Objective To evaluate the perioperative safety of lung surgery for patients with corona virus disease 2019 (COVID-19). Methods We retrospectively analyzed the clinical data of the patients recovered from COVID-19 infection and received lung surgery from December 2022 to February 2023 in the Department of Thoracic Surgery at Beijing Hospital. Patients who received lung surgery and without COVID-19 at the same time were selected as a control group. Perioperative data between the two groups were compared. Results A total of 103 patients were included with 44 males and 49 females at an average age of (62.2±12.1) years. All surgeries were performed by uniportal video-assisted thoracoscopic surgery (VATS). Among patients who recovered from COVID-19, 53 (51.5%) received lobectomy, 30 (29.1%) received segmentectomy, and 20 (19.4%) received wedge resection. The interval between diagnosis of infection and lung surgery was ≤1 month in 32 (31.1%) patients, and >1 month in 71 (68.9%) patients. The results of virus nucleic acid test for all patients before surgery were negative. A total of 13 (12.6%) patients had positive IgM, and 100 (97.1%) patients had positive IgG. A total of 20 patients experienced perioperative complications (13 patients with pulmonary air leakage, 3 patients with chylothorax, 2 patients with atrial fibrillation, and 2 patients with severe pulmonary complications). There was one perioperative death. Comparing the patients who recovered from COVID-19 with those without COVID-19, we found no statistical difference in perioperative outcomes including surgical duration, postoperative drainage, duration of thoracic tube, and duration of postoperative stay (P>0.05). There was no significant difference in perioperative complications between the two groups (P>0.05). Multivariable logistical regression analysis demonstrated that positive IgM before surgery (OR=7.319, 95%CI 1.669 to 32.103, P=0.008), and longer duration of surgery (OR=1.016, 95%CI 1.003 to 1.028, P=0.013) were independent risk factors of perioperative complications for patients who recovered from COVID-19. Conclusion It is safe for patients recover from COVID-19 to receive lung surgery when symptoms disappear and the nucleic acid test turn negative. However, positive COVID-19 IgM is an independent risk factor for perioperative complications. We suggest that lung surgery could be performed when the nucleic acid test and COVID-19 IgM are both negative for patients recover from COVID-19 infection.

Phosphatidylinositol-3-kinase (PI3K) inhibitors can increase the sensitivity of tumor cells to Poly ADP-ribose polymerase-1 (PARP-1) inhibitors. Therefore, the simultaneous inhibition of the PARP-1 and PI3K activities are expected to overcome the drug resistance of PARP-1 inhibitors.In our previous work, two compounds XW-1 and WZ-1 with excellent activities against PARP-1 and PI3K were obtained with the limitation to further study due to their poor water solubility.Therefore, XW-1 and WZ-1 were chosen as lead compounds to optimize their solubility by introducing a salt-forming site via a urea group, and 11 novel compounds were designed and synthesized. The structure of all target compounds was confirmed by 1H NMR, 13C NMR, and HRMS.The enzyme activities of the compounds against PARP-1 and PI3K were measured, and the results showed that most of the compounds demonstrated good inhibitory activities against PARP-1 and PI3K.Based on the above result, the inhibitory activities of compounds 8b, 8e, and 8f against MDA-MB-231, MDA-MB-468, HCC1937, HCT116, and olaparib-resistant HCT116R were determined by MTT, respectively.Additionally, the structure-activity relationship was discussed. The results showed that these compounds displayed excellent antiproliferation activity.Among them, compound 8f demonstrated antiproliferation remarkably against all five tumor cells, which was more potent than that of olaparib, and was comparable to that of BKM120.Furthermore, the solubility of hydrochloride salts of compound 8b and 8f was significantly improved compared to the lead compounds.The results of this study will provide a theoretical basis for the further development of PARP-1 and PI3K dual-target inhibitors with good pharmaceutical properties and strong inhibitory activities.

