Interpretation of methodological standards for the design, implementation, and analysis of randomized trials in cardiac surgery: A scientific statement from the American Heart Association in 2022 / 中国胸心血管外科临床杂志

@#Cardiac surgery presents specific challenges in conducting randomized controlled trials (RCTs). The American Heart Association made a scientific statement of methodological standards, with the purpose to review key concepts and standards in design, implementation, and analysis of cardiac surgery RCTs, and to provide recommendations. Recommendations include an evaluation of the suitability of the research question, clinical equipoise, feasibility of enrolling a representative patient cohort, impact of practice variations on the effect of the study intervention, likelihood and impact of crossover, and duration of follow-up. Trial interventions and study end points should be predefined, and adequate deliverability of the trial interventions should be ensured. Every effort must be made to keep a high completeness of follow-up. Trial design and analytic techniques must be tailored to the specific research question and trial setting. In this paper, the authors made an interpretation of this scientific statement based on their practical experience.

Analysis of prognosis and influencing factors of No. 253 lymph node metastasis in descending colon, sigmoid colon, and rectal cancer: a multicenter study / 中华外科杂志

Objectives: To analyze the influencing factors of No. 253 lymph node metastasis in descending colon cancer, sigmoid colon cancer, and rectal cancer, and to investigate the prognosis of No. 253 lymph node-positive patients by propensity score matching analysis. Methods: A retrospective analysis was performed on clinical data from patients with descending colon cancer, sigmoid colon cancer, rectosigmoid junction cancer, and rectal cancer who underwent surgery between January 2015 and December 2019 from the Cancer Hospital of the Chinese Academy of Medical Sciences, China-Japan Friendship Hospital, Peking Union Medical College Hospital, General Hospital of the Chinese People's Liberation Army, and Peking University Cancer Hospital. A total of 3 016 patients were included according to inclusion and exclusion criteria, comprising 1 848 males and 1 168 females, with 1 675 patients aged≥60 years and 1 341 patients aged<60 years. Clinical and pathological factors from single center data were subjected to univariate analysis to determine influencing factors of No. 253 lymph node metastasis, using a binary Logistic regression model. Based on the results of the multivariate analysis, a nomogram was constructed. External validation was performed using data from other multicenter sources, evaluating the effectiveness through the area under the receiver operating characteristic curve and the calibration curve. Using data from a single center, the No. 253 lymph node-positive group was matched with the negative group in a 1∶2 ratio (caliper value=0.05). Survival analysis was performed using the Kaplan-Meier method and Log-rank test. The Cox proportional hazards model was used to determine independent prognostic factors. Results: (1) The tumor diameter≥5 cm (OR=4.496,95%CI:1.344 to 15.035, P=0.015) T stage (T4 vs. T1: OR=11.284, 95%CI:7.122 to 15.646, P<0.01), N stage (N2 vs. N0: OR=60.554, 95%CI:7.813 to 469.055, P=0.043), tumor differentiation (moderate vs. well differentiated: OR=1.044, 95%CI:1.009 to 1.203, P=0.044; poor vs. well differentiated: OR=1.013, 95%CI:1.002 to 1.081, P=0.013), tumor location (sigmoid colon vs. descending colon: OR=9.307, 95%CI:2.236 to 38.740, P=0.002), pathological type (mucinous adenocarcinoma vs. adenocarcinoma: OR=79.923, 95%CI:15.113 to 422.654, P<0.01; signet ring cell carcinoma vs. adenocarcinoma: OR=27.309, 95%CI:4.191 to 177.944, P<0.01), and positive vascular invasion (OR=3.490, 95%CI:1.033 to 11.793, P=0.044) were independent influencing factors of No. 253 lymph node metastasis. (2) The area under the curve of the nomogram prediction model was 0.912 (95%CI: 0.869 to 0.955) for the training set and 0.921 (95%CI: 0.903 to 0.937) for the external validation set. The calibration curve demonstrated good consistency between the predicted outcomes and the actual observations. (3) After propensity score matching, the No. 253 lymph node-negative group did not reach the median overall survival time, while the positive group had a median overall survival of 20 months. The 1-, 3- and 5-year overall survival rates were 83.9%, 61.3% and 51.6% in the negative group, and 63.2%, 36.8% and 15.8% in the positive group, respectively. Multivariate Cox analysis revealed that the T4 stage (HR=3.067, 95%CI: 2.357 to 3.990, P<0.01), the N2 stage (HR=1.221, 95%CI: 0.979 to 1.523, P=0.043), and No. 253 lymph node positivity (HR=2.902, 95%CI:1.987 to 4.237, P<0.01) were independent adverse prognostic factors. Conclusions: Tumor diameter ≥5 cm, T4 stage, N2 stage, tumor location in the sigmoid colon, adverse pathological type, poor differentiation, and vascular invasion are influencing factors of No. 253 lymph node metastasis. No. 253 lymph node positivity indicates a poorer prognosis. Therefore, strict dissection for No. 253 lymph node should be performed for colorectal cancer patients with these high-risk factors.

