Objective To evalute the drug resistance characteristics of tuberculosis(TB)patients of all ages in Guangdong Province during 2014-2020,and provide prevention and treatment strategies of tuberculosis.Method We used 39,048 clinical isolates of Mycobacterium tuberculosis(MTB)belonging to patients with confirmed TB from 2014 to 2020,from 32 TB drug-resistant surveillance sites in Guangdong Province,and we retrospectively analyzed the laboratories data of patients with drug-resistant TB,and grouped patients by age and region,to explore the trend of drug-resistance of MTB clinical isolates,the trend and incidence differences of multi-resistant TB(including monodrug-resistant TB(MR-TB),polydrug-resistant TB(PDR-TB),multidrug-resistant TB(MDR-TB)and exten-sively drug-resistant TB(XDR-TB)),and resistance characteristics of MTB clinical isolates to drugs in focus(rifam-picin and ofloxacin).Result The differences in the resistance rates of MTB clinical isolates to nine antituberculosis drugs among patients at 32 TB drug resistance surveillance sites in Guangdong Province from 2014 to 2020 were not statistically significant(P>0.05).The rates of MR-TB,PDR-TB,MDR-TB,XDR-TB,and total resistance isolates of MTB clinical isolates were 14.46%,5.16%,5.16%,4.58%,and 1.29%,respectively.he pediatric group had a higher MR rate(15.4%)than the adult and geriatric groups,while the adult and geriatric groups had higher MDR rates(5.0%and 5.0%,respectively).The geriatric group also had a higher XDR rate(2.1%),with statistically significant differences(P<0.001).The rates of MR-TB(14.8%),PDR-TB(5.3%),MDR-TB(4.7%),XDR-TB(1.4%),ofloxacin resistance(11.33%)and rifampicin resistance(6.92%)of MTB clinical isolates were higher in patients from the Pearl River Delta than in other regions of Guangdong Province,with statistically significant differ-ences(P<0.001).Conclusion According to the data from the surveillance sites,the epidemiological trend of drug-resistant TB in Guangdong Province is leveling off during the period 2014-2020.However,the incidence of drug-resistant TB is higher in specific populations(e.g.children and the elderly),and the incidence of drug-resistant TB and the rate of drug resistance to drugs in focus are higher in the Pearl River Delta than in other regions of Guang-dong Province,necessitating further investigation and the development of novel prevention and control strategies.

Monosodium urate (MSU)-induced the gouty arthritis (GA) model was used to investigate the effect of Nod-like receptor protein 3 (NLRP3) inhibitor N14 in alleviating GA. Firstly, the effect of NLRP3 inhibitor N14 on the viability of mouse monocyte macrophage J774A.1 was examined by the cell counting kit-8 (CCK-8) assay. The expression of mature interleukin 1β (IL-1β) and cysteinyl aspartate specific proteinase-1 (caspase-1) p20 in the cell supernatant and the expression of NLRP3, caspase-1 and pro-IL-1β proteins in the cell lysates was detected by Western blot for the inhibitory effect of N14 on the MSU-induced NLRP3 inflammasome activation in J774A.1 cells. Animal behavioral tests were used to detect redness, swelling, heat and pain in mice with gouty arthritis. Hematoxylin-eosin (H&E) staining revealed pathologic changes and inflammatory infiltration in foot sections. Protein expression of NLRP3, caspase-1, and pro-IL-1β in mouse hind paw tissues were assessed by Western blot. The effect of N14 on the plasma levels of alanine transaminase (ALT), aspartate transaminase (AST), creatinine (CRE), urea, and uric acid (UA) was investigated by the MSU-induced gouty arthritis model in mice. All animal experiments in this paper were approved by the Scientific Ethics Review Board of Qingdao Marine Biomedical Research Institute (grant No. E-MBWNL-2024-20). The experimental results showed that N14 did not exhibit cytotoxicity in mouse monocyte macrophage J774A.1 cells at concentrations up to 100 μmol·L^-1, and N14 effectively prevented MSU-induced activation of NLRP3 inflammasome. In the mouse gouty arthritis model, N14 significantly ameliorated the redness, swelling, heat and pain caused by GA, and down-regulated the levels of NLRP3 inflammasome-associated proteins in mouse hind paw tissues. Meanwhile, N14 appeared to be well tolerated, as it did not significantly affect various biochemical indices in mouse plasma. In conclusion, N14 effectively alleviated GA in mice by inhibiting the NLRP3 inflammasome pathway, which is important for both prevention and treatment of related diseases.

