Colorectal cancer （CRC） is one of the most common cancers， with its incidence ranking high among cancers. It stands as the second leading cause of cancer-related death worldwide. In the early stages， CRC lacks specific symptoms， and most patients are diagnosed at advanced stages， making it a major research focus in the field of gastrointestinal tumors. Currently， clinical CRC treatments face several common challenges， including high surgical risks， frequent metastasis and recurrence， drug resistance， and significant side effects from chemotherapy and radiation therapy. With the development and application of traditional Chinese medicine （TCM）， it has been found that TCM and its active ingredients can effectively inhibit CRC cell proliferation， invasion， migration， and angiogenesis， and promote apoptosis and autophagy， thereby slowing the progression of CRC. This has become a key focus of CRC treatment research. Salvia Miltiorrhiza has multiple pharmacological effects， including activating blood circulation to dispel blood stasis， unlocking meridians to relieve pain， clearing heat to calm irritability， and cooling blood to reduce abscesses. It contains a variety of chemical components， including diterpenoids， phenolic acids， flavonoids， polysaccharides， nitrogen-containing compounds， steroids， and lactone compounds. This review summarized the molecular mechanisms of Salvia miltiorrhiza and its active ingredients in the treatment of CRC. It is found that these ingredients exert anti-CRC effects through various molecular mechanisms， including cell cycle arrest， promotion of apoptosis， inhibition of cell invasion and migration， induction of autophagy， suppression of tumor angiogenesis， and remodeling of the tumor microenvironment. The review aims to provide new insights for the drug development and clinical application of Salvia miltiorrhiza in CRC treatment.

OBJECTIVE To evaluate the efficacy and safety of amoxicillin combined with proton pump inhibitor （PPI） or potassium-competitive acid blocker （P-CAB） for Helicobacter pylori （Hp） eradication. METHODS Randomized controlled trial （RCTs） on amoxicillin combined with PPI or P-CAB for Hp eradication were retrieved from PubMed， Embase， the Cochrane Library， Web of Science， CNKI， Wanfang， and VIP data. The search time frame was from database inception to September 5， 2025. After literature screening， data extraction， and quality assessment， a network meta-analysis was performed using Stata 17.0 software. RESULTS A total of 12 RCTs involving 5 515 patients were included， encompassing 8 therapeutic regimens： PPI combined with high-dose amoxicillin for 14 days （TR1）， PPI combined with low-dose amoxicillin for 14 days （TR2）， P-CAB combined with high-dose amoxicillin for 7 days （TR3）， P-CAB combined with high-dose amoxicillin for 14 days （TR4）， P-CAB combined with high-dose amoxicillin for 10 days （TR5）， P-CAB combined with low-dose amoxicillin for 7 days （TR6）， P-CAB combined with low-dose amoxicillin for 14 days （TR7）， and P-CAB combined with low-dose amoxicillin for 10 days （TR8）. The network meta-analysis results showed that， in terms of intention-to-treat Hp eradication rates， the eradication rates of TR5 and TR4 were significantly higher than those of TR3， TR8， TR6 and TR1 （ P ＜0.05）. The surface under the cumulative ranking curve （SUCRA） values from highest to lowest were： TR4 （89.7%）＞TR5 （82.3%）＞TR7 （71.5%）＞ TR2 （48.6%）＞TR1 （43.9%）＞TR8 （28.7%）＞TR3 （22.7%）＞TR6 （12.6%）. Regarding safety， the incidence of adverse reactions in TR3 and TR5 was significantly lower than that in TR1 （ P ＜0.05）. The SUCRA values from highest to lowest were： TR1 （91.3%）＞TR4 （79.8%）＞TR5 （55.0%）＞TR7 （50.9%）＞TR8 （41.3%）＞TR2 （36.4%）＞TR3 （27.6%） ＞TR6 （17.7%）. CONCLUSIONS Although the regimen of P-CAB combined with high-dose amoxicillin for 14 days demonstrates the best efficacy， the combination of P-CAB with high-dose amoxicillin for 10 days exhibits a better balanced profile in terms of both efficacy and safety.

