Objective To investigate the effects and underlying mechanisms of a spray prepared from exosomes derived from M2 macrophages induced by interleukin-4 （IL-4） and tantalum particles （Ta） on the healing of pressure ulcers. Methods Bone marrow-derived macrophages were polarized into M2 macrophages using IL-4 or Ta, and exosomes （Exo-IL-4/Exo-Ta） were extracted. The regulatory effects of Exo-IL-4/Exo-Ta on M1 macrophage phenotypes and fibroblast matrix secretion were evaluated in vitro. Proteomic analysis was conducted to explore the biological processes and regulatory networks associated with Exo-Ta. A rat pressure ulcer model was used to assess the effects of Exo-IL-4/Exo-Ta spray on wound healing rate, inflammatory cell infiltration, and collagen deposition. Results In vitro, Exo-IL-4/Exo-Ta induced the polarization of M1 macrophages to M2 macrophages, reduced the secretion of pro-inflammatory factors, and promoted the expression of anti-inflammatory substances. Additionally, Exo-IL-4/Exo-Ta enhanced the production of collagen and fibronectin in fibroblasts. Proteomic analysis revealed that Exo-Ta primarily participated in biological processes such as energy metabolism and macromolecule biosynthesis. In vivo, Exo-IL-4/Exo-Ta spray accelerated wound healing, reduced inflammatory infiltration, and improved tissue remodeling in the rat pressure ulcer model. Conclusion Exosome sprays derived from M2 macrophages could accelerate pressure ulcer healing by modulating inflammation and promoting tissue regeneration, which demonstrated excellent clinical application potential.

ObjectiveTo investigate the potential targets and mechanisms of Draconis Sanguis (DS), a valuable traditional Chinese medicine derived from the resin of the palm tree Daemonorops draco Bl (D. Sanguis, Xue Jie), in the treatment of myocardial infarction (MI).MethodsWe explored the potential mechanisms of DS in the treatment of MI using network pharmacology, bioinformatic techniques, and transcriptomic analysis, followed by validation through in vivo and in vitro experiments.ResultsNetwork pharmacology and bioinformatic analyses identified five genes (Fpr1, Glul, Mme, Mmp9, and Pla2g7) as potential targets for MI treatment. Moreover, DS significantly ameliorated cardiac function, inflammatory responses, and MI-induced myocardial fibrosis in vivo. Transcriptomic and bioinformatic analyses identified Pla2g7 as the most critical target in the DS treatment of MI. Molecular docking revealed that the key active ingredient in DS has a strong affinity for this gene. Furthermore, DS reduced the expression of Pla2g7 (P = .0009), NLRP3 (P = .003), interleukin-18 (P .001), and interleukin-1β (P = .004) mRNAs in vivo.ConclusionsThe results indicate that DS can downregulate the expression of Pla2g7 and reduce the inflammatory response. This demonstrates the potential therapeutic target of DS and the mechanism underlying its cardioprotective effects.

Objective: To evaluate the efficacy and safety of adding toripalimab to bevacizumab and platinum-based chemotherapy as first-line treatment for refractory recurrent or metastatic (R/M) cervical cancer (CC). Methods: Patients were administered toripalimab (240 mg) + bevacizumab (7.5 mg/kg) combined with platinum-based chemotherapy once every three weeks for six cycles, followed by the maintenance therapy involving toripalimab + bevacizumab once every 3 weeks for 12 months or when disease progression or intolerable toxicity occurred. The primary endpoint was the objective response rate (ORR) per Response Evaluation Criteria in Solid Tumors version 1.1. The secondary endpoints were safety profiles, disease control rate (DCR), progression-free survival (PFS), and overall survival (OS). Results: Twenty-four patients were enrolled in this study and in the final analysis. The median follow-up duration was 18.6 (range, 3.3–28.5) months. The ORR was 83.3% (95% confidence interval [CI]=62.6–95.3) and the DCR was 95.8% (95% CI=78.9–99.9); 9 (37.5%) patients achieved complete response, 11 (45.8%) achieved partial response, and 3 (12.5%) had stable disease. The median PFS was 22.6 (95% CI=10.4–34.7) months and the median OS was not reached. The most common grade 3 treatment-related adverse events (AEs) were neutropenia (41.7%) and leukopenia (16.7%). The most common immune-related AEs (irAEs) were thyroid dysfunction (37.5%) and increased adrenocorticotropic hormone (37.5%) and serum cortisol levels (33.3%). No grade ≥3 irAEs were observed. Conclusion Toripalimab combined with bevacizumab and platinum-based chemotherapy show promising clinical efficacy and favorable safety profile, providing an alternative firstline treatment option for patients with R/M CC.

