Transdermal delivery of iguratimod and colchicine ethosome by dissolving microneedle patch for the treatment of recurrent gout.

This study introduces a novel approach of repetitive modeling to simulate the pathological process of recurrent gout attacks in humans. This methodology addresses the instability issues present in rat models of gout, providing a more accurate representation of the damage recurrent gout episodes inflict on human skeletal systems. A soluble nanoneedle system encapsulating colchicine and iguratimod ethosomal formulations was developed. This system aims to modulate inflammatory cytokines and inhibit osteoclast activity, thereby treating inflammatory pain and bone damage associated with recurrent gout. Additionally, a comprehensive evaluation of the microneedles' appearance, morphology, mechanical properties, and penetration capability confirmed their effectiveness in penetrating the stratum corneum. Dissolution tests and skin irritation assessments demonstrated that these microneedles dissolve rapidly without irritating the skin. In vitro permeation studies indicated that transdermal drug delivery via these microneedles is more efficient and incurs lower drug loss compared to traditional topical applications. In vivo pharmacodynamic assessments conducted in animal models revealed significant analgesic and anti-inflammatory effects when both types of microneedles were used together. Further analyses, including X-ray imaging, hematoxylin and eosin (H&E) staining, Safranin-O/fast green staining, tartrate-resistant acid phosphatase staining, and quantification of osteoclasts, confirmed the bone-protective effects of the microneedle combination. In conclusion, the findings of this research underscore the potential of this novel therapeutic approach for clinical application in the treatment of recurrent gout.

Spontaneous splenic rupture as the initial symptom of splenic angiosarcoma: case report and literature review.

Spontaneous splenic rupture is an extremely rare occurrence, often attributed to tumorous pathologies. Among these, primary splenic angiosarcoma stands as a malignancy arising from the endothelial cells within the spleen. While sporadic cases have been reported globally, there remains a lack of comprehensive consensus on standardized approaches for diagnosis and treatment. We report a case of an 83-year-old male who underwent emergency enhanced CT due to sudden shock, revealing significant intra-abdominal fluid accumulation. Emergency surgery revealed splenic rupture necessitating splenectomy. Histopathological examination confirmed the diagnosis of splenic angiosarcoma. Despite successful surgery, the patient succumbed to severe complications two weeks postoperatively.

Fast Organic Cation Exchange in Colloidal Perovskite Quantum Dots toward Functional Optoelectronic Applications.

Colloidal quantum dots with lower surface ligand density are desired for preparing the active layer for photovoltaic, lighting, and other potential optoelectronic applications. In emerging perovskite quantum dots (PQDs), the diffusion of cations is thought to have a high energy barrier, relative to that of halide anions. Herein, we investigate the fast cross cation exchange approach in colloidal lead triiodide PQDs containing methylammonium (MA+) and formamidinium (FA+) organic cations, which exhibits a significantly lower exchange barrier than inorganic cesium (Cs+)-FA+ and Cs+-MA+ systems. First-principles calculations further suggest that the fast internal cation diffusion arises due to a lowering in structural distortions and the consequent decline in attractive cation-cation and cation-anion interactions in the presence of organic cation vacancies in mixed MA+-FA+ PQDs. Combining both experimental and theoretical evidence, we propose a vacancy-assisted exchange model to understand the impact of structural features and intermolecular interaction in PQDs with fewer surface ligands. Finally, for a realistic outcome, the as-prepared mixed-cation PQDs display better photostability and can be directly applied for one-step coated photovoltaic and photodetector devices, achieving a high photovoltaic efficiency of 15.05% using MA0.5FA0.5PbI3 PQDs and more precisely tunable detective spectral response from visible to near-infrared regions.

