Effect of Animal-Assisted Therapy (AAT) on Social Interaction and Quality of Life in Patients with Schizophrenia during the COVID-19 Pandemic: An Experimental Study

Purpose@#Most patients with schizophrenia exhibit low willingness to return to society because of negative social experiences. The COVID-19 pandemic led to severe social isolation for schizophrenia patients. However, animal-assisted therapy (AAT) can improve individuals' empathy, social functions, and quality of life. The study aimed to evaluate the effectiveness of AAT in improving social interactions and quality of life in patients with chronic schizophrenia during the COVID-19 pandemic. @*Methods@#An experimental study was conducted, with six institutions for psychiatric rehabilitation in Taiwan as the case institutions. Patients in these institutions were randomly allocated to the experimental group, which received 60 minutes of AAT once a week for 12 weeks, or the control group, which engaged in routine discussion groups and watched short films about animals. Comparisons between the two groups were made before and after the intervention on social function, social adaptive function, and quality of life. Data were collected before the intervention (T1), immediately after the intervention (T2), and 3 months after the intervention (T3). @*Results@#Comparison between groups showed that social functioning was significantly higher in the experimental group than in the control group at T2. However, there was no sign of improvement in social adaptive functions of the experimental group. The experimental group exhibited significantly higher quality of life than the control group at T2 and T3. @*Conclusions@#There was an impact of COVID-19 on the studied effects. AAT improved social functioning and quality of life in patients with chronic schizophrenia. The effect on quality of life lasted only up to 3 months after the intervention. AAT should be promoted for use as a community-based rehabilitation tool in patients with chronic schizophrenia.Trial registrationChinese Clinical Trial Registry, ChiCTR2200061715. https://www.chictr.org.cn.

Guidelines on Clinical Research Evaluation of Artificial Intelligence in Ophthalmology(2023) / 国际眼科杂志(Guoji Yanke Zazhi)

With the upsurge of artificial intelligence(AI)technology in the medical field, its application in ophthalmology has become a cutting-edge research field. Notably, machine learning techniques have shown remarkable achievements in diagnosing, intervening, and predicting ophthalmic diseases. To meet the requirements of clinical research and fit the actual progress of clinical diagnosis and treatment of ophthalmic AI, the Ophthalmic Imaging and Intelligent Medicine Branch and the Intelligent Medicine Special Committee of Chinese Medicine Education Association organized experts to integrate recent evaluation reports of clinical AI research at home and abroad and formed a guideline on clinical research evaluation of AI in ophthalmology after several rounds of discussion and modification. The main content includes the background and method of developing this guideline, introduction to international guidelines on the clinical research evaluation of AI, and the evaluation methods of ophthalmic AI models. This guideline introduces general evaluation methods of clinical ophthalmic AI research, evaluation methods of clinical AI models, and common indices and formulae for clinical AI model evaluation in detail, and amply elaborates the evaluation method of clinical ophthalmic AI trials. This guideline aims to provide guidance and norms for clinical researchers of ophthalmic AI, promote the development of regularization and standardization, and further improve the overall level of clinical ophthalmic AI research evaluations.

Inhibitor of growth protein-2 silencing alleviates angiotensin Ⅱ-induced cardiac remodeling in mice by reducing p53 acetylation / 南方医科大学学报

