Toripalimab plus axitinib versus sunitinib as first-line treatment for advanced renal cell carcinoma: RENOTORCH, a randomized, open-label, phase III study.

BACKGROUND: Immune checkpoint inhibitors in combination with tyrosine kinase inhibitors are standard treatments for advanced clear cell renal cell carcinoma (RCC). This phase III RENOTORCH study compared the efficacy and safety of toripalimab plus axitinib versus sunitinib for the first-line treatment of patients with intermediate-/poor-risk advanced RCC. PATIENTS AND METHODS: Patients with intermediate-/poor-risk unresectable or metastatic RCC were randomized in a ratio of 1 : 1 to receive toripalimab (240 mg intravenously once every 3 weeks) plus axitinib (5 mg orally twice daily) or sunitinib [50 mg orally once daily for 4 weeks (6-week cycle) or 2 weeks (3-week cycle)]. The primary endpoint was progression-free survival (PFS) assessed by an independent review committee (IRC). The secondary endpoints were investigator-assessed PFS, overall response rate (ORR), overall survival (OS), and safety. RESULTS: A total of 421 patients were randomized to receive toripalimab plus axitinib (n = 210) or sunitinib (n = 211). With a median follow-up of 14.6 months, toripalimab plus axitinib significantly reduced the risk of disease progression or death by 35% compared with sunitinib as assessed by an IRC [hazard ratio (HR) 0.65, 95% confidence interval (CI) 0.49-0.86; P = 0.0028]. The median PFS was 18.0 months in the toripalimab-axitinib group, whereas it was 9.8 months in the sunitinib group. The IRC-assessed ORR was significantly higher in the toripalimab-axitinib group compared with the sunitinib group (56.7% versus 30.8%; P < 0.0001). An OS trend favoring toripalimab plus axitinib was also observed (HR 0.61, 95% CI 0.40-0.92). Treatment-related grade ≥3 adverse events occurred in 61.5% of patients in the toripalimab-axitinib group and 58.6% of patients in the sunitinib group. CONCLUSION: In patients with previously untreated intermediate-/poor-risk advanced RCC, toripalimab plus axitinib provided significantly longer PFS and higher ORR than sunitinib and had a manageable safety profile TRIAL REGISTRATION: ClinicalTrials.gov NCT04394975.

Single-Atom Verification of the Optimal Trade-Off between Speed and Cost in Shortcuts to Adiabaticity.

The approach of shortcuts to adiabaticity enables the effective execution of adiabatic dynamics in quantum information processing with enhanced speed. Owing to the inherent trade-off between dynamical speed and the cost associated with the transitionless driving field, executing arbitrarily fast operations becomes impractical. To understand the accurate interplay between speed and energetic cost in this process, we propose theoretically and verify experimentally a new trade-off, which is characterized by a tightly optimized bound within s-parametrized phase spaces. Our experiment is carried out in a single ultracold ^{40}Ca^{+} ion trapped in a harmonic potential. By exactly operating the quantum states of the ion, we execute the Landau-Zener model as an example, where the quantum speed limit as well as the cost are governed by the spectral gap. We witness that our proposed trade-off is indeed tight in scenarios involving both initially eigenstates and initially thermal equilibrium states. Our work helps understanding the fundamental constraints in shortcuts to adiabaticity and illuminates the potential of underutilized phase spaces that have been traditionally overlooked.

Energy-Conversion Device Using a Quantum Engine with the Work Medium of Two-Atom Entanglement.

Although entanglement is considered as an essential resource for quantum information processing, whether entanglement helps for energy conversion or output in the quantum regime is still lack of experimental witness. Here, we report on an energy-conversion device operating as a quantum engine with the working medium acted by two entangled ions confined in a harmonic potential. The two ions are entangled by virtually coupling to one of the vibrational modes shared by the two ions, and the quantum engine couples to a quantum load, which is another shared vibrational mode. We explore the energy conversion efficiency of the quantum engine and investigate the useful energy (i.e., the maximum extractable work) stored in the quantum load by tuning the two ions in different degrees of entanglement as well as detecting the change of the phonons in the load. Our observation provides, for the first time, quantitative evidence that entanglement fuels the useful energy produced by the quantum engine, but not helpful for the energy conversion efficiency. We consider that our results may be useful to the study of quantum batteries for which one of the most indexes is the maximum extractable energy.

Dynamic contrast-enhanced magnetic resonance imaging in cervical cancer: correlation between quantitative parameters and molecular markers hypoxia-inducible factors-1-alpha, vascular endothelial growth factor, and Ki-67.

