Inflammatory diseases (IDs) are a general term of diseases characterized by chronic inflammation as the primary pathogenetic mechanism, which seriously affect the quality of patient′s life and cause significant social and medical burden. Current drugs for IDs include nonsteroidal anti-inflammatory drugs, corticosteroids, immunomodulators, biologics, and antioxidants, but these drugs may cause gastrointestinal side effects, induce or worsen infections, and cause non-response or intolerance. Given the outstanding performance of metal polyphenol network (MPN) in the fields of drug delivery, biomedical imaging, and catalytic therapy, its application in the diagnosis and treatment of IDs has attracted much attention and significant progress has been made. In this paper, we first provide an overview of the types of IDs and their generating mechanisms, then sort out and summarize the different forms of MPN in recent years, and finally discuss in detail the characteristics of MPN and their latest research progress in the diagnosis and treatment of IDs. This research may provide useful references for scientific research and clinical practice in the related fields.

Aim To discover the potential active compounds and possible mechanisms in rheumatoid arthritis (RA) treatment with Zhi-Huang-Zhi-Tong powder (ZHZTP) by using network pharmacology and in vitro study. Methods The active ingredient targets and disease targets of Zhihuang Zhitong Powder were searched and screened by database; they intersected to get a common target; and the "drug-component-target" relationship network diagram was constructed for GO and KEGG enrichment analysis of the overlapping genes; then the core components were docked with the core targets. Finally, based on the inflammation model of HUVECs in vitro, the efficacy and mechanism of Zhihuang Zhitong powder were verified by MTT method, plate scratch test and Western blot. Results Active compounds involved in RA treatment were screened in the present study, and the top two were ursolic acid and emodin, all playing crucial roles in RA treatment with ZHZTP. Additionally, the key target was AKTA, TNF and IL-6. GO and KEGG enrichment analysis revealed that ZHZTP regulated BP, MF and CC, and also focused on regulating AKTA, TNF and IL-6 signaling pathway. Molecular docking showed that interactions between key active compounds and key targets were stable. In vitro ZHZTP significantly inhibited cell viability and migration of TNF-a-stimulated HUVECs, and the involved mechanism may be associated with PI3K/AKT/m-TOR signaling. Conclusions The present study reveals that the potential active compounds of ZHZTP are ursolic acid and emodin, and moreover, the involved mechanisms of ZHZTP for RA treatment are associated with PI3 K/AKT/m-TOR signaling.

BACKGROUND:The mechanism,manifestation,prevention and treatment of ischemia-reperfusion injury have been reported in the past.However,there are few studies on the ischemia-reperfusion injury of lower limb skeletal muscle caused by total knee arthroplasty.This article focuses on the pathogenesis,clinical impact,prevention and treatment of the ischemia-reperfusion injury of lower limb caused by total knee arthroplasty. OBJECTIVE:To summarize the related literature of lower limb ischemia-reperfusion injury caused by total knee arthroplasty,analyze the mechanism and significance,and give hints for further research on skeletal muscle ischemia-reperfusion injury. METHODS:The relevant articles on PubMed,CNKI,WanFang and VIP databases published from January 1,2000 to April 30,2022 were searched by computer with the Chinese and English search terms of"ischemia-reperfusion injury,total knee arthroplasty,tourniquet,mechanism,pathophysiology,skeletal muscle,treatment".After excluding repetitive research and some basic articles with low correlation,68 articles were finally selected for review. RESULTS AND CONCLUSION:(1)The pathogenesis of ischemia-reperfusion injury is related to oxygen free radicals,intracellular calcium overload,neutrophil activation,as well as high concentration of nitric oxide,no reflow phenomenon,apoptosis and other mechanisms.More detailed mechanism research can provide basis for future prevention and treatment.(2)Ischemia-reperfusion injury of lower limbs will cause local skeletal muscle injury,which may be caused by the trauma of the operation itself or the role of ischemia-reperfusion injury.More targeted research is needed to distinguish the relationship between the two.(3)Ischemia-reperfusion injury of lower limbs may even affect the distal organs,causing kidney and lung damage.It also affects local and systemic circulation.(4)To clarify the effect of ischemia-reperfusion injury can point out the direction for future prevention and treatment.The current prevention and treatment measures mainly include ischemic preconditioning,anesthetic,antioxidant and other drug prevention.(5)The detailed review of ischemia-reperfusion injury of lower limb skeletal muscle caused by total knee arthroplasty can provide basis for future diagnosis and treatment decisions.

