Serine/threonine-protein kinase D2-mediated phosphorylation of DSG2 threonine 730 promotes esophageal squamous cell carcinoma progression.

Desmoglein-2 (DSG2) is a transmembrane glycoprotein belonging to the desmosomal cadherin family, which mediates cell-cell junctions; regulates cell proliferation, migration, and invasion; and promotes tumor development and metastasis. We previously showed serum DSG2 to be a potential biomarker for the diagnosis of esophageal squamous cell carcinoma (ESCC), although the significance and underlying molecular mechanisms were not identified. Here, we found that DSG2 was increased in ESCC tissues compared with adjacent tissues. In addition, we demonstrated that DSG2 promoted ESCC cell migration and invasion. Furthermore, using interactome analysis, we identified serine/threonine-protein kinase D2 (PRKD2) as a novel DSG2 kinase that mediates the phosphorylation of DSG2 at threonine 730 (T730). Functionally, DSG2 promoted ESCC cell migration and invasion dependent on DSG2-T730 phosphorylation. Mechanistically, DSG2 T730 phosphorylation activated EGFR, Src, AKT, and ERK signaling pathways. In addition, DSG2 and PRKD2 were positively correlated with each other, and the overall survival time of ESCC patients with high DSG2 and PRKD2 was shorter than that of patients with low DSG2 and PRKD2 levels. In summary, PRKD2 is a novel DSG2 kinase, and PRKD2-mediated DSG2 T730 phosphorylation promotes ESCC progression. These findings may facilitate the development of future therapeutic agents that target DSG2 and DSG2 phosphorylation. © 2024 The Pathological Society of Great Britain and Ireland.

Health effects and externalities of the popularization of sanitary toilets: evidence from Rural China.

BACKGROUND: This study aimed to assess the impact of the increased prevalence of sanitary toilets in rural areas on the health of rural residents, and whether the popularity thereof has a positive externality. This study investigates whether the broader use of sanitary toilets has had a positive effect on the health of people who do not have access to them. METHODS: Data from the China Family Panel Studies from 2012 to 2014 and a two-way fixed effect model were used to investigate the relationship between the prevalence of village sanitary toilets and the health of rural residents of all ages. RESULTS: The results showed that: (1) the increase in the prevalence of sanitary toilets in villages is conducive to improving the health level of rural residents; (2) the widespread adoption of sanitary toilets in rural areas has improved the health of not only residents with access to these toilets but also residents without access; (3) the health of children is more sensitive to improvements in sanitary conditions of toilets; and (4) there are significant regional differences in the impact of the popularity of sanitary toilets on the health of rural residents. CONCLUSIONS: This study found that the popularity of sanitary toilets has externalities, improving not only the health of residents who use them but also the health of other residents. This study enriches the literature in the field of health effects of sanitation improvement, while providing a reference for developing countries to further enhance the living environment in rural areas. In the future, the popularization of sanitary toilets should be vigorously promoted to reduce the incidence of diseases.

Obstructive sleep apnea in patients with ischemic stroke: mechanism, diagnosis, and treatment / 国际脑血管病杂志

Ischemic stroke is the main cause of death and disability in adults, and its incidence is increasing year by year. Obstructive sleep apnea (OSA) is the most common type of sleep-disordered breathing, which can increase the risk of ischemic stroke and affect the outcomes of patients. There is an increasing amount of research on the relationship between OSA and ischemic stroke. This article reviews the bidirectional relationship between OSA and ischemic stroke, the mechanism of OSA causing ischemic stroke, and the diagnosis and treatment of OSA in patients with ischemic stroke.

Carotid plaque and ischemic stroke / 国际脑血管病杂志

Carotid atherosclerosis is closely associated with ischemic stroke. Research shows that the rupture of vulnerable carotid plaque is an important reason for carotid atherosclerosis leading to thromboembolic events. Therefore, early identification of vulnerable carotid plaques is of great significance for the diagnosis, treatment, and prevention of ischemic stroke. This article reviews the pathophysiological features, imaging evaluation of carotid plaque and its relationship with ischemic stroke.

