OBJECTIVE To investigate the effects of subanesthetic dose of esketamine on postoperative anxiety and recovery in patients undergoing laparoscopic cholecystectomy. METHODS A total of 200 patients scheduled for laparoscopic cholecystectomy at Suzhou Ninth Hospital Affiliated to Soochow University from January 2023 to December 2024 were randomly assigned to control group （n＝100） and observation group （n＝100）. One minute before the initiation of anesthesia， patients in the control group received intravenous injections of Propofol emulsion injection， Sufentanil citrate injection， and Succinylcholine chloride injection. On this basis， patients in the observation group received an intravenous injection of Esketamine hydrochloride injection. The anxiety status of patients in both groups was compared， along with their general intraoperative conditions （including sufentanil dosage， duration of pneumoperitoneum， operative time， anesthesia time， and extubation time）， postoperative recovery， incidence of adverse reactions， and the need for dezocine rescue analgesia. Heart rate and mean arterial pressure， entropy index （state entropy and response entropy）， inflammatory marker levels [interleukin-6 （IL-6） and C-reactive protein （CRP）]， numerical rating scale （NRS） for pain intensity were compared between the two groups at different time points. RESULTS No significant differences were found between the two groups in pneumoperitoneum duration， operative time， anesthesia time，extubation time， incidence of postoperative dry mouth， entropy index or length of stay in the post-anesthesia care unit （P＞0.05）. Compared with the control group， the observation group showed significantly lower postoperative STAI-S scores， reduced intraoperative sufentanil consumption， decreased incidence of postoperative nausea， vomiting， and shivering， the need for dezocine rescue analgesia， as well as lower plasma IL-6 and CRP levels at 24 h after surgery， and NRS （P＜0.05）. The heart rate and mean arterial pressure of patients in the observation group at the start of surgery， end of surgery， and during extubation were all significantly higher than those in the control group （P＜0.05）. CONCLUSIONS Subanesthetic dose of esketamine can effectively alleviate postoperative anxiety， reduce intraoperative opioid consumption， suppress postoperative inflammatory response， relieve postoperative pain， and promote recovery in patients undergoing laparoscopic cholecystectomy.

Flap transplantation is a critical surgical strategy for the reconstruction of tissue defects caused by trauma, tumor resection, and congenital malformations, and its survival rate directly determines surgical efficacy and patient prognosis. Following transplantation, flaps inevitably undergo ischemia-reperfusion (I/R) injury, during which oxidative stress, inflammatory responses, and metabolic disturbances are intricately intertwined, ultimately leading to cellular injury and tissue necrosis. Recent studies have demonstrated that multiple forms of programmed cell death—including apoptosis, pyroptosis, ferroptosis, necroptosis, and PANoptosis—play central roles in flap I/R injury. The extensive crosstalk and molecular interactions among these pathways form a highly complex cell death network. Specifically, apoptosis is mediated by the imbalance of Bcl-2 family proteins and the activation of cysteine-dependent aspartate-specific protease (caspase) cascades; pyroptosis is driven by the NLRP3-caspase-1-GSDMD axis, resulting in membrane pore formation and the release of pro-inflammatory cytokines; ferroptosis is characterized by iron-dependent lipid peroxidation and dysfunction of glutathione peroxidase 4 (GPX4); necroptosis is triggered by the receptor-interacting serine/threonine-protein kinase 1 (RIPK1)-RIPK3-MLKL signaling complex, leading to membrane rupture; and PANoptosis represents an integrated form of inflammatory cell death that coordinates multiple death pathways. Importantly, these forms of programmed cell death are not independent but are interconnected through extensive signaling crosstalk. Key regulatory molecules, including caspase-8, reactive oxygen species (ROS), nuclear factor-κB (NF-κB), and nuclear factor erythroid 2-related factor 2 (Nrf2), collectively modulate the dynamic balance among these pathways. Therefore, the multidimensional interplay and spatiotemporal dynamics of programmed cell death constitute a fundamental pathological basis of flap I/R injury. This review systematically summarizes the latest advances in the mechanisms and interactions of various programmed cell death pathways in flap I/R injury, aiming to elucidate the underlying regulatory network. These insights may provide novel theoretical foundations for optimizing flap protection strategies, improving flap survival, and promoting tissue repair.

