Clinical observation of warm acupuncture combined with external application of Tibetan medicine Baimai Ointment in the treatment of low-back pain with cold-dampness type / 国际中医中药杂志

Objective:To evaluate the clinical efficacy of warm acupuncture combined with external application of Tibetan medicine Baimai Ointment in the treatment of low-back pain with cold-dampness type.Methods:Randomized controlled trial. Totally 60 outpatients in Tibetan Medicine Hospital of Cuona County from May to July of 2021 were selected as the observation objects, and they were divided into two groups by random number table method, with 30 cases in each group. The control group was treated with Baimai Ointment, and the treatment group was treated with warm acupuncture and Baimai Ointment. Both groups were treated for 2 weeks and followed up for 3 months. VAS scale and Oswestry disability index (ODI) were used to evaluate the low-back pain and dysfunction, and the clinical efficacy was evaluated.Results:The VAS scores of the treatment group were lower than those in the control group immediately after treatment and at the last follow-up ( t=-18.17, -6.05, P<0.01). The ODI score of the treatment group was lower than that of the control group at the last follow-up ( t=-15.86, P<0.01). The total effective rate was 96.7% (29/30) in the treatment group and 93.3% (28/30) in the control group, without statistical significance ( χ2=0.001, P=1.000). Conclusion:Warm acupuncture combined with Tibetan medicine Baimai Ointment can effectively improve the clinical symptoms of low-back pain with cold-dampness type, improve the quality of life of patients, and the clinical effect is satisfactory.

Research progress on the mechanism of phenotypic transformation of pulmonary artery smooth muscle cells induced by hypoxia / 浙江大学学报·医学版

Phenotypic transformation of pulmonary artery smooth muscle cells (PASMCs) is a key factor in pulmonary vascular remodeling. Inhibiting or reversing phenotypic transformation can inhibit pulmonary vascular remodeling and control the progression of hypoxic pulmonary hypertension. Recent studies have shown that hypoxia causes intracellular peroxide metabolism to induce oxidative stress, induces multi-pathway signal transduction, including those related to autophagy, endoplasmic reticulum stress and mitochondrial dysfunction, and also induces non-coding RNA regulation of cell marker protein expression, resulting in PASMCs phenotypic transformation. This article reviews recent research progress on mechanisms of hypoxia-induced phenotypic transformation of PASMCs, which may be helpful for finding targets to inhibit phenotypic transformation and to improve pulmonary vascular remodeling diseases such as hypoxia-induced pulmonary hypertension.

Long-term outcome of transcatheter repair of paravalvular leak post surgical mitral valve replacement / 中华心血管病杂志

Objective: To explore the long-term clinical efficacy of transcatheter repair of mitral paravalvular leak (PVL) post surgical mitral valve replacement. Methods: This study is a retrospective study. Patients who completed transcatheter repair of paravalvular leak after surgical mitral valve replacement at Shanghai Chest Hospital, Shanghai Jiaotong University School of Medicine from March 2010 to December 2018 were included. Technical success was defined as the occluder being stably implanted in the paravalvular leak site without affecting the function of the mitral valve and surrounding tissues; and there were no intervention-related complications, such as new hemolysis or aggravated hemolysis, and echocardiography confirmed mitral paravalvular regurgitation reduced by more than 1 grade. Patients were followed up at 30 days, 1, and 3 years after the intervention. The main endpoints were all-cause death and re-surgery due to interventional failure or serious complications. The occurrence of occluder-mediated hemolysis and chronic renal insufficiency was recorded, and patients were monitored with echocardiography during follow up. Results: A total of 75 patients were included, aged (54.3±22.9) years old, and 38 patients were males. All patients had decreased cardiac function and/or hemolysis before intervention. Procedural success was achieved in 54 patients (72.0%). Incidence of device-mediated hemolysis was 18.7% (14/75). During the follow-up period, all-cause death occurred in 7 patients (9.3%), and 3 were cardiac deaths.The 3-year event-free survival rate was 81.3% (61/75). The need for cardiac surgery was 9.3% (7/75): 3 cases due to severe device-mediated hemolysis, 2 cases due to prosthetic valve failure and 2 cases due to moderate to severe residual regurgitation. The echocardiography follow-up results showed that the position of the occluder was stable, there was no impact on the artificial valve function and surrounding structures, and the residual regurgitation was stable without progressive increase in event-free patients. Compared with pre-intervention, the left ventricular end systolic diameter ((33.9±7.4)mm vs. (38.3±8.9) mm, P=0.036), end diastolic diameter ((53.7±8.3) mm vs. (58.4±9.1) mm, P=0.045) and left atrial diameter (59.3 (44.5, 90.7) mm vs. 64.3 (44.8, 96.6) mm, P=0.049) were significantly reduced, pulmonary artery systolic pressure was also significantly decreased ((36.5±15.8) mmHg vs. (46.3±14.9) mmHg, P=0.022, 1 mmHg=0.133 kPa). There was no significant difference between 3 years and 1 year after transcatheter repair of mitral paravalvular leak post surgical mitral valve replacement (all P>0.05). Conclusion: Transcatheter repair of mitral paravalvular leak post surgical mitral valve replacement is an effective treatment option in selective patients.