Influence of Modified Shashen Maidong Decoction Combined with Camrelizumab Immunotherapy Plus Chemotherapy on the Efficacy,Survival Status,and Serum CYFRA21-1 and NSE Levels in Patients with Advanced Non-Small Cell Lung Cancer / 广州中医药大学学报

Objective To investigate the influence of modified Shashen Maidong Decoction combined with Camrelizumab immunotherapy plus chemotherapy on the efficacy,survival status and serum cytokeratin 19 fragment(CYFRA21-1)and neuron-specific enolase(NSE)levels in patients with advanced non-small cell lung cancer(NSCLC).Methods Forty patients with advanced NSCLC of lung-stomach yin deficiency with intense heat-toxin type were randomly divided into a control group and a study group,with 20 patients in each group.The patients in the control group were given Camrelizumab immunotherapy plus chemotherapy,and the patients in the study group were given modified Shashen Maidong Decoction combined with Camrelizumab immunotherapy plus chemotherapy,with 21 days as a course of treatment and for a total of 4 courses of treatment.The changes of serum NSE and CYFRA21-1 levels in the two groups before and after treatment were observed,and the clinical efficacy,survival status and the incidence of toxic and side effects were compared between the two groups.Results(1)After 4 courses of treatment,the total effective rate of the study group was 70.00%(14/20),which was significantly higher than that of the control group(9/20,45.00%),but the intergroup comparison(tested by chi-square test)showed that the difference was not statistically significant(P＞0.05).(2)After 2 years of follow-up,the overall survival(OS),time to progression(TTP),and progression-free survival(PFS)of the patients in the study group were significantly prolonged compared with those in the control group(P＜0.01).(3)After treatment,the serum NSE and CYFRA21-1 levels of the patients in the two groups were decreased compared with those before treatment(P＜0.05),and the decrease of serum NSE and CYFRA21-1 levels in the study group was significantly superior to that in the control group(P＜0.01).(4)The incidence of toxic and side effects in the study group was 25.00%(5/20),which was significantly lower than that of 65.00%(13/20)in the control group,and the intergroup comparison showed that the difference was statistically significant(P＜0.05).Conclusion Modified Shashen Maidong Decoction combined with Camrelizumab immunotherapy plus chemotherapy has satisfactory therapeutic effect on patients with advanced NSCLC,which can reduce the toxic and side effects of chemotherapy,lower the level of serum tumor markers,and prolong the survival period and time to progression(TTP)of the patients.

Preliminary construction of a measurement tool for atrial fibrillation patient's experience of catheter ablation / 复旦学报（医学版）

Objective To construct a measurement tool for atrial fibrillation(AF)patients'experience of catheter ablation,in order to provide quantifiable basis for improving the patients'perioperative experience.Methods From Jun 2022 to Apr 2023,literature analysis,qualitative research,Delphi expert consultation,and analytic hierarchy process were used to determine the content and weight of various indicators of the measurement tool.Results The enthusiasm of experts in 3 rounds was 100%.The authority coefficient of experts was 0.946,0.961 and 0.976.The Kendal harmony coefficients of the 2 and 3 rounds of expert consultation was 0.130 and 0.370(P＜0.001).The final measurement tool included 46 items and 5 dimensions,including operational and technical quality experience,comfort management experience,information and communication experience,emotional support experience,service process and response experience.Conclusion The preliminary construction of measurement tool for AF patients'experience of catheter ablation,which were based on the features of specialty,could not only evaluate the patients'experience accurately,but also provide a basis for targeted improvement of medical and nursing service quality.

Establishment and validation of a prediction model of hip fracture risk factors in elderly stroke patients / 中国组织工程研究

