Onco-critical care has emerged as an important subspecialty at the intersection of critical care medicine and oncology, attracting increasing attention in recent years. With continuous innovations in cancer therapies, patient survival has improved significantly; however, the incidence of associated critical complications has also increased. The reasons for cancer patients requiring intensive care unit admission are diverse and can be broadly categorized into three groups: progression of the underlying malignancy, treatment-related complications, and coexisting classical critical illnesses. Traditional critical care concepts and practices face limitations in addressing the multidimensional and heterogeneous challenges of onco-critical care. Based on the core mechanism of critical illness development—host/organ unregulated response (HOUR)—this article systematically elaborates on how this framework advances understanding and clinical practice into onco-critical care, with emphasis on its manifestations in neuroendocrine, immune-inflammatory, and coagulation-metabolic pathways. The review summarizes recent advances in clinical assessment and phenotyping systems for onco-critical illness and discusses a multidisciplinary, integrated management strategy centered on the "Disease Control, Host Response Modulation, Organ Support" triad. Finally, major challenges and future directions in this field are outlined. By integrating existing evidence and theoretical insights, this review aims to provide new perspectives and a theoretical foundation for the clinical management of onco-critical illness, thereby promoting its evolution toward precision and standardization.

ObjectiveTo explore the effect of timosaponin BⅡ （TBⅡ） combined with icariin （ICA） on osteoclast （OC）-osteoblast （OB） coupling and decipher the mechanism from the cellular level. MethodsThe cell counting kit-8 （CCK-8） was used to assess the effects of different concentrations of TBⅡ and different concentrations of TBⅡ+ICA on the growth of RAW264.7 cells. Soluble receptor activator of nuclear factor-κB ligand （sRANKL） was used to induce the differentiation of RAW264.7 pre-osteoclasts into osteoclasts. The cells were allocated into sRANKL， TBⅡ （1， 5， 10 μmol·L^-1）， and TBⅡ+ICA groups. Tartrate-resistant acid phosphatase staining was performed to assess the effects of TBⅡ and TBⅡ+ICA on osteoclast differentiation. Real-time quantitative polymerase chain reaction （Real-time PCR） was conducted to examine the effects of TBⅡ+ICA on the expression of key genes involved in osteoclast differentiation and osteoclast-derived coupling factors. The osteogenic differentiation conditioned medium mixed with osteoclast supernatant was used to induce osteogenic differentiation of MC3T3-E1 cells. Alkaline phosphatase staining and alizarin red S staining were employed to determine the effect of TBⅡ+ICA on osteogenic differentiation. Real-time PCR was employed to evaluate the effects of conditioned medium on key genes involved in osteogenic differentiation. ResultsTBⅡ at 1， 5， 10 μmol·L^-1 had no significant effect on the cell survival rate. Compared with the sRANKL group， TBⅡ inhibited osteoclast differentiation in a dose-dependent manner and achieved the best effect at 10 μmol·L^-1 （P<0.01）. Compared with the sRANKL group， different concentrations of TBⅡ down-regulated the mRNA levels of osteoclast differentiation-related genes c-Fos， RANK， and RANKL （P<0.05）. None of 10 μmol·L^-1 TBⅡ， 10 μmol·L^-1 TBⅡ+10^-4 μmol·L^-1 ICA， or 10 μmol·L^-1 TBⅡ+10^-3 μmol·L^-1 ICA affected the viability of RAW264.7 cells. TBⅡ and/or ICA inhibited osteoclast differentiation （P<0.01）， and TBⅡ + ICA had the best effect （P<0.01）. Compared with the sRANKL group， TBⅡ and/or ICA down-regulated the mRNA levels of c-Fos， RANK， and RANKL （P<0.05）. The single application of TBⅡ and ICA had no significant effect on the mRNA levels of Wnt10b， Cthrc1， and C3a， while TBⅡ+ICA exerted up-regulating effects （P<0.05）. Compared with those in the blank group， the bone differentiation and mineralization abilities of the normal osteogenic induction group and each osteogenic induction + osteoclast supernatant group were improved （P<0.01）. Compared with the blank group， the normal osteogenic induction group and the osteogenic induction + osteoclast supernatant group showed up-regulated mRNA levels of Runx2 and OCN （P<0.01）. ConclusionTBⅡ+ICA can inhibit osteoclast differentiation， maintain the normal osteoclast-osteoblast coupling， and promote osteogenic differentiation.