AIM: To understand the publication status, research trends, and cutting-edge and hot topics in this field by conducting a bibliometrics analysis of relevant literatures on the pathogenesis of primary open angle glaucoma(POAG)in the past 30 a.METHODS:A total of 986 relevant literatures on the pathogenesis of POAG published on the core databases of China National Knowledge Infrastructure(CNKI)and Web of Science(WOS)from 1 September 1993 to 1 September 2023 were retrieved. CiteSpace(6.2.R.4)and VOSviewer(1.6.18)software were used to conduct knowledge graph analysis on the retrieved literature, including publication volume, author, research institution, country/region, and keywords.RESULTS:The United States(243 articles)has the highest number of publications, followed by China(121 articles). The foreign institution with the highest number of publications is Harvard University(37 articles), while domestic institutions such as Zhongshan Ophthalmic Center, Sun Yat-sen University, ophthalmology department of Xuanwu Hospital of Capital Medical University, and Peking University First Hospital tied for the highest number of publications. Louis R. Pasquale(21 articles)is the most prolific English author. Wang Ningli is the most active Chinese researcher in this field. Keywords include trabecular meshwork, intraocular pressure, aqueous humor, glucocorticoid, hemorheology, etc.CONCLUSION: The research on the pathogenesis of POAG is in a period of vigorous development. The United States has the largest number of publications in this field, and Harvard University is a leading institution in this field. The research focus in the field of POAG has shifted from the structural aspect to the genetic level, and gene research and traditional Chinese medicine treatment have broad application prospects in this field.

Objects To explore the effectiveness and safety of using the Cardio-O-Fix Plug occluder in the treatment of muscular ventricular septal defect(mVSD)in children.Methods 14 patients with mVSD were taken to the cardiology department of First Affiliated Hospital of Kunming Medical University from July 2015 to June 2021 as research subjects.They were divided into two groups:14 children who received Cardi-O-Fix Plug occluder as the experimental group,and 10 children who received Cardi-O-O-Fix mVSD occluder as the control group.Electrocardiogram and transthoracic echocardiography were used to evaluate the occlusive efficacy and incidence of complications 1 day after surgery and 1 month,3 months,and 6 months of follow-up.Results Among the 24 pediatric patients,22 cases were successfully occluded,and 2 cases were unsuccessful(1 in the experi-mental group and 1 in the control group).The success rate of the experimental group was 92.8%(13/14),while the success rate of the control group was 90.0%(9/10).The average surgical duration of the experimental group was(71.93±14.85)minutes,while the average surgical duration of the control group was(90.70±19.78)minutes.There was a significant statistical difference between the two groups(P<0.05).Both the experimental group and the control group did not experience serious complications during surgery and follow-up.There was no significant difference in cardiac ultrasound indicators(including left ventricular ejection fraction,left ventricular end-diastolic diameter,and pulmonary artery pressure)between the two groups at different time points(P>0.05).Conclusion Trans-catheter closure of mVSD using Cardi-O-Fix Plug occluder in children is both safe and effective.The incidence of arrhythmia is low in the short,medium and long term.

Bacterial biofilms gave rise to persistent infections and multi-organ failure, thereby posing a serious threat to human health. Biofilms were formed by cross-linking of hydrophobic extracellular polymeric substances (EPS), such as proteins, polysaccharides, and eDNA, which were synthesized by bacteria themselves after adhesion and colonization on biological surfaces. They had the characteristics of dense structure, high adhesiveness and low drug permeability, and had been found in many human organs or tissues, such as the brain, heart, liver, spleen, lungs, kidneys, gastrointestinal tract, and skeleton. By releasing pro-inflammatory bacterial metabolites including endotoxins, exotoxins and interleukin, biofilms stimulated the body’s immune system to secrete inflammatory factors. These factors triggered local inflammation and chronic infections. Those were the key reason for the failure of traditional clinical drug therapy for infectious diseases.In order to cope with the increasingly severe drug-resistant infections, it was urgent to develop new therapeutic strategies for bacterial-biofilm eradication and anti-bacterial infections. Based on the nanoscale structure and biocompatible activity, nanobiomaterials had the advantages of specific targeting, intelligent delivery, high drug loading and low toxicity, which could realize efficient intervention and precise treatment of drug-resistant bacterial biofilms. This paper highlighted multiple strategies of biofilms eradication based on nanobiomaterials. For example, nanobiomaterials combined with EPS degrading enzymes could be used for targeted hydrolysis of bacterial biofilms, and effectively increased the drug enrichment within biofilms. By loading quorum sensing inhibitors, nanotechnology was also an effective strategy for eradicating bacterial biofilms and recovering the infectious symptoms. Nanobiomaterials could intervene the bacterial metabolism and break the bacterial survival homeostasis by blocking the uptake of nutrients. Moreover, energy-driven micro-nano robotics had shown excellent performance in active delivery and biofilm eradication. Micro-nano robots could penetrate physiological barriers by exogenous or endogenous driving modes such as by biological or chemical methods, ultrasound, and magnetic field, and deliver drugs to the infection sites accurately. Achieving this using conventional drugs was difficult. Overall, the paper described the biological properties and drug-resistant molecular mechanisms of bacterial biofilms, and highlighted therapeutic strategies from different perspectives by nanobiomaterials, such as dispersing bacterial mature biofilms, blocking quorum sensing, inhibiting bacterial metabolism, and energy driving penetration. In addition, we presented the key challenges still faced by nanobiomaterials in combating bacterial biofilm infections. Firstly, the dense structure of EPS caused biofilms spatial heterogeneity and metabolic heterogeneity, which created exacting requirements for the design, construction and preparation process of nanobiomaterials. Secondly, biofilm disruption carried the risk of spread and infection the pathogenic bacteria, which might lead to other infections. Finally, we emphasized the role of nanobiomaterials in the development trends and translational prospects in biofilm treatment.

