Establishment of pharmaceutical care model for lower extremity artery disease based on patients’disease self-management ability / 中国药房

OBJECTIVE To construct the integrated pharmaceutical care model of in-hospital pharmaceutical care+out-hospital pharmacy outpatient service for patients with lower extremity artery disease （LEAD）， so as to improve patients’ disease self- management ability， and the efficacy and safety of therapy. METHODS The in-hospital pharmaceutical care and out-hospital pharmacy outpatient service model was constructed for LEAD patients， including pharmaceutical evaluation， self-management ability education， and pharmacy follow-up， to perform long-term management of patients. Totally 65 LEAD patients admitted to the vascular surgery department of our hospital， receiving pharmacist management， from September， 2021 to December， 2022 were selected as the study objects， and pharmacists conducted in-hospital pharmaceutical care+continuous out-patient management. The efficacy indicators， safety indicators， and patients’s disease self-management ability indicators were compared before and after 3 months of pharmacist management. RESULTS After 3 months of pharmacists’ participation in the management of 65 patients， Fontaine stage decreased in 55 patients， there was the significant difference in Fontaine stage before and after management （P＜ 0.001）. The proportion of patients who completely followed the guidelines for medication increased from 63.1% to 96.9%； the incidence of small bleeding was reduced by 7.7% after pharmacists’ management. The scores of Morisky medication compliance and patients’ disease self-management ability were higher than 3 months ago （P＜0.001）. Patient proportion with “good” medical satisfaction increased by 18.4%. CONCLUSIONS The in-hospital pharmaceutical care and out-hospital pharmacy outpatient service model of LEAD patients can effectively improve patients’ disease self-management ability， and improve the efficacy and safety of therapy.

Consensus statement on research and application of Chinese herbal medicine derived extracellular vesicles-like particles (2023 edition) / 中草药·英文版

To promote the development of extracellular vesicles of herbal medicine especially the establishment of standardization, led by the National Expert Committee on Research and Application of Chinese Herbal Vesicles, research experts in the field of herbal medicine and extracellular vesicles were invited nationwide with the support of the Expert Committee on Research and Application of Chinese Herbal Vesicles, Professional Committee on Extracellular Vesicle Research and Application, Chinese Society of Research Hospitals and the Guangdong Engineering Research Center of Chinese Herbal Vesicles. Based on the collation of relevant literature, we have adopted the Delphi method, the consensus meeting method combined with the nominal group method to form a discussion draft of "Consensus statement on research and application of Chinese herbal medicine derived extracellular vesicles-like particles (2023)". The first draft was discussed in online and offline meetings on October 12, 14, November 2, 2022 and April and May 2023 on the current status of research, nomenclature, isolation methods, quality standards and research applications of extracellular vesicles of Chinese herbal medicines, and 13 consensus opinions were finally formed. At the Third Academic Conference on Research and Application of Chinese Herbal Vesicles, held on May 26, 2023, Kewei Zhao, convenor of the consensus, presented and read the consensus to the experts of the Expert Committee on Research and Application of Chinese Herbal Vesicles. The consensus highlights the characteristics and advantages of Chinese medicine, inherits the essence, and keeps the righteousness and innovation, aiming to provide a reference for colleagues engaged in research and application of Chinese herbal vesicles at home and abroad, decode the mystery behind Chinese herbal vesicles together, establish a safe, effective and controllable accurate Chinese herbal vesicle prevention and treatment system, and build a bridge for Chinese medicine to the world.

Exploration of antidepressant effect and mechanism of icariside Ⅱ based on GABAergic nervous system / 中国药房