OBJECTIVE@#To investigate the effect of inhibitor of growth protein-2 (Ing2) silencing on angiotensin Ⅱ (AngⅡ)-induced cardiac remodeling in mice and explore the underlying mechanism.@*METHODS@#An adenoviral vector carrying Ing2 shRNA or empty adenoviral vector was injected into the tail vein of mice, followed 48 h later by infusion of 1000 ng · kg-1 · min-1 Ang Ⅱ or saline using a mini-osmotic pump for 42 consecutive days. Transthoracic echocardiography was used to assess cardiac geometry and function and the level of cardiac hypertrophy in the mice. Masson and WGA staining were used to detect myocardial fibrosis and cross-sectional area of cardiomyocytes, and myocardial cell apoptosis was detected with TUNEL assay. Western blotting was performed to detect myocardial expressions of cleaved caspase 3, ING2, collagen Ⅰ, Ac-p53(Lys382) and p-p53 (Ser15); Ing2 mRNA expression was detected using real-time PCR. Mitochondrial biogenesis, as measured by mitochondrial ROS content, ATP content, citrate synthase activity and calcium storage, was determined using commercial assay kits.@*RESULTS@#The expression levels of Ing2 mRNA and protein were significantly higher in the mice with chronic Ang Ⅱ infusion than in saline-infused mice. Chronic infusion of AngⅡ significantly increased the left ventricular end-systolic diameter (LVESD) and left ventricular end-diastolic diameter (LVEDD) and reduced left ventricular ejection fraction (LVEF) and left ventricular fractional shortening (LVFS) in the mice. Ing2 silencing obviously alleviated AngⅡ-induced cardiac function decline, as shown by decreased LVEDD and LVESD and increased LVEF and LVFS, improved myocardial mitochondrial damage and myocardial hypertrophy and fibrosis, and inhibited cardiomyocyte apoptosis. Chronic AngⅡ infusion significantly increased myocardial expression levels of Ac-p53(Lys382) and p-p53(Ser15) in the mice, and Ing2 silencing prior to AngⅡ infusion lessened AngⅡ- induced increase of Ac-p53(Lys382) without affecting p53 (ser15) expression.@*CONCLUSION@#Ing2 silencing can inhibit AngⅡ-induced cardiac remodeling and dysfunction in mice by reducing p53 acetylation.

Quercetin Attenuates Atherosclerosis via Modulating Apelin Signaling Pathway Based on Plasma Metabolomics / 中国结合医学杂志

OBJECTIVE@#To interpret the pharmacology of quercetin in treatment of atherosclerosis (AS).@*METHODS@#Fourteen apolipoprotein E-deficient (ApoE-/-) mice were divided into 2 groups by a random number table: an AS model (ApoE-/-) group and a quercetin treatment group (7 in each). Seven age-matched C57 mice were used as controls (n=7). Quercetin [20 mg/(kg·d)] was administered to the quercetin group intragastrically for 8 weeks for pharmacodynamic evaluation. Besides morphological observation, the distribution of CD11b, F4/80, sirtuin 1 (Sirt1) and P21 was assayed by immunohistochemistry and immunofluorescence to evaluate macrophage infiltration and tissue senescence. Ultra-performance liquid chromatography/tandem mass spectrometry (UPLC-MSC/MS) was performed to study the pharmacology of quercetin against AS. Then, simultaneous administration of an apelin receptor antagonist (ML221) with quercetin was conducted to verify the possible targets of quercetin. Key proteins in apelin signaling pathway, such as angiotensin domain type 1 receptor-associated proteins (APJ), AMP-activated protein kinase (AMPK), peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α), tissue plasminogen activator (TPA), uncoupling protein 1 (UCP1) and angiotensin II receptor 1 (AT1R), were assayed by Western blot.@*RESULTS@#Quercetin administration decreased lipid deposition in arterial lumen and improved the morphology of ApoE-/- aortas in vivo. Quercetin decreased the densities of CD11b, F4/80 and P21 in the aorta and increased the level of serum apelin and the densities of APJ and Sirt1 in the aorta in ApoE-/- mice (all P<0.05). Plasma metabolite profiling identified 118 differential metabolites and showed that quercetin affected mainly glycerophospholipids and fatty acyls. Bioinformatics analysis suggested that the apelin signaling pathway was one of the main pathways. Quercetin treatment increased the protein expressions of APJ, AMPK, PGC-1α, TPA and UCP1, while decreased the AT1R level (all P<0.05). After the apelin pathway was blocked by ML221, the effect of quercetin was abated significantly, confirming that quercetin attenuated AS by modulating the apelin signaling pathway (all P<0.05).@*CONCLUSION@#Quercetin alleviated AS lesions by up-regulation the apelin signaling pathway.

Ethyl Lithospermate Reduces Lipopolysaccharide-Induced Inflammation through Inhibiting NF-κB and STAT3 Pathways in RAW 264.7 Cells and Zebrafish / 中国结合医学杂志

