ObjectivePancreatic ductal adenocarcinoma (PDAC) exhibits a limited response to current treatments due to its dense fibrotic stroma and highly immunosuppressive tumor microenvironment. In recent years, advancements in cellular immunotherapy, particularly chimeric antigen receptor macrophage (CAR-M) therapy, have offered new hope for pancreatic cancer treatment. Although CAR-M therapy demonstrates dual potential in directly killing tumor cells and remodeling the immune microenvironment, it still faces challenges such as complex in vitro preparation processes and low in vivo targeting and delivery efficiency. Therefore, developing strategies for efficient and targeted in vivo delivery of CAR genes has become crucial for overcoming current therapeutic limitations. This study aims to develop an orally administrable nano-gene delivery system for the targeted delivery of CAR genes to pancreatic tumor sites. MethodsCore nano-gene particles (PNP/pCAR) were constructed by loading plasmid DNA encoding CAR (pCAR) with cationic polypeptides (PNP). Subsequently, PNP/pCAR was surface-modified with β-glucan to prepare the targeted nanoparticles (βGlus-PNP/pCAR). The loading efficiency of PNP for pCAR was quantitatively assessed by gel retardation assay. The particle size, Zeta potential, morphology, and storage stability of PNP/pCAR were characterized using a Malvern particle size analyzer and transmission electron microscopy. At the cellular level, RAW 264.7 macrophages were selected. The cytotoxicity of PNP/pCAR was evaluated using the CCK-8 assay. The cellular uptake efficiency and lysosomal escape ability of the nanoparticles were assessed via flow cytometry and confocal microscopy. Transfection efficiency was quantitatively evaluated by detecting the expression of the reporter gene GFP using flow cytometry. At the in vivo level, an orthotopic pancreatic cancer mouse model was established. Cy7-labeled βGlus-PNP/pCAR nanoparticles were administered orally, and the fluorescence distribution in mice was dynamically monitored at 1, 2, 4, 8, and 16 h post-administration using a small animal in vivo imaging system. Forty-eight hours after oral gavage, the mice were euthanized, and pancreatic tumor tissues were collected for further analysis of intratumoral fluorescence signals using the imaging system. Additionally, βGlus-PNP/pCAR-GFP nanoparticles loaded with the reporter gene (GFP) were administered orally. Forty-eight hours post-administration, pancreatic tumor tissues were harvested to prepare frozen sections, and GFP expression was observed and analyzed under a fluorescence microscope. ResultsThe PNP carrier exhibited a high loading capacity for pCAR. The successfully prepared PNP/pCAR nanoparticles were regular spheres with a hydrodynamic diameter of approximately (120±10) nm and a Zeta potential of about +(6±1) mV. They maintained good structural stability after incubation in PBS buffer for 7 d. Cell experiments demonstrated that PNP/pCAR exhibited no significant cytotoxicity in RAW 264.7 cells while being efficiently internalized and effectively escaping lysosomal degradation. The transfection positive rate of PNP/pCAR-GFP in RAW 264.7 cells reached (25±3)%, surpassing that of Lipofectamine 2000-loaded pCAR-GFP (Lipo/pCAR-GFP), which was (20±1)%.In vivo experiments revealed that, compared to unmodified PNP/pCAR, βGlus-PNP/pCAR exhibited strongerin situ pancreatic tumor targeting ability after oral administration. Furthermore, oral administration of βGlus-PNP/pCAR-GFP resulted in significant GFP protein expression detectable within pancreatic tumor tissues. ConclusionThis study successfully constructed and validated an orally administrable, pancreatic cancer-targeting polypeptide-based nano-gene delivery system. It provides an important technological foundation in delivery systems and experimental basis for the subsequent development of in situ CAR-M-based therapeutic strategies for pancreatic cancer.