Effect of Scutellaria baicalensis Georgi on metabolism in RSV infection mice based on metabolomics / 药学学报

This study, aiming at finding biomarkers which can assist in the diagnosis of respiratory syncytial virus (RSV) pneumonia and analyzing the metabolic pathways of anti-RSV activity of Scutellaria baicalensis Georgi (SG)., explores the improvement effect of SG on mice models infected by RSV with the metabolomics technology based on UPLC-Q-Exactive HF X-MS. Mice models affected by RSV are established by nasal drip method and the changes of body weight, rectal temperature and pathological damage of lung tissue are evaluated. The lung tissue samples of mice in each group are collected and analyzed by UPLC-Q-Exactive HF X-MS. The differential metabolites of SG drug intervention are explored by metabolomics technology, and the metabolic pathways regulated by SG are analyzed. The results show that SG can significantly improve the pathological state of the lung tissue of the mice and make its body weight and rectal temperature tend to be normal. In the lung tissue samples, 46 biomarkers, such as guanine, L-asparagine, and arachidonic acid, are screened for disease development in RSV model mice. SG improved RSV infection by recalling 22 potential biomarkers, such as uric acid, arachidonic acid, and alanine. The 22 potential markers mainly involved 11 abnormal metabolic pathways, including phenylalanine, tyrosine, and tryptophan biosynthesis, and arachidonic acid metabolism, alanine, aspartic acid and glutamate metabolism are closely related to the five metabolic pathways. SG improves RSV-infected mice mainly by regulating amino acids, lipids, cofactors and vitamins and nucleotide metabolites. All animal experiments were conducted under the guidance and approval of the Animal Ethics Review Committee of Shandong University of Traditional Chinese Medicine. (approval number: SDUTCM20210311001).

Mechanism of Shenqi Yiliu Prescription Combined with Cisplatin on H22 Liver Cancer-bearing Mice Based on NLRP3/Caspase-1/GSDMD Pyroptosis Pathway / 中国实验方剂学杂志

