Protein arginine methyltransferase 5 (PRMT5) acts as an oncogene in liver cancer, yet its roles and in-depth molecular mechanisms within the liver cancer immune microenvironment remain mostly undefined. Here, we demonstrated that disruption of tumor-intrinsic PRMT5 enhances CD8⁺ T-cell-mediated antitumor immunity both in vivo and in vitro. Further experiments verified that this effect is achieved through downregulation of the inhibitory immune checkpoint molecule, fibrinogen-like protein 1 (FGL1). Mechanistically, PRMT5 catalyzed symmetric dimethylation of transcription factor 12 (TCF12) at arginine 554 (R554), prompting the binding of TCF12 to FGL1 promoter region, which transcriptionally activated FGL1 in tumor cells. Methylation deficiency at TCF12-R554 residue downregulated FGL1 expression, which promoted CD8⁺ T-cell-mediated antitumor immunity. Notably, combining the PRMT5 methyltransferase inhibitor GSK591 with PD-L1 blockade efficiently inhibited liver cancer growth and improved overall survival in mice. Collectively, our findings reveal the immunosuppressive role and mechanism of PRMT5 in liver cancer and highlight that targeting PRMT5 could boost checkpoint immunotherapy efficacy.

Gastrointestinal (GI) cancers are a leading cause of cancer morbidity and mortality worldwide. Despite advances in treatment, cancer relapse remains a significant challenge, necessitating novel therapeutic strategies. In this study, we engineered nanobody-based chimeric antigen receptor (CAR) natural killer (NK) cells targeting cadherin 17 (CDH17) for the treatment of GI tumors. In addition, to enhance the efficacy of CAR-NK cells, we also incorporated CV1, a CD47-SIRPα axis inhibitor, to evaluate the anti-tumor effect of this combination. We found that CDH17-CAR-NK cells effectively eliminated GI cancers cells in a CDH17-dependent manner. CDH17-CAR-NK cells also exhibit potent in vivo anti-tumor effects in cancer cell-derived xenograft and patient-derived xenograft mouse models. Additionally, the anti-tumor activity of CDH17-CAR-NK cells is synergistically enhanced by CD47-signal regulatory protein α (SIRPα) axis inhibitor CV1, likely through augmented macrophages activation and an increase in M1-phenotype macrophages in the tumor microenvironment. Collectively, our findings suggest that CDH17-targeting CAR-NK cells are a promising strategy for GI cancers. The combination of CDH17-CAR-NK cells with CV1 emerges as a potential combinatorial approach to overcome the limitations of CAR-NK therapy. Further investigations are warranted to speed up the clinical translation of these findings.

Metabolic reprogramming plays a central role in tumors. However, the key drivers modulating reprogramming of gluconeogenesis/lipogenesis are poorly understood. Here, we try to identify the mechanism by which histone acetyltransferase 1 (HAT1) confers reprogramming of gluconeogenesis/lipogenesis in liver cancer. Diethylnitrosamine (DEN)/carbon tetrachloride (CCl₄)-induced hepatocarcinogenesis was hardly observed in HAT1-knockout mice. Multi-omics identified that HAT1 modulated gluconeogenesis and lipogenesis in liver. Protein phosphatase 2 scaffold subunit alpha (PPP2R1A) promoted gluconeogenesis and inhibited lipogenesis by phosphoenolpyruvate carboxykinase 1 (PCK1) serine 90 dephosphorylation to suppress the tumor growth. HAT1 succinylated PPP2R1A at lysine 541 (K541) to block the assembly of protein phosphatase 2A (PP2A) holoenzyme and interaction with PCK1, resulting in the depression of dephosphorylation of PCK1. HAT1-succinylated PPP2R1A contributed to the remodeling of gluconeogenesis/lipogenesis by PCK1 serine 90 phosphorylation, leading to the inhibition of gluconeogenic enzyme activity and activating sterol regulatory element-binding protein 1 (SREBP1) nuclear accumulation-induced lipogenesis gene expression, which enhanced the tumor growth. In conclusion, succinylation of PPP2R1A lysine 541 by HAT1 converses the role in modulation of gluconeogenesis/lipogenesis remodeling through PCK1 S90 phosphorylation to support liver cancer. Our finding provides new insights into the mechanism by which post-translational modifications (PTMs) confer the conversion of tumor suppressor function to oncogene.