BACKGROUND:Dexmedetomidine has the effect of anti-ischemia-reperfusion injury,but the comprehensive and systematic review of its signaling pathway is less. OBJECTIVE:To focus on the review of dexmedetomidine's signaling pathway in the mechanisms of antioxidant stress,inhibition of inflammation,anti-apoptosis,autophagy,and so on. METHODS:The relevant articles on PubMed,CNKI,WanFang,and VIP databases were searched by computer with the key words"ischemia-reperfusion inquiry;dexmedetomidine;signal path;oxidative stress;inflammation;apoptosis"in Chinese and English.After excluding repetitive research and some basic articles with low correlation,57 articles were finally included for review. RESULTS AND CONCLUSION:(1)Dexmedetomidine plays an important role in organ protection through many mechanisms,such as anti-oxidative stress injury,anti-inflammation,anti-apoptosis and autophagy.This involves many pathways,including Nrf2 and its downstream protein antioxidant stress pathway,Toll-like receptor 4 family and nuclear factor-κB-related anti-inflammatory pathway,JAK2/STAT3-related anti-inflammatory pathway,and cholinergic anti-inflammatory pathway,and the cholinergic pathway is the upstream mechanism of many nuclear factor-κB signaling pathways.(2)PI3K/Akt pathway plays different roles according to its activated downstream signals,inhibiting the activation of NLRP3 inflammatory body,activating signal molecules endothelial nitric oxide synthase,mammalian target of rapamycin,and hypoxia-inducible factor 1α to play an anti-inflammatory role,and activate Bad or Bax residues to play an anti-apoptotic role,and PI3K/Akt activates glycogen synthetase kinase-3β.It can also play an anti-inflammatory and anti-apoptotic role.(3)Dexmedetomidine activates SIRT3 to mediate anti-apoptosis and inhibit endoplasmic reticulum stress to produce anti-apoptosis.(4)The detailed review of the anti-ischemia-reperfusion injury signaling pathway of dexmedetomidine can provide a basis for future mechanism research and diagnosis and treatment decisions.

Objective:To analyze the characteristics of patients with chronic rhinosinusitis (CRS) in the South China region based on pathological tissue biomarkers for regional comparison.Methods:The study population consisted of CRS in-patients in the First Affiliated Hospital of Sun Yat-sen University from October 2019 to June 2022. Among all the 181 cases, 123 of them were male and 58 were female, with an average age of 40. Retrospectively collected clinical data included demographic information, preoperative symptom scores, preoperative endoscopic images, preoperative paranasal sinus computed tomography scanning images, and inflammatory serological features. In addition, 52 variables of pathological tissue biomarkers including cytokines, chemokines and remodeling factors were collected for analysis. Cluster analysis was performed on the integrated data of training set through centroid-based clustering algorithm, and the inflammatory characteristics, post-operation control status, and airway diseases comorbidity of each endotype were analyzed. R project (version 4.2.2) was used in statistical analysis.Results:Cluster analysis divided 181 patients with CRS into 4 endotypes. Cluster 1 ( n=101, 55.80%) showed a locally low inflammatory status. Cluster 2 ( n=23, 12.71%) showed a mixed type of inflammation with predominantly neutrophilic inflammation and tissue remodeling. Cluster 3 ( n=11, 6.08%) was characterized by type Ⅱ inflammation without tissue remodeling. Cluster 4 ( n=46, 25.41%) was mainly characterized by type Ⅱ inflammation with tissue remodeling, showing higher comorbidity rate of asthma and allergic rhinitis. This cluster presented more severe symptoms, significant olfactory dysfunction, extensive overall inflammation based on objective examination results, a notable increase in total eosinophil count and proportion in peripheral blood, and the highest uncontrolled rate observed one year post-surgery. In comparison to other regions, the endotype classification of CRS in Southern China was characterized by a predominant pattern of locally low inflammatory status, a moderate level of type Ⅱ inflammation with tissue remodeling, and a lesser presence of neutrophilic inflammation. Conclusion:CRS distribution in Southern China is mainly characterized by low inflammatory endotype and type Ⅱ inflammation with tissue remodeling. The latter shows more severe clinical manifestations and higher uncontrol rate after surgery.