OBJECTIVE To explore the antidepressant effect and potential mechanism of icariside Ⅱ （ICSⅡ） based on the GABAergic nervous system. METHODS The male Kunming mice were randomly divided into a control group （group C， 10 mice） and a modeling group （50 mice）. The depression model was induced by chronic unpredictable mild stress （CUMS） method in the modeling group. After 21 days of stimulation， the rats of modeling group were randomly divided into depression model group （NS group）， positive control group [ECS group， oxalate escitalopram 15 mg/（kg·d）] and ICSⅡ low-dose， medium-dose and high-dose groups [ICSⅡ-L group， ICSⅡ-M group， ICSⅡ-H group； ICSⅡ 10， 20， 30 mg/（kg·d）]， with 10 mice in each group. Administration groups were given relevant medicine intragastrically， once a day， for 14 consecutive days. The sugar water preference rate， total exercise distance， immobility time in tail suspension and forced swimming experiments were detected in each group. The morphology of neurons and Nissl bodies in the hippocampal CA3 region were observed； the contents of γ-aminobutyric acid （GABA） and glutamic acid （Glu）， GABA/Glu ratio， and the expressions of GABAergic nervous system-related proteins （GABA A receptor α1， GABA B receptor 1， vesicular GABA transporter， glutamate decarboxylase 67， GABA membranal transporter 3） were detected in hippocampus. RESULTS Compared with group C， the sugar water preference rate and the total exercise distance significantly reduced in NS group， while the values of immobility time in the tail suspension test and forced swimming test were significantly prolonged （P＜0.05）. The morphology of neurons in the CA3 area of the hippocampus was irregular and the Nissl bodies were reduced， with a significant decrease in the number of structurally intact neurons （P＜0.05）； the content of Glu was significantly increased， while the content of GABA， GABA/Glu ratio， and the expressions of GABAergic nervous system-related proteins were significantly decreased （P＜0.05）. Compared with NS group， depression behavior in each administration group was improved， and the above indexes were mostly reversed （P＜0.05）. CONCLUSIONS ICSⅡ can improve depression behavior of depression model mice. The mechanisms may be associated with regulating the balance of GABA and Glu， increasing the synthesis， transport and release of GABA， and regulating the expressions of GABA-related receptors， so as to improve GABAergic nervous system.

Study on processing and enhance the curative effects of Arisaematis rhizomz preparatum based on network pharmacology / 中国药理学通报

Aim To explore the mechanism of process¬ing and increasing efficiency of Arisaematis rhizomz preparatum. Methods UPLC-Q-TOF-MS/MS tech¬nology was used to detect the chemical components be¬fore and after processing of Arisaematis rhizomz prepara¬tum, and its mechanism of action was analysed in the treatment of 44 asthma and phlegm " by using network pharmacology. A rat model of allergic asthma was es- tablished to compare the efficacy of Arisaematis rliizoma before and after processing. Results A total of 27 chemical components were identified, among which cur- cumin ,6-gingerol and other components increased after processing. Combined with the database prediction, the action mechanism of the 36 chemical components in the treatment of 44 asthma and phlegm" diseases was dis¬cussed and predicted through network pharmacology. The results of animal experiments showed that the effect of processed Arisaematis rhizoma on allergic asth¬ma was better than that of Arisaematis rhizoma, but there was no significant difference. Conclusions The addition of curcumin, 6-gingerol, camphor, demethyl- curcumin and other components after the processed Ari¬saematis rhizomz preparatum may be the reason for the synergistic effect of Arisaematis rhizomz preparatum in the treatment of allergic asthma.

Effect of a novel phosphodiesterase type 5 inhibitor, CPD1, on carbon tetrachloride-induced liver fibrosis in mice / 中国药理学通报

Aim To investigate the effects of CPD1, a novel phosphodiesterase 5 inhibitor, on liver pathological phenotype and hepatic stellate cells (HSCs) activation in hepatic fibrosis model mice caused by carbon tetrachloride ( CCl

Erratum: Author correction to 'Mevalonate improves anti-PD-1/PD-L1 efficacy by stabilizing CD274 mRNA' Acta Pharmaceutica Sinica B 13 (2023) 2585-2600

[This corrects the article DOI: 10.1016/j.apsb.2023.04.002.].

Effects of occupational therapy on upper extremity for patients with stroke: a systematic review using WHO-FICs / 中国康复理论与实践

