Objective To evaluate the bioequivalence and safety of two cilostazol tablets 50 mg in healthy Chinese subjects.Methods This study was an open-lable,randomized,two-period crossover design.A total of 32 subjects respectively for fasting state were given a single oral dose of test or reference tedizolid phosphate tablets 50 mg.The plasma concentration of cilostazol was determined by liquid chromatography tandem mass spectrometry(LC-MS/MS),and the concentration-time data was processed by SAS 9.4,the model method of the non-compartmental was used to calculate the pharmacokinetic parameters of tedizolid and to evaluate the bioequivalence.Results The Cmax of cilostazol test and reference were(358.10±125.80)and(346.90±115.30)ng·mL-1;tmax were 3.50 and 4.00 h;t1/2 were(9.63±7.12)and(8.57±5.15)h;AUC0_twere(5 235.00±2 268.00)and(5 190.00±1 747.00)h·ng·mL-1;AUC0-∞ were(5 377.00±2 367.00)and(5 308.00±1 848.00)h·ng·mL-1.The 90％confidence intervals of the geometric mean ratios of the main pharmacokinetic parameters of the test drug and reference drug were within the range of 80.00％to 125.00％.Conclusion Single oral test and reference cilostazol tablets were bioequivalent and safe in healthy Chinese subjects.

Objective: To examine the safety and effectiveness of inflatable video-assisted mediastinoscopic transhiatal esophagectomy (IVMTE). Methods: Totally 269 patients admitted to the Anhui Provincial Hospital of Anhui Medical University who underwent IVMTE (IVMTE group, n=47) or thoracoscopy combined with minimally invasive Mckeown esophageal cancer resection (MIME group, n=222) from September 2017 to December 2021 were analyzed retrospectively. There were 31 males and 16 females in IVMTE group, aged (68.6±7.5) years (range: 54 to 87 years). There were 159 males and 63 females in MIME group, aged (66.8±8.8) years (range: 42 to 93 years). A 1∶1 match was performed on both groups by propensity score matching, with 38 cases in each group. The intraoperative conditions and postoperative complication rates of the two groups were compared by t test, Wilcoxon rank, χ² test, or Fisher exact probability method. Results: Patients in IVMTE group had less intraoperative bleeding ((96.0±39.2) ml vs. (123.8±49.3) ml, t=-2.627, P=0.011), shorter operation time ((239.1±47.3) minutes vs. (264.2±57.2) minutes, t=-2.086, P=0.040), and less drainage 3 days after surgery (85(89) ml vs. 675(573) ml, Z=-7.575, P<0.01) compared with that of MIME group. There were no statistically significant differences between the two groups in terms of drainage tube-belt time, postoperative hospital stay, and lymph node dissection stations and numbers (all P>0.05). The incidence of Clavien-Dindo grade 1 to 2 pulmonary infection (7.9%(3/38) vs. 31.6%(12/38), χ²=6.728, P=0.009), total complications (21.1%(8/38) vs. 47.4%(18/38), χ²=5.846, P=0.016) and total lung complications (13.2%(5/38) vs. 42.1%(16/38), χ²=7.962, P=0.005) in the IVMTE group were significantly lower. Conclusion: Inflatable video-assisted mediastinoscopic transhiatal esophagectomy combined with laparoscopic esophagectomy is safe and feasible, which can reach the same range of oncology as thoracoscopic surgery.
Male ; Female ; Humans ; Retrospective Studies ; Esophagectomy/methods* ; Treatment Outcome ; Laparoscopy ; Thoracoscopy ; Lymph Node Excision/methods* ; Esophageal Neoplasms/surgery* ; Postoperative Complications