OBJECTIVE@#To explore the anti-inflammatory effects of ethyl lithospermate in lipopolysaccharide (LPS)-stimulated RAW 264.7 murine-derived macrophages and zebrafish, and its underlying mechanisms.@*METHODS@#3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazoliumbromide (MTT) assays were performed to investigate the toxicity of ethyl lithospermate at different concentrations (12.5-100 µ mol/L) in RAW 264.7 cells. The cells were stimulated with LPS (100 ng/mL) for 12 h to establish an inflammation model in vitro, the production of pro-inflammatory cytokines interleukin (IL)-6 and tumor necrosis factor α (TNF-α) were assessed by enzyme linked immunosorbent assay (ELISA). Western blot was used to ascertain the protein expressions of signal transducer and activator of transcription 3 (STAT3), nuclear factor kappa B (NF-κB) p65, phospho-STAT3 (p-STAT3, Tyr705), inhibitor of NF-κB (IκB) α, and phospho-I κB α (p-IκB α, Ser32), and confocal imaging was used to identify the nuclear translocation of NF-κB p65 and p-STAT3 (Tyr705). Additionally, the yolk sacs of zebrafish (3 days post fertilization) were injected with 2 nL LPS (0.5 mg/mL) to induce an inflammation model in vivo. Survival analysis, hematoxylin-eosin (HE) staining, observation of neutrophil migration, and quantitative real-time polymerase chain reaction (qRT-PCR) were used to further study the anti-inflammatory effects of ethyl lithospermate and its probable mechanisms in vivo.@*RESULTS@#The non-toxic concentrations of ethyl lithospermate have been found to range from 12.5 to 100 µ mol/L. Ethyl lithospermate inhibited the release of IL-6 and TNF-α(P<0.05 or P<0.01), decreased IκBα degradation and phosphorylation (P<0.05) as well as the nuclear translocation of NF-κB p65 and p-STAT3 (Tyr705) in LPS-induced RAW 264.7 cells (P<0.01). Ethyl lithospermate also decreased inflammatory cells infiltration and neutrophil migration while increasing the survival rate of LPS-stimulated zebrafish (P<0.05 or P<0.01). In addition, ethyl lithospermate also inhibited the mRNA expression levels of of IL-6, TNF-α, IκBα, STAT3, and NF-κB in LPS-stimulated zebrafish (P<0.01).@*CONCLUSION@#Ethyl lithospermate exerts anti-Inflammatory effected by inhibiting the NF-κB and STAT3 signal pathways in RAW 264.7 macrophages and zebrafish.

Analysis of Factors Affecting Effectiveness of Medical Device Registration Self-inspection from Perspective of Technical Evaluation / 中国医疗器械杂志

Type inspection is a necessary precondition of technical evaluation of medical device. The implementation of The Provisions for Administration of Self-Test for Medical Device Registration facilitates the registration pathway for applicants. How to improve the effectiveness of registration self-test has drawn attention from many stakeholders. In this study, we analyzed and discussed the factors affecting the validity of registration self-test from technical evaluation perspective, and proposed suggestions for improvement accordingly. The aim of this article is to boost the reliability and effectiveness of registration self-test and offer a reference for applicants to carry out registration self-test.

Risk Management Analysis of Medical Device Registration Self-inspection / 中国医疗器械杂志

Through the analysis of laws and policies related to registration self-inspection, visiting and researching enterprises, holding symposiums, and issuing nationwide questionnaires, the risks in the registration self-inspection process were summarized, analyzed, and evaluated. From the aspects of regulatory departments and manufacturing enterprises, we suggest to improve China's medical device registration regulations system and reduce the risks of all parties in the registration self-inspection work.

Advances in AAV-CRISPR/Cas9-Mediated Hemophilia A Gene Therapy --Review / 中国实验血液学杂志

Hemophilia A(HA) is an X-linked recessive bleeding disorder caused by mutations in coagulation factor VIII. Nowadays, exogenous coagulation factor replacement therapy is the main treatment. With the continuous development of gene therapy, new research directions have been provided for the treatment of hemophilia A. CRISPR-Cas9 technology was applied to select suitable target sites, and mediate the targeted knock-in and efficient expression of exogenous B-domain-deleted FⅧ variant gene through corresponding vectors for the treatment of hemophilia A.CRISPR-Cas9 technology is an emerging gene editing tool with great efficiency, safety and effectiveness, and has been widely used in hemophilia gene therapy research. This paper reviews the vector selection, construction of therapeutic genes, gene editing technology and selection of expression target sites for hemophilia A gene therapy at this stage.

