Heat stroke is a heat-related illness caused by an imbalance between the body's heat production and heat dissipation,which could lead to multiple organ dysfunction syndrome with a high mortality rate.Rapid and effective reduction of core body temperature is key to successful treatment.This article reviews recent progress in the treatment of heat stroke,including new understandings of organ injury mechanisms,the timing,velocity and goals of cooling treatment,evaluation and selection of traditional cooling techniques(such as cold water immersion),and scientific evaluation of new cooling technologies(such as blood purification technology and intravascular heat exchange cooling technology),aiming to promote understanding and treatment of heat stroke.

Objective To investigate the inhibitory effect of antimicrobial peptide WK-13-3D on the proliferation of triple negative breast cancer MDA-MB-231 cells and its potential mechanism.Methods The effect of antimicrobial peptide WK-13-3D at concentrations of 0,10,15,20,25,30,35,and 40 μmol/L on MDA-MB-231 cells proliferation was assessed using the CCK-8 assay.A pull-down assay was conducted to identify interacting proteins of antimicrobial peptide WK-13-3D with MDA-MB-231 cells.MDA-MB-231 cells were obtained and divided into the following groups:(1)control group and treatment groups with 10 and 20 μmol/L antimicrobial peptide WK-13-3D.Apoptosis was evaluated using flow cytometry and Western blotting was conducted to detect the expression change of heavy chain binding protein(BiP),protein kinase R-like endoplasmic reticulum kinase(PERK),eukaryotic translation initiation factor 2α(eIF2α),phosphorylated eIF2α(p-eIF2α),and Bax proteins within the cells.(2)Control group(transfected with no-load plasmid),si-BiP-592 group(transfected with si-BiP-592 interference plasmid)and si-BiP-592+WK-13-3D group(co-treated with si-BiP-592 interference plasmid and 10 μmol/L antimicrobial peptide WK-13-3D).Western blotting was used to detect the expression changes of BiP,PERK,eIF2α,p-eIF2α and Bax proteins.Twelve BALB/c mice were randomly divided into PBS group(n=4),taxol(TAX)group(n=4)and WK-13-3D group(n=4).All mice were subcutaneously injected with MDA-MB-231 cells to establish a triple-negative breast cancer transplant tumor model.WK-13-3D group received local injections of antimicrobial peptide WK-13-3D[200 mg/(kg·d)],TAX group was administered TAX intraperitoneally at the same dose[200 mg/(kg·d)],and PBS group was injected with an equivalent volume of PBS.Two weeks post-injection,the mice were killed,and the tumor weight and volume were measured and photographed.Immunohistochemistry staining was performed to evaluate the expressions of BiP and Ki-67 proteins in the tumor tissues.Results CCK-8 assay showed a gradual decrease in MDA-MB-231 cell survival rates with increasing concentrations of WK-13-3D,with an inhibitory concentration 50(IC50)of 19.82 μmol/L.The pull-down assay identified 268 interacting proteins of antimicrobial peptides and MDA-MB-231 cells,mainly including heavy-chain binding protein(BiP),heat shock protein 90 beta family member 1(HSP90B1),valerin-containing protein(VCP),heat shock cognate 71 kD protein(HSPA8).Compared with control group,treatment with 10 and 20 μmol/L antimicrobial peptide WK-13-3D significantly increased the apoptosis rate of MDA-MB-231 cells(P<0.05 or P<0.01),decreased BiP protein expression(P<0.05),and increased the expression levels of PERK,p-eIF2α,and Bax(P<0.05 or P<0.01),with no significant change in eIF2α protein expression(P>0.05).Compared with control group,si-BiP-592 group showed BiP protein expression significantly decreased(P<0.05),and the expression of PERK,p-eIF2α,and Bax proteins was significantly increased(P<0.05),with no significant change in eIF2α protein expression(P>0.05);Compared with si-BiP-592 group,si-BiP-592+WK-13-3D group showed a decrease in BiP protein expression(P<0.05)and an increase in PERK,p-eIF2α,and Bax protein expression(P<0.05 or P<0.01),with no significant change in eIF2α protein expression(P>0.05).Tumor volumes in mice treated with antimicrobial peptide WK-13-3D and TAX were significantly smaller than those in PBS group(P<0.05),and the immunohistochemical staining showed that the proportion of Ki-67 and BiP positive cells in tumor tissues of WK-13-3D treated mice was significantly lower than that in PBS group(P<0.01).Conclusion Antimicrobial peptide WK-13-3D could inhibit the proliferation of MDA-MB-231 cells and its mechanism may involve the activation of endoplasmic reticulum stress and the induction of cell apoptosis.