BACKGROUND:Prevention of fractures after stroke is very important,and there are currently no models to predict the occurrence of hip fractures after stroke. OBJECTIVE:To investigate the risk factors leading to hip fracture in stroke patients and to establish a risk prediction model to visualize this risk. METHODS:A total of 439 stroke patients were selected from the Affiliated Hospital of Xuzhou Medical University from June 2014 to June 2017,including 107 males and 332 females,with a mean age of(71.38±9.74)years.They were divided into fracture group(n=35)and non-fracture group(n=404)according to the presence or absence of hip fracture.Univariate and multivariate analyses were used to determine the risk factors for hip fracture after stroke.The data were randomly divided into training set(70%)and test set(30%).Nomogram predicting the risk of hip fracture occurrence was created based on the results of the multifactor analysis,and performance was evaluated using receiver operating characteristic curve,calibration curves,and decision curve analysis.A web calculator was created to facilitate a more convenient interactive experience for clinicians. RESULTS AND CONCLUSION:(1)Univariate analysis showed significant differences between the two groups in the number of falls,smoking,hypertension,glucocorticoids,number of strokes,Mini-Mental State Examination,visual acuity level,National Institute of Health Stroke Scale,Berg Balance Scale,and Stop Walking When Talking scale scores(P<0.05).(2)Multivariate analysis showed that number of falls[OR=17.104,95%CI(3.727-78.489),P=0.000],National Institute of Health Stroke Scale[OR=1.565,95%CI(1.193-2.052),P=0.001],Stop Walking When Talking[OR=12.080,95%CI(2.398-60.851),P=0.003]were independent risk factors positively associated with new hip fractures.Bone mineral density[OR=0.155,95%CI(0.044-0.546),P=0.012]and Berg Balance Scale[OR=0.840,95%CI(0.739-0.954),P=0.007]were negatively associated with new hip fractures after stroke.(3)The AUC values of nomogram were 0.956 and 0.907 in the training and test sets,respectively,and the calibration curves showed a high agreement between predicted and actual status with an area under the decision curve of 0.038 and 0.030,respectively.(4)These findings conclude that the number of falls,low bone mineral density,low Berg Balance Scale score,high National Institute of Health Stroke Scale score,and positive Stop Walking When Talking are risk factors for hip fracture after stroke.Based on this,a nomogram with high accuracy was developed and a web calculator(https://stroke.shinyapps.io/DynNomapp/)was created.

Effects of l-tetrahydropalmatine on different stages of conditioned place preference in ketamine dependent rats and the mechanism of DA / 中国法医学杂志

Objective To observe the effects of Levo-tetrahydropalmatine(l-THP)on the expression,regression and relapse of conditioned place preference(CPP)in ketamine induced rats,and to detect the content of dopamine(DA)in the striatum(caudate putamen,CPu)of the rat brain at different time points.Methods Ketamine addiction rat model was established by CPP.The effects of l-THP on the expression,regression and relapse of ketamine induced rat CPP were investigated using CPP score as the index.The content of DA in CPu of rats was determined by ultra-performance liquid chromatography coupled to tandem mass spectrometry(UPLC-MS/MS)after ketamine administration and l-THP intervention at 30 min,60 min,90 min,120 min and 150 min.Results It indicated that 1-THP could decrease the expression of CPP in ketamine induced rats,promote the process of CPP resolution and inhibit the process of relapse.In addition,l-THP combined with ketamine administration significantly inhibited the ketamine-induced increase in DA content in the CPu of the rats.Conclusion The mechanism of l-THP inhibiting the reward effect of ketamine may be related to blocking DA receptors and reducing the release of DA neurotransmitters.l-THP has potential implications for the treatment of ketamine addiction.

Accelerating GW Calculations of Point Defects with the Defect-Patched Screening Approximation.

The GW approximation has been widely accepted as an ab initio tool for calculating defect levels with the many-electron effect included. However, the GW simulation cost increases dramatically with the system size, and unfortunately, large supercells are often required to model low-density defects that are experimentally relevant. In this work, we propose to accelerate GW calculations of point defects by reducing the simulation cost of many-electron screening, which is the primary computational bottleneck. The random-phase approximation of many-electron screening is divided into two parts: one is the intrinsic screening, calculated using a unit cell of pristine structures, and the other is the defect-induced screening, calculated using the supercell within a small energy window. Depending on specific defects, one may only need to consider the intrinsic screening or include the defect contribution. This approach avoids the summation of many conduction states of supercells and significantly reduces the simulation cost. We have applied it to calculate various point defects, including neutral and charged defects in two-dimensional and bulk systems with small or large bandgaps. The results are consistent with those from the direct GW simulations. This defect-patched screening approach not only clarifies the roles of defects in many-electron screening but also paves the way to fast screen defect structures/materials for novel applications, including single-photon sources, quantum qubits, and quantum sensors.

