Obiective Alzheimer’s disease (AD) is a degenerative disease of the central nervous system (CNS) caused by a variety of risk factors. There are various pathological changes, but apoptosis of the neurological meridian cells is one of the most important pathological bases. Hyperlipidemia is a high-risk factor for the development of AD, which can lead to increased levels of oxidized low-density lipoprotein (ox-LDL) in brain tissues. PCSK9 is a protease closely related to lipid metabolism, but studies have shown that it may be related to the development of AD. LRP1 is abundantly expressed in neuronal cells, and it is an important transporter for the clearance of Aβ. There is now a large amount of literature confirming that PCSK9 can induce the degradation of LRP1. PI3K/AKT is an important signaling pathway in vivo, which plays an important role in apoptosis, and there is now a large amount of literature confirming that LRP1 activates the PI3K/AKT pathway, which has an anti-apoptotic effect. So can PCSK9 affect the PI3K/AKT pathway through LRP1 and thus regulate neuronal apoptosis? This deserves further investigation.The aim of this study was to explore the role of PCSK9 in mediating ox-LDL pro-apoptotic neuronal cell death and its mechanism, and then further elaborate the mechanism of hyperlipidemia leading to neurodegenerative diseases such as AD. MethodsFirstly, PC12 cells were treated with different concentrations of ox-LDL (0, 25, 50, 75 and 100 mg/L) for 24 h. Oil red O staining was used to detect lipid accumulation in PC12 cells, Hoechst33258 staining and flow cytometry to detect apoptosis in PC12 cells, ELISA to detect the content of Aβ secreted by PC12, Western blot to detect expression of SREBP2, PCSK9 and LRP1. Then PC12 cells were treated with 75 mg/L ox-LDL for different times (0, 6, 12, 24, 48 h), and Western blot were performed to detect the expression of SREBP2, PCSK9 and LRP1. Finally, after transfecting 100 nmol/L PCSK9 siRNA into PC12 cells for 48 h, PC12 cells were treated with 75 mg/L ox-LDL for 24 h, Hoechst33258 staining and flow cytometry to detect apoptosis rate of PC12 cells, and Western blot to detect PCSK9, LRP1, PI3K, AKT, P-PI3K , P-AKT, NF-κB, Bcl-2, Bax, Caspase-9 and Caspase-3 expression, and ELISA detected Aβ content secreted by PC12 cells. Resultsox-LDL increased lipid accumulation and promoted apoptosis and Aβ secretion in PC12 cells, as well as increasing the expression of SREBP2 and PCSK9 and decreasing the expression of LRP1 in PC12 cells. pCsk9 siRNA could be inhibited through the PI3K/AKT pathway and the NF-κB-Bcl-2/Bax-Caspase-9/3 pathway to inhibit ox-LDL-induced apoptosis in PC12 cells while increasing Aβ secretion in PC12 cells. Conclusionox-LDL plays a bidirectional regulatory role in ox-LDL-induced apoptosis of PC12 cells by inducing an increase in PCSK9 expression and a decrease in LRP1 expression in PC12 cells, which in turn affects different signaling pathways downstream.

BACKGROUND: Weather conditions are a possible contributing factor to age-related macular degeneration (AMD), a leading cause of irreversible loss of vision. The present study evaluated the joint effects of meteorological factors and fine particulate matter (PM_2.5) on AMD. METHODS: Data was extracted from a national cross-sectional survey conducted across 10 provinces in rural China. A total of 36,081 participants aged 40 and older were recruited. AMD was diagnosed clinically by slit-lamp ophthalmoscopy, fundus photography, and spectral domain optical coherence tomography (OCT). Meteorological data were calculated by European Centre for Medium-Range Weather Forecasts (ECMWF) reanalysis and were matched to participants' home addresses by latitude and longitude. Participants' individual PM_2.5 exposure concentrations were calculated by a satellite-based model at a 1-km resolution level. Multivariable-adjusted logistic regression models paired with interaction analysis were performed to investigate the joint effects of meteorological factors and PM_2.5 on AMD. RESULTS: The prevalence of AMD in the study population was 2.6% (95% CI 2.42-2.76%). The average annual PM_2.5 level during the study period was 63.1 ± 15.3 µg/m³. A significant positive association was detected between AMD and PM_2.5 level, temperature (T), and relative humidity (RH), in both the independent and the combined effect models. For PM_2.5, compared with the lowest quartile, the odds ratios (ORs) with 95% confidence intervals (CIs) across increasing quartiles were 0.828 (0.674,1.018), 1.105 (0.799,1.528), and 2.602 (1.516,4.468). Positive associations were observed between AMD and temperature, with ORs (95% CI) of 1.625 (1.059,2.494), 1.619 (1.026,2.553), and 3.276 (1.841,5.830), across increasing quartiles. In the interaction analysis, the estimated relative excess risk due to interaction (RERI) and the attributable proportion (AP) for combined atmospheric pressure and PM_2.5 was 0.864 (0.586,1.141) and 1.180 (0.768,1.592), respectively, indicating a synergistic effect between PM_2.5 and atmospheric pressure. CONCLUSIONS This study is among the first to characterize the coordinated effects of meteorological factors and PM_2.5 on AMD. The findings warrant further investigation to elucidate the relationship between ambient environment and AMD.
Humans ; Adult ; Middle Aged ; Cross-Sectional Studies ; Air Pollutants/analysis* ; Particulate Matter/analysis* ; China/epidemiology* ; Macular Degeneration/etiology* ; Meteorological Concepts