Hematological Neoplasms Secondary to Malignant Solid Tumors with Radiotherapy and Chemotherapy: a Clinical and Prognostic Analysis / 中国实验血液学杂志

OBJECTIVE@#To explore the clinical characteristics, treatment and prognosis of therapy-related hematological neoplasms patients secondary to malignant solid tumors.@*METHODS@#The clinical features, treatment and prognosis of 36 hematological neoplasms patients secondary to malignant solid tumors with radiotherapy and chemotherapy in the Second Hospital of Shanxi Medical University were retrospectively analyzed.@*RESULTS@#The 36 patients with therapy-related hematological neoplasms had a median age of 60 (47-81) years, 14 were male and 22 were female. Among them, 22 cases were acute myeloid leukemia, 5 cases were acute lymphoblastic leukemia, 4 cases were multiple myeloma, 3 cases were myelodysplastic syndrome, and 2 cases were non-hodgkin's lymphoma. The median latency of malignant tumor to hematological neoplasm was 42.5 (12-120) months. The median survival time of therapy-related hematological neoplasms was 10.5 (1-83) months, and the 3-year overall survival (OS) rate was 24.3%. The therapy-related acute myeloid leukemia patients had a very poor prognosis, with a median survival of 7 (1-83) months and a 3-year OS rate of 21.4%.@*CONCLUSION@#The prognosis of therapy-related hematological neoplasms secondary to malignant solid tumors with radiotherapy and chemotherapy is poor, and individualized treatment should be implemented according to the clinical situation of patients.

Dihydrotanshinone I preconditions myocardium against ischemic injury via PKM2 glutathionylation sensitive to ROS

Ischemic preconditioning (IPC) is a potential intervention known to protect the heart against ischemia/reperfusion injury, but its role in the no-reflow phenomenon that follows reperfusion is unclear. Dihydrotanshinone I (DT) is a natural compound and this study illustrates its role in cardiac ischemic injury from the aspect of IPC. Pretreatment with DT induced modest ROS production and protected cardiomyocytes against oxygen and glucose deprivation (OGD), but the protection was prevented by a ROS scavenger. In addition, DT administration protected the heart against isoprenaline challenge. Mechanistically, PKM2 reacted to transient ROS via oxidization at Cys423/Cys424, leading to glutathionylation and nuclear translocation in dimer form. In the nucleus, PKM2 served as a co-factor to promote HIF-1α-dependent gene induction, contributing to adaptive responses. In mice subjected to permanent coronary ligation, cardiac-specific knockdown of Pkm2 blocked DT-mediated preconditioning protection, which was rescued by overexpression of wild-type Pkm2, rather than Cys423/424-mutated Pkm2. In conclusion, PKM2 is sensitive to oxidation, and subsequent glutathionylation promotes its nuclear translocation. Although IPC has been viewed as a protective means against reperfusion injury, our study reveals its potential role in protection of the heart from no-reflow ischemia.

Laser acupuncture combined with auricular acupressure improves low-back pain and quality of life in nurses: A randomized controlled trial / 中西医结合学报

BACKGROUND@#Low-back pain (LBP) in nurses is a major health concern that affects their quality of life and ability to work, with consequences for their economic status.@*OBJECTIVE@#This study evaluates the effect of low-level laser acupuncture combined with auricular acupressure (LAA) on pain intensity, pain interference and quality of life in nurses with LBP.@*DESIGN, SETTING, PARTICIPANTS AND INTERVENTIONS@#This randomized controlled trial recruited a convenience sample of hospital-based nurses from one teaching hospital in Taiwan, China. Participants were randomly assigned to the LAA group (n = 38) receiving low-level laser acupuncture and auricular acupressure for 4 weeks, and the control group (n = 38) receiving only sham laser acupuncture treatment without laser energy output.@*MAIN OUTCOME MEASURES@#Data were collected for the primary pain outcome using the Short Form of the Brief Pain Inventory, while the secondary outcome, quality of life, was evaluated using the Roland-Morris Disability Questionnaire. Both primary and secondary outcomes were scored before the intervention, and after 2-week and 4-week intervention. The rate of LBP recurrence was evaluated at the 4th week and 8th week after the end of intervention.@*RESULTS@#After controlling for prior pain, the result of linear mixed model analysis showed trends in significant between-group differences in the level of current pain occurring in week 4 (P < 0.001), worst pain in week 2 (P < 0.001) and week 4 (P < 0.001), least pain in week 2 (P = 0.032) and week 4 (P < 0.001), pain interference in week 2 (P = 0.009) and week 4 (P < 0.001), and in the life dysfunction in week 2 (P < 0.001) and week 4 (P < 0.001). Recurrence rates of LBP at the 4th and 8th weeks after the end of intervention were 0% and 36.89% in the LAA group, and 69.44% and 36.11% in the control group.@*CONCLUSION@#This study shows that 4-week LAA intervention reduced pain intensity and pain interference, and improved quality of life for hospital-based nurses with LBP. These effects were maintained continuously for at least 4 weeks after the intervention. The nonpharmacological intervention, LAA, may be another efficacious, feasible, noninvasive, analgesic intervention for LBP.@*TRIAL REGISTRATION@#This study is registered at Clinicaltrials.gov (registration number NCT04423445).