Objective:To evaluate the safety of thymic surgery in patients aged 65 years and over.Methods:A total of 696 patients who underwent thymectomy/thymoma resection in the Department of Thoracic Surgery of Beijing Hospital from November 2011 to March 2022 were collected and divided into two groups according to the age of 65 years old.The preoperative course of disease, MG stage, dosage of pyridostigmine bromide, American College of Anesthesiologists(ASA)score, surgical method, intraoperative bleeding, postoperative drainage, postoperative complications, Clavien-dindo score(CDC), and myasthenic crisis were recorded and statistically analyzed.Results:A total of 696 patients were enrolled, including 364 males and 332 females, aged 15~86 years, with an average age of 49.1 years.There were 309 patients with thymoma, 565 patients with MG, and 178 patients with both.There were 124 cases in the elderly group(≥65 years old)and 572 cases in the non-elderly group(<65 years old). The incidence of thymoma was higher in the elderly group(54.8 % versus 42.1 %, χ2=6.664, P=0.010), while the incidence of MG was lower(67.7 % versus 84.1 %, χ2=17.827, P<0.001). The ASA score of the elderly group was higher than that of the non-elderly group( χ2=52.372, P=0.000), and the preoperative ventilation function FEV1 and FEV1/FVC were also significantly lower than those of the non-elderly group( z=8.187, 4.580, P=0.000 for all). The drainage volume in the first 3 days after operation and postoperative drainage tube time in the elderly group were significantly higher than those in the non-elderly group( P=0.018, P=0.003). The incidence of postoperative myasthenia crisis in the elderly group was higher than that in the non-elderly group( P=0.034). There was no significant difference in the incidence of postoperative complications between the two groups, but after Clavien-dindo classification, the score of the elderly group was higher than that of the non-elderly group( P=0.003). Although the ASA score and Clavien-dindo score of the elderly group were both higher than those of the non-elderly group, there was no correlation between the two. Conclusions:Although the preoperative ASA score and pulmonary function of elderly patients were poorer than those in the non-elderly group, while the incidence of postoperative myasthenia crisis was higher, and the incidence of postoperative complications was not higher, the Clavien-dindo classification, however, was higher in elderly patients than that of the non-elderly group.After careful preoperative evaluation and strengthening perioperative management, most elderly patients can receive thymus surgery safely with acceptable risks.

Objective:To explore the influencing factors of acute rejection (AR) within one year after pediatric kidney transplantation (KT) and the effect of AR onset time on prognosis.Methods:From January 2011 to October 2021, a total of 112 patients aged under 18 years at the time of transplantation were selected.After excluding 6 of them with early renal non-function caused by non-rejection, 106 cases were examined.There were 63 males and 43 females with the age of 15(12, 16) years.The donors were living related (n=26) and deceased (n=80).According to the presence/absence and onset time of AR, they were assigned into three groups of AR within one year, AR after one year and non-AR.The relevant clinical data of donor/recipient, influencing factors of AR and therapeutic outcomes of AR were retrospectively compared.One-way ANOVA or Kruskal-Wallis test was utilized for comparing 1-year renal function after the occurrence of AR among three groups.With graft-function loss as an end-point event of follow-up, the effects of AR within one year and AR after one year on survival rate and function of graft-kidney were analyzed by Kaplan-Meier survival curve.Results:The median follow-up period of 106 pediatric KT recipients was 35 months.During follow-ups, 19 episodes of AR occurred in 17(16.0%) patients and 89 recipients exhibited no AR episode by the end of follow-up (non-AR group).As for initial AR, 9 episodes of AR occurred within one year (AR within one year group) and 8 episodes of AR after one year (AR after one year group).After anti-rejection treatment, 8 patients (47.1%) achieved full recovery and 6 patients (35.3%) failed to completely normalize and 3 patients (17.6%) developed graft failure.Univariate analysis indicated that, as compared with non-AR group, female recipients, donors aged under 8 years and early postoperative infection with parvovirus B19 were risk factors of AR within one year ( P=0.032, P=0.039, P=0.047).Kaplan-Meier survival analysis revealed that the incidence rates of AR within one year in patients with donors aged under 8 years and early postoperative parvoviral infection were 14.5%(8/55) and 30.0%(3/10) respectively.They were significantly higher than 2.0%(1/51) and 6.3%(6/96) of patients with donors aged above 8 years and those without parvoviral infection ( P=0.012, P=0.004).With graft-function loss as an end-point event of follow-up, Kaplan-Meier survival analysis showed that 10-year kidney graft survival rate in AR within one year and AR after one year groups were 88.9% and 65.6%.Both were significantly lower than that in non-AR group (98.9%).And the inter-group differences were statistically significant ( χ2=4.286, P=0.038; χ2=7.787, P=0.005).However, no significant difference existed in survival rate between AR within one year and AR after one year groups ( P=0.689).One-way ANOVA and Kruskal-Wallis test indicated that estimated glomerular filtration rates at 3/6/12 months after an onset of AR in AR within one year group were (76.8±51.6), (80.6±56.6) and (85.6±40.2) ml·min -1·1.73 m -2.The values of 3/6 months were lower than (125.3±39.2) and (124.7±38.2) ml·min -1·1.73 m -2 in AR after one year group.And the inter-group differences were statistically significant ( P=0.021, P=0.039).The values of 3/6/12 months were lower than (112.2±34.2), (115.3±33.2) and (117.4±30.2) ml·min -1·1.73 m -2 in non-AR group.And the inter-group differences were also statistically significant ( P=0.019, P=0.020, P=0.020). Conclusions:Female recipients, donors aged under 8 years and early postoperative infection with parvovirus B19 may elevate the risks of AR in children within one year of KT.AR within one year affects the survival rate of graft-kidney and renal function.