OBJECTIVE To investigate the effect and potential mechanism of toosendanin in enhancing the antileukemic activity of cytosine arabinoside against acute myeloid leukemia （AML） based on the mammalian target of rapamycin complex 1 （mTORC1） signaling pathway.METHODS Female NSG immunodeficient mice were used to establish an AML model via a single γ-ray irradiation followed by a single tail-vein injection of a U937 cell suspension. The effects of cytosine arabinoside （2.5 mg/kg）， toosendanin （1.0 mg/kg）， and cytosine arabinoside+toosendanin （2.5 mg/kg+1.0 mg/kg） on body weight， survival time， peripheral blood routine indicators， histopathological morphology， and the expressions of autophagy-related proteins were explored. Using U937 cells as the subject， the effects of cytosine arabinoside （1 μmol/L）， toosendanin （160 nmol/L）， and cytosine arabinoside+toosendanin （1 μmol/L+160 nmol/L） on the expressions of autophagy-related proteins， mTORC1 signaling pathway-related proteins and mRNAs were investigated. The targeting relationship between toosendanin and the selective autophagy ligand 1 （also known as p62） was validated， and the Gene Ontology （GO） and Kyoto Encyclopedia of Genes and Genomes （KEGG） enrichment analyses， as well as molecular docking， were performed. A p62 -knockdown U937 stable cell line was constructed， and the underlying mechanism of toosendanin-induced sensitization was verified.RESULTS Animal experiments confirmed that the combination of toosendanin and cytosine arabinoside significantly improved body weight， survival time and peripheral blood routine indicators in AML mice （ P ＜0.05）， alleviated pathological changes such as leukemic cell infiltration and focal necrosis in bone marrow， liver， and spleen tissues， and modulated the expressions of autophagy-related proteins. Cell experiments confirmed that toosendanin could reverse cytosine arabinoside-induced activation of the autophagy cascade （manifested by downregulation of the protein expressions of microtubule-associated protein 1 light chain 3B and Beclin-1， upregulation the protein expression of p62）， and might inhibit the expression of the downstream Unc-51-like autophagy activating kinase 1 （ULK1） complex （including ULK1， ULK2， autophagy-related protein 13， and FAK family interacting protein of 200 kDa） by activating the mTORC1 signaling pathway （ P ＜0.05）. The sensitizing effect of toosendanin was associated with the inhibition of autophagy and the regulation of the mTORC1 signaling pathway； it could stably bind to p62 via hydrophobic interactions. Mechanism verification experiments indicated that upon p62 knockdown， toosendanin was no longer able to activate the mTORC1 signaling pathway or inhibit autophagy.CONCLUSIONS Toosendanin may enhance chemo-sensitivity of AML cells to cytosine arabinoside by directly targeting the p62 protein， which subsequently activates the mTORC1 signaling pathway， and thereby suppresses cytosine arabinoside-induced protective autophagy.

Creutzfeldt-Jakob disease(CJD)is a rapidly progressive and fatal neurodegenerative disorder caused by prions,with certain infectivity and iatrogenic transmission risks.With the rapid progress and application of new dia-gnostic biomarkers and detection methods,as well as the construction and improvement of surveillance and reporting systems,the detection of CJD in patients domestically and internationally has shown an increasing trend year by year.Due to its long incubation period and heterogeneity of early symptoms,early identification and diagnosis of the disease is difficult,increasing the risk of transmission within medical institutions.Currently,there is a lack of con-sensus on the infection prevention and control of CJD.In order to timely identify and diagnose CJD as well as effec-tively block its transmission in medical institutions,this consensus summarizes 15 clinical concerns and formulates 24 specific recommendations based on the latest domestic and international research findings and clinical evidence,as well as combines with clinical practice,aiming to standardize healthcare-associated infection prevention and control measures for CJD and reduce its transmission risk in medical institutions.