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 nutritional risk status of children in PICU and analyze its influencing factors.Methods:From July 2021 to February 2023,all children aged 1 to 18 years admitted to PICU of Beijing Children's Hospital were investigated by using the pediatric Yorkhill Malnutrition Scoring tool(PYMS)and the clinical data questionnaire.Results:A total of 492 children in PICU were enrolled.The first nutritional risk screening results showed that there were 32 cases of no/low nutritional risk(6.5%),76 cases of medium risk(15.4%),and 384 cases of high risk(78.1%).The incidence of medium/high nutritional risk was as high as 93.5%.The PYMS score of nutritional risk in PICU was(2.61±1.42).The results of multiple linear regression analysis showed that weight,fever time before admission,white blood cells,body mass index,primary diagnosis,father's education,and diet before illness were the main influencing factors of nutritional risk of children in PICU(P<0.05).Conclusion:Children in PICU are in a state of high nutritional risk.It is suggested that children in PICU should carry out nutritional screening in a standardized manner,identify children with high nutritional risk and its influencing factors early.To actively conduct nutritional assessment and nutritional intervention could improve the clinical outcome of children in PICU.

Objective:To analyze the molecular characteristics of prevalent Bordetella pertussis (Bp) isolates in Liaocheng City, Shandong Province in 2024. Methods:From March to August 2024, oropharyngeal swabs were collected from suspected pertussis cases at Liaocheng People′s Hospital in Shandong Province for Bp isolation. A total of 99 Bp isolates were obtained. Whole-genome sequencing was performed on all isolates, followed by Multilocus Sequence Typing (MLST), vaccine antigen-related gene typing (including ptxP, ptxA, ptxB, ptxC, ptxD, ptxE, fhaB, fim2, fim3, and prn), 23S rRNA gene typing, and phylogenetic analysis. To capture the differences between Bp isolates and vaccine strains in Liaocheng City, the international vaccine strain Tohama I and the Chinese vaccine strain CS were included in the analysis. Antimicrobial resistance testing against 11 agents was performed on 52 isolates. Results:The throat swabs of 99 Bp isolates were collected from patients aged 44 days to 42 years, and the median age of the patients was 7 (5, 8) years. All isolates ptxP were ptxP3 type. 74 isolates (74.75%) carried the prn150, while 21 isolates (21.21%) were prn-deficient. The predominant antigenic profile was ptxP3/ ptxA1/ ptxB1/ ptxC4/ ptxD1/ ptxE4/ fhaB1/ fim2-1/ fim3-1/ prn150, found in 72 isolates (72.73%). All 99 isolates carried the A2047G mutation in the 23S rRNA gene. Antimicrobial susceptibility testing showed that the MICs of macrolides and clindamycin for all 52 Bp isolates were all >256 mg/L. However, the isolates showed low MIC for seven other antimicrobials tested, including trimethoprim-sulfamethoxazole, amoxicillin, and levofloxacin. MLST typing revealed that 94 isolates (94.95%) were identified as ST-2, while 5 isolates (5.05%) belonged to a novel sequence type (ST-118). Phylogenetic analysis demonstrated that all 99 Bp isolates were highly homologous but clustered in evolutionary branches distinct from vaccine strains. Conclusion:In 2024, Bordetella pertussis isolates in Liaocheng City exhibit distinct clonal epidemic characteristics, with the predominant antigenic genotype being ptxP3/ ptxA1/ ptxB1/ ptxC4/ ptxD1/ ptxE4/ fhaB1/ fim2-1/ fim3-1/ prn150. All isolates are resistant to macrolide antibiotics.

Aim To explore the MST1 knockdown at-tenuates the inhibitory effect of salvianolic acid B(Sal B)on pERK anti-renal fibrosis.Methods In vitro experiments stimulated human renal cortical proximal tubular epithelial cells(HK-2)with XMU-XP-1(10μmol·L-1)inhibitor;in vivo experiments induced wild-type(WT)and MST1 systemic knockout mouse(MST1-/-)renal fibrosis models with DEN/CCl4/C2H5OH(DCC)and interfered with Sal B(15 mg·kg-1·d-1,ig)intervention.Renal histopathology was observed by HE and Masson staining;α-SMA and pERK protein expression was detected by Western blot;and pERK protein expression was detected by im-munofluorescence.Results In vitro results showed that Sal B could inhibit pERK protein expression.In vivo results showed that Sal B could improve DCC-in-duced renal tissue pathological injury and inhibit α-SMA and pERK protein expression;MST1-/-aggrava-ted pathological injury and significantly up-regulated α-SMA and pERK protein expression.Conclusion Sal B reduces the stimulatory effect of XMU-MP-1 on HK-2 cells by inhibiting the phosphorylation of ERK protein;Sal B exerts its anti-renal fibrosis effect by inhibiting the phosphorylation of α-SMA protein and ERK pro-tein;and MST1-/-,aggravating the pathological inju-ry of renal tissue,significantly up-regulated the expres-sion of α-SMA and pERK protein,which in turn atten-uated the antirenal fibrosis effect of Sal B.

