ObjectiveHepatocellular carcinoma (HCC) represents 90% of all primary liver cancers. The main risk factors associated with HCC include viral hepatitis (B and/or C), alcohol abuse, and metabolic dysfunction-associated steatotic liver disease (MASLD), which progressively advance to liver fibrosis, cirrhosis, and ultimately evolve into HCC. Surgical resection represents the most effective treatment for HCC, while recent advances in immunotherapy, including immune checkpoint inhibitors and adoptive cell therapies, have provided improved treatment prospects for patients with unresectable HCC. However, the complex metabolic heterogeneity of HCC limits the therapeutic efficacy. Metabolic intermediates acyl-CoA not only provide energy and substrates for numerous biochemical reactions but also serve as donors for protein lysine acylation, a major class of post-translational modification (PTM). Therefore, a deeper understanding of the molecular mechanisms underlying protein lysine acylation and hepatocarcinogenesis is urgently needed. MethodsThe levels of protein lysine acylation and silence information regulator 5 (SIRT5) expression levels in clinical HCC samples were analyzed by Western blot. Quantitative malonylome and succinylome of HCC samples were analyzed by antibody-based affinity enrichment coupled with tandem mass spectrometry. The proliferation of HCC cells was analyzed with Cell Counting Kit-8 (CCK-8) assays, the apoptosis was quantified by Annexin V-FITC/propidium iodide (PI) staining coupled with flow cytometry, and the ability of cells to migrate was assayed by Transwell assays. The enzymatic activity of glutathione S-transferase Mu 1 (GSTM1) was quantified. Transgenic mice with hepatic overexpression of SIRT5 were constructed using CRISPR-Cas9, and primary hepatocarcinogenesis was induced by administration of diethylnitrosamine. ResultsWestern blot analysis indicated that the expression level of SIRT5 was elevated in clinical samples from HCC patients, and the levels of lysine malonylation, glutarylation, and succinylation were significantly reduced in HCC tissues. Knockout of SIRT5 in MHCC-97H and MHCC-97L hepatoma cells suppressed cell proliferation, and increased the percentage of apoptotic cells significantly. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses of the differentially malonylome and succinylome of HCC samples revealed significant enrichment in two major classes of biological processes: core energy metabolism (e.g., glycolysis/gluconeogenesis, tricarboxylic acid metabolic process, fatty acid beta oxidation) and detoxification and oxidative stress response (e.g., response to toxic substance, chemical carcinogenesis, reactive oxygen species (ROS)). SIRT5 removes malonylation from lysine residues in GSTM1 and restores its detoxification activity, which is crucial for the survival of hepatocytes under stressed conditions. More importantly, in vivo experiment indicated that hepatic-specific overexpression of SIRT5 in mice accelerated diethylnitrosamine-induced liver fibrosis and hepatocarcinogenesis, indicating the critical role of SIRT5 in HCC progression. ConclusionThis study highlights the previously unrecognized SIRT5-GSTM1 axis as a key regulator in hepatocarcinogenesis, and suggests a potential target for the treatment of patients with HCC.

Objective:To investigate the clinical efficacy of extended abdominal wall resec-tion combined with reconstruction for abdominal wall aggressive fibromatosis (AF).Methods:The retrospective and descriptive study was conducted. The clinical data of 70 patients with abdominal wall AF who were admitted to 3 medical centers, including The First Affiliated Hospital of the University of Science and Technology of China, between January 2009 and July 2024 were collected. There were 6 males and 64 females, aged (36±13)years. All patients underwent extended abdominal wall resection combined with abdominal wall reconstruction. Observation indicators: (1) surgical situations; (2) tumor recurrence and postoperative complications. Comparisons of measurement data with skewed distribution between groups was conducted using the Mann-Whitney U test. Comparison of count data between groups was conducted using the chi-square test. Results:(1)Surgical situations. All 70 patients underwent extended abdominal wall resection combined with abdominal wall recons-truction. The operation time was 90(91)minutes and duration of postoperative hospital stay was 10(6)days. Of the 70 patients, 41 patients underwent abdominal wall AF resection plus polypropylene mesh abdominal wall reconstruction, with a defect area of 60(54)cm2. The mesh placement method was uniformly Sublay repair. The remaining 29 patients underwent abdominal wall AF resection plus direct suture repair, with a defect area of 34(31)cm2. There was a significant difference in the abdominal wall defect area between the two groups ( U=291.00, P<0.05). All 70 patients achieved R 0 resection. The distance from surgical margin to tumor edge was 2-3 cm in 39 cases and >3 cm in 31 cases. (2) Tumor recurrence and postoperative complications. All 70 patients were followed up for 78(90)months. During follow-up, 10 patients developed tumor recurrence (5 cases with mesh reinforced abdominal wall reconstruction and 5 cases with direct suture repair). Among them, one case was monitored, one case underwent radiotherapy, and neither received further surgical treatment. The remaining 8 patients underwent repeat R 0 resection, and no further recurrence occurred. There was no significant difference in recurrence rate between the patients with mesh reconstruction and patients with direct suture repair ( χ2=0.06, P>0.05). The postoperative recurrence rate was 9.7%(3/31) in patients with the distance from surgical margin to tumor edge >3 cm, versus 17.9%(7/39) in patients with the distance from surgical margin to tumor edge of 2-3 cm, showing no significant difference between them ( χ2=0.97, P>0.05). Sixty patients had no tumor recurrence. During follow-up, none of the 70 patients developed incisional hernia. Two patients experienced postoperative wound infection, and 6 cases developed postoperative chronic pain. Conclusion:Extended abdominal wall resection combined with reconstruction is safe and feasible for abdominal wall AF.