Establishment and bioinformatics evaluation of the ethanol combined with palmitic acid-induced mouse hepatocyte AFLD model (the Hu-Qiu Model).

Chronic alcoholic liver disease has brought great harm to human health. Alcoholic fatty liver disease is the first stage in the progression of all chronic alcoholic liver diseases. At present, there is no cell model that fully matches the etiology (high-fat diet + alcohol) of human alcoholic fatty liver disease. We used 100 mM ethanol +6.25 µM PA to establish the ethanol combined with PA-induced mouse hepatocyte AFLD model (EP-AFLD hepatocyte model) and performed the RNA-seq transcriptome sequencing. Through bioinformatics analysis and comparison, we discovered that the EP-AFLD hepatocyte model was more suitable for studying the pathological mechanism of AFLD than the mouse AFLD hepatocyte model induced by ethanol alone. And through bioinformatics analysis, we further discovered that 77 genes from the differential expression gene set of EP-AFLD hepatocyte model were engaged in the pathological process of mouse AFLD and 40 genes were involved in the pathogenesis of both mouse AFLD and human AFLD. In this study, a novel mouse hepatocyte AFLD model was successfully established by combining ethanol and PA, which can be used to study the molecular mechanism of the pathogenesis of AFLD in mice or humans. This study will provide a brand-new in vitro experimental platform for the in-depth study of AFLD pathogenesis and the screening of AFLD therapeutic drugs.

Interface-Tuning of Ferroelectricity and Quadruple-Well State in CuInP2S6 via Ferroelectric Oxide.

Ferroelectric van der Waals CuInP2S6 possesses intriguing quadruple-well states and negative piezoelectricity. Its technological implementation has been impeded by the relatively low Curie temperature (bulk TC ∼ 42 °C) and the lack of precise domain control. Here we show that CuInP2S6 can be immune to the finite size effect and exhibits enhanced ferroelectricity, piezoelectricity, and polar alignment in the ultrathin limit when it is interfaced with ferroelectric oxide PbZr0.2Ti0.8O3 films. Piezoresponse force microscopy studies reveal that the polar domains in thin CuInP2S6 fully conform to those of the underlying PbZr0.2Ti0.8O3, where the piezoelectric coefficient changes sign and increases sharply with reducing thickness. High temperature in situ domain imaging points to a significantly enhanced TC of >200 °C for 13 nm CuInP2S6 on PbZr0.2Ti0.8O3. Density functional theory modeling and Monte Carlo simulations show that the enhanced polar alignment and TC can be attributed to interface-mediated structure distortion in CuInP2S6. Our study provides an effective material strategy to engineer the polar properties of CuInP2S6 for flexible nanoelectronic, optoelectronic, and mechanical applications.

[Trapping array-based preparative two-dimensional liquid chromatography for the purification of four components in tobacco leaves].

Two-dimensional liquid chromatography (2D-LC) has gained increased attention because of its high peak capacity for separating complex samples. However, preparative 2D-LC aimed at isolating compounds is significantly different compared with one-dimensional liquid chromatography (1D-LC) in terms of method development and system configuration; thus, it is less developed than its analytical counterpart. The use of 2D-LC in large-scale product preparation has rarely been reported. Hence, a preparative 2D-LC system was developed in this study. The system was composed of one set of preparative LC modules as a separation system, with a dilution pump, switch valves, and trap column array as the interface, to enable the simultaneous isolation of several compounds. Tobacco was used as a sample, and the developed system was applied to isolate nicotine, chlorogenic acid, rutin, and solanesol. The chromatographic conditions were developed by investigating the trapping efficiency of different types of trap column packings, and chromatographic behaviors under different overload conditions. The four compounds were isolated in one 2D-LC run with high purity. The developed system features low cost because it employs medium-pressure isolation, excellent automation owing to its use of an online column switch, high stability, and capability for large-scale production. The isolation of chemicals from tobacco leaves as pharmaceutical raw materials could aid in the development of the tobacco industry and promote the local agricultural economy.

Construction and application of enhanced recovery after surgery-optimized management system with nurse-led multidisciplinary cooperation.