Tibetan medicine is an essential part of Chinese medicine and has unique theoretical experience and therapeutic advantages. According to the development principle of inheriting the essence, sticking to the truth, and keeping innovative, the supervision department should give clear and reasonable guidance considering the characteristics of Tibetan medicine, establish a standard system for quality control, clinical verification and evaluation, and accelerate the research and commercialization of new drugs. In view of the needs of drug supply-side reform and the current situation of Tibetan medicine and new pharmaceutical research, we ponder and provide suggestions on the confusion faced by the current supervision of Tibetan drug registration, hoping to contribute to the supervision strategy of Tibetan drug registration and the high-quality development of Tibetan medicine industry.
Tibet ; Medicine, Tibetan Traditional ; Quality Control ; Pharmaceutical Research ; Drug Industry

Emodin is a common Chinese medicine compound with anti-inflammatory, antibacterial, anti-oxidant and lipid-lowering effects. Modern studies have found that emodin activates adenylate-activated protein kinase (AMPK) signaling molecules and regulates transcriptional factors and biological functions of relevant pathways. Nonalcoholic fatty liver disease is a chronic liver disease with a high incidence in China. With the global prevalence of obesity and metabolic syndrome, the development of nonalcoholic fatty liver disease (NAFLD) is closely related to the expression of the metabolism-related signal molecule AMPK. AMPK is a key enzyme in glycolipid metabolism that can involve different stages of NAFLD development to non-alcoholic steatohepatitis (NASH) by regulating energy metabolism in the body. In recent years, many studies have suggested that the activation of AMPK signaling molecules is related to the function realization of emodin, and lipid synthesis, fatty acid oxidation, insulin sensitivity and mitochondrial function-related transcription factors affected by AMPK downstream signaling molecules and other biological effects can be interacted with each other. The detailed mechanism of action associated with AMPK activation provides new thought about the treatment of NAFLD by emodin. This paper mainly summarizes the research progress of emodin by participating in the various stages of NAFLD by AMPK-related signaling pathways through literature retrieval and comprehensive analysis. It lays a foundation for further research on the therapeutic effect and mechanism of emodin on NAFLD.

The ongoing pandemic of COVID-19 has presented multiple challenges to global healthcare services, dictating changes in almost every aspect of daily medical practice. Performing aerosol generating procedures (AGPs) in the field of interventional pulmonology can lead to profound formation of aerosols, leading to a high risk of infection among healthcare workers (HCWs). We share our experiences on performing AGPs in the midst of a COVID-19 pandemic by focusing on changes in AGP practices. In a pandemic, HCWs ought to adapt to the ever-changing situation and use available resources to provide the best possible healthcare to patients, ensure safety of staff, and continue medical education of future pulmonologists.
Aerosols ; Bronchoscopy/trends* ; COVID-19/transmission* ; COVID-19 Testing ; Humans ; Infection Control/trends* ; Infectious Disease Transmission, Patient-to-Professional/prevention & control* ; Malaysia ; Practice Patterns, Physicians'/trends* ; Tertiary Care Centers ; Thoracoscopy/trends*

Cosmetics containing botanic ingredients have been used from thousands of years up to now in China. Because of the consumers' demand for health and beauty,the number of products about " botanic" have been growing rapidly in the cosmetics market,which has played an important role in upgrading the industry and enhancing the international competitiveness nowadays. Therefore,to strengthen the management about used botanic raw materials in cosmetics products and revise the application regulation of new raw materials has become an important work to ensure product quality,promote the healthy and stable development of cosmetic business. The article summarizes the related mandatory regulations and standards about botanic ingredients which used as activity function in major cosmetic business countries or regions. Furthermore,the information of botanic ingredients commonly used in non-special cosmetics notification and special cosmetic registration system were described to expect the better application and development.
China ; Consumer Product Safety ; Cosmetics/standards* ; Government Regulation ; Plant Preparations/standards*