Objective To investigate the protective effect and mechanism of hyperoside(HYP)on paraquat(PQ)-induced acute lung injury in rats.Methods Rats were randomly divided into the control group,the PQ group,the low-dose hyperoside group(HYP-L group),the middle-dose hyperoside group(HYP-M group)and the high-dose hyperoside group(HYP-H group),with 12 rats in each group.After 7 days of corresponding treatment,the levels of interleukin(IL)-1β,IL-6 and macrophage inflammatory protein-2(MIP-2)in bronchoalveolar lavage fluid(BALF)of rats in each group,as well as the levels of malondialdehyde(MDA)and superoxide dismutase(SOD)in lung tissue were detected.The degree of lung injury and fibrosis of rats were evaluated by hematoxylin-eosin(HE)staining and Masson's trichrome staining.The expression levels of E-cadherin,α-smooth muscle actin(α-SMA),Vimentin,and protein expression levels of nuclear factor erythroid 2-related factor 2(Nrf2),nuclear factor-κB(NF-κB)p65,p-NF-κB p65,transforming growth factor-β1(TGF-β1),Smad3 and p-Smad3 in lung tissue were detected by Western blot.Results Compared with the control group,the levels of IL-1β,IL-6 and MIP-2 in BALF of rats in the PQ group increased(P<0.05),the level of SOD in the lung tissue decreased,while the level of MDA increased(P<0.05),and the lung tissue showed obvious damage and fibrosis(P<0.05).Compared with the PQ group,the levels of IL-1β,IL-6 and MIP-2 in BALF of rats in the HYP-L group,the HYP-M group and the HYP-H group decreased(P<0.05),the levels of SOD in the lung tissue increased(P<0.05),while the levels of MDA decreased(P<0.05),and the lung tissue damages were alleviated,and the fibrosis score decreased(P<0.05).Compared with the control group,the expression level of E-cadherin in the lung tissue of rats in the PQ group decreased(P<0.05),the expression levels of α-SMA and Vimentin increased(P<0.05),the protein expression level of Nrf2 decreased(P<0.05),the protein expression level of TGF-β1 and the phosphorylation levels of NF-κB p65 and Smad3 proteins increased(P<0.05).Compared with the PQ group,the expression levels of E-cadherin in the lung tissues of rats in the HYP-L group,the HYP-M group and the HYP-H group increased(P<0.05),the expression levels of α-SMA and Vimentin decreased(P<0.05),the protein expression levels of Nrf2 increased(P<0.05),the protein expression level of TGF-β1 and the phosphorylation levels of NF-κB p65 and Smad3 proteins decreased(P<0.05).Conclusion Hyperoside effectively alleviates paraquat-induced acute lung injury in rats,and it may reduce lung oxidative stress,inflammation and fibrosis by regulating Nrf2,NF-κB and TGF-β1/Smad2/3 signal pathways.

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease affecting both upper and lower motor neurons. ALS patients develop progressive muscle atrophy, muscle weak and paralysis, finally died of respiratory failure. ALS is characterized by fast aggression and high mortality. What' s more, the disease is highly heterogeneous with unclear pathogenesis and lacks effective drugs for therapy. In this review, we summarize the main pathological mechanisms and the current drugs under development for ALS, which may provide a reference for the drug discovery in the future.

