Palmitoylation of the pore-forming subunit of Ca(v)1.2 controls channel voltage sensitivity and calcium transients in cardiac myocytes.

Mammalian voltage-activated L-type Ca2+ channels, such as Ca(v)1.2, control transmembrane Ca2+ fluxes in numerous excitable tissues. Here, we report that the pore-forming α1C subunit of Ca(v)1.2 is reversibly palmitoylated in rat, rabbit, and human ventricular myocytes. We map the palmitoylation sites to two regions of the channel: The N terminus and the linker between domains I and II. Whole-cell voltage clamping revealed a rightward shift of the Ca(v)1.2 current-voltage relationship when α1C was not palmitoylated. To examine function, we expressed dihydropyridine-resistant α1C in human induced pluripotent stem cell-derived cardiomyocytes and measured Ca2+ transients in the presence of nifedipine to block the endogenous channels. The transients generated by unpalmitoylatable channels displayed a similar activation time course but significantly reduced amplitude compared to those generated by wild-type channels. We thus conclude that palmitoylation controls the voltage sensitivity of Ca(v)1.2. Given that the identified Ca(v)1.2 palmitoylation sites are also conserved in most Ca(v)1 isoforms, we propose that palmitoylation of the pore-forming α1C subunit provides a means to regulate the voltage sensitivity of voltage-activated Ca2+ channels in excitable cells.

[Diagnosis and surgical treatment of high-risk anomalous aortic origin of coronary artery].

Objective: To analyze the diagnosis and surgical treatment of high-risk anomalous aortic origin of coronary artery (AAOCA). Methods: This is a retrospective case series study. From January 2016 to July 2023, 24 cases of high-risk AAOCA underwent surgical treatment in Department of Cardiac Surgery, Guangdong Provincial People's Hospital. There were 18 males and 6 females, operatively aged (M (IQR)) 13 (26) years (range: 0.3 to 57.0 years). They were confirmed by cardiac ultrasound and cardiac CT, all of which had anomalous coronary running between the aorta and the pulmonary artery. There were 15 cases of the right coronary artery from the left aortic sinus of Valsalva, 6 cases of left coronary artery from the right aortic sinus of Valsalva, 3 cases of the sigle coronary artery. Only 3 patients had no obvious related symptoms (2 cases were complicated with a positive exercise stress test and 1 case with other intracardiac malformations), 21 cases had a history of chest tightness, chest pain, or syncope after exercise. Three patients suffered syncope after exercise and underwent cardiopulmonary resuscitation (2 cases were treated with an extracorporeal membrane oxygenerator (ECMO)). The gap from the first symptom to the diagnosis was 4.0 (11.5) months (range: 0.2 to 84.0 months). The detection rate of coronary artery abnormalities suggested by the first cardiac ultrasound was only 37.5% (9/24). Seven patients were complicated with other cardiac diseases (4 cases with congenital heart defects, 2 cases with coronary atherosclerotic heart disease, 1 case with mitral valve disease). Results: All 24 patients underwent surgical treatment (23 cases underwent abnormal coronary artery unroofing, 1 case underwent coronary artery bypass grafting), and 5 patients underwent other intracardiac malformation correction at the same time. There were no death or surgery related complications in the hospital for 30 days after the operation. A patient with preoperative extracorporeal cardiopulmonary resuscitation was continuously assisted by ECMO after emergency AAOCA correction and had complications such as limb ischemia necrosis and renal dysfunction after the operation. During the follow-up of 2.2 (3.3) years (range: 1 month to 7.2 years), one patient who previously underwent percutaneous transluminal coronary angioplasty with a stent implant experienced significant postoperative symptomatic relief, and the other discharged patients had no related symptoms. Conclusions: The accurate rate of initial diagnosis for high-risk AAOCA is still low, but the risk of cardiovascular accidents is high. For sports-related chest pain and other symptoms, more attention should be paid to the detection of AAOCA, especially for adolescents. Exercise stress testing can be helpful in evaluating the cardiovascular risk of asymptomatic AAOCA. Instant surgical treatment can achieve satisfactory curative effects.

Development and multicenter validation of a novel radiomics-based model for identifying eosinophilic chronic rhinosinusitis with nasal polyps.

