CCTA based clinical value analysis of ΔCT-FFR in evaluating coronary artery function in patients with severe calcification / 解放军医学杂志

Objective To investigate the clinical value of coronary computed tomography angiography(CCTA)based CT derived fractional flow reserve(CT-FFR)and ΔCT-FFR in improving the diagnostic efficiency for coronary abnormal hemodynamics in patients with severe calcification.Methods We retrospectively analyzed the clinical data of coronary artery disease(CAD)patients who underwent CCTA,CT-FFR,invasive coronary angiography(ICA)and FFR during hospitalization from January 2018 to June 2019 in Chinese PLA General Hospital.Severe calcification was defined as coronary artery calcium score(CACS)≥100 on single vessel level.A total of 107 CAD patients with 149 coronary arteries were included in the present study.The enrolled coronary arteries were assigned to CACS≥100 group(n=56)and CACS<100 group(n=93).CT-FFR was performed on the deep FFR platform based on machine learning(ML)algorithms and ΔCT-FFR was defined as CT-FFR difference between proximal and distal to the coronary lesion.The correlation and consistency between CT-FFR and FFR values were analyzed by Pearson and Bland-Altman methods.We attempted to analyze the incremental value of ΔCT-FFR for coronary functional evaluation,especial for coronary arteries with severe calcification,regarding FFR≤0.8 as the diagnostic gold standard.Comparison of receiver operating characteristic curves(ROC)between different diagnostic methods was presented by Delong test.Results Pearson and Bland-Altman analyses showed appreciable correlation(CACS≥100 group,r=0.71,P<0.01;CACS<100 group,r=0.73,P<0.01)and consistency(CACS≥100 group,Mean=-0.01,P=0.25;CACS<100 group,Mean=0,P=0.96)between CT-FFR and FFR values in both groups.FFR(0.80±0.08 vs.0.84±0.09,P=0.004)and CT-FFR(0.81±0.06 vs.0.85±0.06,P<0.001)levels were significant lower in CACS≥100 group than those in CACS<100 group,while ΔCT-FFR(0.14±0.06 vs.0.09±0.06,P<0.001)levels were significant higher in CACS≥100 group.Moreover,the diagnostic efficiency of CT-FFR in CACS≥100 group was inferior to that in CACS<100 group[AUC=0.792(95%CI 0.663-0.889)vs.AUC=0.929(95%CI 0.856-0.972),P=0.04],while it achieved significant improvement after ΔCT-FFR adjustment[AUC=0.876(95%CI 0.760-0.949)vs.AUC=0.792(95%CI 0.663-0.889),P=0.02]and was similar to that in CACS<100 group(P=0.37).Conclusion For coronary arteries with severe calcification,CT-FFR demonstrated significant incremental value in improving the diagnostic efficiency of coronary abnormal hemodynamics after ΔCT-FFR adjustment.

Clinical prediction models of radiation-induced rectal injury after brachytherapy combined with external beam radiation therapy for cervical cancer / 中华放射医学与防护杂志

Objective:To explore the dosimetric differences of different dose accumulation method for brachytherapy combined with external beam radiation therapy (EBRT) of cervical cancer and establish clinical prediction models for radiation-induced late rectal injury (RLRI) after radiotherapy.Methods:A retrospective analysis was conducted for the clinical data of patients who received radical concurrent chemoradiotherapy (CCRT) for cervical cancer in the Department of Oncology of the Affiliated Hospital of North Sichuan Medical College from January 1, 2020 to November 30, 2021. EBRT combined with brachytherapy was employed for the patients, and dose assessment was performed in two means: the direct accumulation using equivalent dose in 2-Gy fractions (EQD2) and deformable image registration (DIR)-based dose accumulation of 3D planning images. The toxicity criteria of the Radiation Therapy Oncology Group were adopted as the RLRI grading criteria. The prediction models of RLRI using both dose assessment method were constructed. The areas under the receiver operating characteristic (ROC) curves were calculated to assess the predictive accuracy of the different dose assessment method.Results:In the case of brachytherapy, the D95% and D90% EQD2 doses to high-risk clinical target volumes (HR-CTVs) were 2.18 and 2.92 Gy higher respectively and the D2 cm 3, D1 cm 3, and D0.1 cm 3 EQD2 doses to the rectal were 1.74, 2.28, and 2.26 Gy higher, respectively compared to DIR-based dose accumulation ( t = 3.82, 5.21, 4.58, 5.17, 2.05, P < 0.05). For EBRT combined with brachytherapy, the D2 cm 3, D1 cm 3, and D0.1 cm 3 EQD2 doses to the rectal were 6.22, 7.61, 9.56 Gy higher than DIR-based doses, respectively, and the dosimetric differences were statistically significant ( t = 9.40, 10.59, 7.87, P < 0.001). The joint prediction model yielded an area under the ROC curve of 0.788. The sensitivity and specificity of the optimal cut-off value were 0.850 and 0.660, respectively. Furthermore, the Hosmer-Lemeshow goodness-of-fit tests indicated high goodness-of-fit ( P > 0.05). The prediction model for DIR-based dose accumulation of traditional predictors yielded areas under the ROC curves for D2 cm 3 and D1 cm 3 to the rectal of 0.784 and 0.763, respectively. The sensitivities of the optimal cut-off values were 0.850 and 0.750, respectively, and the specificities were 0.679 and 0.717, respectively. Conclusions:There are dosimetric differences between the direct dose accumulation using EQD2 and DIR-based dose accumulation of 3D planning images for brachytherapy combined with EBRT. Both the joint prediction model and the DIR-based dose accumulation of D2 cm 3 and D1 cm 3 to the rectal are effective in predicting RLRI. Given the complex calculation of the joint prediction model, it is recommended that RLRI should be predicted through DIR-based dose accumulation of D2 cm 3 and D1 cm 3 to the rectal clinically.