AIM: To evaluate the effect of enhanced recovery after surgery (ERAS)-optimized management system with nurse-led multidisciplinary cooperation. DESIGN: A quasi-experimental design. METHODS: Nursing department cooperated with medical and clinical department to establish an ERAS-optimized management system. After the system was developed, it was applied in surgical departments of the hospital. Using convenience sampling, 220 selective surgical patients, 82 nurses and 98 doctors from January 1st, 2021 to July 31st, 2021 were selected as the trial group. 220 selective surgical patients, 82 nurses and 98 doctors were selected as the control group from January 1st, 2020 to July 31st, 2020. ERAS observation indicators were compared between the two groups before and 6 months after implementation. The nurse professional identity scores and satisfaction of medical cooperation scores of the two groups at different time points were analysed by repeated analysis of variance. RESULTS: After the implementation, ERAS observation indicators in the trial group were better than the control group (p < 0.05). There were significant differences in the group main effect, time main effect and interaction effect of nurse professional identity scores, satisfaction of medical cooperation scores and scores in all dimensions between the two groups (p < 0.05). The scores of the experimental group at 3 months and 6 months after implementation were better than those of the control group (p < 0.05). CONCLUSIONS: Enhanced recovery after surgery-optimized management system with nurse-led multidisciplinary cooperation was an effective working method. It could promote patients recovery and enhance nurse professional identity.

Ultrathin Lithiophilic 3D Arrayed Skeleton Enabling Spatial-Selection Deposition for Dendrite-Free Lithium Anodes.

Lithium metal batteries are promising to become a new generation of energy storage batteries. However, the growth of Li dendrites and the volume expansion of the anode are serious constraints to their commercial implementation. Herein, a controllable strategy is proposed to construct an ultrathin 3D hierarchical host of honeycomb copper micromesh loaded with lithiophilic copper oxide nanowires (CMMC). The uniquely designed 3D hierarchical arrayed skeletons demonstrate a surface-preferred and spatial-selective effect to homogenize local current density and relieve the volume expansion, effectively suppressing the dendrite growth. Employing the constructed CMMC current collector in a half-cell, >400 cycles with 99% coulombic efficiency at 0.5 mA cm-2 is performed. The symmetric battery cycles stably for >2000 h, and the full battery delivers a capacity of 166.6 mAh g-1 . This facile and controllable approach provides an effective strategy for constructing high-performance lithium metal batteries.

Metformin reduces myogenic contracture and myofibrosis induced by rat knee joint immobilization via AMPK-mediated inhibition of TGF-ß1/Smad signaling pathway.

PURPOSE: The two structural components contributing to joint contracture formation are myogenic and arthrogenic contracture, and myofibrosis is an important part of myogenic contracture. Myofibrosis is a response to long-time immobilization and is described as a condition with excessive deposition of endomysial and perimysial connective tissue components in skeletal muscle. The purpose of this study was to confirm whether metformin can attenuate the formation of myogenic contracture and myofibrosis through the phosphorylation level of adenosine monophosphate-activated protein kinase (AMPK) and inhabitation of subsequent transforming growth factor beta (TGF-ß) 1/Smad signaling pathway. MATERIALS AND METHODS: An immobilized rat model was used to determine whether metformin could inhibit myogenic contracture and myofibrosis. The contents of myogenic contracture of knee joint was calculated by measuring instrument of range of motion (ROM), and myofibrosis of rectus femoris were determined by ultrasound shear wave elastography and Masson staining. Protein expression of AMPK and subsequent TGF-ß1/Smad signaling pathway were determined by western blot. Subsequently, Compound C, a specific AMPK inhibitor, was used to further clarify the role of the AMPK-mediated inhibition of TGF-ß1/Smad signaling pathway. RESULTS: We revealed that the levels of myogenic contracture and myofibrosis were gradually increased during immobilization, and overexpression of TGF-ß1-induced formation of myofibrosis by activating Smad2/3 phosphorylation. Activation of AMPK by metformin suppressed overexpression of TGF-ß1 and TGF-ß1-induced Smad2/3 phosphorylation, further reducing myogenic contracture and myofibrosis during immobilization. In contrast, inhibition of AMPK by Compound C partially counteracted the inhibitory effect of TGF-ß1/Smad signaling pathway by metformin. CONCLUSION: Notably, we first illustrated the therapeutic effect of metformin through AMPK-mediated inhibition of TGF-ß1/Smad signaling pathway in myofibrosis, which may provide a new therapeutic strategy for myogenic contracture.

