Whole-process individualized pharmaceutical care for a case of melioidosis sepsis / 中国药房

OBJECTIVE To provide reference for the adjustment of antibiotic treatment regimens， identification of adverse reactions， and individualized pharmaceutical care for melioidosis sepsis （MS）. METHODS Clinical pharmacists participated in the intensive and eradicating therapeutic processes for an MS patient by using blood concentration and gene detection. Based on the literature， antibiotic treatment regimens of MS were adjusted by determining the blood concentrations of β-lactam and trimethoprim/ sulfamethoxazole （TMP/SMZ） and calculating PK/PD parameters. The causes of adverse drug reactions were analyzed and addressed by detecting drug-related gene polymorphisms through high-throughput sequencing. RESULTS Clinical pharmacists used blood concentration and genetic testing methods to propose adjustments to imipenem-cilastatin sodium dosage and analyze the causes of various adverse drug reactions. PK/PD targets were calculated by measuring the blood concentrations of β-lactam and TMP/SMZ. Clinical pharmacists explained to clinical doctors the compliance status of patients with melioidosis in sepsis and non- sepsis stages through reviewing guidelines and literature； the results of blood concentration and genetic test were used to analyze the correlation of neurotoxicity of MS patients with B14） IMP cmin， and it was found that nephrotoxicity was not related to the cmax of TMP/SMZ， but to the patient’s water intake. After whole-process antibiotic treatment， the patient’s condition improved and was discharged， and the adverse reactions were effectively treated. CONCLUSIONS Clinical pharmacists use blood concentration and genetic tests to assist clinicians in formulating MS treatment regimens， and provide whole-course pharmaceutical care for a MS patient. This method has improved the safety and effectiveness of clinical drug therapy.

Identification and 3D architecture analysis of the LIPC gene mutation in a pedigree with familial hypercholesterolemia-like phenotype / 中华心血管病杂志

Objective: To identify and analyze 3D architecture of the mutational sites of susceptible genes in a pedigree with familial hypercholesterolemia-like phenotype (FHLP). Methods: This is a case series study. A pedigree with suspected familial hypercholesterolemia was surveyed. The proband admitted in Beijing Anzhen Hospital in April 2019. Whole-exome sequencing was performed to determine the mutational sites of susceptible genes in the proband. Polymerase chain reaction (PCR) sequencing was used to verify the pathogenic variant on proband's relatives. The structural and functional changes of the proteins were analyzed and predicted by Discovery Studio 4.0 and PyMol 2.0. Results: The patients in the pedigree showed abnormal lipid profiles, especially elevated levels of total cholesterol(TC). The genetic screening detected the c.1330C>T SNP in the exon 8 of lipase C (LIPC) gene, this mutation leads to an amino acid substitution from arginine to cysteine at position 444 (Arg444Cys), in the proband and proband's father and brother. In this family, members with this mutation exhibited elevated TC, whereas lipid profile was normal from the proband's mother without this mutation. This finding indicated that LIPC: c.1330C>T mutation might be the mutational sites of susceptible genes. The analysis showed that Arg444Cys predominantly affected the ligand-binding property of the protein, but had a limited impact on catalytic function. Conclusion: LIPC: c.1330C>T is a new mutational site of susceptible genes in this FHLP pedigree.

Establishment of leukemia cell model with inducible AML1-ETO expression and its effect on fatty acid metabolism in leukemia cells / 中华血液学杂志

Objective: To investigate the effect of the AML1-ETO (AE) fusion gene on the biological function of U937 leukemia cells by establishing a leukemia cell model that induces AE fusion gene expression. Methods: The doxycycline (Dox) -dependent expression of the AE fusion gene in the U937 cell line (U937-AE) were established using a lentivirus vector system. The Cell Counting Kit 8 methods, including the PI and sidanilide induction, were used to detect cell proliferation, cell cycle-induced differentiation assays, respectively. The effect of the AE fusion gene on the biological function of U937-AE cells was preliminarily explored using transcriptome sequencing and metabonomic sequencing. Results: ①The Dox-dependent Tet-on regulatory system was successfully constructed to regulate the stable AE fusion gene expression in U937-AE cells. ②Cell proliferation slowed down and the cell proliferation rate with AE expression (3.47±0.07) was lower than AE non-expression (3.86 ± 0.05) after inducing the AE fusion gene expression for 24 h (P<0.05). The proportion of cells in the G(0)/G(1) phase in the cell cycle increased, with AE expression [ (63.45±3.10) %) ] was higher than AE non-expression [ (41.36± 9.56) %] (P<0.05). The proportion of cells expressing CD13 and CD14 decreased with the expression of AE. The AE negative group is significantly higher than the AE positive group (P<0.05). ③The enrichment analysis of the transcriptome sequencing gene set revealed significantly enriched quiescence, nuclear factor kappa-light-chain-enhancer of activated B cells, interferon-α/γ, and other inflammatory response and immune regulation signals after AE expression. ④Disorder of fatty acid metabolism of U937-AE cells occurred under the influence of AE. The concentration of the medium and short-chain fatty acid acylcarnitine metabolites decreased in cells with AE expressing, propionyl L-carnitine, wherein those with AE expression (0.46±0.13) were lower than those with AE non-expression (1.00±0.27) (P<0.05). The metabolite concentration of some long-chain fatty acid acylcarnitine increased in cells with AE expressing tetradecanoyl carnitine, wherein those with AE expression (1.26±0.01) were higher than those with AE non-expression (1.00±0.05) (P<0.05) . Conclusion: This study successfully established a leukemia cell model that can induce AE expression. The AE expression blocked the cell cycle and inhibited cell differentiation. The gene sets related to the inflammatory reactions was significantly enriched in U937-AE cells that express AE, and fatty acid metabolism was disordered.

