The recombinant human thyroid-stimulating hormone (rhTSH) can be used for differentiated thyroid cancer (DTC) preparation before ¹³¹I therapy, and follow-up. Since its approval by the American Food and Drug Administration (FDA) in 1998, rhTSH has been clinically used in European countries, the United States, and other countries for nearly 30 years. In April 2024, China’s first independently developed rhTSH agent was approved. Based on clinical experience and evidence from domestic and international studies, an expert consensus on the application of rhTSH has been developed following thorough consultations among experts. The consensus offers evidence-based recommendations to guide the appropriate use of rhTSH in clinical practice.

Objective To explore the role of the protein kinase R-like endoplasmic reticulum kinase(PERK)-mediated endoplasmic reticulum stress pathway in a model of lipopolysaccharide(LPS)-induced microglia inflammation.Methods To investigate its effects on endoplasmic reticulum(ER)stress,an inflammation model of microglia was established by stimulating with LPS at gradient concentrations for 24 hours and with 1 mg/L LPS for different durations.Cell viability was assessed by the CCK-8 assay;The mRNA and protein expression levels of related inflammatory factors were measured by Real-time PCR and ELISA kits.Cellular oxidative stress was evaluated by detecting reactive oxygen species(ROS),and Real-time PCR and Western blotting were used to examine the mRNA and protein expression levels of ER stress pathway markers associated with inflammation.Results 1.The effects of different concentrations of LPS on cell viability and morphology were not statistically significant after acting on BV-2 cells for 24 hours(P＞0.05);2.1 mg/L LPS incubated with BV-2 cells for different times and the cell viability decreased with the increase of time;3.Compared with the 0 hour group,the levels of pro-inflammatory cytokine interleukin(IL)-1β,tumor necrosis factor-α(TNF-α)mRNA and protein expression increased significantly(P＜0.05)in the LPS-stimulated 9 hours,12 hours,and 24 hours groups,and the inflammation model was successfully established;4.Compared with the 0 hour group,the protein and mRNA expression levels of the endoplasmic reticulum stress pathway-related indexes in the LPS-stimulated 9 hours,12 hours,and 24 hours groups increased significantly(P＜0.01),which showed the time-dependence;5.After adding the PERK inhibitor GSK2606414,the mRNA and protein expression levels of endoplasmic reticulum stress-related indicators in the PERK inhibitor group were significantly reduced compared with those in the LPS group(P＜0.05);6.The mRNA and protein expression levels of pro-inflammatory cytokines and the fluorescence intensity of ROS in the PERK inhibitor group were significantly reduced compared with those in the LPS group(P＜0.01).Conclusion Targeting PERK-mediated endoplasmic reticulum stress inhibits LPS-induced inflammatory responses in microglia.

Objective To establish a human intestinal organ-on-a-chip model using a multi-array chip array to simulate the microphysiological structure of the human intestine and to investigate the impact of ionizing radiation on radiation-induced damage to human intestinal cells.Methods Caco-2 and human umbilical vein endothelial cells(HUVECs)were co-cultured in an organ chip.The cells were subjected to fluid shear stress via a precision shaker.After 7 days of dynamic culture,the morphological structure of intestinal epithelial cells and venous endothelial cells within the intestinal organ chip was examined using phase contrast microscopy,immunofluorescence staining,and confocal microscopy for three-dimensional(3D)imaging.γ-H2AX and TUNEL immunofluorescence staining were employed to assess DNA damage and apoptosis in intestinal epithelial cells two days post-irradiation.Villin immunofluorescence staining was used to evaluate villus height three days post-irradiation.EdU incorporation assay and Ki67 immunofluorescence staining were conducted to observe the effects of ionizing radiation on the proliferation of intestinal epithelial cells.Results After 7 days of dynamic culture,phase contrast microscopy and immunofluorescence staining combined with confocal 3D imaging revealed that the upper intestinal epithelial cells in the middle compartment of the chip formed a 3D intestinal villus structure,while the vascular endothelial cells in the lower compartment developed a vascular network structure.The chip was subsequently irradiated by 10 Gy X-ray.Immunofluorescence staining results indicated that the mean fluorescence intensity of γ-H2AX and TUNEL in the irradiated group was significantly higher than in the non-irradiated group 2 days after irradiation(P＜0.01),and that the proportion of EDU+and Ki67+cells in the irradiated group was significantly lower than in the non-irradiated group three days after irradiation(P＜0.05).Conclusion Caco-2 cells and HUVECs co-culture on an organ chip can generate the biomimetic structure of human intestinal villus.Ionizing radiation has been found to shorten intestinal villus,increase DNA damage and apoptosis in intestinal epithelial cells,and inhibit the proliferation of these cells.

