Protein tyrosine phosphatase nonreceptor type 2 (PTPN2) is a promising target for sensitizing solid tumors to immune checkpoint blockades. However, the highly polar active sites of PTPN2 hinder drug discovery efforts. Leveraging small interfering RNA (siRNA) technology, we developed a novel glutathione-responsive nano-platform HPssPT (HA/PEIss@siPtpn2) to silence PTPN2 and enhance immunotherapy efficacy in hepatocellular carcinoma (HCC). HPssPT showed potent transfection and favorable safety profiles. PTPN2 deficiency induced by HPssPT amplified the interferon γ signaling in HCC cells by increasing the phosphorylation of Janus-activated kinase 1 and signal transducer and activator of transcription 1, resulting in enhanced antigen presentation and T cell activation. The nano-platform was also able to promote the M1-like polarization of macrophages in vitro. The unique tropism of HPssPT towards tumor-associated macrophages, facilitated by hyaluronic acid coating and CD44 receptor targeting, allowed for simultaneous reprogramming of both tumor cells and tumor-associated macrophages, thereby synergistically reshaping tumor microenvironment to an immunostimulatory state. In HCC, colorectal cancer, and melanoma animal models, HPssPT monotherapy provoked robust antitumor immunity, thereby sensitizing tumors to PD-1 blockade, which provided new inspiration for siRNA-based drug discovery and tumor immunotherapy.

Acute respiratory distress syndrome (ARDS) is the leading cause of respiratory failure with high morbidity and mortality. Pulmonary surfactant (PS)-based complementary therapies have exhibited potential for ARDS healing and applied as an adjunctive therapy strategy. Coacervate (Coac) has the characteristics of softness, deformability and excellent molecular enrichment properties, and has attracted extensive attention in the biomedical field. Here PS and coacervate were combined for the potential ARDS treatment. The Coac, fabricated from polyallylamine hydrochloride (PAH) and adenosine triphosphate (ATP) by simple mixing, exhibited soft droplet property and high enrichment for dexamethasone sodium phosphate (DSP). To avoid the fusion effect of membraneless coacervate and endow it with biological functions of PS, liposomes with PS-biomimetic lipid components (PS-lipo) were further introduced to construct PS-biomimetic membranized coacervate (DSP@PS-Coac). The DSP@PS-Coac demonstrated high lung targeting effect and significant penetration efficiency after intravenous injection. Furthermore, PS-lipo replenished the endogenous PS pool and facilitated the distribution of DSP in inflammatory cells in the lung. In the ARDS mouse model, PS-Coac and DSP exerted synergetic anti-inflammatory functions, via reducing the recruitment of inflammatory neutrophils and modulating macrophages into anti-inflammatory phenotype. The overall results confirmed that DSP@PS-Coac may provide a promising delivery option for the treatment of ARDS.