A metabonomic study of intragastric local hypothermia intervention in rats with pancreatitis / 中华急诊医学杂志

Objective:To investigate the effect and mechanism of local gastric hypothermia in rats with pancreatitis based on a GC?MS and LC?MS dual metabolomics strategy.Methods:Eighteen SD rats were randomly divided into the sham operation (SO), acute pancreatitis (AP) and acute pancreatitis hypothermia (APH) groups. The AP model was established by retrograde injection of 3.5% sodium taurocholate solution into the pancreaticobiliary duct in the AP and APH groups. In the APH group, gastrotomy was performed near the cardia, and a cooling balloon with 2 silicone catheters was placed in the stomach. After the successful establishment of the rat pancreatitis model in the APH group, the speed of ice water circulation was controlled and the output power of the heating pad was adjusted to achieve pancreatic surface temperature reduction while avoiding systemic hypothermia. Temperatures were not monitored and controlled in the SO and AP groups. Serum amylase was detected by ELISA. Pancreatic tissues were stained with HE and histopathologically scored. The expression of NF-κB, IL-6, TNF-α and IκBα in pancreatic tissue was detected by Western blotting. The AP and APH groups were compared by full-scan analysis, and the serum differential metabolites and metabolic pathways were detected by GC?MS- and LC?MS-based metabolomics strategies.Results:Compared with the SO group, the serum amylase level in the AP group and APH group were increased (all P<0.05). Compared with the AP group, the amylase levels at 3 h and 5 h after the operation were decreased in the APH group (both P<0.05). The pathological scores of the AP and APH groups were higher than those of the SO group (both P<0.05), and the pathological damage to pancreatic tissue in the APH group was less than that in the AP group ( P<0.05). IL-6, TNF-α and NF-κB were decreased and IκBα was increased in the APH group compared with the AP group by Western blotting (all P<0.05). A total of 53 differential metabolites were identified by GC?MS, and 236 differential metabolites were identified by LC?MS in the serum samples of the APH group compared with the AP group. The differential metabolites obtained from the blood samples of the APH group and AP group were imported into MetaboAnalyst 4.0 software for analysis, and the root data-log ( P value)>2, P<0.05, three major metabolic pathways were obtained, including ascorbate and aldarate metabolism, pentose and glucuronate interconversions and tryptophan metabolism. Conclusions:Local gastric hypothermia has a protective effect on the expression of inflammatory factors and alleviates pathological damage in rats with acute pancreatitis, which may be related to ascorbate and aldarate metabolism, pentose and glucuronate interconversions and tryptophan metabolism.

Research progress on continuous blood purification in the treatment of severe acute pancreatitis / 中国医师杂志

Severe acute pancreatitis (SAP) is a common gastrointestinal disease, often accompanied by systemic inflammatory reactions and organ dysfunction. SAP has an acute onset, severe condition, rapid progression, and poor prognosis. The development of SAP is closely related to the excessive release of inflammatory factors. In the comprehensive treatment of SAP, continuous blood purification (CBP) can clear inflammatory mediators, improve the stability of Internal environment, improve organ function, reduce blood lipids, regulate immunity, and significantly improve the condition of SAP patients. It is an important means of treating SAP. This article reviews the research progress of CBP in the treatment of SAP.

Identification Strategy of Biological Half Sibling Relationship / 法医学杂志

OBJECTIVES@#To compare the application value of the likelihood ratio (LR) method and identity by state (IBS) method in the identification involving half sibling relationships, and to provide a reference for the setting of relevant standards for identification of half sibling relationship.@*METHODS@#(1) Based on the same genetic marker combinations, the reliability of computer simulation method was verified by comparing the distributions of cumulated identity by state score (CIBS) and combined full sibling index in actual cases with the distributions in simulated cases. (2) In different numbers of three genetic marker combinations, the simulation of full sibling, half sibling and unrelated individual pairs, each 1 million pairs, was obtained; the CIBS, as well as the corresponding types of cumulative LR parameters, were calculated. (3) The application value of LR method was compared with that of IBS method, by comparing the best system efficiency provided by LR method and IBS method when genetic markers in different amounts and of different types and accuracy were applied to distinguish the above three relational individual pairs. (4) According to the existing simulation data, the minimum number of genetic markers required to distinguish half siblings from the other two relationships using different types of genetic markers was estimated by curve fitting.@*RESULTS@#(1) After the rank sum test, under the premise that the real relationship and the genetic marker combination tested were the same, there was no significant difference between the simulation method and the results obtained in the actual case. (2) In most cases, under the same conditions, the system effectiveness obtained by LR method was greater than that by IBS method. (3) According to the existing data, the number of genetic markers required for full-half siblings and half sibling identification could be obtained by curve fitting when the system effectiveness reached 0.95 or 0.99.@*CONCLUSIONS@#When distinguishing half sibling from full sibling pairs or unrelated pairs, it is recommended to give preference to the LR method, and estimate the required number of markers according to the identification types and the population data, to ensure the identification effect.

