The seat of human intelligence is the human cerebral cortex, which is responsible for our exceptional cognitive abilities. Identifying principles that lead to the development of the large-sized human cerebral cortex will shed light on what makes the human brain and species so special. The remarkable increase in the number of human cortical pyramidal neurons and the size of the human cerebral cortex is mainly because human cortical radial glial cells, primary neural stem cells in the cortex, generate cortical pyramidal neurons for more than 130 days, whereas the same process takes only about 7 days in mice. The molecular mechanisms underlying this difference are largely unknown. Here, we found that bone morphogenic protein 7 (BMP7) is expressed by increasing the number of cortical radial glial cells during mammalian evolution (mouse, ferret, monkey, and human). BMP7 expression in cortical radial glial cells promotes neurogenesis, inhibits gliogenesis, and thereby increases the length of the neurogenic period, whereas Sonic Hedgehog (SHH) signaling promotes cortical gliogenesis. We demonstrate that BMP7 signaling and SHH signaling mutually inhibit each other through regulation of GLI3 repressor formation. We propose that BMP7 drives the evolutionary expansion of the mammalian cortex by increasing the length of the neurogenic period.
Animals ; Mice ; Humans ; Ependymoglial Cells/metabolism* ; Hedgehog Proteins/metabolism* ; Ferrets/metabolism* ; Cerebral Cortex ; Neurogenesis ; Mammals/metabolism* ; Neuroglia/metabolism* ; Bone Morphogenetic Protein 7/metabolism*

Objective:To further improve the understanding of paroxysmal nocturnal hemoglobinuria (PNH), we retrospectively analyzed and summarized the clinical characteristics, treatment status, and survival status of patients with PNH in Zhejiang Province.Methods:This study included 289 patients with PNH who visited 20 hospitals in Zhejiang Province. Their clinical characteristics, comorbidity, laboratory test results, and medications were analyzed and summarized.Results:Among the 289 patients with PNH, 148 males and 141 females, with a median onset age of 45 (16-87) years and a peak onset age of 20-49 years (57.8% ). The median lactic dehydrogenase (LDH) level was 1 142 (604-1 925) U/L. Classified by type, 70.9% (166/234) were classical, 24.4% (57/234) were PNH/bone marrow failure (BMF), and 4.7% (11/234) were subclinical. The main clinical manifestations included fatigue or weakness (80.8%, 235/289), dizziness (73.4%, 212/289), darkened urine color (66.2%, 179/272), and jaundice (46.2%, 126/270). Common comorbidities were hemoglobinuria (58.7% ), renal dysfunction (17.6% ), and thrombosis (15.0% ). Moreover, 82.3% of the patients received glucocorticoid therapy, 70.9% required blood transfusion, 30.7% used immunosuppressive agents, 13.8% received anticoagulant therapy, and 6.3% received allogeneic hematopoietic stem cell transplantation. The 10-year overall survival (OS) rate was 84.4% (95% CI 78.0% -91.3% ) . Conclusion:Patients with PNH are more common in young and middle-aged people, with a similar incidence rate between men and women. Common clinical manifestations include fatigue, hemoglobinuria, jaundice, renal dysfunction, and recurrent thrombosis. The 10-year OS of this group is similar to reports from other centers in China.

The clinical manifestations of Japanese encephalitis virus infection are often acute encephalitis, and etiological diagnosis is a common diagnostic method. It is difficult to detect and isolate viruses clinically, and the types of pathogens detected are relatively limited. Metagenomics second-generation sequencing (mNGS) is a rapid and accurate molecular diagnostic method, which can improve the detection rate and types of pathogenic microorganisms. Pathogens uncommon in central nervous system infections can be detected. This paper reports a 27-year-old male patient with nausea and vomiting, high fever, disturbance of consciousness, and multiple organ failure as the main clinical manifestations. Japanese encephalitis virus was considered clinically, but etiological evidence was lacking. Japanese encephalitis virus was detected by cerebrospinal fluid mNGS, which greatly improved the accuracy of diagnosis of Japanese encephalitis virus infection.