Objective: Anti-programmed cell death protein 1 (PD-1) therapy has demonstrated favorable therapeutic responses in patients with chemorefractory gestational trophoblastic neoplasia.The need for combined surgery to remove resistant foci in patients treated with anti-PD-1 therapy after complete remission (CR), however, has not been investigated. We therefore compared the prognosis of patients with high-risk chemorefractory or relapsed choriocarcinoma who underwent anti-PD-1 therapy with or without surgery. Methods: Patients with high-risk chemorefractory or relapsed choriocarcinoma who experienced CR following immunotherapy in conjunction with either surgical or non-surgical interventions were selected at Peking Union Medical College Hospital (PUMCH) between August 2018 and December 2023. Study endpoints included progression-free survival (PFS) and overall survival (OS). The results were analyzed using Mann–Whitney U tests and Kaplan–Meier analysis. Results: Forty-three patients who received andi-PD-1 therapy were enrolled in this study, including 18 patients with surgery and 25 without. Most of the foci in the surgery group were solitary (77.8%). The median maximum diameters of resistant foci before immunotherapy were 2.9 (0.7–7.3) cm and 1.4 (0.8–11.2) cm in the surgery and non-surgery groups, respectively (p=0.184). The 2-year PFS rate was both 91.5% in the non-surgery group and 90.9% in the surgery group. The 2-year and 3-year OS rates were 100.0% in both groups.There was no significant difference in PFS (p=0.849) or OS (p=0.371) between the 2 groups. Conclusion These results suggest that surgical resection of drug-resistant lesions may not be necessary in patients with high-risk chemorefractory or relapsed choriocarcinoma who achieve CR after anti-PD-1 therapy.

Objective To investigate the protective mechanism of Wenyang Fuyuan Prescription on nerve injury by improving brain iron metabolism in rats with cerebral ischemia-reperfusion injury(CIRI)based on ferroptosis.Methods A total of 72 SD rats were randomly divided into sham-operation group,CIRI model group,Wenyang Fuyuan Prescription group(18.0 g·kg-1,gavage),ferroptosis inducer group(100 mg·kg-1,intraperitoneal injection),Wenyang Fuyuan Prescription(18.0 g·kg-1,gavage)+ ferroptosis inducer group(intraperitoneal injection)and ferroptosis inhibitor group(5 mg·kg-1,intraperitoneal injection),12 rats in each group.All the procedures adopted in the sham group were the same as those in the model group.But nylon thread was inserted into the internal carotid artery at a depth of 9 mm and un-plugged middle cerebral artery.The rest of the groups were used to construct middle cerebral artery occlusion/reperfusion(MCAO/R)model by thread embolism method.Ferroptosis inducer(100 mg·kg-1)and ferroptosis inhibitor(5 mg·kg-1)were administered intraperitoneally to rats according to the grouping 24 hours before modeling.Wenyang Fuyuan Prescription(18.0 g·kg-1)was administered by gavage 2 hours after anesthesia and awakening.All intervention were given once daily for 7 consecutive days.The Longa scoring standard was used to evaluate the neurological deficit on 1,3,and 7 days after MCAO/R surgery,respectively.At the end of the treatment period,brain tissues were taken to observe the morphological changes of rat neurons in each group by hematoxylin eosin staining(HE).The ultrastructural changes of neuron mitochondria in each group were observed by transmission electron microscope.The biochemical kit was used to detect the content of iron ions(Fe2+)and reduced glutathione(GSH)in brain tissue.The protein and mRNA expressions of transferrin receptor 1(TFR1),iron regulatory protein 1(IRP1)and ferroportin(FPN)were detected by real-time quantitative polymerase chain reaction(RT-qPCR)and Western Blot.Results① Compared with sham group,the neurological deficit scores of rats in model group increased at each time point(P＜0.01).HE staining showed neurons were sparse and disordered,the nuclei underwent pyknosis,and vacuoles appeared at the edges.Under electron microscopy,it was observed that the number of neuronal mitochondria decreased,the density of mitochondrial membranes increased,massive numbers of mitochondrial membranes ruptured and dissolved,and mitochondrial cristae disappeared.The content of Fe2+,both mRNA and protein expressions of TFR1 were significantly increased(P＜0.01),while GSH content,as well as expressions of mRNA and protein for IRP1 and FPN were significantly decreased(P＜0.05,P＜0.01).② Compared with the model group,the neurological deficit scores of rats in the Wenyang Fuyuan Prescription group decreased at various time points(P＜0.05).The number of neurons increased,their arrangement was relatively neat,the morphology of the nucleus is complete and clear,the mitochondrial structure of neurons was relatively complete,the mitochondrial membrane was relatively intact,and the mitochondrial cristae were clear.The content of Fe2+,both mRNA and protein expressions of TFR1 were decreased(P＜0.05,P＜0.01),while GSH content,as well as expressions of mRNA and protein for IRP1 and FPN increased(P＜0.05,P＜0.01).③ Compared with the Wenyang Fuyuan Prescription group,the neurological deficit scores of rats in ferroptosis inducer group and the Wenyang Fuyuan Prescription + ferroptosis inducer group increased at all time points(P＜0.05).Distribution of neurons was in disorder,the nucleus shrinked,and vacuoles appeared at the edges.The density of mitochondrial membranes increased,some ruptured and dissolved mitochondrial membranes were found.The number of mitochondria decreased and mitochondrial cristae disappeared.The content of Fe2+,both TFR1 mRNA and protein expression increased(P＜0.05,P＜0.01),while the content of GSH,as well as expressions of mRNA and protein for IRP1 and FPN decreased(P＜0.05,P＜0.01).However,there was no statistically significant difference in all observed indicators between the ferroptosis inhibitor group and the Wenyang Fuyuan Prescription group(P＞0.05).Conclusion Wenyang Fuyuan Prescription can improve the neurological function and pathological damage of CIRI rats.Its mechanism may be related to regulating the expression of IRP1 protein,improving the brain iron metabolism pathway,and inhibiting ferroptosis.

