OBJECTIVE To evaluate the cost-effectiveness of rezivertinib versus gefitinib as first-line treatment for epidermal growth factor receptor （EGFR） mutation-positive advanced non-small cell lung cancer （NSCLC） from the perspective of the Chinese healthcare system. METHODS A Markov model was constructed based on the REZOR trial data， with a cycle length of 3 weeks and a study duration of 5 years. Both costs and health outcomes were discounted at an annual rate of 5%. A cost-utility analysis was conducted using 3 times China’s 2024 per capita gross domestic product as the willingness-to-pay （WTP） threshold. The economic differences between the rezivertinib regimen versus the gefitinib regimen were evaluated using the incremental cost- effectiveness ratio （ICER） and incremental net monetary benefit （INMB）. Sensitivity and scenario analyses were performed to verify the robustness of the model. RESULTS Compared to the gefitinib regimen， the rezivertinib regimen saved 225 310.47 yuan and gained an additional 0.57 quality- adjusted life years （QALYs）， resulting in an ICER of －395 562.80 yuan/QALY， which was much lower than the WTP threshold of this study， indicating that rezivertinib had an absolute economic advantage. The INMB analysis （389 041.26 yuan） further validated this conclusion. One-way and probabilistic sensitivity analyses confirmed the robustness of the model. Scenario analysis， incorporating a 15% reduction in drug prices and adjustments to the utility values for progression free survival and progression disease， yielded consistent results with the base case analysis. CONCLUSIONS Compared to gefitinib， rezivertinib as a first-line treatment for EGFR mutation-positive advanced NSCLC has an absolute economic advantage.

Oral inflammatory diseases caused by odontogenic infections cover a wide range and have a high incidence rate,which can affect the morphology and function of the maxillofacial area and seriously en-danger oral health.Macrophages are important immunoactive cells in oral tissues,which can be polarized into M1/M2 type in different microenvironments,and then exert pro-inflammatory or anti-inflammatory effects,and are widely involved in the progression of odontogenic infectious diseases.In infections caused by oral mi-crobial factors such as bacteria,the distribution characteristics and polarization direction of macrophages in tis-sues are specific.At present,the research on macrophage polarization-related inflammatory diseases has attrac-ted more and more attention,and the regulation of macrophage M1/M2 polarization is gradually being used in the treatment of related diseases,and many research progress has been made in the diagnosis and treatment of odontogenic infectious diseases.In this paper,we elaborate on the distribution characteristics,polarization trends and related applications of macrophage polarization in common oral inflammatory diseases such as pul-pitis,apical periodontitis,periodontitis and peri-implantitis which are mainly caused by dental infections.The aim is to provide new ideas and targets for the diagnosis and treatment of oral inflammatory diseases.

Objective To explore the role and mechanism of warm malate ringer's solution(MR)in resuscitation of the lethal triad caused by severe trauma.Methods A rat model of severe trauma was established in SPF-grade SD rats(half male and half female,weighing 200～220 g)using combined multiple injuries and hemorrhagic shock,and the rats were randomly divided into 8 groups(n=8):Sham group,only arterial and venous catheterization;Trauma(Tra)groups with different time points(10,30,60,90,120,180 min)and a Trauma group that were observed without any treatment for 180 min after model establishment.The changes of activated clotting time(ACT),reaction time(R),maximum amplitude(MA),and rate of blood clot formation(Angle)at different time points were detected by using thromboelastography,and tail bleeding,core body temperature and arterial blood gas parameters,were also observed and detected.The plasma von Willebrand Factor(vWF)level,mitochondrial respiratory control ratio in pulmonary venous endothelium,and expression levels of vascular endothelial cadherin(VE-Cadherin),peroxisome proliferator activating receptor gamma coactivator 1α(PGC1α),dynamin-related protein 1(Drp1),p-Drp1,and mitofusin 2(Mfn2)were detected to evaluate the vascular endothelial injury and mitochondrial dysfunction.Another group of SD rats were randomly divided into severe trauma group(no treatment for 180 min after injury),and MR solution at room temperature and at 37 ℃ groups.MR solution at room temperature or at 37 ℃ was given to the rats using a medical blood transfusion apparatus at 60 min post-trauma.Above indicators were observed and detected to investigate the resuscitation effect of the MR solution.Results Compared with the Sham group,the severely traumatic rats at 180 min after injury had significantly prolonged ACT and R values(P＜0.05),shortened MA and decreased Angle values(P＜0.05),extended tail bleeding time(P＜0.05),lower partial pressure of carbon dioxide(PCO2)and HCO3-and base excess(BE)levels(P＜0.05),and continuously increasing K+(P＜0.05)and decreasing Na+(P＜0.05)and Ca2+levels(P＜0.05).Additionally,plasma vWF level(P＜0.05)and protein levels of VE-cadherin,PGC1α and Mfn2 in pulmonary vein endothelium were significantly reduced(P＜0.05),the expression of p-Drp1 was enhanced and the mitochondrial respiration control rate was declined in the rats at 180 min after injury(P＜0.05).MR solution resuscitation shortened tail bleeding time(P＜0.05),increased core body temperature(P＜0.05),elevated plasma vWF level(P＜0.05),increased protein levels of VE-cadherin,PGC1α and Mfn2(P＜0.05),and decreased that of p-Drp1 protein expression(P＜0.05)when compared with the rats at 180 min after severe traumatic injury.The above effects were more significant in the rats infused with the solution at 37 ℃ than those at room temperature.Conclusion Warm MR solution significantly improves the lethal triad in rats after severe trauma,which may be associated with its improving mitochondrial function and attenuating vascular endothelial damage.