This article focused on the significant public health issue of comorbidities in the elderly population and highlighted the important role of traditional Chinese medicine(TCM) in the prevention and treatment of comorbidities in the elderly. It suggested that TCM should fully utilize its advantages in holistic perspective, syndrome differentiation and treatment, and preventive medicine in the process of preventing and treating comorbidities in the elderly. At the same time, in response to the significant shift in the disease spectrum of the elderly, the increasingly innovative concepts in diagnosis and treatment, the growing demand for proactive health by the el-derly population, and the current emphasis on patient-centered evaluation standards, it is necessary to further conduct basic theoretical and experimental research on comorbidities in the elderly using TCM, emphasize clinical research on comorbidities in the elderly, explore appropriate efficacy evaluation systems, improve TCM prevention and treatment strategies and comprehensive intervention programs for comorbidities in the elderly, and leverage the unique role of TCM in the rehabilitation of elderly comorbidity patients. By analyzing the potential of TCM in the field of comorbidities in the elderly, this article is expected to provide new insights for future clinical practice and scientific research.
Aged ; Humans ; Medicine, Chinese Traditional ; Public Health ; Comorbidity ; Drugs, Chinese Herbal/therapeutic use*

Objective: To evaluate the predictive value of the proportion of hibernating myocardium (HM) in total perfusion defect (TPD) on reverse left ventricle remodeling (RR) after coronary artery bypass graft (CABG) in patients with heart failure with reduced ejection fraction (HFrEF) by ^99mTc-methoxyisobutylisonitrile (MIBI) single photon emission computed tomography (SPECT) myocardial perfusion imaging (MPI) combined with ¹⁸F-flurodeoxyglucose (FDG) gated myocardial imaging positron emission computed tomography (PET). Methods: Inpatients diagnosed with HFrEF at the Cardiac Surgery Center, Anzhen Hospital of Capital Medical University from January 2016 to January 2022 were prospectively recruited. MPI combined with ¹⁸F-FDG gated PET was performed before surgery for viability assessment and the patients received follow-up MPI and ¹⁸F-FDG gated PET at different stages (3-12 months) after surgery. Δ indicated changes (post-pre). Left ventricular end-systolic volume (ESV) reduced at least 10% was defined as RR, patients were divided into reverse remodeling (RR+) group and the non-reverse group (RR-). Binary logistic regression analysis was used to identify predictors of RR. Receiver operating characteristic (ROC) curve analysis was performed and the area under the curve (AUC) was calculated to assess the cut-off value for predicting RR. Additionally, we retrospectively enrolled inpatients with HFrEF at the Cardiac Surgery Center, Anzhen Hospital of Capital Medical University from January 2021 to January 2022 as the validation group, who underwent MPI and ¹⁸F-FDG gated PET before surgery. Echocardiography was performed before CABG and after CABG (3-12 months). In the validation group, the reliability of obtaining the cut-off value for the ROC curve was verified. Results: A total of 28 patients with HFrEF (26 males; age (56.9±8.7) years) were included in the prospective cohort. HM/TPD was significantly higher in the RR+ group than in the RR- group ((51.8%±17.9%) vs. (35.7%±13.9%), P=0.016). Binary logistic regression analysis revealed that HM/TPD was an independent predictor of RR (Odds ratio=1.073, 95% Confidence interval: 1.005-1.145, P=0.035). ROC curve analysis revealed that HM/TPD=38.3% yielded the highest sensitivity, specificity, and accuracy (all 75%) for predicting RR and the AUC was 0.786 (P=0.011). Meanwhile, a total of 100 patients with HFrEF (90 males; age (59.7±9.6) years) were included in the validation group. In the validation group, HM/TPD=38.3% predicted RR in HFrEF patients after CABG with the highest sensitivity, specificity and accuracy (82%, 60% and 73% respectively). Compared with the HFrEF patients in the HM/TPD<38.3% group (n=36), RR and cardiac function improved more significantly in the HM/TPD≥38.3% group (n=64) (all P<0.05). Conclusions: Preoperative HM/TPD ratio is an independent factor for predicting RR in patients with HFrEF after CABG, and HM/TPD≥38.3% can accurately predict RR and the improvement of cardiac function after CABG.
Male ; Humans ; Middle Aged ; Aged ; Stroke Volume ; Heart Failure ; Fluorodeoxyglucose F18 ; Retrospective Studies ; Reproducibility of Results ; Prospective Studies ; Coronary Artery Bypass ; Ventricular Dysfunction, Left ; Tomography, Emission-Computed, Single-Photon ; Perfusion ; Myocardium

