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.

Objective:To compare the medium and long-term efficacy between the deltoid split approach and the conventional deltopectoral approach in locking plate fixation for proximal humerus fractures.Methods:A retrospective study was performed in the 65 patients with proximal humerus fracture who had been operatively treated at Department of Orthopedics, The Third People's Hospital of Nantong from January 2018 to December 2020. They were 20 males and 45 females with an age of (64.6±9.2) years. Of them, 34 were assigned to fixation with proximal humerus internal locking system (PHILOS) through the deltoid split approach (minimally invasive group), and 31 to PHILOS fixation through the deltopectoral approach (conventional group). The 2 groups were compared in terms of general data, operation time, intraoperative blood loss, hospital stay, fracture union time, intraoperative fluoroscopy, postoperative 2-year imaging scores, and Constant-Murley shoulder score at the last follow-up.Results:There was no significant difference in the preoperative general data between the 2 groups, showing comparability ( P>0.05). In the minimally invasive group and the conventional group, respectively, the intraoperative blood loss was (97.9±16.6) mL and (155.8±27.4) mL, and the frequency of intraoperative fluoroscopy (12.0±1.8) times and (6.7±1.8) times, both showing a statistically significant difference ( P<0.05). There was no significant difference in operation time, hospital stay, or fracture union time ( P>0.05). All patients were followed up for (43.9±5.5) months. There was no statistically significant difference between the 2 groups in postoperative 2-year imaging scores ( P>0.05). Compared with the conventional group, patients in the minimally invasive group had significantly lower Constant-Murley strength scores and significantly lower Constant-Murley scores for the Neer four-part fractures ( P<0.05). Postoperatively, one case of screw protrusion and one case of complete ischemic necrosis occurred in both groups while one case of partial ischemic necrosis was observed in the minimally invasive group and 3 cases of partial ischemic necrosis were observed in the conventional group. Conclusions:In locking plate fixation for proximal humerus fractures, compared with the deltopectoral approach, the deltoid split approach shows advantages of less soft tissue damage, less intraoperative bleeding, and less destruction of the blood supply to the humeral head. However, the deltopectoral approach may be more appropriate for the Neer four-part fractures.

Chronic refractory wound (CRW) is one of the most challengeable issues in clinic due to complex pathogenesis, long course of disease and poor prognosis. Experts need to conduct systematic summary for the diagnosis and treatment of CRW due to complex pathogenesis and poor prognosis, and standard guidelines for the diagnosis and treatment of CRW should be created. The Guideline forthe diagnosis and treatment of chronic refractory wounds in orthopedic trauma patients ( version 2023) was created by the expert group organized by the Chinese Association of Orthopedic Surgeons, Chinese Orthopedic Association, Chinese Society of Traumatology, and Trauma Orthopedics and Multiple Traumatology Group of Emergency Resuscitation Committee of Chinese Medical Doctor Association after the clinical problems were chosen based on demand-driven principles and principles of evidence-based medicine. The guideline systematically elaborated CRW from aspects of the epidemiology, diagnosis, treatment, postoperative management, complication prevention and comorbidity management, and rehabilitation and health education, and 9 recommendations were finally proposed to provide a reliable clinical reference for the diagnosis and treatment of CRW.

Objective:To explore the indications and effect of surgical treatment of autoimmune pancreatitis.Methods:Clinical data of these 15 patients with autoimmune pancreatitis diagnosed and treated at the Department of General Surgery, the First Hospital of Peking University from 2010 to 2021 were retrospectively analyzed.Results:The main clinical symptoms were obstructive jaundice, abdominal pain, distension and weight loss. The diagnosis of AIP was confirmed by EUS-FNA in 6 patients,among them, 4 did not relapse after oral hormone treatment, 2 did not receive relevant treatment, and 1 developed gastric cancer one year later. Under a suspicion of malignancy, 9 patients underwent surgical laparotomy ,and the diagnosis was established by pathology. There was no recurrence after oral hormone therapy in 1 patient who underwent laparotomy and pancreatic biopsy. One out of the 3 patients with choledochojejunostomy relapsed after 3 years. Of the 5 patients who underwent pancreatectomy, 4 had no obvious recurrence, and 1 had recurrence after 3 years.Conclusions:Untypical autoimmune pancreatitis is likely to be misdiagnosed as pancreatic cancer. For patients with suspicious malignancy, operational management and biopsy may benefit.

