Objective To investigate the relationship between the therapeutic effect of anti-vascular endothelial growth factor(VEGF)and cytokines in aqueous humor in patients with diabetic retinopathy(DR).Methods From July 2023 to December 2023,50 DR patients(56 eyes)who were treated with anti-VEGF drugs in the Department of Ophthal-mology,the Third Affiliated Hospital of Xinxiang Medical University were included in this study.The patients were divided into the diabetic macular edema(DME)group(30 patients,36 eyes)and the proliferative DR(PDR)group(20 patients,20 eyes).Patients in the DME group received an intravitreal injection of aflibercept once a month for three consecutive times,with aqueous humor extracted before each injection.Patients in the PDR group received an intravitreal injection of aflibercept one week before vitrectomy,with aqueous humor extracted before injection and during vitrectomy,respective-ly.The concentrations of vascular endothelial growth factor A(VEGF-A),placental growth factor(PLGF),interleukin(IL)-1β,IL-23,IL-17A,and tumor necrosis factor-α(TNF-α)in the aqueous humor were detected using the Luminex as-say.Before injection therapy,all patients underwent best corrected visual acuity(BCVA)and central macular thickness(CMT)examinations,and their correlations with cytokine concentrations in DR patients before injection therapy were ana-lyzed.Results Compared to before injection therapy,the concentrations of VEGF-A,PLGF,and IL-23 in the aqueous humor of patients in the DME group decreased significantly after treatment(all P＜0.05);additionally,the CMT de-creased,and the BCVA increased(both P＜0.05).After injection therapy,the concentrations of VEGF,PLGF,IL-1β,IL-23,IL-17A,and TNF-α in the aqueous humor of patients in the PDR group significantly decreased compared to before injec-tion therapy(all P＜0.05).Before injection therapy,the levels of VEGF-A,PLGF,and IL-23 in the aqueous humor of pa-tients in the DME group were higher than those in the PDR group,and the differences were statistically significant(all P＜0.05).The correlation analysis results showed that before injection therapy,VEGF was negatively correlated with BCVA(r=-0.767,P=0.004)and was positively correlated with CMT(r=0.662,P=0.019)and IL-23(r=0.765,P=0.004)in the DME group.There was no correlation between the cytokines in the aqueous humor of patients in the PDR group be-fore injection therapy(all P＞0.05).Conclusion Changes in the concentration of VEGF-A,PLGF,and IL-23 are closely related to the occurrence and development of DR.Anti-VEGF treatment can improve BCVA and decrease CMT in DME pa-tients.The expression level of IL-23 in aqueous humor can serve as a predictive factor for the anti-VEGF efficacy in DR pa-tients,providing new targets for early diagnosis and treatment of DR.

Objective To monitor the susceptibility of clinical isolates to antimicrobial agents in tertiary hospitals in major regions of China in 2022.Methods Clinical isolates from 58 hospitals in China were tested for antimicrobial susceptibility using a unified protocol based on disc diffusion method or automated testing systems.Results were interpreted using the 2022 Clinical &Laboratory Standards Institute(CLSI)breakpoints.Results A total of 318 013 clinical isolates were collected from January 1,2022 to December 31,2022,of which 29.5％were gram-positive and 70.5％were gram-negative.The prevalence of methicillin-resistant strains in Staphylococcus aureus,Staphylococcus epidermidis and other coagulase-negative Staphylococcus species(excluding Staphylococcus pseudintermedius and Staphylococcus schleiferi)was 28.3％,76.7％and 77.9％,respectively.Overall,94.0％of MRSA strains were susceptible to trimethoprim-sulfamethoxazole and 90.8％of MRSE strains were susceptible to rifampicin.No vancomycin-resistant strains were found.Enterococcus faecalis showed significantly lower resistance rates to most antimicrobial agents tested than Enterococcus faecium.A few vancomycin-resistant strains were identified in both E.faecalis and E.faecium.The prevalence of penicillin-susceptible Streptococcus pneumoniae was 94.2％in the isolates from children and 95.7％in the isolates from adults.The resistance rate to carbapenems was lower than 13.1％in most Enterobacterales species except for Klebsiella,21.7％-23.1％of which were resistant to carbapenems.Most Enterobacterales isolates were highly susceptible to tigecycline,colistin and polymyxin B,with resistance rates ranging from 0.1％to 13.3％.The prevalence of meropenem-resistant strains decreased from 23.5％in 2019 to 18.0％in 2022 in Pseudomonas aeruginosa,and decreased from 79.0％in 2019 to 72.5％in 2022 in Acinetobacter baumannii.Conclusions The resistance of clinical isolates to the commonly used antimicrobial agents is still increasing in tertiary hospitals.However,the prevalence of important carbapenem-resistant organisms such as carbapenem-resistant K.pneumoniae,P.aeruginosa,and A.baumannii showed a downward trend in recent years.This finding suggests that the strategy of combining antimicrobial resistance surveillance with multidisciplinary concerted action works well in curbing the spread of resistant bacteria.