BACKGROUND: Reliable noninvasive methods are needed to identify endotypes of chronic rhinosinusitis with nasal polyps (CRSwNP) to facilitate personalized therapy. Previous computed tomography (CT) scoring system has limited and inconsistent performance in identifying eosinophilic CRSwNP. We aimed to develop and validate a radiomics-based model to identify eosinophilic CRSwNP. METHODS: Surgical patients with CRSwNP were recruited from Tongji Hospital and randomly divided into training (n = 232) and internal validation cohort (n = 61). Patients from two additional hospitals served as external validation cohort-1 (n = 84) and cohort-2 (n = 54), respectively. Data were collected from October 2013 to May 2021. Eosinophilic CRSwNP was determined by histological criterion. The least absolute shrinkage and selection operator and the logistic regression (LR) algorithm were used to develop a radiomics model. Univariate and multivariate LR were employed to build models based on CT scores, clinical characteristics, and the combination of radiological and clinical characteristics. Model performance was evaluated by assessing discrimination, calibration, and clinical utility. RESULTS: The radiomics model based on 10 radiomic features achieved an area under the curve (AUC) of 0.815 in the training cohort, significantly better than the CT score model based on ethmoid-to-maxillary sinus score ratio with an AUC of 0.655. The combination of radiomic features and blood eosinophil count had a further improved performance, achieving an AUC of 0.903. The performance of these models was confirmed in all validation cohorts with satisfying predictive calibration and clinical application value. CONCLUSIONS: A CT radiomics-based model is promising to identify eosinophilic CRSwNP. This radiomics-based method may provide novel insights in solving other clinical concerns, such as guiding personalized treatment and predicting prognosis in patients with CRSwNP.

[Preliminary survey report on the clinical validation of in-use electronic sphygmomanometers in China].

Objective: To explore the percentage of in-use electronic sphygmomanometers independently validated clinically in China. Methods: We conducted a cross-sectional survey and Beijing, Shenzhen, Shijiazhuang, Datong, and Shihezi were selected according to the geographical location and economic level. In each site, one tertiary hospital, two community health centers, and 20 families with electronic sphygmomanometers in use were chosen. The information of electronic sphygmomanometers including brand, model, manufacturer and production date were obtained by the trained staff. Ten electronic sphygmomanometers from each hospital, five electronic sphygmomanometers from each community health center, and one electronic sphygmomanometer from each family were surveyed, and the user's subjective judgment results and judgment basis on the accuracy of the electronic sphygmomanometer measurement were collected. We searched six registration websites (Medaval, Stride BP, dabl Educational Trust, British and Irish Hypertension Society, American Medical Association and Hypertension Canada) and two research databases (PubMed and CNKI) for the clinical validation status of each electronic sphygmomanometer. Results: A total of 200 electronic sphygmomanometers were investigated in this study, of which only 29.0% (58/200) passed independent clinical validation. When stratified by users, the percentage of being clinical validated was 46.0% (23/50) for electronic sphygmomanometers in hospitals, 42.0% (21/50) for those in community health centers and 14.0% (14/100) for those in home use, respectively, and the proportions between the three groups were significantly difference (P<0.001). Doctors in tertiary hospitals and community health service centers judged the accuracy of electronic sphygmomanometers mainly on the basis of "regular correction" (41.0% (41/100)) and "comparison with other electronic sphygmomanometers" (20.0% (20/100)), while among home users, 41.0% (41/100) were not clear about the accuracy of electronic sphygmomanometers, and 40.0% (40/100) made the judgment by "comparison with the devices in hospitals". Conclusion: The clinical validation of in-use electronic sphygmomanometers in China is low. Most of users, including healthcare professionals, are not aware of clinical validation of electronic sphygmomanometers.

The link between cutaneous inflammation and cognitive impairment.

Cognitive impairment is a symptom of neurological disorders, including dementia and Alzheimer's disease; and mild cognitive impairment can be a precursor of both disorders. Aged humans and animal models with other systemic disorders, such as cardiovascular diseases and diabetes, display a higher incidence of cognitive decline. Epidemiological studies have shown that the incidence of cognitive impairment also is higher in subjects with certain inflammatory skin disorders, including psoriasis and chronic eczematous dermatitis. Chronologically aged individuals exhibit increased cutaneous inflammation and elevated circulating cytokine levels, linked to alterations in epidermal function, which itself can induce cutaneous inflammation. Conversely, strategies that improve epidermal function can lower cytokine levels in both the skin and circulation. Thus, it seems likely that epidermal dysfunction could contribute, at least in part, to the development of chronic low-grade inflammation, also termed 'inflammaging', in the elderly. The evidence of cognitive impairment in patients with inflammatory dermatoses suggests a link between cutaneous inflammation and cognitive impairment. Because of the pathogenic role of epidermal dysfunction in ageing-associated cutaneous inflammation, improvements in epidermal function could be an alternative approach for mitigation of the ageing-associated decline in cognitive function.