Objective To evaluate the value of tripartite motif-containing protein 21(TRIM21)mRNA expression in alveolar macrophages for the serverity and prognosis of patients with severe pneumonia complicated by acute respiratory distress syndrome(SP-ARDS).Methods A retrospective analysis was conducted on 42 SP-ARDS patients(SP-ARDS group)and 15 outpatient healthy controls(control group)admitted to the Department of Respiratory and Critical Care Medicine,Jinling Hospital Affilicated to Medical School of Nanjing University,from November 2023 to June 2024.Bronchoalveolar lavage fluid was collected,and alveolar macrophages were isolated.The expression levels of TRIM21 mRNA were quantified using qPCR.Differences in TRIM21 mRNA expression levels,clinical characteristics,and relevant laboratory test results were compared between the two groups.Correlations between TRIM21 mRNA expression and SP-ARDS severity,28-day mortality,inflammatory indicators,acute physiology and chronic health evaluation Ⅱ(APACHE Ⅱ)scores,duration of mechanical ventilation,and ICU stay were analyzed using Pearson or Spearman correlation analysis.Logistic regression analysis was used to identify risk factors for 28-day mortality,and the predictive value of each factor was evaluated using receiver operating characteristic(ROC)curves.Results Compared with control group,the expression levels of TRIM21 mRNA,white blood cell counts,neutrophil-to-lymphocyte ratio(NLR),and C-reactive protein(CRP),and procalcitonin(PCT)levels increased(P<0.05),and hemoglobin levels decreased(P<0.05)in SP-ARDS group.No significant differences were observed in gender,age,smoking history,alcohol consumption,underlying disease history,and platelet count between the two groups(P>0.05).TRIM21 mRNA expression level in SP-ARDS patients was positively correlated with ARDS severity(P<0.05).Additionally,non-survivors within 28 days had a significantly higher expression level of TRIM21 mRNA compared to survivors(P<0.001).Correlation analysis indicated that the relative expression level of TRIM21 mRNA in SP-ARDS patients was positively correlated with CRP(r=0.309,P<0.05),NLR(r=0.422,P<0.01),PCT(r=0.561,P<0.001),APACHE Ⅱ score(r=0.615,P<0.001),and duration of mechanical ventilation(r=0.665,P<0.001).Logistic regression analysis revealed that elevated expression levels of TRIM21 mRNA(OR=2.886,P=0.043)and higher APACHE Ⅱ scores(OR=1.546,P=0.037)were independent risk factors for 28-day mortality in SP-ARDS patients.The areas under the ROC curves(AUCs)for predicting 28-day mortality using TRIM21 mRNA expression level and APACHE Ⅱ score were 0.889 and 0.874,respectively,with optimal cut-off values of 5.21 and 20.5 points,respectively.The combined AUC for prediction was 0.962.Conclusion Increased TRIM21 mRNA expression in alveolar macrophages of SP-ARDS patients is positively correlated with disease severity and may serve as a potential predictive marker for 28-day survival in SP-ARDS patients.

Objective:To investigate lymph node metastasis(LNM)in the prostatic anterior fat pad(PAFP)of PCa patients after robot-assisted radical prostatectomy(RARP),and analyze the clinicopathological features and prognosis of LNM in the PAFP.Methods:We retrospectively analyzed the clinicopathological data on 1 003 cases of PCa treated by RARP in the Department of Urolo-gy of PLA General Hospital from January 2017 to December 2022.All the patients underwent routine removal of the PAFP during RARP and pathological examination,with the results of all the specimens examined and reported by pathologists.Based on the pres-ence and locations of LNM,we grouped the patients for statistical analysis,compared the clinicopathological features between different groups using the Student's t,Mann-Whitney U and Chi-square tests,and conducted survival analyses using the Kaplan-Meier and Log-rank methods and survival curves generated by Rstudio.Results:Lymph nodes were detected in 77(7.7％)of the 1 003 PAFP samples,and LNM in 11(14.3％)of the 77 cases,with a positive rate of 1.1％(11/1 003).Of the 11 positive cases,9 were found in the upgraded pathological N stage,and the other 2 complicated by pelvic LNM.The patients with postoperative pathological stage≥T3 constituted a significantly higher proportion in the PAFP LNM than in the non-PAFP LNM group(81.8％[9/11]vs 36.2％[359/992],P=0.005),and so did the cases with Gleason score ≥8(87.5％[7/8]vs 35.5％[279/786],P=0.009).No statisti-cally significant differences were observed in the clinicopathological features and biochemical recurrence-free survival between the pa-tients with PAFP LNM only and those with pelvic LNM only.Conclusion:The PAFP is a potential route to LNM,and patients with LNM in the PAFP are characterized by poor pathological features.There is no statistically significant difference in biochemical recur-rence-free survival between the patients with PAFP LNM only and those with pelvic LNM only.Routine removal of the PAFP and inde-pendent pathological examination of the specimen during RARP is of great clinical significance.