Objective To investigate the clinical characteristics and prognosis of pneumococcal meningitis(PM),and drug sensitivity of Streptococcus pneumoniae(SP)isolates in Chinese children.Methods A retrospective analysis was conducted on clinical information,laboratory data,and microbiological data of 160 hospitalized children under 15 years old with PM from January 2019 to December 2020 in 33 tertiary hospitals across the country.Results Among the 160 children with PM,there were 103 males and 57 females.The age ranged from 15 days to 15 years,with 109 cases(68.1% )aged 3 months to under 3 years.SP strains were isolated from 95 cases(59.4% )in cerebrospinal fluid cultures and from 57 cases(35.6% )in blood cultures.The positive rates of SP detection by cerebrospinal fluid metagenomic next-generation sequencing and cerebrospinal fluid SP antigen testing were 40% (35/87)and 27% (21/78),respectively.Fifty-five cases(34.4% )had one or more risk factors for purulent meningitis,113 cases(70.6% )had one or more extra-cranial infectious foci,and 18 cases(11.3% )had underlying diseases.The most common clinical symptoms were fever(147 cases,91.9% ),followed by lethargy(98 cases,61.3% )and vomiting(61 cases,38.1% ).Sixty-nine cases(43.1% )experienced intracranial complications during hospitalization,with subdural effusion and/or empyema being the most common complication[43 cases(26.9% )],followed by hydrocephalus in 24 cases(15.0% ),brain abscess in 23 cases(14.4% ),and cerebral hemorrhage in 8 cases(5.0% ).Subdural effusion and/or empyema and hydrocephalus mainly occurred in children under 1 year old,with rates of 91% (39/43)and 83% (20/24),respectively.SP strains exhibited complete sensitivity to vancomycin(100% ,75/75),linezolid(100% ,56/56),and meropenem(100% ,6/6).High sensitivity rates were also observed for levofloxacin(81% ,22/27),moxifloxacin(82% ,14/17),rifampicin(96% ,25/26),and chloramphenicol(91% ,21/23).However,low sensitivity rates were found for penicillin(16% ,11/68)and clindamycin(6% ,1/17),and SP strains were completely resistant to erythromycin(100% ,31/31).The rates of discharge with cure and improvement were 22.5% (36/160)and 66.2% (106/160),respectively,while 18 cases(11.3% )had adverse outcomes.Conclusions Pediatric PM is more common in children aged 3 months to under 3 years.Intracranial complications are more frequently observed in children under 1 year old.Fever is the most common clinical manifestation of PM,and subdural effusion/emphysema and hydrocephalus are the most frequent complications.Non-culture detection methods for cerebrospinal fluid can improve pathogen detection rates.Adverse outcomes can be noted in more than 10% of PM cases.SP strains are high sensitivity to vancomycin,linezolid,meropenem,levofloxacin,moxifloxacin,rifampicin,and chloramphenicol.[Chinese Journal of Contemporary Pediatrics,2024,26(2):131-138]

Objective To investigate the distribution and antimicrobial susceptibility of clinically isolated bacteria from intensive care units(ICUs)in hospitals of Hunan Province Antimicrobial Resistance Surveillance System from 2012 to 2021.Methods According to China Antimicrobial Resistance Surveillance System,data of clinically isolated bacterial strains and antimicrobial susceptibility testing results of bacteria from ICUs reported by all member units of Hunan Province Antimicrobial Resistance Surveillance System were analyzed with WHONET 2022 software.Results From 2012 to 2021,the total number of bacteria isolated from ICUs of member units of the Hunan Province Antimi-crobial Resistance Surveillance System was 5 777-22 369,with Gram-negative bacteria accounting for 76.1％-78.0％annually.Staphylococcus aureus ranked first among isolated Gram-positive bacteria each year.The top 5 bacteria among Gram-negative bacteria were Acinetobacter baumannii,Klebsiella pneumoniae,Escherichia coli,Pseudo-monas aeruginosa,and Stenotrophomonas maltophilia.Detection rate of methicillin-resistant Staphylococcus