Background Meteorological factors are among the key extrinsic triggers for the onset and exacerbation of cardiovascular and cerebrovascular diseases (CVD). Against the backdrop of sustained global warming, elucidating the impact of ambient temperature and atmospheric pressure on CVD, especially on pre-hospital CVD emergent events, has become imperative for evidence-based prevention and emergency preparedness. Objective To quantify the temporal trends of daily mean temperature and atmospheric pressure and their associations with pre-hospital CVD emergent events in Yantai, and to explore effect modification by demographic subgroups and geographic areas, thereby providing an empirical basis for the rational allocation of emergency medical resources. Methods Pre-hospital CVD emergency data from January 1, 2016 to December 31, 2022 were selected from the Yantai 120 Emergency Medical Command System. Synchronous meteorological factors and environmental pollutant data were obtained from the websites of the National Oceanic and Atmospheric Administration and the National Centers for Environmental Information of the United States. Time-series analysis combined with distributed lag non-linear model was used to analyze the association between daily temperature, atmospheric pressure, and pre-hospital CVD emergencies. Average annual percentage changes (AAPC) were calculated using Joinpoint (version 5.2.0.0) to reflect temporal trends. Spearman correlation analysis was employed to screen variables with low collinearity for inclusion in the multi-pollutant adjusted models. Results From 2016 to 2022, a total of 268275 pre-hospital CVD emergency cases were recorded in Yantai City, showing an increasing annual trend (AAPC=7.16%, P=0.002). Emergency volume, daily temperature, atmospheric pressure, and PM₁₀ displayed marked seasonal patterns, with summer bottoms and winter peaks for emergencies, daily temperature higher in summer and lower in winter, and the inverse for atmospheric pressure. Correlation analysis showed that both daily temperature and atmospheric pressure were positively correlated with O₃, with correlation coefficients of 0.745 and 0.723, respectively; negatively correlated with PM_2.5, with correlation coefficients of −0.246 and −0.235, respectively; and negatively correlated with PM₁₀, with correlation coefficients of −0.241 and −0.229, respectively (P < 0.05). A U-shaped correlation was revealed between daily temperature and pre-hospital CVD emergency risk. Using 24 °C as the reference, risk was elevated at both low and high daily temperatures, with the strongest cold effect at –11 ℃ (RR=1.53, 95%CI: 1.35, 1.73) and strongest heat effect at 30 ℃ (RR=1.06, 95%CI: 1.01, 1.11); cold effects were prolonged (lag0–14d) compared to heat effects. Atmospheric pressure exhibited a positive association with emergencies; using a median of 1012.2 hPa as the reference, the maximum risk occurred at 1037 hPa (RR=1.25, 95%CI: 1.03, 1.52), with a 0–5 d lag. In the subgroup analysis, the impact of low temperature was more pronounced among females (RR_{−9 ℃}=1.66), people over 60 years (RR_{−9 ℃}=1.91), and rural residents (RR_{−9 ℃}=1.76). High atmospheric pressure significantly increased the risk of pre-hospital CVD emergency among females (RR_{1035 hPa}=1.54), people under 18 years (RR_{1035 hPa}=3.62), and rural residents (RR_{1035 hPa}=1.46). The sensitivity analysis results indicated that, after excluding the impact of pandemic and the degrees of freedom for time variations, the effects of daily average temperature and atmospheric pressure on pre-hospital CVD emergency volume were consistent with the primary analysis findings. Conclusion Both non-optimal temperature and atmospheric pressure significantly increase the pre-hospital CVD emergency volume; therefore, emergency medical services should develop targeted response protocols, optimize resource allocation, and intensify public health education to mitigate the pre-hospital burden attributable to temperature and pressure fluctuations.