Postoperative infection of internal fixation of closed fractures the lower limbs in adults represents a devastating complication, characterized by diagnostic challenges, prolonged treatment duration and high disability rates. Current management of these infections faces multiple challenges, such as difficulties in early accurate diagnosis, and various controversies about the treatment plan, leading to poor overall diagnosis and treatment results. To address these issues, based on evidence-based medicine and principles with emphasis on scientific rigor, clinical applicability and innovation, the Trauma Branch of the Chinese Medical Association, Orthopedic Branch of the Chinese Medical Doctor Association, Orthopedics Branch of the Chinese Medical Association, and Trauma Orthopedics and Polytrauma Group of the Resuscitation and Emergency Committee of the Chinese Medical Doctor Association have collaboratively organized a panel of relevant experts to develop the Guideline for diagnosis and treatment of infection after internal fixation of closed lower limb fractures in adults ( version 2025). The guideline proposed 10 recommendations, aiming to provide a foundation for standardized diagnosis and treatment of postoperative infection in adults with closed lower limb fractures.

Sacroiliac complex injuries are commonly seen in high-energy pelvic fractures. The injuries make a big difference in treatment patterns due to the diverse injury types, posing considerable challenges in formulating optimal treatment strategies, and hence are persistent clinical difficulties in orthopedic trauma. The clinical management of sacroiliac complex injuries presents several key challenges such as a non-negligible rate of missed diagnoses in associated vascular and visceral injuries, absence of standardized protocols for surgical approaches and reduction-fixation strategies across different injury patterns, and ongoing controversies regarding surgical indications and optimal timing for patients combined with concomitant lumbosacral plexus injuries. Currently, no systematic clinical guidelines are available for the diagnosis and treatment of sacroiliac complex injuries both domestically and internationally. To this end, the Pelvic and Acetabular Surgery Group, Orthopedic Branch, China International Exchange and Promotive Association for Medical and Health Care and Orthopedic Physician Branch, Chinese Medical Doctor Association organized a panel of domestic experts in the field to develop the Clinical guideline for the diagnosis and treatment of sacroiliac complex injuries ( version 2025), based on evidence-based medicine and adhering to the principles of scientific rigor, clinical applicability, and innovation. These guidelines provided 11 recommendations covering diagnosis, therapeutic principles and techniques, management protocols for lumbosacral plexus injuries, outcome evaluation, and postoperative rehabilitation pathways, etc., aiming to standardize the clinical management of sacroiliac complex injuries.

[Purpose]To analyze the trends in incidence,mortality and potential life loss of esophageal cancer in Linzhou City of Henan Province from 2010 to 2019.[Methods]The data of esophageal cancer incidence and mortality from 2010 to 2019 were collected from Linzhou cancer registries.The crude incidence and mortality rates,age-standardized rates(ASR)by sex and age group,the potential years of life lost(PYLL),average potential years of life lost(APYLL),and potential years of life lost rate(PYLLR)were calculated.The average annual percentage change(AAPC)from 2010 to 2019 were analyzed with Joinpoint software.[Results]From 2010 to 2019,there were a total of 8 447 newly diagnosed cases and 6 475 deaths of esophageal cancer in Linzhou.The ASR incidence and ASR mortality of esophageal cancer in the total population,males,females all showed significant downward trends,with AAPCs of-3.97％,-4.35％,-3.29％and-3.78％,-2.68％,-4.95％,respectively(all P＜0.05).The crude incidence and mortality rates in all age groups also showed significant downward trends.The AAPCs of incidence rate for the age groups of 0～49,50～59,60～69,and ≥70 years old were-9.92％,-8.27％,-1.41％,and-3.86％,respectively(all P＜0.05),and the AAPCs of mortality rate were-950％,-12.36％,-2.61％,and-2.98％,respectively(all P＜0.05).From 2010 to 2019,the total PYLL caused by esophageal cancer was 60 880 person years,APYLL was 13.73 person years,and PYLLR was 5.77‰.The PYLL,APYLL,and the PYLLR of the total population and those stratified by sex all showed a decreasing trend(all P＜0.05).[Con-clusion]From 2010 to 2019,the incidence,mortality and potential life loss of esophageal cancer in Linzhou City all decreased,and the long-term effect and screening programs is significant.How-ever,the risk of esophageal cancer among men and the elderly is still relatively high,indicating that more targeted prevention and control strategies should be developed.