A resting-state functional MRI study on amplitude of low-frequency fluctuation and functional connectivity alteration of parkinson′s disease with apathy / 中华放射学杂志

Objective:To investigate the alterations of amplitude of low frequency fluctuation (ALFF) and functional connectivity (FC) in patients with Parkinson′s disease (PD) with apathy.Methods:From May 2016 to August 2019, PD patients and age-, gender-and education level-matched healthy controls (HC) in the First Affiliated Hospital of Nanjing Medical University were prospectively recruited. The clinical and resting-state functional MRI (rs-fMRI) data of PD patients and HC were analyzed. According to the Starkstein Apathy Scale (SAS) scores, PD patients were divided into PD with apathy (PD-A) group and PD without apathy (PD-NA) group. Rs-fMRI images were processed by DPABI based on MATLAB. ALFF values were calculated and the standard ALFF (zALFF) were obtained. ANOVA and Post-Hoc t test were performed to compare the differences in local brain activity among the three groups. The brain regions with significant different zALFF values were selected as the seeds to calculate the FC values of the whole brain. The associations between FC values and the SAS scores were performed using pearson correlation analyses. Results:A total of 75 PD patients (50 males, 25 females, aged from 44 to 88 years) and 41 HC (25 males, 16 females, aged from 54 to 72 years) were enrolled. There were 42 patients in the PD-A group and 33 patients in the PD-NA group. Significant differences were found in zALFF values among the PD-A, PD-NA and HC groups ( P<0.05). After Post-Hoc t test, compared with the HC group, zALFF values were significantly increased in the right middle frontal gyrus in the PD-A group ( P<0.05) and significantly decreased in the left precuneus in the PD-NA group; The zALFF values of the right middle frontal gyrus and left precuneus in the PD-A group were significantly higher than those in PD-NA group ( P<0.05). Brain regions with different zALFF values were used as seeds for whole-brain FC. Compared with PD-NA group, FC values between the right middle frontal gyrus and bilateral precuneus, left superior frontal gyrus and its medial side, left middle frontal gyrus, left angular, left anterior cingulate gyrus, left posterior cingulate gyrus, left parahippocampal gyrus were significantly decreased in the PD-A group ( P<0.05). Additionally, FC values of PD patients between the right middle frontal gyrus with the left precuneus, the left superior frontal gyrus and its medial side, and the left middle frontal gyrus were negatively correlated with SAS scores ( r=-0.31, -0.30 and -0.34, both P<0.05). Conclusion:PD-A and PD-NA patients have different brain functional activities and connections in the frontal lobe, parietal lobe and limbic system, suggesting that apathy in PD may be associated with the abnormal functional connections of the frontal-parietal cortical circuit and the frontal-limbic-striatal loop.

Triaging patients in the outbreak of COVID-2019 / 中国感染控制杂志

In the outbreak of COVID-19,triage procedures based on epidemiology were implemented in a local hospital in Changsha to control the transmission of SARS-CoV-2 and avoid healthcare-associated infection.This re-trospective study analyzed the data collected during the triage period and found that COVID-19 patients were en-riched 7 folds into the Section A designated for patients with obvious epidemiological history.On the other side,nearly triple amounts of visits were received at the Section B for patients without obvious epidemiological history.8 COVID-19 cases were spotted out of 247 suspected patients.More than 50％of the suspected patients were submi-tted to multiple rounds of nucleic acid analysis for SARS-CoV-2 infection.Of the 239 patients who were diagnosed as negative of the virus infection,188 were successfully revisited and none was reported as COVID-19 case.Of the 8 COVID-19 patients,3 were confirmed only after multiple rounds of nucleic acid analysis.Besides comorbidities,delayed sharing of epidemiological history added complexity to the diagnosis in practice.The triaging experience and strategy will be helpful for the control of infectious diseases in the future.

Oral mucosal drug delivery system based on nano technology / 药学学报

Oral mucosal drug delivery has the advantages of rapid drug absorption, no first-pass effect and good patient compliance. However, factors such as low drug dissolution, saliva carrying the drug into the gastrointestinal tract and the existence of physiological barriers in the mucosa may affect the mucosal permeation and bioavailability of the drug. Nanotechnology applied to drug oral mucosa delivery can overcome the above disadvantages and obtain efficient absorption effect. This paper describes the physiological structure of oral mucosa and the factors affecting the absorption of drugs in oral mucosa, reviews the application of nanotechnology such as liposomes, solid lipid nanoparticles, nanostructured lipid carriers, nanoemulsions, polymer nanoparticles, polymer micelles and nanohybrid suspensions in oral mucosal drug delivery and the mechanism of promoting drug absorption, summarizes the main problems of current research, and gives an outlook on the application of nano oral mucosal drug delivery system. The main problems of current research are summarized, and the prospects for the application of nano oral mucosal drug delivery systems are discussed.