ObjectiveTo construct a framework of PICO for occupational therapy to improve upper extremity function in stroke patients based on World Health Organization Family of International Classifications (WHO-FICs), and to analyze the functional outcome of major occupational therapies to improve upper extremity in stroke. MethodsUsing the WHO-FICs framework, the databases such as Web of Science, PubMed, CNKI and SinoMed were searched for literature related to occupational therapy interventions for upper extremity function in stroke patients from the date of establishment to October, 2022, and the contents of the literature were extracted for a systematic review. ResultsTen randomized controlled trials from six countries were finally included, involving 382 participants (≥ 18 years old). The literatures were mainly from the fields of rehabilitation medicine, physics and rehabilitation medicine, neuroscience, bioengineering medicine, occupational therapy and other research fields, and were published mainly after 2013. The quality of the included literatures was evaluated using Physiotherapy Evidence Database (PEDro) scale with a mean score of 7.5. Based on the WHO-FICs framework, the types of diseases included intracerebral haemorrhage (8B00), cerebral ischemic stroke (8B11), subarachnoid hemorrhage (8B01), abnormality of tonus and reflex (MB47), and hemiplegia (MB53). The main dysfunctions of the upper extremity after stroke included mobility of joint functions (b710), stability of joint functions (b715), muscle power functions (b730), muscle tone functions (b735), motor reflex functions (b750), control of voluntary movement functions (b760), involuntary movement functions (b765). Activity and participation included activity of upper limb, such as lifting and carrying objects (d430), hand and arm use (d445), and fine hand use (d440); and the daily life activities and social participation, such as self-care (d510-d570), domestic life (d610-d660), major life areas (d810-d879), community, social and civic life (d910-d950). Therapeutic interventions on body functions included electrical stimulation of muscle functions (MU2.SC.BP), assistance and guidance of exercise for involuntary movement reaction (MV2.PG.ZZ); therapeutic interventions involving activity and participation were training in lifting and carrying (SIA.PH.ZZ), training in fine hand use (SIG.PH.ZZ), exercises of arm and hand use (SIJ.PH.ZZ), self care (SM1-SMH), household tasks (SO2-SOD), and playing games (SXD.PH.ZZ); 15 to 60 minutes a time, three to ten times a week, for three to eight weeks, in hospital or at home. The outcomes of the intervention were divided into three levels. At the body function level, patients had improved neuromotor conduction function, reflex function, casual motor control, coordination and speed, joint mobility, and grip strength. At the activity and participation level, there were enhancements in upper limb mobility and speed, fine hand function and speed, frequency and quality of upper limb activity participation, and the capacities of daily living and reduced difficulty in daily activity tasks. In terms of whole functioning, patients had acquired quality of life and well-being and acquainted a feeling of pleasure and accomplishment. ConclusionA PICO framework was constructed for occupational therapy based on WHO-FICs. The health conditions included intracerebral haemorrhage, cerebral ischemic stroke, subarachnoid hemorrhage, abnormality of tonus and reflex, and hemiplegia. Upper extremity motor dysfunction mainly included dysfunction of voluntary motor control, low or hyperactive motor reflexes, abnormalities in muscle tone, impaired muscle coordination, poor stability of joint activities, and reduced muscle strength, etc. Activity limitation and participation restriction were manifested as functioning in the fields of arm and hand activity participation, fine manual activity, and activities of daily living and social participation. Therapeutic interventions at body function level included brain-computer interface-based functional electrical stimulation and unimanual mirror therapy; therapeutic interventions at activity and participation level included action observation training, bimanual mirror therapy, task-oriented training, bilateral arm training and upper extremity robotics training. The health and functional benefits included the improvements in upper extremity motor function, upper extremity mobility and participation levels, activities of daily living and social participation, and quality of life and well-being.

Comparative study of corneal thickness and thinnest point position of keratoconus measured by Pentacam HR and RTVue OCT / 国际眼科杂志(Guoji Yanke Zazhi)

