Objective To investigate the expression of carcinoembryonic antigen-related cell adhesion molecule 6 (CEACAM6) in esophageal squamous cell carcinoma (ESCC) and analyze its correlation with immune cell infiltration and patient prognosis. Methods Three ESCC datasets (GSE161533, GSE26886, and GSE23400) from the GEO database were analyzed to identify differentially expressed genes. CEACAM6 was identified as a key gene through survival analysis. Its expression, prognostic value, and relationship with immune cell infiltration were further explored using databases, such as TIMER. Tissue samples were collected from 162 patients with ESCC. Immunohistochemistry was performed to detect the expression of CEACAM6, immune cell markers (CD4, CD8, CD20, and CD56), and immune checkpoint molecules (HHLA2 and CD40LG). Correlations between CEACAM6 expression and clinicopathological features, immune cell infiltration, and immune checkpoints were analyzed. Results Bioinformatic analysis and clinical sample validation confirmed that CEACAM6 expression was significantly upregulated in ESCC tissues compared with adjacent nontumor tissues (P<0.05). High CEACAM6 expression was closely associated with advanced clinical stage (AJCC Ⅲ-Ⅳ), high T stage (T3-T4), lymph node metastasis, nonulcerative type, and poor prognosis. Furthermore, CEACAM6 expression levels were positively correlated with the infiltration density of CD8⁺ T cells, CD4⁺ T cells, and CD20⁺ B cells within the tumor microenvironment and with the expression of the immune checkpoint molecules HHLA2 and CD40LG (all P<0.05). Conclusion CEACAM6 serves as an independent poor prognostic factor for ESCC. Its high expression is implicated in the modulation of the tumor immune microenvironment by correlating with specific immune cell infiltration and immune checkpoint molecules, suggesting its potential as a novel prognostic biomarker and immunotherapeutic target for ESCC.

ObjectiveTo observe the short-term and long-term efficacy of traditional Chinese medicine （TCM） surgical operations in treating mixed hemorrhoids. MethodsA multi-center retrospective cohort study was conducted， collecting clinical data from 17，831 mixed hemorrhoid surgery patients in 8 top-tier TCM hospitals in Jiangsu Province. Standardized and structured datasets were obtained through artificial intelligence models. Patients who underwent western surgical treatment were categorized into the western surgery group （11,646 cases）， and those receiving TCM surgical operations were categorized into the TCM surgery group （6185 cases）. Propensity score matching （1∶1 matching） was used to balance baseline data between groups. The primary outcome was the one-year recurrence rate， and secondary outcomes included the main symptoms （rectal bleeding， degree of prolapse） and secondary symptoms （anal distension， anal edema， wound secretion and exudation， anal stenosis， residual skin tags， perianal itching， and anal pain） measured on days 7， 28， and 60 after discharge. ResultsAfter matching， 2194 patients were included in each group. Symptom scores showed that at 28 days after discharge， the TCM surgical group had superior improvement in rectal bleeding ［OR=5.786， 95%CI （3.092，10.827）］， degree of prolapse ［OR=4.510， 95%CI （1.649，12.333）］， and anal edema ［OR=3.188， 95%CI （1.295，7.845）］ compared to the western surgical group. At 60 days post-discharge， the TCM group still showed advantages in improving rectal bleeding ［OR=5.237， 95%CI （1.077，25.464）］ and anal pain ［OR=11.697， 95%CI （1.186，115.336）］ （P＜0.05）. Long-term follow-up showed that the one-year recurrence rate in the TCM surgery group was 1.1% （8/726）， while that in the western surgery group was 2.3% （10/444）， with no statistically significant difference between the two groups （P＞0.05）. ConclusionBased on real-world data， TCM surgical treatment for mixed hemorrhoids shows significant short-term symptom improvement， particularly in terms of hemostasis， reducing swelling， and alleviating prolapse of anal masses.

Breviscapine （Bre）， the effective flavonoid fraction extracted from Erigeron breviscapus ， contains more than 90% scutellarin. It exerts pharmacological effects including cardiovascular protection， neuroprotection， anti-tumor activity and immunomodulation. Nevertheless， Bre has several drawbacks such as low solubility， low permeability， poor stability and short half-life， which greatly restrict its clinical application. Novel drug delivery systems （NDDS） are carriers that integrate multi-dimensional technologies including solubilization， penetration enhancement， sustained/controlled release and targeted delivery to achieve efficient drug delivery. This paper systematically summarizes the research progress of Bre-NDDS， which mainly covers oral preparations （sustained/controlled-release drug delivery systems， immediate-release drug delivery systems）， injectable preparations （liposomes， solid lipid nanoparticles， lipid emulsions， polymeric nanoparticles， polymeric micelles）， mucosal delivery systems （nasal mucosal drug delivery systems， buccal mucosal drug delivery systems， pulmonary mucosal drug delivery systems） and transdermal delivery systems. The preparation routes as well as in vitro and in vivo performances of various Bre-NDDS are analyzed. The design principles for NDDS based on pharmacokinetics/pharmacodynamics are put forward， which can provide scientific evidence for the research， development and industrialization of high-efficiency and safe new Bre preparations.