Objective To establish a rapid analysis method for cyanide based on a ratiometric fluores-cent probe,providing a quantitative strategy for on-site visual and rapid detection of cyanide.Methods A dual-emission ratiometric fluorescent probe(AuNCs-FL)was constructed by using bovine serum al-bumin(BSA)-stabilized gold nanoclusters(AuNCs,fluorescence emission at 660 nm)as the responsive signal unit and fluorescein(FL,emission at 515 nm)as the internal reference.Results The etching effect of cyanide on AuNCs resulted in fluorescence quenching at 660 nm,while the fluorescence inten-sity of FL at 515 nm remained unchanged,enabling a rapid response analysis of cyanide shift from red to green fluorescence.The developed probe enabled rapid analysis of cyanide within 3 min,with a limit of detection(LOD)of 3.4 mg/L and a visual detection range of 10-100 mg/L.Conclusion The AuNCs-FL fluorescent probe is structurally simple,low-cost,and easy to operate,delivering rapid and accurate results.It also avoids the interference from sulfides encountered in commercial cyanide test kits,making it suitable for the on-site rapid detection of suspected powder samples in cyanide poisoning cases.

Objective To investigate the effects of organophosphate flame retardant tri(2-chloroethyl)phosphate(TCPP)on reproductive function in male mice by the approach of non-targeted metabolomics.Methods A total of twelve 6-week-old SPF male CD-1 mice were randomly divided into control group and TCPP group,with 6 mice in each group.TCPP group was given TCPP(at the dose of 100 mg/kg/d)intragastrically,and control group was intragastrically adminis-trated with the same amount of corn oil(solvent control).After 6 weeks,the mice were killed,and the sperm were isolated from the epididymis.The sperm concentration and viability were analyzed.Testicular tissue sections were stained with he-matoxylin,and ki67 expression was detected by immunohistochemistry.Non-targeted metabolomics was used to detect the difference of metabolites in testicular tissue between the two groups,and to analyze the difference of metabolites and related pathway changes between the two groups.Results Compared with control group,the total sperm motility of mice in TCPP treatment group was significantly decreased(P＜0.05).HE staining showed irregular arrangement of spermatogenic tubule supporting cell layer in TCPP treatment group.The expression level of ki67 in testicular tissue of mice treated with TCPP was significantly decreased(P＜0.05).Non-targeted metabolomics detected 266 up-regulated metabolites with statistical difference.And 554 down-regulated metabolites with statistical difference,among which the largest difference multiples were organic acids and amino acid metabolites.The pathways with the highest concentration of differential metabolites in-cluded purine metabolism,nucleotide metabolism,amino acid metabolism,cofactor synthesis,etc.,which were mainly re-lated to basic cell life activities,pathophysiology and chemical carcinogenesis.Conclusion TCPP can significantly re-duce sperm motility and ki67 expression in mice at the dosage of 100 mg/kg/d,which might be related to its influence on key metabolic pathways such as purine,amino acid and pyruvate.

Objective To examine the changing prevalence and antimicrobial resistance profiles of Burkholderia cepacia in 52 hospitals across China from 2015 to 2021.Methods A total of 9 261 strains of B.cepacia were collected from 52 hospitals between January 1,2015 and December 31,2021.Antimicrobial susceptibility of the strains was tested using Kirby-Bauer method or automated antimicrobial susceptibility testing systems according to a unified protocol.The results were interpreted according to the breakpoints released in the Clinical & Laboratory Standards Institute(CLSI)guidelines(2023 edition).Results A total of 9 261 strains of B.cepacia were isolated from all age groups,especially elderly patients.The proportion was 11.1％(1 032 strains)in children,significantly lower than the proportion in adults.About half(46.5％,4 310/9 261)of the strains were isolated from patients at least 60 years old and 42.3％(3 919/9 261)of the strains were isolated from young adults.Most isolates(71.1％)were isolated from sputum and respiratory secretions,followed by urine(10.7％)and blood samples(8.1％).B.cepacia isolates were highly susceptible to the five antimicrobial agents recommended in the CLSI M100 document(33rd edition,2023).B.cepacia isolates showed relatively higher resistance rates to meropenem and levofloxacin.However,the resistance rates to ceftazidime,trimethoprim-sulfamethoxazole,and minocycline remained below 8.1％.The percentage of B.cepacia strains resistant to levofloxacin was the highest compared to other antibiotics in any of the three age groups(from 12.4％in the patients＜18 years old to 20.6％in the patients aged 60 years or older).Conclusions B.cepacia is one of the clinically important non-fermenting gram-negative bacteria.Accurate and timely reporting of antimicrobial susceptibility test results and ongoing antimicrobial resistance surveillance are helpful for rational prescription of antimicrobial agents and proper prevention and control of nosocomial infections.