Objective To detect the expression changes of interleukin-10(IL-10)and transforming growth factor-β1(TGF-β1)during the development of deep vein thrombosis in mice,and to explore the application value of them in thrombus age estimation.Methods The mice in the experimental group were subjected to ligation of inferior vena cava.The mice were sacrificed by excessive anesthesia at 1 d,3 d,5 d,7 d,10 d,14 d and 21 d after ligation,respectively.The inferior vena cava segment with thrombosis was extracted below the ligation point.The mice in the control group were not ligated,and the inferior vena cava segment at the same position as the experimental group was extracted.The ex-pression changes of IL-10 and TGF-β1 were detected by immunohistochemistry(IHC),Western blot-ting and real-time qPCR.Results IHC results revealed that IL-10 was mainly expressed in monocytes in thrombosis and TGF-β1 was mainly expressed in monocytes and fibroblast-like cells in thrombosis.Western blotting and real-time qPCR showed that the relative expression levels of IL-10 and TGF-β1 in each experimental group were higher than those in the control group.The mRNA and protein levels of IL-10 reached the peak at 7 d and 10 d after ligation,respectively.The mRNA expression level at 7 d after ligation was 4.72±0.15 times that of the control group,and the protein expression level at 10 d after ligation was 7.15±0.28 times that of the control group.The mRNA and protein levels of TGF-β1 reached the peak at 10 d and 14 d after ligation,respectively.The mRNA expression level at 10 d after ligation was 2.58±0.14 times that of the control group,and the protein expression level at 14 d after ligation was 4.34±0.19 times that of the control group.Conclusion The expressions of IL-10 and TGF-β1 during the evolution of deep vein thrombosis present time-dependent sequential changes,and the expression levels of IL-10 and TGF-β1 can provide a reference basis for thrombus age estimation.

Pharmacokinetics of traditional Chinese medicine(TCM)is a discipline that adopts pharmacokinetic research methods and techniques under the guidance of TCM theories to elucidate the dynamic changes in the absorption,distribution,metabolism and excretion of active ingredients,active sites,single-flavour Chinese medicinal and compounded formulas of TCM in vivo.However,the sources and components of TCM are complex,and the pharmacodynamic substances and mechanisms of action of the majority of TCM are not yet clear,so the pharmacokinetic study of TCM is later than that of chemical medicines,and is far more complex than that of chemical medicines,and its development also confronts with challenges.The pharmacokinetic study of TCM originated in the 1950s and has experienced more than 70 years of development from the initial in vivo study of a single active ingredient,to the pharmacokinetic and pharmacodynamic study of active ingredients,to the pharmacokinetic study of compound and multi-component of Chinese medicine.In recent years,with the help of advanced extraction,separation and analysis technologies,gene-editing animals and cell models,multi-omics technologies,protein purification and structure analysis technologies,and artificial intelligence,etc.,the pharmacokinetics of TCM has been substantially applied in revealing and elucidating the pharmacodynamic substances and mechanisms of action of Chinese medicines,research and development of new drugs of TCM,scientific and technological upgrading of large varieties of Chinese patent medicines,as well as guiding the rational use of medicines in clinics.Pharmacokinetic studies of TCM have made remarkable breakthroughs and significant development in theory,methodology,technology and application.In this paper,the history of the development of pharmacokinetics of TCM and the progress of cutting-edge research was reviewed,with the aim of providing ideas and references for the pharmacokinetics of TCM and related research.

Objective:To explore the application value and surgical experience of neuroendoscopic resection for pediatric patients with cerebellar tumors.Methods:This was a case series study.The clinical data and outcomes of 30 pediatric patients with cerebellar tumors treated through neuroendoscopic surgery in the Department of Neurosurgery, the Guizhou Hospital of Shanghai Children′s Medical Center and Guizhou Provincial People′s Hospital from January 2021 to January 2024 were retrospectively analyzed.Results:Twenty-six patients underwent total resection, 3 patients underwent subtotal resection, and 1 patient underwent biopsy.Postoperative pathological findings showed 9 cases of medulloblastoma, 3 cases of ependymoma, 17 cases of astrocytoma (5 cases of World Health Organization Grade Ⅰ, 3 cases of Grade Ⅱ, and 9 cases of Grade Ⅲ), and 1 case of cerebellar benign lesion.During the perioperative period, malignant arrhythmia occurred and induced death in 1 case, cerebellar mutism occurred in 12 cases, and ataxia occurred in 22 cases.During the 1-36 months of follow-up, 2 cases developed communicating hydrocephalus at the 2 nd and the 6 th month, respectively, and improved after ventriculoperitoneal shunt; cerebellar mutism was relieved to varying degrees after an average postoperative follow-up period of (115±23) days(46-194 days), and ataxia was alleviated after an average postoperative follow-up period of (127±42) days(27-173 days).Tumors relapsed in 5 cases during the last follow-up. Conclusions:Neuroendoscopy provides an alternative to the microscope for experienced operators to achieve the surgical exposure requirements during the resection of pediatric cerebellar vermis tumors.