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.

Objective:To explore the expression changes of nerve growth factor (NGF)/tropomyosin receptor kinase A (TrkA) signaling pathway of dorsal root ganglia (DRG) in incisional rat remifentanil-induced hyperalgesia and its effect on the expression of membrane delta opioid receptor (DOR).Methods:A total of 48 SPF male SD rats were randomly divided into 6 groups based on body weight matching, with 8 in each group, which were control group (infusion of 0.9% NaCl solution via the tail vein), incision pain group (incision pain model established using the Brennan method), remifentanil group (infusion of remifentanil via the tail vein), incision pain+ remifentanil model group (incision pain model established using the Brennan method, followed by infusion of remifentanil via the tail vein), NGF group and TrkA inhibitor group(established incision pain+ remifentanil model after intrathecal injection of NGF (0.06 μg/g) or K252a (0.3 μg/g, TrkA inhibitor)). Mechanical paw withdrawal threshold (PWT) was used to assess pain sensitivity in rats. Western blot was employed to measure the expression of NGF, TrkA, and the total DOR(tDOR) and the membrane DOR(mDOR) in DRG tissues. Immunoelectron microscopy was used to detect subcellular DOR expression in DRG. Data were processed using SPSS 24.0 software. Multiple comparisons among groups were conducted by repeated measures ANOVA or one-way ANOVA, and post-hoc comparisons were performed using the Bonferroni test.Results:(1) The results of pain behavior showed that there was a significant interaction effect between time and group in the comparison of PWT among the six groups of rats before and after intervention ( F=345.817, P<0.001). At each time point after intervention, the PWTs of the incision pain+ remifentanil group were lower than those of the incision pain group and remifentanil group, the PWTs of the NGF group were lower than those of the incision pain+ remifentanil group, and the PWTs of the TrkA inhibitor group were higher than those of the incision pain+ remifentanil group and NGF group (all P<0.05). (2)The Western blot results showed that there were statistically significant differences in the relative levels of NGF, TrkA, and mDOR in the DRG tissues of the six groups of rats ( F=156.2, 163.8, 421.2, all P<0.001). The levels of NGF, TrkA, and mDOR proteins in the incision pain+ remifentanil group (1.45±0.07, 1.46±0.04, 3.01±0.20) were higher than those in the incision pain group (1.25±0.05, 1.24±0.04, 1.84±0.05) and remifentanil group (1.24±0.04, 1.26±0.03, 1.84±0.04) (all P<0.05). The levels of NGF, TrkA, and mDOR in the NGF group (1.57±0.03, 1.58±0.07, 3.74±0.25) were higher than those in the incision pain+ remifentanil group (all P<0.05). The relative expression levels of TrkA, and mDOR in the TrkA inhibitor group (1.25±0.04, 1.68±0.07) were lower than those in the incision pain+ remifentanil group and the NGF group (all P<0.05). (3)The results of immunoelectron microscopy showed that there were statistically significant differences in the localization of DOR in the cell membrane, subcellular sites of synthesis pathways, and subcellular localization of degradation pathways among the six groups of rat DRG tissues ( F=140.3, 60.63, 60.28, all P<0.01). The DOR of the synthesis pathway of incision pain+ remifentanil group was higher than that of the incision pain group and remifentanil group, while the DOR of the synthesis pathway of NGF was higher than that of the incision pain+ remifentanil group.The DOR of the synthesis pathway of TrkA inhibitor group was lower than that of the incision pain+ remifentanil group and NGF group (both P<0.05). The DOR of the degradation pathway in the incision pain+ remifentanil group was lower than that in the incision pain group and remifentanil group, the DOR of the degradation pathway in the NGF group was lower than that in the incision pain+ remifentanil group, and the DOR of the degradation pathway in the TrkA inhibitor group was higher than that in the incision pain+ remifentanil group and NGF group (both P<0.05). Conclusion:The NGF/TrkA signaling pathway is involved in rat incisional pain-remifentanil hyperalgesia by upregulating the delta opioid receptor of the dorsal root ganglia.