[Purpose]To analyze the trends of incidence and mortality of malignant tumors in Linzhou City of Henan Province from 2010 to 2019.[Methods]The incidence and mortality data of malignant tumors of Linzhou cancer registration areas from 2010 to 2019 were collected and evaluated for data quality.The crude incidence/mortality rates and age-standardized incidence/mortality rates by Chinese standard population(ASIRC/ASMRC)were calculated by sex,age and can-cer type.Joinpoint software was used to calculate the average annual percentage change(AAPC)to analyze the trends from 2010 to 2019.[Results]From 2010 to 2019,the crude incidence of malig-nant tumors in Linzhou City showed an upward trend,with an AAPC of 2.09％(95％CI:0.58％～3.63％),while the ASIRC tended to be stable.The incidence of malignant tumors showed a signifi-cant upward trend in the 15～29 and 60～69 age groups,and a significant downward trend in the 70～79 age group.From 2010 to 2019,the ASIRC of esophageal cancer and stomach cancer in both men and women showed a significant downward trend,while that of lung cancer and prostate cancer increased in men,and the incidences of thyroid cancer,uterus cancer,cervical cancer,lung cancer and breast cancer increased significantly in women.From 2010 to 2019,the crude mortality of malignant tumors in Linzhou showed a significant upward trend,with an AAPC of 1.18％(95％CI:0.88％～1.48％),while ASMRC showed a significant downward trend,with an AAPC of-1.63％(95％CI:-1.86％～-1.40％).The mortality increased in the group aged 80 and above,while the other age groups remained in a downward or stable state.From 2010 to 2019,the ASMRC of stomach cancer and esophageal cancer in both men and women showed a down-ward trend,while those of prostate cancer,and malignant tumors of the lip,oral cavity and pha-ryngeal in men increased,and that of ovarian cancer in women increased significantly.[Conclu-sion]The disease burden of malignant tumors in Linzhou City is still heavy.The incidence of common cancer types such as thyroid cancer,prostate cancer and lung cancer shows a significant-ly increasing trends from 2010 to 2019.

Objective:To investigate the impacts of different surgical fixation sequences on the post-operative functional outcomes in patients with ankle fracture combined with Lisfranc injury.Methods:A retrospective study was conducted to analyze the 20 patients with ankle fracture and concomitant Lisfranc injury who had been treated between January 2014 and December 2023 at Department of Orthopedics, The 82nd Group Army Hospital of PLA. The cohort included 16 males and 4 females, with an age of (41.3±12.3) years. Patients were divided into 2 groups based on their surgical sequence: an ankle-first group ( n=12) treated first by open reduction and internal fixation of the ankle fracture and then by additional incision reduction and fixation of the Lisfranc injury, and a foot-first group ( n=8) treated first by open reduction and fixation of the Lisfranc injury and then by another incision for open reduction and internal fixation of the ankle fracture. The surgical time, intraoperative fluoroscopy frequency, postoperative Lisfranc articular step-off, postoperative arch height index (AHI), and American Orthopedic Foot and Ankle Society (AOFAS) ankle-hindfoot score and incidence of traumatic arthritis at 1 year after surgery were compared between the 2 groups. Results:There was no statistically significant difference in the preoperative general data between the 2 groups, indicating comparability ( P>0.05). All patients were followed up for (18.3±3.2) months after surgery. There was no statistically significant difference in surgical time or incidence of traumatic arthritis between the 2 groups ( P>0.05). In the ankle-first group, the intra-operative fluoroscopy frequency [(16.6±2.6) times] was significantly higher than that in the foot-first group [(13.6±2.5) times], and the postoperative Lisfranc articular step-off [0.0 (0.0, 0.8) mm], postoperative AHI [0.31 (0.29, 0.32)], and AOFAS ankle-hindfoot score at 1 year after surgery [(85.2±2.2) points] were all significantly better than those in the foot-first group [(1.3±1.3) mm, 0.29±0.01, and (81.0±4.1) points] (all P<0.05). Conclusion:In the treatment of ankle fracture combined with Lisfranc injury, prioritizing ankle fixation provides a stable biomechanical foundation for subsequent midfoot reduction, leading to improved functional recovery and radiographic outcomes, but requires increased intraoperative fluoroscopy.