Objective: To evaluate the oncological and reproductive outcomes in patients with seromucinous borderline ovarian tumors (SMBOT) treated with fertility-sparing surgery (FSS). Methods: We retrospectively reviewed the medical records of patients with SMBOT who underwent surgery between 2000 and 2019. A centralized histological review was performed and recurrence rates were compared between different surgical procedures. Results: A total of 105 patients fulfilled the inclusion criteria, of whom 65 underwent FSS and 40 were treated with radical surgery. Fourteen patients had recurrent disease after a median follow-up time of 59.6 months (range: 22.1–256.8 months). All but one relapsed with SMBOT. There was no significant difference in disease-free survival (DFS) between the 2 groups (p=0.141). Multivariate analysis showed that only bilateral involvement was associated with increased recurrence (p=0.008). In the subgroup of patients treated with conservative surgery, there was no significant difference in DFS with regard to surgical procedures (ovarian cystectomy vs. salpingo-oophorectomy, p=0.487). Of the 12 patients in the FSS group who developed recurrence, 11 underwent a second round of FSS and all remained alive with no evidence of disease at the end of follow-up. Of 20 patients desiring pregnancy, 16 patients were successful and resulted in 17 term deliveries. Conclusion FSS is feasible for young patients who wish to preserve their fertility. Patients initially treated with ovarian cystectomy may be managed by close surveillance if post-operative imaging are negative. Repeat FSS remains a valuable alternative for young patients with recurrent SMBOT after thorough communication.

Objective: To investigate the clinical characteristics, treatments, and prognostic factors among patients with gestational trophoblastic neoplasia (GTN) exhibiting brain metastases who underwent craniotomy. Methods: Thirty-five patients with GTN who had brain metastases and subsequently underwent craniotomies between January 1990 and December 2018 at Peking Union Medical College Hospital were identified using the GTN database. Their clinical manifestations, treatments, outcomes, and prognostic factors were retrospectively analyzed. Results: All 35 patients underwent decompressive craniotomy, hematoma removal, and metastatic tumor resection combined with multiagent chemotherapy. Eighty percent (28/35) achieved complete remission, 11.4% (4/35) achieved partial remission, and 8.6% (3/35) had progressive disease. Not counting 2 patients who were lost to follow-up, 81.8% of the patients (27/33) were alive after a median follow-up of 72 months. The 5-year overall survival rate was 80.4%. Univariate analysis revealed that a history of chemotherapy failure (p=0.020) and a >1-week interval between craniotomy and chemotherapy commencement (p=0.027) were adverse risk factors for survival. Multivariate analysis showed that previous chemotherapy failure remained an independent risk factor for poor survival (odds ratio=11.50; 95% confidence interval=1.55–85.15; p=0.017). Conclusion Decompressive craniotomy is a life-saving option if metastatic hemorrhage and intracranial hypertension produce a risk of cerebral hernia in patients with GTN who have brain metastases. Higher survival rates and improved prognoses can be achieved through perioperative multidisciplinary cooperation and timely standard postoperative chemotherapy.

