Objective To explore the feasibility and clinical experience of the middle hepatic vein splitting-reconstruction technique in split liver transplantation from low-age donor livers. Methods A retrospective analysis was conducted on the cases of two low-age donor livers that underwent middle hepatic vein splitting-reconstruction, which were transplanted into four child recipients at the Liver Transplantation Center of the Third Affiliated Hospital of Sun Yat-sen University from January 2017 to July 2023. The surgical and postoperative conditions were summarized and analyzed. Results Donor 1 was a 6-year-old and 4-month-old girl with a body weight of 21 kg, and the obtained donor liver weighed 496 g. After splitting, the left and right liver weights were 201 g and 280 g, and transplanted into a 9-month-old boy weighing 6.5 kg and a 9-month-old boy weighing 7.5 kg, respectively. The graft to recipient weight ratio (GRWR) was 3.09% and 3.73%, respectively. Donor 2 was a 5-year-old and 8-month-old boy with a body weight of 19 kg, and the donor liver weighed 673 g. After splitting, the left and right liver weights were 230 g and 400 g, and transplanted into a 13-month-old girl weighing 9.5 kg and a 15-month-old boy weighing 12 kg. The GRWR was 2.42% and 3.33%, respectively. Both donor livers were split ex vivo, with the middle hepatic vein being completely split in the middle and reconstructed using allogeneic iliac vein and iliac artery vascular patches. According to GRWR, none of the 4 transplant livers were reduced in volume. Among the 4 recipients, one died due to postoperative portal vein thrombosis and non-function of the transplant liver, while the other three cases recovered smoothly without early or late complications. Regular follow-up was conducted until July 31, 2023, and liver function recovered well. Conclusions Under the premise of detailed assessment of the donor liver and meticulous intraoperative operation, as well as matching with suitable child recipients, low-age donor livers may be selected for splitting. The complete splitting and reconstruction of the middle hepatic vein in the middle may effectively ensure the adequate venous return of the left and right liver and provide sufficient functional liver volume.

Objective To explore the technical process and clinical application of laparoscopic combined upper midline incision minimally invasive liver transplantation. Methods A retrospective analysis was conducted on 30 cases of laparoscopic combined upper midline incision minimally invasive liver transplantation. The cases were divided into cirrhosis group (15 cases) and liver failure group (15 cases) based on the primary disease. The surgical and postoperative conditions of the two groups were compared. Results All patients successfully underwent laparoscopic "clockwise" liver resection, with no cases of passive conversion to open surgery or intolerance to pneumoperitoneum. In 6 cases, the right lobe was relatively large, and the right hepatic ligaments could not be completely mobilized. One case required an additional reverse "L" incision during open surgery. All patients successfully completed the liver transplantation, with no major intraoperative bleeding, cardiovascular events, or other occurrences in the 30 patients. The model for end-stage liver disease (MELD) score in the cirrhosis group was lower than that in the liver failure group (P<0.001). There were no statistically significant differences between the two groups in terms of age, surgical time, blood loss, anhepatic phase, or cold ischemia time (all P>0.05). During the perioperative period, there was 1 case of hepatic artery embolism, 1 case of portal vein anastomotic stenosis, no complications of hepatic vein and inferior vena cava, and 3 cases of biliary anastomotic stenosis, all of which occurred in the liver failure group. Conclusions In strictly selected cases, the minimally invasive liver transplantation technique combining laparoscopic hepatectomy with upper midline incision for graft implantation has the advantages of smaller incisions, less bleeding, relatively easier operation, and faster postoperative recovery, which is worthy of clinical promotion and application.

Objective To investigate the diagnosis and treatment strategy of the portal vein complications in children undergoing split liver transplantation. Methods The clinical data of 88 pediatric recipients who underwent split liver transplantation were retrospectively analyzed. Intraoperative anastomosis at the bifurcating site of the portal vein or donor iliac vein bypass anastomosis was performed depending on the internal diameter and development of the recipient's portal vein. A normalized portal venous blood stream monitoring was performed during the perioperative stage. After operation, heparin sodium was used to bridge warfarin for anticoagulation therapy. After portal vein stenosis or thrombosis was identified with enhanced CT or portography, managements including embolectomy, systemic anticoagulation, interventional thrombus removal, balloon dilatation and/or stenting were performed. Results Among the 88 recipients, a total of 10 children were diagnosed with portal vein complications, of which 4 cases were diagnosed with portal vein stenosis at 1 d, 2 months, 8 months, and 11 months after surgery, and 6 cases were diagnosed with portal vein thrombosis at intraoperative, 2 d, 3 d (n=2), 6 d, and 11 months after surgery, respectively. One patient with portal vein stenosis and one patient with portal vein thrombosis died perioperatively. The fatality related to portal vein complications was 2% (2/88). Of the remaining 8 patients, 1 underwent systemic anticoagulation, 2 underwent portal venous embolectomy, 1 underwent interventional balloon dilatation, and 4 underwent interventional balloon dilatation plus stenting. No portal venous related symptoms were detected during postoperative long term follow up, and the retested portal venous blood stream parameters were normal. Conclusions The normalized intra- and post-operative portal venous blood stream monitoring is a useful tool for the early detection of portal vein complications, the early utilization of useful managements such as intraoperative portal venous embolectomy, interventional balloon dilatation and stenting may effectively treat the portal vein complications, thus minimizing the portal vein complication related graft loss and recipient death.