Mechanism of Cistanches Herba in treatment of cancer-related fatigue based on network pharmacology and experimental verification / 中国中药杂志

This study aimed to explore the mechanism of Cistanches Herba in the treatment of cancer-induced fatigue(CRF) by network pharmacology combined with in vivo and in vitro experiments to provide a theoretical basis for the clinical medication. The chemical constituents and targets of Cistanches Herba were searched from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP). The targets of CRF were screened out by GeneCards and NCBI. The common targets of traditional Chinese medicine and disease were selected to construct a protein-protein interaction(PPI) network, followed by Gene Ontology(GO) functional and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment analyses. A visual signal pathway rela-ted to Chinese medicine and disease targets was constructed. The CRF model was induced by paclitaxel(PTX) in mice. Mice were divided into a control group, a PTX model group, and low-and high-dose Cistanches Herba extract groups(250 and 500 mg·kg~(-1)). The anti-CRF effect in mice was evaluated by open field test, tail suspension test, and exhaustive swimming time, and the pathological morphology of skeletal muscle was evaluated by hematoxylin-eosin(HE) staining. The cancer cachexia model in C2C12 muscle cells was induced by C26 co-culture, and the cells were divided into a control group, a conditioned medium model group, and low-, medium-, and high-dose Cistanches Herba extract groups(62.5, 125, and 250 μg·mL~(-1)). The reactive oxygen species(ROS) content in each group was detected by flow cytometry, and the intracellular mitochondrial status was evaluated by transmission electron microscopy. The protein expression levels of hypoxia-inducible factor-1α(HIF-1α), BNIP3L, and Beclin-1 were detected by Western blot. Six effective constituents were screened out from Cistanches Herba. The core genes of Cistanches Herba in treating CRF were AKT1, IL-6, VEGFA, CASP3, JUN, EGFR, MYC, EGF, MAPK1, PTGS2, MMP9, IL-1B, FOS, and IL10, and the pathways related to CRF were AGE-RAGE and HIF-1α. Through GO enrichment analysis, it was found that the main biological functions involved were lipid peroxidation, nutrient deficiency, chemical stress, oxidative stress, oxygen content, and other biological processes. The results of the in vivo experiment showed that Cistanches Herba extract could significantly improve skeletal muscle atrophy in mice to relieve CRF. The in vitro experiment showed that Cistanches Herba extract could significantly reduce the content of intracellular ROS, the percentage of mitochondrial fragmentation, and the protein expression of Beclin-1 and increase the number of autophagosomes and the protein expression of HIF-1α and BNIP3L. Cistanches Herba showed a good anti-CRF effect, and its mechanism may be related to the key target proteins in the HIF-1α signaling pathway.

Value of metagenomic next-generation sequencing in children with hematological malignancies complicated with infections / 中国当代儿科杂志

OBJECTIVES@#To explore the value of metagenomic next-generation sequencing (mNGS) in the pathogen identification in children with hematological malignancies complicated with infections.@*METHODS@#A retrospective analysis was conducted on clinical data and pathogenic test results of 43 children with hematological malignancies who underwent microbial culture and mNGS due to infections in the Third Xiangya Hospital of Central South University between June 2020 and July 2022. Differences in detection rates and characteristics of pathogenic microorganisms detected by mNGS and microbial culture were compared.@*RESULTS@#A total of 54 specimens were examined, and the overall detection rate of pathogen by mNGS (80%, 43/54) was significantly higher than that by microbial culture (30%, 16/54) (P<0.001). The most commonly detected infection type by mNGS was viral infection, followed by fungal infection combined viral infection, while that by microbial culture was bacterial infection, followed by fungal infection. The detection rate of fungi by mNGS (33%, 18/54) was higher than that by microbial culture (6%, 3/54) (P<0.001). The detection rate of two or more pathogenic microorganisms by mNGS was higher at 48% compared to microbial culture at 9% (P<0.05). The detection rate of two or more types of pathogenic microorganisms by mNGS was also significantly higher at 33% compared to microbial culture at 2% (P<0.05). The most commonly detected bacteria and fungi by mNGS were Pseudomonas aeruginosa and Candida tropicalis, respectively, in peripheral blood, while Streptococcus pneumoniae and Pneumocystis jirovecii were most commonly detected in bronchoalveolar lavage fluid. Treatment adjustments based on mNGS results were beneficial for 35% (15/43) of the cases.@*CONCLUSIONS@#mNGS has a higher detection rate than microbial culture and has obvious advantages in diagnosing mixed and fungal infections, making it a useful supplementary diagnostic method to microbial culture.