A topical emollient mitigates the progression of cognitive impairment in the elderly: a randomized, open-label pilot trial.

BACKGROUND: Cognitive impairment is common in the elderly. Prior studies suggest a link between chronic inflammation and cognitive dysfunction, while aging-associated epidermal dysfunction has been connected to elevations in circulating cytokines. OBJECTIVE: We assessed here whether improvements in epidermal function can mitigate the progression of cognitive impairment. METHODS: This randomized, open-label pilot trial was carried out in two cities in northern China. A total of 200 participants aged ≥65 years were randomly assigned to the emollient-treated and untreated groups at 1:1 ratio. Participants in the treated group were treated topically with Atopalm cream® twice-daily from November to the following May each year for three consecutive years, while the untreated subjects served as controls. The Global Deterioration Scale (GDS) was used to assess the severity of cognitive impairment, while epidermal biophysical properties were measured on the forearms and the shins in parallel. RESULTS: Over the three-year trial, GDS significantly increased from baseline (P < 0.0001) in the controls, while in the treated group, GDS stabilized. While stratum corneum hydration on the forearms did not change significantly in the controls, transepidermal water loss rates (TEWL), significantly increased by the end of the trial compared to baselines in the controls (P < 0.0001). On the forearms of the treated group, stratum corneum hydration increased (P < 0.0001) while skin surface pH decreased from baseline (P < 0.0001). CONCLUSIONS: These results suggest that improvements in epidermal function with topical emollient can mitigate the progression of cognitive impairment. However, the sample size was relatively small, and trials in a larger cohort are needed to validate the present results.

Management of calcaneus fractures by a new "Below-the-ankle" ilizarov frame: A series of 10 cases.

Background: The optimal management of intra-articular calcaneal fractures is still controversial. Open reduction and internal fixation are always associated with serious complications. Aim: Various alternative methods have been used with variable effects. This retrospective study aimed to analyze the clinical efficacy and safety of a new "below-the-ankle" Ilizarov frame in patients with calcaneal fractures caused by high-energy trauma. Patients and Methods: We retrospectively explored ten patients with calcaneal fractures, of which four, five, and one were Sanders type II, III, and IV, respectively. All fractures were caused by high-energy trauma and were followed up for an average period of 21 months (range: 9-29 months). Clinical outcomes were primarily assessed by radiological criteria, functional scores of the foot and ankle, rate of complications, and ankle range of movement. Results: The Ilizarov frame was removed after an average period of 12 weeks (range: 11-15 weeks). Only two patients developed pin-tract infections, and none developed osteomyelitis, deep infections, neurovascular injury, malunion, and ankle arthrodesis. Based on the radiological assessment of the reduction of the subtalar joint and fracture fragments, all patients had excellent restored joint structure, with eight and two patients having good-to-excellent and fair ankle scores, respectively. The ranges of plantarflexion and dorsiflexion were 25°-43° and 8°-22°, respectively. Conclusion: The Ilizarov frame could be safe and effective for calcaneal fractures caused by high-energy trauma. This treatment protocol provides an effective approach to treat severe calcaneal fractures caused by high-energy events; however, long-term outcomes are still unknown.

Programmed death ligand-1 induction restrains the cytotoxic T lymphocyte response against microglia.

Microglial cells are the main reservoir for HIV-1 within the brain and potential exists for negative immune checkpoint blockade therapies to purge this viral reservoir. Here, we investigated cytolytic responses of CD8+ T lymphocytes against microglia loaded with peptide epitopes. Initially, flow cytometric analysis demonstrated efficient killing of HIV-1 p24 AI9 or YI9 peptide-loaded splenocytes in MHC-matched recipients. Cytolytic killing of microglia was first demonstrated using ovalbumin (OVA) as a model antigen for in vitro cytotoxic T lymphocyte (CTL) assays. Peptide-loaded primary microglia obtained from programmed death ligand (PD-L) 1 knockout (KO) animals showed significantly more killing than cells from wild-type (WT) animals when co-cultured with activated CD8+ T-cells isolated from rAd5-OVA primed animals. Moreover, when peptide loaded-microglial cells from WT animals were treated with neutralizing α-PD-L1 Ab, significantly more killing was observed compared to either untreated or IgG isotype-treated cells. Most importantly, significantly increased in vivo killing of HIV-1 p24 YI9 peptide-loaded microglia from PD-L1 KO animals, as well as AI9 peptide-loaded BALB/c microglial cells treated with α-PD-L1, was observed within brains of rAd5-p24 primed-CNS boosted C57BL/6 or BALB/c mice, respectively. Finally, ex vivo responses of brain CD8+ T-cells in response to AI9 stimulation showed significantly increased IFN-γ and IL-2 production when treated with α-PD-1 Abs. Greater proliferation of CD8+ T-cells from the brain was also observed following blockade. Taken together, these studies demonstrate that PD-L1 induction on microglia restrains CTL responses and indicate that immune checkpoint blockade targeting this pathway may be beneficial in clearing viral brain reservoirs.