Clinical value of the MeltPro MTB assays in detection of drug-resistant tuberculosis in paraffin-embedded tissues / 中华病理学杂志

Objective: To evaluate the clinical value of the MeltPro MTB assays in the diagnosis of drug-resistant tuberculosis. Methods: A cross-sectional study design was used to retrospectively collect all 4 551 patients with confirmed tuberculosis between January 2018 and December 2019 at Beijing Chest Hospital, Capital Medical University. Phenotypic drug sensitivity test and GeneXpert MTB/RIF (hereafter referred to as "Xpert") assay were used as gold standards to analyze the accuracy of the probe melting curve method. The clinical value of this technique was also evaluated as a complementary method to conventional assays of drug resistance to increase the detective rate of drug-resistant tuberculosis. Results: By taking the phenotypic drug susceptibility test as the gold standard, the sensitivity of the MeltPro MTB assays to detect resistance to rifampicin, isoniazid, ethambutol and fluoroquinolone was 14/15, 95.7%(22/23), 2/4 and 8/9,respectively; and the specificity was 92.0%(115/125), 93.2%(109/117), 90.4%(123/136) and 93.9%(123/131),respectively; the overall concordance rate was 92.1%(95%CI:89.6%-94.1%),and the Kappa value of the consistency test was 0.63(95%CI:0.55-0.72).By taking the Xpert test results as the reference, the sensitivity of this technology to the detection of rifampicin resistance was 93.6%(44/47), the specificity was100%(310/310), the concordance rate was 99.2%(95%CI:97.6%-99.7%), and the Kappa value of the consistency test was 0.96(95%CI:0.93-0.99). The MeltPro MTB assays had been used in 4 551 confirmed patients; the proportion of patients who obtained effective drug resistance results increased from 83.3% to 87.8%(P<0.01); and detection rate of rifampicin, isoniazid, ethambutol, fluoroquinolone resistance, multidrug and pre-extensive drug resistance cases were increased by 3.2%, 14.7%, 22.2%, 13.7%, 11.2% and 12.5%, respectively. Conclusion: The MeltPro MTB assays show satisfactory accuracy in the diagnosis of drug-resistant tuberculosis. This molecular pathological test is an effective complementary method in improving test positivity of drug-resistant tuberculosis.

Qirong Tablets inhibits apoptosis of ovarian granulosa cells via PI3K/Akt/ HIF-1 signaling pathway / 中国中药杂志

