% and 6.25%, respectively (P<0.01). Carriers of ALDH2 variant genotypes/CYP2E1-RsaI (c2/c2) had a high risk of OSCC (OR=9.792, 95%CI=3.583-12.472). The percentage of alcohol consumption was significantly higher in OSCC group than in the control group (OR=2.861, 95% CI=1.541-4.781, P<0.01), and ALDH2 variant genotypes and CYP2E1-RsaI (c2/c2) showed synergic effects with alcohol consumption for the increased risk of OSCC (OR=41.152, 95%CI=19.903-67.551). Conclusion The polymorphisms of ALDH2 and CYP2E1-RsaI genes and alcohol consumption, independently and synergically, increase the risk of OSCC.

Objective To evaluate application value of apparent diffusion coefficient (ADC) in di- fferentiating brain radiation-injuries and glioma recurrence. Methods Totally 23 patients [18 men and 5 women aged 32 to 67 years (mean: 47 years)] with previously resected and irradiated glioma were examined by using a 3.0T MR Scanner, including conventional and diffusion weighted image (DWI) sequences. All the cases were proved by pathology or clinical follow-up. Postprocessing of ADC maps was performed by using Functool software (AW 4.3, GE Healthcare), and the regions of interest (ROIs) were manually drawn on ADC maps in the area corresponding to the contrast-enhancing area on post-contrast axial T1-weighted images, avoiding the hemorrhage or necrosis. The ADC values were calculated automatically. ADC values were measured 10 times in order to reduce errors, and mean ADC value, maximum ADC value, and minimum ADC value were acquired. Results Both recurrent glioma and irradiated necrosis tended to have hemorrhage, necrosis, and edema. The mean ADC value and maximum ADC value were lower in the recurrent tumor group than in the radiation-injuries group, but no statistical difference was achieved. However, the minimum ADC value was significantly lower in the recurrent tumor group than in the radiation-injuries group (P=0.016). Conclusion The minimum ADC value can be used as an useful tool in differentiating tumor recurrence from radiation-injuries.

Objective To study the clinical characteristics and outcomes of the hereditary medullary thyroid carcinoma (HMTC) and the sporadic medullary thyroid carcinoma (SMTC). Methods The clinical data of 78 patients with medullary thyroid carcinoma who underwent surgery in our hospital between July 1980 and May 2011 were retrospectively analyzed. Results Of these 78 patients, there were 23 HMTC cases and 55 SMTC cases. The HMTC group was significantly younger age of onset [(36.4±13.5) years vs. (46.6±11.2) years, P<0.01] and a lower pre/post-operative serum calcitonin levels [(850.4±110.20) ng/L vs. (1450.4±118.3) ng/L, P<0.01 and (410.8±133.2) ng/L vs. (1585.4±129.5) ng/L, P<0.01] than the SMTC group. In addition, the mean tumor diameter was also significantly smaller in the HMTC group (14.3 mm vs. 21.0 mm in SMTC group, P<0.05). Tumor multifocality was seen in a significantly higher proportion of HMTC cases compared with the SMTC cases (56.6% vs. 29.1%, P<0.05). The overall 10-year survival was 100% in HMTC group and 80.2% in SMTC group (P<0.05). Conclusion HMTC has a better prognosis than SMTC.

Objective To explore the pathoclinical features of adult primary mediastinal liposarcoma and their correlation with the prognosis. Methods The clinical data of 19 patients with adult primary mediastinal liposarcoma who were treated in our hospital between 1970 and 2011 were retrospectively analyzed. Eighteen patients underwent open thoracic tumor excisions for at least one time, and the remaining one patient only received biopsy surgery. Histopathological results after surgery revealed that 6 well-differentiated type tumors, 6 myxoid type tumors, 3 pleomorphic type tumors, 2 mixed type tumors, and 2 un-classified tumors. Results Among 6 patients with well-differentiated type tumors, 1 died after having been survived for 10 years; 5 were still alive, with a mean duration of 126.2 months,the 5-year survival rate was 100%. Among 6 patients with myxoid type tumors, 5 patients had follow-up data, with a mean survival of 26.2 months. Among 3 patients with pleomorphic type tumors, only one patient had follow-up data: the patient finally died, with a survival of 34 months. Of 2 patients with mixed type tumors, only one patient had follow-up data: the patient survived 8 months and died. Of 2 patients with un-classified type tumors, one had follow-up data: the patient lived for 24 months and died. Conclusions Mediastinal liposarcoma is a rare disease. Surgery is the primary therapeutic modality. Different pathological subtypes have different epidemiological features, biological behaviors, and malignant potentials. Pathological subtype is an important prognosis factor. Patients with well-differentiated tumors have much better prognosis than those with other subtypes.