Second tumor risk in children treated with proton therapy.

BACKGROUND: Out-of-field neutron dissemination during double-scattered proton therapy has raised concerns of increased second malignancies, disproportionally affecting pediatric patients due to the proportion of body exposed to scatter dose and inherent radiosensitivity of developing tissue. We sought to provide empiric data on the incidence of early second tumors. METHODS: Between 2006 and 2019, 1713 consecutive children underwent double-scattered proton therapy. Median age at treatment was 9.1 years; 371 were ≤3 years old. Thirty-seven patients (2.2%) had tumor predisposition syndromes. Median prescription dose was 54 Gy (range 15-75.6). Median follow-up was 3.3 years (range 0.1-12.8), including 6587 total person-years. Five hundred forty-nine patients had ≥5 years of follow-up. A second tumor was defined as any solid neoplasm throughout the body. RESULTS: Eleven patients developed second tumors; the 5- and 10-year cumulative incidences were 0.8% (95% CI, 0.4-1.9%) and 3.1% (95% CI, 1.5-6.2%), respectively. Using age- and gender-specific data from the Surveillance, Epidemiology, and End Results (SEER) program, the standardized incidence ratio was 13.5; the absolute excess risk was 1.5/1000 person-years. All but one patient who developed second tumors were irradiated at ≤5 years old (p < .0005). There was also a statistically significant correlation between patients with tumor predisposition syndromes and second tumors (p < .0001). Excluding patients with tumor predisposition syndromes, 5- and 10-year rates were 0.6% (95% CI, 0.2-1.7%) and 1.7% (95% CI, 0.7-4.0%), respectively, with all five malignant second tumors occurring in the high-dose region. CONCLUSION: Second tumors are rare within the decade following double-scattered proton therapy, particularly among children irradiated at >5 years old and those without tumor predisposition syndrome.

[Selection of neck dissection operation for head neck cancer].

As the primary surgical procedure of treating and preventing cervical lymph node metastasis in head and neck cancers, neck dissection (ND) have increasingly becoming standardized and reasonable since the past hundred years. However, the preoperative uncertainty of cervical lymph node metastasis for patient with head neck cancer, whether perform ND and the dissection region often confuse the surgeons. Provide a currently standardized ND operation manner according to the metastatic characteristics and operative wound degree as a reference to surgeons may facilitate the therapeutic and prevent effects on patients with head and neck cancer.

[The human body burden of polychlorinated biphenyls in serum of residents in an area from Hubei Province].

Concentrations of dioxin-like polychlorinated biphenyls (dl-PCBs) and non-dioxin-like PCBs (ndl-PCBs) in 26 serum samples of the residents from Hubei Province were analyzed via high-resolution gas chromatograph tandem high-resolution mass spectrometer (HRGC-HRMS) method. Total concentrations of twelve dl-PCBs (Σdl-PCBs) were in range of 366.30-4 945.77 pg/g fat, with the mean value (2 093.76 pg/g fat), and PCB 118 was the predominant congener. For six ndl-PCBs, total concentrations (Σndl-PCBs) were in range of 2 671.32-20 626.26 pg/g fat (mean 12 505.45 pg/g fat), and PCB 153 was the predominant congener. Mean concentration of Σdl-PCBs were significantly and positively associated with age (rs=0.574, P=0.002). The mean World Health Organization toxicity equivalent (WHO-TEQ) of dl-PCBs (ΣTEQdl-PCBs) were range from 0.07 to 8.69 pg/g fat.

[Serological study of Lyme disease antibody in 2 311 patients with arthritis symptoms in Hainan Province].