ObjectiveTo explore the anti-tumor effect and mechanism of Shenqi Yiliu prescription in the intervention of pyroptosis. MethodTen male BALB/c mice were randomly selected and assigned to the blank group. The remaining 40 mice underwent the induction of the liver cancer xenograft model. After 5 days of modeling， 40 surviving mice were randomly divided into model group， cisplatin group ［2.5×10-3 g·kg-1·（3 d）-1］， Shenqi Yiliu prescription group （27 g·kg-1·d-1）， and a combination group （Shenqi Yiliu prescription group + cisplatin）. The mice in the blank group and the model group were treated with an equal volume of normal saline for 10 days. The general conditions of mice in each group were observed. After the intervention， the tumor weight of the mice was weighed and the tumor inhibition rate was calculated. Hematoxylin-eosin （HE） staining was used to observe the pathological changes in tumor tissues. The levels of mouse liver function indicators， including alanine aminotransferase （ALT） and aspartate aminotransferase （AST） were detected. The TdT-mediated dUTP-biotin nick end labeling （TUNEL） assay was used to detect DNA damage in mouse tumor tissue cells. Immunohistochemistry （IHC）， immunofluorescence （IF）， and Western blot were used to detect the protein expression levels of NOD-like receptor protein 3 （NLRP3）， cysteinyl aspartate-specific protease-1 （Caspase-1）， and gasdermin D （GSDMD） in tumor tissues. The levels of interleukin-1β （IL-1β） and interleukin-18 （IL-18） in tumor tissues were detected by enzyme-linked immunosorbent assay （ELISA）. ResultCompared with the mice in the blank group， those in the model group were in a poor mental state， sleepy， and lazy， and their fur color was dull， with increased levels of serum ALT and AST in liver function tests （P<0.01）. Compared with the model group， the groups with drug intervention showed improved mental state， inhibited tumor growth to varying degrees， and decreased tumor weight， and the tumor inhibition rate in the combination group was the highest （P<0.01）. HE staining showed that the pathological and morphological lesions of the tumor tissues in the model group were significant， while those in all groups with drug intervention were improved to a certain extent. The karyolysis and nuclear rupture in the Shenqi Yiliu prescription group and the combination group were more significant. In the liver function test， the serum ALT and AST levels of mice in the Shenqi Yiliu prescription group and the combination group decreased （P<0.01）， and the inflammatory factors IL-1β and IL-18 in each group with drug intervention decreased （P<0.05， P<0.01）. Among them， the declining trend of IL-1β and IL-18 in the Shenqi Yiliu prescription group was the most significant （P<0.01）. TUNEL staining showed that the positive TUNEL staining in each group with drug intervention decreased after intervention （P<0.05， P<0.01）， especially the cisplatin group and Shenqi Yiliu prescription group （P<0.01）. Western blot， IHC， and IF found that the protein expression levels of NLRP3， Caspase-1， and GSDMD in each group with drug intervention decreased （P<0.05， P<0.01）. Compared with the mice in the cisplatin group， those in the Shenqi Yiliu prescription group and the combination group had better mental state and regular tumor morphology， and the tumor weight of the mice in the combination group decreased （P<0.05）. The levels of ALT and AST in the Shenqi Yiliu prescription group decreased （P<0.05）， and the levels of IL-1β and IL-18 in the Shenqi Yiliu prescription group and the combination group decreased （P<0.05， P<0.01）， especially in the combination group （P<0.01）. The results of IHC showed that the expression of GSDMD protein in the tumor tissues of mice in the combination group was reduced （P<0.01）. IF detection showed that the expression of NLRP3 in the tumor tissues of the Shenqi Yiliu prescription group was reduced （P<0.01）. The results of Western blot showed that the expression level of NLRP3 protein in the Shenqi Yiliu prescription group and the combination group decreased （P<0.01）， and the expression level of Caspase-1 protein in the combination group decreased （P<0.01）. The decrease in GSDMD protein expression was not significant， and the difference was not statistically significant. ConclusionShenqi Yiliu prescription combined with cisplatin has an obvious anti-tumor effect， which may be achieved by down-regulating the NLRP3/Caspase-1/GSDMD inflammatory pyroptosis pathway to inhibit cell pyroptosis， and relieve the inflammatory response in mice with liver cancer.

Progress of BCR-ABL fusion gene and JAK2 V617F mutation double-positive myeloproliferative neoplasms / 白血病·淋巴瘤

Myeloproliferative neoplasms (MPN) are a group of clonal disorders of hematopoietic stem cells, and JAK2 V617F gene mutation is the main basis for the diagnosis of MPN. Previous studies have shown that BCR-ABL fusion gene and JAK2 V617F gene mutation are mutually exclusive in MPN patients, but in recent years, patients with a double mutation of both genes are often reported. The article synthesizes the relevant domestic and foreign literature in recent years, and reviews the BCR-ABL fusion gene and JAK2 V617F mutation double-positive MPN.

Effect of Intravesical Instillation Therapy on Cancer-specific Survival Rate of Stage T1 Non-muscle-invasive Bladder Transitional Cell Carcinoma Patients After Transurethral Resection / 肿瘤防治研究

Objective To investigate the effect of transurethral resection of bladder tumor (TURBT) with or without intravesical instillation therapy on cancer-specific-survival rate (CSS) of T1 stage non-muscle-invasive bladder transitional cell carcinoma (BTCC) patients. Methods The data of patients diagnosed with T1 stage non-muscle-invasive BTCC from 2010 to 2015 were obtained from the SEER database. The different dividing groups were based on TURBT with or without intravesical instillation therapy. A 1:1 PSM method was used to balance the differences in baseline data between each group. Herein, Kaplan-Meier methods were used to draw survival curves, and the difference between OS and CSS were compared by Log rank test. In addition, univariate and multivariate Cox regressionanalyses were used to explore the independent risk factors of CSS. Results The OS and CSS of patients in the TURBT combined with intravesical instillation therapy group were higher than those of the TURBT alone group (P < 0.05). TURBT combined with intravesical instillation therapy was a protective factor in prognosis with T1 stage non-muscle-invasive BTCC patients (HR=0.783, 95%CI: 0.650-0.942, P < 0.01). Conclusion TURBT combined with intravesical instillation therapy improves the CSS of patients with T1 stage non-muscle-invasive BTCC.