This study was aimed at preliminarily investigating the genetic and antimicrobial resistance characteristics of Salmonella Alachua isolates through whole-genome analyses.Five Salmonella Alachua isolates from various sources(both hu-man and non-human)were collected and identified.Phenotype and serotype verification,antimicrobial susceptibility testing,and whole-genome sequencing were performed.Virulence genes,antimicrobial resistance genes,and plasmid replicons were predicted according to globally available Salmonella Alachua genomic data.A phylogenetic tree was constructed to explore the genetic background.The first report of Salmonella Alachua in China emerged in Shanghai in 2015,and patients presented pri-marily with diarrhea.The isolates have been found predominantly in the eastern and southern coastal regions.Among the five i-solates analyzed,four belonged to sequence type(ST)2061,and one belonged to ST1298.All isolates were susceptible to most commonly used clinical antibiotics.Whole-genome analyses revealed that two ST2061 strains carried the blaKPC-2 gene,and one ST1298 strain carried the fosA7 gene.Phylogenetic analysis of global Salmonella Alachua populations indicated that the ST2061 clone belonged to the C1 clade,which was closely related to strains from the UK,whereas the ST1298 clone was found in the C4 clade,a globally disseminated fosA 7-positive lineage.This study provides initial insights into the genetic and antimi-crobial resistance characteristics of Salmonella Alachua in China,highlighting the presence of strains carrying blaKPC-2 and fo-sA7 genes.These findings may provide a reference for future large-scale molecular epidemiological surveillance and source-trac-ing efforts,and they underscore the importance of enhanced resistance monitoring for Salmonella Alachua.

Objective:To investigate the predictive value of endothelial activation and stress index(EASIX)for the prognosis of patients with mantle cell lymphoma(MCL).Methods:A retrospective analysis was conducted to assess prognosis and compare the clinical features of patients diagnosed with MCL who were admitted to the Affiliated Hospital of Xuzhou Medical University from January 2010 to June 2023,had therapeutic indications and received standard treatment.Results:A total of 66 patients were included and divided into high EASIX group and low EASIX group,according to a cutoff value of 0.97 determined by the receiver operating characteristic(ROC)curve.Multivariate Cox regression analysis showed that prealbumin＜0.2 g/L,high EASIX,and ECOG PS score ≥2 were independent risk factors influencing overall survival(OS)in MCL patients.The median OS of patients in the high and low EASIX group was 13.0 and 37.5 months,and the median progression-free survival was 8.8 and 26.0 months,respectively.The proportions of patients with ECOG PS score ≥2 and prealbumin＜0.2 g/L at onset significantly increased in the high EASIX group compared to those in the low EASIX group.Conclusion:At the time of initial diagnosis,EASIX can serve as an independent prognostic indicator impacting OS in patients with MCL.Furthermore,patients in the high EASIX group experience a poorer prognosis and shorter survival duration compared with those in the low EASIX group.