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 understand the changing composition and antibiotic resistance of bacterial species in the clinical isolates from outpatient and emergency department(hereinafter referred to as outpatients)and inpatient children over time in various hospitals,and to provide laboratory evidence for rational antibiotic use.Methods The data on clinically isolated pathogenic bacteria and antimicrobial susceptibility of isolates from outpatients and inpatient children in the CHINET program from 2015 to 2021 were collected and analyzed.Results A total of 278 471 isolates were isolated from pediatric patients in the CHINET program from 2015 to 2021.About 17.1％of the strains were isolated from outpatients,primarily group A β-hemolytic Streptococcus,Escherichia coli,and Staphylococcus aureus.Most of the strains(82.9％)were isolated from inpatients,mainly SS.aureus,E.coli,and H.influenzae.The prevalence of methicillin-resistant S.aureus(MRSA)in outpatients(24.5％)was lower than that in inpatient children(31.5％).The MRSA isolates from outpatients showed lower resistance rates to the antibiotics tested than the strains isolated from inpatient children.The prevalence of vancomycin-resistant Enterococcus faecalis or E.faecium and penicillin-resistant S.pneumoniae was low in either outpatients or inpatient children.S.pneumoniae,β-hemolytic Streptococcus and S.viridans showed high resistance rates to erythromycin.The prevalence of erythromycin-resistant group A β-hemolytic Streptococcus was higher in outpatients than that in inpatient children.The prevalence of β-lactamase-producing H.influenzae showed an overall upward trend in children,but lower in outpatients(45.1％)than in inpatient children(59.4％).The prevalence of carbapenem-resistant Klebsiella pneumoniae(CRKpn),carbapenem-resistant Pseudomonas aeruginosa(CRPae)and carbapenem-resistant Acinetobacter baumannii(CRAba)was 14％,11.7％,47.8％in outpatients,but 24.2％,20.6％,and 52.8％in inpatient children,respectively.The prevalence of multidrug-resistant E.coli,K.pneumoniae,Proteus mirabilis,P.aeruginosa and A.baumannii strains was lower in outpatients than in inpatient children.The prevalence of fluoroquinolone-resistant E.coli,ESBLs-producing K.pneumoniae,ESBLs-producing P.mirabilis,carbapenem-resistant E.coli(CREco),CRKpn,and CRPae was lower in children in outpatients than in inpatient children,but the prevalence of CRAba in 2021 was higher than in inpatient children.Conclusions The distribution of clinical isolates from children is different between outpatients and inpatients.The prevalence of MRSA,ESBL,and CRO was higher in inpatient children than in outpatients.Antibiotics should be used rationally in clinical practice based on etiological diagnosis and antimicrobial susceptibility test results.Ongoing antimicrobial resistance surveillance and prevention and control of hospital infections are crucial to curbing bacterial resistance.

Objective To investigate the changing antibiotic resistance profiles of E.coli isolated from patients in the 52 hospitals participating in the CHINET program from 2015 to 2021.Methods Antimicrobial susceptibility was tested for clinical isolates of E.coli according to the unified protocol of CHINET program.WHONET 5.6 and SPSS 20.0 software were used for data analysis.Results Atotal of 289 760 nonduplicate clinical strains ofE.coli were isolated from 2015 to 2021,mainly from urine samples(44.7±3.2)％.The proportion of E.coli strains isolated from urine samples was higher in females than in males(59.0％vs 29.5％).The proportion of E.coli strains isolated from respiratory tract and cerebrospinal fluid samples was significantly higher in children than in adults(16.7％vs 7.8％,0.8％vs 0.1％,both P＜0.05).The isolates from internal medicine department accounted for the largest proportion(28.9±2.8)％with an increasing trend over years.Overall,the prevalence of ESBLs-producing E.coli and carbapenem resistant E.coli(CREco)was 55.9％and 1.8％,respectively during the 7-year period.The prevalence of ESBLs-producing E.coli was the highest in tertiary hospitals each year from 2015 to 2021 compared to secondary hospitals.The prevalence of CREco was higher in children's hospitals compared to secondary and tertiary hospitals each year from 2015 to 2021.The prevalence of ESBLs-producing E.coli in tertiary hospitals and children's hospitals and the prevalence of CREco in children's hospitals showed a decreasing trend over the 7-year period.The prevalence of CREco in secondary and tertiary hospitals increased slowly.Antibiotic resistance rates changed slowly from 2015 to 2021.Carbapenem drugs(imipenem,meropenem)were the most active drugs amongβ-lactams against E.coli(resistance rate≤2.1％).The resistance rates of E.coli to β-lactam/β-lactam inhibitor combinations(piperacillin-tazobactam,cefoperazone-sulbactam),aminoglycosides(amikacin),nitrofurantoin and fosfomycin(for urinary isolates only)were all less than 10％.The resistance rate of E.coli strains to antibiotics varied with the level of hospitals and the departments where the strains were isolated,especially for cefazolin and ciprofloxacin,to which the resistance rate of E.coli strains from children in non-ICU departments was significantly lower than that of the strains isolated from other departments(P＜0.05).The E.coli isolates from ICU showed higher resistance rate to most antimicrobial agents tested(excluding tigecycline)than the strains isolated from other departments.The E.coli strains isolated from tertiary hospitals showed higher resistance rates to the antimicrobial agents tested(excluding tigecycline,polymyxin B,cefepime and carbapenems)than the strains from secondary hospitals and children's hospitals.Conclusions E.coli is an important pathogen causing clinical infection.More than half of the clinical isolates produced ESBL.The prevalence of CREco is increasing in secondary and tertiary hospitals over the 7-year period even though the overall prevalence is still low.This is an issue of concern.