Development and validation of a prognostic prediction model for patients with stage Ⅰ to Ⅲ colon cancer incorporating high-risk pathological features / 中华外科杂志

Objective: To examine a predictive model that incorporating high risk pathological factors for the prognosis of stage Ⅰ to Ⅲ colon cancer. Methods: This study retrospectively collected clinicopathological information and survival outcomes of stage Ⅰ~Ⅲ colon cancer patients who underwent curative surgery in 7 tertiary hospitals in China from January 1, 2016 to December 31, 2017. A total of 1 650 patients were enrolled, aged (M(IQR)) 62 (18)years (range: 14 to 100). There were 963 males and 687 females. The median follow-up period was 51 months. The Cox proportional hazardous regression model was utilized to select high-risk pathological factors, establish the nomogram and scoring system. The Bootstrap resampling method was utilized for internal validation of the model, the concordance index (C-index) was used to assess discrimination and calibration curves were presented to assess model calibration. The Kaplan-Meier method was used to plot survival curves after risk grouping, and Cox regression was used to compare disease-free survival between subgroups. Results: Age (HR=1.020, 95%CI: 1.008 to 1.033,P=0.001), T stage (T3:HR=1.995,95%CI:1.062 to 3.750,P=0.032;T4:HR=4.196, 95%CI: 2.188 to 8.045, P<0.01), N stage (N1: HR=1.834, 95%CI: 1.307 to 2.574, P<0.01; N2: HR=3.970, 95%CI: 2.724 to 5.787, P<0.01) and number of lymph nodes examined (≥36: HR=0.438, 95%CI: 0.242 to 0.790, P=0.006) were independently associated with disease-free survival. The C-index of the scoring model (model 1) based on age, T stage, N stage, and dichotomous variables of the lymph nodes examined (<12 and ≥12) was 0.723, and the C-index of the scoring model (model 2) based on age, T stage, N stage, and multi-categorical variables of the lymph nodes examined (<12, 12 to <24, 24 to <36, and ≥36) was 0.726. A scoring system was established based on age, T stage, N stage, and multi-categorical variables of lymph nodes examined, the 3-year DFS of the low-risk (≤1), middle-risk (2 to 4) and high-risk (≥5) group were 96.3%(n=711), 89.0%(n=626) and 71.4%(n=313), respectively. Statistically significant difference was observed among groups (P<0.01). Conclusions: The number of lymph nodes examined was an independent prognostic factor for disease-free survival after curative surgery in patients with stage Ⅰ to Ⅲ colon cancer. Incorporating the number of lymph nodes examined as a multi-categorical variable into the T and N staging system could improve prognostic predictive validity.

Prediction of Coagulation Factor Ⅷ Level in Chinese Hemophilia A Patients by the Pharmacokinetic Management Tool myPKFiT / 中国医学科学院学报

Objective To evaluate the performance of myPKFiT,a tool guiding the dosing of antihemophilic factor (recombinant) plasma/albumin-free method (rAHF-PFM),in maintaining the coagulation factor Ⅷ (FⅧ) level above a target threshold at the steady state and estimating the pharmacokinetics (PK) parameters in hemophilia A patients in China. Methods The data of 9 patients with severe hemophilia A in a trial (CTR20140434) assessing the safety and efficacy of rAHF-PFM in the Chinese patients with hemophilia A were analyzed.The myPKFiT was used to predict the adequate dose to maintain a patient's FⅧ level above target threshold at the steady state.Furthermore,the performance of myPKFiT in estimating the pharmacokinetics parameters of individuals was evaluated. Results Twelve combinations of two dosing intervals and six sparse sampling schedules were investigated,and 57%-88% of the patients remained the FⅧ level above the target threshold of 1 U/dl (1%) for at least 80% of the dosing interval.The clearance and time to FⅧ level of 1% obtained from sparse sampling by myPKFiT were similar to those obtained from extensive sampling. Conclusions The myPKFiT can provide adequate dose estimates to maintain the FⅧ level above the target threshold at the steady state in Chinese patients with severe hemophilia A.Moreover,it demonstrates good performance for estimating key pharmacokinetics parameters,including clearance and time to FⅧ level of 1%.

Treatment of rheumatoid arthritis by injection of sinomenine solid lipid nanoparticles under a fluorescence endoscopic laser confocal microscope / 中国中药杂志

A fluorescence endoscopic laser confocal microscope(FELCM) was used to direct the injection of sinomenine solid lipid nanoparticles(Sin-SLN) into the joint, and the in vitro effectiveness of Sin-SLN in the treatment of rheumatoid arthritis(RA) was evaluated. Sin-SLN was prepared with the emulsion evaporation-low temperature curing method. The Sin-SLN prepared under the optimal conditions showed the encapsulation efficiency of 64.79%±3.12%, the drug loading of 3.84%±0.28%, the average particle size of(215.27±4.21) nm, and the Zeta potential of(-32.67±0.84) mV. Moreover, the Sin-SLN demonstrated good stability after sto-rage for 30 days. The rabbit model of RA was established by the subcutaneous injection of ovalbumin and complete Freund's adjuvant. Five groups were designed, including a control group, a model group, a Sin(1.5 mg·kg~(-1)) group, a Sin-SLN(1.5 mg·kg~(-1)) group, and a dexamethasone(positive drug, 1.0 mg·kg~(-1), ig) group. The control group and the model group only received puncture treatment without drug injection. After drug administration, the local skin temperature and knee joint diameter were monitored every day. The knee joint diameter and the local skin temperature were lower in the drug administration groups than in the model group(P<0.05, P<0.01). FELCM recorded the morphological alterations of the cartilage of knee joint. The Sin-SLN group showed compact tissue structure and smooth surface of the cartilage. Enzyme-linked immunosorbent assay(ELISA) was employed to determine the serum le-vels of interleukin-1(IL-1) and tumor necrosis factor-α(TNF-α). The findings revealed that the Sin-SLN group had lower IL-1 and TNF-α levels than the model group(P<0.05, P<0.01). Hematoxylin-eosin(HE) staining was employed to reveal the pathological changes of the synovial tissue, which were significantly mitigated in the Sin-SLN group. The prepared Sin-SLN had uniform particle size and high stability. Through joint injection administration, a drug reservoir was formed. Sin-SLN effectively alleviate joint swelling and cartilage damage of rabbit, down-regulated the expression of inflammatory cytokines, and inhibited the epithelial proliferation and inflammatory cell infiltration of the synovial tissue, demonstrating the efficacy in treating RA.