Application progress on anti-skin aging effect of traditional Chinese medicine / 药学学报

With the aging of population intensifies and the level of population health have improved, thus much attention has been directed to how to delaying or preventing skin aging. Skin aging is associated with age, ultraviolet and lifestyle, mainly characterized as skin sagging, wrinkles, pigmentation, so it is urgent to seek traditional Chinese medicine and related cosmetics to solve the problem of skin aging. Traditional Chinese medicine has the functions of anti-oxidation, enhancing human immunity, promoting body metabolism and regulating endocrine, therefore, it has become a research focus in anti-skin aging. This article reviews the skin aging mechanism and the research advances of traditional Chinese medicine anti-skin aging, in order to provide a reference for future research and development of anti-aging traditional Chinese medicine.

Quality evaluation of Bupleuri Radix in Shanxi Province by LC-MS based pseudotargeted metabonomics / 药学学报

Bupleuri Radix is commonly used in the traditional Chinese medicine, and saikosaponins are the important active ingredients. In this study, we first established a relative quantitative method for 25 saikosaponins using ultra high performance liquid chromatography-triple quadrupole mass spectrometry (UHPLC-QTrap-MS) in the scheduled multiple reaction monitoring (sMRM) mode. The established method showed good intra-day and intra-day precision, linearity, repeatability and stability. Then the method was applied to compare 37 batches of Bupleuri Radix from different planting areas. The results showed that there was no significant difference in the saikosaponins composition of Bupleuri Radix from different planting areas in Shanxi Province, which indicating that Bupleuri Radix is well adapted to the environment, so it is suitable for widely planting. However, Bupleuri Radix harvested at spring and autumn were differed from those harvested at summer, which indicated that the traditional harvesting experience was reasonable. Correlation analysis showed that saikosaponins a and d were positively correlated with some saponins, and 4 saponins (such as clinoposaponin XII) showed bigger content variation were identified by coefficient of variation analysis. The LC-MS based pseudotargeted metabonomic method established in this study can be applied to the comprehensive detection of saikosaponins, which providing new method for the quality evaluation of Bupleuri Radix.

Mechanism of Dahuang Zhechongwan in Treating Myocardial Fibrosis of Rats via TGF-β1/Smads/miR29 Pathway / 中国实验方剂学杂志

ObjectiveTraditional Chinese medicine， namely Dahuang Zhechongwan （DHZCW） was used to treat myocardial fibrosis in model rats， observe its effect on myocardial fibrosis in rats， and explore its action mechanism. MethodThirty-six SPF male Kunming rats were divided into blank group， model group， low-， medium-， high-dose groups of DHZCW （0.056， 0.084， 0.168 g·kg-1）， captopril group （10 mg·kg-1）， with six rats in each group. Except for the blank group， the other groups were intraperitoneally injected isoproterenol solution of 5 mg·kg-1 for 15 consecutive days to replicate the myocardial fibrosis model. At the beginning of modeling， the rats in each group took drugs， and they were sacrificed 28 days after administration. Serum and heart tissue were collected for the corresponding detection. Hematoxylin-eosin （HE） staining and Masson staining were used to observe tissue inflammation， cellular degeneration， necrosis， and fibrosis. The contents of hydroxyproline （HYP）， tumor necrosis factor-α （TNF-α）， interleukin-1β （IL-1β）， interleukin-6 （IL-6）， hyaluronic acid （HA）， laminin （LN）， type-Ⅲ procollagen （PC Ⅲ） in serum of rats and rats were determined by enzyme-related immunosorbent assay （ELISA）. The expression levels of key pathway proteins transforming growth factor-β1 （TGF-β1）， α-smooth muscle actin （α-SMA）， Smad2， Smad3， and Smad7 were detected by Western blot. The expression levels of key pathway genes TGF-β1， α-SMA， Smad2， Smad3， Smad7， miR-29a-5p， miR-29b-2-5p， and miR-29c-5p were detected by Real-time quantitative polymerase chain reaction （Real-time PCR）. ResultCompared with the blank group， the pathological changes of fibrosis in the model group were obvious， the contents of serum HYP， TNF-α， IL-1β， IL-6， HA， LN， and PCⅢ were increased （P<0.01）， the protein expression levels of TGF-β1， α-SMA， Smad2， and Smad3 were increased； the protein expression level of Smad7 was decreased （P<0.01）. The mRNA expression levels of TGF-β1， α-SMA， Smad2， and Smad3 were increased （P<0.05， P<0.01）， while those of Smad7， miR-29a-5p， miR-29b-2-5p， and miR-29c-5p were decreased （P<0.01）. Compared with the model group， after 28 days of administration， serum HYP， TNF-α， IL-1β， IL-6， HA， LN， and PCⅢ in high-， medium-， and low-dose groups of DHZCW and captopril groups were decreased （P<0.01）. Except for the low-dose group， the protein contents of TGF-β1， α-SMA， Smad2， and Smad3 were decreased， while the protein content of Smad7 was increased （P<0.01）. The mRNA expression levels of TGF-β1， Smad2， α-SMA， and Smad3 in high-dose group of DHZCW were decreased （P<0.05，P<0.01）， while those of Smad7， miR-29a-5p， miR-29b-2-5p， and miR-29c-5p were increased （P<0.05）. The mRNA expressions of TGF-β1， Smad2， and Smad3 in the medium-dose group of DHZCW were decreased （P<0.05， P<0.01）， while mRNA expression of Smad7 was increased （P<0.01）. The mRNA levels of TGF-β1 and Smad2 in the low-dose group of DHZCW were decreased （P<0.01）. ConclusionDHZCW can improve myocardial fibrosis in rats， and its action mechanism may be related to the regulation of the TGF-β1/Smads/miR-29 pathway. In addition， there is dose dependence in the range of 0.056-0.168 g·kg-1， and the effect of the high-dose group is more stable.