aureus showed a downward trend year by year.No Staphylococcus spp.were found to be resistant to vancomycin,teico-planin and linezolid.Detection rates of vancomycin-resistant Enterococcus faecalis and vancomycin-resistant Entero-coccus faecium were 0.6-1.1％and 0.6％-2.2％,respectively.Resistance rates of Escherichia coli and Kleb-siella pneumoniae to imipenem were 3.1％-5.7％and 7.7％-20.9％,respectively.Resistance rates of Pseudo-monasaeruginosa and Acinetobacter baumannii to imipenem were 24.6％-40.1％and 76.1％-80.9％,respective-ly.Detection rates of carbapenem-resistant Pseudomonas aeruginosa declined year by year.Acinetobacter baumannii maintained high susceptibility to polymyxin B,with resistance rate＜10％.Conclusion Antimicrobial resistance of bacteria from ICUs is serious.Carbapenem-resistant Enterobacteriales has an upward trend after 2019.It is nece-ssary to strengthen the surveillance of bacterial resistance and carry out multidisciplinary collaboration.

Objective To explore early postoperative gait characteristics and clinical outcomes after total knee arthroplasty(TKA).Methods From February 2023 to July 2023,26 patients with unilateral knee osteoarthritis(KOA)were treated with TKA,including 4 males and 22 females,aged from 57 to 85 years old with an average of(67.58±6.49)years old;body mass in-dex(BMI)ranged from 18.83 to 38.28 kg·m-2 with an average of(26.43±4.15)kg·m-2;14 patients on the left side,12 pa-tients on the right side;according to Kellgren-Lawrence(K-L)classification,6 patients with grade Ⅲ and 20 patients with grade Ⅳ;the courses of disease ranged from 1 to 14 years with an average of(5.54±3.29)years.Images and videos of standing up and walking,walking side shot,squatting and supine kneeling were taken with smart phones before operation and 6 weeks after operation.The human posture estimation framework OpenPose were used to analyze stride frequency,step length,step length,step speed,active knee knee bending angle,stride length,double support phase time,as well as maximum hip flexion angle and maximum knee bending angle on squatting position.Western Ontario and McMaster Universities(WOMAC)arthritis index and Knee Society Score(KSS)were used to evaluate clinical efficacy of knee joint.Results All patients were followed up for 5 to 7 weeks with an average of(6.00±0.57)weeks.The total score of WOMAC decreased from(64.85±11.54)before op-eration to(45.81±7.91)at 6 weeks after operation(P＜0.001).The total KSS was increased from(101.19±9.58)before opera-tion to(125.50±10.32)at 6 weeks after operation(P＜0.001).The gait speed,stride frequency and stride length of the affected side before operation were(0.32±0.10)m·s-1,(96.35±24.18)steps·min-1,(0.72±0.14)m,respectively;and increased to(0.48±0.11)m·s 1,(104.20±22.53)steps·min-1,(0.79±0.10)m at 6 weeks after operation(P＜0.05).The lower limb support time and active knee bending angle decreased from(0.31±0.38)sand(125.21±11.64)° before operation to(0.11±0.04)s and(120.01±13.35)° at 6 weeks after operation(P＜0.05).Eleven patients could able to complete squat before operation,13 patients could able to complete at 6 weeks after operation,and 9 patients could able to complete both before operation and 6 weeks after operation.In 9 patients,the maximum bending angle of crouching position was increased from 76.29° to 124.11° before operation to 91.35° to 134.12° at 6 weeks after operation,and the maximum bending angle of hip was increased from 103.70° to 147.25° before operation to 118.61° to 149.48° at 6 weeks after operation.Conclusion Gait analysis technology based on artificial intelligence image recognition is a safe and effective method to quantitatively identify the changes of pa-tients'gait.Knee pain of KOA was relieved and the function was improved,the supporting ability of the affected limb was im-proved after TKA,and the patient's stride frequency,stride length and stride speed were improved,and the overall movement rhythm of both lower limbs are more coordinated.