Objective: To understand the infectious status of Lyme disease among patients with arthritis symptoms in Hainan Province, and to provide a theoretical basis for prevention and control of Lyme disease. Methods: From 2013 to 2018, sampling surveys had been conducted in medical institutions in 8 cities in Hainan Province(Haikou, Sanya, Danzhou, Dongfang, Wenchang, Qionghai, Qiongzhong, Wuzhishan), 2 311 patients serum samples were collected with arthritis symptoms, and descriptive research were conducted base on the collected clinical data. The Indirect Fluorescent-Antibody Test (IFA) method was used for preliminary screening of Lyme disease antibody, the Western Blot (WB) method was used for IFA positive samples confirmation. Statistical analysis using χ2 test. Results: 2 311 serum samples were tested by IFA, and 166 were positive with the positive rate of 7.18%. Further confirmed by WB method, 62 samples were positive, the positive rate of Lyme disease antibody was 2.68%(62/2 311). The positive rate of Lyme disease antibody among patients with arthritis in different regions of Hainan was statistically significant (χ²=40.636,P<0.001), and the positive rate in Qiongzhong city was the highest (8.81%, 14/159). Danzhou's positive rate was the second highest, 5.62%(5/89). Dongfang city had the lowest positive rate (0.51%, 2/394). The positive rates of Lyme disease serum antibody in men and women were 2.79% (33/1 182) and 2.57% (29/1 129), respectively; the positive rates of antibodies between each age groups were in the range of 1.74% to 3.64%. The antibody positive rate of Lyme disease showed no significant difference between gender and age (χ²=0.110,P=0.740 ;χ²=1.938,P=0.747). Conclusion: Patients with arthritis symptoms caused by Borrelia burgdorferi infection were found in 8 cities in Hainan province, but the Lyme disease antibody positive rate was different among cities, with Qiongzhong County being the highest.

[Efficacy of three-dimensional visualization technology in the precision diagnosis and treatment for primary liver cancer: a retrospective multicenter study of 1 665 cases in China].

Objective: To evaluate the efficacy of three-dimensional(3D) visualization technology in the precision diagnosis and treatment for primary liver cancer. Methods: A total of 1 665 patients with primary liver cancer who admitted to seven medical centers in China between January 2009 to January 2019, diagnosed and treated by 3D visualization protocol were analyzed, and their clinical data were retrospectively reviewed. There were 1 255 males(75.4%) and 410 females(24.6%), with age of (52.9±11.9) years (range: 18 to 86 years). The acquisition of high-quality CT images with submillimeter spatial resolution were conducted using a quality control system. By means of homogenization methods, 3D reconstruction and 3D visualization analysis were performed. Postoperative observation: pathology reports, microvascular invasion, perioperative complications and follow-up. SPSS 25.0 statistical software was used for statistical description and analysis of clinical data. Kaplan-Meier curve was used to calculate overall survival and disease-free survival rate. Results: (1)In the sample of 1 265 patients, 3D reconstructed models clearly displayed as follows. tumor size: ≤2 cm in 155 cases (9.31%), >2 cm to 5 cm in 551 cases (33.09%), >5 cm to 10 cm in 636 cases (38.20%), >10 cm in 323 cases (19.40%). (2) Classification of hepatic blood vessels. Hepatic artery: type Ⅰ(normal type) in 1 494 cases(89.73%),variant hepatic artery in 171 cases (10.27%), including type Ⅱ in 35 cases, type Ⅲ in 38 cases, and other types in 98 cases. Hepatic vein: type Ⅰ (normal) in 1 195 cases (71.77%),variant hepatic veins in 470 cases(28.23%), including type Ⅱ in 376 cases and type Ⅲ in 94 cases. Portal vein:normal type in 1 315 cases (78.98%), variant portal veins in 350 cases (21.02%), including type Ⅰ in 189 cases, type Ⅱin 103 cases, type Ⅲ in 50 cases, type Ⅳ in 8 cases. Hepatic artery variation coexisting with portal vein variation in 24 cases (1.44%). Hepatic vein variation coexisting with portal vein variation in 113 cases (6.79%). Three types of vascular variation in 4 cases (0.24%), including coexistence of type Ⅱ hepatic artery variation or type Ⅰ portal vein variation with type Ⅲ hepatic vein variation in 2 cases,coexistence of type Ⅲ hepatic artery variation or type Ⅲ portal vein variation with type Ⅱ hepatic vein variation in 2 cases. (3) Preoperative liver volume calculation:1 499.3 (514.4)ml (range:641.7 to 6 637.0 ml) of total liver volume, including 479.1 (460.1) ml (range:10.5 to 2 086.8 ml) for liver resection and 959.9 (460.4)ml (range:306.1 to 5 638.0 ml) for residual function. (4)Operative methods: anatomical hepatectomy in 1 458 cases (87.57%); non-anatomic hepatectomy in 207 cases (12.43%). (5)the median operation time was 285(165)minutes (range: 40 to720 minutes). (6)The median intraoperative blood loss was 200(250)ml (range:10 to 4 200 ml) and 346 cases (20.78%) had intraoperative transfusion. (7)Pathology reports: hepatocellular carcinoma in 1 371 cases (82.34%), cholangiocarcinoma in 260 cases (15.62%) and mixed hepatocellular carcinoma in 34 cases (2.04%). Microvascular invasion: M0 in 199 cases, M1 in 64 cases, and M2 in 27 cases. (8)Postoperative complications in 207 cases (12.43%), including Clavien-Dindo grade Ⅰ or Ⅱ in 57 cases, grade Ⅲ or Ⅳ in 147 cases and grade Ⅴ in 3 cases.There were 13 cases (0.78%) of liver failure and 3 cases (0.18%) of perioperative death. (9) The follow-up time was 3.0 to 96.0 months, with a median time of 21.0(17.8) years. The overall 3-year survival and disease-free survival rates were 80.0% and 56.5%, respectively. The overall 5-year survival and disease-free survival rates were 59.7% and 30.0%, respectively. Conclusion: 3D visualization technology plays an important role in realizing accurate diagnosis of anatomical location and morphology of primary liver cancer, improving the success rate of surgery and reducing the incidence of complications.