Objective:To understand the characteristics of sexualized drug use (SDU) among men who have sex with men (MSM) in Chengdu and classify their behavioral patterns by applying the two-step cluster (TSC) algorithm and by exploring the association between SDU patterns and high risk sexual behaviors, in order to provide a reference basis for the development of HIV prevention interventions.Methods:Supported by an MSM-friendly organization in Chengdu from December 2021 to February 2022, MSM were recruited by on-site survey and peer referral to collect information on sociodemographics, SDU characteristics, sexual behaviors, STD diagnosis, and HIV status. TSC was performed to classify the characteristics of SDU, and the differences between groups were compared. Chi-square test and multiple binary logistic regressions were used to identify the relationship between SDU clusters and HIV-related risk sexual behaviors.Results:A total of 727 MSM were surveyed, and 39.8% (289/727) of the respondents reported SDU experience with a same-sex partner in the last six months. TSC clustered SDU-MSM into three behavioral pattern groups. There were significant differences in monthly income, types of drugs used for SDU, mode, frequency, polydrug use, multiple sexual partners, non-adherence to condom use, and group sex among the three groups of SDU-MSM ( P<0.05). Multivariate binary logistic regression analysis showed that the third category of SDU-MSM was 2.22 (95% CI: 1.06-4.66) times more likely than the first category not to use condoms consistently; the third and second categories were 2.82 (95% CI: 1.18-6.77) times and 8.78 (95% CI: 3.42-22.42) times. Conclusions:The prevalence of SDU among MSM in Chengdu was more than 1/3, and different SDU clustering pattern was associated with high-risk sexual behaviors. MSM with higher SDU frequency, drug use, and polydrug abuse are more difficult to adhere to condom use and more likely to have group sex and high risk sexual behaviors, increasing the risk of STD and HIV infection, and need to strengthen SDU surveillance and intervention.

Accurate classification of the acetabular injuries and appropriate treatment plan are great challenges for orthopedic surgeons because of the irregular anatomical structure of the acetabulum and aggregation of important vessels and nerves around it. Letournel-Judet classification system has been widely applied to classify acetabular fractures. However, there are several limitations, including incomplete inclusion of fracture types, difficulty in understanding and insufficient guidance for surgical treatment, etc. Serious complications such as traumatic arthritis are common due to wrong classification and diagnosis and improper selection of surgical strategy, which brings a heavy burden to the society and families. Three-column classification, based on anatomic characteristics, has advantages of containing more fracture types and being easy to understand, etc. To solve the problems existing in the diagnosis and treatment process based on Letournel-Judet classification, achieve accurate diagnosis and treatment of patients with acetabular fractures, and obtain satisfactory prognosis, the Orthopedic Trauma Emergency Center of Third Hospital of Hebei Medical University and the Trauma Orthopedic Branch of the Chinese Orthopedic Association organized experts from relevant fields to formulate the Expert consensus on the accurate diagnosis and treatment of acetabular fractures based on three-column classification ( version 2023) in terms of principles of evidence-based medicine. Based on the three-column classification, 15 recommendations were proposed, covering the diagnosis, treatment, complication prevention and management, etc, so as to provide reference for accurate diagnosis and treatment of acetabular fractures.