Objective: To investigate independent risk factors for lower extremity amputation (LEA) in hospitalized patients with diabetic foot ulcers ( DFUs) . Methods: A multicenter retrospective analysis was conducted on the clinical data of 329 DFUs hospitalized patients with diabetic foot ulcers from four general hospitals across the na⁃tion. A multivariate Logistic regression model was constructed , and prediction analysis was performed using R 4. 2. 1 . The discriminative ability of the model was assessed using receiver operating characteristic curves , while calibration accuracy and clinical applicability were evaluated via calibration curves and decision curve analysis. Results : The study revealed that patients with higher education backgrounds showed lower disease severity (Wagnergrade) (Z = - 4. 331 , P < 0. 05) . A history of amputation , pre⁃existing lower extremity vascular disease , abnormal dorsalis pedis artery pulsation , and a history of coronary heart disease were significantly associated with the severity of DFUs , resulting in higher Wagner scores (P < 0. 05) . In the amputation prognosis analysis , prolonged duration of diabetes and elevated white blood cell count were positively correlated with amputation risk ( both P < 0. 01) .Multivariable regression identified non⁃higher education , low hemoglobin levels , decreased total cholesterol , and abnormally elevated platelet counts as independent risk factors for high Wagner grades ( ≥ grade 3 ) ( all P <0. 05) . The integrated predictive model incorporating these factors demonstrated strong discriminative performance ,with an area under curve of 0. 880 (95% CI: 0. 801 - 0. 960) . The calibration curve slope approached the ideal value , and decision curve analysis confirmed the model ′s clinical net benefit within a threshold probability range of 10% - 65% . Conclusion Lower education level , poor baseline nutritional status , infection , hypercoagulability ,and underlying vascular diseases collectively constitute key factors contributing to elevated amputation risk in DFUs patients. The developed predictive model exhibits high accuracy and may assist clinicians in formulating individual⁃ized intervention strategies.

Objective:To compare bowel function 12 months after surgery between side-to-end anastomosis (SEA) and end-to-end anastomosis (EEA) groups of patients who had undergone rectal cancer resection.Methods:This single-center, prospective, open-label, phase III randomized controlled trial was approved by the Ethics Committee of Peking University People's Hospital (2018PHB040-01) and registered at ClinicalTrials. org (NCT03669237). Inclusion criteria were as follows: (1) histologically confirmed rectal adenocarcinoma; (2) tumor located 0 to 12 cm from the anal verge; (3) age≥18 years; and (4) planned R0 resection with primary reconstruction. Exclusion criteria included: (1) emergency surgery; (2) cognitive impairment; (3) non-primary anastomosis; (4) history of left-sided colonic or anorectal surgery; and (5) preexisting chronic defecation dysfunction. Eligible rectal cancer patients scheduled for elective sphincter-preserving surgery at Peking University People's Hospital were prospectively enrolled between October 2018 and March 2021 and randomly assigned to either the EEA group or the SEA group via computer-generated numbers prior to entering the operating room. All patients underwent standard radical tumor resection. Bowel function was evaluated by the low anterior resection syndrome (LARS) questionnaire. It consists of five single-choice questions and yields a total score ranging from 0 to 42. Defecation function is categorized into three levels: no LARS (0-20 points), minor LARS (21-29 points), and major LARS (30-42 points). The primary endpoint was the LARS score 12 months after surgery. Secondary endpoints included LARS scores from 1 to 11 months and during long-term follow-up(>12 months). The final follow-up was completed in July 2022. All randomized patients were included in the intention-to-treat set (ITTS). The full analysis set (FAS) was defined as ITTS patients with valid outcome data. All primary statistical analyses were performed in the FAS, and results were further compared in the per-protocol set (PPS) based on the actual treatment received.Results:A total of 323 patients underwent eligibility assessment, of whom 71 did not meet the inclusion criteria and 52 declined to participate. Ultimately, 200 patients were randomized. Median age was 64 years and 85 were women. The SEA and EEA groups comprised 102 and 98 patients, respectively. A total of 181 patients (90.5%) were included in the FAS, and 170 (85.0%) were included in the PPS. Among these, the 12-month LARS score was evaluated in 178 patients (98.3%) in the FAS and in 167 (98.2%) in the PPS. Median LARS score at 1–12 months were significantly lower in the SEA group in both the FAS dataset [12 months:8 (interquartile range [IQR], 0–22) vs. 14 (IQR, 8–29); Z=2.687, P=0.007] and the PPS dataset [12 months: 8 (IQR, 0–22) vs. 14 (IQR, 6–29); Z=2.543, P=0.011]. During long-term follow-up, the median LARS score was also significantly lower in the SEA group in the FAS dataset [2 (IQR, 0–4) vs. 11 (IQR, 2–23); Z=2.968, P=0.003] and the PPS dataset [2 (IQR, 0–14) vs. 11 (2, 27); Z=2.687, P=0.007]. Conclusion:Compared with the EEA group, bowel function was superior in the SEA group 1 year after surgery and during long-term follow-up.