Objective: To investigate the relationship between the examined number of lymph nodes at the N1 station and the clinicopathological characteristics and prognosis of patients with pT1-3N0M0 non-small cell lung cancer (NSCLC). Methods: A total of 337 patients with pT1-3N0M0 NSCLC who underwent radical lung cancer surgery at the Provincial Hospital Affiliated to Anhui Medical University from January 2013 to March 2015 were selected. The receiver operating characteristic (ROC) curve analysis was used to determine the optimal cut-off value for predicting 5-year survival in pT1-3N0M0 NSCLC patients by the examined number of lymph nodes at the N1 station. The relationships between the examined number of lymph nodes at the N1 station and the clinicopathological characteristics and prognosis of patients with pT1-3N0M0 NSCLC were analyzed according to the optimal cut-off group. Results: A total of 1 321 lymph nodes at N1 station were examined in 337 patients, with a mean of 3.9 nodes per patient. The median survival time was 42.0 months, with 1-, 3- and 5-year survival rates of 82.2%, 57.1% and 24.9%, respectively. ROC curve analysis showed that the optimal cut-off value of 4.5 lymph nodes examined at the N1 station was used to predict 5-year survival in patients with pT1-3N0M0 NSCLC. After rounding off the number, the number of lymph nodes examined at the N1 station was 5 as the cut-off value, and the patients were divided into the group with <5 lymph nodes examined (212 cases) and the group with ≥5 lymph nodes examined (125 cases). The proportion of patients received adjuvant chemotherapy was 19.2% in the group with ≥5 lymph nodes examined, which was higher than 9.0% in the group with <5 lymph nodes examined (P=0.007), and the differences in other clinicopathological characteristics between the two groups were not statistically significant (P>0.05). The median survival time for patients in the group with <5 lymph nodes examined was 38.0 months, with 1-, 3- and 5-year survival rates of 80.1%, 52.5% and 15.6%, respectively. The median survival time for patients in the group with ≥5 lymph nodes examined was 48.0 months, and the 1-, 3- and 5-year survival rates were 85.6%, 64.0% and 36.0%, respectively. The survival rate of patients in the group with ≥5 lymph nodes examined was better than that in the group with <5 lymph nodes examined (P=0.002). Multifactorial Cox regression analysis showed that T stage (OR=1.408, 95% CI: 1.118-1.670) and the examined number of lymph nodes at N1 station (OR=0.670, 95% CI: 0.526-0.853) were independent influence factors for the prognosis of pT1-3N0M0 NSCLC patients. Conclusion: The examined number of lymph nodes at the N1 station is associated with the prognosis of patients with pT1-3N0M0 NSCLC, and the examination of at least 5 lymph nodes at N1 station at the time of postoperative pathological examination improves the 5-year survival rate of patients.
Carcinoma, Non-Small-Cell Lung/surgery* ; Humans ; Lung Neoplasms/surgery* ; Lymph Nodes/surgery* ; Lymphatic Metastasis/pathology* ; Neoplasm Staging ; Prognosis ; Retrospective Studies