Serum DSG2 as a potential biomarker for diagnosis of esophageal squamous cell carcinoma and esophagogastric junction adenocarcinoma.

BACKGROUND: Exploration of serum biomarkers for early detection of upper gastrointestinal cancer is required. Here, we aimed to evaluate the diagnostic potential of serum desmoglein-2 (DSG2) in patients with esophageal squamous cell carcinoma (ESCC) and esophagogastric junction adenocarcinoma (EJA). METHODS: Serum DSG2 levels were measured by enzyme-linked immunosorbent assay (ELISA) in 459 participants including 151 patients with ESCC, 96 with EJA, and 212 healthy controls. Receiver operating characteristic (ROC) curves were used to evaluate diagnostic accuracy. RESULTS: Levels of serum DSG2 were significantly higher in patients with ESCC and EJA than those in healthy controls (P<0.001). Detection of serum DSG2 demonstrated an area under the ROC curve (AUC) value of 0.724, sensitivity of 38.1%, and specificity of 84.8% for the diagnosis of ESCC in the training cohort, and AUC 0.736, sensitivity 58.2%, and specificity 84.7% in the validation cohort. For diagnosis of EJA, measurement of DSG2 provided a sensitivity of 29.2%, a specificity of 90.2%, and AUC of 0.698. Similar results were observed for the diagnosis of early-stage ESCC (AUC 0.715 and 0.722, sensitivity 36.3 and 50%, and specificity 84.8 and 84.7%, for training and validation cohorts, respectively) and early-stage EJA (AUC 0.704, sensitivity 44.4%, and specificity 86.9%). Analysis of clinical data indicated that DSG2 levels were significantly associated with patient age and histological grade in ESCC (P<0.05). CONCLUSION: Serum DSG2 may be a diagnostic biomarker for ESCC and EJA.

Adaptive thermal refocusing system for a high-resolution space camera.

To solve the problem of camera imaging quality degradation caused by defocusing during on-orbit operation, we propose an adaptive thermal refocusing system for high-resolution space cameras-the system comprising active and passive thermal refocusing. Using a space camera with a Ritchey-Chretien optical system as an example, the secondary mirror assembly was determined to be a passive thermal refocusing system, the primary mirror assembly being an active thermal refocusing system. We analyzed the system through structure/thermal/optics performance simulation when temperature variation ΔT was 5°C, 10°C, and 15°C; thermal vacuum experiments verified that the axial displacement of the active system was 0.0032, 0.0061, and 0.0090 mm, and the passive system was 0.00015, 0.00030, and 0.00069 mm, respectively. The data demonstrated the adaptive refocusing system theory to be consistent with the simulations and experiment, exhibiting high stability and reliability.

20 cases of robotic assisted thoracoscopic surgery for the treatment of pulmonary sequestration in children / 中华胸心血管外科杂志

Objective:To analyze the application of robot-assisted thoracoscopic surgery in the treatment of pulmonary sequestration in children.Methods:The clinical data of 20 children with pulmonary sequestration admitted to the Children's Hospital Zhejiang University School of Medicine from May to November 2020 were analyzed retrospectively. There were 13 males and 7 females, ages ranged from 6 months to 5 years old, with median age of 10 months. Body weight ranged from 7.5 to 18.0 kg, with mean weight of(9.95±2.46)kg. Abnormal blood supply vessels in pulmonary sequestration were found by chest enhanced CT and were further confirmed during surgery. All the other 19 cases were found to have pulmonary lesions by prenatal ultrasound except 1 case due to repeated infection. The lesions were located in left lung in 15 cases and right lung in 5 cases.Results:1 case was converted to thoracotomy due to failure of intraoperative single lung ventilation and inability of artificial pneumothorax to collapse the lung lobe, and other 19 cases were successfully completed by robot-assisted thoracoscopic surgery. The operation time ranged from 40 to 270 min, mean(88.25±55.68) min. All 10 patients with extralobar sequestration underwent simple pneumonectomy, including 2 patients with intra-diaphragmatic pulmonary sequestration. In 10 cases of intralobar sequestration, 2 cases underwent wedge resection, 2 cases underwent segmental resection, and 6 cases underwent lobectomy. No operative death occurred. The postoperative hospital time ranged from 3 to 10 days, mean(5.00±1.89) days. All patients recovered well and no complications such as pleural effusion and atelectasis were observed during 1-6 months follow-up.Conclusion:The robotic surgical system is safe and effective for the treatment of pulmonary sequestration in children.