Ischemia-free liver transplantation improves the prognosis of recipients using functionally marginal liver grafts

Background/Aims@#The shortage of donor liver hinders the development of liver transplantation. This study aimed to clarify the poor outcomes of functionally marginal liver grafts (FMLs) and provide evidence for the improvement of ischemia-free liver transplantation (IFLT) after FML transplantation. @*Methods@#Propensity score matching was used to control for confounding factors. The outcomes of the control group and FML group were compared to demonstrate the negative impact of FMLs on liver transplantation patients. We compared the clinical improvements of the different surgical types. To elucidate the underlying mechanism, we conducted bioinformatic analysis based on transcriptome and single-cell profiles. @*Results@#FMLs had a significantly greater hazard ratio (HR: 1.969, P=0.018) than did other marginal livers. A worse 90-day survival (Mortality: 12.3% vs. 5.0%, P=0.007) was observed in patients who underwent FML transplantation. Patients who received FMLs had a significant improvement in overall survival after IFLT (Mortality: 10.4% vs 31.3%, P=0.006). Pyroptosis and inflammation were inhibited in patients who underwent IFLT. The infiltration of natural killer cells was lower in liver grafts from these patients. Bulk transcriptome profiles revealed a positive relationship between IL-32 and Caspase 1 (R=0.73, P=0.01) and between IL-32 and Gasdermin D (R=0.84, P=0.0012). @*Conclusions@#FML is a more important negative prognostic parameter than other marginal liver parameters. IFLT might ameliorate liver injury in FMLs by inhibiting the infiltration of NK cells, consequently leading to the abortion of IL-32, which drives pyroptosis in monocytes and macrophages.

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.

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.

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.

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.

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.

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.

Application of superficial peroneal artery perforator flap in tiled reconstruction of thumbs and fingers / 中华显微外科杂志

Objective:To summarise the clinical application and results of superficial peroneal artery perforator flaps in tiled reconstruction of thumbs and fingers.Methods:From June 2020 to June 2022, 8 patients with finger or thumb defects (4 thumbs, 2 index fingers and 2 middle fingers) received digit reconstruction in the Department of Hand Surgery, Suzhou Ruihua Orthopaedic Hospital. Two thumbs (2 patients) were reconstructed with a free partial hallux nail flap combined with a free perforator flap of superficial peroneal artery and an iliac bone graft, 1 thumb was reconstructed with a free partial hallux nail flap combined with a free perforator flap of superficial peroneal artery, 1 thumb and 2 middle fingers were reconstructed with free perforator flaps of superficial peroneal artery combined with iliac bone grafts, and 2 index fingers were reconstructed with lobulated free perforator flaps of superficial peroneal artery. The sizes of the flaps were 1.8 cm×3.2 cm-4.0 cm×10.0 cm. Lengths of iliac crest were 1.5-4.0 cm. The donor sites were directly sutured in 5 patients, skin grafts in 2 and superficial peroneal artery perforator flap reconstruction in 1 patient. Postoperative observations included survival of the digits and healing of the bone grafts. Monthly scheduled postoperative follow-ups were conducted at outpatient clinics and via telephone or WeChat reviews, covering function and appearance of the reconstructed digits, impact on the function and appearance of donor sites as well as the satisfaction of patients.Results:All 8 reconstructed digits survived in one stage and all the 5 bone grafts healed at 3 to 4 months after surgery. The mean postoperative follow-up period was 10 months, ranged 4 to 20 months. The texture of the reconstructed digits was close to that of the recipient site and good in elasticity, without purplish while in cold, nor ulceration, obvious bloating and pigmentation. Sensation of the digit pulps was recovered to S 2 to S 3, and the sensation in touch, pain and temperature were restored. TPD was not checked. There was no noticeable hyperplasia nor pain in the recipient and donor sites. There was no obvious hyperplasia or pain at the donor sites for the hallux nail flap, and the skin grafts or flaps in the donor sites survived well without ulceration or pain and the function of the donor feet were not affected. Functions of the reconstructed digits were assessed according to the Functional Assessment Criteria for Thumb and Finger Reconstruction of the Society for Evaluation Standard of Upper Limb Partial Functional of Hand Surgery of Chinese Medical Association, 4 patients achieved in excellent and 4 in good. According to the University of Michigan Hand Profile Questionnaire (MHQ), patient satisfaction was found very satisfied with 4 patients and satisfied with the other 4 patients. Conclusion:The superficial peroneal artery perforator flap has advantages of thin and large area with pleasant texture, better sensation recovery and less damage to the donor site. It is an ideal flap for reconstruction of thumbs and fingers.