AIM: To investigate whether dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) has the potential to non-invasively detect microenvironmental condition by quantitatively measuring blood perfusion, vessel wall permeability, and vascularity, and to elucidate the possible correlations between DCE-MRI quantitative parameters and the expression level of hypoxia, vascularity, and cell proliferation related molecular biomarkers. MATERIALS AND METHODS: In this prospective single center clinical study, 58 patients diagnosed with cervical cancer underwent DCE-MRI before anticancer treatment were enrolled. Ktrans, Kep, Ve, and Vp were generated from Extended Toft's model. Then patients conducted colposcopy biopsy within 1 week after DCE-MRI. Pretreatment expression levels of HIF-1α, VEGF and Ki-67 were assessed and scored by immunohistochemistry on colposcopy obtained tumor specimens. RESULTS: In HIF-1α low-expression group, Ktrans (p=0.031) and Kep (p=0.012) values were significantly higher than the high-expression group. In VEGF high-expression group, Ktrans (p=0.044) and Ve values (p=0.021) were significantly higher than the low-expression group. In Ki-67 high-expression group, Ktrans (p=0.026) and Kep (p=0.033) were significantly higher than the low-expression group. Multiple linear regression analyses and Pearson correlation revealed that Ktrans independently negatively correlated with HIF-1α expression, Ve independently positively correlated with VEGF, and Kep independently positively correlated with Ki-67. The area under the ROC curves of Ktrans for HIF-1α, Ve for VEGF, and Kep for Ki-67 were 0.728, 0.743, 0.730, respectively. CONCLUSION: Our results suggest that DCE-MRI quantitative parameters could be potentially used as imaging markers for non-invasively detecting microenvironmental hypoxia, vascularity and proliferation in cervical cancer patients.

[The prognostic evaluation of coronary artery calcification score and CT fractional flow reserve for patients with stable coronary artery disease].

Objective: To investigate the prognostic value of coronary artery calcium score (CACS) and computed tomography-derived fractional flow reserve (CT-FFR) for major adverse cardiovascular events (MACE) in patients with stable coronary artery disease (CAD). Methods: The data for this prospective study were derived from a prospective clinical trial at a single center. This trial enrolled stable CAD patients who underwent coronary CT angiography (CCTA) in General Hospital of Eastern Theater Command from April 2018 to March 2019 and had coronary artery stenosis of 25%-80%. Patients were assigned to either the control group or trial group according to CCTA time. Patients in control group were provided with only a standard CCTA report, while patients in trial group were provided with both a standard CCTA report and the corresponding CT-FFR results. The study included patients who underwent ECG-gated calcium scoring CT scans in this trial. CT-FFR value at 2 cm distal to the narrowest stenosis of each vessel was calculated. The minimum CT-FFR value was recorded as the patient level and CT-FFR≤0.80 was defined as a positive result. All patients were followed up for MACE, including all-cause death, nonfatal myocardial infarction, and acute coronary syndrome leading to unplanned revascularization. Multivariable Cox proportional hazards regression analysis was used to identify variables associated with MACE occurrence, and the Concordance index (C-index) was used to represent the performance of the models for predicting MACE occurrence based on clinical, anatomical, and CT-FFR parameters. Results: A total of 783 patients were finally statistically analyzed, with a age of (62.0±10.8) years, of whom 64.6% (506 cases) were male. There were 383 patients in the trial group and 400 patients in the control group, with a median follow-up time of 35.3 months. A total of 81 MACE cases occurred during the follow-up. The incidence of MACE in trial group (8.1%, 31/383) was significantly lower than that in control group (12.5%, 50/400)(χ2=4.095, P=0.043). CACS≥300, stenosis≥70% and CT-FFR≤0.80 [HR (95%CI) were 2.14 (1.01-4.52), 5.38 (3.44-8.42) and 16.91 (9.21-31.04), all P<0.05] showed predictive value for MACE. The predictive ability of the CT-FFR model is significantly better than that of the CACS model and the stenosis degree model [C-index (95%CI) were 0.850 (0.823-0.874), 0.653 (0.618-0.686) and 0.718 (0.685-0.749), all P≤0.001]. The comprehensive model with added CACS and stenosis degree did not significantly improve the predictive value of the CT-FFR model [C-index (95%CI) were 0.867 (0.841-0.890), 0.850 (0.823-0.874), P=0.584]. Conclusions: CT-FFR has a high predictive value for MACE in patients with stable CAD, the combination of CT-FFR and CACS did not increase the predictive power of CT-FFR.

Enhancement of Quantum Heat Engine by Encircling a Liouvillian Exceptional Point.

Quantum heat engines are expected to outperform the classical counterparts due to quantum coherences involved. Here we experimentally execute a single-ion quantum heat engine and demonstrate, for the first time, the dynamics and the enhanced performance of the heat engine originating from the Liouvillian exceptional points (LEPs). In addition to the topological effects related to LEPs, we focus on thermodynamic effects, which can be understood by the Landau-Zener-Stückelberg process under decoherence. We witness a positive net work from the quantum heat engine if the heat engine cycle dynamically encircles a LEP. Further investigation reveals that a larger net work is done when the system is operated closer to the LEP. We attribute the enhanced performance of the quantum heat engine to the Landau-Zener-Stückelberg process, enabled by the eigenenergy landscape in the vicinity of the LEP, and the exceptional point-induced topological transition. Therefore, our results open new possibilities toward LEP-enabled control of quantum heat engines and of thermodynamic processes in open quantum systems.

[Efficacy and safety evaluation of immunotherapy combined with targeted therapy as second-line treatment in patients with metastatic non-clear cell renal cell carcinoma].