Mechanism of silica-induced ROS over synthsis in NLRP3-dependent macrophage pyroptosis / 环境与职业医学

Background Macrophages are essential components of the natural immune system. They play a significant role in resisting foreign bodies in the respiratory tract and maintaining the homeostasis of the internal environment of lung tissue. Objective To investigate the mechanism of macrophage pyroptosis induced by silica dust with different particle sizes. Methods The modified murine macrophage cell line, RAW-ASC cells, was cultured and divided into a blank control group, a lipopolysaccharide (LPS) group (1 μg·mL−1 LPS), a nano-SiO2 group (1 μg·mL−1 LPS+100 μg·mL−1 nano-SiO2), a micro-SiO2 group (1 μg·mL−1 LPS+750 μg·mL−1 micro-SiO2), and a positive control group [1 μg·mL−1 LPS+3 mmol·L−1 adenosine triphosphate (ATP)]. Apart from the blank control group, cells in other groups were pretreated with LPS for 6 h, and then exposed to SiO2 or ATP for 4 h. According to the molecular target NOD-like receptor pyrin domain-containing protein 3 (NLRP3) and reactive oxygen species (ROS), we applied MCC950 (NLRP3 inhibitor) and N-acetyl cysteine (NAC, ROS scavenger) to macrophages. CCK-8 assay was used to detect cell viability; 5-ethynyl-2'-deoxyuridine (EdU) staining was used to detect cell proliferation; lactate dehydrogenase (LDH) assay kit was used to detect LDH in supernatant; calcein AM/PI fluorescent double-staining was applied to evaluate cell rupture; 2',7'-dichlorofluorescin diacetate (DCFH-DA) fluorescent probe was used to measure the content of ROS; Western blotting was used to measure the expressions of NLRP3, apoptosis-associated speck-like protein containing CARD (ASC), Caspase-1, gasdermin D (GSDMD), and interleukin-1β (IL-1β). Results Compared with the blank group, 100 μg·mL-1nano-SiO2 and 750 μg·mL-1micro-SiO2 dust exposure reduced the cell viability to 40% and 68% (P<0.05), and the cell proliferation rate to 30% and 33% (P<0.01), respectively; they also induced cell lysis and ROS release, upregulated NLRP3, ASC, Caspase-1, GSDMD, and IL-1β at protein level (P<0.05), and induced macrophage pyroptosis. After intervening with MCC950 (10 μmol·L-1) and NAC (10 mmol·L-1), the expressions of NLRP3, ASC, Caspase-1, and IL-1β decreased (P<0.05), and, specifically, NAC effectively reduced ROS levels (P<0.05). Conclusion Both nano- and micro-SiO2 dust have cytotoxicity, can upregulate ROS level, activate NLRP3 inflammasome, and promote the release of cytokines, leading to pyroptosis. These results are helpful to reveal the molecular mechanism of macrophage pyroptosis induced by SiO2 dust.

β-arrestin2 recruitment by β-adrenergic receptor agonists and antagonists / 生理学报

A large number of β-adrenergic receptor (β-AR) agonists and antagonists are widely used in the treatment of cardiovascular diseases and other diseases. Nonetheless, it remains unclear whether these commonly used β-AR drugs can activate downstream β- arrestin-biased signaling pathways. The objective of this study was to investigate β-arrestin2 recruitment effects of β-AR agonists and antagonists that were commonly used in clinical practice. We used TANGO (transcriptional activation following arrestin translocation) assay to detect the β-arrestin2 recruitment by β-AR ligands in HEK293 cell line (HTLA cells) stably transfected with tetracycline transactivator protein (tTA) dependent luciferase reporter and β-arrestin2-TEV fusion gene. Upon activation of β-AR by a β-AR ligand, β-arrestin2 was recruited to the C terminus of the receptor, followed by cleavage of the G protein-coupled receptors (GPCRs) fusion protein at the TEV protease-cleavage site. The cleavage resulted in the release of tTA, which, after being transported to the nucleus, activated transcription of the luciferase reporter gene. The results showed that β-AR non-selective agonists epinephrine, noradrenaline and isoprenaline all promoted β-arrestin2 recruitment at β1-AR and β2-AR. β1-AR selective agonists dobutamine and denopamine both promoted β-arrestin2 recruitment at β1-AR. β2-AR selective agonists procaterol and salbutamol promoted β-arrestin2 recruitment at β2-AR. β-AR non-selective antagonists alprenolol and pindolol promoted β-arrestin2 recruitment at β1-AR. β1-AR selective antagonists celiprolol and bevantolol showed β-arrestin2 recruitment at β1-AR. β2-AR selective antagonists butoxamine showed β-arrestin2 recruitment at β1-AR. These results provide some clues for the potential action of β-AR drugs, and lay a foundation for the screening of β-arrestin-biased β-AR ligands.