Objective:To investigate the correlation between membranous urethral length (MUL) and early urinary continence recovery after robot-assisted radical prostatectomy (RARP).Methods:A retrospective analysis was conducted on 71 prostate cancer patients who underwent RARP by a single surgeon at the PLA General Hospital between January 2020 and December 2023. Patient characteristics included: age of (65.32±6.04) years, BMI (25.21 ± 2.59) kg/m 2, prostate volume 32.41 (24.75, 44.40) ml, PSA 11.67 (8.22, 22.66) ng/ml. Gleason score [6/7/8/9-10: 15 (21.2%)/29 (40.8%)/16 (22.5%)/11 (15.5%)], Clinical stage [cT 1/cT 2/cT 3: 4 (5.6%)/61 (85.9%)/6 (8.5%)]. Measured MUL using multiparametric prostate MRI, median MUL was 13.25 (10.41-14.99) mm. Neurovascular bundle (NVB) preservation in 13 (18.3%) cases. Patients were grouped based on continence recovery at 1 and 3 months post-catheter removal. Age, BMI, prostate volume, PSA, Gleason score, clinical stage, NVB preservation, pathological stage, catheter indwelling time, and MUL were compared between groups. Multivariate analysis identified independent predictors of continence recovery. Results:All 71 surgeries were successful, pathological stage [pT 2/pT 3-4: 47 (66.2%)/24 (33.8%)], and catheter indwelling time 2.7 (2.0, 3.0) weeks. Follow-up data at 2 months were available for 71 patients, at 1 month, 42 patients achieved continence (continence group) and 29 had incontinence (incontinence group).No significant differences were observed between continence and incontinence groups in age [(64.93±6.48)years vs. (65.79±5.89) years], BMI [(26.26±2.52)kg/m 2 vs. (24.52±2.42) kg/m 2], prostate volume [32.00 (24.12, 41.11)ml vs. 33.00 (25.27, 47.97) ml], PSA [12.55 (8.31, 24.00) ng/ml vs. 11.30 (7.92, 20.65) ng/ml], Gleason score [6/7/8/9-10: 6 (14.2%)/18 (42.9%)/12 (28.6%)/6 (14.3%) vs. 9 (31.0%)/11 (37.9%)/4 (13.8%)/5 (17.3%)], clinical stage [cT 1/cT 2/cT 3: 2 (4.8%)/35 (83.3%)/5 (11.9%) vs. 2 (6.9%)/26 (89.7%)/1 (3.4%)], NVB preservation [7 (16.7%) vs. 6 (20.7%)], pathological stage [pT 2/pT 3-4: 27 (64.3%)/15 (35.7%) vs. 20 (69.0%)/9 (31.0%)], or catheter indwelling time [2.6(2.0, 3.0) weeks vs. 2.9 (2.0, 3.4) weeks]. However, MUL was significantly longer in the continence group [13.77 (11.70, 15.32) mm vs. 10.32 (9.65, 13.57) mm, P<0.01]. Follow-up data at 3 months were available for 69 patients, At 3 months, 61 patients achieved continence (continence group) and 8 remained incontinent (incontinence group). No significant differences were observed in age [(64.89±6.25)years vs. (68.13±4.09) years], BMI [(25.34±2.64)kg/m 2 vs. (24.36±2.49) kg/m 2], prostate volume [32.41 (24.44, 44.16)ml vs. 36.13 (27.48, 48.26) ml], PSA [12.50 (8.28, 22.76)ng/ml vs. 13.34 (5.88, 23.39) ng/ml], Gleason score [6/7/8/9-10: 12 (19.7%)/25 (41.0%)/14 (23.0%)/10 (16.3%) vs. 3 (37.5%)/3 (37.5%)/2 (25.0%)/0], clinical stage [cT 1/cT 2/cT 3: 3 (4.9%)/52 (85.2%)/6 (9.8%) vs. 1 (12.5%)/7 (87.5%)/0], NVB preservation [9 (14.8%) vs. 3 (37.5%)], pathological stage [pT 2/pT 3-4: 41 (67.2%)/20 (32.8%) vs. 5 (62.5%)/9 (31.0%)], or catheter indwelling time [2.7(2.0, 3.0)weeks vs. 3.0 (2.3, 3.7) weeks]. MUL remained significantly longer in the continence group [13.57 (10.57, 15.10)mm vs. 10.12 (9.36, 10.42) mm, P=0.002]. Multivariate logistic regression incorporating age, BMI, prostate volume, MUL, NVB preservation, and catheter indwelling time identified MUL as an independent protective factor for continence recovery at both 1 month [ OR=0.62, 95 CI 0.49-0.79, P<0.01] and 3 months [ OR=0.61, 95 CI 0.41-0.92, P=0.017]. Conclusions:MUL is independently associated with early urinary continence recovery after RARP, serving as a protective predictor at both 1 and 3 months after catheter removal.