PLGA/ß-TCP composite scaffold incorporating cucurbitacin B promotes bone regeneration by inducing angiogenesis.

OBJECTIVES: Vascularization is an essential step in successful bone tissue engineering. The induction of angiogenesis in bone tissue engineering can be enhanced through the delivery of therapeutic agents that stimulate vessel and bone formation. In this study, we show that cucurbitacin B (CuB), a tetracyclic terpene derived from Cucurbitaceae family plants, facilitates the induction of angiogenesis in vitro. METHODS: We incorporated CuB into a biodegradable poly (lactide-co-glycolide) (PLGA) and ß-tricalcium phosphate (ß-TCP) biomaterial scaffold (PT/CuB) Using 3D low-temperature rapid prototyping (LT-RP) technology. A rat skull defect model was used to verify whether the drug-incorporated scaffold has the effects of angiogenesis and osteogenesis in vivo for the regeneration of bone defect. Cytotoxicity assay was performed to determine the safe dose range of the CuB. Tube formation assay and western blot assay were used to analyze the angiogenesis effect of CuB. RESULTS: PT/CuB scaffold possessed well-designed bio-mimic structure and improved mechanical properties. CuB was linear release from the composite scaffold without affecting pH value. The results demonstrated that the PT/CuB scaffold significantly enhanced neovascularization and bone regeneration in a rat critical size calvarial defect model compared to the scaffold implants without CuB. Furthermore, CuB stimulated angiogenic signaling via up-regulating VEGFR2 and VEGFR-related signaling pathways. CONCLUSION: CuB can serve as promising candidate compound for promoting neovascularization and osteogenesis, especially in tissue engineering for repair of bone defects. THE TRANSLATIONAL POTENTIAL OF THIS ARTICLE: This study highlights the potential use of CuB as a therapeutic agent and strongly support its adoption as a component of composite scaffolds for tissue-engineering of bone repair.

Yeast Lipid Extraction and Analysis by HPTLC.

The diversity of lipid structures, properties, and combinations in biological tissues makes their extraction and analysis an experimental challenge. Accordingly, even for one of the simplest single-cellular fungi, the budding yeast (Saccharomyces cerevisiae), numerous extraction and analysis protocols have been developed to separate and quantitate the different molecular lipid species. Among them, most are quite sophisticated and tricky to follow. Herein, we describe a yeast total lipids extraction procedure with a relatively good yield, which is appropriate for subsequent thin-layer chromatography (TLC) or liquid chromatography-mass (LC-MS) analysis. We then discuss the most widely used solvent systems to separate yeast phospholipids and neutral lipids by TLC. Finally, we describe an easy and rapid method for silica gel staining by a Coomassie Brilliant Blue-methanol mixture. The stained lipid species can then be quantitated using imaging software such as ImageJ. Overall, the methods described in this protocol are time-saving and novice-friendly.

Noninvasive treatment of recurrent and acquired pectus excavatum with vacuum disk / 中华胸心血管外科杂志