AIM: To investigate the difference, correlation, and consistency of corneal thickness and the thinnest point position detected by Pentacam HR corneal topography map and RTVue optical coherence tomography(OCT)in patients with keratoconus.METHODS: Cross-sectional comparative study. The corneal curvature map, corneal thickness map, thinnest point position, and thinnest point thickness were detected by Pentacam HR and RTVue OCT. Paired sample t-test was used for data consistent with normal distribution, and paired sample rank sum test was used for data inconsistent with normal distribution. Spearman correlation analysis and Bland-Altman analysis were used for the correlation and consistency of the two measurement methods.RESULTS: A total of 63 patients(105 eyes)with keratoconus were included in this study, including 49 males(77.8%)and 14 females(22.2%), aged 22.24±6.19 years; among them, relevant data of Pentacam HR topographic map: Km was 47.85±4.73D and Kmax was 55.43±8.72D. In measuring central corneal thickness and the thinnest point thickness of keratoconus, the Pentacam HR was 4.70μm and 19.46μm thicker than the mean value measured by RTVue OCT(P<0.05). There was no significant difference between the horizontal and vertical coordinates of the thinnest points measured by the two devices(P>0.05). The central corneal thickness and the thinnest point thickness measured by the two devices were highly correlated, the horizontal coordinate of the thinnest point was moderately correlated, and the vertical coordinate of the thinnest point was weakly correlated. Bland-Altman analysis showed that the central corneal thickness, the thinnest point thickness, the horizontal coordinate of the thinnest point, and the vertical coordinate of the thinnest point were 95.2%(100/105)and 93.3%(98/105), 95.2%(100/105), 95.2%(100/105)respectively, which were within the 95% consistency limit, while the consistency ranges were -36.00～+26.62μm, -42.27～+3.36μm, -0.80～+0.84mm, and -1.95～+1.06mm, respectively.CONCLUSION: In keratoconus, the central corneal thickness and the thinnest point thickness measured by Pentacam HR were higher than those measured by RTVue OCT. It is not recommended that the central corneal thickness and the thinnest point thickness measured by the two instruments be interchangeable in clinical use because of the wide range of consistency between the two instruments' results. The position of the thinnest corneal point measured by the two instruments is similar and consistent, so it could be considered to replace the measured values of the two instruments in clinical use.

Humanistic Characteristics and Enlightenment of Life View in Huang Di Nei Jing / 中国医学伦理学

The view of life in Huang Di Nei Jing discusses the essence of human life by exploring the origin, structure and existence of human life, elucidates the overall quality of human life by observing the state and length of human life, and summarizes the characteristics of human life by analyzing the commonalities and unique characteristics of human life with other lives. On the one hand, this life view respects the objectivity and regularity of life, and enabling people to calmly face death but actively seeking higher possibilities of life, which reflects the reasonable self-awareness of ancient doctors towards human life. On the other hand, it affirms the intrinsic value of life, advocates meeting the subjective value of life and pursuing the external value of life, and expresses the self-pursuit of exploring the existence value of human life, which makes the life view in Huang Di Nei Jing quite humanistic. This humanistic life view has important reference significance for modern medical practice. Reasonable absorbing the humanistic spirit of the life view in Huang Di Nei Jing is conducive to the return of modern medicine to the medical essence of saving the dying and healing the wounded, as well as the establishment of the medical value of people-oriented.

Advances of Congenital Alopecia/Hypotrichosis in Genetics Research / 罕见病研究

Congenital alopecia/hypotrichosis is a rare group of monogenic genetic hair disorders characterized by congenital limited or diffuse hair loss and scarcity, without any effective treatment. Genetic testing to identify the causative gene mutation is the gold standard for confirming the diagnosis of this group of disorders. Because of the heterogeneity in clinical features and genetic pattern of this group of diseases, it is very easy to misdiagnose and mistreat them as diffuse baldness or androgenic alopecia and other acquired alopecia, so clinicians should improve their understanding of this group of diseases. With the continuous development of molecular biology techniques in recent years, a variety of causative genes for congenital alopecia/hypotrichosis have been identified so far, and the pathogenesis of some of these genes and their corresponding subtypes have been clarified. In this paper, we reviewed the clinical manifestations and genetic research progress of non-syndromic congenital alopecia/ hypotrichosis, in order to facilitate clinicians' comprehensive understanding of these rare hair diseases and improve clinical diagnosis and treatment.

Effectiveness of TiRobot-assisted and free-hand percutaneous kyphoplasty via pedicle of vertebra in treatment of osteoporotic vertebral compression fracture of thoracic vertebra / 中国修复重建外科杂志