This study aims to observe the effect and explore the mechanism of Qirong Tablets in the treatment of premature ovarian insufficiency(POI) in mice via the phosphatidylinositol 3-kinase(PI3K)/protein kinase B(Akt)/hypoxia inducible factor 1(HIF-1) signaling pathway. Sixty SPF female BALB/c mice were randomly divided into normal group, model group, positive control group, Qirong Tablets low-, medium-and high-dose group. The normal group was intraperitoneally injected with the same amount of normal saline, and the other groups were intraperitoneally injected with cyclophosphamide 120 mg·kg~(-1)·d~(-1) once to establish a POI animal model. After the model was successfully established, the low-, medium-and high-dose groups of Qirong Tablets were administered orally with 0.6, 1.2, 2.4 mg·kg~(-1)·d~(-1) respectively. The positive control group was given 0.22 mg·kg~(-1)·d~(-1) Clementine Tablets by intragastric administration, and the normal group and model group were given intragastric administration with the same amount of normal saline, and the treatment was 28 d as a course of treatment. After drug intervention, enzyme-linked immunosorbent assay(ELISA) was employed to measure the levels of estradiol(E_2), follicle-stimulating hormone(FSH), luteinizing hormone(LH), and anti-mullerian hormone(AMH) in peripheral blood, and hematoxylin-eosin(HE) staining to observe the ovarian tissue. Terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling(TUNEL) assay was used to detect the apoptosis of granulosa cells, and Western blot to determine the expression levels of B-cell lymphoma-2(Bcl-2), Bcl-2-associated X protein(Bax), caspase-3, PI3K, Akt, and HIF-1. Compared with the normal group, the modeling of POI caused loose or destroyed ovarian tissue with vacuolar structures, edema and fibrosis in the ovarian interstitium, disordered or loose arrangement of granulosa cells, and reduced normal follicles. Compared with the model group, drug interventions restored the ovarian tissue and follicles at all the development stages and reduced atretic follicles. Compared with the normal group, the modeling of POI lowered the serum level of E_2 and AMH(P<0.01), and elevated the level of FSH and LH(P<0.01). Compared with the model group, high-dose Qirong Tablets elevated the levels of E_2 and AMH(P<0.05), and lowered the levels of FSH and LH(P<0.05). Compared with the normal group, the modeling of POI up-regulated the protein levels of PI3K, Akt, HIF-1, Bax, and caspase-3 and down-regulated the protein level of Bcl-2 in the ovarian tissue(P<0.01). Compared with the model group, low-, medium-, and high-dose Qirong Tablets down-regulated the protein levels of PI3K, Akt, HIF-1, Bax, and caspase-3 proteins and up-regulated the protein level of Bcl-2 in the ovarian tissue(P<0.05). In conclusion, Qirong Tablets can up-regulate the expression Bcl-2, down-regulate the expression of Bax and caspase-3 in POI mice. Qirong Tablets may inhibit the apoptosis of follicular granulosa cells in mice, thereby delaying ovarian aging, improving reproductive axis function, and strengthening ovarian reserve capacity, which may be associated with the inhibition of PI3K/Akt/HIF-1 pathway.

Drug resistance and genomic characteristics of a strain of O139 Vibrio cholerae isolated from human bloodstream infection / 中华预防医学杂志

Objective: To analyze the drug resistance and genomic characteristics of a strain of serogroup O139 Vibrio cholerae producing cholera toxin isolated from the bloodstream of a person with bacteremia. Methods: The broth dilution method and automatic drug sensitivity analyzer were used to determine the antibiotic sensitivity of the strain. The complete genome sequence of the strain was obtained by using second-generation gene sequencing and nanopore sequencing. BLAST software was used for comparison and analysis with CARD, Resfinder, ISfinder, VFDB, and other databases. The drug-resistant genes, insertion sequences and virulence genes carried by the strain were identified. MEGA 5.1 software was used to construct a genetic phylogenetic tree based on the core genomic single nucleotide polymorphisms. Results: V. cholerae SH400, as the toxigenic strain, carried multiple virulence-related genes and four virulence islands. The strain was resistant to streptomycin, tetracycline and cotrimoxazole, carrying corresponding drug-resistant genes. The strain also carried IncA/C plasmid with the size of 172914 bp and contained 10 drug-resistant genes. Combined with the genomic evolutionary relationship, this study found that the drug-resistant genes and drug-resistant plasmids carried among strains showed certain aggregation. The traditional ST type of strain SH400 was ST69, and the cgMLST type was a new type highly similar to cgST-252. Conclusion: This strain of serogroup O139 V. cholerae carries the ctxAB gene, multiple drug-resistant genes and IncA/C plasmid, and there are multiple drug-resistant islands.