Efficacy and safety of tenecteplase in the treatment of acute ischemic stroke：a meta-analysis / 中国药房

OBJECTIVE To systematically evaluate the efficacy and safety of intravenous bolus of tenecteplase in the treatment of acute ischemic stroke （AIS）， in order to provide evidence-based support for the clinic’s choice of intravenous thrombolytic drugs. METHODS Randomized controlled trials （RCTs） about the efficacy and safety of tenecteplase versus alteplase （control） in the treatment of AIS were collected from PubMed， Embase， the Cochrane Library， Web of Science， Sinomed， CNKI， Wanfang Data， and VIP during the inception to June 2022. Two evaluators independently screened the literature， extracted data from the literature， assessed the bias risk of included study， and then conduct meta-analysis by using Stata 15 software. RESULTS A total of 8 literature were included， involving 2 129 patients. Meta-analysis results showed that the early improvement rate of neurological function [OR（95%CI）＝2.44（1.09，5.46），P＝0.030] and the good rate of neurological function recovery （modified Rankin scale score 0-2 after 90 days of intravenous thrombolysis treatment） [OR（95%CI）＝1.54（1.00，2.36），P＝0.048] were higher in 0.25 mg/kg tenecteplase group （medium dose） than alteplase group. According to meta-analysis of other outcome indicators （including recanalization rate， percentage of reperfusion lesions， excellent rate of neurological function recovery， the incidence rate of bleeding， the incidence rate of symptomatic intraventricular hemorrhage and all-cause mortality rate within 90 d）， the tenecteplase group had no statistically significant difference with alteplase group （P＞0.05）. CONCLUSIONS Compared with alteplase， medium dose of tenecteplase has some advantages in terms of early neurological function improvement and neurological function recovery， and it does not increase the risk of adverse events.

Evaluation of macular microvasculature alterations in patients with proliferative diabetic retinopathy after vitrectomy by swept-source optical coherence tomography angiography / 国际眼科杂志(Guoji Yanke Zazhi)

AIM: To investigate the changes in retinal and choroidal blood flow after pars plana vitrectomy(PPV)for proliferative diabetic retinopathy(PDR).METHODS: A cross-sectional study was conducted on 35 patients(35 eyes)who were diagnosed as monocular PDR and received 23GPPV in ophthalmology department of the Second People's Hospital of Hefei between September 2020 and July 2022. All eyes underwent swept-source optical coherence tomography angiography(SS-OCTA)examination. Retinal and choroidal vascular parameters within 3mm×3mm of macular zone were measured by built-in analyzer, and its correlation with postoperative best corrected visual acuity(BCVA)was analyzed.RESULTS: The follow-up was 1～22(average 9.72±6.67)mo. At the last follow-up, flow area(FA)of intermediate capillary plexus(ICP)layer in paranasal foveal region was significantly reduced in PPV eyes(0.31±0.06mm2)compared with contralateral eyes(0.38±0.05mm2), and FA of deep capillary plexus(DCP)in temporal foveal region was significantly lower in PPV eyes(0.19±0.08mm2)than contralateral eyes(0.27±0.07mm2; all P&#x003C;0.05). Choroidal vascularity index(CVI)were lower in PPV eyes than contralateral eyes in parafoveal subregions except temporal region(P&#x003C;0.05). After PPV, BCVA had a certain correlation with the density and FA of middle and deep retinal vessels.CONCLUSIONS: Eyes with severe PDR may be prone to having a decrease in the DCP and parafoveal choroidal perfusion in the parafoveal regions after PPV than contralateral eyes.

