Ischemic stroke (IS) is a globally life-threatening disease. Presently, few therapeutic medicines are available for treating IS, and rt-PA is the only drug approved by the US Food and Drug Administration (FDA) in the US. In fact, many agents showing excellent neuroprotection but no blood flow-improving activity in animals have not achieved ideal clinical efficacy, while thrombolytic drugs only improving blood flow without neuroprotection have limited their wider application. To address these challenges and meet the huge unmet clinical need, we have designed and identified a novel compound AAPB with dual effects of neuroprotection and cerebral blood flow improvement. AAPB significantly reduced cerebral infarction and neural function deficit in tMCAO rats, pMCAO rats, and IS rhesus monkeys, as well as displayed exceptional safety profiles and excellent pharmacokinetic properties in rats and dogs. AAPB has now entered phase I of clinical trials fighting IS in China.

This study was performed to investigate the features of HBV-specific CD8+T cell reactivity in patients with chronic hepatitis B(CHB),HBV-induced liver cirrhosis(LC)or hepatocellular carcinoma(HCC).A total of 124 CHB patients,36 LC patients,and 114 HCC patients were enrolled in this study.The reactive HBV-specific CD8+T cells in peripheral blood were enumerated using an innovative ELISPOT system.In addition,19 CHB patients and 20 HCC patients were longitudinally monitored with an interval of 3-5 months.Data showed that the numbers of reactive HBV-specific CD8+T cells in CHB group were not significantly different from that in LC group,but obviously lower than that in HCC group(P=0.009 9),especially HBsAg-,HBpol-and HBe/cAg-specific CD8+T cells.In CHB group,the patients with normal ALT level,AST level,or low HBV-DNA load showed significantly more reactive HBV-specific CD8+T cells than the patients with abnormal ALT level,abnormal AST level,or high HBV-DNA load.Furthermore,the duration of NUCs treatment had an impact on the HBV-specific CD8+T cell reactivity in CHB patients,while different NUCs at the same treatment duration did not bring different reactivity of HBV-specific T cells.In LC group,the HBeAg-positive patients presented much more reactive HBV-specific CD8+T cells than the HBeAg-negative patients did.In HCC group,the numbers of reactive HBV-specific CD8+T cells in the patients with normal AFP level or normal DCP level were significantly higher than that in the patients with abnormal AFP level or abnormal DCP level.Longitudinal monitoring results showed that HBV-specific CD8+T cell reactivity displayed a slow upward trend in the CHB patients undergoing NUCs treatment,and an obvious increasing in the HCC patients undergoing combined treatment of targeted drugs and immunotherapy.Taken together,the features of HBV-specific CD8+T cell reactivity are distinct among the CHB,LC and HCC patients,and are influenced by virological indicators,tumor markers and treatment regimens.Therefore,more attention should be paid to the changes of HBV-specific CD8+T cell reactivity during clinical treatment.

Objective: To analyze the clinicopathological characteristics of 11 cases of chronic lymphocytic leukemia (CLL) with t (14;19) (q32;q13) . Methods: The case data of 11 patients with CLL with t (14;19) (q32;q13) in the chromosome karyotype analysis results of the Blood Diseases Hospital, Chinese Academy of Medical Sciences from January 1, 2018, to July 30, 2022, were retrospectively analyzed. Results: In all 11 patients, t (14;19) (q32;q13) involved IGH::BCL3 gene rearrangement, and most of them were accompanied by +12 or complex karyotype. An immunophenotypic score of 4-5 was found in 7 patients and 3 in 4 cases. We demonstrated that CLLs with t (14;19) (q32;q13) had a mutational pattern with recurrent mutations in NOTCH1 (3/7), FBXW7 (3/7), and KMT2D (2/7). The very-high-risk, high-risk, intermediate-risk, and low-risk groups consisted of 1, 1, 6, and 3 cases, respectively. Two patients died, 8 survived, and 2 were lost in follow-up. Four patients had disease progression or relapse during treatment. The median time to the first therapy was 1 month. Conclusion: t (14;19) (q32;q13), involving IGH::BCL3 gene rearrangement, is a rare recurrent cytogenetic abnormality in CLL, which is associated with a poor prognosis.
Humans ; Leukemia, Lymphocytic, Chronic, B-Cell/genetics* ; Retrospective Studies ; Translocation, Genetic ; Chromosome Aberrations ; Karyotyping