O-GlcNAcylation in Ventral Tegmental Area Dopaminergic Neurons Regulates Motor Learning and the Response to Natural Reward / 神经科学通报·英文版

Protein O-GlcNAcylation is a post-translational modification that links environmental stimuli with changes in intracellular signal pathways, and its disturbance has been found in neurodegenerative diseases and metabolic disorders. However, its role in the mesolimbic dopamine (DA) system, especially in the ventral tegmental area (VTA), needs to be elucidated. Here, we found that injection of Thiamet G, an O-GlcNAcase (OGA) inhibitor, in the VTA and nucleus accumbens (NAc) of mice, facilitated neuronal O-GlcNAcylation and decreased the operant response to sucrose as well as the latency to fall in rotarod test. Mice with DAergic neuron-specific knockout of O-GlcNAc transferase (OGT) displayed severe metabolic abnormalities and died within 4-8 weeks after birth. Furthermore, mice specifically overexpressing OGT in DAergic neurons in the VTA had learning defects in the operant response to sucrose, and impaired motor learning in the rotarod test. Instead, overexpression of OGT in GABAergic neurons in the VTA had no effect on these behaviors. These results suggest that protein O-GlcNAcylation of DAergic neurons in the VTA plays an important role in regulating the response to natural reward and motor learning in mice.

Salidroside inhibits phenotypic transformation of rat pulmonary artery smooth muscle cells induced by hypoxia / 中国中药杂志

This study investigated the effect of salidroside on phenotypic transformation of rat pulmonary artery smooth muscle cells(PASMCs) induced by hypoxia. Rat pulmonary arteries were isolated by tissue digestion and PASMCs were cultured. The OD values of cells treated with salidroside at different concentrations for 48 hours were measured by cell counting kit-8(CCK-8) to determine the appropriate concentration range of salidroside. The cells were divided into a normal(normoxia) group, a model(hypoxia) group, and three hypoxia + salidroside groups(40, 60, and 80 μg·mL~(-1)). Quantitative real-time PCR(qRT-PCR) was used to detect the mRNA expression of cell contractile markers in each group, such as α-smooth muscle actin(α-SMA), smooth muscle 22(SM22), and calcium-binding protein(calponin), and synthetic marker vimentin. The expression levels of cell phenotypic markers and proliferating cell nuclear antigen(PCNA) were detected by Western blot. The proliferation of cells in each group was detected by the 5-ethynyl-2'-deoxyuridine(EdU) assay. Cell migration was measured by Transwell assay. As revealed by results, compared with the normal group, the model group showed decreased mRNA and protein expression of contractile phenotypic markers of PASMCs and increased mRNA and protein expression of synthetic markers. Compared with the conditions in the model group, salidroside could down-regulate the mRNA and protein expression of synthetic markers in PASMCs and up-regulated the mRNA and protein expression of contractile phenotypic markers. Compared with the normal group, the model group showed potentiated proliferation and migration. Compared with the model group, the hypoxia + salidroside groups showed blunted proliferation and migration of cells after phenotypic transformation. The results suggest that salidroside can inhibit the expression of synthetic markers in PASMCs and promote the expression of contractile markers to inhibit the hypoxia-induced phenotypic transformation of PASMCs. The mechanism of salidroside in inhibiting the proliferation and migration of PASMCs is related to the inhibition of the phenotypic transformation of PASMCs.