Objective     To compare the clinical effects of coronary artery bypass grafting (CABG) via the left anterior small thoracotomy (LAST) versus lower-end sternal splitting (LESS) approach in the treatment of coronary heart disease. Methods     The patients who underwent LAST CABG in Tianjin Chest Hospital from October 2015 to December 2020 were allocated to an observation group (LAST group), and the patients who underwent LESS CABG at the same period were allocated to a LESS group. Propensity score matching method was applied with a ratio of 1∶1. The baseline data, perioperative data and grafts data were compared between the two groups after matching. Results     Before matching, there were 110 patients in the LAST group, and 206 patients in the LESS group. After matching, there were 110 patients in each group. In the LAST group, there were 83 males and 27 females with an average age of 60.6±8.3 years. In the LESS group, there were 80 males and 30 females with an average age of 61.0±9.6 years. There was no statistical difference in baseline data between the two groups after matching (P>0.05). The hospital stay time (t=2.255, P=0.025) and ventilator using time (t=−2.229, P=0.027) in the LAST group were significantly shorter than those in the LESS group. There were no statistical differences between the two groups in the postoperative hospital stay time, ICU stay time, postoperative left ventricular ejection fraction, postoperative left ventricular end-diastolic diameter, average number of grafts, secondary intubation, secondary thoracotomy, postoperative wound infection, sternal complications, postoperative atrial fibrillation, postoperative pulmonary infection or main adverse cardiovascular and cerebrovascular events (P>0.05). There was no statistical difference in the distribution of target vessels in the anterior descending branch, diagonal branch or posterior descending branch between the two groups (P>0.05). The grafts of the LAST group were significantly more than those of the LESS group in the area of obtuse marginal branch and posterior ventricular branch, and the grafts of the LESS group were significantly more than those of the LAST group in the area of right coronary artery (P<0.05). Post-operative computerized tomography angiography indicated that 1 patient in the LAST group had obtuse marginal branch vein bridge vessel occlusion, and the bridge vessels in the other patients were unobstructed. Conclusion     Minimally invasive CABG via both LAST and LESS approaches is safe and effective. LAST approach can achieve complete revascularization for multi-vessel lesions, and it is safe and reliable, with the advantages of less trauma and aesthetic appearance. However, it requires a certain learning curve of surgical techniques and certain surgical indications.

Cell Differentiation ; Humans ; Hyperthermia, Induced ; Stem Cells

Animals ; Chloroquine/pharmacology* ; Longevity ; Rats

Animals ; Antlers ; Exosomes ; Mesenchymal Stem Cells ; Osteoarthritis/therapy*

Objective:To compare the clinical outcome of navigation-assisted percutaneous cannulated screw fixation and posterior percutaneous plate fixation for Day type II crescent fracture dislocation of pelvis (CFDP).Methods:A retrospective cohort analysis was performed on clinical data of 40 patients with Day type II CFDP treated in General Hospital of Central Theater Command of PLA from January 2012 to June 2021. There were 23 males and 17 females, with age range of 42-73 years [(54.2±7.8)years]. A total of 19 patients were treated with navigation-assisted percutaneous cannulated screw fixation (navigation group) and 21 with posterior percutaneous plate fixation (plate group). The incision length, operation time, intraoperative blood loss and in-hospital time were compared between the two groups. The reduction quality was evaluated by Matta radiographic standard at day 2 after surgery. The functional recovery was assessed by Majeed functional score at 3 and 6 months after surgery. The postoperative complications were observed.Results:All patients were followed up for 10-24 months [(13.6±2.9)months]. The incision length, operation time, intraoperative blood loss and in-hospital time was (2.4±0.3)cm, (43.1±5.2)minutes, (48.4±18.4)ml and (14.4±1.9)days in navigation group, showing significant difference compared with plate group [(8.8±0.4)cm, (132.2±19.4)minutes, (302.9±57.5)ml, (18.9±3.7)days] (all P<0.01). According to Matta radiographic standard at day 2 after surgery, the excellent and good rate was 89% in navigation group (excellent in 13 patients, satisfactory in 4 and poor in 2) and 95% in plate group (excellent in 15 patients, satisfactory in 5 and poor in 1) ( P>0.05). According to Majeed criteria at 3 months after surgery, the excellent and good rate was 89% in navigation group (excellent in 12 patients, good in 5 and poor in 2) and 95% in plate group (excellent in 15 patients, good in 5 and poor in 1) ( P>0.05). According to Majeed criteria at 6 months after surgery, the excellent and good rate was 95% in navigation group (excellent in 14 patients, good in 4 and poor in 1) and 95% in plate group (excellent in 17 patients, good in 3 and poor in 1) ( P>0.05). There was no iatrogenic neurovascular injury. The incidence of complications was 11% (2/19) in navigation group, including one patients with sacroiliac screw loosening and one with posterior iliac screw penetrating the medial cortex of the bone, while that was 29% (6/21) in plate group, including two patients with skin tenderness, two with deep vein thrombosis in the lower extremity and two with incision infection ( P<0.05). Conclusions:For Day type II CFDP, both navigation-assisted percutaneous cannulated screw fixation and posterior percutaneous plate fixation can attain satisfactory efficacy, but the former has advantages of shorter operation time, less surgical trauma, less bleeding, shorter in-hospital time and lower incidence of complications.