OBJECTIVE@#To compare the effectiveness of TiRobot-assisted and C-arm X-ray fluoroscopy assisted percutaneous kyphoplasty (PKP) via pedicle of vertebra in the treatment of osteoporotic vertebral compression fracture (OVCF) of thoracic vertebrae.@*METHODS@#The clinical data of 85 patients with OVCF of thoracic vertebrae who were admitted between January 2020 and March 2023 and met the selection criteria was retrospectively analyzed including 40 patients (50 vertebrae) undergoing PKP assisted by TiRobot (group A) and 45 patients (50 vertebrae) undergoing PKP assisted by C-arm X-ray fluoroscopy (group B). There was no significant difference in the comparison of baseline data such as gender, age, body mass index, bone mineral density T-value, fracture segment, trauma history, and preoperative numerical rating scale (NRS) score, Oswestry disability index (ODI), and Cobb angle of injured vertebra between the two groups ( P>0.05). The effectiveness evaluation indexes of the two groups, including the operation time, the volume of injected cement, the times of fluoroscopies, the length of hospital stay, and the occurrence of postoperative complications were collected and compared. Anteroposterior and lateral X-ray films and CT of the injured vertebra were reviewed at 1 day after operation to observe whether there was cement leakage and to evaluate the distribution of cement in the injured vertebra. Before and after operation, pain was assessed using the NRS score, dysfunction was assessed using the ODI, and vertebral height recovery was assessed by measuring the Cobb angle of the injured vertebrae by X-ray films.@*RESULTS@#Both groups of patients successfully completed the operation, the operation time, the volume of injected cement, the times of fluoroscopies, and the length of hospital stay in group A were significantly less than those in group B ( P<0.05). The patients in two groups were followed up 4-12 months (mean, 9.6 months). Bone cement leakage occurred in 5 vertebrae in group A and 15 vertebrae in group B after operation, all of which leaked to the intervertebral space and around the vertebral body, and the patients had no obvious clinical symptoms. The difference of bone cement leakage between the two groups was significant ( P<0.05). No severe complication such as intraspinal leakage, infection, or vascular embolism was found in the two groups. At 1 day after operation, the distribution index of bone cement in group A was mostly grade Ⅴ, which was well dispersed; while in group B, it was mostly grade Ⅱ and grade Ⅴ; the difference of bone cement distribution index between the two groups was significant ( P<0.05). The NRS score, ODI, and Cobb angle of injured vertebra in both groups were significantly improved at 1 day after operation when compared with preoperative ones ( P<0.05). There was no significant difference in the difference of the above indexes between the two groups before and after operation ( P>0.05).@*CONCLUSION@#TiRobot-assisted unilateral PKP in the treatment of OVCF of thoracic vertebrae is safe and effective, which can reduce the X-ray transmission times during operation, shorten the operation time, reduce the volume of bone cement injection, and thus decrease incidence of bone cement leakage.

Research progress on the mechanism of exosomes in diabetic retinopathy / 国际眼科杂志(Guoji Yanke Zazhi)

Exosomes are nanoscale extracellular vesicles that are secreted by a variety of cells in the body. They carry particular miRNA, protein molecules, transcription factors, and other information molecules, and they play a role in the pathophysiological regulation of a number of diseases in the body. Exosomes can persist steadily in biological tissues and bodily fluids. Exosomes have quickly advanced in ophthalmology in recent years due to the extensive studies of exosomes in a variety of fields, such as diabetic retinopathy, age-related macular degeneration, autoimmune uveitis, corneal disease, glaucoma, and other diseases. The number of people who are blind caused by diabetic retinopathy is rising as living standards rise. However, it is still unclear how diabetic retinopathy works. In recent years, many studies have found that exosomes play an important role in diabetic retinopathy. In this paper, the most recent developments in exosome studies as they relate to the pathogenesis and progression of diabetic retinopathy are reviewed.

Pathogenic characterization of Klebsiella pneumoniae resistant to carbapenems and polymyxin / 中华预防医学杂志

Objective: Analysis and investigation of pathogenic characteristics of polymyxin-and carbapenem-resistant Klebsiella pneumoniae (PR-CRKP). Methods: A total of 23 PR-CRKP strains isolated from clinical specimens from the General Hospital of Southern Theater Command from March 2019 to July 2021 were retrospectively collected, Whole-genome sequencing was performed on 23 PR-CRKP strains, resistance genes were identified by comparison of the CARD and the ResFinder database, high-resolution typing of PR-CRKP strains was analyzed by core genomic multilocus sequencing (cgMLST) and single nucleotide polymorphism (SNP); polymyxin resistance genes were determined by PCR and sequencing. Results: All PR-CRKP strains were KPC-2 producing ST11 types. cgMLST results showed that the evolutionary distance between the PR-CRKP strains and Klebsiella pneumoniae in mainland China was 66.44 on average, which is more closely related than foreign strains; the 23 PR-CRKP strains were divided into 3 main subclusters based on SNP phylogenetic trees, with some aggregation among Clade 2-1 in the isolation department and date. The two-component negative regulatory gene mgrB has seven mutation types including point mutations, different insertion fragments and different insertion positions. Conclusion: The close affinity of PR-CRKP strains indicate the possibility of nosocomial clonal transmission and the need to strengthen surveillance of PR-CRKP strains to prevent epidemic transmission of PR-CRKP.