Objective To investigate the feasibility and clinical value of site-specific pathology in breast reduction mammoplasty. Methods Totally 127 patients who underwent breast reduction mammoplasty from June 2007 to June 2010 were included. Pathologic specimens were sent for frozen pathology according to the clock-wise method. Patients with confirmed cancer were arranged for conservative breast surgery. Results Of the 127 patients, 53 patients (41.7%) had gland hyperplasia; 7 had fibroadenoma (5.5%); 1 (0.79%) had ductal carcinoma in situ, who underwent breast conserving surgery, following by chemotherapy and radiotherapy, no relapse was noted during the three-year follow-up. Conclusion Clock-wise method is useful to locate the tumor and ensure the patients to receive skin-spared breast resection even cancer is detected.

Metabonomies is a systematic science that mainly studies the dynamic changes of endogenous metabolites after a biological system is stimulated or disturbed. Its application in cardiovascular diseases has increasingly been explored, with an attempt to find valuable biomarkers and explore the underlying pathogenesis of cardiovascular diseases by profiling the metabolism in these patients. This article summarized recent advances in this topic and outlines prospects for future developments.

MicroRNAs (miRNAs) are a class of highly conserved single-stranded RNA molecules that modulate gene translation. By targeting the mRNA of protein- coding genes, miRNAs play a critical role in neuronal differentiation, cell proliferation, apoptosis and metabolism. There are a lot of miRNAs in central nervous system, which are not only closely linked to development, differentiation and function of nerve cells, also play an important role in nerve lesions and dysfunction after cerebral ischemia. Specific miRNA through their own changes affect their target gene expression levels after focal cerebral ischemia, involving in the protection against apoptosis in neurons and regeneration after cerebral ischemia. A full understanding of the specific microRNA function and its underlying mechanism in the brain can provide a new strategy for the prevention, diagnosis, and treatment of ischemic cerebral injury at gene level.

Weightless environment is a rare phenomenon on the ground where the interactions among cells and internal cellular structures disappear or become weakened. Studies on the biological features and molecular expression of tumors cells in weightlessness condition may provide new clues to the tumor initiation, process, diagnosis, and therapy.

G protein-coupled inward rectifier K⁺ channel 4(GIRK4) is a G protein-coupled inward rectifier potassium channel family member. Encoded by the KCNJ5, it is widely distributed in the mammalian heart, brain, and other tissues and organs. Recent studies have demonstrated that the abnormal expression of GIRK4 gene is associated with atrial fibrillation, and meanwhile may be closely related to obesity, metabolic syndrome, and many other clinical conditions. Further research on the role the GIRK4 gene in the pathophysiology of these clinical conditions will definitely facilitate their clinical diagnosis and treatment.

Obesity is becoming increasingly prevalent and thus has been a global public concern. Studies have demonstrated that obesity and its complications can cause an early onset of cardiovascular diseases (CVD), reduce the therapeutic effecacy of medical and invasive treatment, and thus increase the mortality. Meanwhile, it can also cause damage to the structure, electrophysiology, and myocardial function of heart. It can be a particularly important issue for women. On the other hand, heart injury can also affect the weight loss options and their outcomes. This article elucidates the relationship between obesity and its complications and CVD, and meanwhile proposes some new perspectives about the prevention of CVD.