Objective: This study aimed to evaluate the efficacy and safety of programmed death-1 (PD-1) inhibitor combined tyrosine kinase inhibitor (TKI) therapy versus TKI monotherapy as the second-line regimen for patients with metastatic non-clear cell renal carcinoma (nccRCC) who failed first-line TKI therapy. Methods: The clinicopathological data of 67 patients with metastatic nccRCC who failed first-line TKI therapy between October 2011 and September 2020 were retrospectively analyzed, including 22 patients who received TKI monotherapy and 45 patients who received TKI plus PD-1 inhibitor as the second-line therapy. The efficacy was assessed according to Response Evaluation Criteria in Solid Tumors version 1.0/1.1 (RECIST 1.0/1.1), the Kaplan-Meier method was used to plot the survival curves, and the Log rank test was used to analyze the differences in the survival between the two groups. Treatment-related adverse events (AEs) after treatment were observed in both groups. Results: The overall objective response rate (ORR) and disease control rate (DCR) were 37.3% (25/67) and 56.7% (38/67), respectively. The overall second-line progression-free survival (PFS) was 7.7 months and Overall Survival (OS) was 25.2 months. The ORR and DCR of patients in the combination therapy group were 48.9% (22/45) and 71.1% (32/45), respectively, which were significantly improved compared with the TKI monotherapy group [13.6% (3/22) and 27.3% (6/22), respectively] (P=0.007 and P=0.001, respectively). The median PFS of 9.2 months for second-line treatment was longer in patients in the combination therapy group than in the TKI monotherapy group (5.2 months, P=0.001), but the median OS was not statistically different between the two groups (28.2 months vs 20.8 months, P=0.068). Common treatment-related AEs included hypertension, diarrhea, fatigue, stomatitis, hand-foot syndrome, and hypothyroidism. The incidence of hypothyroidism was higher in the combination therapy group [40.0% (18/45)] than in the TKI monotherapy group [22.7% (5/22), P=0.044]; the incidence of other treatment-related AEs between the two groups were not statistically significant (all P>0.05). Conclusion: Immune-targeted combination therapy was more effective than TKI monotherapy alone and was well tolerated in the treatment of metastatic nccRCC patients who failed first-line TKIs.

[Establishment and validation of a novel nomogram to predict overall survival after radical nephrectomy].

Objective: To establish a nomogram prognostic model for predicting the 5-, 10-, and 15-year overall survival (OS) of non-metastatic renal cell carcinoma patients managed with radical nephrectomy (RN), compare the modelled results with the results of pure pathologic staging, the Karakiewicz nomogram and the Mayo Clinic Stage, Size, Grade, and Necrosis (SSIGN) score commonly used in foreign countries, and stratify the patients into different prognostic risk subgroups. Methods: A total of 1 246 non-metastatic renal cell carcinoma patients managed with RN in Sun Yat-sen University Cancer Center (SYSUCC) from 1999 to 2020 were retrospectively analyzed. Multivariate Cox regression analysis was used to screen the variables that influence the prognosis for nomogram establishment, and the bootstrap random sampling was used for internal validation. The time-receiver operating characteristic curve (ROC), the calibration curve and the clinical decision curve analysis (DCA) were applied to evaluate the nomogram. The prediction efficacy of the nomogram and that of the pure pathologic staging, the Karakiewicz nomogram and the SSIGN score was compared through the area under the curve (AUC). Finally, patients were stratified into different risk subgroups according to our nomogram scores. Results: A total of 1 246 patients managed with RN were enrolled in this study. Multivariate Cox regression analysis showed that age, smoking history, pathological nuclear grade, sarcomatoid differentiation, tumor necrosis and pathological T and N stages were independent prognostic factors for RN patients (all P<0.05). A nomogram model named SYSUCC based on these factors was built to predict the 5-, 10-, and 15-year survival rate of the participating patients. In the bootstrap random sampling with 1 000 iterations, all these factors occurred for more than 800 times as independent predictors. The Harrell's concordance index (C-index) of SYSUCC was higher compared with pure pathological staging [0.770 (95% CI: 0.716-0.823) vs 0.674 (95% CI: 0.621-0.728)]. The calibration curve showed that the survival rate as predicted by the SYSUCC model simulated the actual rate, while the clinical DCA showed that the SYSUCC nomogram has a benefit in certain probability ranges. In the ROC analysis that included 857 patients with detailed pathological nuclear stages, the nomogram had a larger AUC (5-/10-year AUC: 0.823/0.804) and better discriminating ability than pure pathological staging (5-/10-year AUC: 0.701/0.658), Karakiewicz nomogram (5-/10-year AUC: 0.772/0.734) and SSIGN score (5-/10-year AUC: 0.792/0.750) in predicting the 5-/10-year OS of RN patients (all P<0.05). In addition, the AUC of the SYSUCC nomogram for predicting the 15-year OS (0.820) was larger than that of the SSIGN score (0.709), and there was no statistical difference (P<0.05) between the SYSUCC nomogram, pure pathological staging (0.773) and the Karakiewicz nomogram (0.826). The calibration curve was close to the standard curve, which indicated that the model has good predictive performance. Finally, patients were stratified into low-, intermediate-, and high-risk subgroups (738, 379 and 129, respectively) according to the SYSUCC nomogram scores, among whom patients in intermediate- and high-risk subgroups had a worse OS than patients in the low-risk subgroup (intermediate-risk group vs. low-risk group: HR=4.33, 95% CI: 3.22-5.81, P<0.001; high-risk group vs low-risk group: HR=11.95, 95% CI: 8.29-17.24, P<0.001), and the high-risk subgroup had a worse OS than the intermediate-risk group (HR=2.63, 95% CI: 1.88-3.68, P<0.001). Conclusions: Age, smoking history, pathological nuclear grade, sarcomatoid differentiation, tumor necrosis and pathological stage were independent prognostic factors for non-metastasis renal cell carcinoma patients after RN. The SYSUCC nomogram based on these independent prognostic factors can better predict the 5-, 10-, and 15-year OS than pure pathological staging, the Karakiewicz nomogram and the SSIGN score of patients after RN. In addition, the SYSUCC nomogram has good discrimination, agreement, risk stratification and clinical application potential.