DNA Barcode Technology and Its Application Prospects in Forensic Medicine.

ABSTRACT: Traditional species identification has gone through five stages -- morphology, cytology, biochemistry, immunology and molecular biology. At present, the use of DNA technology for species identification has become a research hotspot. In the use of DNA for species identification, the presentation and application of DNA barcode is of epoch-making significance. With the successful application of new technology in species identification, forensic species identification has also made corresponding development, and is expected to play an important role in forensic related fields. This paper briefly describes the general situation and principles of DNA barcode technology as well as its advantages and limitations when applied to biological classification, and discusses the future significance and feasibility of DNA barcode technology in forensic applications, in order to provide new ideas for future forensic identification.

Long noncoding RNA SNHG12 promotes the progression of cervical cancer via modulating miR-125b/STAT3 axis.

Increasing evidence showed that long noncoding RNAs (lncRNAs) played an important role in the occurrence and development of tumors. To date, lncRNA small nucleolar RNA host gene 12 (SNHG12) has revealed an oncogenic role in various tumors. However, the role of SNHG12 in cervical cancer is still unclear. Therefore, we focused on the biological function and molecular mechanism of SNHG12 in the tumorigenesis of cervical cancer. In this study, the expression of miR-125b was observably downregulated in cervical cancer cells. Meanwhile, the expression of SNHG12 was obviously upregulated in cervical cancer cell lines (HeLa, SiHa, Caski, C4-1, and C33A) compared with the immortalized cervical epithelial cells. The further assay showed that miR-125b was a target of SNHG12 in cervical cancer. Moreover, a negative relationship between miR-125b and SNHG12 was found in cervical cancer. In addition, SNHG12 inhibition restrained the proliferation, migration, and invasion of cervical cancer cells. Meanwhile, miR-125b mimics repressed the expression of signal transducer and activator of transcription 3 (STAT3). The further assay showed that STAT3 was a target of miR-125b in cervical cancer. In addition, sh-STAT3 repressed the migration and invasion of cervical cancer cells. Furthermore, it showed that miR-125b inhibitors reversed STAT3 expression restrained by the reduction of SNHG12 expression. In general, SNHG12 modulated STAT3 by sponging miR-125b in cervical cancer and played an important role in the development of cervical cancer.

Citronellal prevents endothelial dysfunction and atherosclerosis in rats.

BACKGROUND: Atherosclerosis is a chronical inflammatory disease in arterial walls, which is involved in oxidative stress and endothelial dysfunction. Aromatherapy is one of the complementary therapies that use essential oils as the major therapeutic agents to treat several diseases. Citronellal (CT) is a monoterpene predominantly formed by the secondary metabolism of plants, producing antithrombotic, antiplatelet, and antihypertensive activities. AIM: The aim of the present study is to explore whether aromatherapy with CT improves endothelial function to prevent the formation of atherosclerotic plaque in vivo. METHODS: An AS model in carotid artery was induced by balloon injury and vitamin D3 injection in rats fed with a high-fat diet. The size of the carotid atherosclerotic plaque was determined by ultrasound, oil red, and hematoxylin-eosin staining. Endothelial function was assessed by measuring acetylcholine-induced vessel relaxation in an organ chamber. RESULTS: Administrations of CT (50, 100, and 150 mg/kg) as well as lovastatin dramatically reduced the size of carotid atherosclerotic plaque in rats in a dose-dependent manner, compared with atherosclerotic rats fed with a high-fat diet plus balloon injury and vitamin D3. Mechanically, CT improved endothelial dysfunction, increased cell migration, and suppressed oxidative stress and inflammation in vascular endothelium in rats feeding on the high-fat diet plus balloon injury. Further, CT downregulated the protein levels of sodium-hydrogen exchanger 1 in rats with atherosclerosis. CONCLUSION: CT improves endothelial dysfunction and prevents the growth of atherosclerosis in rats by reducing oxidative stress. Clinically, CT is potentially considered as a medicine to treat patients with atherosclerosis.