Rac1 Signaling in Amygdala Astrocytes Regulates Fear Memory Acquisition and Retrieval / 神经科学通报·英文版

The importance of astrocytes in behavior control is increasingly appreciated, but little is known about the effects of their dynamic activity in regulating learning and memory. In the present study, we constructed AAVs of photoactivatable and photoinactivatable Ras-related C3 botulinum toxin substrate 1 (Rac1) under the mGFAP promoter, which enabled the manipulation of Rac1 activity in astrocytes by optical stimulation in free-moving mice. We found that both up-regulation and down-regulation of astrocytic Rac1 activity in the basolateral amygdala (BLA) attenuated memory acquisition in a fear conditioning mouse model. Meanwhile, neuronal activation in the BLA induced by memory acquisition was inhibited under both the up- and down-regulation of astrocytic Rac1 activity during training. In terms of the impact on fear memory retrieval, we found both up- and down-regulation of BLA astrocytic Rac1 activity impaired memory retrieval of fear conditioning and memory retrieval-induced neuronal activation. Notably, the effect of astrocytic Rac1 on memory retrieval was reversible. Our results demonstrate that the normal activity of astrocytic Rac1 is necessary for the activation of neurons and memory formation. Both activation and inactivation of astrocytic Rac1 activity in the BLA reduced the excitability of neurons, and thereby impaired fear memory acquisition and retrieval.

China experts' consensus on preventive and interceptive orthodontic treatments of malocclusions of children / 华西口腔医学杂志

Malocclusion is one of the three most common oral diseases reported by World Health Organization(WHO). In China, its incidence rate is rising. Malocclusion seriously affects the dental and maxillofacial function, facial appearance and growth development of nearly 260 million children in China, and what is more, it affects their physical and mental health development. Malocclusion occurrence is related to genetic and environmental factors. Early treatment of malocclusion can create a good dental and maxillofacial development environment, correct abnormal growth and control the adverse effects of abnormal genetic factors. It can effectively reduce the prevalence of children's malocclusion and enhance their physical and mental health. This is an urgent need from the economic perspective of our society, so it has great practical and social significance. Experts from the project group "standard diagnose and treatment protocols for early orthodontic intervention of malocclusions of children" which initiated by China National Health Institute of Hospital Administration wrote the "China Experts' Consensus on Preventive and Interceptive Orthodontic Treatments of Malocclusions of Children", which aims to guide and popularize the clinical practice, improve the clinical theory and practice level, and accelerate the disciplinary development of early treatment of children's malocclusion in China. The consensus elaborates the harmfulness of malocclusion and the necessity of early treatment, and brings up the principles and fundamental contents. Based on the law of dental and maxillofacial development, this paper puts forward the guiding suggestions of preventive and interceptive treatments in different stages of dental development ranging from fetus to early permanent dentition. It is a systematic project to promote and standardize the early treatment of malocclusion. Through scientific and comprehensive stratified clinical practice and professional training, the clinical system of early treatment of malocclusion in China will eventually be perfected, so as to comprehensively care for children's dental and maxillofacial health, and improve their oral and physical health in China.

Efficacy of remimazolam-propofol-sufentanil for anesthesia in patients undergoing painless gastroscopy / 中华麻醉学杂志

Objective:To evaluate the efficacy of remimazolam-propofol-sufentanil for anesthesia in patients undergoing painless gastroscopy.Methods:Eighty American Society of Anesthesiologists physical statusⅠor Ⅱ patients, aged 20-59 yr, weighing 44-69 kg, scheduled for elective painless gastroscopy, were divided into 2 groups ( n=40 each) using a random number table method: remimazolam-propofol-sufentanil group (group RPS) and propofol-sufentanil group (group PS). The patients in group RPS received successive intravenous injection of sufentanil 0.1 μg/kg, remimazolam 0.15 mg/kg and propofol (at a rate of 4 mg/s). The patients in group PS received intravenous injection of sufentanil 0.1 μg/kg and propofol (at a rate of 4 mg/s). When Observer′ s Assessment of Alertness/Sedation Scale score was 0, gastroscopy was performed.The consumption of propofol, time of anesthesia, time for gastroscopy, emergence time and discharge time were recorded.The number of intraoperative assisted respiration cases, body movement and occurrence of adverse reactions at the time of discharge were observed. Results:Compared with group PS, the consumption of propofol was significantly decreased, and the time of anesthesia, emergence time and discharge time were shortened in group RPS ( P<0.05). There was no significant difference in the time for gastroscopy, the number of intraoperative assisted respiration cases, body movement and the occurrence of adverse reactions at discharge time between the 2 groups ( P>0.05). Conclusion:Remimazolam-propofol-sufentanil produces better efficacy for anesthesia than propofol-sufentanil in patients undergoing painless gastroscopy.