Objective:To investigate the risk factors for positive surgical margins（PSM）after robot-assisted radical prostatectomy（RARP），and to develop and validate a predictive nomogram.Methods:We retrospectively analyzed the clinicopathological data of 874 prostate cancer patients who underwent RARP performed by a single surgeon at the First Medical Center of Chinese PLA General Hospital between January 2012 and December 2018. Patients were divided into positive surgical margin（n=327）and negative surgical margin（n=547）groups based on postoperative margin status.The PSM group had significantly higher preoperative median tPSA［31.200（19.050，54.400）ng/ml vs. 15.050（9.840，27.590）ng/ml， P<0.01］，higher proportion of patients with PSAD>1 ng/ml 2［49.5%（162/327）vs. 21.2%（116/547）， P<0.01］，biopsy Gleason score ≥8［33.3%（109/327）vs. 21.2%（116/547）， P<0.01］，ISUP grade 4-5［33.3%（109/327）vs. 21.2%（116/547）， P<0.01］，clinical T stage ≥cT 3［11.3%（37/327）vs. 4.2%（23/547）， P<0.01］，and high-risk classification［82.3%（269/327）vs. 55.9%（306/547）， P<0.01］compared to the negative surgical margin group. Conversely，the PSM group had a lower prevalence of hypertension［29.7%（97/327）vs. 40.2%（220/547）， P=0.002］.Patients were randomly split into a training cohort（n=656，75%）and an internal validation cohort（n=218，25%）. An external validation cohort included 71 patients who underwent RARP by different surgeons between January 2014 and December 2016. No significant differences in baseline characteristics were observed between cohorts（ P>0.05）.Univariate and multivariate logistic regression analyses identified independent predictors of PSM，which were incorporated into a nomogram. Predictive performance was assessed using receiver operating characteristic（ROC）curves，decision curve analysis（DCA），and calibration curve. Internal and external validations were performed. Results:The PSM group had longer postoperative hospitalization［6（5，8）vs. 6（5，7）days， P=0.028］，higher rates of pathologic Gleason score ≥8［41.5%（115/277）vs. 24.9%（111/446）， P<0.01］，ISUP grade 4-5［41.5%（115/277）vs. 24.9%（111/446）， P<0.01］，pT 3 stage［52.3%（171/327）vs. 17.4%（95/547）， P<0.01］，pN 1 stage［12.8%（42/327）vs. 3.8%（21/547）， P<0.01］，extracapsular extension［52.3%（171/327）vs. 17.4%（95/547）， P<0.01］，and seminal vesicle invasion［34.6%（113/327）vs. 9.1%（50/547）， P<0.01］.Multivariate analysis identified elevated tPSA（ OR=1.014，95% CI 1.004—1.024，P=0.006）and PSAD ≥0.15 ng/（ml/g）（ OR=11.638，95% CI 1.450—93.396，P=0.021）as independent risk factors for PSM. The area under the ROC curve（AUC）of the nomogram constructed based on the above variables was 0.770（95% CI 0.735—0.805）. The AUC values for the internal and external validation sets were 0.698（95% CI 0.630—0.767）and 0.643（95% CI 0.513—0.774），respectively. The calibration curve demonstrated good agreement between the predicted and observed outcomes，and the DCA indicated that the predictive model has potential clinical utility in decision-making. Conclusion:tPSA and PSAD were identified as independent risk factors for PSM. The nomogram constructed based on these two independent predictive variables effectively predicted PSM after RARP.