Objective To stratify the estrogen receptor(ER)positive while human epidermal growth factor receptor 2(HER2)negative breast cancer patients by the expression level of ER,providing new evidence for prognostic prediction and guiding precision endocrine therapy(ET)for those with different ER expression levels.Methods A retrospective cohort study was conducted on 1 962 ER-positive/HER2-negative breast cancer patients treated in our department from January 1,2013 to December 31,2018.X-tile was used to calculate the optimal cutoff point of ER expression level,and then based on the results,they were divided into low(1%～10%),moderate(11%～30%),and high expression(31%～100%)groups.After propensity score matching(PSM)was performed to balance baseline characteristics,their prognostic outcomes were compared and the responses to ET were analyzed in the groups.Cox proportional risk regression model was applied to analyze the prognostic factors,and subgroup analysis was further performed.Results After PAM,129(11.5%)were assigned into a low ER expression group,151(13.5%)and 840(75%)into moderate and high ER expression groups,respectively.Statistical differences were observed in disease-free survival(DFS)and overall survival(OS)among the 3 groups(P=8e-6,P=8e-14).In the low ER expression group,the patients treated with selective estrogen receptor modulators(SERMs)showed no significant differences in DFS and OS than those treated with aromatase inhibitors(AIs)(P>0.05).However,the patients from the moderate and high ER expression groups demonstrated significantly better DFS when treated with AI than with SERM(P=0.02,P=0.03).Multivariate analysis showed that compared with the moderate ER expression group,the high ER expression group exhibited significantly lower risk of disease recurrence/metastasis(HR=0.62,95%CI:0.43～0.88,P=0.009)and risk of death(HR=0.49,95%CI:0.26～0.93,P=0.03).Subgroup analysis revealed that when compared with the high ER expression group,the moderate ER expression group exhibited notably worse DFS in the following subgroups:oral SERM,non-breast-conserving surgery,lymph node metastasis,TNM stage Ⅱ,and chemotherapy,and shorter OS in the subgroups of oral SERM,non-breast-conserving surgery,lymph node metastasis,TNM stage Ⅱ subgroup,and chemotherapy.Conclusion Taking ER expression of 11%～30%as an independent stratification criterion can guide more accurate prognostic assessment and more rational ET selection in ER-positive/HER2-negative breast cancer patients.

This study presents a case of a girl of three year and 4 month old with ataxia and severe sen-sorineural hearing loss for 2 years.In order to improve hearing,she was hospitalized in the PUMC Hospital.Ge-netic testing performed found compound heterozygous variants of c.1186C＞T(p.P396S)and c.1357C＞T(p.R453W)in TWNK gene.After a multidisciplinary discussion of the case,the team suspected mitochondrial DNA depletion syndrome type 7(hepatocerebral type).The patient has shown nervous system impairment in-volvement but no evidence of liver dysfunction.The efficacy of cochlear implantation is uncertain and general anesthesia if applied will accelerate the progress of encephalopathy and might lead to multiple organ failure.Unsure of the perioperative safety,the parents of the girl did not chose the option of hearing intervention tempo-rarily,but chose oral symptomatic supportive treatment with coenzyme Q10,folate,levocarnitine,and complex vitamins as recommended.