BRICS report of 2018-2019: the distribution and antimicrobial resistance profile of clinical isolates from blood culture in China / 中华临床感染病杂志

Objective:To investigate the distribution and antimicrobial resistance profile of clinical bacteria isolated from blood culture in China.Methods:The clinical bacterial strains isolated from blood culture from member hospitals of Blood Bacterial Resistant Investigation Collaborative System (BRICS) were collected during January 2018 to December 2019. Antibiotic susceptibility tests were conducted with agar dilution or broth dilution methods recommended by US Clinical and Laboratory Standards Institute (CLSI). WHONET 5.6 was used to analyze data.Results:During the study period, 14 778 bacterial strains were collected from 50 hospitals, of which 4 117 (27.9%) were Gram-positive bacteria and 10 661(72.1%) were Gram-negative bacteria. The top 10 bacterial species were Escherichia coli (37.2%), Klebsiella pneumoniae (17.0%), Staphylococcus aureus (9.7%), coagulase-negative Staphylococci (8.7%), Pseudomonas aeruginosa (3.7%), Enterococcus faecium (3.4%), Acinetobacter baumannii(3.4%), Enterobacter cloacae (2.9%), Streptococci(2.8%) and Enterococcus faecalis (2.3%). The the prevalence of methicillin-resistant S. aureus (MRSA) and methicillin-resistant coagulase-negative Staphylococcus were 27.4% (394/1 438) and 70.4% (905/1 285), respectively. No glycopeptide-resistant Staphylococcus was detected. More than 95% of S. aureus were sensitive to amikacin, rifampicin and SMZco. The resistance rate of E. faecium to vancomycin was 0.4% (2/504), and no vancomycin-resistant E. faecalis was detected. The ESBLs-producing rates in no carbapenem-resistance E. coli, carbapenem sensitive K. pneumoniae and Proteus were 50.4% (2 731/5 415), 24.6% (493/2001) and 35.2% (31/88), respectively. The prevalence of carbapenem-resistance in E. coli and K. pneumoniae were 1.5% (85/5 500), 20.6% (518/2 519), respectively. 8.3% (27/325) of carbapenem-resistance K. pneumoniae was resistant to ceftazidime/avibactam combination. The resistance rates of A. baumannii to polymyxin and tigecycline were 2.8% (14/501) and 3.4% (17/501) respectively, and that of P. aeruginosa to carbapenem were 18.9% (103/546). Conclusions:The surveillance results from 2018 to 2019 showed that the main pathogens of bloodstream infection in China were gram-negative bacteria, while E. coli was the most common pathogen, and ESBLs-producing strains were in majority; the MRSA incidence is getting lower in China; carbapenem-resistant E. coli keeps at a low level, while carbapenem-resistant K. pneumoniae is on the rise obviously.

The Kv12 voltage-gated K / 生理学报

Accumulating evidence demonstrates that the nucleus tractus solitarii (NTS) neurons serve as central respiratory chemoreceptors, but the underlying molecular mechanisms remain undefined. The present study investigated the expression of acid-sensitive ether-à-go-go-gene-like (Elk, Kv12) channels in the NTS of mice. Immunofluorescence staining was used to observe the distribution and cellular localization of the Kv12 channels in NTS neurons. Western blot and quantitative real-time PCR (qPCR) were used to evaluate protein and mRNA expression levels of Kv12 channels. The results showed that all of the three members (Kv12.1, Kv12.2, Kv12.3) of the Kv12 channel family were expressed in NTS neurons, and their expressions were co-localized with paired-like homeobox 2b gene (Phox2b) expression. The expression of Kv12.1 mRNA was the largest, whereas the expression of Kv12.3 was the least in the NTS. The results suggest Kv12 channels are expressed in Phox2b-expressing neurons in the NTS of mice, which provides molecular evidence for pH sensitivity in Phox2b-expressing NTS neurons.

Cadmium promotes apoptosis of mouse spermatogenic cells via regulation of JNK/c-Jun signaling pathway / 公共卫生与预防医学