ObjectivePancreatic ductal adenocarcinoma (PDAC) exhibits a limited response to current treatments due to its dense fibrotic stroma and highly immunosuppressive tumor microenvironment. In recent years, advancements in cellular immunotherapy, particularly chimeric antigen receptor macrophage (CAR-M) therapy, have offered new hope for pancreatic cancer treatment. Although CAR-M therapy demonstrates dual potential in directly killing tumor cells and remodeling the immune microenvironment, it still faces challenges such as complex in vitro preparation processes and low in vivo targeting and delivery efficiency. Therefore, developing strategies for efficient and targeted in vivo delivery of CAR genes has become crucial for overcoming current therapeutic limitations. This study aims to develop an orally administrable nano-gene delivery system for the targeted delivery of CAR genes to pancreatic tumor sites. MethodsCore nano-gene particles (PNP/pCAR) were constructed by loading plasmid DNA encoding CAR (pCAR) with cationic polypeptides (PNP). Subsequently, PNP/pCAR was surface-modified with β-glucan to prepare the targeted nanoparticles (βGlus-PNP/pCAR). The loading efficiency of PNP for pCAR was quantitatively assessed by gel retardation assay. The particle size, Zeta potential, morphology, and storage stability of PNP/pCAR were characterized using a Malvern particle size analyzer and transmission electron microscopy. At the cellular level, RAW 264.7 macrophages were selected. The cytotoxicity of PNP/pCAR was evaluated using the CCK-8 assay. The cellular uptake efficiency and lysosomal escape ability of the nanoparticles were assessed via flow cytometry and confocal microscopy. Transfection efficiency was quantitatively evaluated by detecting the expression of the reporter gene GFP using flow cytometry. At the in vivo level, an orthotopic pancreatic cancer mouse model was established. Cy7-labeled βGlus-PNP/pCAR nanoparticles were administered orally, and the fluorescence distribution in mice was dynamically monitored at 1, 2, 4, 8, and 16 h post-administration using a small animal in vivo imaging system. Forty-eight hours after oral gavage, the mice were euthanized, and pancreatic tumor tissues were collected for further analysis of intratumoral fluorescence signals using the imaging system. Additionally, βGlus-PNP/pCAR-GFP nanoparticles loaded with the reporter gene (GFP) were administered orally. Forty-eight hours post-administration, pancreatic tumor tissues were harvested to prepare frozen sections, and GFP expression was observed and analyzed under a fluorescence microscope. ResultsThe PNP carrier exhibited a high loading capacity for pCAR. The successfully prepared PNP/pCAR nanoparticles were regular spheres with a hydrodynamic diameter of approximately (120±10) nm and a Zeta potential of about +(6±1) mV. They maintained good structural stability after incubation in PBS buffer for 7 d. Cell experiments demonstrated that PNP/pCAR exhibited no significant cytotoxicity in RAW 264.7 cells while being efficiently internalized and effectively escaping lysosomal degradation. The transfection positive rate of PNP/pCAR-GFP in RAW 264.7 cells reached (25±3)%, surpassing that of Lipofectamine 2000-loaded pCAR-GFP (Lipo/pCAR-GFP), which was (20±1)%.In vivo experiments revealed that, compared to unmodified PNP/pCAR, βGlus-PNP/pCAR exhibited strongerin situ pancreatic tumor targeting ability after oral administration. Furthermore, oral administration of βGlus-PNP/pCAR-GFP resulted in significant GFP protein expression detectable within pancreatic tumor tissues. ConclusionThis study successfully constructed and validated an orally administrable, pancreatic cancer-targeting polypeptide-based nano-gene delivery system. It provides an important technological foundation in delivery systems and experimental basis for the subsequent development of in situ CAR-M-based therapeutic strategies for pancreatic cancer.