Objective:To evaluate the effect of vacuum disk(VD) for non-invasive treatment of recurrent and acquired pectus excavatum(PE).Methods:From June 2017 to June 2019, 29 patients recruited from our outpatient clinic were included in this retrospective study and followed-up every 3 month according to the schedule. The patients were distributed into three groups(group 1 treated ≤6 months; group 2 treated from 6 months to 12 months; group 3 treated >12 months). The device should be applied regularly for more than 2 hours daily. The deformity chest wall was scanned by three-dimensional(3D)scanner at clinic, and the 3D-depth(3D-DE) and 3D-Haller index(3D-HI) of PE were calculated through Geomagic software.Results:In this cohort, 29 patients were eligible, 18 symmetrical PE and 11 asymmetric PE. The application time ranged from 3 months to 15 months(average 7.6 months). 4 paitents was lifted to a normal level, 23 patients were differently improved. However, 2 paitents had no improvement. The average of the depth and 3D-HI of all patients were improved from 17.7 mm to 11.6 mm and 1.739 to 1.598, respectively. It’s no statistically significant difference for the elevation of 3D-DE and 3D-HI between symmetrical and asymmetric PE( t=-2.821, P=0.558; t=0.074, P=0.068). When comparing the improvement of 3D-DE or 3D-HI of PE to the patient's treatment time, a statistically significant difference was proved between the group 2 and group 1( t=-2.261, P=0.014; t=-0.436, P=0.043), but not between the group 3 and group 2( t=-1.240, P=0.139; t=0.622, P=0.568). The main side effects include moderate subcutaneous hematoma(84%), petechial bleeding(27%), thoracalgia(32%) and chest tightness(17%), no other side effect appear till now. Conclusion:VD for treatment of recurrent and acquired PE is convenient, safe and noninvasive, which can be an alternative treatment for recurrent and acquired PE, However, long term of efficacy evaluation is still needed.

The application of thoracoscopic segmentectomy in children and infants with congenital pulmonary diseases / 中华胸心血管外科杂志

Objective:To evaluate the efficacy of anatomic thoracoscopic pulmonary segmentectomy in the treatment of congenital pulmonary diseases in children and infants.Methods:There were 38 cases, 21 males and 17 females, aged from 6 months to 10 years old and 2 months, mean(28.1±20.7) months, and weight 6.0-27.5 kg, mean(11.93±4.05) kg who were scheduled to undergo thoracoscopic segmental pneumonectomy from July 2019 to March 2020. Among the 38 cases, there were 27 cases of congenital pulmonary airway malformation and 11 cases of intralobar pulmonary sequestrations, including 1 case of intralobar pulmonary sequestrations with extralobar pulmonary sequestrations and 1 case of intralobar pulmonary sequestrations with bronchial cyst. 3D computed tomography bronchography and angiography(3D-CTBA) was performed before operation to identify the specific lung segment of the lesion. According to the results to plan the operation plan, determine the specific resection of the lung segment.Results:The operation was completed successfully in all groups. The operation time was(72.5±18.2)min, the bleeding volume was(17.3±2.9) ml, chest tube drainage time was(3.1±0.8) days, and the postoperative discharge time was(8.1±2.8) days. Postoperative complications included infection(1 case), atelectasis(1 case), hydropneumothorax(1 case) and pneumothorax(1 case). There was no conversion to thoracotomy and enlarged pulmonary lobectomy. There was no recurrence during the follow-up of 1-9 months.Conclusion:Lung-preserving segmentectomy is technically feasible and safe for congenital pulmonary diseases in children. The 3D-CTBA technique can be used to understand the specific pulmonary segments invaded by the lesions and the relationship between the corresponding pulmonary vessels and bronchi before operation, which is of positive significance for the resection of complex pulmonary segments and good preoperative surgical planning.

Effect of modified auricle cartilage nasal septum extension stent on rhinoplasty / 中华医学美学美容杂志

Objective:To introduce a modified stent technique of nasal septal extension graft (SEG) with auricle cartilage, and to explore its effect on rhinoplasty.Methods:For 116 patients that underwent rhinoplasty, the cartilage of bilateral auricula was sutured with shell alignment and the dovetail was modified to prepare SEG stent; PTFE or silicone prosthesis was used for nasal dorsal graft. The patients were follow up for 6-18 months after surgery. A number of indicators including length of nose, tip projection, nasal tip and nasolabial angle morphology were used to assess surgical outcomes.Results:The 116 patients obtained satisfactory appearance immediately after operation. Length of nasal extension was 3-6 mm, tip projection was extended by 2-5 mm. Following up for 6-18 months showed stable effect (0.5-1.5 mm retraction) and satisfactory nose tip and nasolabial angle. The skin color was normal. No deformity occured in the ear cartilage donor area existed with no obvious scar.Conclusions:The modified SEG stent of auricle cartilage has good support and stability. It has a good effect on the slight and moderate extension of the short nose. In addition, the elevation of the nasal tip and the severe short nose of the first rhinoplasty and secondary rhinoplasty with mild contracture are also improved.

A versatile photodetector assisted by photovoltaic and bolometric effects.