Impeding the combination of astrocytic ASCT2 and NLRP3 by talniflumate alleviates neuroinflammation in experimental models of Parkinson's disease

Alanine-serine-cysteine transporter 2 (ASCT2) is reported to participate in the progression of tumors and metabolic diseases. It is also considered to play a crucial role in the glutamate-glutamine shuttle of neuroglial network. However, it remains unclear the involvement of ASCT2 in neurological diseases such as Parkinson's disease (PD). In this study, we demonstrated that high expression of ASCT2 in the plasma samples of PD patients and the midbrain of MPTP mouse models is positively correlated with dyskinesia. We further illustrated that ASCT2 expressed in astrocytes rather than neurons significantly upregulated in response to either MPP+ or LPS/ATP challenge. Genetic ablation of astrocytic ASCT2 alleviated the neuroinflammation and rescued dopaminergic (DA) neuron damage in PD models in vitro and in vivo. Notably, the binding of ASCT2 to NLRP3 aggravates astrocytic inflammasome-triggered neuroinflammation. Then a panel of 2513 FDA-approved drugs were performed via virtual molecular screening based on the target ASCT2 and we succeed in getting the drug talniflumate. It is validated talniflumate impedes astrocytic inflammation and prevents degeneration of DA neurons in PD models. Collectively, these findings reveal the role of astrocytic ASCT2 in the pathogenesis of PD, broaden the therapeutic strategy and provide a promising candidate drug for PD treatment.

Insights into the biosynthesis of septacidin l-heptosamine moiety unveils a VOC family sugar epimerase

l-Heptopyranoses are important components of bacterial polysaccharides and biological active secondary metabolites like septacidin (SEP), which represents a group of nucleoside antibiotics with antitumor, antifungal, and pain-relief activities. However, little is known about the formation mechanisms of those l-heptose moieties. In this study, we deciphered the biosynthetic pathway of the l,l-gluco-heptosamine moiety in SEPs by functional characterizing four genes and proposed that SepI initiates the process by oxidizing the 4'-hydroxyl of l-glycero-α-d-manno-heptose moiety of SEP-328 ( 2) to a keto group. Subsequently, SepJ (C5 epimerase) and SepA (C3 epimerase) shape the 4'-keto-l-heptopyranose moiety by sequential epimerization reactions. At the last step, an aminotransferase SepG installs the 4'-amino group of the l,l-gluco-heptosamine moiety to generate SEP-327 ( 3). An interesting phenomenon is that the SEP intermediates with 4'-keto-l-heptopyranose moieties exist as special bicyclic sugars with hemiacetal-hemiketal structures. Notably, l-pyranose is usually converted from d-pyranose by bifunctional C3/C5 epimerase. SepA is an unprecedented monofunctional l-pyranose C3 epimerase. Further in silico and experimental studies revealed that it represents an overlooked metal dependent-sugar epimerase family bearing vicinal oxygen chelate (VOC) architecture.

Nomogram based on clinical, ultrasonic and BRAF V600E gene for predicting cervical lymph node metastasis in patients with papillary thyroid carcinoma / 中国医师进修杂志

Objective:To Constructing a nomogram based on clinical, ultrasound and BRAF V600E gene for predicting cervical lymph node metastasis in patients with papillary thyroid carcinoma (PTC).Methods:The clinical data of 287 patients with PTC (374 malignant nodules) from December 2019 to December 2021 in the First Affiliated Hospital of Hunan Normal University were analyzed retrospectively. Among them, there were 205 nodes with cervical lymph node metastasis and 169 nodes without cervical lymph node metastasis. The echo type, capsule, boundary, shape, number, diameter, location, cystic and solid properties, aspect ratio, blood flow signal, echo distribution, ultrasonic classification, microcalcification and enlarged lymph nodes were observed by ultrasound. The mutation of BRAF V600E gene was detected by fluorescence polymerase chain reaction. The nomograph model for predicting neck lymph node metastasis in patients with PTC was constructed and validated by R3.6.3 software.Results:Univariate analysis result showed that gender, age, microcalcifications, aspect ratio, morphology, blood flow signal, diameter, echo distribution, enlarged lymph nodes, ultrasound classification and BRAF V600E gene were the risk factors for cervical lymph node metastasis in patients with PTC ( P<0.05 or <0.01). Multivariate Logistic regression analysis result showed that age (<40 years old), ultrasonic classification (≥4a) and diameter (>1 cm) were independent risk factors for cervical lymph node metastasis in patients with PTC ( OR = 2.847, 1.436 and 2.475; 95% CI 1.827 to 4.436, 1.075 to 1.918 and 1.505 to 4.069; P<0.01 or <0.05). The age, ultrasonic classification and diameter were included as predictors for constructing the nomogram model. The receiver operating characteristic curve analysis result shows that the area under the curve predicted by the nomogram model for neck lymph node metastasis in patients with PTC was 0.692 (95% CI 0.631 to 0.753). Conclusions:Nomogram based on age, ultrasonic classification and diameter is of high value in predicting neck lymph node metastasis in patients with PTC.