The Medical Cases of WU Jutong （《吴鞠通医案》） proposes the principle of "treating all Bi （痹） diseases through taiyin"， which forms the basis for analyzing WU Jutong's understanding of the causes， mechanisms， and treatments of Bi （痹） diseases， providing a reference for clinical diagnosis and treatment. Through an interpretation of the phrase "treating all Bi （痹） diseases through taiyin"， it is suggested that Bi （痹） diseases is primarily caused by dampness， necessitating a focus on spleen and lung in treatment. WU emphasized four main causes of Bi （痹） diseases （wind， cold， dampness， and heat）， with dampness being the predominant factor. The disease location is initially in lung， for which external dampness invades lung first， and internal dampness obstructs the source of water metabolism， impeding lung qi and qi failing to disperse， then dampness further accumulates in the joints， leading to Bi （痹） diseases. WU Jutong proposed the modified Mufangji Decoction （木防己汤） as the foundational prescription for treating Bi （痹） diseases. By comparing the similarities and differences between the modified and original Mufangji Decoction， and analyzing the adjustments in herbal prescriptions， the clinical characteristic of "treating all Bi （痹） diseases through taiyin" is further substantiated.

Thoracolumbar spine fracture often leads to severe pain, functional impairments, and neurological deficits, for which open reduction and internal fixation can effectively restore the spinal structural stability. Open decompression and reduction with internal fixation can help relieve spinal cord compression and improve spinal function in cases of concomitant cord injury. Although spinal stability can be restored through surgery, patients often face chronic pain and functional impairments postoperatively. A postoperative rehabilitation program is critical in optimizing therapeutic outcomes, reducing complications, and minimizing the risk of secondary injuries. However, current rehabilitation methods, such as physical therapy, functional training, and pain management, are confronted with problems in clinical practice, including significant variation in efficacy, poor patient adherence, and prolonged rehabilitation period. There is an urgent need for a unified rehabilitation strategy to address these problems. To this end, the Spinal Trauma Group of the Orthopedic Physicians Branch of the Chinese Medical Association and the Spine Health Professional Committee of the Chinese Human Health Technology Promotion Association organized experts from relevant fields to formulate Evidence-based guidelines for rehabilitation treatment after internal fixation of thoracolumbar spine fracture in adults ( version 2025) by integrating evidences from clinical researches and advanced rehabilitation concepts at home and abroad. A total number of 14 recommendations concerning the rehabilitation treatment with multimodal analgesia, psychological intervention, deep vein thrombosis prevention, core muscle and extremity exercise, appropriate use of braces, early weight-bearing, device-aided rehabilitation exercise, neuroregulatory therapy, rehabilitation team were put forward, aiming to standardize the post-operative rehabilitation process following internal fixation, promote the functional recovery, and enhance patients′ quality of life.

Acute symptomatic osteoporotic thoracolumbar compression fracture (ASOTLF) can lead to chronic low back pain, kyphosis deformity, pulmonary dysfunction, loss of mobility, and even life-threatening complications. Vertebral augmentation is currently the mainstream treatment method for this condition. In 2019, the Editorial Board of Chinese Journal of Trauma and the Spinal Trauma Group of Orthopedic Surgeons Branch of Chinese Medical Doctor Association collaboratively led the development of Clinical guideline for vertebral augmentation for acute symptomatic osteoporotic thoracolumbar compression fractures. Six years later, with advances in clinical diagnosis and treatment techniques as well as accumulating evidence in related fields, the 2019 guideline requires updating. To this end, the Spinal Trauma Group of Orthopedic Surgeons Branch of Chinese Medical Doctor Association, the Spinal Health Professional Committee of China Human Health Science and Technology Promotion Association, and the Minimally Invasive Orthopedics Professional Committee of Shaanxi Medical Doctor Association have organized experts in the field to develop the Clinical guideline for vertebral augmentation of acute symptomatic osteoporotic thoracolumbar compression fractures ( version 2025) , based on the latest evidence-based medical researches. This guideline incorporates 3 recommendations retained from the 2019 version with updated strength of evidence, along with 12 new recommendations. It provides recommendations from six aspects of diagnosis, pain management, treatment option selection, prevention of postoperative complications, anti-osteoporosis therapy, and postoperative rehabilitation, aiming to provide a reference for standard treatment of vertebral augmentation for ASOTLF in hospitals at all levels.