Objective:To investigate the correlation between membranous urethral length (MUL) and early urinary continence recovery after robot-assisted radical prostatectomy (RARP).Methods:A retrospective analysis was conducted on 71 prostate cancer patients who underwent RARP by a single surgeon at the PLA General Hospital between January 2020 and December 2023. Patient characteristics included: age of (65.32±6.04) years, BMI (25.21 ± 2.59) kg/m 2, prostate volume 32.41 (24.75, 44.40) ml, PSA 11.67 (8.22, 22.66) ng/ml. Gleason score [6/7/8/9-10: 15 (21.2%)/29 (40.8%)/16 (22.5%)/11 (15.5%)], Clinical stage [cT 1/cT 2/cT 3: 4 (5.6%)/61 (85.9%)/6 (8.5%)]. Measured MUL using multiparametric prostate MRI, median MUL was 13.25 (10.41-14.99) mm. Neurovascular bundle (NVB) preservation in 13 (18.3%) cases. Patients were grouped based on continence recovery at 1 and 3 months post-catheter removal. Age, BMI, prostate volume, PSA, Gleason score, clinical stage, NVB preservation, pathological stage, catheter indwelling time, and MUL were compared between groups. Multivariate analysis identified independent predictors of continence recovery. Results:All 71 surgeries were successful, pathological stage [pT 2/pT 3-4: 47 (66.2%)/24 (33.8%)], and catheter indwelling time 2.7 (2.0, 3.0) weeks. Follow-up data at 2 months were available for 71 patients, at 1 month, 42 patients achieved continence (continence group) and 29 had incontinence (incontinence group).No significant differences were observed between continence and incontinence groups in age [(64.93±6.48)years vs. (65.79±5.89) years], BMI [(26.26±2.52)kg/m 2 vs. (24.52±2.42) kg/m 2], prostate volume [32.00 (24.12, 41.11)ml vs. 33.00 (25.27, 47.97) ml], PSA [12.55 (8.31, 24.00) ng/ml vs. 11.30 (7.92, 20.65) ng/ml], Gleason score [6/7/8/9-10: 6 (14.2%)/18 (42.9%)/12 (28.6%)/6 (14.3%) vs. 9 (31.0%)/11 (37.9%)/4 (13.8%)/5 (17.3%)], clinical stage [cT 1/cT 2/cT 3: 2 (4.8%)/35 (83.3%)/5 (11.9%) vs. 2 (6.9%)/26 (89.7%)/1 (3.4%)], NVB preservation [7 (16.7%) vs. 6 (20.7%)], pathological stage [pT 2/pT 3-4: 27 (64.3%)/15 (35.7%) vs. 20 (69.0%)/9 (31.0%)], or catheter indwelling time [2.6(2.0, 3.0) weeks vs. 2.9 (2.0, 3.4) weeks]. However, MUL was significantly longer in the continence group [13.77 (11.70, 15.32) mm vs. 10.32 (9.65, 13.57) mm, P<0.01]. Follow-up data at 3 months were available for 69 patients, At 3 months, 61 patients achieved continence (continence group) and 8 remained incontinent (incontinence group). No significant differences were observed in age [(64.89±6.25)years vs. (68.13±4.09) years], BMI [(25.34±2.64)kg/m 2 vs. (24.36±2.49) kg/m 2], prostate volume [32.41 (24.44, 44.16)ml vs. 36.13 (27.48, 48.26) ml], PSA [12.50 (8.28, 22.76)ng/ml vs. 13.34 (5.88, 23.39) ng/ml], Gleason score [6/7/8/9-10: 12 (19.7%)/25 (41.0%)/14 (23.0%)/10 (16.3%) vs. 3 (37.5%)/3 (37.5%)/2 (25.0%)/0], clinical stage [cT 1/cT 2/cT 3: 3 (4.9%)/52 (85.2%)/6 (9.8%) vs. 1 (12.5%)/7 (87.5%)/0], NVB preservation [9 (14.8%) vs. 3 (37.5%)], pathological stage [pT 2/pT 3-4: 41 (67.2%)/20 (32.8%) vs. 5 (62.5%)/9 (31.0%)], or catheter indwelling time [2.7(2.0, 3.0)weeks vs. 3.0 (2.3, 3.7) weeks]. MUL remained significantly longer in the continence group [13.57 (10.57, 15.10)mm vs. 10.12 (9.36, 10.42) mm, P=0.002]. Multivariate logistic regression incorporating age, BMI, prostate volume, MUL, NVB preservation, and catheter indwelling time identified MUL as an independent protective factor for continence recovery at both 1 month [ OR=0.62, 95 CI 0.49-0.79, P<0.01] and 3 months [ OR=0.61, 95 CI 0.41-0.92, P=0.017]. Conclusions:MUL is independently associated with early urinary continence recovery after RARP, serving as a protective predictor at both 1 and 3 months after catheter removal.