Objective To investigate the physiological characteristics of Bacillus thuringiensis subspecies israelensis (Bti) with double mutations of cwlE and sigK genes and to assess the activity of Bti against larvae of Culex pipiens pallens under different external factors, so as to provide the theoretical evidence for the use of engineered bacteria of Bti for effective mosquito control. Methods B. thuringiensis wild-type strain Bt-59 and Bt-59 strain with cwlE mutation [Bt-59 (ΔcwlE)] were cultured in nutrient broth media for 24 hours, and Bt-59 strains with sigK mutation [Bt-59 (ΔsigK)] and double mutations of cwlE and sigK [Bt-59 (ΔcwlE-sigK)] were cultured in nutrient broth media for 48 hours. Then, 5 μL of culture media were transferred to glass sides, and cell morphology and mother cell lysis were observed under an optical microscope. The optical densities of Bti strain culture media were measured at different time points of culture, and the growth curves of Bt-59, Bt-59 (ΔcwlE), Bt-59 (ΔsigK), and Bt-59 (ΔcwlE-sigK) strains were plotted. The differences in carbon source metabolism of four Bti strains were analyzed using the Biolog microplate culture method, and the metabolic activity of these strains was estimated with average well color development (AWCD). The fermentation media of these four Bti strains were diluted into final concentrations of 2.000, 1.000, 0.500, 0.250, and 0.125 μL/L, and the median lethal concentrations (LC₅₀ values) of these four strains against the third instar larvae of Cx. pipiens pallens were determined. In addition, the fermentation media of Bti strains were processed as follows: pH adjusted to 5, 7 and 9; treated at 30, 40 ℃ and 50 ℃ for 12 hours; and exposed to irradiation with ultraviolet lights for 0 hour and 6 hours. Then, 20 third instar larvae of Cx. pipiens pallens were exposed to the above processed fermentation media at a final concentration of 1 μL/L in 200 mL of water at 26 ℃ for 24 hours, and the mosquito mortality was estimated to evaluate the effects of pH, temperature and ultraviolet irradiation on the larvicidal activity of four Bti strains. Results The growth curves of the Bt-59 strain and its mutants shared a similar changing trend, and both experienced a stable phase 6 hours post-culture. Both spores and crystal proteins were found in Bt-59 and Bt-59 (ΔcwlE) cells, and only crystal proteins were found in Bt-59 (ΔsigK) and Bt-59 (ΔcwlE-sigK) cells. No lysis was found in the cell wall of the Bt-59 (ΔcwlE-sigK) strain, and the crystal protein was embedded in the mother cell. Biolog microplate culture assay showed that the AWCD values of four Bti strains showed a similar changing trend over time, and 33 carbon sources were found to be metabolized by all of the four strains, including dextrin, D-maltose and D-trehalose. The LC50 values of the fermentation media of Bt-59, Bt-59 (ΔcwlE), Bt-59 (ΔsigK), and Bt-59 (ΔcwlE-sigK) strains were 0.60, 0.51, 0.70 μL/L and 0.72 μL/L against Cx. pipiens pallens, respectively. The adjusted mortality of larval Cx. pipiens pallens reduced by 76.60%, 76.00%, 66.67%, and 0 following exposure to the fermentation media of Bt-59, Bt-59 (ΔcwlE), Bt-59 (ΔsigK), and Bt-59 (ΔcwlE-sigK) strains at a pH of 5 relative to at a pH of 7, and the adjusted mortality reduced by 49.02%, 51.06%, 36.36%, and 4.44% following 6-hour exposure to ultraviolet irradiation relative to 0-hour exposure, while the adjusted