The Chinese Pharmacopoeia 2025 Edition added the 9213 Guideline for validation,verification,and transfer of microbiological analytical methods.Based on the characteristics of pharmaceutical microbiological analyt-ical methods and practical applications,it specified definitions of relevant terms and application scenarios,estab-lished technical indicators and acceptance criteria for methodological evaluation,and introduced key statistical tools and evaluation principles.This article systematically elaborates on the drafting background and process of the Guideline,and interprets its key content,aiming to offer theoretical guidance and practical reference for relevant practitioners in applying this guideline.This guideline strengthens the foundation of pharmaceutical microbial analytical methods in China and enhances the scientificity and accuracy of the pharmaceutical microbial standards system.

The Chinese Pharmacopoeia 2025 Edition added the 9213 Guideline for validation,verification,and transfer of microbiological analytical methods.Based on the characteristics of pharmaceutical microbiological analyt-ical methods and practical applications,it specified definitions of relevant terms and application scenarios,estab-lished technical indicators and acceptance criteria for methodological evaluation,and introduced key statistical tools and evaluation principles.This article systematically elaborates on the drafting background and process of the Guideline,and interprets its key content,aiming to offer theoretical guidance and practical reference for relevant practitioners in applying this guideline.This guideline strengthens the foundation of pharmaceutical microbial analytical methods in China and enhances the scientificity and accuracy of the pharmaceutical microbial standards system.

Objective:To compare the impact of different treatment strategies on the survival outcomes in rectal cancer patients with poor response to neoadjuvant therapy, and to explore the survival-related influencing factors.Methods:A retrospective cohort study was conducted. Between January 2018 and November 2022, the clinical, pathological, and follow-up data of 106 rectal cancer patients who received neoadjuvant therapy and were evaluated as grade 4 or 5 based on the Magnetic Resonance Tumor Regression Grade (mrTRG) from the rectal cancer database at Peking Union Medical College Hospital were retrospectively collected. Based on the post-neoadjuvant therapy assessment, patients were classified into three groups: the chemotherapy-radiotherapy group (23 patients), the consolidation therapy group (18 patients), and the standard treatment group (65 patients). General condition, pathological findings, selection of neoadjuvant therapy, comorbidities, as well as 3-year expected DMFS and OS were observed in the three groups.Results:All 106 patients were followed up, with a median follow-up time of 28 (21, 38) months. The overall 3-year DMFS rate was 60%, and the 3-year OS rate was 74%. The 3-year DMFS in the standard treatment and consolidation therapy groups were 74% and 72%, respectively; the 3-year OS were 84%, 81%, respectively. The Log-rank test showed that there was no significant difference in the 3-year expected DMFS and OS between the standard treatment group and the consolidation therapy group (both P>0.05), but both groups had better survival outcomes than the chemotherapy-radiotherapy group (10% and 39%, respectively; all P<0.001). Multivariate Cox regression analysis indicated that the chemotherapy-radiotherapy only regimen was an independent risk factor for DMFS (HR=12.425, 95% CI: 4.436–34.594, P<0.001), and the independent risk factors for OS were chemotherapy-radiotherapy only regimen (HR=8.991, 95%CI:2.220–36.403, P=0.002) and age≥65 years (HR=3.495, 95%CI: 1.017–12.009, P=0.047). Stratified analysis showed that chemotherapy-radiotherapy only regimen was the independent risk factors for DMFS and OS in patients with extramural vascular invasion (EMVI) positive ( n=66) and mesorectal fascial invasion (MRF) positive (n=56) (all P<0.05). Whether consolidation therapy was added to the standard neoadjuvant treatment regimen was not an independent factor affecting 3-year expected DMFS or OS in rectal cancer patients with poor response to neoadjuvant therapy. Further comparisons between the standard neoadjuvant treatment and consolidation therapy groups showed no statistically significant differences in spincter-preservation rate or postoperative complication rates (both P>0.05). However, the consolidation therapy group had a longer interval between the end of radiotherapy and surgery [80.1 (50.8, 109.4) days vs. 61.8 (48.8, 74.8) days, P<0.001], and a higher incidence of chemotherapy-related adverse effects ([10/18] vs. 26.2% [17/65], P=0.018). Conclusion:In rectal cancer patients with poor response to neoadjuvant therapy and clear adverse prognostic features before surgery (locally advanced stage, MRF positive or EMVI positive), the addition of short- or long-course chemotherapy-based systemic therapy does not provide short- or long-term survival benefits. Moreover, an extended chemotherapy duration increases the incidence of chemotherapy-related adverse effects.