Childhood primary renal tubular diseases are chronic kidney diseases characterized by impaired renal tubular reabsorption. Primary renal tubular disease has diverse clinical manifestations and lacks of specificity. Laboratory tests are limited，making it prone to missed diagnosis and misdiagnosis. Based on the current knowledge of renal tubular diseases，authors propose early warning signals of renal tubular diseases such as family history of primary tubular diseases，unexplained polyhydramnios during pregnancy，polydipsia，polyuria，delayed growth and development or rickets，decreased muscle strength and tone，unexplained electrolyte disturbance，hyperuricemia，acid-base disturbance，positive urine sugar test，renal tubular proteinuria，urinary imaging examination suggesting kidney stones，calcium deposition，renal cysts and early onset of eye，ear，joint and neuron injury.Meanwhile，some universal management strategies for primary renal tubular disease are proposed，emphasizing the importance of multidisciplinary collaboration，genetic testing and individualized intervention to improve the long-term prognosis of childhood primary renal tubular diseases.

Objective:To explore the expression and ultrastructure distribution of cofilin and its potential mecha-nisms in postsynaptic mitochondrial anchoring and synaptic plasticity in the pre-B?tzinger complex(pre-B?tC)in rats.Methods:Using neurokinin 1 receptor(NK1R)as a morphological marker of the pre-B?tC,we examined the expres-sion and ultrastructure distribution of cofilin in pre-B?tC neurons of normoxic(NOR)and acute intermittent hypoxic(AIH)rats by combining Western blot,RT-qPCR,immunofluorescence,and immunoelectron microscopy.Results:Cofilin was expressed in the nuclei,somata and dendrites of NK1R-positive neurons in the pre-B?tC and its expression decreased after AIH intervention in this region detected.The results of immunoelectron microscopy showed that cofilin was expressed in the dendritic spines and postsynaptic filamentous or flocculent structures of pre-B?tC neurons.A total of 317 synapses were detected in pre-B?tC(NOR:122;AIH:195).In the NOR group,65.6％of the postsynaptic had cofilin expression,while in the AIH group,the proportion decreased to 47.2％.Combining with the role of cofilin in the regulation of actin severing,it is suggested that the severing effect of cofilin on postsynaptic actin is weakened af-ter AIH intervention,which may further enhance the postsynaptic mitochondrial anchoring.Conclusion:Cofilin,an ac-tin binding protein,plays a crucial role in regulating shearing and depolymerization of actin.Decreased cofilin expres-sion induced by AIH suggests an enhanced actin polymerization,which may be involved in the postsynaptic anchoring of mitochondria and the regulation of synaptic plasticity in the pre-B?tC.

Objective:To investigate the anticipatory grief and to explore its correlates among family caregiv-ers of patients with advanced gastrointestinal cancer.Methods:A total of 283 family caregivers of patients with ad-vanced digestive cancer in the gastroenterology ward of a hospital were assessed using the Perceptive Social Support Scale(PSSS),Simplified Coping Style Questionnaire(SCSQ),Mishel Illness Uncertainty Scale for Family Member(MULS-FM)and Anticipatory Grief Scale(AGS).Results:The median AGS score was 91.00(80.00,98.00).Multiple linear regression analysis revealed that the AGS scores were negatively correlated with PSSS scores(β=-0.21),positive coping scores(β=-0.43),education level(β=-4.99)and age(β=-4.23),but positively correlated with MULS-FM scores(β=0.24).Conclusion:Family caregivers exhibited moderate-to-high anticipato-ry grief,which significantly influenced by age,perceived social support,positive coping style,illness uncertainty and education level.