Inhibitory effect of long non-coding RNA Neat1 on ultraviolet B-induced pyroptosis of human lens epithelial cells and its mechanism / 中华实验眼科杂志

Objective:To investigate the role of long non-coding RNA nuclear paraspeckle assembly transcript 1 (Neat1) in pyroptosis of ultraviolet B (UVB)-induced human lens epithelial cells (LECs) and to explore the possible mechanism.Methods:The human lens epithelial cell line HLE-B3 was cultured in vitro, and cells at log phase were exposed to ultraviolet B for 0, 2, 4 and 8 hours, respectively.The expression of cysteine aspartic acid-specific protease-1 (caspase-1), a protein related to pyroptosis, was detected by Western blot.The relative expression level of Neat1 in cells after different irradiation durations was determined by real-time quantitative PCR.Cell viability was determined by the cell counting kit-8 (CCK-8) method to screen the optimal irradiation duration for UVB-induced LECs pyroptosis, which was finally determined to be 4 hours.HLE-B3 cells were divided into negative siRNA transfection group, siRNA Neat1 transfection group, negative siRNA transfection+ irradiation group and siRNA Neat1 transfection+ irradiation group, and were transfected with corresponding reagents for 24 hours.The negative siRNA transfection+ irradiation group and siRNA Neat1 transfection+ irradiation group were irradiated with UVB for 4 hours after transfection.The cell viability was detected by the CCK-8 method.The pyroptosis rate was detected by flow cytometry.The expression levels of caspase-1, gasdermin D (GSDMD) and nod-like receptor protein 3 (NLRP3) proteins were detected by Western blot.The concentration of interleukin (IL)-1β was detected by enzyme-linked immunosorbent assay (ELISA). Ultrastructural changes in HLE-B3 cells were observed under a transmission electron microscope. Results:The grayscale of caspase-1 protein bands increased with the extension of irradiation duration.The relative expression levels of caspase-1 protein at 0, 2, 4 and 8 hours of irradiation were 0.05±0.01, 0.25±0.07, 0.51±0.04 and 0.74±0.02, respectively, with a statistically significant overall difference ( F=168.223, P<0.001), and significant differences were found in paired comparisons (all at P<0.05). With prolonged irradiation, the relative expression level of Neat1 mRNA increased and the cell viability decreased, with statistically significant differences in paired comparisons (all at P<0.05). Compared with negative siRNA transfection group, the cell viability was increased in siRNA Neat1 transfection group and decreased in negative siRNA transfection+ irradiation group, with statistically significant differences (both at P<0.01). Compared with negative siRNA transfection+ irradiation group, the cell viability was increased in siRNA Neat1 transfection+ irradiation group, showing a statistically significant difference ( P<0.05). The pyroptosis rate was significantly lower in negative siRNA transfection group and siRNA Neat1 transfection+ irradiation group than in negative siRNA transfection+ irradiation group, and the differences were statistically significant (both at P<0.01). The relative expression levels of caspase-1, NLRP3 and GSDMD proteins in negative siRNA transfection+ irradiation group were higher than those in negative siRNA transfection group and siRNA Neat1 transfection+ irradiation group and the differences were statistically significant (all at P<0.01). The concentration of IL-1β was significantly higher in negative siRNA transfection+ irradiation group than in negative siRNA transfection group and siRNA Neat1 transfection+ irradiation group, and the differences were statistically significant (all at P<0.05). Cell swelling, formed cell membrane pores, vacuolated cells and fuzzy mitochondrial cristae were seen in negative siRNA transfection+ irradiation group and siRNA Neat1 transfection+ irradiation group by transmission electron microscopy.Compared with negative siRNA transfection+ irradiation group, slighter cell swelling, fewer cell membrane pores and lighter mitochondrial swelling were seen in siRNA Neat1 transfection+ irradiation group. Conclusions:Neat1 is involved in human LECs pyroptosis induced by UVB through the classic pyroptosis pathway mediated by caspase-1.Knockdown of Neat1 can inhibit the pyroptosis of human LECs.

Application of blood purification technology in children with acute and critical diseases / 中国小儿急救医学

Objective:To explore the scope, mode, anticoagulation mode and complications of blood purification in children with acute and critical illness.Methods:A total of 377 times of treatment of 102 children treated with blood purification in PICU at the First Affiliated Hospital of Xinxiang Medical College from January 2018 to December 2020 were retrospectively analyzed.Results:Among 102 critically ill children treated with blood purification, acute and chronic renal failure ranked the first in terms of disease distribution, with 23 cases in total, followed by 16 cases of severe viral encephalitis (meningoencephalitis), 11 cases of septic shock, seven cases of acute poisoning, five cases of severe allergic purpura, five cases of necrotic encephalopathy.In terms of clinical prognosis, 51(50.0%) cases were cured, 29(28.4%) cases were improved, 10(9.8%) cases died, and 12 cases abandoned treatment.In 2019, the blood purification application frequency was the highest, with a total of 47 cases, which was higher than those in 2018 and 2020( P<0.05). Continuous veno-venous hemofiltration was used in the largest number of children, with a total of 56 cases.There was a statistically significant difference in the application ratio of this mode during 3 years ( P<0.05), while there was no statistically significant difference in the application ratio of other modes.In terms of the selection of anticoagulation methods, the proportions of systemic anticoagulation and extracorporeal anticoagulation had significantly difference among different years( P<0.05), and the application of extracorporeal anticoagulation had increased year by year.There was no statistically significant difference in the proportion of patients without anticoagulants.The incidence of complications of blood purification was the highest in 2019, with catheter related thrombus in the majority (30 person-times), followed by hypothermia, catheter filter coagulation, hematoma formation, catheter related infection, hypotension, heparin-induced thrombocytopenia, etc.There was statistically significant difference in the total complications among different years( P<0.05). Conclusion:Blood purification is widely used in children with acute and critical illness, with a variety of diseases.The most commonly used mode is continuous veno-venous hemofiltration and in vitro anticoagulation.Catheter-related thrombosis is the most common complication.