[Long-term survival analysis of 1 367 patients treated with radical nephrectomy from a single center].

Objective: To report the long-term survival of renal cell carcinoma (RCC) patients treated with radical nephrectomy in Sun Yat-sen University Cancer Center. Methods: We retrospectively analyzed the clinical, pathological and follow-up records of 1 367 non-metastatic RCC patients treated with radical nephrectomy from 1999 to 2020 in this center. The primary endpoint of this study was overall survival rate. Survival curves were estimated using the Kaplan-Meier method, and group differences were compared through Log-rank test. Univariate and multivariate Cox analysis were fit to determine the clinical and pathological features associated with overall survival rate. Results: A total of 1 367 patients treated with radical nephrectomy with complete follow-up data were included in the study. The median follow-up time was 52.6 months, and 1 100 patients survived and 267 died, with the median time to overall survival not yet reached. The 5-year and 10-year overall survival rates were 82.8% and 74.9%, respectively. The 5-year and 10-year overall survival rates of Leibovich low-risk patients were 93.3% and 88.2%, respectively; of Leibovich intermediate-risk patients were 82.2% and 72.3%, respectively; and of Leibovich high-risk patients were 50.5% and 30.2%, respectively. There were significant differences in the long-term survival among the three groups (P<0.001). The 10-year overall survival rates for patients with pT1, pT2, pT3 and pT4 RCC were 83.2%, 73.6%, 55.0% and 31.4%, respectively. There were significant differences among pT1, pT2, pT3 and pT4 patients(P<0.001). The 5-year and 10-year overall survival rates of patients with lymph node metastasis were 48.5% and 35.6%, respectively, and those of patients without lymph node metastasis were 85.1% and 77.5%, respectively. There was significant difference in the long-term survival between patients with lymph node metastasis and without lymph node metastasis. The 10-year overall survival rate was 96.2% for nuclear Grade 1, 81.6% for nuclear Grade 2, 60.5% for nuclear Grade 3, and 43.4% for nuclear Grade 4 patients. The difference was statistically significant. There was no significant difference in the long-term survival between patients with localized renal cancer (pT1-2N0M0) who underwent open surgery and minimally invasive surgery (10-year overall survival rate 80.5% vs 85.6%, P=0.160). Multivariate Cox analysis showed that age≥55 years (HR=2.11, 95% CI: 1.50-2.96, P<0.001), T stage(T3+ T4 vs T1a: HR=2.37, 95% CI: 1.26-4.46, P=0.008), local lymph node metastasis (HR=3.04, 95%CI: 1.81-5.09, P<0.001), nuclear grade (G3-G4 vs G1: HR=4.21, 95%CI: 1.51-11.75, P=0.006), tumor necrosis (HR=1.66, 95% CI: 1.17-2.37, P=0.005), sarcomatoid differentiation (HR=2.39, 95% CI: 1.31-4.35, P=0.005) and BMI≥24kg/m(2) (HR=0.56, 95%CI: 0.39-0.80, P=0.001) were independent factors affecting long-term survival after radical nephrectomy. Conclusions: The long-term survival of radical nephrectomy in patients with renal cell carcinoma is satisfactory. Advanced age, higher pathological stage and grade, tumor necrosis and sarcomatoid differentiation were the main adverse factors affecting the prognosis of patients. Higher body mass index was a protective factor for the prognosis of patients.

[Clinical characteristics and risk factors of programmed death-1 inhibitors associated with thyroid gland injury].