Background and Aims:Intrahepatic cholangiocarcinoma(ICC)is a highly malignant liver tumor,with an increasing incidence worldwide,particularly in Asia.Although radical surgical resection is currently the only potentially curative treatment,the high recurrence rate and low postoperative overall survival(OS)rate of ICC remain major clinical challenges.Adjuvant therapy(AT)and neoadjuvant therapy(NAT)are important strategies to reduce postoperative recurrence and prolong OS.Several studies have shown certain efficacy of these treatments.However,the specific efficacy and safety of combined NAT and AT in ICC treatment require further validation.This study was conducted to evaluate the value of combining NAT and AT in improving the therapeutic outcomes of ICC patients through a multicenter retrospective analysis,so as to provide scientific evidence for optimizing treatment strategies.Methods:The clinicopathologic data of 576 patients with ICC who underwent radical resection and were pathologically confirmed from 13 hospitals in China between December 2011 and December 2017 were retrospectively collected.Patients were grouped based on their treatment modality:NAT+AT group,AT group,and non-NAT/AT group.The three patient groups were matched pairwise in a 1∶1 ratio using propensity score matching(PSM)to balance baseline data.The Kaplan-Meier method was used to analyze OS and disease-free survival(DFS),and subgroup analyses were conducted according to the 8th edition of the AJCC TNM staging system.Results:A total of 395 ICC patients were included in the final analysis,with 42 patients(10.6%)in the NAT+AT group,62 patients(15.7%)in the AT group,and 291 patients(73.7%)in the non-NAT/AT group.Before PSM,significant differences were observed between groups in terms of CA19-9,liver function Child-Pugh classification,intraoperative blood loss,surgical margin,differentiation grade,vascular invasion,ECOG score,and lymph node dissection ratio(all P<0.05).After PSM,there were no significant differences in baseline characteristics between the groups(all P>0.05).After matching,the median OS and DFS in the NAT+AT group were significantly better than in the AT and non-NAT/AT groups(both P<0.05),while there were no significant differences in OS and DFS between the AT and non-NAT/AT groups(both P>0.05).Subgroup analysis showed that in TNM stage I patients,DFS in the NAT+AT group was significantly better than in the non-NAT/AT group(P<0.05),but OS was not significantly different(P>0.05).In TNM stage Ⅱ and Ⅲ patients,both OS and DFS in the NAT+AT and AT groups were significantly better than in the non-NAT/AT group(both P<0.05),and DFS in the NAT+AT group was significantly better than in the AT group in TNM stage Ⅲ patients(P<0.05).Conclusion:NAT combined with AT provides better survival benefits for patients with locally advanced ICC,but its benefit for early-stage ICC patients is limited.However,the retrospective design and sample size limitations of this study may affect the stability of the results,and future large-sample,multicenter,prospective studies are needed for further validation.