Objective:To investigate the protective effect of human umbilical cord mesenchymal stem cell conditioned medium (HucMSC-cm) against lipopolysaccharide (LPS)-induced acute lung injury (ALI) and relevant mechanism of action.Methods:Forty 6-week-old male C57BL/6 mice were selected and randomized (random number) into the sham group, LPS group, LPS + HucMSC-cm (LPS+cm) group, and LPS+HucMSC-cm+Compound C (LPS+cm+cc) group, with 10 mice in each group. Mice were intratracheally injected with LPS (5 mg/kg) to establish ALI model, and intratracheally injected with hucMSC-CM (50 μL) 4 h after LPS treatment. Mice in the LPS+cm+cc group were intraperitoneally treated with Compound C (15 mg/kg) prior to LPS treatment. Neutrophils in peripheral blood were counted with the automated hematology analyzer 72 h after LPS administration. After that, mice were sacrificed, and the lung tissue pathology was observed using hematoxylin eosin (HE) staining. Besides, the expressions of IL-6, ICAM-1, VCAM-1 and P-AMP-activated protein kinase (P-AMPK) in the lung tissues were analyzed by Western blot and immunohistochemical assay. In vitro, human lung microvascular endothelial cells (HuLEC-5a) were cultured and divided into three groups: control group, LPS group (10 μg/ mL), and LPS + HucMSC-cm group. After 24 h of treatment, the expressions of p-AMPK and AMPK were detected by Western blot, and the expressions of IL-6 and IL-8 were detected by real-time fluorescence quantitative PCR. Oneway analysis of variance was used to compare the mean values of normally distributed measurement data between groups. Comparisons between two groups were performed using the Tukey’s multiple comparison test. Results:Compared with the sham group, the LPS group showed lungs with congestion and swelling, thickened pulmonary septum, and inflammatory cell infiltration. Moreover, in the LPS group, the protein expressions of IL-6 ( P=0.003), ICAM-1 ( P<0.001) and VCAM-1 ( P=0.001) were increased significantly, while the expression of p-AMPK was decreased ( P=0.013), accompanied by an increase in the proportion of neutrophils in peripheral blood ( P<0.001). Compared with the LPS group, the LPS+HucMSC-cm group demonstrated eased congestion, edema and pathological injury of lung tissue, reversed protein expressions of IL-6 ( P=0.003), ICAM-1 ( P=0.002), VCAM-1 ( P=0.006) and P-AMPK ( P=0.002), as well as decreased proportion of neutrophils in peripheral blood ( P<0.005). Compared with the LPS+HucMSC-cm group, the LPS+cm+cc group exhibited more severe lung histopathological injury, significantly increased protein expressions of IL-6, ICAM-1 and VCAM-1 in lung tissues, as well as decreased expression of P-AMPK protein. The results of immunohistochemistry were consistent with those of protein. In vitro experiment, after LPS treatment, the mRNA expressions of IL-6 ( P<0.001) and IL-8 ( P=0.027) were increased and p-AMPK protein expression ( P=0.005) was decreased as compared with the control group. In comparison with the LPS group, the LPS+HucMSC-cm group showed decreased mRNA expression levels of IL-6 ( P=0.003) and IL-8 ( P=0.002), but increased protein level of p-AMPK ( P=0.003). Conclusions:HucMSC-cm has a protective effect against LPS-induced acute lung injury, which is mainly attributed to the inhibited expression of adhesion molecules and inflammatory factors under the activation of AMPK.