Objective To investigate the distribution and antimicrobial resistance profiles of common pathogens isolated from cerebrospinal fluid(CSF)in CHINET program from 2015 to 2021.Methods The bacterial strains isolated from CSF were identified in accordance with clinical microbiology practice standards.Antimicrobial susceptibility test was conducted using Kirby-Bauer method and automated systems per the unified CHINET protocol.Results A total of 14 014 bacterial strains were isolated from CSF samples from 2015 to 2021,including the strains isolated from inpatients(95.3％)and from outpatient and emergency care patients(4.7％).Overall,19.6％of the isolates were from children and 80.4％were from adults.Gram-positive and Gram-negative bacteria accounted for 68.0％and 32.0％,respectively.Coagulase negative Staphylococcus accounted for 73.0％of the total Gram-positive bacterial isolates.The prevalence of MRSA was 38.2％in children and 45.6％in adults.The prevalence of MRCNS was 67.6％in adults and 69.5％in children.A small number of vancomycin-resistant Enterococcus faecium(2.2％)and linezolid-resistant Enterococcus faecalis(3.1％)were isolated from adult patients.The resistance rates of Escherichia coli and Klebsiella pneumoniae to ceftriaxone were 52.2％and 76.4％in children,70.5％and 63.5％in adults.The prevalence of carbapenem-resistant E.coli and K.pneumoniae(CRKP)was 1.3％and 47.7％in children,6.4％and 47.9％in adults.The prevalence of carbapenem-resistant Acinetobacter baumannii(CRAB)and Pseudomonas aeruginosa(CRPA)was 74.0％and 37.1％in children,81.7％and 39.9％in adults.Conclusions The data derived from antimicrobial resistance surveillance are crucial for clinicians to make evidence-based decisions regarding antibiotic therapy.Attention should be paid to the Gram-negative bacteria,especially CRKP and CRAB in central nervous system(CNS)infections.Ongoing antimicrobial resistance surveillance is helpful for optimizing antibiotic use in CNS infections.

Objective To investigate the antimicrobial resistance of clinical isolates from elderly patients(≥65 years)in major medical institutions across China.Methods Bacterial strains were isolated from elderly patients in 52 hospitals participating in the CHINET Antimicrobial Resistance Surveillance Program during the period from 2015 to 2021.Antimicrobial susceptibility test was carried out by disk diffusion method and automated systems according to the same CHINET protocol.The data were interpreted in accordance with the breakpoints recommended by the Clinical and Laboratory Standards Institute(CLSI)in 2021.Results A total of 514 715 nonduplicate clinical isolates were collected from elderly patients in 52 hospitals from January 1,2015 to December 31,2021.The number of isolates accounted for 34.3％of the total number of clinical isolates from all patients.Overall,21.8％of the 514 715 strains were gram-positive bacteria,and 78.2％were gram-negative bacteria.Majority(90.9％)of the strains were isolated from inpatients.About 42.9％of the strains were isolated from respiratory specimens,and 22.9％were isolated from urine.More than half(60.7％)of the strains were isolated from male patients,and 39.3％isolated from females.About 51.1％of the strains were isolated from patients aged 65-＜75 years.The prevalence of methicillin-resistant strains(MRSA)was 38.8％in 32 190 strains of Staphylococcus aureus.No vancomycin-or linezolid-resistant strains were found.The resistance rate of E.faecalis to most antibiotics was significantly lower than that of Enterococcus faecium,but a few vancomycin-resistant strains(0.2％,1.5％)and linezolid-resistant strains(3.4％,0.3％)were found in E.faecalis and E.faecium.The prevalence of penicillin-susceptible S.pneumoniae(PSSP),penicillin-intermediate S.pneumoniae(PISP),and penicillin-resistant S.pneumoniae(PRSP)was 94.3％,4.0％,and 1.7％in nonmeningitis S.pneumoniae isolates.The resistance rates of Klebsiella spp.(Klebsiella pneumoniae 93.2％)to imipenem and meropenem were 20.9％and 22.3％,respectively.Other Enterobacterales species were highly sensitive to carbapenem antibiotics.Only 1.7％-7.8％of other Enterobacterales strains were resistant to carbapenems.The resistance rates of Acinetobacter spp.(Acinetobacter baumannii 90.6％)to imipenem and meropenem were 68.4％and 70.6％respectively,while 28.5％and 24.3％of P.aeruginosa strains were resistant to imipenem and meropenem,respectively.Conclusions The number of clinical isolates from elderly patients is increasing year by year,especially in the 65-＜75 age group.Respiratory tract isolates were more prevalent in male elderly patients,and urinary tract isolates were more prevalent in female elderly patients.Klebsiella isolates were increasingly resistant to multiple antimicrobial agents,especially carbapenems.Antimicrobial resistance surveillance is helpful for accurate empirical antimicrobial therapy in elderly patients.