Antiarrhythmic active components in traditional Chinese medicine acting on potassium channels / 中国中药杂志

Arrhythmia is an external manifestation of cardiac electrophysiological disorder. It exists in healthy people and patients with various heart diseases, which is often associated with other cardiovascular diseases. The contraction and diastole of myocardium are inseparable from the movement of ions. There are many ion channels in the membrane and organelle membrane of myocardium. The dynamic balance of myocardial ions is vital in maintaining myocardial electrical homeostasis. Potassium ion channels that have a complex variety and a wide distribution are involved in the whole process of resting potential and action potential of cardiomyocytes. Potassium ion channels play a vital role in maintaining normal electrophysiological activity of myocardium and is one of the pathogenesis of arrhythmia. Traditional Chinese medicine(TCM)has unique advantages in treating arrhythmia for its complex active components and diverse targets. A large number of TCM preparations have definite effect on treating arrhythmia-related diseases, whose antiarrhythmic mechanism may be related to the effect on potassium channel. This article mainly reviewed the relevant studies on the active components in TCM acting on different potassium channels to provide references for clinical drug use and development.

Effects of primary acquired nasolacrimal duct obstruction on tear film and ocular surface / 国际眼科杂志(Guoji Yanke Zazhi)

AIM: To investigate the effects of primary acquired nasolacrimal duct obstruction(PANDO)on the tear film and ocular surface using LipiView ocular surface interferometer and Keratograph 5M anterior segment analyzer.METHODS: A self-controlled clinical trials. A total of 40 patients diagnosed with unilateral PANDO for at least 6mo who were admitted to our department from September 2021 to March 2022 were enrolled in the study, and the healthy eyes of the patients were assessed as control group. The LipiView ocular surface interferometer and Keratograph 5M anterior segment analyzer were used to measure the changes in related parameters of the tear film and ocular surface in both eyes.RESULTS: The non-invasive tear meniscus height(NITMH), stimulated NITMH, loss rate of upper meibomian gland, nasal and temporal ciliary redness index, temporal conjunctival redness index of the affected eyes were higher than healthy eyes(P&#x003C;0.05), but there were no statistical differences in the non-invasive break-up time(NIBUT), loss rate of lower meibomian gland, nasal conjunctival redness index, dry eye grading, blink responses, partial blink rate and lipid layer thickness(LLT)between the both eyes(P&#x003E;0.05).CONCLUSION: PANDO may lead to the aggravation of ocular surface inflammation and the loss of upper meibomian gland, and damage the ocular surface of patients. Attention should be paid to the early treatment of PANDO.

Research progress of active probes targeting specific aminoacids / 药学学报

Activity-based protein (proteomic) profiling (ABPP) has emerged as a key component of the broad field of chemical techniques capable of directly analyzing enzyme activity in living systems. With the deepening of research on electrophilic warheads and nucleophilic amino acids, and the continuous proposal and improvement of effective development strategies, the application of amino acid-targeting active probes in various biological systems has facilitated the identification, development of new targets in various disease contexts and discovery of inhibitors. The purpose of this review is to summarize the latest progress in the design and application of active probes targeting specific amino acids, in order to provide support for the further development of amino acid-targeted covalent inhibitordrugs.

Design, synthesis and antidiabetic activity studies of purine derivatives / 药学学报

Based our previous work, twelve purine derivatives were designed and synthesized as dual modulators of GPR119 and DPP-4by conjugating the GPR119 activating and DPP-4 inhibiting fragments with the position 6 and 9 of purine core via an approach of merged pharmacophores. Compound 11, bearing 2-fluoro-4-methylsulphonyl anilide and cyanopyrrolidine moieties, exhibited the most potent GPR119 agonistic activities (EC50 = 0.33 μmol·L-1, IA = 71.1%) and DPP-4 inhibitory (58.4% inhibition at 10 μmol·L-1, 21.2% inhibition at 1 μmol·L-1) activities in the in vitro antidiabetic study. Subsequently, we performed studies on structure activity relationships and molecular docking to guide the further drug design.