The advent of low-dimensional materials with peculiar structure and superb band properties provides a new canonical form for the development of photodetectors. However, the limited exploitation of basic properties makes it difficult for devices to stand out. Here, we demonstrate a hybrid heterostructure with ultrathin vanadium dioxide film and molybdenum ditelluride nanoflake. Vanadium dioxide is a classical semiconductor with a narrow bandgap, a high temperature coefficient of resistance, and phase transformation. Molybdenum ditelluride, a typical two-dimensional material, is often used to construct optoelectronic devices. The heterostructure can realize three different functional modes: (i) the p-n junction exhibits ultrasensitive detection (450 nm-2 µm) with a dark current down to 0.2 pA and a response time of 17 µs, (ii) the Schottky junction works stably under extreme conditions such as a high temperature of 400 K, and (iii) the bolometer shows ultrabroad spectrum detection exceeding 10 µm. The flexible switching between the three modes makes the heterostructure a potential candidate for next-generation photodetectors from visible to longwave infrared radiation (LWIR). This type of photodetector combines versatile detection modes, shedding light on the hybrid application of novel and traditional materials, and is a prototype of advanced optoelectronic devices.

Excess diacylglycerol at the endoplasmic reticulum disrupts endomembrane homeostasis and autophagy.

BACKGROUND: When stressed, eukaryotic cells produce triacylglycerol (TAG) to store nutrients and mobilize autophagy to combat internal damage. We and others previously reported that in yeast, elimination of TAG synthesizing enzymes inhibits autophagy under nitrogen starvation, yet the underlying mechanism has remained elusive. RESULTS: Here, we show that disruption of TAG synthesis led to diacylglycerol (DAG) accumulation and its relocation from the vacuolar membrane to the endoplasmic reticulum (ER). We further show that, beyond autophagy, ER-accumulated DAG caused severe defects in the endomembrane system, including disturbing the balance of ER-Golgi protein trafficking, manifesting in bulging of ER and loss of the Golgi apparatus. Genetic or chemical manipulations that increase consumption or decrease supply of DAG reversed these defects. In contrast, increased amounts of precursors of glycerolipid synthesis, including phosphatidic acid and free fatty acids, did not replicate the effects of excess DAG. We also provide evidence that the observed endomembrane defects do not rely on Golgi-produced DAG, Pkc1 signaling, or the unfolded protein response. CONCLUSIONS: This work identifies DAG as the critical lipid molecule responsible for autophagy inhibition under condition of defective TAG synthesis and demonstrates the disruption of ER and Golgi function by excess DAG as the potential cause of the autophagy defect.

Genistein inhibits angiogenesis developed during rheumatoid arthritis through the IL-6/JAK2/STAT3/VEGF signalling pathway.

BACKGROUND: Angiogenesis plays an important role in the development of rheumatoid arthritis (RA), which increases the supply of nutrients, cytokines, and inflammatory cells to the synovial membrane. Genistein (GEN), a soy-derived isoflavone, has been validated that can effectively inhibit the angiogenesis of several tumours. We thus carried out a study in vitro to investigate the effect of GEN in vascular endothelial growth factor (VEGF) expression and angiogenesis induced by the inflammatory environment of RA. METHODS: MH7A cells were used to verify whether GEN can inhibit the expression of VEGF in MH7A cells under inflammatory conditions and demonstrate the mechanism. EA.hy926 â€‹cells were used to verify whether GEN can inhibit the migration and tube formation of vascular endothelial cells in inflammatory environment. RESULTS: GEN dose-dependently inhibited the expression and secretion of interleukin (IL)-6 and VEGF, as well as the nucleus translocation of Signal transducer and activator of transcription 3 (STAT3) in MH7A. Furthermore, GEN inhibited IL-6-induced vascular endothelial cell migration and tube formation in vitro. CONCLUSION: GEN inhibits IL-6-induced VEGF expression and angiogenesis partially through the Janus kinase 2 (JAK2)/STAT3 pathway in RA, which has provided a novel insight into the antiangiogenic activity of GEN in RA. THE TRANSLATIONAL POTENTIAL OF THIS ARTICLE: Our study provides scientific guidance for the clinical translational research of GEN in the RA treatment.