Objective　To observe the molluscicidal effect of a new molluscicide, 10% chlorosalicylicamide (LDS), against the intermediate hosts of Schistosoma mansoni - Biomphalaria glabrata and Biomphalaria straminea, thus to provide the experimental foundation for the field application of this molluscicide. Methods　The 10% LDS was formulated into the series of standard solutions with effective concentrations of 0.400 0, 0.200 0, 0.100 0, 0.050 0, 0.025 0 mg/L and 0.012 5 mg/L, respectively. B. glabrata and B. straminea were separately immersed in these solutions in the laboratory. The deaths of the above snails were observed after immersing into the solutions for 24, 48, and 72 h, and the mortalities of each group were computed, as well as the median lethal concentration LC50 (s) and relative toxicity indexes were calculated. Meanwhile, 50% wettable power of niclosamide ethanolamine salt (WPN) was set as the drug group, and dechlorinated water as the blank control group. Results　 The effective concentration of LDS at or above 0.100 0 mg/L, or WPN at or above 0.200 0 mg/L resulted in a 100% mortality rate for B. glabrata and B. straminea after immersing 24, 48, and 72 h. The LC50 (s) at 24, 48, and 72 hours for Biomphalaria glabrata immersed in the LDS series concentration solution was 0.047 95, 0.046 52, and 0.037 10 mg/L, respectively; while the LC50 (s) of B. glabrata in WPN serial solutions was 0.063 48, 0.057 05, 0.057 05 mg/L for 24, 48 and 72 h, respectively. For Biomphalaria straminea, the LC50 (s) at 24, 48, and 72 hours in the LDS solution was 0.012 35, 0.013 99, and 0.008 40 mg/L, respectively; and for the WPN solution, it was 0.058 95, 0.025 71, and 0.0237 5 mg/L. Using WPN as the standard drug which had higher value of LC50, and the relative toxicity index of WPN was set to 1.00, the relative toxicity indexes of LDS against B. glabrata were 1.32, 1.23 and 1.54 for 24, 48 h and 72 h, respectively, while for B. straminea, it was 4.77, 1.84, and 2.83. After 24, 48, and 72 hours of immersion in LDS, the number of surviving B. glabrata was significantly higher than that of B. straminea, with a statistical significance (χ2=8.044, 5.263, 4.658, P<0.05, respectively). Conclusions　Compared to the traditional molluscicide WPN, 10% LDS shows a superior molluscicidal effect on B. glabrata and B. straminea, especially demonstrating heightened sensitivity and efficacy on B. straminea, suggesting its potential as a substitute agent for snail control.

Periodontitis is a chronic inflammatory disease caused by plaque biofilm,and the homeostasis of the periodontal microenvironment is crucial for periodontal health.The epigenetics explores how the environmental and other non-genetic factors regulate the gene expression without changing the DNA nucleotide sequence,thereby affecting the occurrence and development of this disease.The histone acetylation modification is one of the common epigenetic modifications,primarily regulated by the histone acetyltransferases and histone deacetylases.Imbalance in this regulation can lead to the gene regulatory disorders,causing the chronic inflammation,autoimmune diseases and cancer.Recent studies have shown there is a clear correlation between histone acetylation modifications and the development of periodontitis.This paper discusses the changes in histone acetylation modifications in the gingival epithelial cells,immune cells,and periodontal ligament stem cells during periodontitis,elucidating the role and molecular mechanisms of histone acetylation modifications in the development of periodontitis and providing the basis for the epigenetic treatment of periodontitis.

Heart failure(HF)is a highly morbid syndrome that seriously affects the physical and mental health of patients and generates an enormous socio-economic burden.In addition to cardiac myocyte oxidative stress and apoptosis,which are considered mechanisms for the development of HF,alterations in cardiac energy metabolism and pathological autophagy also contribute to cardiac abnormalities and ultimately HF.Silent information regulator 1(Sirt1)and adenosine monophosphate-activated protein kinase(AMPK)are nicotinamide adenine dinucleotide(NAD+)-dependent deacetylases and phosphorylated kinases,respectively.They play similar roles in regulating some pathological processes of the heart through regulating targets such as peroxisome proliferator-activated receptor γ coactivator 1α(PGC-1α),protein 38 mitogen-activated protein kinase(p38 MAPK),peroxisome proliferator-activated receptors(PPARs),and mammalian target of rapamycin(mTOR).We summarized the synergistic effects of Sirt1 and AMPK in the heart,and listed the traditional Chinese medicine(TCM)that exhibit cardioprotective properties by modulating the Sirt1/AMPK pathway,to provide a basis for the development of Sirt1/AMPK activators or inhibitors for the treatment of HF and other cardiovascular diseases(CVDs).

Objective:To investigate the current status of the technological pedagogical content knowledge (TPACK) levels of youth teachers in a military medical university, and to provide a practical basis for improving youth teachers' ability to teach with technologies.Methods:Youth teachers (with less than 3 years of teaching experience) in a military medical university were selected by convenience sampling for a survey on TPACK abilities using a modified TPACK questionnaire. The questionnaire was distributed through the internet, and 119 valid responses were returned. SPSS 20.0 software was used to perform the independent samples t-test and one-way analysis of variance.Results:The youth teachers scored highest in technological knowledge [TK; (3.68±0.74)] and lowest in TPACK (3.17±0.74). There were no significant differences in TPACK abilities between youth teachers in different majors. Youth teachers of different educational attainments showed significant differences in the levels of technological knowledge (TK; F=12.99, P<0.001), content knowledge (CK; F=13.64, P<0.001), technological pedagogical knowledge (TPK; F=4.38, P=0.015), technological content knowledge (TCK; F=3.83, P=0.025), and TPACK ( F=3.63, P=0.029)—the TK, CK, TPK, and TCK levels of teachers with doctoral degrees were significantly higher than those with bachelor's and master's degrees. Conclusions:Efforts should be made to design a TPACK ability development system throughout the growth cycle of youth teachers, build teaching practice communities, and improve the system guarantees.

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.