Objective:To explore the role of arthroscopic exploration in the treatment of tibial plateau fractures with homeopathic double reverse traction reduction and internal fixation.Methods:A retrospective analysis was conducted on the data of 188 patients with tibial plateau fractures treated by homeopathic double reverse traction reduction assisted internal fixation and arthroscopic exploration at the Third Hospital of Hebei Medical University from January 2019 to December 2021. There were 129 males and 59 females, aged 46.7±11.8 years (range, 14-80 years); 115 cases on the left and 73 cases on the right. Schatzker classification of fractures: 81 cases of type II, 15 cases of type III, 23 cases of type IV, 29 cases of type V, and 40 cases of type VI. The time from injury to surgery was 1-14 days, with an average of 10±5 days. The surgery was performed with double reverse traction assisted reduction, locking bone plate and self-breaking compression bolt fixation. Then, arthroscopy was used to explore the quality of fracture reduction, meniscus and ligament damage, and the corresponding intra-articular lesions were treated, such as partial meniscus resection, complete meniscus resection, or suturing. The Rasmussen score was used to evaluate the quality of fracture reduction after surgery, and the Hospital for Special Surgery (HSS) knee joint score was used to evaluate the postoperative function of the knee joint.Results:All patients successfully completed fracture reduction, fixation, and arthroscopic exploration. The average surgical time was 95±21 min (range, 30-120 min); The average intraoperative bleeding volume was 120±58 ml (range, 50-300 ml). All patients were followed up for 10-24 months, with an average of 18±6.5 months. All patients' fractures achieved clinical healing after surgery, with a healing time of 2.5-6.0 months, with an average of 3±2.4 months. Among them, 165 patients (87.8%, 165/188) healed within 3 months after surgery, while the remaining 23 patients healed within 4-6 months after surgery. Arthroscopic exploration revealed that 188 patients had good fracture reduction and a flat articular surface. Among them, 97 cases (51.6%, 97/188) were complicated with meniscus injury, with longitudinal tear (29%, 28/97) being the most common, suture treatment was performed under arthroscopy; the remaining 69 patients underwent partial meniscectomy. All the patient's knee function recovered well at the last follow-up. 29 cases (15.4%, 29/188) were complicated with cruciate ligament injury, none of them underwent primary repair and were fixed with plaster or brace after operation. The Rasmussen score for the final follow-up after surgery was 16.8±2.4 points (range, 6-18 points), with 152 cases being excellent and 36 cases being good, with a 100% excellent and good rate. The HSS knee joint scores were 79.8±9.2 points, 85.1±10.1 points, and 94.9±7.6 points at 3, 6 months after surgery, and at the last follow-up, respectively, with statistically significant differences ( F=52.53, P<0.001). Superficial skin infection occurred in 2 cases after operation, which was cured by regular dressing change and anti-infection treatment with antibiotics. Deep vein thrombosis occurred in 7 cases within 1 week after operation, and low molecular weight heparin anticoagulation therapy was given. Conclusion:After using double reverse traction assisted reduction and internal fixation, arthroscopic examination can not only evaluate the quality of reduction for tibial plateau fractures, but also handle combined meniscus injuries and evaluate the condition of cruciate ligament injuries.

Objective:To explore the potential relationship of urethral pressure profilometry and the complications of artificial urethral sphincter (AUS) implantation.Methods:The clinical data of patients who underwent AUS implantation in Beijing Hospital from March 2019 to March 2022 were retrospectively analyzed. All the patients were male. The average course of disease was 43.1 months(ranging 11-120 months). The average age was (68.6±13.2) years. The median number of pads used was 4.5 (3.0, 6.0). The preoperative maximum urethral pressure (MUP) was (84.6±25.5) cmH 2O, and the maximum urethral closure pressure (MUCP) was 51.0 (41.0, 74.0) cmH 2O. AUS implantation was performed through a single perineal incision in all patients. The sleeve size was mainly determined by the measured urethral circumference of the patient. After installation of all components, the urethral pressure profilometry was performed under the state of device inactivation and activation. The pump was activated 6 weeks after the operation, and telephone follow-up was performed 3 months after the activation of the device. The urinary control and complications were recorded. The results of follow-up were compared with the results of urethral pressure profilometry, and the preliminary conclusions were drawn. Results:In this study, 3 patients (20%) received 4.0cm cuffs, 10 patients (66.7%) received 4.5cm cuffs, and 2 patients (13.3%) received 5.0cm cuffs. The MUP and MUCP of AUS device in inactivated state were (82.5±30.2) cmH 2O and 51.0(48.0, 77.0) cmH 2O. In the activated state, MUP was (138.9±21.7) cmH 2O and MUCP was 109.0(94.0, 133.0) cmH 2O. Compared with that before operation, the urethral pressure in the inactivated state did not increase significantly (all P > 0.05), while the urethral pressure in the activated state increased significantly (all P < 0.001). The patients were followed-up for 3-33 months. Thirteen patients (86.7%) used the initial installation device, and all of them met the standard of social continence. One patient died of cerebrovascular accident. One patient took out the device due to urethral erosion. The incidence of complications was 26.7% (4/15), including painless hematuria in 2 cases, scrotum and penis infection in 1 case, and urethral erosion in 1 case. The MUP and MUCP of these patients were (100.0 ± 40.7) cmH 2O and (80.8 ± 39.7) cmH 2O respectively. In the intraoperative active state, the MUP was (151.5 ± 15.3) cmH 2O and the MUCP was (123.0 ± 17.2) cmH 2O. The MUP of the other 3 patients in the device activation state was significantly higher than the average value, and all of them were above 150 cm H 2O, except one patient who was infected due to cognitive problems and chronic urinary retention. In 11 patients without complications, the MUP and MUCP were (76.1±24.7) cmH 2O and (55.1±20.0) cmH 2O respectively. In the intraoperative active state, the MUP was (134.4±22.5) cmH 2O and the MUCP was (108.5±29.8) cmH 2O. Conclusions:AUS implantation has a definite curative effect. Poor comprehension, and MUP higher than 150 cmH 2O in the activated state of the device may be risk factors for complications.