Objective: To investigate the clinical characteristics and related risk factors of thyroid gland injury (TGI) in patients with a malignant tumor treated with a programmed death-1 (PD-1) inhibitor. Methods: A Retrospective case-control study. Data from 198 patients with a malignant tumor who received treatment with a PD-1 inhibitor in Chinese PLA General Hospital from October 2019 to October 2021 were collected and analyzed retrospectively. According to the TGI incurred after receiving treatment with a PD-1 inhibitor, patients were divided into a thyroid gland normal (TGN) group and TGI group. The prevalence, type, time of occurrence, and outcome of TGI were analyzed. The risk factors that may contribute to TGI were analyzed further by logistic regression. Results: TGI prevalence was 29.8% (59/198 cases) after treatment with a PD-1 inhibitor. There were significant differences with respect to previous radiotherapy and targeted therapy between the TGN group and TGI group (P<0.01 for both), but there were no significant differences with regard to sex, age, tumor type, previous surgery, previous chemotherapy, tumor metastasis, or type of PD-1 inhibitor (P>0.05 for all). Patients in the TGI group included those with subclinical hypothyroidism (32.2%, n=19), hypothyroidism (27.1%, n=16), thyrotoxicosis (23.7%, n=14), subclinical thyrotoxicosis (10.2%, n=6), and thyroiditis with normal thyroid function (6.8%, n=4), and the median time of occurrence (months) was 3.00, 3.00, 1.50, 1.50, and 0.80 after treatment with a PD-1 inhibitor, respectively. Among 20 patients who presented initially with thyrotoxicosis or subclinical thyrotoxicosis, 12 cases developed hypothyroidism or subclinical hypothyroidism subsequently. Logistic regression analysis suggested that previous radiotherapy (OR=3.737, 95%CI 1.390-10.046), targeted therapy (OR=3.763, 95%CI 1.553-9.117), thyroglobulin antibodies at baseline (OR=12.082, 95%CI 1.199-121.775), and thyroid-peroxidase antibodies at baseline (OR=10.874, 95%CI 1.010-117.047) were risk factors associated with the TGI caused by treatment with a PD-1 inhibitor. Conclusions: After treatment with a PD-1 inhibitor, TGI prevalence was high, especially in those with hypothyroidism or subclinical hypothyroidism. Some patients had a transition from thyrotoxicosis to hypothyroidism. Patients who underwent radiotherapy previously, had targeted therapy, or were thyroid autoantibody-positive at baseline may carry an increased risk of TGI following treatment with a PD-1 inhibitor.

[Reproducibility evaluation of air-charged catheter for rest urethral pressure profilometry].

We retrospectively included 53 (9 males, 44 females) patients who underwent rest urethral pressure profilometry (RUPP) due to lower urinary tract symptoms (LUTS) in Beijing Chaoyang Hospital from May 2021 to March 2022. The age of patients was (55±16) (25-76) years old. The clinical diagnoses of the included patients with lower urinary tract symptoms were classified as: benign prostatic hyperplasia in 9 cases, interstitial cystitis in 1 case, stress urinary incontinence in 11 cases and non-obstructive dysuria in 32 cases. The full set of urodynamic examination was composed of bladder pressure measurement during the filling period, pressure flow study (PFS) and RUPP. All the urodynamic examination was performed by air-charged catheter (ACC) and corresponding equipment. All patients underwent RUPP measurements twice. The vesical pressure (Pves) values were (35.30±6.15), (35.81±5.91) cmH2O (1 cmH2O=0.098 kPa); the Pura@max were (141.91±36.53), (145.02±38.85) cmH2O; functional urethral length were (41.70±16.34), (42.55±16.40) mm; the maximum urethral closure pressure for the two RUPP measurements were (106.57±36.44), (109.41±39.27) cmH2O. There was no statistical difference between the two RUPP measurements (P>0.05). The reproducibility of the RUPP measurements obtained by ACC is good and deserves further study.

[Analysis of reproductive outcomes in the first IVF-ET cycle after laparoscopic treatment in patients with endometriosis].

Objective: To explore the effect of endometriosis (EM) on reproductive outcomes of young patient with EM after laparoscopic treatment in the first in vitro fertilization-embryo transfer (IVF-ET) cycle. Methods: The clinical data and reproductive outcomes of 394 infertile patients with EM after laparoscopic treatment (EM group) and 3 242 infertile patients caused by gamete transport disorder (control group) in the first IVF-ET cycle were collected in Chongqing Health Center for Women and Children from January 2016 to June 2021. The information included baseline characteristics, oocyte retrieval, embryo development, clinical pregnancy, miscarriage, and live birth. Propensity score matching (PSM) method was used to perform 1∶2 matching between EM group and control group. The impact of EM on reproductive outcomes was analyzed in the retrospective observational study. Results: In the initial data, compared with control group, the number of two pronucleus (2PN) zygotes (9.7±4.8 vs 9.0±4.4), the number of transferable embryos (6.2±3.6 vs 5.5±3.4) and the rate of transferable embryos (64.0% vs 60.8%) on the third day were significantly lower in EM group, and the differences were statistically significant (all P<0.05). After PSM was performed, there were 394 and 787 cases in EM group and control group, respectively. Compared with control group, the number of 2PN zygotes (9.7±4.9 vs 9.0±4.4), the 2PN fertility rate (77.1% vs 75.3%), the number of transferable embryos on the third day (6.2±3.6 vs 5.5±3.4), the transferable embryos rate on the third day (63.8% vs 60.8%) were significantly lower in EM group, and the differences were statically significant (all P<0.05). The study did not find the effect of EM on embryo implantation rate, pregnancy rate, early miscarriage rate, live birth rate and preterm birth rate (all P>0.05). Conclusions: EM might interfere with the development of oocytes and embryos. Obtaining top-quality embryos may be an effective way to improve the prognosis of patients with EM after laparoscopic treatment.