Objectives To study the effect of cadmium (Cd) on the proliferation and apoptosis of mouse spermatocyte (GC-2 spd) cells and explore the underlying molecular mechanism. Methods GC-2 spd cells were cultured with 0, 5, 10, 15, 20 and 30 μM CdCl2, respectively, for 24 hours. The cell viability and IC50 of Cd were estimated based on CCK-8 data. The apoptosis of GC-2 spd cells and cellular concentration of ROS were analyzed by flow cytometry after treatment of the cells with different concentrations of CdCl2 (0, 5, 10 μM) for 24 hours. The expression levels of JNK/c-Jun signaling pathway regulatory proteins, pro-apoptotic factor Bax and anti-apoptotic factor Bcl-2, were determined by Western blot. Results Cd inhibited the proliferation of GC-2 spd cells with IC50 value of 12.99 μM, 95% CI [11.95, 14.00]. Exposure to 5 and 10 μM CaCl2 resulted in increases in apoptosis and cellular ROS generation in a dose-dependent manner, which was statistically significant compared with the control (P 0.05), the phosphorylation level of JNK and c-Jun in Cd group was highly increased as compared to the control (P < 0.05). In addition, Cd exposure significantly increased the expression of Bax protein but decreased the expression Bcl-2 protein (P < 0.05). Conclusions Cadmium induces GC-2 spd cell apoptosis by increasing concentration of ROS and regulating the JNK/c-Jun signaling pathway.

Clinical features of preterm infants with a birth weight less than 1 500 g undergoing different intensities of resuscitation: a multicenter retrospective analysis / 中国当代儿科杂志

OBJECTIVE@#To evaluate the clinical features of preterm infants with a birth weight less than 1 500 g undergoing different intensities of resuscitation.@*METHODS@#A retrospective analysis was performed for the preterm infants with a birth weight less than 1 500 g and a gestational age less than 32 weeks who were treated in the neonatal intensive care unit of 20 hospitals in Jiangsu, China from January 2018 to December 2019. According to the intensity of resuscitation in the delivery room, the infants were divided into three groups:non-tracheal intubation (@*RESULTS@#Compared with the non-tracheal intubation group, the tracheal intubation and ECPR groups had significantly lower rates of cesarean section and use of antenatal corticosteroid (@*CONCLUSIONS@#For preterm infants with a birth weight less than 1 500 g, the higher intensity of resuscitation in the delivery room is related to lower rate of antenatal corticosteroid therapy, lower gestational age, and lower birth weight. The infants undergoing tracheal intubation or ECRP in the delivery room have an increased incidence rate of adverse clinical outcomes. This suggests that it is important to improve the quality of perinatal management and delivery room resuscitation to improve the prognosis of the infants.

Wiedemann-Steiner syndrome due to novel nonsense variant of KMT2A gene in a case / 中华医学遗传学杂志

OBJECTIVE@#To explore the genetic basis for a child with unexplained global developmental delay (GDD), seizure, and facial deformity.@*METHODS@#Whole exome sequencing (WES) was carried out for the patient. Candidate variants were verified by Sanger sequencing of the patient and his parents.@*RESULTS@#WES revealed that the patient has carried a previously unreported de novo heterozygous nonsense c.4906C>T (p.Arg1636Ter) variant of the KMT2A gene, Based on the American College of Medical Genetics and Genomics standards and guidelines, the c.4906C>T variant of KMT2A gene was predicted to be pathogenic (PVS1+ PS2+ PM2+PP3).@*CONCLUSION@#The heterozygous nonsense c.4906C>T (p.Arg1636Ter) variant of the KMT2A gene probably underlay the disease in the child. Above finding has enriched the spectrum of pathogenic variants of the KMT2A gene.

Influence of metformin on glycolipid metabolism in patients with polyeystic ovarian syndrome / 中国医师杂志

Objective To investigate the influence of metformin on glycolipid metabolism and sex hormone in patients with polycystic ovarian syndrome (PCOS).Methods 98 patients with PCOS were randomly divided into two groups,with 49 cases in each group.The control group were treated with clomifene,while the observation group were treated with clomifene combined metformin.The endometrial thickness and ovarian volume were observed in two groups before and after treatment.The changes of glycolipid metabolism and sex hormone indexes in two groups were analyzed before and after treatment.Results The endometrial thickness of observation group was significantly better than control group after treatment,while the sex hormone levels,ovarian volume and antral follicle count (AFC) were lower than control group (P ＜ 0.05).The glycolipid metabolism indexes of total cholesterol (TC),triacylglycerol (TG),fasting blood glucose (FBG),fasting insulin (FIN) and homeostasis model assessment-insulin resistance (HOMA-IR) in observation group were significantly better than control group after treatment (P ＜ 0.05).The rate of ovulation and pregnancy in observation group was significantly higher than control group after treatment (P ＜ 0.05).Conclusions Clomifene combined metformin can significantly improve glycolipid metabolism and sex hormone of patients with PCOS.It is helpful in promoting ovulation and improving clinical pregnancy rate.