The paper reports a 32-year-old female acute myeloid leukemia patient who developed graft-versus-host disease after paternal hematopoietic stem cell transplantation, which subsequently led to renal thrombotic microangiopathy. She subsequently required a kidney transplant from the same donor 5 years later due to renal failure. Considering that both the bone marrow and kidney were from the same donor and the recovery of renal function was favorable, immunosuppressive therapy was discontinued after a short course of anti-rejection treatment, with maintained stable kidney function. This case suggests that under the condition of high chimerism, allogeneic hematopoietic stem cell transplantation and kidney transplantation from the same donor can achieve immune tolerance, potentially improving solid organ transplantation success rate. The findings provide a novel therapeutic approach for solid organ transplantation following allogeneic hematopoietic stem cell transplantation.

Objective:To evaluate the safety and effectiveness of fuzuloparib for the treatment of ovarian epithelial cancer patients in the real world setting.Methods:A retrospective analysis was conducted on the baseline data of 4 620 ovarian cancer patients who had received fuzuloparib monotherapy or combination therapy. Another 224 ovarian cancer patients who were willing to receive fuzuloparib monotherapy or combination therapy were prospectively enrolled, and their baseline characteristics, drug effectiveness, and safety data were analyzed.Results:(1) Among the 4 620 patients in the retrospective cohort, the median age of patients was 60 years; tumor types: 89.8% (4 149/4 620) had ovarian cancer. Among patients with clearly documented information, the vast majority had a histological type of serous carcinoma (82.9%, 3 770/4 546) and International Federation of Gynecology and Obstetrics (FIGO) staging of Ⅲ-Ⅳ (90.9%, 1 537/1 691). (2) Among the 224 patients in the prospective cohort, the median age of patients was 57 years; tumor types: 83.9% (188/224) had ovarian cancer. Among patients with clearly documented records, the predominant pathologic type was serous carcinoma (91.9%, 193/210), and FIGO stage was Ⅲ-Ⅳ in 79.9% (139/174). (3) Among the 224 prospective patients: 84 patients received first-line fluzoparib maintenance therapy, 92 patients received fluzoparib maintenance therapy after platinum-sensitive recurrence, 23 patients received direct fluzoparib treatment after platinum-sensitive recurrence, 19 patients received direct fluzoparib treatment after platinum-resistant recurrence. The median follow-up durations were 8.5, 8.7, 7.9, and 6.7 months, respectively. The median durations of fluzoparib treatment were 6.7, 4.8, 3.1, and 1.9 months, respectively. The median progression-free survival (PFS) times were not reached during follow-up, 12.6 months, not reached during follow-up, and 4.8 months, respectively. The 1-year PFS rates were 84.1%, 55.0%, 69.8%, and 45.5%, respectively. The remaining 6 patients received other fluzoparib regimens. (4) Among the 224 patients in the prospective dataset, 205 had safety data recorded. Of these, 127 patients (62.0%, 127/205) experienced treatment-related adverse events, with common events including anemia (24.4%, 50/205), thrombocytopenia (21.0%, 43/205), and leukopenia (19.5%, 40/205). Among the 205 patients, 43 (21.0%, 43/205) experienced grade 3 or higher treatment-related adverse events, with common events including anemia (8.3%, 17/205) and thrombocytopenia (8.3%, 17/205).Conclusions:The effectiveness of fuzuloparib in clinical application is generally consistent with other drugs in the same class, with good safety. This study provids new clinical evidence for the treatment of ovarian cancer with fuzuloparib.