Objective: To evaluate the advantages and safety of Plerixafor in combination with granulocyte colony-stimulating factor (G-CSF) in autologous hematopoietic stem cell mobilization of lymphoma. Methods: Lymphoma patients who received autologous hematopoietic stem cell mobilization with Plerixafor in combination with G-CSF or G-CSF alone were obtained. The clinical data, the success rate of stem cell collection, hematopoietic reconstitution, and treatment-related adverse reactions between the two groups were evaluated retrospectively. Results: A total of 184 lymphoma patients were included in this analysis, including 115 cases of diffuse large B-cell lymphoma (62.5%) , 16 cases of classical Hodgkin's lymphoma (8.7%) , 11 cases of follicular non-Hodgkin's lymphoma (6.0%) , 10 cases of angioimmunoblastic T-cell lymphoma (5.4%) , 6 cases of mantle cell lymphoma (3.3%) , and 6 cases of anaplastic large cell lymphoma (3.3%) , 6 cases of NK/T-cell lymphoma (3.3%) , 4 cases of Burkitt's lymphoma (2.2%) , 8 cases of other types of B-cell lymphoma (4.3%) , and 2 cases of other types of T-cell lymphoma (1.1%) ; 31 patients had received radiotherapy (16.8%) . The patients in the two groups were recruited with Plerixafor in combination with G-CSF or G-CSF alone. The baseline clinical characteristics of the two groups were basically similar. The patients in the Plerixafor in combination with the G-CSF mobilization group were older, and the number of recurrences and third-line chemotherapy was higher. 100 patients were mobilized with G-CSF alone. The success rate of the collection was 74.0% for one day and 89.0% for two days. 84 patients in the group of Plerixafor combined with G-CSF were recruited successfully with 85.7% for one day and 97.6% for two days. The success rate of mobilization in the group of Plerixafor combined with G-CSF was substantially higher than that in the group of G-CSF alone (P=0.023) . The median number of CD34(+) cells obtained in the mobilization group of Plerixafor combined with G-CSF was 3.9×10(6)/kg. The median number of CD34(+) cells obtained in the G-CSF Mobilization group alone was 3.2×10(6)/kg. The number of CD34(+) cells collected by Plerixafor combined with G-CSF was considerably higher than that in G-CSF alone (P=0.001) . The prevalent adverse reactions in the group of Plerixafor combined with G-CSF were grade 1-2 gastrointestinal reactions (31.2%) and local skin redness (2.4%) . Conclusion: The success rate of autologous hematopoietic stem cell mobilization in lymphoma patients treated with Plerixafor combined with G-CSF is significantly high. The success rate of collection and the absolute count of CD34(+) stem cells were substantially higher than those in the group treated with G-CSF alone. Even in older patients, second-line collection, recurrence, or multiple chemotherapies, the combined mobilization method also has a high success rate of mobilization.
Humans ; Granulocyte Colony-Stimulating Factor/therapeutic use* ; Hematopoietic Stem Cell Mobilization/methods* ; Hematopoietic Stem Cell Transplantation ; Heterocyclic Compounds/adverse effects* ; Lymphoma/drug therapy* ; Lymphoma, T-Cell/therapy* ; Multiple Myeloma/drug therapy* ; Retrospective Studies ; Transplantation, Autologous

Objective: To compare the clinical features and the outcome of in-hospital mortality between patients with myocardial infarction with non-obstructive coronary arteries(MINOCA)and myocardial infarction with obstructive coronary artery disease (MI-CAD). Methods: This is a retrospective study. The clinical data of acute myocardial infarction (AMI) patients admitted to Qilu Hospital of Shandong University from January 2017 to May 2021, who underwent coronary angiography, were collected. Patients were divided into MINOCA group and MI-CAD group according to the degree of coronary stenosis (<50% or ≥50%). Baseline clinical characteristics, electrocardiograph during hospitalization, myocardial bridge, length of stay in hospital, discharge medication and the outcome of in-hospital mortality were collected and compared between the two groups. Univariate and multivariate logistic regression analysis was used to screen the related factors of MINOCA and the factors predicting the nosocomial death outcome of patients with AMI. Results: A total of 3 048 AMI patients were enrolled, age was 62 (54, 69) years, 741 (24.3%) patients were women including 165 patients (5.4%) in the MINOCA group and 2 883 patients (94.6%) in the MI-CAD group. Compared with MI-CAD patients, MINOCA patients were younger, had a higher proportion of females and a higher incidence of NSTEMI, and had a lower history of smoking, diabetes, coronary heart disease and myocardial infarction. Baseline inflammatory markers such as neutrophil count, monocyte count, neutrophil count/lymphocyte count (NLR), and monocyte count/high-density lipoprotein count (MHR) were lower, creatinine, N-terminal pro-brain B-type Natriuretic peptides (NT-proBNP), creatine kinase-MB, hypersensitive troponin I, fibrinogen, baseline blood glucose levels were lower, high-density lipoprotein cholesterol was higher, and the incidence of myocardial bridge, arrhythmia, tachycardia and atrial fibrillation was higher (P<0.05). The application rates of calcium antagonists and non-vitamin K antagonists oral anticoagulants were higher in MINOCA group (P<0.05), and there was no statistical difference in hospitalization days and in-hospital death between the two groups (P>0.05). Multiple logistic regression analysis showed that young age, female, non-smoker, no history of coronary heart disease and low MHR were risk factors of MINOCA (P<0.05). MINCOA was not associated with higher in-hospital death (P>0.05). Patients with AMI and a history of coronary heart disease, chronic renal failure, higher baseline blood glucose, higher NLR, and higher D-dimer were risk factors of in-hospital death (P<0.05). Conclusions: Compared with MI-CAD patients, MINOCA patients are younger, more likely to be female and non-smokers and on history of coronary heart disease, and have lower baseline MHR. MINOCA is often associated with myocardial bridge and atrial fibrillation. The incidence of in-hospital death in MINCOA patients is similar as in MI-CAD patients.
Atrial Fibrillation/complications* ; Blood Glucose ; Coronary Artery Disease/complications* ; Female ; Hospital Mortality ; Humans ; Lipoproteins, HDL ; MINOCA ; Male ; Myocardial Infarction/complications* ; Retrospective Studies