Relationship between nutrient-related dietary pattern and mild cognitive impairment in middle-aged and elderly people in 15 provinces of China / 中华流行病学杂志

Objective: To explore the relationship between nutrient-related dietary pattern and mild cognitive impairment (MCI) in middle-aged and elderly people. Methods: A total of 6 444 middle-aged and elderly people aged ≥55 years were selected in 2018 China Health and Nutrition Survey. MCI was evaluated by Mini-Mental State Examination, and the intakes of various foods were obtained by consecutive 3-day 24-hour dietary survey and weighing method. The intakes of various nutrients and total dietary energy were calculated based on the food composition table. Demographic and social information, lifestyle and health status of the respondents were obtained through questionnaire survey and physical measurements. In this study, vitamin C, vitamin E, zinc, iron, copper and selenium were selected as dependent variables. Nutrient-related dietary patterns were extracted by reduced rank regression method, and the relationship between dietary patterns and MCI was analyzed by multivariate logistic regression model. Results: Six dietary patterns were extracted in this study, and dietary pattern 1 with the highest explanatory degree was selected for subsequent analysis. Dietary pattern 1 was characterized by higher intakes of legume products, vegetables, fruits, nuts, pork, aquatic products and plant oil. Multivariate logistic regression analysis showed that the risk of MCI was lower in Q4 dietary score group than in Q1 dietary score group (OR=0.69, 95%CI: 0.49-0.98) in the 55-64 age group. In people with sleep duration of 8 hours per day, the risk of MCI was reduced in Q2, Q3 and Q4 dietary score groups compared with the Q1 dietary score group, with OR values of 0.68 (95%CI: 0.51-0.92), 0.67 (95%CI: 0.49-0.92) and 0.65 (95%CI: 0.45-0.92), respectively. Interaction analysis showed that the risk for MCI increased in those aged 65-74 years and ≥75 years compared with those aged 55-64 years in Q1 dietary score group. However, the risk for MCI decreased in both age groups as dietary pattern scores increased. Compared with those with sleep duration less or more than 8 hours per day in Q1 dietary score group, those with sleep duration of 8 hours per day in Q2 and Q3 dietary score groups had a reduced risk for MCI. Conclusion: Dietary patterns with higher intakes of legume products, vegetables, fruits, nuts, pork, aquatic products, and plant oil are negatively associated with MCI in people aged 55-64 years and those who slept 8 hours per day, and may reduce the risk of MCI with aging.

Toxic Epidermal Necrolysis Induced by Sintilimab: A Case Report

Sintilimab is an anti-programmed cell death receptor-1 antibody. The phase III clinical trial ORIENT-12 confirmed the safety of sintilimab combined with pemetrexed/platinum in the treatment of advanced squamous non-small cell lung cancer. Skin reactions are the most commonly reported adverse events of immune checkpoint inhibitors and are rarely severe.We describe a case of toxic epidermal necrolysis related to sintilimab in an elderly oncologic patient. 3 weeks after immunotherapy, the patient developed an extensive rash and diffuse itching, rapidly evolving into macules, blisters, bullae and erosions. Causal evaluation was performed based on the algorithm of drug causality for epidermal necrolysis and national Food and Drug Administration qualitative analysis. The patient responded to high-dose glucocorticosteroid and supportive therapy, alongside with local wound care. If immune checkpoint inhibitors need to be extrapolated clinically, strictly following evidence-based research, promptly detecting and treating adverse reactions is crucial.

Non-Coding RNAs of Extracellular Vesicles: Key Players in Organ-Specific Metastasis and Clinical Implications.

Extracellular vesicles (EVs) are heterogeneous membrane-encapsulated vesicles released by most cells. They act as multifunctional regulators of intercellular communication by delivering bioactive molecules, including non-coding RNAs (ncRNAs). Metastasis is a major cause of cancer-related death. Most cancer cells disseminate and colonize a specific target organ via EVs, a process known as "organ-specific metastasis". Mounting evidence has shown that EVs are enriched with ncRNAs, and various EV-ncRNAs derived from tumor cells influence organ-specific metastasis via different mechanisms. Due to the tissue-specific expression of EV-ncRNAs, they could be used as potential biomarkers and therapeutic targets for the treatment of tumor metastasis in various types of cancer. In this review, we have discussed the underlying mechanisms of EV-delivered ncRNAs in the most common organ-specific metastases of liver, bone, lung, brain, and lymph nodes. Moreover, we summarize the potential clinical applications of EV-ncRNAs in organ-specific metastasis to fill the gap between benches and bedsides.