Objective:To explore the correlation between serum hepcidin antimicrobial peptide (HAMP), secreted phosphoprotein 1 (SPP1), and regulator of G protein signaling 2 (RGS2) levels and the clinical pathological characteristics of gastric cancer patients, and their predictive value for postoperative recurrence or metastasis.Methods:A total of 92 gastric cancer patients treated at Handan First Hospital from March 2021 to March 2023 were selected as the gastric cancer group, and 92 healthy individuals who underwent physical examinations during the same period were selected as the control group. The serum levels of HAMP, SPP1 and RGS2 were compared between the two groups. According to the mean levels of HAMP, SPP1, and RGS2 in the serum of gastric cancer patients, they were divided into HAMP high level group and HAMP low level group, SPP1 high level group and SPP1 low level group, RGS2 high level group and RGS2 low level group. The clinicopathological characteristics of gastric cancer patients with different levels of HAMP, SPP1 and RGS2 were compared respectively. After a median follow-up of 18 months, gastric cancer patients were divided into a non-recurrence or metastasis group ( n=59) and a recurrence and metastasis group ( n=33) based on whether the tumor recurred or metastasized. The serum levels of HAMP, SPP1, and RGS2 were compared between the two groups of patients. The predictive value of HAMP, SPP1 and RGS2 for postoperative recurrence or metastasis in patients with gastric cancer was analyzed by using the receiver operator characteristic (ROC) curve. Results:Compared with the control group, the gastric cancer group had higher levels of serum HAMP [ (52.28±5.44) ng/ml vs. (31.22±4.18) ng/ml] and SPP1 [ (55.96±6.43) ng/ml vs. (36.99±5.25) ng/ml] ( t=29.44, P<0.001; t=21.92, P<0.001), and lower level of RGS2 [ (3.72±0.66) mg/L vs. (5.11±0.87) mg/L) ] ( t=12.21, P<0.001). There were statistically significant differences in maximum tumor diameter ( χ2=13.07, P<0.001; χ2=6.71, P=0.010; χ2=10.56, P=0.001), TNM staging ( χ2=7.42, P=0.006; χ2=6.36, P=0.012; χ2=5.39, P=0.020), lymph node metastasis ( χ2=23.41, P<0.001; χ2=6.52, P=0.011; χ2=13.11, P<0.001), and differentiation degree ( χ2=9.01, P=0.003; χ2=7.97, P=0.005; χ2=15.29, P<0.001) between the gastric cancer patients in the HAMP high level group ( n=44) and the HAMP low level group ( n=48), the SPP1 high level group ( n=43) and the SPP1 low level group ( n=49), and the RGS2 high level group ( n=50) and the RGS2 low level group ( n=42). Compared with the non-recurrence or metastatic group, the recurrence and metastatic group had higher levels of serum HAMP [ (59.26±5.66) ng/ml vs. (48.37±4.28) ng/ml] and SPP1 [ (62.85±6.36) ng/ml vs. (52.11±5.38) ng/ml] level ( t=10.40, P<0.001; t=8.60, P<0.001), and lower level of RGS2 [ (3.01±0.48) mg/L vs. (4.12±0.69) mg/L] ( t=8.19, P<0.001). ROC curve analysis showed that the area under the curve (AUC) values of serum HAMP, SPP1, and RGS2 levels alone for predicting postoperative recurrence or metastasis in gastric cancer patients were 0.777, 0.813, and 0.778, respectively. The AUC value of the combination of the three indicators for predicting postoperative recurrence or metastasis in gastric cancer patients was 0.871. The predictive efficacy of the combination of the three indicators for predicting postoperative recurrence or metastasis in gastric cancer patients was better than that alone ( Z=2.51, P=0.035; Z=2.61, P=0.032; Z=2.71, P=0.029) . Conclusions:The levels of HAMP and SPP1 in the serum of gastric cancer patients increase, while the level of RGS2 decreases, and the levels of the three are related to the maximum tumor diameter, TNM staging, lymph node metastasis and differentiation degree, and their combined detection has higher predictive value for postoperative recurrence or metastasis in gastric cancer patients.

