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Background: Hyperlipidaemic acute pancreatitis (HLAP) has become the most common cause of acute pancreatitis (AP) not due to gallstones or alcohol (Mosztbacher et al, Pancreatology 20:608-616, 2020; Yin et al, Pancreas 46:504-509, 2017). Therapeutic plasma exchange (TPE) has been reported to be effective in reducing serum TG levels which is important in management of HLAP (World J Clin Cases 9:5794-803, 2021). However, studies on TPE are mostly focusing on cases reports, TPE remains poorly evaluated till date and need to be compared with conservative therapy with a well-designed study. Methods: A retrospectively cohort study on HLAP patients between January 2003 and July 2023 was conducted. Factors correlated with efficacy of TPE were included in a propensity model to balance the confounding factors and minimize selection bias. Patients with and without TPE were matched 1:2 based on the propensity score to generate the compared groups. Lipid profiles were detected on admission and consecutive 7 days. The triglyceride (TG) level decline rates, percentage of patients to reach the target TG levels, early recurrence rate, local complications and mortality were compared between groups. Results: A total of 504 HLAP patients were identified. Since TPE was scarcely performed on patients with TG < 11.3 mmol/L, 152 patients with TG level 5.65 to 11.3 mmol/L were excluded while 352 with TG ≧11.3 mmol/L were enrolled. After excluding 25 cases with incomplete data or pregnancy, 327 patients, of whom 109 treated without TPE while 218 treated with TPE, were included in data analysis. One-to-two propensity-score matching generated 78 pairs, 194 patients with well-balanced baseline characteristics. Of 194 patients enrolled after matching done, 78 were treated without while 116 with TPE. In the matched cohort (n = 194), patients treated with TPE had a higher TG decline rate in 48 h than those without TPE (70.00% vs 54.00%, P = 0.001); the early recurrence rates were 8.96% vs 1.83%, p = 0.055. If only SAP patients were analyzed, the early recurrence rates were 14.81% vs 0.00% (p = 0.026) respectively. For patients with CT severity index (CTSI) rechecked within 14 days, early CTSI improment rate were 40.90% vs 31.91%. Local complications checked 6 months after discharge were 44.12% vs 38.30%. Mortality was 1.28% vs 1.72%. No differences were found in early stage CTSI improment rate (P =.589), local complications (P =.451) or motality between two groups. Conclusions: TPE reduces TG levels more quickly in 48 h compared with those with conservative treatment, but no difference in the consecutive days. TPE tends to reduce the early recurrence rate comparing with conventional therapy, but TPE has no advantages in improving CTSI in early stage, and no improvement for outcomes including local complications and mortalty. [ABSTRACT FROM AUTHOR]

Cisplatin-induced acute kidney injury (CIAKI) is a common complication in patients receiving cisplatin-based chemotherapy. But the effective therapies for CIAKI are not available. Retinoic acid (RA), the main derivative of vitamin A, has the potential to reduce inflammation and fibrosis in renal injury. However, the effect and mechanism of RA on CIAKI are still unclear. The aim of this study is to investigate whether RA can alleviate CIAKI through activation of autophagy. In this study, we evaluated the effect of RA, RA's effect on autophagy and apoptosis after cisplatin-induced injury on renal tubular epithelial cells (RTECs) by LDH assay, immunoblotting and TUNEL staining. Then we established Atg5flox/flox:Cagg-Cre mice in which Cagg-Cre is tamoxifen inducible, and Atg5 is conditional deleted after tamoxifen injection. The effect of RA and RA's effect on autophagy on CIAKI model were evaluated by biochemical assessment, hematoxylin and eosin (HE) staining, and immunoblotting in the control and autophagy deficient mice. In vitro , RA protected RTECs against cisplatin-induced injury, activated autophagy, and inhibited cisplatin-induced apoptosis. In vivo , RA attenuated cisplatin-induced tubular damage, shown by improved renal function, decreased renal cast formation, decreased NGAL expression, and activated autophagy in the control mice. Furthermore, the nephrotoxicity of cisplatin was aggravated, and the protective effect of RA was attenuated in autophagy deficient mice, indicating that RA works in an autophagy-dependent manner on CIAKI. RA activates autophagy and alleviates CIAKI in vivo and in vitro.Thus RA may be a renoprotective adjuvant for cisplatin-based chemotherapy. [ABSTRACT FROM AUTHOR]