Objective:To investigate the changes of home blood pressure from weekdays to weekends and its influencing factors.Methods:This study was a national multicenter prospective registry study. Data came from the registry study on the “Action of controlling home blood pressure to target in ten thousand patients”. Hypertension patients receiving antihypertensive drugs in the above study were included, and the general clinical data of the enrolled patients were collected. Patients′ office and home blood pressure were measured at baseline, followed by home blood pressure measurements for 7 consecutive days, and blood pressure trends over a one-week period were analyzed. Multivariate linear stepwise regression was used to investigate the influencing factors of blood pressure change from weekdays to weekends, and subgroup analysis was conducted according to body mass index, alcohol consumption, fasting blood glucose ≥6.1 mmol/L or diabetes mellitus. Kappa consistency test was used to analyze the influence of removing weekend blood pressure data on home blood pressure monitoring results. Results:A total of 3 228 hypertensive patients aged (66.2±7.6) years were included, including 1 612 (49.9%) males. The weekly blood pressure changes of the study subjects showed a trend of gradually increasing during working days (Monday to Friday) and decreasing during weekends (Saturday to Sunday). The blood pressure on weekends was lower than that on weekdays, but the difference was not statistically significant ((128.2±13.7)/(79.7±8.7) mmHg vs. (128.3±12.9)/(79.8±8.3) mmHg, all P>0.05; 1 mmHg=0.133 kPa). The blood pressure on Sunday was significantly lower than that on Friday ((127.9±13.3)/(79.6±9.1) mmHg vs. (128.5±13.3)/(80.0±9.0) mmHg, all P<0.05). Subgroup analysis showed that hypertensive patients who were overweight and obese, drank alcohol, and had fasting blood glucose≥6.1 mmol/L or combined diabetes mellitus had a smaller decrease or increasing trend in home blood pressure from weekdays to weekends. Consistency test results showed that the mean blood pressure after removing the 2-day home blood pressure data on weekends was consistent with the mean blood pressure of one week ( Kappa=0.90). The mean blood pressure after removing only the blood pressure data of Sunday was slightly less consistent with the mean blood pressure of one week ( Kappa=0.88). Conclusions:The home blood pressure level of hypertensive patients receiving antihypertensive drugs showed a trend of gradually increasing during working days and decreasing at weekends. People with hypertension who were overweight and obese, drank alcohol, had high fasting blood sugar, or had combined diabetes mellitus, and their home blood pressure decreased less or increased from weekdays to weekends. The removal of 1-day Sunday blood pressure data but not 2-day weekend blood pressure data had impact on the one-week home blood pressure monitoring results.

Objective:To report the nationwide surveillance results of pathogenic profiles and antimicrobial resistance patterns of Gram-positive bloodstream infections in China in 2023.Methods:The clinical isolates of Gram-posttive bacteria from blood cultures were collected in member hospitals of National Bloodstream Infection Bacterial Resistant Investigation Collaborative System（BRICS）during January to December 2023. Antimicrobial susceptibility testing was performed using the dilution method recommended by the Clinical and Laboratory Standards Institute（CLSI）. Statistical analyses were conducted using WHONET 5.6 and SPSS 25.0 software.Results:A total of 4 385 Gram-positive bacterial isolates were obtained from 60 participating center. The top five pathogens were Staphylococcus aureus（ n=1 544，35.2%），coagulase-negative Staphylococci（ n=1 441，32.9%）， Enterococcus faecium（ n=574，13.1%）， Enterococcus faecalis（ n=385，8.8%），and α-hemolytic Streptococci（ n=187，4.3%）. The prevalence of methicillin-resistant Staphylococcus aureus（MRSA）and methicillin-resistant coagulase-negative Staphylococci（MRCNS）was 26.2%（405/1 544）and 69.8%（1 006/1 441），respectively. Notably，all Staphylococci remained susceptible to glycopeptide or daptomycin. Staphylococcus aureus demonstrated excellent susceptibility（>97.0%）to cephalobiol，rifampicin，trimethoprim-sulfamethoxazole，linezolid，minocycline，tigecycline，and eravacycline. No Enterococcus exhibiting resistance to linezolid were detected. Glycopeptide resistance was uncommon but more frequent in Enterococcus faecium（resistance to vancomycin and teicoplanin：both 1.7%）compared to Enterococcus faecalis（both 0.3%）. The detection rates of MRSA and MRCNS exhibited significant regional variations across the country（ χ2=17.674 and 148.650，respectively，both P<0.001）. No vancomycin-resistant Enterococci were detected in central China. Institutional comparison demonstrated higher prevalence of MRSA（ χ2=14.111， P<0.001）and MRCNS（ χ2=4.828， P=0.028）in provincial hospitals than that in municipal hospitals. Socioeconomic analysis identified elevated detection rates of both MRSA（ χ2=18.986， P<0.001）and MRCNS（ χ2=4.477， P=0.034）in less developed regions（per capita GDP