Expressions of inflammatory factors of aqueous humor before the surgery of chronic primary angle-closure glaucoma and its influence on prognosis / 国际眼科杂志(Guoji Yanke Zazhi)

AIM: To investigate the expression level of inflammatory factors of aqueous humor before trabeculectomy in binocular chronic primary angle-closure glaucoma(CPACG)and its correlation with postoperative filtration bleb and intraocular pressure.METHODS: A total of 15 cases(30 eyes)with binocular CPACG who admitted to the Affiliated Eye Hospital of Nanjing Medical University from September to December 2021 and received trabeculectomy were selected. The surgery interval between two eyes was 7d, and the preoperative expression levels of monocyte chemoattractant protein-1(MCP-1), interleukin-17(IL-17), transforming growth factor-β(TGF-β), and interferon-γ(IFN-γ)of the aqueous humor in both eyes were respectively detected by enzyme-linked immunosorbent assay(ELISA). Furthermore, the intraocular pressure(IOP)and the morphology of filtering blebs at 1mo after surgery were measured.RESULTS: The concentrations of MCP-1, IL-17, TGF-β, and IFN-γ in aqueous humor from the first eye before surgery were 330.4±46.2, 357.3±46.9, 2347.5±363.8 and 527.7±101.6pg/mL respectively, and those concentrations in aqueous humor from the fellow eye were 298.2±40.7, 309.1±53.5, 1938.3±426.0 and 628.2±104.9pg/mL respectively. The preoperative expression levels of inflammatory factors of aqueous humor in both eyes were statistically significant(P≤0.05). Furthermore, the expression levels of IL-17 and TGF-β in the aqueous humor of patients with CPACG correlated with IOP and the height of filtering blebs at 1mo after surgery(P&#x0026;#x003C;0.05).CONCLUSION: There may be changes in the expression levels of inflammatory factors of aqueous humor in the fellow eye after surgery of the first eye. Moreover, the preoperative expression level of IL-17 and TGF-β in aqueous humor possibly related to postoperative IOP and the height of filtering bleb.

Analysis of prognosis and influencing factors of No. 253 lymph node metastasis in descending colon, sigmoid colon, and rectal cancer: a multicenter study / 中华外科杂志