The mediating effect of self-care on the relationship between stress response and job performance of nurses in emergency department / 中国实用护理杂志

Objective:To investigate the status quo of stress response, self-care and job performance among nurses in emergency department, and to analyze whether self-care has a mediating effect between stress response and job performance.Methods:This was a cross-sectional survey. From February to April 2022, 467 emergency department nurses from 11 tertiary hospitals in Changsha were investigated and analyzed by using random cluster sampling method, general data questionnaire, Stress Response Questionnaire, Self-Compassion Scale and Nursing Performance Scale.Results:The total score of nurses′ Stress Response Questionnaire was (78.02 ± 26.78) points, the total score of Self-Compassion Scale was (81.75 ± 22.23) points, and the total score of Nursing Performance Scale was (74.05 ± 21.57) points. Stress response was negatively correlated with self-care and work performance ( r=-0.452, -0.572, both P<0.01), and self-care was positively correlated with work performance ( r=0.515, P<0.01). Self-care played a partial mediating role between stress response and job performance, accounting for 26.98% of the total effect. Conclusions:Self-care is an intermediary variable between emergency department nurses′ stress response and work performance. Nursing managers should pay attention to emergency department nurses′self-care and stress response levels, and evaluate them regularly in order to take timely intervention measures to improve their self care ability, reduce stress response, and improve work performance of emergency department nurses.

The role of Huaiqihuang Granules in the long-term management of bronchial asthma in young children: a multicenter real-world study / 中华实用儿科临床杂志

Objective:To observe the role of Huaiqihuang Granules (HQ) in the long-term management of bronchial asthma in young children, and the effective effect on concomitant rhinitis.Methods:A prospective real-world multicenter study was conducted in children aged 2-5 years with asthma diagnosed in the outpatient department (from April 2016 to March 2019)who received either inhaled corticosteroid (ICS)/leukotriene receptor antagonist (LTRA)(control group); inhaled ICS/LTRA plus HQ(combination group), or HQ alone(HQ group). All patients were followed up at week 4, 8, 12 after treatment. The number of days with asthma symptoms, the frequency of severe asthma attacks, the level of asthma control, and the days with rhinitis symptoms in the last 4 weeks were recorded. Differences before and after treatment, and those among groups after treatment were compared using Kruskal- Wallis H test or Wilcoxon rank-sum test. Results:A total of 2 234 eligible patients were recruited, and 2 147 cases completed followed-up visits, including 477, 1 374 and 296 cases in the control group, combination group, and HQ group, respectively. After the treatment, all 3 groups showed significant declines in the days with asthma symptoms, frequency of severe asthma attack and the days with rhinitis symptoms (all P<0.01), and the rate of well-controlled asthma increased significantly ( P<0.01). It lasted until the end of follow-up. Among groups, patients in the combination group showed significantly less days of asthma symptoms than those of the other 2 group at week 8 and 12[0(0, 0.9) d vs.0(0, 0.3) d, P<0.05; 0(0, 0.1) d vs. 0(0, 1.0) d, P<0.01]. Patients in the combination group and HQ group showed a significantly lower rate of severe asthma attacks than that of the control group at week 12 [0(0, 1), 0(0, 1), 0(0, 2), all P<0.05]. The well-controlled rate of asthma in the combination group was significantly higher than that of the control group and HQ group at week 8 and 12 (89.6% vs. 85.9% vs.82.1%, H=15.28; 90.9% vs. 84.1% vs. 81.8%, χ2=29.32, all P<0.01). Conclusions:HQ can significantly alleviate symptoms of asthma and rhinitis, severe attack of asthma, and increase the control rate of asthma when used as an additional treatment or used alone.