Serious hypoglycemia, lactic acidosis and pancytopenia caused by Linezolid in elderly patients: a case report and literature review / 中华老年医学杂志

Objective:To analyze and summarize adverse reactions such as hypoglycemia, lactic acidosis and pancytopenia caused by Linezolid in elderly patients, in order to enhance clinicians' awareness of adverse reactions of Linezolid.Methods:One case with Linezolid-induced lactic acidosis, pancytopenia and hypoglycemia was reported in a patient receiving long-term and repeated use of Linezolid for recurrent urinary tract infections(RUTI)in Beijing Hospital.National and international literature on the three severe and rare adverse reactions caused by Linezolid before December 2018 was reviewed, and the risk factors, clinical characteristics and prognosis of the three severe adverse reactions caused by Linezolid were summarized and analyzed.Results:A total of 86 cases with Linezolid-induced adverse reactions such as hypoglycemia, lactic acidosis and pancytopenia were analyzed.Among them, the ratio of males to females was 1.8∶1.0, the median age was 64.5 years, and 44 cases were over 65 years, accounting for 51.2%.Among the 57 patients with lactic acidosis, 25 lactic acidosis cases were combined with liver and kidney diseases, which were the most commonly involved organs(43.9%, 25/57). The time of onset for lactic acidosis was 4 h-109 d, with a median value of 32 d, and the peak values of blood lactate were 2.6-38.1 mmol/L, with a median value of 13.3 mol/L.Pancytopenia occurred 4 h-120 days after the treatment, and the median value was 21 days.The time of onset for hypoglycemia was 8 h-26, and the median time was 10.3 days.The lowest value of blood glucose was 0.2 mmol/L.Of the 86 cases, 61(70.9%)patients improved, and 12 cases of 51 patients with lactic acidosis died, with a mortality rate of 23.5%.Conclusions:Clinicians should be aware of serious adverse reactions including hypoglycemia, lactic acidosis and pancytopenia during Linezolid treatment in elderly patients.It is recommended to monitor changes in blood glucose, blood lactate and blood cell count during Linezolid treatment, and to avoid long-term use of Linezolid, so as to maximize the benefits for patients.

A Validated Set of Fluorescent-Protein-Based Markers for Major Organelles in Yeast (Saccharomyces cerevisiae).

Eukaryotic cells share a basic scheme of internal organization featuring membrane-based organelles. The use of fluorescent proteins (FPs) greatly facilitated live-cell imaging of organelle dynamics and protein trafficking. One major limitation of this approach is that the fusion of an FP to a target protein can and often does compromise the function of the target protein and alter its subcellular localization. The optimization process to obtain a desirable fusion construct can be time-consuming or even unsuccessful. In this work, we set out to provide a validated set of FP-based markers for major organelles in the budding yeast (Saccharomyces cerevisiae). Out of over 160 plasmids constructed, we present a final set of 42 plasmids, the recommendations for which are backed up by meticulous evaluations. The tool set includes three colors (green, red, and blue) and covers the endoplasmic reticulum (ER), nucleus, Golgi apparatus, endosomes, vacuoles, mitochondria, peroxisomes, and lipid droplets. The fidelity of the markers was established by systematic cross-comparison and quantification. Functional assays were performed to examine the impact of marker expression on the secretory pathway, endocytic pathway, and metabolic activities of mitochondria and peroxisomes. Concomitantly, our work constitutes a reassessment of organelle identities in this model organism. Our data support the recognition that "late Golgi" and "early endosomes," two seemingly distinct terms, denote the same compartment in yeast. Conversely, all other organelles can be visually separated from each other at the resolution of conventional light microscopy, and quantification results justify their classification as distinct entities.IMPORTANCE Cells contain elaborate internal structures. For eukaryotic cells, like those in our bodies, the internal space is compartmentalized into membrane-bound organelles, each tasked with specialized functions. Oftentimes, one needs to visualize organelles to understand a complex cellular process. Here, we provide a validated set of fluorescent protein-based markers for major organelles in budding yeast. Yeast is a commonly used model when investigating basic mechanisms shared among eukaryotes. Fluorescent proteins are produced by cells themselves, avoiding the need for expensive chemical dyes. Through extensive cross-comparison, we make sure that each of our markers labels and only labels the intended organelle. We also carefully examined if the presence of our markers has any negative impact on the functionality of the cells and found none. Our work also helps answer a related question: are the structures we see really what we think they are?