AIM To investigate the clinical effects of Supplemented Gegen Qinlian Decoction combined with acupuncture on patients with ulcerative colitis of Large Intestinal Dampness-heat Pattern.METHODS One hundred and twenty patients were randomly assigned into control group(60 cases)for 1-month administration of Pefikang Capsules and Mesalazine Sustained Release Granules,and observation group(60 cases)for 1-month administration of Supplemented Gegen Qinlian Decoction,acupuncture,Pefikang Capsules and Mesalazine Sustained Release Granules.The changes in clinical effects,symptom remission time,TCM syndrome scores,Geboes index,lesion activity index,Baron score,inflammatory factors(IL-6,IL-8,TNF-α),immune function indices(IgA,IgG,IgM),IBDQ score and recurrence rate were detected.RESULTS The observation group demonstrated higher total effective rate than the control group(P＜0.05),along with shorter symptom remission time(P＜0.05)and lower recurrence rate(P＜0.05).After the treatment,the two groups displayed decreased TCM syndrome scores,Geboes index,lesion activity index,Baron score,inflammatory factors,IgG,IgM(P＜0.05),and increased IBDQ score(P＜0.05),especially for the observation group(P＜0.05).CONCLUSION For the patients with ulcerative colitis of Large Intestinal Dampness-heat Pattern,Gegen Qinlian Decoction combined with acupuncture can improve clinical symptoms,promote disease recovery,enhance immune functions and life quality,and reduce recurrence rate.

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.

Purpose Discover new prostate cancer-related single nucleotide variants.Methods Tissue wax blocks from 21 prostate cancer patients who underwent radical surgery and had relatively complete clinical data were collected for somatic mutation detection to analyze new mutated genes associated with prostate cancer.The levels of cor-responding proteins in the urine of prostate cancer patients were tested according to the results of the selected genes.Results All 21 prostate cancer patients showed obvious somatic mutations,and the mutation types were dominated by C＞T and G＞A.The number of somatic mutations was 521,of which 27 genes had high mutation proportions(≥2 ca-ses),including ZSWIM6(5/21),FOXA1(4/21),SPTA1(2/21),FAM47C(2/21),FLG2(2/21),PRSS3(2/21),TP53(2/21),FLG(2/21),UBR4(2/21),and the mutations occurring in ZSWIM6 were all deletion muta-tions,and the mutations occurring in FOXA1 were missense mutations,deletion mutations,and deletion insertion mu-tations.The urinary levels of UPF1,SPTA1,and IDH1 proteins of the 10 prostate cancer patients were significantly different than those of the healthy controls.Correlation analysis showed that FOXA1 was positively correlated with UBR4(r=0.669,P=0.001),SPTA1 was positively correlated with FLG2(r=1.000,P＜0.001),FAM47C was positively correlated with PRSS3(r=1.000,P＜0.001),and there was a significant positive correlation between TP53 and FLG(r=1.000,P＜0.001).ZSWIM6 and FOXA1 were not correlated with biochemical recurrence.SP-TA1 mutation affected progression-free survival(PFS)[(66.0±0)months vs(30.0±7.8)months,P=0.008].FAM47C was positively correlated with PFS[(66.0±0)months vs(19.0±0)months,P＜0.001].ZNF676 was correlated with PFS[(66.0±0)months vs(26.0±5.0)months,P=0.008].FLG2 was correlated with PFS[(66.0±0)months vs(30.0±7.8)months,P=0.008].PRSS3 was correlated with PFS[(66.0±0)months vs(19.0±0)months,P＜0.001].Conclusion All 21 prostate cancer patients harbored somatic mutations,including ZSWIM6(5/21)and FOXA1(4/21)mutations.SPTA1,FAM47C,ZNF676,FLG2,and PRSS3 may be associated with prognosis.