Cortical interneurons can be categorized into distinct populations based on multiple modalities, including molecular signatures and morpho-electrical (M/E) properties. Recently, many transcriptomic signatures based on single-cell RNA-seq have been identified in cortical interneurons. However, whether different interneuron populations defined by transcriptomic signature expressions correspond to distinct M/E subtypes is still unknown. Here, we applied the Patch-PCR approach to simultaneously obtain the M/E properties and messenger RNA (mRNA) expression of >600 interneurons in layer V of the mouse somatosensory cortex (S1). Subsequently, we identified 11 M/E subtypes, 9 neurochemical cell populations (NCs), and 20 transcriptomic cell populations (TCs) in this cortical lamina. Further analysis revealed that cells in many NCs and TCs comprised several M/E types and were difficult to clearly distinguish morpho-electrically. A similar analysis of layer V interneurons of mouse primary visual cortex (V1) and motor cortex (M1) gave results largely comparable to S1. Comparison between S1, V1, and M1 suggested that, compared to V1, S1 interneurons were morpho-electrically more similar to M1. Our study reveals the presence of substantial M/E variations in cortical interneuron populations defined by molecular expression.
Mice ; Animals ; Neocortex/physiology* ; Mice, Transgenic ; Interneurons/physiology*

Animals ; Brain Diseases/pathology* ; Cell Cycle ; Interneurons/pathology* ; Median Eminence/pathology* ; Mice

A fundamental challenge that arises in biomedicine is the need to characterize compounds in a relevant cellular context in order to reveal potential on-target or off-target effects. Recently, the fast accumulation of gene transcriptional profiling data provides us an unprecedented opportunity to explore the protein targets of chemical compounds from the perspective of cell transcriptomics and RNA biology. Here, we propose a novel Siamese spectral-based graph convolutional network (SSGCN) model for inferring the protein targets of chemical compounds from gene transcriptional profiles. Although the gene signature of a compound perturbation only provides indirect clues of the interacting targets, and the biological networks under different experiment conditions further complicate the situation, the SSGCN model was successfully trained to learn from known compound-target pairs by uncovering the hidden correlations between compound perturbation profiles and gene knockdown profiles. On a benchmark set and a large time-split validation dataset, the model achieved higher target inference accuracy as compared to previous methods such as Connectivity Map. Further experimental validations of prediction results highlight the practical usefulness of SSGCN in either inferring the interacting targets of compound, or reversely, in finding novel inhibitors of a given target of interest.
Drug Delivery Systems ; Proteins ; Transcriptome

Studies have shown that most of the sequence in the mammalian genome is transcribed into long noncoding RNAs (lncRNAs). Their crucial roles in gene regulation are becoming a hotspot in current biomedical research. LncRNAs can control gene activities through multiple mechanisms such as: 1) direct or indirect regulation of gene expression via cis-/trans-action or function as protein baits in the nucleus; 2) affecting the stability and the translational process of mRNA; 3) functioning as competitors to regulation of microRNA; 4) binding to transcription factors. Recent studies have highlighted the significance of lncRNAs in development and diseases, and their potentials in future clinical application.