Objective:To investigate the risk factors for positive surgical margins（PSM）after robot-assisted radical prostatectomy（RARP），and to develop and validate a predictive nomogram.Methods:We retrospectively analyzed the clinicopathological data of 874 prostate cancer patients who underwent RARP performed by a single surgeon at the First Medical Center of Chinese PLA General Hospital between January 2012 and December 2018. Patients were divided into positive surgical margin（n=327）and negative surgical margin（n=547）groups based on postoperative margin status.The PSM group had significantly higher preoperative median tPSA［31.200（19.050，54.400）ng/ml vs. 15.050（9.840，27.590）ng/ml， P<0.01］，higher proportion of patients with PSAD>1 ng/ml 2［49.5%（162/327）vs. 21.2%（116/547）， P<0.01］，biopsy Gleason score ≥8［33.3%（109/327）vs. 21.2%（116/547）， P<0.01］，ISUP grade 4-5［33.3%（109/327）vs. 21.2%（116/547）， P<0.01］，clinical T stage ≥cT 3［11.3%（37/327）vs. 4.2%（23/547）， P<0.01］，and high-risk classification［82.3%（269/327）vs. 55.9%（306/547）， P<0.01］compared to the negative surgical margin group. Conversely，the PSM group had a lower prevalence of hypertension［29.7%（97/327）vs. 40.2%（220/547）， P=0.002］.Patients were randomly split into a training cohort（n=656，75%）and an internal validation cohort（n=218，25%）. An external validation cohort included 71 patients who underwent RARP by different surgeons between January 2014 and December 2016. No significant differences in baseline characteristics were observed between cohorts（ P>0.05）.Univariate and multivariate logistic regression analyses identified independent predictors of PSM，which were incorporated into a nomogram. Predictive performance was assessed using receiver operating characteristic（ROC）curves，decision curve analysis（DCA），and calibration curve. Internal and external validations were performed. Results:The PSM group had longer postoperative hospitalization［6（5，8）vs. 6（5，7）days， P=0.028］，higher rates of pathologic Gleason score ≥8［41.5%（115/277）vs. 24.9%（111/446）， P<0.01］，ISUP grade 4-5［41.5%（115/277）vs. 24.9%（111/446）， P<0.01］，pT 3 stage［52.3%（171/327）vs. 17.4%（95/547）， P<0.01］，pN 1 stage［12.8%（42/327）vs. 3.8%（21/547）， P<0.01］，extracapsular extension［52.3%（171/327）vs. 17.4%（95/547）， P<0.01］，and seminal vesicle invasion［34.6%（113/327）vs. 9.1%（50/547）， P<0.01］.Multivariate analysis identified elevated tPSA（ OR=1.014，95% CI 1.004—1.024，P=0.006）and PSAD ≥0.15 ng/（ml/g）（ OR=11.638，95% CI 1.450—93.396，P=0.021）as independent risk factors for PSM. The area under the ROC curve（AUC）of the nomogram constructed based on the above variables was 0.770（95% CI 0.735—0.805）. The AUC values for the internal and external validation sets were 0.698（95% CI 0.630—0.767）and 0.643（95% CI 0.513—0.774），respectively. The calibration curve demonstrated good agreement between the predicted and observed outcomes，and the DCA indicated that the predictive model has potential clinical utility in decision-making. Conclusion:tPSA and PSAD were identified as independent risk factors for PSM. The nomogram constructed based on these two independent predictive variables effectively predicted PSM after RARP.

Immune checkpoint inhibitors (ICIs) are currently used in the treatment of various tumors and play an important role in tumor treatment, resulting in many adverse reactions related to the immune system. Type 1 diabetes (T1DM) is a rare endocrine system complication, which is rarely reported at present. We report a case of T1DM after using ICIs to treat gastric cancer. The patient was a 34 year old male who developed diabetes ketoacidosis after 206 days of sintilimab monoclonal antibody use, with fasting blood glucose of 15.78 mmol/L and glycosylated hemoglobin of 8.6%. Islet related antibody: Glutamate decarboxylase antibody: 119.2 IU/mL; Insulin antibody:<2 IU/L. Fasting insulin: 0.21 mU/L; Fasting C-peptide: 0.12 μg/L. Through the analysis of patients' clinical data, it aims to improve clinicians' understanding of immune related type 1 diabetes and provide ideas for correct diagnosis and treatment.