Influencing factors of hospitalization costs for lung cancer patients in Wuhan in 2018-2020 / 公共卫生与预防医学

Objective To summary the hospitalization costs of lung cancer patients, and analyze the influence factors in these patients, and provide basis for controlling hospitalization costs of lung cancer patients. Methods The hospitalization costs data of hospitalized lung cancer cases in Wuhan from 2018 to 2020 were collected from medical records. Nonparametric test was used to analysis the data for single factor analysis. The patients were divided into two groups according on the upper quartile value of hospitalization cost, that is high-cost group (the cost ≥ the upper quartile value) and normal cost group (the cost “four major hospitals in Hubei” respectively. The hospital type is an independent influencing factors, compared with specialized hospital, the OR is 4.726 for general hospital. The hospitalization days is the independent influencing factors, more hospitalization days has high cost. The treatment mode is the independent influencing factors, compared with non-operative treatment, the OR is 556.129, 18.156 and 5.212 for surgical model, radio therapy model and interventional model respectively. Conclusion The age, hospital level, hospital type, hospitalization days and treatment mode are the independent influencing factors of hospitalization costs. To reduce the hospitalization cost of lung cancer patients, we should standardize the diagnosis of lung cancer patients, and focus on standardizing the treatment mode, also considering other influencing factors, such as hospital level, hospital type.

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).

Type III secretory protein SINC of Chlamydia psittaci promotes host cell autophagy by activating the MAPK/ERK signaling pathway / 南方医科大学学报

OBJECTIVE@#To investigate the effects of SINC, a secreted protein of Chlamydia psittaci, on autophagy of host cells and the role of MAPK/ERK signaling pathway in mediating SINC-induced autophagy.@*METHODS@#RAW 264.7 cells treated with recombinant SINC were examined for changes in expression levels of LC3-II, Beclin-1, phosphorylated and total ERK1/2 using Western blotting. The expression level of LC3 in the treated cells was detected using immunofluorescence analysis, and the formation of autophagosomes and autolysosomes was observed with transmission electron microscopy (TEM). The effect of pretreatment with U0126 (a specific ERK inhibitor) on the expression levels of LC3-II and Beclin-1 in RAW 264.7 cells exposed to different concentrations of SINC was examined using Western blotting, and LC3 puncta in the cells was detected with immunofluorescence analysis.@*RESULTS@#The expression levels of LC3-II and Beclin-1 were the highest in RAW 264.7 cells treated with 2 μg/mL SINC for 12h. Immunofluorescence analysis showed exposure to SINC significantly increased the number of cells containing LC3 puncta, where the presence of autophagosomes and autolysosomes was detected. Exposure to 2 μg/mL SINC for 15 min resulted in the most significant increase of the ratios of p-ERK1/2/ERK1/2 in RAW 264.7 cells. Pretreatment of the cells with U0126 prior to SINC exposure significantly decreased the ratio of p-ERK1/2/ERK1/2, lowered the expression levels of LC3-II and Beclin-1, and decreased LC3 aggregation in the cells.@*CONCLUSIONS@#SINC exposure can induce autophagy in RAW 264.7 cells by activating the MAPK/ERK signaling pathway.

Joint effects of meteorological factors and PM2.5 on age-related macular degeneration: a national cross-sectional study in China

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 (PM2.5) 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 PM2.5 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 PM2.5 on AMD.@*RESULTS@#The prevalence of AMD in the study population was 2.6% (95% CI 2.42-2.76%). The average annual PM2.5 level during the study period was 63.1 ± 15.3 µg/m3. A significant positive association was detected between AMD and PM2.5 level, temperature (T), and relative humidity (RH), in both the independent and the combined effect models. For PM2.5, 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 PM2.5 was 0.864 (0.586,1.141) and 1.180 (0.768,1.592), respectively, indicating a synergistic effect between PM2.5 and atmospheric pressure.@*CONCLUSIONS@#This study is among the first to characterize the coordinated effects of meteorological factors and PM2.5 on AMD. The findings warrant further investigation to elucidate the relationship between ambient environment and AMD.