Objective:To evaluate the clinical characteristics and the surgical safety in patients aged 65 years and over with thymic epithelial tumor, and analyze the prognosis of 3-10 years postoperative tumor and myasthenia gravy.Methods:A total of 228 patients diagnosed as thymic tumor and undergoing surgical surgery to remove the tumor in Beijing Hospital from Jan.2011 to Dec.2018 were retrospectively enrolled.Patients were divided into a young(≤ 65 yrs)and old(>65 yrs)groups.The operation time, intra-operative bleeding, drainage volume in the first 3 days after operation, days with drainage tube after operation, postoperative days of hospital stays, the diameter of the tumors, pathological classification, Tumor-Node-Metastasis(TNM)staging, Masaoka-Koga staging, whether or not complicated with myasthenia gravis and complications were compared between two groups.The patients were followed up by outpatient or telephone, and recurrence of thymoma, survival status and improvement of myasthenia gravis were tracked.Results:There were significant differences in pathological classification between the two groups( P=0.002). The postoperative days with drainage tube were longer in patients≥65 years old than in patients<65 years old[4(2-17)days and 3(1-9), Z=2.316, P=0.021]. Thymic atrophy was more common in patients ≥ 65 years old than in patients <65 years old(10.2% and 1.7%, χ2=5.937, P=0.015). Incidence of thymoma plus myasthenia gravis were higher in patients aged <65 years than those aged ≥65years(68.2% vs.40.8%, χ2=12.240, P<0.001), and incidence of thymic hyperplasia were higher in patients aged <65 years than those aged ≥65years(58.1% and 38.8%, χ2=2.316, P=0.016). The recurrence of thymoma was a poor prognostic factor affecting the survival of patients.Meanwhile, Masaoka-Koga stage Ⅲ and Ⅳ and TNM stage Ⅲ and Ⅳ were independent risk factors for postoperative recurrence of thymoma. Conclusions:Thymectomy is safe and effective in the patients aged 65 and over, and may have a better long-term prognosis.

Objective:To proceed a comparative study of characteristics and safety of video-assisted thoracoscopic thymectomy between artificial pneumothorax combining subxiphoid-costal margin approach versus right thoracic cavity approach.Methods:From January 2018 to December 2021, 251 patients(including myasthenia gravis with thymic hyperplasia or thymoma, thymic cysts and anterior mediastinal occupying lesions)undergoing thoracoscopic extended thymectomy in our department were retrospectively studied, and their clinical data were collected.The surgical methods were divided into artificial pneumothorax combining xiphoid costal margin approach(artificial pneumothorax group, n=165)and via right thoracic approach(right thoracic group, n=86). Clinical data such as preoperative information, operative duration, blood loss, postoperative drainage, drainage duration, and surgical complication were compared between two groups.Results:There were no statistical differences in age, gender and pathology between two groups(all P>0.05). Compared with the right thoracic group, operative duration[(108.6±45.2)min vs.(127.6±42.1)min, t=-3.628, P=0.000], intraoperative blood loss[(37.9±131.7)ml vs.(107.4±284.8)ml, t=-8.215, P=0.000], postoperative drainage volume[(379.0±285.5)ml vs.(646.6±373.3 ml), t=-6.277, P=0.000]and drainage duration[(2.2±1.0)d vs.(3.1±1.0)d, t=-7.275, P=0.000]were statistically significantly decreased in the artificial pneumothorax group.No significant difference was found(all P>0.05)in phrenic nerve injury(1/165 vs.0/86, P=1.000), myasthenia crisis(3/89 vs.2/66, χ2=0.014, P=0.906), and the conversion to thoracotomy(3/165 vs.2/86, P=1.000). Conclusions:VATS thymectomy by artificial pneumothorax combining subxiphoid-costal margin approach is a safer method, having a less trauma, less bleeding and less incidence rate of complication.Especially, it is more suitable for elderly female patients who cannot be intubated in double lumen, cannot tolerate one-lung ventilation, and have pulmonary insufficiency.