ObjectiveTo explore the application of simultaneous bilateral uniportal video-assisted thoracic surgery in the treatment of bilateral multiple pulmonary nodules. MethodsThe clinical and pathological characteristics ， and perioperative data were analyzed in thoracic surgery from August 2021 to August 2021 at Department of Thoracic Surgery， the First Affiliated Hospital of University of Science and Technology of China. During the study period， 40 patients were included in the study， of which 12 were male， 28 were female， the average age was （52±8.8） ［52.5（47.25～58）］ years. ResultsA total of 107 nodules were resected， with 85 malignancy nodules， including 30 patients with bilateral primary lung cancer， 6 patients with primary lung cancer on one side. All patients underwent bilateral uniportal video-assisted thoracoscopic surgery （Uni-portal VATS）， the average intraoperative blood loss was （48.87±19.29） ［40（30～67.5）］ mL， the average operation time was （147.70±54.24） ［145（113.5～170）］ min， the average number of resected lymph nodes was （6.20±9.13） ［3（0～12）］，the average NRS score in the 1^th postoperative day was （5.08±2.23）， the average pleural drainage was （375.95±243.69） ［292.5（215.0～517.5）］ mL. the average thoracic drainage time was（3.38±1.49） ［3（3～4）］ days， and the average postoperative hospital stay was （4.08±1.81） ［4（3～5）］ days. Postoperative complications including： 2 cases of infection， 3 cases of atrial fibrillation， 1 case of hemoptysis for more than 1 week and 1case of persistent air leakage for more than 3 days. All of them improved after treatment， and there were no serious complications and deaths in perioperative period. ConclusionSimultaneous bilateral pulmonary resections via uniportal VATS is a safe and feasible minimally invasive procedure for patients with bilateral multiple pulmonary nodules.

Objective: Exposure to microgravity results in postflight cardiovascular deconditioning in astronauts. Vascular oxidative stress injury and mitochondrial dysfunction have been reported during this process. To elucidate the mechanism for this condition, we investigated whether mitochondrial oxidative stress regulates calcium homeostasis and vasoconstriction in hindlimb unweighted (HU) rat cerebral arteries. Methods: Three-week HU was used to simulate microgravity in rats. The contractile responses to vasoconstrictors, mitochondrial fission/fusion, Ca Results: An increase of cytoplasmic Ca Conclusion The present results suggest that mitochondrial oxidative stress enhances cerebral vasoconstriction by regulating calcium homeostasis during simulated microgravity.
Animals ; Calcium/metabolism* ; Cerebral Arteries ; Homeostasis ; Male ; Mitochondria/physiology* ; Myocytes, Smooth Muscle/physiology* ; Oxidative Stress ; Rats ; Rats, Sprague-Dawley ; Vasoconstriction/physiology* ; Weightlessness Simulation

OBJECTIVE: Plant-derived cytotoxic transgene expression, such as trichosanthin (tcs), regulated by recombinant adeno-associated virus (rAAV) vector is a promising cancer gene therapy. However, the cytotoxic transgene can hamper the vector production in the rAAV producer cell line, human embryonic kidney (HEK293) cells. Here, we explored microRNA-122 (miR122) and its target sequence to limit the expression of the cytotoxic gene in the rAAV producer cells. METHODS: A miR122 target (122T) sequence was incorporated into the 3' untranslated region of the tcs cDNA sequence. The firefly luciferase (fluc) transgene was used as an appropriate control. Cell line HEK293-mir122 was generated by the lentiviral vector-mediated genome integration of the mir122 gene in parental HEK293 cells. The effects of miR122 overexpression on cell growth, transgene expression, and rAAV production were determined. RESULTS: The presence of 122T sequence significantly reduced transgene expression in the miR122-enriched Huh7 cell line (in vitro), fresh human hepatocytes (ex vivo), and mouse liver (in vivo). Also, the normal liver physiology was unaffected by delivery of 122T sequence by rAAV vectors. Compared with the parental cells, the miR122-overexpressing HEK293-mir122 cell line showed similar cell growth rate and expression of transgene without 122T, as well as the ability to produce liver-targeting rAAV vectors. Fascinatingly, the yield of rAAV vectors carrying the tcs-122T gene was increased by 77.7-fold in HEK293-mir122 cells. Moreover, the tcs-122T-containing rAAV vectors significantly reduced the proliferation of hepatocellular carcinoma cells without affecting the normal liver cells. CONCLUSION HEK293-mir122 cells along with the 122T sequence provide a potential tool to attenuate the cytotoxic transgene expression, such as tcs, during rAAV vector production.
Animals ; Dependovirus/genetics* ; Genetic Therapy ; Genetic Vectors/genetics* ; HEK293 Cells ; Humans ; Mice ; MicroRNAs/genetics* ; Trichosanthin