Studies have shown that most of the sequence in the mammalian genome is transcribed into long noncoding RNAs (lncRNAs). Their crucial roles in gene regulation are becoming a hotspot in current biomedical research. LncRNAs can control gene activities through multiple mechanisms such as: 1) direct or indirect regulation of gene expression via cis-/trans-action or function as protein baits in the nucleus; 2) affecting the stability and the translational process of mRNA; 3) functioning as competitors to regulation of microRNA; 4) binding to transcription factors. Recent studies have highlighted the significance of lncRNAs in development and diseases, and their potentials in future clinical application.
Animals ; Cell Nucleus ; genetics ; Gene Expression Regulation ; Humans ; MicroRNAs ; genetics ; RNA, Long Noncoding ; RNA, Messenger ; genetics ; Transcription Factors ; genetics

Golgi protein-73 (GP73) is a type-lⅡ Golgi glycoprotein localized on the membrane of the Golgi complex.Recently,a growing number of studies have demonstrated that the expression of GP73 is closely correlated with primary hepatocarcinoma (PHC).GP73 has a higher sensitivity and specificity than alpha-fetoprotein (AFP) and it may be a novel serum marker for the detection of PHC,especially for early PHC.This article reviews the relationship between GP73 and PHC.

Objective To improve the treatment of abnormal calcium-phosphorus metabolism in hemodialysis patients, and observe its influence on the quality of life. Methods Implemented the kidney Disease Outcomes Quality Initiative (K/DOQI) clinical practice guidelines for bone metabolism and disease in hemodialysis patients, improved the treatment of abnormal calcium-phesphoms metabolism in hemodialysis patients. After 1 year, the values were compared between before and after application of K/DOQI guidelines, including albumin-adjusted serum calcium, phosphorus, calcium × phosphorus (Ca × P) product, and intact parathyroid hormone (iPTH) and their achieved target range rates. The quality of life were evaluated by using the kidney disease questionnaire (KDQ). Results One year later, the levels of serum calcium, phosphorus, Ca × P product, and iPTH were all decreased (P<0.01 or <0.05) compared with before the application of K/DOQI guidelines. The percentage of patients fell within the guideline range were as follows: 74.42% (32/43), calcium; 62.79%(27/43), phosphorus; 55.81%(24/43), Ca × P product; 60.47%(26/43), iPTH; 25.58%(11/43), all four criteria, higher than before (P<0.01 or <0.05). The scores of KDQ in global indices and symptom scores of physical symptoms, fatigue, depression, relationships with others and frustration dimension were also all increased (P<0.01). Conclusion The state of calcium-phospberns metabolism in hemodialysis patients is improved, the quality of life is also enhanced.

Objective To screen the altered gene expression profile of hippocampus after traumatic brain injury(TBI)in rats. Methods Rats(n=3)in experimental group underwent moderate fluid-percussion(F-P)brain injury and the hippoeampus sample in the injured hemisphere was removed and conserved in liquid nitrogen three hours later.The rats(n=5)of the control group underwent the same procedure except for injury.Mfymetrix rat genome 230 2.0 array was used to detect the gene expression profile of hippocampus in two groups and find the altered gene expression profile. Results A total of 159 genes in the experimental group changed significantly(≥2 folds)compared with the control group,of which 136 genes were up-regulated and 23 genes down-regulated. Conclusions The significant gene expression changes of hippocampus,especially a large mount of up-regulated genes,are detected after moderate TBI in rats,suggesting that the secondary injury following TBI is a procedure involving multiple factors.