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.

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.

【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.

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 investigate the protective mechanism of Rho protein kinase 2 (ROCK2) inhibitor constructed based on adeno-associated virus vector on vascular dementia (VaD) rat hippocampal neurons.Methods　Forty SD rats were randomly divided into sham operation group,model group,ROCK2 interference group (shROCK2),negative control group.The VaD model was prepared by permanent ligation of bilateral common carotid arteries.AAV9-ROCK2-shRNA was injected into the hippocampus of the rat by stereotaxic technique,the negative control group was injected with the same amount of empty vector adeno-associated virus.After 4 weeks,morris water maze was used to test the learning and memory abilities of rats.RT-PCR and Western blot were used to detect the mRNA and protein expression levels of RhoA,ROCK2,MLC,MLCP.Results　Four weeks after operation.The mRNA and protein expressions of the above 4 indicators in hippocampus increased (P<0.01),the synaptic vesicles disappeared,and the structure of hippocampus was chaotic in the model group.Compared with the model and control group,the learning and memory ability of rats in ROCK2 interference group was significantly improved,the mRNA and protein of the above 4 indicators were significantly decreased (P<0.05),and the pre-synaptic vesicles were normal and the organelles were more complete.Conclusion　Rho protein kinase 2 inhibitors can reduce the expression of downstream related proteins by inhibiting RhoA/ROCK2 signaling pathway,then promote neuronal axon regeneration and alleviate cognitive dysfunction of VaD rats.

Objective:To investigate the therapeutic effect of programmed cell death receptor 1 (PD-1) inhibitor in drug-resistant recurrent gestational trophoblastic neoplasia (GTN).Methods:Clinicopathological features, previous treatments, PD-1 inhibitor treatment and prognosis of 8 patients with drug-resistant recurrent GTN treated with PD-1 inhibitor pembrolizumab， in Peking Union Medical College Hospital of Chinese Academy of Medical Sciences from August 2018 to June 2019 were collected and retrospectively analyzed.Results:(1) Clinicopathological features: the average age of onset of 8 GTN patients was 32.9 years old (31-39 years old); pathological types: choriocarcinoma in 7 cases, epithelioid trophoblastic tumor in 1 case. International Federation of Gynecology and Obstetrics (FIGO) stages: stage Ⅲ in 5 cases, stage Ⅳ in 3 cases; FIGO score: 4 patients with 7-12 points (high-risk group) and 4 patients with ≥13 points (ultra high-risk group). All the 8 patients had lung metastasis, 2 patients with brain metastasis, 1 patient with kidney and 1 patient with intestinal metastasis. (2) Previous treatments: ① Chemotherapy: 8 patients with GTN received an average of 21.1 courses (5-30 courses) of chemotherapy; the main route was systemic intravenous chemotherapy. One patient received intrathecal methotrexate chemotherapy due to brain metastasis. ② Surgery: 7 of 8 patients with GTN received surgical treatment, including 5 cases of pelvic surgury, 6 cases of pulmonary lobectomy and 1 case of right hemicolectomy. ③ Radiotherapy: 2 of 8 patients with GTN received radiotherapy, among which 1 patient received radiotherapy for lung for 8 times due to lung metastasis, and the other one received radiotherapy for lung, right sacroiliac joint and skull for a total of 22 times. (3) PD-1 inhibitor treatment: 8 patients with GTN received PD-1 inhibitor treatment with a mean course of 9 (2-12 courses). Six patients appeared Ⅰ-Ⅱ grade of immune related adverse events (AE), and no severe AE occurred. (4) Prognosis: after 2-3 courses of PD-1 inhibitor treatment, serum β-hCG level came to normalization in 4 patients. They were followed up for 2-7 months without any recurrence after 0-9 courses of consolidation treatment. One patient received 12 courses of PD-1 inhibitor treatment. The serum β-hCG level normalized after the 6th courses but increased 1 months later, and then received bevacizumab treatment due to the progression of the disease. The remaining 3 patients received other chemotherapy regiments due to disease progression during PD-1 inhibitor treatment.Conclusions:PD-1 could be used as a remedial treatment for drug-resistant recurrent GTN, with a high effective rate and relatively mild AE. However, more cases need to be accumulated clinically and efficacy should be comprehensively evaluated in combination with pathology and immunohistochemical examination.

Objective:To evaluate the oncologic outcomes of different laparoscopic radical hysterectomy.Methods:From January 2011 to December 2014, the laparoscopic operation cases of cervical cancer at stage Ⅰb1, Ⅰb2, Ⅱa1 and Ⅱa2, including the histologic subtypes of squamous-cell carcinoma, adenocarcinoma and adenosquamous carcinoma, were collected in five clinical centers. The data were divided into two groups according to the surgical procedures, that is, modified laparoscopic-vaginal radical hysterectomy (mLVRH) and total laparoscopic radical hysterectomy (TLRH). The overall survival rate (OS), disease-free survival rate (DFS) at 5 years were retrospectively analyzed in this study.Results:There were 674 cases in total, including 377 cases of mLVRH, 297 cases of TLRH. (1) The OS at 5 years: the mLVRH was 96.1% and the TLRH was 92.0%, and the mLVRH was higher than that of TLRH （ P=0.010）. Stratify analysis， including stage of disease （Ⅰb1 and Ⅱa1）， histologic subtypes （squamous-cell carcinoma, adenocarcinoma）， lymph node metastasis， revealed that, ① Stage of disease: in stage Ⅰb1, the OS at five years of mLVRH was higher than that in TLRH group （98.6% vs 93.6%, P=0.012）. In stage Ⅱa1, there was significant difference between the two groups, the OS at five years of mLVRH and TLRH were 93.6% and 77.6% （ P=0.007）. ② Histologic subtypes: for the OS at five years of squamous-cell carcinoma, mLVRH and TLRH were 96.1% and 92.3%, and there was significant difference （ P=0.046）； for adenocarcinoma, the OS at five years were 91.0% and 88.6%， and there was no difference between two groups （ P=0.230）. ③ Lymph node metastasis： the mLVRH and TLRH with lymph node metastasis, the OS at five years were 98.6% and 96.4%; the mLVRH and TLRH without lymph node metastasis, the OS at five years were 89.3% and 80.8%. There were no significant differences between the two groups,respectively ( P=0.156， P=0.093）. (2) The DFS at 5 years: there was no significant difference between mLVRH and TLRH (94.1% vs 90.9%, P=0.220). Stratify analysis for stage of disease, the mLVRH group was higher than that in the TLRH group in stage Ⅰb1 (97.0% vs 92.8%, P=0.039). However, for stage Ⅱa1, there was no significant difference between mLVRH and TLRH group （88.2% vs 75.8%, P=0.074）. Conclusions:The results of this retrospective study indicated that different laparoscopy surgical procedures had diverse oncologic outcomes. The OS at 5 years of the mLVRH is superior to the TLRH. The DFS at 5 years in Ⅰb1 stage, the mLVRH is higher than the TLRH. Therefore, the modified laparoscopy is still an alternative surgery for early cervical cancer patients when following the principle of no-tumor-exposure.