Second allogeneic hematopoietic stem cell transplantation with reduced-intensity conditioning and donor changes in relapsed hematological malignancies after the first allogeneic transplant / 中华血液学杂志

Objective: The purpose of this study was to assess the safety and efficacy of a second allogeneic hematopoietic stem cell transplantation (allo-HSCT) with reduced-intensity conditioning (RIC) in patients with hematological malignancies who had relapsed after the first allo-HSCT. Methods: Between April 2018 and June 2021, 44 patients with hematological malignancies (B-ALL 23, T-ALL/T-LBL 4, AML15, and MDS 2) were enrolled and retrospectively examined. Unrelated donors (n=12) or haploidentical donors (n=32) were used. Donors were replaced in all patients for the second allo-HSCT. Hematological and immunological germline predisposition genes and hematopoietic and immune function tests were used to select the best-related donor. Total body irradiation (TBI) /fludarabine (FLU) -based (n=38), busulfan (BU) /FLU-based (n=4), total marrow irradiation (TMI) /FLU-based (n=1), and BU/cladribine-based (n=1) were the RIC regimens used. For graft versus host disease (GVHD) prevention, cyclosporine, mycophenolate mofetil, short-term methotrexate, and ATG were used. Eighteen (40.9%) of 44 patients with gene variations for which targeted medications are available underwent post-transplant maintenance therapy. Results: The median age was 25 years old (range: 7-55). The median interval between the first and second HSCT was 19.5 months (range: 6-77). Before the second allo-HSCT, 33 (75%) of the patients were in complete remission (CR), whereas 11 (25%) were not. All patients had long-term engraftment. The grade Ⅱ-Ⅳ GVHD and severe acute GVHD rates were 20.5% and 9.1%, respectively. Chronic GVHD was found in 20.5% of limited patterns and 22.7% of severe patterns. CMV and EBV reactivation rates were 29.5% and 6.8%, respectively. Hemorrhage cystitis occurred in 15.9% of cases, grade Ⅰ or Ⅱ. The 1-yr disease-free survival (DFS), overall survival (OS), and cumulative recurrence incidence (RI) rates of all patients were 72.5% (95% CI, 54.5%-84.3%), 80.6% (95% CI, 63.4%-90.3%), and 25.1% (95% CI, 13.7%-43.2%), respectively, with a median follow-up of 14 (2-39) months. There were eight deaths (seven relapses and one infection). The rate of non-relapse mortality (NRM) was only 2.3%. The CR patients' 1-yr RI rate was significantly lower than the NR patients (16.8% vs 48.1%, P=0.026). The DFS rate in CR patients was greater than in NR patients, although there was no statistical difference (79.9% vs 51.9%, P=0.072). Univariate analysis revealed that CR before the second allo-HSCT was an important prognostic factor. Conclusion: With our RIC regimens, donor change, and post-transplant maintenance therapy, the second allo-HSCT in relapsed hematological malignancies after the first allo-HSCT is a safe and effective treatment with high OS and DFS and low NRM and relapse rate. The most important factor influencing the prognosis of the second allo-HSCT is the patient's illness condition before the transplant.

Clinical Features and CT Imaging Findings of Melioidosis Pneumonia / 中山大学学报(医学科学版)

ObjectiveTo summarize and analyze the clinical features and CT imaging findings of melioidosis pneumonia in order to increase awareness of this disease. MethodsA retrospective study was done on clinical and CT imaging data of 68 cases with melioidosis pneumonia diagnosed from January 1， 2012 to April 1， 2023. ResultsOf the 68 cases， 62 presented with acute infection and 6 chronic infection， 88.2% were male， 85.3% were native residents of Hainan， 85.3% were farmers， 77.9% had onset in summer and autumn， 66.2% had diabetes， 100% had fever as the first clinical symptom， and 88.2% were confirmed positive by blood culture. In most patients， white blood cell count， neutrophil ratio， C-reactive protein and calcitonin levels increased， while lymphocyte ratio decreased， but no statistical difference was found between acute and chronic infection groups （P > 0.05）. Of the patients， 36.8% recovered， 42.6% got better， 11.8% patients became therapy-resistant and 8.8% died. CT image showed pathomorphological changes including nodules/masses， patchy ground-glass attenuation or large patchy consolidation or all of these at the same time. Acute and chronic infection groups had significant difference in pathomorphological changes （P = 0.01）， but no statistical difference in other imaging findings. Moreover， 36.8% of the patients developed extrapulmonary infections， 8.8% of which multi-site abscess formation. ConclusionsMelioidosis Pneumonia should be considered if the patient is the sojourner from epidemic area， or has diabetes， high fever and rapid-developing disease， with additional presence of multiple inflammatory lesions in lung CT.