Objective To explore the effects of the Otago Exercise Program(OEP)on activities of daily living,muscle strength,balance,and physical function in older adults with sarcopenia,to compare OEP with conventional exercise training,and to provide a basis for clinical rehabilitation programs for older adults with sarcopenia.Methods In this randomized controlled trial,120 older adults clinically diagnosed with sarcopenia were enrolled.The participants were randomly assigned to the OEP intervention group(experimental group)and the conventional exercise intervention group(control group),with 60 in each group.The experimental group underwent 12 weeks of OEP training,three times a week,with each session lasting 45 minutes.The control group underwent conventional exercise training following the same schedule.The Modified Barthel Index was used as the primary outcome measure to assess activities of daily living.Secondary outcome measures included muscle strength,gait stability,dynamic balance,and physical function status,evaluated using grip strength,6-meter walking speed,the Timed Up and Go Test(TUGT),and the Short Physical Performance Battery(SPPB).Results A total of 120 older adults with sarcopenia were included.The mean age of the participants was(80.17±8.48)years.Baseline data before treatment showed no statistically significant differences between the two groups.Both groups completed the treatment within 12 weeks without experiencing any adverse events.The baseline data for the experimental group were as follows,MBI at(67.00±22.76)points,hand grip strength at(15.29±4.94)kg,gait speed at(0.61±0.26)m/s,TUGT time at(15.05±6.74)s,and SPPB score at(6.17±1.40)points,while the corresponding post-intervention findings were as follows,(78.72±15.83)points,(17.67±5.83)kg,(0.77±0.28)m/s,(13.49±6.16)s,and(9.25±1.71)points,respectively.The experimental group showed improvements in all measures from baseline to post-intervention(P＜0.05 for all measures).As for the control group,the baseline data for the corresponding measures were as follows,(67.20±22.12)points,(15.00±5.35)kg,(0.58±0.23)m/s,(17.29±6.90)s,and(6.00±1.24)points,respectively.The post-intervention findings increased to(71.13±20.28)points,(15.47±5.72)kg,(0.64±0.28)m/s,(16.50±6.99)s,and(6.73±1.61)points,respectively,but the changes were not statistically significant(P＞0.05).Furthermore,an intergroup comparison of intervention effects(post-intervention minus preintervention)revealed significant differences in mean changes from baseline.The experimental group demonstrated improvements of(+11.72±6.32)points in modified Barthel Index,(+11.72±6.32)kg in grip strength,(+0.16±0.09)m/s in gait speed,(—1.56±1.32)s in TUGT time,and(—1.56±1.32)points in SPPB score.In contrast,the control group showed smaller changes of(+3.93±5.65)points,(+0.47±1.37)kg,(+0.06±0.07)m/s,(—0.79±1.54)s,and(+0.73±1.12)points,respectively(all P＜0.05).Intergroup comparisons revealed superior outcomes in the experimental group across all measures.Conclusion OEP significantly enhances activities of daily living,improves muscle strength,balance,and physical function in older adults,and is more effective than conventional rehabilitation exercise programs,making it suitable for extensive clinical application.

Facing of mounting resource constraints and rising demands for personalization in medical education,regional anatomy teaching urgently requires transformation.In this paper,we focus on the regional anatomy of the thoracic wall,in order to explore a novel AI-driven teaching paradigm.Anchored in the core principle of"virtual-real integration with cadaveric dissection as the cornerstone,"the paradigm redefines educational objective and constructs an intelligent,closed-loop teaching model integrating students,computers,and instructors.Leveraging the robust support of digital intelligence(e.g.,DeepSeek),this paradigm incorporates interactive method including group collaboration,branching instruction,and gamified assessments.It achieves a comprehensive intelligent transformation of the entire teaching process-from goal setting and plan customization to activity implementation,task completion,outcome exchange,multidimensional evaluation,and reflective iteration.This new paradigm centers on medical students and leverages digital intelligence to activate deep personalized learning potential.It seamlessly integrates fundamental anatomical knowledge with clinical scenarios(e.g.,key anatomy in breast cancer surgery,flap design in breast reconstruction),and significantly enhances clinical decision-making abilities,scientific research and innovative thinking,as well as medical humanistic literacy,paving a new path for intelligent medical education.