[Effects of electrospun collagen nanofibrous matrix on the biological behavior of human dental pulp cells].

OBJECTIVE: To compare cell adhesion, proliferation and odontoblastic differentiation of human dental pulp cells (hDPCs) on electrospun collagen nanofibrous matrix (Col_NFM) with that on collagen flat film (Col-FF), to investigate the biological effect of collagen nanofibrous matrix on hDPCs. METHODS: The surface morphology of the two different collagen scaffold was analyzed by scanning electron microscopy (SEM), and the contact angle and the swelling ratio were also measured. Then hDPCs were implanted on the two different collagen scaffolds, the cell morphology was observed using SEM and laser scanning microscope (LSM), and cell proliferation was evaluated by the CCK-8 assay. After hDPCs cultured on the two different collagen scaffold with odontoblastic medium for 14 days, the expression of odontoblastic differentiation related genes was detected by real-time PCR, and alizarin red staining was used to test the formation of mineralized nodules. RESULTS: From the SEM figures, the fibers' diameter of Col_NFM was (884±159) nm, and there were abundant three dimensional connected pore structures between the fibers of Col_NFM, while the surface of Col_FF was completely flat without pore structure. The contact angle at 0 s of Col_NFM was 85.03°±4.45°, and that of Col_FF was 98.98°±5.81°. The swelling ratio of Col_NFM was approximately 3 folds compared with dry weight sample, while that of Col_FF was just 1 fold. Thus Col_NFM indicated better hydrophilicity and swelling property. SEM and LSM showed that hDPCs on Col_NFM presented an irregular and highly branched phenotype, and could penetrate into the nanofibrous scaffold. In contrast, the cells were spread only on the surface of Col_FF with a spindle-shaped morphology. CCK-8 assays showed that hDPCs on Col_NFM showed higher proliferation rate than on Col_FF. After hDPCs were cultured on the two different collagen scaffolds with odontoblastic medium for 14 days, more expressions of odontoblastic differentiation related genes, such as dentin sialophosphoprotein (DSPP) and dentin matrix proten-1 (DMP1) were determined in Col_NFM group (P<0.05), and more mineralization depositions were also observed in Col_NFM group according to the results of alizarin red staining. CONCLUSION: Col_NFM with nanoscale microstructure achieves better hydrophilic and swelling properties than Col_FF, and hDPCs cultured with Col_NFM present higher activity on cell adhesion, proliferation and odontoblastic differentiation.

[Three-dimensional visual assessment and virtual reality study of centrally located hepatocellular carcinoma on the axis of blood vessels].