ObjectiveDirected differentiation of human induced pluripotent stem cells （hiPSCs） into spinal cord γ-aminobutyric acid （GABA）-ergic progenitor cells were implanted into an decellularized optical nerve （DON） bioscaffold to construct a hiPSC-derived inhibitory neural network tissue with synaptic activities. This study aimed to provide a novel stem cell-based tissue engineering product for the study and the repair of central nervous system injury. MethodsThe combination of stepwise directional induction and tissue engineering technology was applied in this study. After hiPSCs were directionally induced into human neural progenitor cells （hNPCs） in vitro， they were seeded into a DON for three-dimensional culture， allowing further differentiation into inhibitory GABAergic neurons under the specific neuronal induction environment. Transmission electron microscopy and whole cell patch clamp technique were used to detect whether the hiPSCs differentiated neurons could form synapse-like structures and whether these neurons had spontaneous inhibitory postsynaptic currents， respectively， in order to validate that the hiPSC-derived neurons would form neural networks with synaptic transmission potentials from a structural and functional perspective. ResultsThe inhibitory neurons of GABAergic phenotype were successfully induced from hiPSCs in vitro， and maintained good viability after 28 days of culture. With the transmission electron microscopy， it was observed that many cell junctions were formed between hiPSC-derived neural cells in the three-dimensional materials， some of which presented a synapse- like structure， manifested as the slight thickness of cell membrane and a small number of vesicles within one side of the cell junctions， the typical structure of a presynatic component， and focal thickness of the membrane of the other side of the cell junctions， a typical structure of a postsynaptic component. According to whole-cell patch-clamp recording， the hiPSC-derived neurons had the capability to generate action potentials and spontaneous inhibitory postsynaptic currents were recorded in this biotissue. ConclusionsThe results of this study indicated that hiPSCs can be induced to differentiate into GABAergic progenitor cells in vitro and can successfully construct iPSC-derived inhibitory neural network tissue with synaptic transmission after implanted into a DON for three-dimensional culture. This study would provide a novel neural network tissue for future research and treatment of central nervous system injury by stem cell tissue engineering technology.

[This corrects the article DOI: 10.1016/j.apsb.2021.08.015.].

Entinostat plus exemestane in hormone receptor-positive (HR+) advanced breast cancer (ABC) previously showed encouraging outcomes. This multicenter phase 3 trial evaluated the efficacy and safety of entinostat plus exemestane in Chinese patients with HR + ABC that relapsed/progressed after ≥1 endocrine therapy. Patients were randomized (2:1) to oral exemestane 25 mg/day plus entinostat (n = 235) or placebo (n = 119) 5 mg/week in 28-day cycles. The primary endpoint was the independent radiographic committee (IRC)-assessed progression-free survival (PFS). The median age was 52 (range, 28-75) years and 222 (62.7%) patients were postmenopausal. CDK4/6 inhibitors and fulvestrant were previously used in 23 (6.5%) and 92 (26.0%) patients, respectively. The baseline characteristics were comparable between the entinostat and placebo groups. The median PFS was 6.32 (95% CI, 5.30-9.11) and 3.72 (95% CI, 1.91-5.49) months in the entinostat and placebo groups (HR, 0.76; 95% CI, 0.58-0.98; P = 0.046), respectively. Grade ≥3 adverse events (AEs) occurred in 154 (65.5%) patients in the entinostat group versus 23 (19.3%) in the placebo group, and the most common grade ≥3 treatment-related AEs were neutropenia [103 (43.8%)], thrombocytopenia [20 (8.5%)], and leucopenia [15 (6.4%)]. Entinostat plus exemestane significantly improved PFS compared with exemestane, with generally manageable toxicities in HR + ABC (ClinicalTrials.gov #NCT03538171).