[The mechanism of berberine on Methicillin resistant Staphylococcus aureus in vitro].

Objective: To explore the impact of traditional Chinese medicine berberine (BBR) on membrane integrity and permeability of Methicillin-resistant Staphylococcus aureus (MRSA) and the change of bacterial cell wall structure, laying a foundation for the clinical application of berberine in antibacterial. Methods: This study used a non-randomized concurrent controlled trial. The 3 MRSA strains were isolated and cultured from lower respiratory tract samples of geriatric patients from Shanghai Eighth People's Hospital between 2019 and 2020.The Meirier VETEK MS fully automated rapid microbial mass spectrometry detection system and VETEK 2 Compact fully automated microbial identification instrument were used to identify bacterial drug sensitivity experiments to detect bacterial species and drug sensitivity. The minimal inhibitory concentration (MIC) of BBR on MRSA strains was determined by broth microdilution. This study used conductivity tests to assess the changes in membrane permeability in response to different concentration of BBR on MRSA, while also investigating the changes in MRSA morphology by transmission electron microscopy. GraphPad Prism5 was used to analyze the differences in the electrical conductivity experimental results. Results: The MIC of BBR on MRSA was 64 µg/ml. After co-culturing MRSA with BBR for 4 h at 8 µg/ml, 16 µg/ml, 32 µg/ml, 64 µg/ml and 128 µg/ml, respectively, the electrical conductivity increased, compared with the control group, by 24.49%,34.59%,208.92%,196.40% and 208.68%, respectively. By transmission electron microscopy, This study found that low concentration of BBR (8 µg/ml,1/8 MIC) caused no significant damage to MRSA, and the bacterial structure of MRSA remained intact. The cell wall of MRSA became thinner after treatment with berberine at medium concentration (64 µg/ml,1 MIC), while high concentration of BBR (512 µg/ml,8 MIC) induced the destruction and dissolution of MRSA cell wall structure and the leakage of bacterial contents, leading to bacterial lysis. Conclusion: Berberine can kill bacteria by altering the permeability of MRSA cell membrane and destroying and dissolving the structure of the cell wall.

[Diagnosis and treatment of malignant mesothelioma of the tunica vaginalis testis: a series of 7 cases].

Objective: To investigate the clinical features, diagnosis, prognosis of malignant mesothelioma of the tunica vaginalis testis (MMTVT). Methods: The clinicopathological data of 7 patients with MMTVT who treated at Sun Yat-sen University Cancer Center between January 2010 and October 2022 were retrospectively reviewed. Cases were first diagnosed at (M (IQR)) 49 (23) years old (range: 27 to 64 years old). The main clinical manifestations were scrotal enlargement (7 cases) and hydrocele (2 cases). Results: Three patients underwent radical orchiectomy as initial treatment, 2 cases underwent hydrocelectomy due to diagnosis of hydrocele, followed by radical orchiectomy at Sun Yat-sen University Cancer Center, and 2 cases underwent transscrotal orchiectomy. Common tumor markers of testicular cancer were not significantly elevated in MMTVT. The expression of tumor PD-L1 was positive in 2 out of the 3 cases. One patient received adjuvant chemotherapy and 2 patients received first-line chemotherapy after tumor recurrence. Chemotherapy regimens used include cisplatin+pemetrexed. Up to October 2022, 3 cases relapsed, of which 2 cases died. The median overall survival was 35 months (range: 4 to 87 months) and the median progression-free survival was 6 months (range: 2 to 87 months). Conclusions: MMTVT at early stage should be treated with early radical orchiectomy and followed up closely after surgery. The cisplatin+pemetrexed regimen is a common option for the treatment of metastatic MMTVT, while whether immune checkpoint inhibitors could serve as a second-line treatment option deserves further research.

[Relation factor analysis for the short-term preservation of ipsilateral renal function after partial nephrectomy].