Progress in clinical studies in cardiovascular surgery 2022 / 中国胸心血管外科临床杂志

@#In 2022, many excellent clinical studies emerged in the field of cardiovascular surgery. Selecting papers published in The New England Journal of Medicine and other top medicine and cardiology journals, this review focused on the research progress on 7 topics in the field of cardiovascular surgery: coronary artery surgery, vascular surgery, valvular surgery, structural heart disease, congenital heart disease, heart transplantation, perioperative management, and special population.

Analysis of biochemical failure rate and its influencing factors in patients with high-risk localized prostate cancer after radical prostatectomy / 中华泌尿外科杂志

Objective:To analyze the biochemical failure rate and its predictive factors after radical prostatectomy (RP) in patients with high-risk localized prostate cancer.Methods:The data of 166 patients with high-risk localized prostate cancer who underwent RP surgery in Peking university cancer hospital from January 2015 to November 2021 were retrospectively reviewed. The average age was 65.4±6.2 years old, and the average body mass index (BMI) was 24.86±3.23 kg/m 2. The median prostate-specific antigen (PSA) was 19.84 (10.98, 44.47) ng/ml, PSA density was 0.68 (0.34, 1.32)ng/ml 2, and prostate volume was 31.20 (25.58, 40.23) ml. Biopsy pathology Gleason score according to the International society of Urological Pathology(ISUP) grade group: 18 cases of group 1, 33 cases of group 2, 30 cases of group 3, 51 cases of group 4, and 33 cases of group 5, 1 case was unknown. The percentage of puncture positive needles was (55.4±25.7)%, and the largest linear length of positive lesions was 80.0% (60.0%, 90.0%). Preoperative clinical stage : 14 cases in ≤T 2b stage, 117 cases in T 2c stage, 13 cases in T 3a stage and 22 cases in ≥T 3b stage; 157 cases in N 0 stage, 9 cases in N 1 stage. One hundred and three patients (62.0%) were assessed by traditional imaging and 63(38.0%) were assessed by PSMA PET-CT. The patients underwent laparoscopic radical prostatectomy. 64 patients (38.6%) received neoadjuvant therapy, including 37 received neoadjuvant therapy for 1-3 months, 23 for 4-6 months and 4 for over 6 months. The postoperative pathological characteristics, treatment and prognosis of the patients were analyzed. The primary endpoint was biochemical failure, including biochemical persistence(BCP, defined as PSA≥0.1ng/ml at 4-6 weeks after operation, and confirmed by re-examination at least 1 week interval) and biochemical recurrence(BCR, PSA falling below 0.1ng/ml after operation and then rising ≥0.2 ng/ml without adjuvant therapy or after the end of adjuvant treatment). Results:Compared with preoperative clinicopathological characteristics, 48(28.9%) cases had postoperative pathological ISUP upgrade, 98 (59.0%)cases had T stage upgrade, and 13 (7.8%) cases had N stage upgrade. The rate of positive margins was 53%, and apex margin was the most common positive site (65.9%). The postoperative PSA in 114 patients (68.7%) decreased to less than 0.1ng/ml, of which 74 patients didn't receive the therapy and 40 patients received adjuvant therapy. 52 patients (31.3%) had postoperative PSA more than 0.1ng/ml and among them, 51 cases received salvage treatment. 5 patients (3.0%) underwent PSA progression during adjuvant or salvage endocrine therapy and were considered to have castration resistance. After a median follow-up time of 25.5 (12.0, 40.0) months, 78 patients (48.4%, 78/161) experienced biochemical failure, including 49 BCP and 29 BCR, the median time of biochemical failure was 30.0 (95% CI 14.5-45.5) months. Adjuvant therapy could reduce the rate of BCR (31.1% and 15.8%, P=0.08). Baseline PSA, PSA density, proportion of pathological ISUP ≥4, proportion of pathological T stage ≥T 3a, adjuvant therapy, and positive surgical margins were significantly associated with biochemical failure ( P=0.034, 0.002, 0.004, 0.025, <0.001and 0.047). Multivariate Cox regression analysis showed that adjuvant therapy ( P<0.001, OR=0.12), PSA density ( P=0.03, OR=1.19) and positive surgical margins ( P=0.034, OR=1.80) were independent factors for biochemical failure. Conclusions:Patients with high-risk localized prostate cancer have a high rate of biochemical failure after RP and need to receive RP-based multimodal therapy. Adjuvant therapy, PSA density and positive surgical margins are independent factors associated with postoperative biochemical failure.