Objectives: To analyze the influencing factors of No. 253 lymph node metastasis in descending colon cancer, sigmoid colon cancer, and rectal cancer, and to investigate the prognosis of No. 253 lymph node-positive patients by propensity score matching analysis. Methods: A retrospective analysis was performed on clinical data from patients with descending colon cancer, sigmoid colon cancer, rectosigmoid junction cancer, and rectal cancer who underwent surgery between January 2015 and December 2019 from the Cancer Hospital of the Chinese Academy of Medical Sciences, China-Japan Friendship Hospital, Peking Union Medical College Hospital, General Hospital of the Chinese People's Liberation Army, and Peking University Cancer Hospital. A total of 3 016 patients were included according to inclusion and exclusion criteria, comprising 1 848 males and 1 168 females, with 1 675 patients aged≥60 years and 1 341 patients aged<60 years. Clinical and pathological factors from single center data were subjected to univariate analysis to determine influencing factors of No. 253 lymph node metastasis, using a binary Logistic regression model. Based on the results of the multivariate analysis, a nomogram was constructed. External validation was performed using data from other multicenter sources, evaluating the effectiveness through the area under the receiver operating characteristic curve and the calibration curve. Using data from a single center, the No. 253 lymph node-positive group was matched with the negative group in a 1∶2 ratio (caliper value=0.05). Survival analysis was performed using the Kaplan-Meier method and Log-rank test. The Cox proportional hazards model was used to determine independent prognostic factors. Results: (1) The tumor diameter≥5 cm (OR=4.496,95%CI:1.344 to 15.035, P=0.015) T stage (T4 vs. T1: OR=11.284, 95%CI:7.122 to 15.646, P<0.01), N stage (N2 vs. N0: OR=60.554, 95%CI:7.813 to 469.055, P=0.043), tumor differentiation (moderate vs. well differentiated: OR=1.044, 95%CI:1.009 to 1.203, P=0.044; poor vs. well differentiated: OR=1.013, 95%CI:1.002 to 1.081, P=0.013), tumor location (sigmoid colon vs. descending colon: OR=9.307, 95%CI:2.236 to 38.740, P=0.002), pathological type (mucinous adenocarcinoma vs. adenocarcinoma: OR=79.923, 95%CI:15.113 to 422.654, P<0.01; signet ring cell carcinoma vs. adenocarcinoma: OR=27.309, 95%CI:4.191 to 177.944, P<0.01), and positive vascular invasion (OR=3.490, 95%CI:1.033 to 11.793, P=0.044) were independent influencing factors of No. 253 lymph node metastasis. (2) The area under the curve of the nomogram prediction model was 0.912 (95%CI: 0.869 to 0.955) for the training set and 0.921 (95%CI: 0.903 to 0.937) for the external validation set. The calibration curve demonstrated good consistency between the predicted outcomes and the actual observations. (3) After propensity score matching, the No. 253 lymph node-negative group did not reach the median overall survival time, while the positive group had a median overall survival of 20 months. The 1-, 3- and 5-year overall survival rates were 83.9%, 61.3% and 51.6% in the negative group, and 63.2%, 36.8% and 15.8% in the positive group, respectively. Multivariate Cox analysis revealed that the T4 stage (HR=3.067, 95%CI: 2.357 to 3.990, P<0.01), the N2 stage (HR=1.221, 95%CI: 0.979 to 1.523, P=0.043), and No. 253 lymph node positivity (HR=2.902, 95%CI:1.987 to 4.237, P<0.01) were independent adverse prognostic factors. Conclusions: Tumor diameter ≥5 cm, T4 stage, N2 stage, tumor location in the sigmoid colon, adverse pathological type, poor differentiation, and vascular invasion are influencing factors of No. 253 lymph node metastasis. No. 253 lymph node positivity indicates a poorer prognosis. Therefore, strict dissection for No. 253 lymph node should be performed for colorectal cancer patients with these high-risk factors.

Population structure of food-borne Staphylococcus aureus in China / 中华流行病学杂志

Objective: To understand the population structure of food-borne Staphylococcus (S.) aureus in China. Methods: Whole genome sequencing was used to analyze 763 food-borne S. aureus strains from 16 provinces in China from 2006 to 2020. Multilocus sequence typing (MLST), staphylococcal protein A gene (spa) typing, and staphylococcal chromosome cassettemec (SCCmec) typing were conducted, and minimum spanning tree based on ST types (STs) was constructed by BioNumerics 7.5 software. Thirty-one S. aureus strains isolated from imported food products were also included in constructing the genome phylogenetic tree. Results: A total of 90 STs (20 novel types) and 160 spa types were detected in the 763 S. aureus isolates. The 72 STs (72/90, 80.0%) were related to 22 clone complexes. The predominant clone complexes were CC7, CC1, CC5, CC398, CC188, CC59, CC6, CC88, CC15, and CC25, accounting for 82.44% (629/763) of the total. The STs and spa types in the predominant clone complexes changed over the years. The methicillin-resistant S. aureus (MRSA) detection rate was 7.60%, and 7 SCCmec types were identified. The ST59-t437-Ⅳa (17.24%, 10/58), ST239-t030-Ⅲ (12.07%, 7/58), ST59-t437-Ⅴb (8.62%, 5/58), ST338-t437-Ⅴb (6.90%, 4/58) and ST338-t441-Ⅴb (6.90%, 4/58) were the main types in MRSA strains. The genome phylogenetic tree had two clades, and the strains with the same CC, ST, and spa types clustered together. All CC7 methicillin sensitive S. aureus strains were included in Clade1, while 21 clone complexes and all MRSA strains were in Clade2. The MRSA strains clustered according to the SCCmec and STs. The strains from imported food products in CC398, CC7, CC30, CC12, and CC188 had far distances from Chinese strains in the tree. Conclusions: In this study, the predominant clone complexes of food-borne strains were CC7, CC1, CC5, CC398, CC188, CC59, CC6, CC88, CC15, and CC25, which overlapped with the previously reported clone complexes of hospital and community-associated strains in China, suggesting that close attention needs to be paid to food, a vehicle of pathogen transmission in community and food poisoning.