Colorectal cancer (CRC) is the third most commonly diagnosed malignancy and the second leading cause of cancer-related mortality worldwide. Despite therapeutic advancements over recent decades, the prognosis for patients with metastatic CRC (mCRC) remains poor. Approximately 2%-4% of mCRC cases exhibit human epidermal growth factor receptor 2 (HER2) amplification or overexpression, defining a distinct molecular subtype. This HER2-positive status is strongly associated with primary resistance to anti-epidermal growth factor receptor (EGFR) therapies, which are the standard of care for patients with RAS wild-type tumors. Beyond its well-established role in breast and gastric cancers, HER2 has emerged as a pivotal biomarker and actionable therapeutic target in mCRC. However, selecting appropriate treatment strategies remains challenging due to patient heterogeneity and diverse molecular subtypes. This review systematically summarizes the molecular biology, diagnostic strategies, and advances in targeted therapies for HER2-positive mCRC. On the diagnostic front, we discuss the applications of immunohistochemistry (IHC), fluorescence in situ hybridization (FISH), next-generation sequencing (NGS), and circulating tumor DNA (ctDNA) detection technologies. We highlight discrepancies in diagnostic criteria across key clinical trials—such as HERACLES, DESTINY, and MOUNTAINEER—underscoring the urgent need for standardized, CRC-specific definitions to ensure consistent patient selection and comparability of efficacy data across studies. Although NGS enables comprehensive genomic profiling, its cost-effectiveness relative to traditional methods must be carefully considered. Therapeutically, we summarize clinical trial data for HER2-directed agents, including tyrosine kinase inhibitors (TKIs) such as tucatinib and lapatinib, monoclonal antibodies like trastuzumab, bispecific antibodies, and antibody-drug conjugates (ADCs) such as trastuzumab deruxtecan. We review dual-targeting strategies and note recent FDA approvals that represent significant milestones in second-line treatment. Additionally, we explore the potential of combining immune checkpoint inhibitors with HER2-targeted therapies to enhance antitumor immunity through mechanisms including antibody-dependent cellular cytotoxicity (ADCC) and modulation of the tumor microenvironment. ADCs enable precise delivery of cytotoxic payloads, reducing off-target toxicity while effectively inhibiting oncogenic pathways. A substantial portion of this review is dedicated to dissecting the molecular mechanisms underlying primary and acquired resistance to HER2-targeted therapies—persistent challenges that limit clinical benefit. These mechanisms include reactivation of downstream signaling pathways such as PI3K/AKT/mTOR and MAPK, concurrent mutations in genes like KRAS or BRAF, and alterations in HER2 expression that compromise treatment efficacy. For instance, specific HER2 mutations (e.g., L755S) can reduce drug binding affinity, while ctDNA monitoring facilitates early detection of emerging resistance clones during disease progression, thereby enabling timely therapeutic adjustments. Tumor heterogeneity and dynamic interactions with the microenvironment further complicate resistance patterns observed in clinical practice. HER2-targeted therapy represents a new frontier in precision oncology for mCRC, offering renewed hope for improving patient outcomes. Realizing this potential will require continued optimization of diagnostic algorithms and treatment workflows. Future efforts must focus on overcoming resistance, validating liquid biopsy approaches for dynamic monitoring, and establishing unified clinical guidelines. HER2 has become an essential biomarker for stratifying mCRC patients beyond traditional RAS and BRAF status, underscoring the shift from empiric treatment to biomarker-driven precision medicine. International, multidisciplinary collaboration will be critical to validate emerging biomarkers and refine treatment algorithms globally.

Background: and Purpose Live cell-based assays (LCBA) are increasingly used for serological antibody detection due to their ability to preserve antigen conformation, offering moderately higher sensitivity than fixed cell-based assays. However, the clinical necessity of prioritizing LCBA for the detection of aquaporin-4 immunoglobulin G (AQP4-IgG) in neuromyelitis optica spectrum disorder (NMOSD) remains unclear, especially when compared to its established role in diagnosing myelin oligodendrocyte glycoprotein antibody-associated disease. Methods: We compared the performance of live cell-based assays using immunofluorescence (LCBA-IF) and fixed cell-based assays using immunofluorescence (FCBA-IF) in detecting AQP4-IgG in 90 cases of NMOSD meeting 2015 International Panel for Neuromyelitis Optica Diagnosis criteria, alongside 40 controls. Additionally, we further investigated the relationship between AQP4-IgG titers as measured by LCBA-IF and FCBA-IF and clinical parameters in NMOSD patients. Results: Results showed 96.9% agreement between LCBA-IF and FCBA-IF (Cohen’s κ=0.935), with a strong Spearman correlation (0.977, p<0.001). Both methods demonstrated 100% specificity, with LCBA-IF showing slightly higher sensitivity compared to FCBA-IF. Within LCBAIF-tested groups, statistically significant differences in annualized relapse rates were observed across all pairwise comparisons (low-titer vs. moderate-titer, low-titer vs. high-titer, and moderate-titer vs. high-titer; all p<0.050). However, this association reached statistical significance in some FCBA-IF-tested groups. Conclusions Overall, there is a strong concordance between LCBA-IF and FCBA-IF in detecting AQP4-IgG, where LCBA-IF shows slightly higher sensitivity. Furthermore, there is a potential link between elevated AQP4-IgG titers and an increased risk of relapse, and this correlation may appear more pronounced when using LCBA-IF.