Tung tree (Vernicia fordii) is an economically important woody oil plant that produces tung oil rich in eleostearic acid. Here, we report a high-quality chromosome-scale genome sequence of tung tree. The genome sequence was assembled by combining Illumina short reads, Pacific Bio-sciences single-molecule real-time long reads, and Hi-C sequencing data. The size of tung tree gen-ome is 1.12 Gb, with 28,422 predicted genes and over 73％ repeat sequences. The V. fordii underwent an ancient genome triplication event shared by core eudicots but no further whole-genome duplication in the subsequent ca. 34.55 million years of evolutionary history of the tung tree lineage. Insertion time analysis revealed that repeat-driven genome expansion might have arisen as a result of long-standing long terminal repeat retrotransposon bursts and lack of efficient DNA deletion mechanisms. The genome harbors 88 resistance genes encoding nucleotide-binding sites;17 of these genes may be involved in early-infection stage of Fusarium wilt resistance. Further, 651 oil-related genes were identified, 88 of which are predicted to be directly involved in tung oil biosynthesis. Relatively few phosphoenolpyruvate carboxykinase genes, and synergistic effectsbetween transcription factors and oil biosynthesis-related genes might contribute to the high oil content of tung seed. The tung tree genome constitutes a valuable resource for understanding genome evolution, as well as for molecular breeding and genetic improvements for oil production.

BACKGROUNDPlasmacytoid dendritic cells (pDCs) and cytokines play an important role in occurrence and recovery of hepatitis B virus (HBV) infection. The aim of this study was to explore the frequency and function of pDC and serum cytokine network profiles in patients with acute or chronic HBV infection.

METHODSThe healthy individuals (HI group), hepatitis B envelope antigen (HBeAg)-positive chronic HBV patients in immune tolerance (IT) phase (IT group), HBeAg-positive chronic HBV patients (CHB group), and acute HBV patients (AHB group) were enrolled in this study. The frequency of cluster of differentiation antigen 86 (CD86) + pDC and the counts of CD86 molecular expressed on surface of pDC were tested by flow cytometer. The quantitative determinations of cytokines, including Fms-like tyrosine kinase 3 ligand (Flt-3L), interferon (IFN)-α2, IFN-γ, interleukin (IL)-17A, IL-6, IL-10, transforming growth factor (TGF)-β1 and TGF-β2, were performed using Luminex multiplex technology.

RESULTSIn this study, there were 13 patients in HI group, 30 in IT group, 50 in CHB group, and 32 in AHB group. Compared with HI group, HBV infected group (including all patients in IT, CHB and AHB groups) had significantly higher counts of CD86 molecular expressed on the surface of pDC (4596.5 ± 896.5 vs. 7097.7 ± 3124.6; P < 0.001). The counts of CD86 molecular expressed on the surface of pDC in CHB group (7739.2 ± 4125.4) was significantly higher than that of IT group (6393.4 ± 1653.6, P = 0.043). Compared with IT group, the profile of cytokines of Flt-3L, IFN-γ, and IL-17A was decreased, IFN-α2 was significantly increased (P = 0.012) in CHB group. The contents of IL-10, TGF-β1, and TGF-β2 in AHB group were significantly increased compared with IT and CHB groups (all P < 0.05).

CONCLUSIONSThis study demonstrated that the function of pDC was unaffected in HBV infection. The enhanced function of pDC and IFN-α2 might involve triggering the immune response from IT to hepatitis active phase in HBV infection. Acute patients mainly presented as down-regulation of the immune response by enhanced IL-10 and TGF-β.