Analysis of failure patterns and survival after SBRT for 147 cases of T 1-2N 0M 0 stage non-small cell lung cancer / 中华放射肿瘤学杂志

Objective:To analyze the failure patterns and survival after stereotactic body radiotherapy (SBRT) in patients with T 1-2N 0M 0 non-small cell lung carcinoma (NSCLC). Methods:Clinical data of early-stage NSCLC patients who received SBRT at Zhejiang Cancer Hospital from January 2012 to September 2018 were retrospectively analyzed. The primary observed endpoint was the pattern of disease progression, which was divided into intra-field recurrence, regional lymph node recurrence and distant metastasis. Overall survival (OS) and progression-free survival (PFS) were calculated by Kaplan-Meier method. Univariate analysis was conducted by log-rank test, and multivariate analysis was performed by Cox's model.Results:A total of 147 patients with 156 lesions were included. The median follow-up time was 44.0 months (16.5-95.5 months). A total of 57 patients (38.8%) progressed: 14 patients (24.5%) had recurrence with the 1-, 3-, and 5-year local recurrence rates of 2.0%, 10.9%, and 14.3%, respectively; 36 patients (63.2%) had Distant metastasis with the 1-, 3- and 5-year distant metastasis rates of 12.2%, 22.4% and 28.6%, respectively; and 7 patients (12.3%) had recurrence complicated with distant metastasis. The 3-, 5- and 7-year OS rates were 80.5%, 64.2% and 49.9% for all patients, respectively. The median OS was 78.4 months. The 3-, 5- and 7-year PFS rates were 64.8%,49.5% and 41.5%, with a median PFS of 57.9 months (95% CI: 42.3-73.5 months). Univariate and multivariate analyses showed that biologically equivalent dose and age were the factors affecting the efficacy of SBRT (both P<0.05). Conclusion:Distant metastasis is the main failure pattern in patients with T 1-2N 0M 0 NSCLC after SBRT. High-risk population should be selected for further systematic treatment to improve the efficacy.

Failure mode and long-term survival after neoadjuvant therapy for locally advanced esophageal squamous cell carcinoma / 中华放射肿瘤学杂志

Objective:To analyze the fail mode of neoadjuvant therapy combined with surgery for locally advanced esophageal squamous cell carcinoma (ESCC) after long-term follow-up.Methods:Clinical data of consecutive 238 patients with locally advanced resectable ESCC who underwent neoadjuvant therapy combined with surgery in Zhejiang Cancer Hospital from September 2012 to October 2019 were retrospectively analyzed. The failure mode in the whole cohort was analyzed after long-term follow-up. The overall survival (OS) and disease free survival (DFS) rates were analyzed by Kaplan-Meier method. Survival differences were determined by log-rank test.Results:The pathological complete response (pCR) rate was 42.0% in 238 patients. After a median follow-up of 46.1 months, tumor progression occurred in 96 patients (40.3%), including 25 patients (10.5%) with local recurrence, 61 patients (25.6%) with distant metastases, and 10 patients (4.2%) with simultaneous local recurrence and distant metastases. The median OS and DFS were 64.7 months and 49.9 months. And the 3-, 5-, and 7-year OS and DFS rates were 70.0%, 52.8%, 36.4% and 63.5%, 42.5%, and 30.0%, respectively. The 3-, 5-, and 7-year locoregional recurrence-free survival rates and distant metastasis-free survival rates were 86.0%, 71.4%, 61.2% and 70.6%, 55.9%, 43.0%. Compared with non-pCR patients, the overall progression rate and distant metastasis rate of pCR patients were lower (26.0% vs. 50.7%, 16.0% vs. 32.6%, both P<0.05). And the 3-, 5-, and 7-year OS (83.0% vs. 60.2%, 69.7% vs. 41.7%, 50.4% vs. 27.7%, all P<0.001) and DFS rates (80.4% vs. 51.4%, 63.9% vs. 31.2%, 45.9% vs. 20.3%, all P<0.001) were significantly better in pCR patients. Conclusions:Distant metastasis is the main failure mode of patients with locally advanced ESCC after neoadjuvant therapy. Patients with postoperative pCR can achieve better long-term survival.

High-throughput screening of SARS-CoV-2 main and papain-like protease inhibitors

The global COVID-19 coronavirus pandemic has infected over 109 million people, leading to over 2 million deaths up to date and still lacking of effective drugs for patient treatment. Here, we screened about 1.8 million small molecules against the main protease (Mpro) and papain like protease (PLpro), two major proteases in severe acute respiratory syndrome-coronavirus 2 genome, and identified 1851Mpro inhibitors and 205 PLpro inhibitors with low nmol/l activity of the best hits. Among these inhibitors, eight small molecules showed dual inhibition effects on both Mpro and PLpro, exhibiting potential as better candidates for COVID-19 treatment. The best inhibitors of each protease were tested in antiviral assay, with over 40% of Mpro inhibitors and over 20% of PLpro inhibitors showing high potency in viral inhibition with low cytotoxicity. The X-ray crystal structure of SARS-CoV-2 Mpro in complex with its potent inhibitor 4a was determined at 1.8 Å resolution. Together with docking assays, our results provide a comprehensive resource for future research on anti-SARS-CoV-2 drug development.

Research Progress on Sport-Related Sudden Cardiac Death / 法医学杂志

Physical exercise can reduce the overall risk of cardiovascular disease, prolong lifespan and improve the quality of life, but some studies have shown that there is a certain correlation between vigorous physical exercise and sudden cardiac death. A number of retrospective or prospective studies on sports-related sudden cardiac death (SrSCD) have been conducted at home and abroad. This article reviews the related studies on the definition, epidemiological characteristics, common causes of SrSCD and effects of excercise on cardiovascular function, pre-exercise screening and evaluation of SrSCD, in order to understand the latest research progress on SrSCD and provide clues and references for SrSCD research.