Objective To investigate the alterations of cerebral blood flow(CBF)in type 2 diabetic mellitus(T2DM) patients without cognitive impairment by using arterial spin labeling(ASL)technique.Methods A total of 23 T2DM patients without cognitive impairment and 23 healthy controls(HC)matched by age,sex,and education attainment were recruited.Their clinical data were collected,and neuropsychological tests and cerebral magnetic resonance imaging were performed.Then,the outcomes of clinical features,neuropsychological tests,and global and regional CBF were compared between the two groups.The significant regional zCBF(z-transformed relative CBF)values were extracted and correlated with clinical data and neuropsychological scores in T2DM patients,controlling age,sex,and education.Results No significant difference was found in whole brain CBF between the two groups(P=0.155),while significantly higher CBF was identified in the left superior temporal gyrus and left insula in the T2DM group(Gaussian random field correction,initial threshold P < 0.001,cluster level P < 0.05).No correlation was observed between the significant regional zCBF values and the clinical data or the neuropsychological scores in T2DM patients(all P>0.05).Conclusion Alterations in cerebral hemodynamics may precede cognitive function changes in T2DM,suggesting that the ASL technique is promising for early monitoring of cerebral hemodynamic changes associated with cognitive impairment in patients with T2DM.
Humans ; Diabetes Mellitus, Type 2/physiopathology* ; Cerebrovascular Circulation ; Middle Aged ; Male ; Female ; Magnetic Resonance Imaging ; Case-Control Studies ; Cognitive Dysfunction ; Neuropsychological Tests ; Aged

Objective To establish a Nomogram model based on serum tumor markers to assess the risk of pleural metastasis in patients with stage Ⅲ lung cancer,and to validate the constructed model.Methods A to-tal of 140 patients with stage Ⅲ lung cancer in the hospital from January 2022 to October 2024 were selected as the research subjects.They were divided into the metastasis group(36 cases)and the non-metastasis group(104 cases)based on whether pleural metastasis occurred.Clinical data of patients in the two groups were col-lected,and the levels of serum tumor markers[carcinoembryonic antigen(CEA),cancer antigen(CA)125,CA15-3,CA19-9]of patients in the two groups were detected simultaneously.The risk factors affecting pleural metastasis in patients with stage Ⅲ lung cancer were screened,and the risk of pleural metastasis in patients with stage Ⅲ lung cancer was evaluated by constructing a Nomogram model based on serum tumor markers,and the constructed prediction model was validated.Results The proportion of smoking history,maximum tumor diameter≥4 cm,lymph node metastasis and low differentiation in metastatic group were higher than those in non-metastatic group(P＜0.05).Compared with non-metastatic group,serum CEA,CA125,CA15-3 and CA19-9 levels in metastatic group were higher(P＜0.05).Multiuariate Logistic regression analysis showed that lymph node metastasis,low differentiation and abnormal increase of CEA,CA125,CA15-3 and CA19-9 levels were independent risk factors for pleural metastasis in stage Ⅲ lung cancer patients(P＜0.05).The area under the receiver operating characteristic curve of the Nomogram model constructed based on serum tumor markers was 0.896(95％CI:0.812-0.991),which proved that the model had good predic-tive efficacy.The calibration curve of the model confirmed that there was a good agreement between the pre-dicted risk and the actual risk,and the Hosmer-Lemeshow goodness of fit curve test x2=1.602,P=0.638.The results of the decision curve analysis show that this model could achieve a relatively high net benefit with-in the range of 0％to 80％.Conclusion The Nomogram model based on serum tumor markers can effectively evaluate the risk of pleural metastasis in patients with stage Ⅲ lung cancer,and has good calibration,goodness of fit and clinical practicability.