Lower Baseline LDL Cholesterol Affects All-cause Mortality in Patients with First Percutaneous Coronary Intervention / 生物医学与环境科学（英文）

OBJECTIVE@#Foreign studies have reported that coronary artery disease (CAD) patients with high baseline low-density lipoprotein cholesterol (LDL-C) may have a good prognosis, which is called the "cholesterol paradox". This study aimed to examine whether the "cholesterol paradox" also exists in the Chinese population.@*METHODS@#A total of 2,056 patients who underwent the first percutaneous coronary intervention (PCI) between 2014 and 2016 were enrolled in this retrospective cohort study and classified into two groups based on baseline LDL-C = 2.6 mmol/L (100 mg/dL). The outcomes of interest included major adverse cardiovascular events (MACE), all-cause mortality, recurrent nonfatal myocardial infarction, unexpected coronary revascularization, or any nonfatal stroke.@*RESULTS@#All-cause mortality occurred in 8 patients (0.7%) from the low-LDL-C group and 12 patients (2.4%) in the high-LDL-C group, with a significant difference between the two groups (adjusted hazard ratio: 4.030, 95% confidence interval: 1.088-14.934; P = 0.037). However, no significant differences existed for the risk of MACE or other secondary endpoints, such as unexpected revascularization, nor any nonfatal stroke in the two groups.@*CONCLUSION@#In this study, a high baseline LDL-C was not associated with a low risk of clinical outcomes in CAD patients undergoing first PCI, which suggested that the "cholesterol paradox" may be inapplicable to Chinese populations.

Mevalonate improves anti-PD-1/PD-L1 efficacy by stabilizing CD274 mRNA

Mevalonate metabolism plays an important role in regulating tumor growth and progression; however, its role in immune evasion and immune checkpoint modulation remains unclear. Here, we found that non-small cell lung cancer (NSCLC) patients with higher plasma mevalonate response better to anti-PD-(L)1 therapy, as indicated by prolonged progression-free survival and overall survival. Plasma mevalonate levels were positively correlated with programmed death ligand-1 (PD-L1) expression in tumor tissues. In NSCLC cell lines and patient-derived cells, supplementation of mevalonate significantly up-regulated the expression of PD-L1, whereas deprivation of mevalonate reduced PD-L1 expression. Mevalonate increased CD274 mRNA level but did not affect CD274 transcription. Further, we confirmed that mevalonate improved CD274 mRNA stability. Mevalonate promoted the affinity of the AU-rich element-binding protein HuR to the 3'-UTR regions of CD274 mRNA and thereby stabilized CD274 mRNA. By in vivo study, we further confirmed that mevalonate addition enhanced the anti-tumor effect of anti-PD-L1, increased the infiltration of CD8+ T cells, and improved cytotoxic function of T cells. Collectively, our findings discovered plasma mevalonate levels positively correlated with the therapeutic efficacy of anti-PD-(L)1 antibody, and provided the evidence that mevalonate supplementation could be an immunosensitizer in NSCLC.

The impact of lipids on the cancer-immunity cycle and strategies for modulating lipid metabolism to improve cancer immunotherapy

Lipids have been found to modulate tumor biology, including proliferation, survival, and metastasis. With the new understanding of tumor immune escape that has developed in recent years, the influence of lipids on the cancer-immunity cycle has also been gradually discovered. First, regarding antigen presentation, cholesterol prevents tumor antigens from being identified by antigen presenting cells. Fatty acids reduce the expression of major histocompatibility complex class I and costimulatory factors in dendritic cells, impairing antigen presentation to T cells. Prostaglandin E2 (PGE2) reduce the accumulation of tumor-infiltrating dendritic cells. Regarding T-cell priming and activation, cholesterol destroys the structure of the T-cell receptor and reduces immunodetection. In contrast, cholesterol also promotes T-cell receptor clustering and relative signal transduction. PGE2 represses T-cell proliferation. Finally, regarding T-cell killing of cancer cells, PGE2 and cholesterol weaken granule-dependent cytotoxicity. Moreover, fatty acids, cholesterol, and PGE2 can improve the activity of immunosuppressive cells, increase the expression of immune checkpoints and promote the secretion of immunosuppressive cytokines. Given the regulatory role of lipids in the cancer-immunity cycle, drugs that modulate fatty acids, cholesterol and PGE2 have been envisioned as effective way in restoring antitumor immunity and synergizing with immunotherapy. These strategies have been studied in both preclinical and clinical studies.