Mid- and long-term outcomes and prognostic factors of drug-coated balloon angioplasty for treatment of femoropopliteal long lesions / 中华外科杂志

Objective: To examine the effective and safe outcomes of drug-coated balloon (DCB) angioplasty for the treatment of femoropopliteal long lesions in mid-term and long-term follow-up. Methods: The clinical data of 114 patients with symptomatic (Rutherford 2 to 6) femoropopliteal long lesions who underwent angioplasty with DCB between June 2016 and May 2021 at Department of Vascular Surgery,Beijing Tsinghua Changgung Hospital were retrospectively analyzed. A total of 75 males and 39 females were enrolled, aged (71.9±8.4)years (range: 49 to 89 years). Among 138 lesions in 114 patients, there were 111 de nove lesions (80.4%, 111/138). Total occlusions were recanalized in 116 limbs (84.1%, 116/138). The lesion length was (280.9±78.7)mm (range: 150 to 520 mm). DCB angioplasty combined with debulking devices was used in 59 lesions (42.8%, 59/138).The bail-out stent implantation was performed in 27 limbs (19.6%, 27/138). The Kaplan-Meier method was used to evaluate cumulative primary patency rate, freedom from the clinically driven target lesion revascularization (CD-TLR) rate and accumulate survival rate. Univariate and multivariate analyses with Cox proportional hazards models were performed to determine the significant prognostic factors for primary patency. Results: DCB angioplasty was completed in 114 patients. The technical success rate was 98.2%(112/114). The mean follow-up time was 18 months (range: 3 to 54 months).The results showed that primary patency rates at 12, 24 and 36 months postoperatively were 87.5%, 75.2% and 55.1%, respectively. Freedom from CD-TLR rate at 12, 24 and 36 months postoperatively were 92.4%, 81.8% and 68.7%, respectively. Accumulate survival rate at 12, 24 and 36 months postoperatively were 96.2%, 94.0% and 80.2%. Multivariate Cox's regression analyses showed that chronic limb-threatening ischemia(CLTI) (HR=2.629, 95%CI:1.519 to 4.547, P<0.01) and hyperlipidemia (HR=2.228, 95%CI: 1.004 to 4.948, P=0.026) were independent prognosis factors for primary patency in DCB treatment of femoropopliteal long lesions. Conclusions: DCB provided favorable outcomes for the treatment of femoropopliteal long lesions. CLTI and hyperlipidemia are independent prognosis factors for restenosis after DCB angioplasty.

Construction of spvD gene deletion mutant and compensation strains in Salmonella enteritidis and its effects on Caco-2 cells / 中华预防医学杂志

Objective: To analyze the effects of spvD gene on invasion and intracellular proliferation of Caco-2 cells and in order to provide insight into the function of that gene and the underlying mechanism of Salmonella caused infection. Methods: Functional verification of spvD gene deletion mutant and compensation strain. The deletion mutant strain was constructed through a suicide plasmid-mediated homologous recombination. The compensation plasmid constructed by cloning the coding sequence of spvD by PCR into plasmid pBAD33 was mobilized into the deletion mutant by conjugation and the pBAD33 was introduced into wild strains and deleted mutant strains as control. The relative expression of spvD mRNA was detected by quantitative reverse transcription PCR. In order to analyze the virulence of spvD against Caco-2 cells, Caco-2 cells was cocultured with wild type Salmonella enteritidis carrying spvD gene, the deletion mutant strain and compensation strain respectively. The expression level of spvD mRNA and the the number of Salmonella enteritidis after Caco-2 cells intervention were compared between the three groups by LSD-t test, and the invasion rate was compared by χ2 test. Results: The expression level of spvD mRNA in wild type Salmonella enteritidis was set as unit "1", the deletion mutant strain was "0.00", and the compensation strain was "2.60" (LSD-twild, deleted=1.11, P=0.31; LSD-twild, compensation=-1.77, P=0.13; LSD-t deleted, compensation=-2.88, P=0.03), which confirmed the successful construction of the deletion mutant strain and the compensation strain. The invasion experiment results of the above three Salmonella enteritidis strains on Caco-2 cells showed that the invasion rate of wild strain was 0.23%, the invasion rate of deleted mutant strain was 0.16%, and the invasion rate of compensation strain was 0.16%, with no statistical significance (χ2=1.13, P=0.570). By comparing the number of Salmonella enteritidis at different time points after Caco-2 cells intervention, it was discovered that the number of Salmonella enteritidis in wild strains (6.50×106 CFU/ml) and compensation strains (7.25×106 CFU/ml) was significantly increased than that in deletion mutant strain (1.90×106 CFU/ml) after 16 h coculture (LSD-twild, deleted=7.95, P=0.00; LSD-twild, compensation=-1.27, P=0.25; LSD-t deleted, compensation=-9.22, P=0.00). Conclusion: It is not considered that spvD gene can affect the invasion of Salmonella enteritidis on Caco-2 cells, but the gene can promote the reproduction of Salmonella enteritidis in Caco-2 cells.