The phosphatidylinositol 3-kinase/protein kinase B/mammalian target of rapamycin(PI3K/Akt/mTOR)signaling pathway plays a crucial role in the regulation of renal fibrosis by participating in inflammatory response,oxidative stress and autophagy.Paeoniflorin exhibits remarkable efficacy in treating myocardial and liver fibrosis.This article provides a comprehensive review on the research progress of paeoniflora in preventing and treating renal fibrosis through modulation of the PI3K/Akt/mTOR signaling pathway,offering novel insights for traditional Chinese medicine-based approaches to prevent and treat renal fibrosis.

Objective To understand the changing composition and antibiotic resistance of bacterial species in the clinical isolates from outpatient and emergency department(hereinafter referred to as outpatients)and inpatient children over time in various hospitals,and to provide laboratory evidence for rational antibiotic use.Methods The data on clinically isolated pathogenic bacteria and antimicrobial susceptibility of isolates from outpatients and inpatient children in the CHINET program from 2015 to 2021 were collected and analyzed.Results A total of 278 471 isolates were isolated from pediatric patients in the CHINET program from 2015 to 2021.About 17.1％of the strains were isolated from outpatients,primarily group A β-hemolytic Streptococcus,Escherichia coli,and Staphylococcus aureus.Most of the strains(82.9％)were isolated from inpatients,mainly SS.aureus,E.coli,and H.influenzae.The prevalence of methicillin-resistant S.aureus(MRSA)in outpatients(24.5％)was lower than that in inpatient children(31.5％).The MRSA isolates from outpatients showed lower resistance rates to the antibiotics tested than the strains isolated from inpatient children.The prevalence of vancomycin-resistant Enterococcus faecalis or E.faecium and penicillin-resistant S.pneumoniae was low in either outpatients or inpatient children.S.pneumoniae,β-hemolytic Streptococcus and S.viridans showed high resistance rates to erythromycin.The prevalence of erythromycin-resistant group A β-hemolytic Streptococcus was higher in outpatients than that in inpatient children.The prevalence of β-lactamase-producing H.influenzae showed an overall upward trend in children,but lower in outpatients(45.1％)than in inpatient children(59.4％).The prevalence of carbapenem-resistant Klebsiella pneumoniae(CRKpn),carbapenem-resistant Pseudomonas aeruginosa(CRPae)and carbapenem-resistant Acinetobacter baumannii(CRAba)was 14％,11.7％,47.8％in outpatients,but 24.2％,20.6％,and 52.8％in inpatient children,respectively.The prevalence of multidrug-resistant E.coli,K.pneumoniae,Proteus mirabilis,P.aeruginosa and A.baumannii strains was lower in outpatients than in inpatient children.The prevalence of fluoroquinolone-resistant E.coli,ESBLs-producing K.pneumoniae,ESBLs-producing P.mirabilis,carbapenem-resistant E.coli(CREco),CRKpn,and CRPae was lower in children in outpatients than in inpatient children,but the prevalence of CRAba in 2021 was higher than in inpatient children.Conclusions The distribution of clinical isolates from children is different between outpatients and inpatients.The prevalence of MRSA,ESBL,and CRO was higher in inpatient children than in outpatients.Antibiotics should be used rationally in clinical practice based on etiological diagnosis and antimicrobial susceptibility test results.Ongoing antimicrobial resistance surveillance and prevention and control of hospital infections are crucial to curbing bacterial resistance.