Alzheimer's disease(AD)is a multifactorial condi-tion characterized by the accumulation of toxic proteins and asso-ciated neurodegeneration.AD is distinguished by the pathologi-cal aggregation of amyloid beta(Aβ)and Tau proteins.The in-teraction between Aβ and Tau can further induce neuroinflamma-tion,mitochondrial autophagy dysfunction,and endoplasmic retic-ulum stress,exacerbating synaptic damage and neuronal death.Neuronal cells are particularly susceptible to protein misfolding due to an imbalance between protein production and degrada-tion.The ubiquitin/26S proteasome system(UPS),a major pathway for protein degradation in eukaryotic cells,plays a cruci-al role in recognizing misfolded or damaged proteins within the nervous system.In UPS,the levels of ubiquitin are tightly regu-lated by both ubiquitin ligases(E3s)and deubiquitylases(DUBs).This article reviews the involvement and mechanisms of E3s and DUBs in the pathogenesis of AD,aiming to provide novel research strategies for its treatment.

Objective:To explore the mediating effect of psychological resilience between family function and post-traumatic growth in young and middle-aged stroke patients,and to provide a theoretical basis for formulating targeted intervention strategies.Methods:This study was a prospective study,a total of 80 young and middle-aged stroke patients admitted in our hospital from February 2023 to August 2024 were selected by the convenient sampling method.The general information of the patients was collected by using a self-made questionnaire,the Connor-Davidson resilience scale(CD-RISC),family care index questionnaire(APGAR)and post-traumatic growth inventory(PTGI)were used to measure psychological resilience,family function and post-traumatic growth levels respectively.The correlations among family function,post-traumatic growth and psychological resilience were analyzed through Person correlation analysis.Construct models of family function and post-traumatic growth to exam ine the mediating effect of psychological resilience,and the scatter plots of correlations and the mediating effect model diagrams were drawn.Results:There were significant differences in the scores of family function,psychological resilience and post-traumatic growth among patients with different characteristics(P＜0.05).The scores of family function,psychological resilience and post-traumatic growth of patients with characteristics such as being married,having a higher educational level,being slightly dependent on daily living skills and having their spouses as the main caregivers were significantly higher(P＜0.05).Pearson correlation analysis showed that family function was significantly positively correlated with psychological resilience(r=0.951,P＜0.05),family function was significantly positively correlated with post-traumatic growth(r=0.939,P＜0.05)and post-traumatic growth was significantly positively correlated with post-traumatic growth(r=0.959,P＜0.05).The structural equation model indicates that psychological resilience plays a partial mediating role between family function and post-traumatic growth,with the mediating effect accounting for 28.42％(95％CI:0.12-0.30)of the total effect.Conclusion:Family function can play an indirect role through psychological resilience to promote post-traumatic growth in young and middle-aged stroke patients,clinically,the collaborative intervention of family function and psychological resilience should be emphasized.

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.

Kv1.3,a voltage-gated potassium channel,is highly expressed in T lymphocytes,the nervous system,and vascular smooth muscle cells.It plays a critical role in membrane excitability and electrical signal transduction,serving as an important target for studying T-cell function and providing a promising direction for developing therapeutics against autoimmune and inflammatory diseases.Therefore,the de-velopment of specific inhibitors of Kv1.3 channel has emerged as a novel therapeutic strategy for these disorders.In this study,we isolated and purified a novel Kv1.3-inhibitory peptide toxin,LmKTx13,from the venom of the scorpion Lychas mucronatus using reversed-phase high-performance liquid chroma-tography(RP-HPLC).LmKTx13 consists of 38 amino acid residues,including six cysteines that form three disulfide bonds.Whole-cell patch-clamp recordings revealed that LmKTx13 potently inhibited Kv1.3 with an IC50 of 7.92±3.0 nmol/L.Selectivity analysis showed that 2 μmol/L LmKTx13 also in-hibited Kv1.2 and Kv1.7,but exhibited no significant effects on other potassium channel subtypes or voltage-gated sodium channels.Further investigation into the mechanism demonstrated that LmKTx13 acts as a pore-blocking inhibitor of Kv1.3.By analyzing the effects of LmKTx13 on Kv1.3 channel gating ki-netics and performing sequence alignment of the pore regions of Kv1.3 and Kv1.5,we constructed site-directed mutants and identified the pore region of Kv1.3 as the critical binding site for LmKTx13.Key residues involved in the interaction included T425,G427,and H451.In summary,we discovered a no-vel pore-blocking Kv1.3 inhibitor,LmKTx13,from L.mucronatus venom,which exhibits high affinity and selectivity for Kv1.3.These findings highlight its potential as a potential lead molecule for developing Kv1.3-targeted therapeutics.