Objective To analyze the peri-procedural complications of coronary rotational atherectomy. Methods A total of 107 consecutive patients with coronary artery disease received rotational atherectomy from January 2012 to December 2016 were enrolled retrospectively. The occurrence rate and the management of peri-procedural complications were summarized. Results ① The serum level of CK-MB and cTnI in patients who received rotational atherectomy were signifi cantly elevated compared with the level before the procedure,[4.1(2.4-14.1)U/L vs.1.5(1.0-2.1)U/L,P<0.001]and[0.28(0.11-1.11)ng/ml vs.0.01 (0.01-0.02) ng/ml, P<0.001], respectively. Of the 107 target lesions, 104 (97.2%) were classifi ed as type B2 or C lesions.②Peri-procedural complications of coronary rotational atherectomy occurred in 21 patients (19.6%). There were 5 cases (4.7%) of coronary slow fl ow, 1 case (0.9%) of severe coronary spasm, 9 cases (8.4%) of coronary dissection after rotational atherectomy and 1 case (0.9%) of side branch occlusion. Six patients (5.6%) had severe sinus bradycardia, but only 1 patient required temporary pacemaker. Burr entrapment happened in 2 patients (1.9%). Peripheral vascular complications occurred in 2 patients (1.9%) with 1 case of femoral artery hematoma at puncture site and the other 1 case of mediastinal hematoma. One patient (0.9%) developed contrast induced nephropathy after the procedure. ③All the peri-procedural complications of rotational atherectomy were benign. The procedure instant success rate was 98.1%, with no acute or sub-acute stent thrombosis, cardiac death, emergent coronary artery bypass graft occurred during hospitalization. Conclusions The complications associated with coronary rotational atherectomy are not rare, but severe complications are not common. The procedure could be safely performed with a high instant success rate.

The Nrf2-Keap1-ARE pathway is an important signaling axis that functions to protect cells against oxidative stress and harmful chemicals through the induction of cytoprotective genes. The maintenance and protective role of Nrf2 pathway has been recognized as a means for chemoprevention. On the other hand, constitutive activation of Nrf2, due to somatic mutations of genes that control Nrf2 degradation, promotes carcinogenesis and imparts chemoresistance to cancer cells. Autophagy is another tightly regulated complex cellular process that functions as a cellular quality control system to remove damaged proteins or organelles. Recently, these two cellular pathways were shown to intersect through the direct interaction between p62 (an autophagy adaptor protein) and Keap1. Dysregulation of autophagy was shown to result in prolonged activation of Nrf2 in a p62-dependent manner, which is associated with the pathogenesis and therapies of several human diseases including cancer. In this review, we discuss the molecular mechanisms of p62-mediated Nrf2 signaling pathway, with a special emphasis on their impact on nervous system disease, cardiovascular disease and cancer.

OBJECTIVETo analyze the CARL gene mutation in the patients with chronic myeloproliferative neoplasm(MPN) and to explore the clinical significance of CALR mutation.

METHODSThe peripheral blood of patients was collected and the genomic DNA was exacted, the 9 exon of CALR gene and the fragment of human thrombopoetic receptor(MPL) gene were amplified by PCR, the mutation of CALR and MPL genes was detected by using the direct sequencing, the JAK2 V617F mutation was detected by using allele spicific PCR.

RESULTSThe CALR mutations were detected in 13 patients out of 55 MPN patients (23.6%). The frequency of CALR mutation was 22.7% (10/44) in 44 essential thrombocythemia(ET) patients. A total of 3 types of CALR mutation were identified (type I c.1092_1143del52bp, n=5; type II c.1154_1155insTTGTC, n=4; type III c.1094_1139del46bp, n=1). CALR mutations occurred at a frequency of 27.2% in primary myelofibrosis (PMF), including type I (n=2) and type II (n=1). The incidence of JAK2 V617F was 58.1%(32/55), that in ET and PMF was 59.1%(26/44) and 54.5% (6/11), respectively. The mutations of MPL W515 were not detectable in all cases, and the simultaneous mutation of CARL and MPL W515 was not detected. The median age of patients with CALR mutation was significantly younger than that of patients with JAK2 mutations (48 vs 64 years of old, P<0.05). The levels of hemoglobin and leukocytes in patients with CARL mutations were significantly lower (P<0.05) but the level of plateletes was higher than that in patients with JAK2 V617F mutations (P<0.05). Deep venous thrombosis occurred in 4 of 35 ET patients with the JAK2 V617F mutation (n=4), but did not occurr in the patients with CALR mutation. Karyotype abnormality was detected in only one case among 48 patients by chromosome karyotype analysis.

CONCLUSIONThe incidence of CALR mutation is high in ET and PMF patients without JAK2 V617F and MPL W515K mutations, which is associated with younger median age, lower leucocyte and hemoglobin levels, higher platelet counts, and rare thrombocytosis, compared with the patients with JAK2 V617F mutation.