OBJECTIVE: To explore the clinical effect of the modified Topping-off technique in the treatment of multiple lumbar degenerative diseases. METHODS: From October 2019 to May 2020, 42 patients who underwent modified Topping-off operation (modified Topping-off group) and 42 patients who underwent multilevel total laminectomy and interbody fusion with screw rod system internal fixation (whole laminectomy group) were observed and analyzed. There were 15 males and 27 females in the modified Topping-off group, aged from 28 to 80 years old, with an average of (59.57±11.85)years old. There were 14 males and 28 females in the whole laminectomy group, aged from 45 to 82 years old, with an average of (64.26±9.19) years old. Visual analogue scale (VAS) and Oswestry Disability Index (ODI) were evaluated before operation, 1 week, 6 weeks and 12 weeks after operation. The intraoperative blood loss, incision length, operation time, postoperative drainage, weight-bearing time, hospitalization time, intervertebral space height, intervertebral foramen height and lumbar mobility were statistically analyzed. RESULTS: All patients were followed up for 12 weeks. The intraoperative blood loss and postoperative drainage in the modified Topping-off group were significantly less than those in the whole lamina group (P<0.05). The incision length, operation time, weight-bearing time and hospital stay in the modified Topping-off group were shorter than those in the whole lamina group(P<0.05). There were significant differences in intervertebral space height, intervertebral foramen height and lumbar mobility between the two groups at 12 weeks after operation(P<0.05). The modified Topping-off group had significantly lower VAS 1, 6, 12 weeks after operation and ODI 12 weeks after operation compared with rhose before operation. The VAS at 1, 6, 12 weeks in the whole lamina group were significantly lower those that before operation(P<0.05). The ODI at 12 weeks in the whole lamina group were significantly lower than those before operation(P<0.01). There were significant differences in VAS scores between the two groups at 1 week, 6 weeks and 12 weeks after operation(P<0.01). There was significant difference in ODI between the two groups 12 weeks after operation(P<0.01). CONCLUSION The application of modified Topping-off technique in the treatment of multi segmental lumbar degenerative diseases can reduce the total length of fusion segments, avoid or slow down the degeneration of adjacent segments, and has a positive effect on maintaining the normal movement of the spine.
Adult ; Aged ; Aged, 80 and over ; Bone Screws ; Female ; Humans ; Lumbar Vertebrae/surgery* ; Lumbosacral Region ; Male ; Middle Aged ; Spinal Fusion/methods* ; Technology