Objective:To analyze the level of fractional exhaled nitric oxide (FeNO) and its influencing factors in patients with chronic obstructive pulmonary disease (COPD).Methods:678 patients with stable COPD(COPD group), 281 patients with asthma-COPD overlap(COPD with asthma group) and 120 healthy nonsmoker controls (healthy control group) were recruited from the outpatient clinics of Xiangya Second Hospital of Central South University and the 1st People′s Hospital of Huaihua from November 2016 to December 2021. The gender, smoking status, age, height, weight, body mass index (BMI), FEV 1% predicted value (FEV 1% pred), forced expiratory volume in 1 second/forced vital capacity (FEV 1/FVC%), and FeNO value among the three groups were compared. Multiple linear regression analysis was performed to analyze the influencing factors of FeNO levels in COPD patients. Results:There was no significant difference in gender, smoking status, age, height, weight and BMI among the three groups (all P>0.05). The FEV 1% and FEV 1/FVC% in COPD group were lower than those in healthy group and COPD combined with asthma group (all P<0.05). The FeNO in COPD group was lower than that in COPD and asthma group, but higher than that in healthy group (all P<0.05). Univariate analysis showed that FeNO levels in COPD patients were associated with height, BMI, Global Initiative for Chronic Obstructive Pulmonary Disease (GOLD) classification, and Chronic Obstructive Pulmonary Disease Assessment Test (CAT) score (all P<0.05). Multiple linear regression analysis showed that FeNO level was positively correlated with height ( β=0.094, P=0.014), CAT score ( β=0.129, P=0.001), and negatively correlated with BMI ( β=-0.093, P=0.016). There was no significant correlation between GOLD grading and FeNO level ( P>0.05). Conclusions:The level of FeNO in patients with COPD is higher than that in healthy subjects, which is related to height, BMI and CAT.

The United States is the first country to implement DRG payment in the world, and its MS-DRG(medical severity DRG)version has been used for reference by many countries and regions. In order to ensure the universal applicability of DRG grouping scheme and adapt to the clinical reality, the MS-DRG grouping scheme should follow such grouping rules as similarity of resource consumption, clinical similarity and easy management of DRG groups. This paper presented the evolution of MS-DRG and expounded on its grouping rules in detail, for reference in the amendment and improvement of grouping rules in CHS-DRG.

【Objective】 To explore the value of deep learning reconstruction algorithm (DLIR) in improving image quality of portal vein. 【Methods】 We retrospectively enrolled 32 patients who underwent double-phasic enhanced abdominal CT scanning. Images at the portal venous phase were reconstructed using the 50% adaptive statistical iterative reconstruction (ASIR-V), DLIR at medium (DLIR-M) and high strength (DLIR-H). The CT value and image noise (standard deviation) of the main portal vein, the right portal vein branch, the left portal vein branch, and the paravertebral muscle were measured, and the contrast-noise-ratio (CNR) for vessels were calculated. Moreover, the edge-rising-slope (ERS) of the main portal vein edge was measured to evaluate image spatial resolution. The overall image noise, image contrast, and portal vein branch display were evaluated using a 5-point grading scale and image artifacts using a 4-point grading scare by two experienced radiologists. In addition, we calculated the display rate of small branches of the portal vein in the three reconstruction algorithms. 【Results】 Image noise of the DLIR images in the main portal vein, right branch and left branch was significantly lower than that of ASIR-V 50% images, of which the DLIR-H images had the lowest noise and highest CNR. The ERS of the DLIR images in the main portal vein was significantly higher than that of the ASIR-V 50% images. For qualitative analyses, the DLIR images were significantly better than the ASIR-V 50% ones (P<0.01). In addition, the display rates of small branches of the portal vein in DLIR images were (DLIR-M: 93.75%; DLIR-H: 100%), significantly higher than that of ASIR-V 50% (68.75%). 【Conclusion】 Compared with ASIR-V 50% images, DLIR images can significantly reduce the image noise and improve the spatial resolution of the portal vein and the display rate of small branches of the portal vein.