Exploration on the experience of long-term external normothermic machine perfusion of discarded human kidney for the first time in China / 中华肾脏病杂志

Objective:To explore the long-term preservation value and repair effect of normothermic machine perfusion (NMP) on clinically discarded kidneys.Methods:A case of clinical discarded donor kidney was collected, and NMP was carried out in vitro for 9 hours with recovered blood. The dynamic changes of renal appearance, blood gas and biochemistry analysis of perfusate and renal pathology were recorded. Results:In the second to fifth hour of NMP, the appearance of renal was pink and ex vivo normothermic perfusion assessment score (EVNP) was grade Ⅰ. While, the sixth hour and beyond of NMP, the appearance of kidney turned to dark red and EVNP was grade Ⅲ. The renal perfusion blood flow maintained above 150 ml/min in the first 6 hours and decreased significantly after that, and at the end, was only 50 ml/min. During the whole process of perfusion, urine output was maintained at about 100 ml/h. PO 2 remained above 100 mmHg in the first 5 hours of perfusion and from the 6th hour, was lower than 80 mmHg and continued to decline, and was close to 0 at the end of perfusion. The results showed that although the K + concentration changes in blood and urine in the first 5 hours of NMP had a good consistency, the lactic acid level had been rising. In addition, there was no significant change in the histopathology at the fourth hour of perfusion compared with that before zero-point puncture, and the fibrinous thrombus in glomeruli was improved compared with that before perfusion. However, at the sixth hour after perfusion and before the end of perfusion, the pathological changes of renal tissue were significantly worse. There were a large of thrombosis in glomerular blood vessels, renal tubular atrophy and acute tubular necrosis. Conclusions:NMP can realize the evaluation of extended criteria donors before transplantation, and it proves the feasibility and repair potential of NMP in kidney to a certain extent. At the same time, NMP also provides a new way to expand the source of donor kidney and to pre-treat organ in vitro.

Feasibility of application of deformable image registration to the dosimetry assessment of fractionated brachytherapy for cervical cancer / 中华放射医学与防护杂志

Objective:To study the differences in the cumulative dose between deformable image registration (DIR) and simple dose-volume histogram (DVH) summation in the fractionated brachytherapy of cervical cancer, and to analyze the feasibility of the application of DIR in the dosimetry assessment of targets and organs-at-risk (OARs) in the brachytherapy.Methods:A retrospective analysis was conducted for 13 cases with primary cervical cancer treated with four fractions of interstitial brachytherapy guided by CT images. The four CT images of each cases were registered using an intensity-based DIR. Then, the cumulative doses (the D2 cm 3, D1 cm 3, and D0.1 cm 3 of the bladder, rectum, intestine, and colon and the D90for targets) after DIR were calculated and compared to those obtained using simple DVH summation. Afterward, the correlation between the dose difference and dice similarity coefficient (DSC) was analyzed. With the dose difference (the remaining dose of OARs caused by the DIR) as limits, a new plan was made for the latest CT to calculate the dose increase to targets. Results:Compared to simple DVH summation, DIR allowed the cumulative doses of the D2 cm 3 and D1 cm 3 of bladder to be decreased by (2.47±1.92) and (2.82±2.73) Gy, respectively on average ( t=-3.65, -2.93, P < 0.05), those of the D2 cm 3, D1 cm 3, and D0.1 cm 3 of rectum to be decreased by (2.05 ± 1.61) Gy, (1.51 ± 1.58), and (3.21 ± 2.50) Gy, respectively on average ( t=-4.02, -3.02, -4.06, P < 0.05), and those of the D2 cm 3, D1 cm 3, and D0.1 cm 3 to be decreased by (1.42 ± 0.99), (1.55 ± 1.28) Gy, and (2.43 ± 1.95) Gy, respectively on average ( t=-3.52, -2.96, -3.06, P < 0.05). There was no significant statistical difference in the D90 of targets, the D0.1 cm 3 of the bladder, and the D2 cm 3, D1 cm 3, D0.1 cm 3 of the colon ( P > 0.05) between both methods, and there was no distinct correlation between DSC and dose difference ( P > 0.05). The DIR increased the dose to targets, with a median value of 150 cGy. However, the accuracy of the DIR should be improved. Conclusions:In clinical practice of multiple fractions of brachytherapy for cervical cancer, it′s still recommended to adopt the simple dose summation method to assess the doses to targets and OARs.

Insights into the clinical studies related to cardiovascular surgery from the American Heart Association’s Scientific Sessions 2021: Part one / 中国胸心血管外科临床杂志

@#In the American Heart Association’s Scientific Sessions 2021, the results of six clinical trials related to cardiovascular surgery were revealed. The PALACS trial demonstrated that posterior left pericardiotomy during open heart surgery was associated with a significant reduction in postoperative atrial fibrillation; the EPICCURE study found that injection of mRNA encoding vascular endothelial growth factor (VEGF-A mRNA) directly into the myocardium of patients undergoing elective coronary artery bypass grafting (CABG) improved patients’ heart function; the VEST trial once again proved the safety and potential value of external stent for vein graft. This article will interpret the above-mentioned three studies.

Repair of two wounds in the same or adjacent digits with free ipsilateral double pedicled superficial peroneal artery perforator flap / 中华显微外科杂志