Purpose To investigate the clinicopathological features of traditional serrated adenoma(TSA).Methods A retrospective analysis was conducted on the clinical data,endoscopic,and pathological features of 200 TSA patients.HE staining and immunohistochemical staining were performed.The clinical pathological features were statistically analyzed using x2 test,and relevant literature was reviewed.Results There were 114 males(57.0％)and 86 females(43.0％),with ages ranging from 27 to 92 years(mean age 56.2 years).Among the patients,147(73.5％)were aged ≥ 50 years,and 53(26.5％)were aged＜50 years.Of the 207 TSA lesions,143(69.1％)were located in the distal colon and rectum,while 57(27.5％)were in the proximal colon and rectum.Endoscopic features included 72 lesions(34.8％)with a perpendiculated appearance,48 lesions(23.2％)with a flat appear-ance,and some exhibiting a pinecone-like appearance.The maximum diameter of the lesions was ≤ 10 mm in 136 ca-ses(65.7％),and＞10 mm in 71 cases(34.3％).The typical histopathological features of TSA included serrated contours,eosinophilic cytoplasm,pencil-like nuclei,and ectopic crypt foci.The most common pathological type was the classic TSA(152 lesions,73.4％),followed by the mucin-rich TSA(39 lesions,18.8％).12 cases(5.8％)of TSA exhibited high-grade intraepithelial neoplasia(HGIN)and 3 case(1.5％)of TSA progressed to carcinoma,con-sistent with TSA-originated colorectal cancer(TSA-CRC).Immunophenotype:in 34 cases TSA,Ki67 showed diffuse positivity in basal cells and scattered positivity on the surface.In all 35 cases TSA,p53 showed weak positive nuclear positivity(1％to 60％),and PTEN and MLH1 were retained.In the 12 cases of TSA with HGIN and 3 cases of TSA-CRC,Ki67 showed diffusely positive,CK20 was strongly positive diffusely,and MLH1 was retained.In 9 cases of TSA with HGIN,p53 was diffusely strongly positive,and in 12 cases,PTEN was lost.All 3 cases of TSA-CRC showed dif-fuse strong nuclear p53 positivity.The molecular detection showed there were BRAF V600E gene mutation in 8 cases.There were 6 cases with KRAS G12V mutation as well as 1 case with KRAS G13D mutation among the 7 cases of KRAS mutation.The primary surgical approach(111 cases,53.6％)was endoscopic mucosal resection(EMR).Conclu-sion TSA exhibits characteristic histological and endoscopic features.Lesions with a maximum diameter＞10 mum are more likely to progress to HGIN or adenocarcinoma.It is crucial to enhance the awareness of pathologists and clini-cians,particularly regarding TSA with atypical hyperplasia or invasive carcinoma,to avoid misdiagnosis and missed di-agnoses.