Objective: To explore a novel method for preoperative precision assessment of centrally located hepatocellular carcinoma(HCC) with blood vessel as axis based on three-dimensional(3D) visualization and virtual reality(VR) technology and its application values. Methods: High-quality thin-layer enhanced CT data were collected from 20 patients with centrally located HCC who treated at First Department of Hepatobiliary Surgery, Zhujiang Hospital, Southern Medical University from March 2017 to August 2018 diagnosed by preoperative examination. There were 18 males and 2 females, aged 28 to 69 years, all of Child-Pugh grade A. First of all, 3D reconstruction was performed by a 3D visualization software; then, the reconstructed 3D image was imported into VR development engine for VR research; afterwards, the analysis and evaluation system with blood vessel as axis was established based on 3D visualization classification of centrally located HCC; therefore, the relationship of the tumor to its major peripheral blood vessels was accurately judged and the surgical planning was formulated. Two images were brought into the operating room for navigation in surgery. The assessments results of preoperative data (CT and (or) MRI) and three-dimensional visualization of blood vessels in VR environment were compared; the values of the preoperative and postoperative hemoglobin, serum albumin and bilirubin were recorded and compared. Chi-square test, t-test and non-parametric test were used for the analysis of counting data, continuous measurement data and non-normal distribution measurement data, respectively. Results: 3D visualization modeling was completed in all of the 20 patients with centrally located HCC. According to the results of 3D visualization classification of centrally located HCC, there were 3 cases of type Ⅰ,1 case of type Ⅱ,4 cases of type Ⅲ,7 cases of type Ⅳ and 5 cases of type Ⅴ; according to the assessment and classification based on blood vessel as the axis, there were 6 cases of type Ⅰa,2 cases of type Ⅰb,2 cases of type Ⅱa,9 cases of type Ⅱb and 1 case of type Ⅱc. All patients underwent successful resection of tumor under the guidance of 3D visualization and VR technology. There were 15 cases whose assessment results based on preoperative CT/MRI were consistent with intraoperative findings, with a coincidence rate of 75.0%(15/20); while in VR environment, the assessment results of 3D visualization with blood vessel as axis were all consistent with the intraoperative findings, with coincidence rate of 100%(20/20). There was a statistically significant difference between the groups (χ(2)=5.714, P=0.017). There was no red blood cell transfusion in all patients during the operation. The preoperative hemoglobin was (128.8±14.9)g/L, and it was (119.8±12.5)g/L on postoperative day 1. There was no significant difference between these two sets of data (t=2.07, P=0.054). No death during the perioperative period and no complications such as hepatic failure, hemorrhage and biliary fistula after operation occurred. Conclusion: Preoperative evaluation based on 3D visualization and VR technology with blood vessel as the axis has significant clinical value for preoperative planning and surgical navigation of centrally located HCC.

Relationship between Changes of Pericyte Number and Wound Age during Repair of Skeletal Muscle Contusion in Mice.

ABSTRACT: Objective To observe the change pattern of pericyte number at different time periods after mice skeletal muscle contusion and discuss its role in wound age estimation. Methods A mice gastrocnemius muscle contusion model was established. The form and number changes of pericytes at 1, 3, 5, 7, 9, 14, and 28 d post-injury were detected by multiple immunofluorescence staining. Results Compared with the slender shape of pericytes in normal skeletal muscles, pericytes in the contusion area had increased volume, rounder form and a round nuclei. Part of pericytes were found to express satellite cell markers paired-box transcription factor （Pax7） or myoblast determination 1 （MyoD1）. The changes of pericyte number in skeletal muscles after contusion were time-dependant, and showed unimodal distribution with the extension of wound age. In the central contusion area, the number of pericytes peaked at 5 d post-injury while in the peripheral contusion area, the number of pericytes peaked at 5 d and 7 d post-injury. Conclusion The number of pericytes in contusion area varies time-dependently after skeletal muscle contusion in mice and might be a reference index for muscle wound age estimation, and is involved in the repair and regeneration of skeletal muscle injury.

Expression of Nrf2 in Different Cells after Human Cerebral Cortex Contusion.

ABSTRACT: Objective To observe the expression changes of nuclear factor-erythroid derived 2-related factors （Nrf2） in different cells at different time points after human cerebral cortex contusion, and to discuss its application in brain wound age estimation. Methods Thirty-six human brain tissues were selected, of which 6 were for control and 30 were cortical contusion at different time points post-injury, which were divided into 0-1 h, 3-6 h, 1-3 d, 5-7 d, and 10-14 d post-injury groups, with 6 cases in each group. Based on paraffin embedded sections, HE staining was used to observe the morphological changes post-injury, and double immunofluorescence staining was used to detect the expression of Nrf2 in neurons, astrocytes, and microglia. The number of positive cells was counted and statistical analysis was made. Results The number of neurons decreased 1-3 d post-injury. The expression of Nrf2 cells in neurons increased after injury, and the rate of positive cells peaked at 1-3 d post-injury. Glial cells were activated 1-3 d post-injury, and the activation peaked at 5-7 d post-injury. The cerebromalacia began to form at 10-14 d post-injury. Glial fibrillary acidic protein （GFAP） positive cells in mice increased gradually after injury and peaked at 5-7 d post-injury, while the proportion of Nrf2 in GFAP positive cells was relatively stable. After injury, ionized calcium-binding adapter molecule 1 （IBA1） positive cells increased and activated gradually. The expression proportion of Nrf2 in IBA1 positive cells increased gradually, reached its peak at 5-7 d post-injury, and then decreased. Conclusion The expression of Nrf2 in different cells involves in the biological function of different cells post-injury, and the dynamic expression of single cells has a time-dependent pattern. This may provide a new reference index for the wound age estimation of brain contusion in human.