Expression of HLA-G in the peripheral blood and cancerous tissues of patients with papillary thyroid cancer / 中华内分泌外科杂志

Objective:To examine the expression of human leukocyte antigen G (HLA-G) in the peripheral blood and cancerous tissues of patients with papillary thyroid carcinoma (PTC) .Methods:The expression of soluble HLA-G (sHLA-G) in the peripheral blood of 50 individuals with PTC (PTC group) , 25 patients with benign thyroid tumors (BTT group) from Department of Thyroid and Breast Surgery, Beilun branch of the First Affiliated Hospital of Zhejiang University and 20 healthy controls (healthy control group) from physical examination center was assessed by ELISA. Immunohistochemical examination of HLA-G levels was also performed on tissue specimens from patients in the PTC and BTT groups, and their correlation with clinicopathological features of thyroid cancer was analyzed. SPSS 19.0 was used for statistical analysis. The measurement data of normal distribution were tested by two independent samples t test. Chi square test was used to compare the rates between the two groups. Results:The sHLA-G expression in peripheral blood was 21.33 (±5.54) , 22.73 (±4.99) , and 18.29 (±4.43) ng/mL in the preoperative PTC, BTT, and healthy control groups, respectively. Compared to the healthy group, sHLA-G levels were considerably higher in the PTC and BTT groups, with statistically significant differences (totally P < 0.05) . There was no significant difference in statistically sHLA-G levels between the BTT and PTC groups ( P > 0.05) . The positive HLA-G expression rate in PTC tissues was 78% (39/50) . There was no evidence of HLA-G expression in common tissues adjacent to PTC. HLA-G was not expressed in benign tumors. HLA-G was linked with the PTC tumor diameter, and the rate of positive expression was considerably greater with tumor diameters >1 cm than with those ≤1 cm ( P<0.05) . The rate of HLA-G positive expression was not significantly correlated with sex, age, multiple foci, extra-glandular invasion, metastasis of lymph nodes, or the TNM stage in PTC individuals ( P > 0.05) . Conclusions:HLA-G is significantly expressed at high levels in PTC tissues, is correlated with the tumor diameter, and may probably have a significant role in this disease. Peripheral blood sHLA-G may be associated with thyroid tumorigenesis, and its value in PTC requires further verification.

Role of TXNIP/NLRP3 pathway in renal interstitial fibrosis after renal ischemia-reperfusion injury / 中华急诊医学杂志

Objective:To explore the role of thioredoxin interaction protein (TXNIP)/NOD-like receptor protein 3 (NLRP3) pathway in renal interstitial fibrosis induced by renal ischemia-reperfusion injury (IRI) in mice.Methods:Adult male C57BL/6J mice aged 6 to 8 weeks and TXNIP knockout mice with the same genetic background were selected. The wild type mice were divided into the sham operation (Sham) group and renal IRI group. The TXNIP knockout mice were divided into the sham+TXNIP KO group and IRI+TXNIP KO group, with 12 mice in each group. The model of renal ischemia-reperfusion injury was established by clamping bilateral renal pedicles for 45 min and then restoring perfusion. The sham operation model was only dissociated bilateral renal arteries without other treatment. Blood creatinine, urea nitrogen, kidney injury molecule-1 (Kim-1) and neutrophil gelatinase-associated lipocalin (NGAL), blood transforming growth factor-β (TGF-β) and interleukin 6 (IL-6) were measured on the 1st, 7th and 28th days after reperfusion. The renal cortex was taken on the 1st and 28th days for Masson staining, in which the renal tubule-interstitial injury score was obtained. TGF-β and IL-6 mRNA expression were detected by qPCR, TXNIP, NLRP3, Pro-IL-1β, IL-1β and α-SMA protein expression were detected by Western blot, and MDA and SOD levels were detected by ELISA. Homogeneity test of variance was performed before the statistics of normal distribution measurement data, one-way ANOVA was used for the comparison between multiple groups, and LSD- t test was used for the comparison between the two groups. Results:On the 1st, 7th and 28th days after IRI, compared with the sham group, the Scr, BUN, Kim-1, NGAL, TGF-β and IL-6 were increased continuously in the IRI group ( P<0.05). On the 28th day after IRI, large areas of collagen fibers and inflammatory cell infiltration were observed in the renal interstitium of the IRI group. In the IRI group, the scores of renal tubular injury and renal interstitial fibrosis on the 28th day were significantly higher than those on the 1st day (all P<0.05). On the 1st, 7th and 28th days after IRI, compared with the IRI group, the levels of Scr, BUN, Kim-1, NGAL, TGF-β and IL-6 were significantly decreased in the IRI+TXNIP KO group (all P<0.05). On the 1st and 28th days after IRI, compared to the IRI group, the areas of collagen fibers and inflammatory cell infiltration in the renal interstitium of the IRI+TXNIP KO group were decreased. The renal tubule injury score [Day 1, (192.2 ± 62.4) vs. (103.2 ± 49.1); Day 28, (154.3 ± 93.6) vs. (64.3 ± 24.8), both P<0.05] and interstitial fibrosis score [Day 1, (7.3 ± 3.2) vs. (4.8 ± 1.7); Day 28, (12.8 ± 3.9) vs. (2.3 ± 0.8), both P<0.05] were all decreased. The expression of TGF-β, IL-6 mRNA, TXNIP, NLRP3, Pro-IL-1 β, IL-1 β and α-SMA protein in renal cortex were significantly decreased (both P<0.05). In renal cortex, MDA level was decreased and SOD level was increased (all P<0.05). Conclusions:TXNIP/NLRP3 pathway is involved in the development of renal interstitial inflammation and fibrosis after renal ischemia and reperfusion. Knockout or inhibition of TXNIP can inhibit the progression of acute renal injury to chronic renal disease.