Objective:To investigate the clinical efficacy of extended abdominal wall resec-tion combined with reconstruction for abdominal wall aggressive fibromatosis (AF).Methods:The retrospective and descriptive study was conducted. The clinical data of 70 patients with abdominal wall AF who were admitted to 3 medical centers, including The First Affiliated Hospital of the University of Science and Technology of China, between January 2009 and July 2024 were collected. There were 6 males and 64 females, aged (36±13)years. All patients underwent extended abdominal wall resection combined with abdominal wall reconstruction. Observation indicators: (1) surgical situations; (2) tumor recurrence and postoperative complications. Comparisons of measurement data with skewed distribution between groups was conducted using the Mann-Whitney U test. Comparison of count data between groups was conducted using the chi-square test. Results:(1)Surgical situations. All 70 patients underwent extended abdominal wall resection combined with abdominal wall recons-truction. The operation time was 90(91)minutes and duration of postoperative hospital stay was 10(6)days. Of the 70 patients, 41 patients underwent abdominal wall AF resection plus polypropylene mesh abdominal wall reconstruction, with a defect area of 60(54)cm2. The mesh placement method was uniformly Sublay repair. The remaining 29 patients underwent abdominal wall AF resection plus direct suture repair, with a defect area of 34(31)cm2. There was a significant difference in the abdominal wall defect area between the two groups ( U=291.00, P<0.05). All 70 patients achieved R 0 resection. The distance from surgical margin to tumor edge was 2-3 cm in 39 cases and >3 cm in 31 cases. (2) Tumor recurrence and postoperative complications. All 70 patients were followed up for 78(90)months. During follow-up, 10 patients developed tumor recurrence (5 cases with mesh reinforced abdominal wall reconstruction and 5 cases with direct suture repair). Among them, one case was monitored, one case underwent radiotherapy, and neither received further surgical treatment. The remaining 8 patients underwent repeat R 0 resection, and no further recurrence occurred. There was no significant difference in recurrence rate between the patients with mesh reconstruction and patients with direct suture repair ( χ2=0.06, P>0.05). The postoperative recurrence rate was 9.7%(3/31) in patients with the distance from surgical margin to tumor edge >3 cm, versus 17.9%(7/39) in patients with the distance from surgical margin to tumor edge of 2-3 cm, showing no significant difference between them ( χ2=0.97, P>0.05). Sixty patients had no tumor recurrence. During follow-up, none of the 70 patients developed incisional hernia. Two patients experienced postoperative wound infection, and 6 cases developed postoperative chronic pain. Conclusion:Extended abdominal wall resection combined with reconstruction is safe and feasible for abdominal wall AF.

AIM To establish the preparation process and quality standard for Zhenggu Pills.METHODS With decoction time,decoction frequency and water addition as influencing factors,comprehensive score for extract yield and transfer rates of epicatechin and naringin as an evaluation index,the decoction process was optimized by orthogonal test.With sugarless paste relative density,medicinal powder fineness,sugarless paste-corn starch ratio,drying temperature and drying time as influencing factors,soft material traits,pill formability,moisture and disintegration time limit as evaluation indices,the formability process was optimized by single factor test.TLC was adopted in the qualitative identification of Dipsaci Radix,salt-processed Psoraleae Fructus,cooked Rhei Radix et Rhizoma and Notoginseng Radix et Rhizoma.HPLC was used for the content determination of paeoniflorin and naringin.RESULTS The optimal decoction process was determined to be 0.5 h for decoction time,two times for decoction frequency,and 10 times for water addition,the comprehensive score was 0.93.The optimal formability process was determined to be 1.21-1.22 for sugarless paste relative density,80 mesh for medicinal powder fineness,1∶0.17-1∶0.18 for sugarless paste-corn starch ratio,70 ℃ for drying temperature,and 24 h for drying time,good soft material traits and pill formability were observable,and moisture and disintegration time limit accored with 2020 edition of Chinese Pharmacopoeia requirements.The TLC spots were clear without negative interference.Two constituents showed good linear relationships within 61.30-490.41 μg/mL(r=0.999 8)and 3.27-26.18 μg/mL(r=0.999 8),whose average recoveries were 100.15％and 98.15％with the RSDs of 0.55％and 2.30％,respectively.CONCLUSION This stable,reliable and specific method can be used for the production and quality evaluation of Zhenggu Pills.