Objective:To explore the surgical method and clinical effect of harvesting 2 ipsilateral free pedicled perforator flaps from a single donor site of superficial peroneal artery in reconstruction of 2 defects in same or adjacent digits.Methods:From November 2017 to August 2021, 12 patients with 2 defects in same or adjacent digits were treated in the Department of Hand Surgery, Suzhou Ruihua Orthopaedic Hospital with 2 ipsilateral free pedicled perforator flaps from a single donor site of superficial peroneal artery. Among the patients, 1 had the defect in dorsal and palmar of index finger, 1 in thumb and index finger, 6 in index and middle fingers, 3 in middle and ring fingers, and 1 in ring and little fingers. The size of digit defects was 1.5 cm×0.8 cm-6.0 cm×3.5 cm. The size of flaps was 2.0 cm× 1.2 cm-8.0 cm×4.0 cm. All the patients were included in postoperative monthly follow-up to assess the recovery of recipient and donor sites at outpatient service, by telephone or WeChat.Results:All 24 flaps in 12 patients survived without vascular compromise and achieved 100% of survival rate. The follow-up period ranged from 4 to 18 months, with an average of 10 months. Six patients were treated with additional flap thinning and plastic surgery at 4 months after the primary surgery due to slightly bloated flaps. Otherwise, all the flaps in the recipient site had neither pigmentation, obvious hyperplasia nor scar pain. All flaps gained the protective sensations, however the assessment of TPD was not conducted. The flaps were wear-resist and had no ulceration. The texture of the flaps was soft with good elasticity, and the flap did not turn to purple or swelling when in cold. The functional recovery of 23 digits in 12 patients was evaluated according to the total active mobility (TAM) of the digits. It achieved excellent in 3 digits, good in 15 digits, and fair in 5 digits, with an excellent and good rate of 78.26%. A linear scar appeared at the donor site without obvious hyperplasia or scar pain. There were normal sensations around the scar and at the digit-tips. The blood supply to the digit-tips was normal.Conclusion:Harvest of multiple free pedicled perforator flaps from a single donor site of superficial peroneal artery is an effective method in reconstruction of 2 defects in same or adjacent digits at the same time. It has advantages of being a simple surgery procedure by sacrificing only one donor site. It achieves a minimal damage to the donor site and a reliable blood supply of the flap.

Comparison on efficacy between fascia-oriented versus vascular-oriented lateral lymph node dissection in patients with rectal cancer / 中华胃肠外科杂志

Objective: To compare the postoperative function, the short-term and long-term outcomes between fascia-oriented and vascular-oriented lateral lymph node dissection (LLND) in patients with rectal cancer. Methods: A retrospective cohort study was performed. Clinical data of patients who received total mesorectal excision (TME) with LLND at National Cancer Center, Cancer Hospital of Chinese Academy of Medical Science from January 2014 to December 2019 were retrospectively collected. Inclusion criteria were as follows: (1) rectal cancer was pathologically diagnosed, and the lower margin was below the peritoneal reflection. (2) resectable advanced rectal cancer with suspected lateral lymph node metastasis was evaluated based on rectal MRI assessment. (3) preoperative MRI showed lateral lymph node short diameter ≥5 mm and/or lymph node morphology (spike, blur, irregular) as well as heterogenous signal intensity. Lymph node shrinkage was less than 60% after receiving neoadjuvant therapy based on the reassessment of rectal MRI. (4) TME+LLND surgery was performed synchronously. Exclusion criteria were as follows: (1) previous history of pelvic surgery; (2) preoperative cystitis, urethritis, moderate and severe prostatic hyperplasia and other diseases resulting in abnormal urination function; (3) preoperative sexual dysfunction or loss of function; (4) patients receiving LLND due to lateral recurrence after TME; (5) distant metastasis of the tumor at initial diagnosis; (6) Incomplete collection of clinical data. A total of 73 consecutive patients were enrolled in this study. Based on the surgical approaches in performing LLND, patients were divided into fascia-oriented group (n=30) and vascular-oriented group (n=43). There were no significant differences in baseline data between the two groups (all P>0.05). The main outcome indicators of this study were the incidence of postoperative urinary and male sexual dysfunction, the efficacy, the number of lateral lymph nodes harvested and the detection rate of positive lymph nodes. Overall survival (OS) rates and progression free survival (PFS) rates were calculated by the Kaplan-Meier method and compared by log-rank test. Results: All patients in both groups completed surgery successfully. There were no significant differences in operation time, intraoperative blood loss, postoperative complications, and the length of hospital stay between the two groups (all P>0.05). In the whole group, the incidence of postoperative urinary dysfunction and male sexual dysfunction was 43.8% (32/73) and 62.5% (25/40), respectively. The median number of lateral lymph nodes harvested was 8.0(4.0,11.0) with a positive rate of 20.5%(15/73). Compared to the vascular-oriented group, the fascia-oriented group demonstrated a decreased rate of urinary dysfunction [26.7% (8/30) vs. 55.8% (24/43), χ(2)=6.098, P=0.014], lower rate of sexual dysfunction in males [6/15 vs. 76% (19/25), χ(2)=5.184, P=0.023], more harvested lateral lymph nodes [M (P25, P75): 9.5 (6.8, 15.3) vs. 6.0 (3.0, 9.0), Z=-2.849, P=0.004]. There was no significant difference in the positvie rate of lateral lymph nodes between the two groups [20% (6/30) versus 20.9% (9/43), χ(2)=0.009, P=0.923]. Three(4.1%) patients were lost during a median follow-up of 34 (1-66) months. The 3-year PFS and OS of the whole cohort were 69.5% and 88.3%, respectively. No significant difference in 3-year PFS rates (79.6% vs. 62.0%, P=0.172) and 3-year OS rates (91.2% vs. 85.9%, P=0.333) were observed between the fascia-oriented group and the vascular-oriented group (both P>0.05). Conclusion: Fascia-oriented LLND is associated with lower risk of postoperative urinary and male sexual dysfunction in patients with rectal carcinoma, and harvest of more lymph nodes, but no significant advantage in long-term survival.