Objectives: To analyze the factors relative to the short-term preservation of ipsilateral renal function after partial nephrectomy. Methods: The clinical data of 83 patients who were treated with partial nephrectomy from December 2014 to December 2019 in the Department of Urology, Sun Yat-sen University Cancer Center were retrospectively analyzed. There were 54 males and 29 females, aging (M (IQR)) 49 (17) years (range: 27 to 74 years). The ischemia time in operation was 25 (18) minutes (range: 10 to 67 minutes). Emission computed tomography scan and CT scan were performed before (within 1 month) and after (3 to 12 months) surgery. The volume of the ipsilateral and contralateral kidney was measured on the basis of preoperative and postoperative CT scans. The glomerular filtration rate (GFR) specifically in each kidney was estimated by emission computed tomography. Recovery from ischemia is determined by the formula: GFR preservation/volume saved×100%. Linear regression was used to explore the factors ralative to the short-term preservation of ipsilateral renal function after partial nephrectomy. Results: The GFR preservation of the ipsilateral kidney was 80.9 (25.2) % (range: 31.0% to 109.4%). The volume loss of the kidney resulted in a decrease of 12.0% (5.8 ml/(min×1.96 m2)) of GFR, while the ischemic injury resulted in a decrease of 6.5% (2.5 ml/(min×1.96 m2)) of GFR. The volume saved from the ipsilateral kidney was 87.1 (12.9) % (range: 27.0% to 131.7%). Recovery from ischemia was 93.5 (17.5) % (range:44.3% to 178.3%). In multivariate analysis, GFR preservation of the ipsilateral kidney was significantly correlated with the volume saved of the ipsilateral kidney (ß=0.383, 95%CI: 0.144 to 0.622, P=0.002). It was not related to the ischemia time (ß=0.046, 95%CI:-0.383 to 0.475, P=0.831). Conclusion: In the condition of limited ischemic time, in the short term ipsilateral renal function after partial nephrectomy is mainly determined by the loss of kidney volume, while ischemic injury only plays a minor role.

[Efficacy of partial nephrectomy in patients with localized renal carcinoma: a 20-year experience of 2 046 patients in a single center].

Objectives: To analyze the long-term survival of patients with localized renal cell carcinoma after partical nephrectomy. Methods: The clinicopathological records and survival follow-up data of 2 046 patients with localized renal cell carcinoma, who were treated with partial nephrectomy from August 2001 to February 2021 in the Department of Urology, Sun Yat-sen University Cancer Center, were retrospectively analyzed. There were 1 402 males and 644 females, aged (M(IQR)) 51 (19) years (range: 6 to 86 years). The primary end point of this study was cancer-specific survival. Survival curves were estimated using the Kaplan-Meier method, and the difference test was performed by Log-rank test. Univariate and multivariate Cox analysis were fitted to determine factors associated with cancer-specific survival. Results: The follow-up time was 49.2 (48.0) months (range: 1 to 229 months), with 1 974 patients surviving and 72 dying. The median cancer-specific survival time has not yet been reached. The 5- and 10-year cancer specific survival rates were 97.0% and 91.2%, respectively. The 10-year cancer-specific survival rates for stage pT1a (n=1 447), pT1b (n=523) and pT2 (n=58) were 95.3%, 81.8%, and 81.7%, respectively. The 10-year cancer-specific survival rates of patients with nuclear grade 1 (n=226), 2 (n=1 244) and 3 to 4 (n=278) were 96.6%, 89.4%, and 85.5%, respectively. There were no significant differences in 5-year cancer-specific survival rates among patients underwent open, laparoscopic, or robotic surgery (96.7% vs. 97.1% vs. 97.5%, P=0.600). Multivariate analysis showed that age≥50 years (HR=3.93, 95%CI: 1.82 to 8.47, P<0.01), T stage (T1b vs. T1a: HR=3.31, 95%CI: 1.83 to 5.99, P<0.01; T2+T3 vs. T1a: HR=2.88, 95%CI: 1.00 to 8.28, P=0.049) and nuclear grade (G3 to 4 vs. G1: HR=2.81, 95%CI: 1.01 to 7.82, P=0.048) were independent prognostic factors of localized renal cell carcinoma after partial nephrectomy. Conclusions: The long-term cancer-specific survival rates of patients with localized renal cancer after partial nephrectomy are satisfactory. The type of operation (open, laparoscopic, or robotic) has no significant effect on survival. However, patients with older age, higher nuclear grade, and higher T stage have a lower cancer-specific survival rate. Grasping surgical indications, attaching importance to preoperative evaluation, perioperative management, and postoperative follow-up, could benefit achieving satisfactory long-term survival.

Experimental Verification of Dissipation-Time Uncertainty Relation.

Dissipation is vital to any cyclic process in realistic systems. Recent research focus on nonequilibrium processes in stochastic systems has revealed a fundamental trade-off, called dissipation-time uncertainty relation, that entropy production rate associated with dissipation bounds the evolution pace of physical processes [Phys. Rev. Lett. 125, 120604 (2020)PRLTAO0031-900710.1103/PhysRevLett.125.120604]. Following the dissipative two-level model exemplified in the same Letter, we experimentally verify this fundamental trade-off in a single trapped ultracold ^{40}Ca^{+} ion using elaborately designed dissipative channels, along with a postprocessing method developed in the data analysis, to build the effective nonequilibrium stochastic evolutions for the energy transfer between two heat baths mediated by a qubit. Since the dissipation-time uncertainty relation imposes a constraint on the quantum speed regarding entropy flux, our observation provides the first experimental evidence confirming such a speed restriction from thermodynamics on quantum operations due to dissipation, which helps us further understand the role of thermodynamical characteristics played in quantum information processing.

Enhanced sequestration of molybdenum(VI) using composite constructed wetlands and responses of microbial communities.