Objective　To explore the difference of cerebral blood perfusion in patients with severe unilateral carotid artery stenosis by CTA,CTP and DSA combined assessment of circle of Willis (CoW) different mTICI compensatory grades.Methods　Sixty-five patients with unilateral carotid artery stenosis≥70% were selected according to CTA,and CTP.Among them,33 patients were confirmed by carotid compression test to have compensated blood supply to the stenosis side through anterior communicating artery and/or posterior communicating artery (mTICI ≥2b),which was called as the well compensated CoW group.The other 32 cases were confirmed by neck compression test that there was no compensatory blood supply to the stenosis side,or inadequate compensation (mTICI ≤2a) was called the poor compensatory CoW group.All patients were given internal carotid artery stenting (CAS) for severe internal carotid artery (ICA) stenosis,and the residual stenosis was ≤30%.CTP examination was completed in all patients within 3 months after operation.The relative cerebral blood volume (rCBV),relative cerebral blood flow (rCBF),relative mean transit time (rMTT) and relative peak time (rTTP) of the middle cerebral artery blood supply area before and after operation were measured and calculated.The self-comparison of perfusion parameters before and after operation and the transverse comparison between the two groups.Results　There were significant differences in rMTT,rTTP and slightly increased rCBV in the poor compensated CoW group before stenting than the well compensated CoW group(P<0.05),but the difference in rCBF was not significant (P=0.14).After stenting,there were no significant differences in rCBV,rCBF,rMTT,and rTTP between the two groups (P>0.05).There was only no significant difference in rCBF between the two groups before and after stenting (P>0.05).Conclusion　For patients with severe unilateral carotid artery stenosis,different compensatory functions of Willis can significantly change the distribution of cerebral blood flow,providing a reference for the choice of carotid artery stent implantation.

Objective:The investigation and research on the application status of Hepatic Venous Pressure Gradient (HVPG) is very important to understand the real situation and future development of this technology in China.Methods:This study comprehensively investigated the basic situation of HVPG technology in China, including hospital distribution, hospital level, annual number of cases, catheters used, average cost, indications and existing problems.Results:According to the survey, there were 70 hospitals in China carrying out HVPG technology in 2021, distributed in 28 provinces (autonomous regions and municipalities directly under the central Government). A total of 4 398 cases of HVPG were performed in all the surveyed hospitals in 2021, of which 2 291 cases (52.1%) were tested by HVPG alone. The average cost of HVPG detection was (5 617.2±2 079.4) yuan. 96.3% of the teams completed HVPG detection with balloon method, and most of the teams used thrombectomy balloon catheter (80.3%).Conclusion:Through this investigation, the status of domestic clinical application of HVPG has been clarified, and it has been confirmed that many domestic medical institutions have mastered this technology, but it still needs to continue to promote and popularize HVPG technology in the future.

Objective　 To compare the differences of the result measuring infarct core and hypoperfusion with imSTROKE and RAPID software.Method　This study collected medical imaging examination data from 611 patients with acute ischemic stroke,349 of them were examined by CTP and 262 of them were examined by PWI,DWI and ADC.The volumes of infarct core and hypoperfusion were respectively analyzed by RAPID and imSTROKE software.We used Bland-Altman analysis and intraclass correlation coefficient (ICC) as agreement assessment method between two software,and 25 ml,50 ml,70 ml set as the assessment point of accuracy for estimating infarct core volumes.45 ml,90 ml,125 ml set as the assessment point of accuracy for estimating infarct core volumes.Result　The median volumes of hypoperfusion and infarct core are 68.20 ml and 29.18 ml with imSTROKE software,while the median volumes of hypoperfusion and infarct core are 68.55 ml and 29.53 ml with RAPID software.ICCs (95%CI) of the result measuring infarct core and hypoperfusion with imSTROKE and RAPID software are 0.9885 (0.9865~0.9902) and 0.9880 (0.9860~0.9898).Conclusion　imSTROKE has high agreement with RAPID in the estimation of infarct core volumes and penumbra volumes.Both of them can be used to measure the volume of hypoperfusion and infarct core.