Objective:To explore the relationship between cardiac radiation dose and prognosis of patients with non-small cell lung cancer (NSCLC).Methods:From August 2015 to September 2018, the clinical data and cardiac dose parameters of 180 patients with locally advanced NSCLC who received radiotherapy in Tangshan people′s Hospital of Hebei Province were analyzed retrospectively.The relationship between cardiac dose parameters and overall survival rate was analyzed by K-M analysis, and the prognostic factors of NSCLC patients were identified by multivariate Cox regression.Results:The median survival time of NSCLC patients was 33.4 months.Univariate analysis indicated prescription dose≥56Gy ( HR 1.54, 95% CI1.28-2.86, P=0.011), hypertension ( HR 1.42, 95% CI1.34-1.89, P=0.012), mean cardiac dose≥13.9Gy ( HR 1.12, 95% CI1.05-2.61, P=0.031), V5≥70% ( HR 1.08, 95% CI1.01-2.16, P=0.044), and V30≥40% ( HR 1.16, 95% CI1.04-3.01, P=0.041), V50≥20% ( HR 1.23, 95% CI1.11-2.81, P<0.001), and V60≥5% ( HR 1.03, 95% CI1.00-1.89, P=0.037) were the prognostic factors of NSCLC patients.After multi-factor adjustments, receiving chemotherapy was a favorable factor for the prognosis of NSCLC patients ( HR 0.711, 95% CI0.35-0.89, P=0.005); hypertension was a factor of poor prognosis ( HR 1.641, 95% CI1.56-1.86, P=0.034); V50≥20% in cardiac dose ( HR 1.161, 95% CI1.13-3.82, P=0.002) was a poor prognostic factor in NSCLC patients. Conclusion:The cardiac dose V50 is an independent predictor of prognosis in patients with advanced NSCLC.The increase of cardiac radiation dose may increase the potential risk of death.In clinical practice, the prognosis of patients may be improved by reducing the cardiac radiation dose.

Objective To summarize the curative effect of repairing large area soft tissue defects in heel and crus by flaps with double blood-supply of posterior tibial artery perforators and saphenous nerve nutrient vessels.Methods From January 2006 to February 2012,twenty cases took operation under the guide of Continuous Wave Doppler and design of tibial artery perforator as rotation point.And in all cases,island flaps with the blood supply from saphenous nerve nutrient vessels and tibial artery perforator were retained to repair large area soft tissue defects in heel and crus.In operations,the range of flap area were ranged from 19 cm × 11 cm to 11 cm × 8 cm.Skin flaps incision was up to the patella margin level,low to medial malleolus on edge,former to crus former median line,rear to after crus median line and farthest to the surface of wound on the metatarsophalangeal joint.Results Nineteen cases survived,and 1 case of skin flap mild necrosis at the farthest side took a second-phase line skin flap to repair.Followed-up from 6 months to 24 months was taken in all cases at the mean time of 10 months,with a result of good recovery and no ulceration for the flaps.To varying degree,all flaps recover sense of pain and deep touch.Conclusion There is no wound to posterior main tibial artery in repairing large area soft tissue defects in heel and crus by flaps with double blood-supply from posterior tibial artery perforators and saphenous nerve nutrient vessels,meanwhile to maintain double blood-supply from posterior tibial artery perforators and saphenous nerve nutrient vessels and expand the range of blood supply of posterior tibial artery perforators.In this operation,a blood circulation for the flap can be guaranteed so as for a large wound in heel and crus.

Objective To study the expression of tumor necrosis factor alpha (TNF-α) in the intestine of mice irradiated by neutron and γ rays.Methods 350 male BALB/c mice were irradiated with neutron and γ rays of different doses, and sacrificed at 6 and 12hours, 1, 2, 3, 4, 5, 7, 10, 14, 21 and 28 days after irradiation.The TNF-α in the mice intestinal tissue was detected by means of immunohistochemistry and image analysis.Results In normal control mice, TNF-α was expressed in the cytoplasm of macrophages in intestinal villus interstitium, submucosa and lymph tissue.After 2.5Gy neutron radiation, TNF-α was decreased progressively within 2 days, increased obviously in macrophages and crypt cells during 3rd～7th day, reached the peak at 5th day and recovered to normal level at 14th day and TNF-α was decreased progressively within 4 days after 4.0 and 5.5Gy neutron and 12Gy ray irradiation.TNF-α was increased obviously in 6～12 hours, decreased at 1st day, increased at 2nd～5th day, peaked at 3rd day and recovered at 10th day after 5.5Gy ray irradiation.Conclusion Neutron and ray radiation induce different expression profile of endogenous TNF-α in small intestine, which may be related with the pathologic courses of irradiation-induced damage and repair of intestine.