Objective To investigate the application effect of cold snare endoscopic mucosal resection(CS-EMR)in the treatment of 6 to 9 mm colorectal small polyps.Methods A total of 82 patients with small colonic polyps in our hospital from March 2022 to August 2023 were collected and divided into the observation group(45 cases received CS-EMR)and the control group[37 cases received hot snare endoscopic mucosal resection(HS-EMR)]according to different surgical methods.The clinical efficacy,polyp resection status,complete polyp resection rate,perioperative indicators and occurrence of complications were compared between the two groups.Results Follow-up for 1 month after operation,the effective rate of treatment in the observation group was higher than that in the control group(P<0.05).There was no statistically significant difference in the polyp resection status or perioperative indicators between the two groups(P>0.05).There was no statistically significant difference in the complete polyp resection rates of patients with different pathological types or total complete resection rate between the two groups(P>0.05).The incidence of delayed bleeding and endoscopic hemostasis rate in the observation group were lower than those in the control group(P<0.05).Conclusion The complete resection rate of 6～9 mm colorectal polyps through CS-EMR was comparable to that of HS-EMR,and CS-EMR has a better efficacy and lower risk of perioperative bleeding,along with higher safety.

Objective To investigate the protective effect of astaxanthin(ASTA)on gouty chondrocyte injury induced by monosodium urate crystal(MSU)and its mechanism.Methods The gout cell model by sodium urate crystals was established.C-28I2 cells were randomly divided into blank group(conventional culture),model group(200 μg·mL-1MSU),experimental-L group(200 μg·mL-1 MSU+20 μmol·mL-1 ASTA),experimental-H group(200 μg·mL-1 MSU+40 μmol·L-1 ASTA),experimental-H+Vector group(transfected with Vector+200 μg·mL-1 MSU+40 μmol·L-1 ASTA),experimental-H+NLRP3 group(transfected with NLRP3 plasmid+200 ig·mL-1 MSU+40 μmol·L-1 ASTA).Cell counting kit-8(CCK-8)assay was used to detect the cell proliferation rate;Western blot assay was used to detect the expression of related proteins;the levels of Hyp and GAG were detected by enzyme-linked immunosorbent assay(ELISA).Results The cell proliferation rate of blank group,model group,experimental-L group and experimental-H group were(100.00±5.40)％,(67.41±4.52)％,(72.69±5.05)％and(81.47±7.73)％,respectively.The above indicators showed statistically significant differences between the model group and the blank group,between the experimental-L,experimental-H groups and the model group(all P＜0.05).Nucleotide binding oligomeric domain-like receptor protein 3(NLRP3)protein expression levels in blank group,model group,experimental-L group,experimental-H group,experimental-H+Vector group and experimental-H+NLRP3 group were 0.44±0.04,0.86±0.06,0.72±0.10,0.52±0.03,0.51±0.03 and 1.13±0.10,respectively;the expression levels of cleaved Caspase-1(Cl-caspase-1)protein were 0.33±0.05,0.73±0.08,0.61±0.07,0.42±0.04,0.39±0.04 and 0.70±0.06,respectively;the mature interleukin(m-IL)-1 β protein expression levels were 0.26±0.03,0.91±0.05,0.70±0.11,0.57±0.08,0.58±0.06 and 0.79±0.08,respectively;the Hyp levels were(1.95±0.22),(3.33±0.25),(2.53±0.18),(2.22±0.21),(2.24±0.20)and(3.25±0.38)μg·mL-1,respectively;the GAG levels were(2.30±0.20),(3.71±0.26),(3.29±0.33),(2.90±0.16),(2.97±0.24)and(3.50±0.34)ng·mL-1,respectively.The above indicators showed statistically significant differences between the model group and the blank group,between the experimental-L,experimental-H groups and the model group,between the experimental-H+NLRP3 group and the experimental-H+Vector group(all P＜0.05).Conclusion Astaxanthin can regulate NLRP3 to play an anti-inflammatory role and has a protective effect on MSU-induced gouty cartilage injury.