mortality was 68.33% to 83.33% following treatment with the fermentation media of four Bti strains at different temperatures. Conclusions Bt-59 (ΔcwlE-sigK) strains do not generate spores, and the absence of cwlE and sigK does not affect the growth, carbon source metabolism, and larvicidal activity of Bti strains against larval Cx. pipiens pallens. Cell wall embedding of Bt-59 (ΔcwlE-sigK) strains may protect larvicidal crystal proteins of Bti strains from external environmental factors, including ultraviolet irradiation, and pH alteration.

Objective To explore the clinical value of endoscopic ultrasonography(EUS)combined with serum serine protease inhibitor Kazal 1(SPINK1)and secretory phosphoprotein 1(SPP1)in early diagnosis of esophageal cancer.Methods 276 patients from June 2021 to May 2023 were selected as the study objects.92 cases of esophageal cancer diagnosed by operation and pathology were esophageal cancer group,another 89 patients diagnosed as benign esophageal lesions through tissue biopsy were selected as the benign lesion group,and 95 healthy individuals who underwent physical examinations were collected as the healthy control group,general information such as age and gender of subjects in three groups were collected and organized;using pathological results as the gold standard,the accuracy of EUS in diagnosing esophageal cancer was verified;the expression of serum SPINK1 and SPP1 was compared among the esophageal cancer group,benign lesion group,and healthy control group;the relationship between the expression of serum SPINK1 and SPP1 in esophageal cancer patients and their clinical and pathological characteristics was explored;efficacy of EUS combined with serum SPINK1,SPP1 levels for early diagnosis of esophageal cancer was analyzed using receiver operator characteristic curve(ROC curve).Results Compared with the gold standard,the results of EUS examination showed that 81 cases were diagnosed with esophageal cancer,79 cases were diagnosed with benign lesions,11 cases were missed diagnosed,and 10 cases were misdiagnosed,with an accuracy rate of 88.40%(160/181);Compared with the healthy control group and the benign lesion group,the expression levels of serum SPINK1 and SPP1 in the esophageal cancer group were obviously increased,the expression levels of serum SPINK1 and SPP1 in the benign lesion group were significantly higher than those in the healthy control group,the differences were statistically significant(P<0.05);Serum SPINK1 expression was linked to tumor diameter>2 cm,presence of lymph node metastasis,lymph node positivity,and tissue grading level 3 in patients(P<0.05).Serum SPP1 expression level was related to tumor diameter>2 cm,presence of lymph node metastasis,lymph node positivity,and estrogen receptor positivity of patients(P<0.05);ROC curve showed that the area under the curve(AUC)of EUS,serum SPINK1,SPP1 levels,and their combination in the early diagnosis of esophageal cancer was 0.862,0.834,0.782,and 0.926,respectively,the clinical efficacy of the combination of the three in the early diagnosis of esophageal cancer was superior to that of EUS,serum SPINK1,and SPP1 alone(Z=2.30,Z=3.70,Z=4.23,P=0.022,P=0.000,P=0.000).Conclusion The expression levels of serum SPINK1 and SPP1 in esophageal cancer patients are abnormally up-regulated.The combination of EUS and serum SPINK1 and SPP1 has high clinical value in early diagnosis of esophageal cancer.