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.

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.

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.

PK/PD model of Chuanxiong gel plaster in treatment of rheumatoid arthritis / 中国中药杂志

In this experiment, the PK/PD fitting model of Chuanxiong(Chuanxiong Rhizoma) in the treatment of rheumatoid arthritis was established in the form of acupoint combined with external application gel paste. Firstly, the rheumatoid arthritis model was induced by ovalbumin, and the articular fluid of rabbits was extracted by microdialysis. The pharmacokinetic process of Chuanxiong in rabbit articular fluid was analyzed by UPLC-MS/MS, and the pharmacokinetic model was established. The pharmacodynamic effects of Chuanxiong on inflammatory factors IL-1β, TNF-α, and IL-6 were analyzed by enzyme-linked immunosorbent assay(ELISA). The pharmacodynamic model was established, and the PK/PD model was obtained by fitting the data of pharmacokinetics and pharmacodynamics. The results of pharmacokinetics showed that the concentration of ligustrolide A in the articular cavity by drug administration on classical acupoint Zusanli(ST 36) was higher than that by Yanglingquan(GB 34), which reflected the advantage of typical acupoint, while ligustrazine concentration was higher after administration through Yanglingquan than through Zusanli, which was different from the traditional acupoint theory. The results of pharmacodynamics showed that the drug had lag effect. The PK/PD model was constructed by fitting the data. When IL-1β was taken as the efficacy index, the PK/PD models of Chuanxiong in typical acupoint Zusanli group, atypical acupoint Yanglingquan group, and non-acupoint group were E=115.28C_e/(3 316.72+C_e), E=108.73C_e/(2 993.47+C_e), and E=101.34C_e/(3 028.51+C_e). When TNF-α was taken as the efficacy index, the PK/PD models of Chuanxiong in typical acupoint Zusanli group, atypical acupoint Yanglingquan group, and non-acupoint group were E=68.31C_e/(3 285.16+C_e), E=59.27C_e/(2 919.86+C_e), and E=53.61C_e/(2 862.87+C_e). When IL-6 was taken as the efficacy index, the PK/PD models of Chuanxiong in typical acupoint Zusanli group, atypical acupoint Yanglingquan group, and non-acupoint group were E=59.92C_e/(3 461.17+C_e), E=58.34C_e/(2 723.51+C_e), and E=49.17C_e/(2 862.76+C_e). The parameters showed that there were significant differences in E_(max), EC_(e50) and k_(eo). The analysis of data found that the PK/PD fitting effect of Zusanli, a typical acupoint, was the best, which proved that it was still the best site for drug administration. To sum up, it shows that there may be bidirectional selectivity between drugs and acupoints.

Preliminary study on coronary artery interventional procedure assisted by guide wire and balloon assisted 360° twisting radial artery straightening technique / 中国介入心脏病学杂志

Objective Coronary arteriography(CAG)and percutaneous coronary intervention(PCI)are the most effective methods for the treatment of coronary atherosclerotic heart disease(CAD),but radial artery vascular variation,especially the presence of 360° tortuous(annular tortuous)radial artery seriously affects the success rate of trans-radial artery approach(TRA)interventional operation.This article provides a preliminary exploration of CAG and PCI through the annular tortuous radial artery.Methods We retrospectively analyzed 15 patients with annular tortuous right radial artery who successfully completed CAG or PCI by annular tortuous radial artery,and summarized the procedures performed through the annular tortuous radial artery.Results We found that the annular tortuous radial artery could be passed through by the catheter with the assistance of percutaneous transluminal coronary angioplasty(PTCA)guide wire or combined with a diameter of 2.0 mm balloon(6-8 atm dilatation state),and then the PTCA wire and the balloon can be replaced with a coronary angiography guide wire after the catheter passed through annular tortuous radial artery,and finally the annular tortuous radial artery could be straightened by fixing the coronary angiography guide wire and rotating and pulling the catheter.Finally,the catheter could be advanced to the coronary orifice and subsequent CAG or PCI could be performed while the annular tortuous radial artery was kept straightening.Both the left and right coronary arteries could perform coronary intervention using this technique,and there were no complications such as forearm hematoma or vascular rupture after this operation.Conclusions It is possible to successfully complete the coronary interventional therapy through annular tortuous radial artery by using the technique with the help of PTCA wire combined with balloon.

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.

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.

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.

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.