OBJECTIVE: To examine whether the combination of Naoxintong Capsule with standard care could further reduce the recurrence of ischemic stroke without increasing the risk of severe bleeding. METHODS: A total of 23 Chinese medical centers participated in this trial. Adult patients with a history of ischemic stroke were randomly assigned in a 1:1 ratio using a block design to receive either Naoxintong Capsule (1.2 g orally, twice a day) or placebo in addition to standard care. The primary endpoint was recurrence of ischemic stroke within 2 years. Secondary outcomes included myocardial infarction, death due to recurrent ischemic stroke, and all-cause mortality. The safety of drugs was monitored. Results were analyzed using the intention-to-treat principle. RESULTS: A total of 2,200 patients were enrolled from March 2015 to March 2016, of whom 143 and 158 in the Naoxintong and placebo groups were lost to follow-up, respectively. Compared with the placebo group, the recurrence rate of ischemic stroke within 2 years was significantly lower in the Naoxintong group [6.5% vs. 9.5%, hazard ratio (HR): 0.665, 95% confidence interval (CI): 0.492-0.899, P=0.008]. The two groups showed no significant differences in the secondary outcomes and safety, including rates of severe hemorrhage, cerebral hemorrhage and subarachnoid hemorrhage (P>0.05). CONCLUSION The combination of Naoxintong Capsule with standard care reduced the 2-year stroke recurrence rate in patients with ischemic stroke without increasing the risk of severe hemorrhage in high-risk patients. (Trial registration No. NCT02334969).
Adult ; Humans ; Secondary Prevention/methods* ; Ischemic Stroke ; Stroke/prevention & control* ; Cerebral Hemorrhage/complications* ; Double-Blind Method ; Platelet Aggregation Inhibitors

Consensus ; Critical Illness ; Humans ; Serum Albumin ; Serum Albumin, Human

Optimal vision and ergonomics are essential factors contributing to the achievement of good results during microsurgery. The three-dimensional (3D) digital image microscope system with a better 3D depth of field can release strain on the surgeon's neck and back, which can improve outcomes in microsurgery. We report a randomized prospective study of vasoepididymostomy and vasovasostomy using a 3D digital image microscope system (3D-DIM) in rats. A total of 16 adult male rats were randomly divided into two groups of 8 each: the standard operating microscope (SOM) group and the 3D-DIM group. The outcomes measured included the operative time, real-time postoperative mechanical patency, and anastomosis leakage. Furthermore, a user-friendly microscope score was designed to evaluate the ergonomic design and equipment characteristics of the microscope. There were no differences in operative time between the two groups. The real-time postoperative mechanical patency rates were 100.0% for both groups. The percentage of vasoepididymostomy anastomosis leakage was 16.7% in the SOM group and 25.0% in the 3D-DIM group; however, no vasovasostomy anastomosis leakage was found in either group. In terms of the ergonomic design, the 3D-DIM group obtained better scores based on the surgeon's feelings; in terms of the equipment characteristics, the 3D-DIM group had lower scores for clarity and higher scores for flexibility and adaptivity. Based on our randomized prospective study in a rat model, we believe that the 3D-DIM can improve surgeon comfort without compromising outcomes in male infertility reconstructive microsurgery, so the 3D-DIM might be widely used in the future.

BACKGROUND: Shenyankangfu Tablet (SYKFT) is a Chinese patent medicine that has been used widely to decrease proteinuria and the progression of chronic kidney disease. OBJECTIVE: This trial compared the efficacy and safety of SYKFT, for the control of proteinuria in primary glomerulonephritis patients, against the standard drug, losartan potassium. DESIGN, SETTING, PARTICIPANTS AND INTERVENTION: This was a multicenter, double-blind, randomized, controlled clinical trial. Primary glomerulonephritis patients, aged 18-70 years, with blood pressure ≤ 140/90 mmHg, estimated glomerular filtration rate (eGFR) ≥ 45 mL/min per 1.73 m MAIN OUTCOME MEASURES: The primary outcome was change in the 24-hour proteinuria level, after 48 weeks of treatment. RESULTS: A total of 735 participants were enrolled. The percent decline of urine protein quantification in the SYKFT group after 48 weeks was 8.78% ± 2.56% (P = 0.006) more than that in the losartan 50 mg group, which was 0.51% ± 2.54% (P = 1.000) less than that in the losartan 100 mg group. Compared with the losartan potassium 50 mg group, the SYKFT plus losartan potassium 50 mg group had a 13.39% ± 2.49% (P < 0.001) greater reduction in urine protein level. Compared with the losartan potassium 100 mg group, the SYKFT plus losartan potassium 100 mg group had a 9.77% ± 2.52% (P = 0.001) greater reduction in urine protein. With a superiority threshold of 15%, neither was statistically significant. eGFR, serum creatinine and serum albumin from the baseline did not change statistically significant. The average change in TCM syndrome score between the patients who took SYKFT (-3.00 [-6.00, -2.00]) and who did not take SYKFT (-2.00 [-5.00, 0]) was statistically significant (P = 0.003). No obvious adverse reactions were observed in any group. CONCLUSION: SYKFT decreased the proteinuria and improved the TCM syndrome scores of primary glomerulonephritis patients, with no change in the rate of decrease in the eGFR. SYKFT plus losartan potassium therapy decreased proteinuria more than losartan potassium therapy alone. TRIAL REGISTRATION NUMBER NCT02063100 on ClinicalTrials.gov.