Objective:To analyze the clinical efficacy of pasteurization-inactivated tumor bone replantation combined with intramedullary vascularized fibula for reconstructing bone defects after surgery for malignant bone tumors in children and adolescents.Methods:A retrospective analysis was performed on the data of 54 patients who underwent pasteurization-inactivated tumor bone replantation combined with intramedullary vascularized fibula reconstruction for bone defects after surgery for malignant bone tumors at the Bone and Soft Tissue Tumor Treatment Center of Peking University People's Hospital from September 2015 to September 2023. There were 39 males and 15 females, with an age of 12.4±5.6 years (range, 4 to 23 years). The tumor types included 33 cases of osteosarcoma, 19 cases of Ewing sarcoma, and 2 cases of soft tissue sarcoma. All cases were at Enneking stage IIB. The tumor locations were 30 cases in the femur, 19 cases in the tibia, 4 cases in the ilium, and 1 case in the humerus. The survival rate, bone healing time, tumor recurrence, and metastasis were observed. The limb function was evaluated using the Musculoskeletal Tumor Society (MSTS)-93 score.Results:All patients successfully completed the surgery and were followed up, with a follow-up time of 44.6±27.1 months (range, 12 to 96 months). The operation time was 527±132 min (range, 150 to 730 min), and the blood loss was 730±591 ml (range, 300 to 2,800 ml). The length of inactivated tumor bone was 16.5±4.5 cm (range, 9.1 to 24.0 cm), the defect length accounted for 43.4%±12.2% of the total length of the affected bone (range, 23.8% to 75.5%), the proximal osteotomy of the long bones in the extremities was 14.1±8.3 cm from the articular surface (range, 1.9 to 31.1 cm), the distal osteotomy was 9.4±6.2 cm from the articular surface (range, 1.7 to 22.9 cm), and the length of the harvested vascularized fibula was 18.0±4.0 cm (range, 11.0 to 26.4 cm). At the last follow-up, 51 patients were alive, including 47 with no evidence of tumor and 4 with tumor; 3 patients died of tumor progression. Local recurrence occurred in 5 patients, including 4 with soft tissue recurrence in the surgical area (3 underwent surgical resection and 1 received radiotherapy) and 1 with recurrence at the site of inactivated bone. Distant metastasis occurred in 11 patients, including 5 with lung metastasis only, 2 with bone metastasis only, and 4 with combined lung and bone metastasis. Among the 5 patients with lung metastasis only, lung metastases were resected, with 3 surviving with tumor, 2 surviving without tumor; the 2 patients with bone metastasis only underwent surgical resection of bone metastases, both surviving without tumor. Among the 4 patients with combined lung and bone metastasis, 3 died of tumor progression and 1 survived with tumor. The Kaplan-Meier curve showed a 5-year survival rate of 90.8%±6.2% and a 5-year recurrence-free and metastasis-free survival rate of 68.7%±7.9%. The osteotomy healing time at the diaphysis was 8.4±2.3 months (range, 4 to 13 months), the osteotomy healing time at the metaphysis was 5.9±1.7 months (range, 3 to 10 months), and the healing time between inactivated tumor bone and fibula was 6.4±2.0 months (range, 4 to 11 months). No nonunion occurred. The MSTS-93 score at the last follow-up was 94.4%±4.8% (range, 80% to 100%).Conclusion:Pasteurization-inactivated tumor bone replantation combined with intramedullary vascularized fibula reconstruction for bone defects after surgery for malignant bone tumors in children and adolescents has satisfactory clinical efficacy, high bone healing rate, and low rates of local recurrence and distant metastasis.

Objective To investigate the correlation between skeletal muscle fat content and diabetic peripheral neuropathy(DPN)in patients with type 2 diabetes mellitus(T2DM).Methods 290 patients with T2DM admitted to our hospital were enrolled in this study from January 2023 to February 2024 and divided into two groups according to whether they were complicated with DPN:simple T2DM group(T2DM,n=98)and T2DM with DPN group(DPN,n=192).The general data,biochemical indexes and fat distribution indexes measured based on quantitative CT were compared between the two groups.Spearman correlation was used to analyze the relationship between fat distribution indexes and DPN,logistic regression analysis of influencing factors of T2DM complicated with DPN.Results Age,DM duration,WHR,FIns,insulin resistance index(HOMA-IR)and FF were higher in DPN group than in T2DM group(P<0.05).Ca,subcutaneous abdominal fat area(SFA)and liver fat content were lower in DPN group than in T2DM group(P<0.05).Spearman correlation analysis showed that DPN was negatively correlated with SFA and liver fat content(r=-0.127,-0.123,P<0.05),and positively correlated with FF(r=0.117,P<0.05).Logistic regression analysis showed that without adjusting for confounding factors and adjusting for DM duration,WHR,HOMA-IR,Ca,SFA and liver fat content,FF was an influential factor for DPN in T2DM patients.Conclusions Skeletal muscle FF was associated with DPN in patients with T2DM.