BACKGROUND: Generalized pustular psoriasis (GPP), a rare and recurrent autoinflammatory disease, imposes a substantial burden on patients and society. Awareness of GPP in China remains limited. METHODS: This cross-sectional survey, conducted between September 2021 and May 2023 across 14 hospitals in China, included GPP patients of all ages and disease phases. Data collected encompassed demographics, clinical characteristics, economic impact, disease severity, quality of life, and treatment-related complications. Risk factors for GPP recurrence were analyzed. RESULTS: Among 127 patients (female/male ratio = 1.35:1), the mean age of disease onset was 25 years (1st quartile [Q1]-3rd quartile [Q3]: 11-44 years); 29.2% had experienced GPP for more than 10 years. Recurrence occurred in 75.6% of patients, and nearly half reported no identifiable triggers. Younger age at disease onset ( P  = 0.021) and transitioning to plaque psoriasis ( P  = 0.022) were associated with higher recurrence rates. The median diagnostic delay was 8 months (Q1-Q3: 2-41 months), and 32.3% of patients reported misdiagnoses. Comorbidities were present in 53.5% of patients, whereas 51.1% experienced systemic complications during treatment. Depression and anxiety affected 84.5% and 95.6% of patients, respectively. During GPP flares, the median Dermatology Life Quality Index score was 19.0 (Q1-Q3: 13.0-23.5). This score showed significant differences between patients with and without systemic symptoms; it demonstrated correlations with both depression and anxiety scores. Treatment costs caused financial hardship in 55.9% of patients, underscoring the burden associated with GPP. CONCLUSIONS The substantial disease and economic burdens among Chinese GPP patients warrant increased attention. Patients with early onset disease and those transitioning to plaque psoriasis require targeted interventions to mitigate the high recurrence risk.
Humans ; Male ; Female ; Psoriasis/pathology* ; Adult ; Cross-Sectional Studies ; Adolescent ; Child ; Young Adult ; Quality of Life ; Middle Aged ; China/epidemiology* ; Recurrence ; Risk Factors ; Surveys and Questionnaires ; East Asian People

Objective: This study aimed to explore the correlation between balance function and core muscle activation in patients with adolescent idiopathic scoliosis (AIS), compared to healthy individuals. Methods: A total of 24 AIS patients and 25 healthy controls were recruited. The limits of stability (LOS) test were conducted to assess balance function, while surface electromyography was used to measure the activity of core muscles, including the internal oblique, external oblique, and multifidus. Diaphragm thickness was measured using ultrasound during different postural tasks. Center of pressure (COP) displacement and trunk inclination distance were also recorded during the LOS test. Results: AIS patients showed significantly greater activation of superficial core muscles, such as the internal and external oblique muscles, compared to the control group (p < 0.05). Diaphragm activation was lower in AIS patients during balance tasks (p < 0.01). Although no significant difference was observed in COP displacement between the groups, trunk inclination was significantly greater in the AIS group during certain tasks (p < 0.05). Conclusion These findings suggest distinct postural control patterns in AIS patients, highlighting the importance of targeted interventions to improve balance and core muscle function in this population.

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.

Objective: This study aimed to explore the correlation between balance function and core muscle activation in patients with adolescent idiopathic scoliosis (AIS), compared to healthy individuals. Methods: A total of 24 AIS patients and 25 healthy controls were recruited. The limits of stability (LOS) test were conducted to assess balance function, while surface electromyography was used to measure the activity of core muscles, including the internal oblique, external oblique, and multifidus. Diaphragm thickness was measured using ultrasound during different postural tasks. Center of pressure (COP) displacement and trunk inclination distance were also recorded during the LOS test. Results: AIS patients showed significantly greater activation of superficial core muscles, such as the internal and external oblique muscles, compared to the control group (p < 0.05). Diaphragm activation was lower in AIS patients during balance tasks (p < 0.01). Although no significant difference was observed in COP displacement between the groups, trunk inclination was significantly greater in the AIS group during certain tasks (p < 0.05). Conclusion These findings suggest distinct postural control patterns in AIS patients, highlighting the importance of targeted interventions to improve balance and core muscle function in this population.