The brainstem is a posterior region of the brain, composed of three parts, midbrain, pons, and medulla oblongata. It is critical in controlling heartbeat, blood pressure, and respiration, all of which are life-sustaining functions, and therefore, damages to or disorders of the brainstem can be lethal. Brain organoids derived from human pluripotent stem cells (hPSCs) recapitulate the course of human brain development and are expected to be useful for medical research on central nervous system disorders. However, existing organoid models are limited in the extent hPSCs recapitulate human brain development and hence are not able to fully elucidate the diseases affecting various components of the brain such as brainstem. Here, we developed a method to generate human brainstem organoids (hBSOs), containing midbrain/hindbrain progenitors, noradrenergic and cholinergic neurons, dopaminergic neurons, and neural crest lineage cells. Single-cell RNA sequence (scRNA-seq) analysis, together with evidence from proteomics and electrophysiology, revealed that the cellular population in these organoids was similar to that of the human brainstem, which raises the possibility of making use of hBSOs in investigating central nervous system disorders affecting brainstem and in efficient drug screenings. [ABSTRACT FROM AUTHOR]

Three-dimensional (3D) organoid models derived from human pluripotent stem cells provide a platform for studying human development and understanding disease mechanisms. Most studies that examine biallelic inactivation of the cell cycle regulator Retinoblastoma 1 (RB1) and the link to retinoblastoma is in mice, however, less is known regarding the pathophysiological role of RB1 during human retinal development. To study the role of RB1 in early human retinal development and tumor formation, we generated retinal organoids from CRISPR/Cas9-derived RB1-null human embryonic stem cells (hESCs). We showed that RB is abundantly expressed in retinal progenitor cells in retinal organoids and loss of RB1 promotes S-phase entry. Furthermore, loss of RB1 resulted in widespread apoptosis and reduced the number of photoreceptor, ganglion, and bipolar cells. Interestingly, RB1 mutation in retinal organoids did not result in retinoblastoma formation in vitro or in the vitreous body of NOD/SCID immunodeficient mice. Together, our work identifies a crucial function for RB1 in human retinal development and suggests that RB1 deletion alone is not sufficient for tumor development, at least in human retinal organoids. A model of the role of RB1 during human retinal development. In wild-type cells, RB1 regulates entry into S-phase. While RB1 mutation in retinal organoids did not result in retinoblastoma formation, either in vitro or when injected into vitreous body of NOD/SCID mice, loss of RB1 promotes an accumulation of cells in S-phase, causes widespread apoptosis, and reduces the number of photoreceptor, ganglion and bipolar cells. Image 1 • RB expression is highest in progenitor cells and downregulated during maturation stages. • RB1 is required for S-phase entry and cell survival in retinal organoids. • RB1 is necessary for photoreceptor, ganglion and bipolar cell differentiation. • Loss of RB1 is not sufficient for retinoblastoma formation in retinal organoids. [ABSTRACT FROM AUTHOR]

Purpose: Complex injuries of the extremity can be very challenging to treat. In the setting of soft tissue infection and vascular defect, arterial reconstructions are at high risk of failure. Historically, there have not been good options to successfully salvage limbs with these serious injuries. We describe our experience of utilizing a cross limb vessel transfer to salvage the limb.Methods: Patients were identified retrospectively with complex vascular injuries of the extremity and wound infection, who were treated with a cross limb vessel transfer. Once the infection has successfully been cleared, flow-through flap transfer was performed for definitive reconstruction of the arterial injury. Data collated included patient demographics, injury and operation details, and post-operative outcomes including blood supply of the limb, wound infection and complications.Results: Between April 2014 and January 2017, 3 patients with an average age of 21 years (range, 16-29) were admitted. The median length of hospital stay was 62 days (range, 26-122). The average number of operation was 7.3 times (range, 6-10). Two patients' upper limb had survived with limited movement, relatively minor donor site morbidity and confirmed flow through the vessel reconstruction using CTA, while one patient had lower limb amputation due to severe infection and prolonged ischemia time.Conclusions: This series of patients demonstrates that cross limb vessel transfer is an invaluable technique to salvage the limb in patients with complex vascular injury and wound infection. However, for lower limb with prolonged ischemia time and severe infection, limb salvage is not recommended. [ABSTRACT FROM AUTHOR]

Introduction: Improving axonal outgrowth and remyelination is crucial for peripheral nerve regeneration. Miconazole appears to enhance remyelination in the central nervous system. In this study we assess the effect of miconazole on axonal regeneration using a sciatic nerve crush injury model in rats.Methods: Fifty Sprague-Dawley rats were divided into control and miconazole groups. Nerve regeneration and myelination were determined using histological and electrophysiological assessment. Evaluation of sensory and motor recovery was performed using the pinprick assay and sciatic functional index. The Cell Counting Kit-8 assay and Western blotting were used to assess the proliferation and neurotrophic expression of RSC 96 Schwann cells.Results: Miconazole promoted axonal regrowth, increased myelinated nerve fibers, improved sensory recovery and walking behavior, enhanced stimulated amplitude and nerve conduction velocity, and elevated proliferation and neurotrophic expression of RSC 96 Schwann cells.Discussion: Miconazole was beneficial for nerve regeneration and functional recovery after peripheral nerve injury. Muscle Nerve 57: 821-828, 2018. [ABSTRACT FROM AUTHOR]