The molybdenum (Mo) non-point source pollution in the mining area has an irreversible impact on the surrounding water and soil ecosystems. Herein, three integrated vertical subsurface flow constructed wetlands (CWs) were constructed to assess the effects of combination substrates and plant on the removal of Mo(VI). Results showed that CW1 with combination substrates and cattail exhibited a favorable removal performance for Mo(VI) at 80.90%. Moreover, most Mo(VI) retained in the CWs was retained in the substrate (58.13-88.04%), and the largest fraction of Mo(VI) retained was the water-soluble fraction on the surface of the combination substrates. Mo(VI) removal was also influenced by the microbial community composition in substrate, especially their co-occurrence networks. The species that showed significant positive correlation with Mo(VI) removal were Planctomycetes, Latescibacteria, Armatimonadetes, and Gemmatimonadetes. Moreover, CWs added plants showed that more co-occurrences interaction between taxa occurs, which means that the wetlands efficiently select recruitment of potential microbial consortia and change the co-occurrences to remove pollution in the substrate. These results could be useful in providing an ecology-based solution for the treatment of Mo(VI) in wastewater, especially in adjusting the microbial communities for Mo(VI) removal at the genetic level.

[Time comparison of artificial airway establishment in operating room and on slope using endotracheal intubation and laryngeal mask].

OBJECTIVE: To compare the completion time of endotracheal intubation and laryngeal mask implantation in operating room and on slope of ski resort, and to discuss the optimal method of estab-lishing artificial airway on slope of ski resort. METHODS: The simulator was placed with the head under the feet on slope of ski resort. The artificial airway was established by tracheal intubation assisted by video laryngoscope (endotracheal intubation group) and laryngeal mask placement (laryngeal mask group) respectively by an anesthesiologist who wore full set of ski suits, helmets, goggles, gloves and ski boots. Each method was repeated 5 times, and the operation time of artificial airway establishment was recorded. While the simulated human was placed flat on the operating table in an operating room of a hospital, and the artificial airway was established by the same anesthesiologist using the same methods. Time was recorded and repeated for 5 times. The completion time of endotracheal intubation and laryngeal mask placement in the operating room and on the ski slope were compared. RESULTS: The operating time of tracheal intubation in the operating room was longer than that of laryngeal mask placement [(79.8±10.4) s vs. (53.4±2.7) s, P=0.005], and the operating time of endotracheal intubation on the ski slope was longer than that of laryngeal mask placement [(209.2±32.7) s vs. (72.2±3.1) s, P=0.001]. The time of endotracheal intubation group on the slope of the ski resort was longer than that in the opera-ting room(t=-7.851, P=0.001). The time of laryngeal mask group on the slope was longer than that in the operating room (t=-19.391, P < 0.001). CONCLUSION: On ski slope, both of tracheal intubation assisted by video laryngoscope and laryngeal mask placement can quickly complete the establishment of artificial airway, but the time required is longer than that in the operating room. The time of laryngeal mask placement to establish artificial airway is shorter than that of tracheal intubation assisted video laryngoscope, which may have a certain advantage in ski rescue.

[Related factors of revision of distal femoral fractures treated with lateral locking plate].

OBJECTIVE: To analyze the factors related to the need for revision surgery due to nonunion or internal fixation failure after the treatment of distal femoral fracture with lateral locking plate (LLP). METHODS: Retrospective analysis was made of the clinical data of 130 cases with distal femoral fracture treated in our hospital from March 2005 to March 2019. SPSS 17.0 software (univariate analysis and Logistic regression analysis) was used to analyze the general condition [gender, age, body mass index (BMI), comorbidities, smoking history], injury related factors (energy of injury, open or closed injury, AO/OTA classification of fracture, fracture area distribution), operation related factors (operation time, reduction quality, postoperative infection) and construct characteristics of internal fixation. RESULTS: Twelve of 130 patients who were included in the study underwent revisional surgery, with a revision rate 9.2%. Univariate analysis showed that there were significant differences in age, BMI, AO/OTA classification, fracture area distribution, operation time, reduction quality, length of plate/fracture area, length of plate/fracture area above condylar between the two groups (P < 0.05). Logistic regression analysis showed that AO/OTA classification (A3), supracondylar involved fracture, operation time, reduction quality and the length of the plate/fracture area above the condylar were the possible related factors (P < 0.05). Destruction of the medial support ability of the femur in comminuted type A3 fracture, supra-condylar cortex area fracture involvement, increase of the bending stress of the LLP due to poor fracture reduction quality, damage of the blood supply of fracture end due to long-time operation, and stress concentration caused by insufficient length of plate might be risk factors of revisional operation after the treatment of distal femoral fracture with LLP. For the patients who needed revision after LLP treatment, additional use of medial minimally invasive plate fixation and autologous bone transplantation, change to intramedullary nail fixation were commonly used clinical treatment strategies. CONCLUSION: AO/OTA classification (A3), supracondylar involved fracture, long operation time, poor reduction quality and the length of the plate/fracture area above the condylar were the possible predictive factors of the revision in distal femoral fractures treated with lateral locking plate. The appropriate application of the locking plate and operation strategy are the key to reduce the revision rate in distal femoral fractures.