AIM To investigate the effects of Rutong Ruanjian Tablets on angiogenesis in cancer tissues of rats with preneoplastic breast cancer(PBC).METHODS 60 female SD rats were randomly divided into a blank group of 10 rats and a model group of 50 rats for the establishment of the PBC models of Liver-Qi Stagnation and Blood Stasis Pattern with 9 weeks of oral administration of 7,12-dimethylbenz[a]anthracene(DMBA)and cervical ligation.After successful modeling,the rats were randomly divided into the model group,the tamoxifen group(3.2 mg/kg),the Rutong Ruanjian Tablets group(128 mg/kg),the 3,5-difluorobenzoyl group(DAPT,5 mg/kg),and the Rutong Ruanjian Tablets(128 mg/kg via gavage)+DAPT(5 mg/kg intraperitoneal injection)group,for 1 month corresponding drug administration,with 10 rats in each group.Then the rats had their cancer progression and syndrome scores observed;their angiogenesis evaluated by assessment of microvascular density(MVD);their vascular endothelial growth factor(VEGF)expression assessed by immunohistochemistry;and their mRNA and protein expressions of proteins related to the DLL4/Notch1/Hes1 pathway measured using RT-qPCR,immunohistochemistry and Western blot.RESULTS During carcinogenesis of rats induced by DMBA,there was gradual disappearance of E-cadherin expression and consistency of HE staining result with the PBC progression confirming the success of the modeling.Compared with the blank group,the model group showed increased MVD values,mRNA expression of Notch1 and Hes1,and protein expressions of VEGF,DLL4,Notch1 and Hes1(P＜0.05,P＜0.01).Compared with the model group,the Rutong Ruanjian Tablets group exhibited reduced MVD values,mRNA expression of Notch1 and Hes1,and protein expressions of VEGF,DLL4,Notch1 and Hes1(P＜0.05,P＜0.01).The Rutong Ruanjian Tablets+DAPT group showed reduced mRNA expression of Notch1 and Hes1,and protein expressions of DLL4,Notch1 and Hes1 compared to the Rutong Ruanjian Tablets group(P＜0.05,P＜0.01).CONCLUSION Rutong Ruanjian Tablets can inhibit angiogenesis and attenuate cancer progression in PBC rats of Liver-Qi Stagnation and Blood Stasis Pattern,and the mechanism may lie in the downregulation of DLL4/Notch1/Hes1 signaling pathway related proteins.

Aim To explore the MST1 knockdown at-tenuates the inhibitory effect of salvianolic acid B(Sal B)on pERK anti-renal fibrosis.Methods In vitro experiments stimulated human renal cortical proximal tubular epithelial cells(HK-2)with XMU-XP-1(10μmol·L-1)inhibitor;in vivo experiments induced wild-type(WT)and MST1 systemic knockout mouse(MST1-/-)renal fibrosis models with DEN/CCl4/C2H5OH(DCC)and interfered with Sal B(15 mg·kg-1·d-1,ig)intervention.Renal histopathology was observed by HE and Masson staining;α-SMA and pERK protein expression was detected by Western blot;and pERK protein expression was detected by im-munofluorescence.Results In vitro results showed that Sal B could inhibit pERK protein expression.In vivo results showed that Sal B could improve DCC-in-duced renal tissue pathological injury and inhibit α-SMA and pERK protein expression;MST1-/-aggrava-ted pathological injury and significantly up-regulated α-SMA and pERK protein expression.Conclusion Sal B reduces the stimulatory effect of XMU-MP-1 on HK-2 cells by inhibiting the phosphorylation of ERK protein;Sal B exerts its anti-renal fibrosis effect by inhibiting the phosphorylation of α-SMA protein and ERK pro-tein;and MST1-/-,aggravating the pathological inju-ry of renal tissue,significantly up-regulated the expres-sion of α-SMA and pERK protein,which in turn atten-uated the antirenal fibrosis effect of Sal B.

Objective:To investigate the molecular mechanisms of bexarotene in treating double hit lymphoma(DHL)based on Weighted Gene Co-expression Network Analysis(WGCNA),thereby providing potential targets and experimental evidence for DHL treatment.Methods:The gene expression datasets GSE44164 and GSE43677 were downloaded from the Gene Expression Omnibus(GEO)database,and differentially expressed genes(DEGs)were identified.WGCNA was employed to identify gene modules associated with DHL.A protein-protein interaction(PPI)network was constructed to screen for key hub genes.Drug-gene association analysis was conducted using the EpiMed platform to identify potential targeted drugs for DHL.The effects of bexarotene on DHL cell proliferation and key protein expression were evaluated using the CCK-8 assay and Western blotting(WB),and its effects on cell apoptosis was evaluated using flow cytometry.Results:WGCNA identified a turquoise module highly associated with DHL,and 10 hub genes(COL1A2,COL3A1,MMP2,COL5A2,DCN,BGN,FN1,MMP9,FBN1,and LUM)were screened from the PPI network.Drug association analysis nominated bexarotene as a potential therapeutic agent.In vitro validation demonstrated that bexarotene significantly inhibited U2932 cell viability(P<0.05),promoted cell apoptosis(P<0.001),and downregulated c-Myc and COL1A2 expression(P<0.05).Conclusion:Bexarotene may exert anti-DHL effects by suppressing the c-Myc signaling pathway and modulating extracellular matrix-related genes.Further studies are warranted to validate its in vivo efficacy and potential for combination therapy.