Objective:To report the results of bacterial resistant investigation collaborative system（BRICS）on the distribution and antimicrobial resistance profile of clinical Gram-negative bacteria isolates from bloodstream infections in China in 2023，and provide reference for clinical tretment of bloodstream infections and prevention and control of bacterial resistance.Methods:The clinical isolates of Gram-negative bacteria from blood cultures in member hospitals of BRICS were collected during January 2023 to December 2023. Antibiotic susceptibility tests were conducted by agar dilution or broth dilution methods recommended by Clinical and Laboratory Standards Institute（CLSI）. WHONET 5.6 and SPSS 25.0 were used to analyze the data.Results:During the study period，11 492 strains of Gram-negative bacteria were collected from 60 hospitals，of which 10 098（87.9%）were Enterobacterales and 1 394（12.1%）were non-fermentative bacteria. The top 5 bacterial species were Escherichia coli（50.0%）， Klebsiella pneumoniae（26.1%）， Pseudomonas aeruginosa（5.1%）， Acinetobacter baumannii complex（5.0%）and Enterobacter cloacae complex（4.1%）. The ESBL-producing rates in Escherichia coli， Klebsiella pneumoniae and Proteus mirablilis were 46.8%（2 685/5 741），18.3%（549/2 999）and 44.0%（77/175），respectively. The prevalence of carbapenem-resistant Escherichia coli（CREC）and carbapenem-resistant Klebsiella pneumoniae（CRKP）were 1.3%（76/5 741）and 15.0%（450/2 999）；32.9%（25/76）and 78.0%（351/450）of CREC and CRKP were sensitive to ceftazidime/avibactam combination，respectively. 94.7%（72/76）and 90.2%（406/450）of CREC and CRKP were sensitive to aztreonam/avibactam combination. Furthermore，57.9%（44/76）and 79.1%（356/450）were sensitive to imipenem/relebactam combination. The prevalence of carbapenem-resistant Acinetobacter baumannii（CRAB）complex was 64.6%（370/573），while more than 80.0% of CRAB complex was sensitive to tigecycline，eravacycline and polymyxin B. The prevalence of carbapenem-resistant Pseudomonas aeruginosa（CRPA）was 17.0%（99/581）. There were differences in the composition ratio of Gram-negative bacteria in bloodstream infections and the prevalence of important Gram-negative bacteria resistance among different regions in China，with statistically significant differences in the prevalence of CREC，CRKP，CRPA and CRAB complex（ χ2=10.6，28.6，10.8 and 19.3， P<0.05）. The prevalence of ESBL-producing Escherichia coli， CREC，CRAB complex and CRKP were higher in provincial hospitals than those in municipal hospitals（ χ2=12.5，9.8，12.7 and 57.8，all P<0.01）. Conclusions:Gram-negative bacteria are the main pathogens causing bloodstream infections in China，and Escherichia coli is ranked in the top，while the trend of Klebsiella pneumoniae increases continuously with time. CRKP infection shows a slow upward trend，CREC infecton maintains a low prevalence level，and CRAB complex infection continues to exhibit a high prevalence rate. The composition and resistance patterns of pathogens causing bloodstream infections vary to some extent across different regions and levels of hospitals in China.

To explore the clinical outcomes of fertility-sparing treatment (FST) in patients with POLE-mutated endometrioid carcinoma (EEC). A total of 9 EEC patients who received FST and were classified to the POLE-mutated subtype in Peking University People's Hospital from April 2020 to October 2023, were retrospectively collected. Clinical and pathological data were analyzed to describe the outcomes of FST in patients with POLE-mutated EEC.A total of 9 patients with EEC including 6 cases with well-differentiated (G1) and 3 cases with moderately-differentiated (G2). The average age was 34.8±2.1 years. POLE mutation sites were P286R (5 cases), V411L (2 cases), L424I (1 cases), and S459F (1 cases), respectively.The median follow-up time was 16 months (9–41 months). The complete response (CR) rate was 88.9% (8/9), with a median time to CR of 5.5 months (3–18 months). The partial response (PR) rate was 11.1% (1/9). The relapse rate was 50.0% (4/8), with a median recurrence time of 9.5 months (5–25 months). Of these, 75% (3/4) underwent secondary FST, with all achieving CR again (3/3). Three of 5 who were out-of-indication patients achieved CR by individual therapy. FST in patients with POLE-mutated EEC achieve a CR rate of 88.9% in this study, the largest number of retrievable reports. In certain patients who are out-ofindication, individualized treatment may also result in remission. However, unlike surgical patients, some patients experience disease recurrence and whether POLE-mutated EEC is sensitive to conventional therapy in FST is controversial given its pathogenesis.