Objective:To investigate the short-term efficacy of Shenmai injection combined with FOLFOX chemotherapy in the treatment of advanced gastric cancer and its effects on immune function and tumor markers. Methods:Eighty-two patients with advanced gastric cancer who received treatment in Shengzhou Hospital of Traditional Chinese Medicine, China between June 2018 and June 2020 were included in this study. They were randomly assigned to receive either FOLFOX chemotherapy (control group, n = 41) or Shenmai injection combined with FOLFOX chemotherapy (observation group, n = 41). All patients received three 21-day courses of treatment. Short-term efficacy of chemotherapy and improvement in quality of life were compared between the two groups. Immune function, expression of tumor markers (carcinoembryonic antigen and carbohydrate antigen 724) and adverse reactions were determined before and after three courses of treatment. Results:Total effective rate in the observation group was significantly higher than that in the control group [70.73% (29/41) vs. 46.34% (19/41), χ2 = 5.025, P < 0.05]. The proportion of patients had improved quality of life in the observation group was significantly higher than that in the control group [78.05% (32/41) vs. 56.10% (23/41), χ2 = 4.473, P < 0.05]. After three courses of treatment, the proportion of CD 3+ and CD 4+ cells and the ratio of CD 4+/CD 8+ cells in the observation group were (58.39 ± 3.14)%, (38.79 ± 2.35)% and (1.54 ± 0.17), respectively, which were significantly higher than those in the control group [(48.10 ± 3.01)%, (30.10 ± 1.78)%, (0.92 ± 0.15), t = 15.148, 18.875, 17.511, all P < 0.05]. After three courses of treatment, serum carcinoembryonic antigen and carbohydrate antigen 724 levels in the observation group were (6.98 ± 1.45) μg/L and (7.85 ± 1.76) μg/L, respectively, which were significantly lower than those in the control group [(15.47 ± 3.21) μg/L, (18.97 ± 3.25) μg/L), t = 15.434, 19.265, both P < 0.05). There was no significant difference in the incidence of adverse reactions between the two groups ( P > 0.05). Conclusion:Shenmai injection combined with FOLFOX chemotherapy in the treatment of advanced gastric cancer exhibits good short-term efficacy, can improve the immune function, and reduce the levels of carcinoembryonic antigen and carbohydrate antigen 724.

Medium spiny neurons (MSNs) in the striatum, which can be divided into D1 and D2 MSNs, originate from the lateral ganglionic eminence (LGE). Previously, we reported that Six3 is a downstream target of Sp8/Sp9 in the transcriptional regulatory cascade of D2 MSN development and that conditionally knocking out Six3 leads to a severe loss of D2 MSNs. Here, we showed that Six3 mainly functions in D2 MSN precursor cells and gradually loses its function as D2 MSNs mature. Conditional deletion of Six3 had little effect on cell proliferation but blocked the differentiation of D2 MSN precursor cells. In addition, conditional overexpression of Six3 promoted the differentiation of precursor cells in the LGE. We measured an increase of apoptosis in the postnatal striatum of conditional Six3-knockout mice. This suggests that, in the absence of Six3, abnormally differentiated D2 MSNs are eliminated by programmed cell death. These results further identify Six3 as an important regulatory element during D2 MSN differentiation.