Preterm birth (PTB), predominantly induced by intraamniotic inflammation, stands as the foremost contributor to neonatal morbidity and mortality globally. Fetal inflammatory response syndrome, stemming from the activation of the innate immune system, signifies the occurrence of funisitis or chorionic vasculitis. Maternal-fetal complications associated with infection-related PTB encompass maternal sepsis, fetal demise, neonatal sepsis, neonatal neurological impairment, and chronic lung disease. The inflammatory cascade is initiated when Toll-like receptors present on immune cells within the fetal membranes and the female reproductive tract encounter pathogen-associated molecular patterns derived from infectious agents. Subsequently, the nuclear factor kappa-light-chain-enhancer of activated B cells facilitates the transcription of cytokines. The accumulation of neutrophils compromises the tissue integrity of the fetal membranes, leading to membrane rupture via the secretion of matrix metalloproteinases. Elevated prostaglandin levels prompt uterine contractions and cervical remodeling, resulting in progressive cervical effacement and dilation, ultimately culminating in fetal delivery. The diagnosis of PTB should encompass three pivotal criteria: gestational age, uterine activity, and the consequences of that uterine activity. The diagnosis of chorioamnionitis is established through a combination of clinical manifestations, laboratory findings, identification of infectious microorganisms, and placental pathology. Fetal monitoring involves antenatal ultrasonography and non-stress testing. The management of infection-related PTB involves controlling and treating the infection, timing delivery to coincide with optimal fetal lung maturity, and optimizing outcomes for both the mother and neonate. Current preventive strategies for PTB primarily focus on inhibiting myometrial contractions that arise from the inflammatory cascade initiating PTB. An understanding of these pathways serves as the cornerstone for the development of therapeutic interventions aimed at preventing PTB.

Aim To explore the possible regulatory effect of leptin on acyl-CoA synthetase long chain fami-ly member ACSL5 and their effect on migration and in-vasion of breast cancer cell,and to explore the underly-ing mechanism.Methods The expression of leptin receptor was detected by immunofluorescence assay.The migration and invasion ability of MCF-7 cells were detected by wound healing assay and Transwell assay respectively.The downstream target gene of leptin was analyzed by PCR microarray data.The expression of ACSL5 in breast cancer and its correlation with the staging and prognosis of breast cancer patients were as-sessed uing bioinformatics methods.The expression of ACSL5 in MCF-7 cells treated with different concentra-tions of leptin was detected using real time fluorescence quantitative polymerase chain reaction(RT-qPCR).Overexpressing ACSL5 was constructed by lentiviral transfection;the expressions of EMT related proteins,AMPK-α and p-AMPK-α were detected by Western blot.Results Leptin promoted breast cancer cell mi-gration and invasion and EMT.ACSL5 was significant-ly low expressed in breast cancer and related to progno-sis.Leptin downregulated the expression of ACSL5 through OBR.Leptin activated AMPK pathway to downregulate ACSL5 and promote migration,invasion and EMT of breast cancer cells.Conclusions Leptin may promote the migration,invasion and EMT of breast cancer by downregulating ACSL5 through activating AMPK pathway.

Objective To investigate the distribution and antimicrobial resistance profiles of clinically isolated Haemophilus influenzae and Moraxella catarrhalis in hospitals across China from 2015 to 2021,and provide evidence for rational use of antimicrobial agents.Methods Data of H.influenzae and M.catarrhalis strains isolated from 2015 to 2021 in CHINET program were collected for analysis,and antimicrobial susceptibility testing was performed by disc diffusion method or automated systems according to the uniform protocol of CHINET.The results were interpreted according to the CLSI breakpoints in 2022.Beta-lactamases was detected by using nitrocefin disk.Results From 2015 to 2021,a total of 43 642 strains of Haemophilus species were isolated,accounting for 2.91％of the total clinical isolates and 4.07％of Gram-negative bacteria in CHINET program.Among the 40 437 strains of H.influenzae,66.89％were isolated from children and 33.11％were isolated from adults.More than 90％of the H.influenzae strains were isolated from respiratory tract specimens.The prevalence of β-lactamase was 53.79％in H.influenzae strains.The H.influenzae strains isolated from children showed higher resistance rate than the strains isolated from adults.Overall,779 strains of H.influenzae did not produce β-lactamase but were resistant to ampicillin(BLNAR).Beta-lactamase-producing strains showed significantly higher resistance rates to these antimicrobial agents than the β-lactamase-nonproducing strains.Of the 16 191 M.catarrhalis strains,80.06％were isolated from children and 19.94％isolated from adults.M.catarrhalis strains were mostly susceptible to both amoxicillin-clavulanic acid and cefuroxime,evidenced by resistance rate lower than 2.0％.Conclusions The emergence of antibiotic-resistant H.influenzae due to β-lactamase production poses a challenge for clinical anti-infective treatment.Therefore,it is very important to implement antibiotic resistance surveillance for H.influenzae and guide rational antibiotic use.All local clinical microbiology laboratories should actively improve antibiotic susceptibility testing and strengthen antibiotic resistance surveillance for H.influenzae.