Humans ; Consensus ; Hypersensitivity ; Desensitization, Immunologic/adverse effects* ; Immunotherapy/adverse effects* ; Injections, Subcutaneous ; Allergens

ObjectiveTo construct a neural network-like tissue with the potential of synaptic formation in vitro by seeding human induced pluripotent stem cell-derived neural precursor cells （hiPSC-NPCs） on decellularized optic nerve （DON）， so as to provide a promising approach for repair of nerve tissue injury. MethodsThrough directional induction and tissue engineering technology， human induced pluripotent stem cells （hiPSCs） and 3D DON scaffolds were combined to construct neural network-like tissues. Then the hiPSCs were directionally induced into human neural precursor cells （hNPCs） and neurons. Immunofluorescence staining was used to identify cell differentiation efficiency. 3D DON scaffolds were prepared. Morphology and cytocompatibility of scaffolds were identified by scanning electron microscopy and Tunnel staining. Induced hiPSC-NPCs were seeded on DON scaffolds. Immunofluorescence staining， scanning electron microscopy， transmission electron microscopy and patch clamp were used to observe the morphology and functional identification of constructed neural network tissues. Results①The results of immunofluorescence staining suggested that most of hiPSC-NPCs differentiated into neurons in vitro. We had successfully constructed a neural network dominated by neurons. ② The results of scanning electron microscopy and immunohistochemistry suggested that a neural network-like tissue with predominating excitatory neurons in vitro was successfully constructed. ③The results of immunohistochemical staining， transmission electron microscopy and patch clamp indicated that the neural network-like tissue had synaptic transmission function. ConclusionA neural network-like tissue mainly composed of excitatory neurons has been constructed by the combination of natural uniform-channel DON scaffold and hiPSC-NPCs， which has the function of synaptic transmission. This neural network plays a significant role in stem cell derived replacement therapy， and offers a promising prospect for repair of spinal cord injury （SCI） and other neural tissue injuries.

As a large family of transcription factors, the MYB family plays a vital role in regulating flower development. We studied the MYB family members in Lonicera macranthoides for the first time and identified three sequences of 1R-MYB, 47 sequences of R2R3-MYB, two sequences of 3R-MYB, and one sequence of 4R-MYB from the transcriptome data. Further, their physicochemical properties, conserved domains, phylogenetic relationship, protein structure, functional information, and expression were analyzed. The results show that the 53 MYB transcription factors had different conserved motifs, physicochemical properties, structures, and functions in wild type and 'Xianglei' cultivar of L. macranthoides, indicating their conservation and diversity in evolution. The transcript level of LmMYB was significantly different between the wild type and 'Xianglei' cultivar as well as between flowers and leaves, and some genes were specifically expressed. Forty-three out of 53 LmMYB sequences were expressed in both flowers and leaves, and 9 of the LmMYB members showed significantly different transcript levels between the wild type and 'Xianglei' cultivar, which were up-regulated in the wild type. The results provide a theoretical basis for further studying the specific functional mechanism of the MYB family.
Transcription Factors/metabolism* ; Lonicera/metabolism* ; Phylogeny ; Plant Proteins/metabolism* ; Gene Expression Regulation, Plant

ObjectiveTo explore the effect of sleep deprivation on vestibular function in normal adults. MethodsThe Pittsburgh sleep quality index （PSQI） and basic data were collected and recorded before the experiment. The 38 medical workers in the experimental group were examined by cervical vestibular evoked myogenic potential （cVEMP）， ocular vestibular evoked myogenic potential， （oVEMP） and video-head impulse test （vHIT） to check vestibular function after normal sleep and night shift， respectively， and the results were compared for their own control. At the same time， 20 normal adults were selected as the control group， and vestibular evoked myogenic potentials （VEMPs） were performed to check vestibular function for comparative analysis between groups. Results①The difference in PSQI scores between the 38 health workers and the control group was statistically significant （P<0.05）. The test group had 11 sleep disorders （ PSQI score >7） ； ②In the sleep deprivation state， the abnormal rate of oVEMP was higher than that of normal sleep （P = 0.02）， the abnormal rate of cVEMP tended to increase， and the rate of interaural asymmetry of cVEMP and oVEMP was higher than that of normal sleep （P < 0.05）， while no significant difference was seen in the abnormal rate of vHIT （P > 0.05）； ③Among the 38 healthcare workers， subjects prone to vestibular function abnormalities （abnormal group） had a higher number of years of service and number of night shift days per month than those without vestibular function abnormalities （normal group） （P < 0.05）. In the abnormal group， there were 5 cases of left-sided amplitude decrease （71%） and 2 cases of right-sided amplitude decrease （29%） in cVEMP； there were 13 cases of left-sided amplitude decrease （76%） and 4 cases of right-sided amplitude decrease （24%） in oVEMP； ④In the same normal sleep state， cVEMP performance in the test group showed statistically significant differences in prolonged P1 latency and interwave period compared with the control group （P < 0.05）. The oVEMP performance of the test group showed statistically significant differences （P < 0.05） in the prolongation of N1 latency and interwave period compared with the control group， manifested by the prolongation of latency and interwave period， and the remaining parameters did not show significant differences （P>0.05）. Conclusions①Sleep deprivation has potential， cumulative damage to otolithic function； ② Long working years and high number of night shifts per month are risk factors for sleep deprivation affecting individual vestibular function； ③Vestibular evoked myogenic potentiometry may serve as a screening tool to determine sleep-related vestibular impairment. The results of vestibular evoked myogenic potentials are more reliable when performed in a state of good recent sleep quality.