Objective:We have demonstrated that angiogenesis in acellular nerve allografts (ANAs) can promote neuroregeneration. The present study aimed to investigate the microvascular regeneration pattern of ANAs in Sprague-Dawley (SD) rats. Methods:Sixty male SD rats were randomly divided into an autologous group and a rat acellular nerve allograft group (rANA), and 10-mm sciatic nerve defects were induced in these rats. On the 7th, 14th and 21st days after surgery, systemic perfusion with Evans Blue (EB) or lead oxide was performed on the rats through carotid intubation. Samples were then collected for gross observation, and the microvessels in the nerves were reconstructed through microscopic CT scans using MIMICS software. The vascular volume fraction (VF, %) and microvessel growth rate (V, mm/d) in both groups were then measured, and 1 month after surgery, NF-200 staining was performed to observe and compare the growth condition of the axons. Results:Early post-operative perfusion with gelatin/EB showed EB permeation around the acellular nerve. Perfusion with gelatin/lead oxide showed that the blood vessels had grown into the allograft from both ends 7 days after the operation. Fourteen days after the operation, the microvessel growth rate of the autologous group was faster than that of the rANA group (0.39 ± 0.17 mm/d vs. 0.26 ± 0.14 mm/d,p < 0.05), and the vascular VF was also higher than that of the rANA group (8.92% ± 1.54% vs. 6.31% ± 1.21%,p < 0.05). Twenty-one days after the operation, the blood vessels at both ends of the allograft had connected to form a microvessel network. The growth rate was not significantly different between the two groups; however, the vascular VF of the autologous group was higher than that of the rANA group (12.18% ± 2.27% vs. 9.92% ± 0.84%,p < 0.05). One month after the operation, the NF-200 fluorescence (IOD) in the autologous group significantly increased compared with that of the rANA group (540,278 ± 17,424 vs. 473,310 ± 14,636, respectively,p < 0.05), suggesting that the results of the repair after nerve injury were significantly better in the autologous group than in the rANA group. Conclusion:Both the autologous nerve and ANAs rely on the permeation of tissue fluids to supply nutrients during the early stage, and microvessel growth mainly starts at both ends of the graft and enters the graft along the long axis. Compared to ANAs, the growth speed of revascularization in autologous nerve grafts was faster, leading to a better outcome in the autologous nerve group. [ABSTRACT FROM PUBLISHER]

Introduction: The reconstruction of extensive three-dimensional defects in the extremities is a difficult challenge. Many attempts have been made to reconstruct such defects using the chimeric flap concept, enabling flaps with larger surface areas to be used while maintaining economical tissue use. The anterolateral thigh (ALT) chimeric flap is one of the most useful tools for the reconstruction of complex three-dimensional defects in the extremities.Methods: From January 2010 to March 2012, Twenty-two patients underwent extremity reconstruction using chimeric ALT perforator flaps, which consists of a skin component on its isolated perforator and a portion of the fascia and muscle flaps on the same pedicle from the descending branch of the lateral circumflex femoral artery (LCFA). The defects were in either a lower (n = 10) or an upper extremity (n = 12). The area of the soft tissue defects ranged from 43 × 35 cm to 19 × 9 cm (mean, 25 × 18 cm), containing extensive, irregular, ring-like soft tissue defects or degloving injuries.Results: The mean dimension of skin flap was 19.8 × 11.2 cm. The mean dimension of fascia flap was 8.9 × 7.1 cm. The mean dimension of muscle flap was 11.1 × 7.5 cm. No total flap loss occurred. One patient presented with venous thrombosis, and re-anastomosis and vein grafting were performed. Two cases exhibiting partial skin graft loss at the site at which the fascia flap was inset were treated via secondary skin grafts. During a follow-up period of 18 months-30 months, patients were satisfied with the functional and aesthetic outcome. No serious donor-site complications occurred.Discussion: Chimeric anterolateral thigh perforator flap can be one of the best choice for reconstruction of complex soft-tissue defects in the extremities.Conclusions: The various tissue components and maximal freedom offered by chimeric tissue flaps associated with the same descending branch of the LCFA provide versatile coverage of large, complex, and irregular soft-tissue defects in the extremities. [ABSTRACT FROM AUTHOR]

Acute pancreatitis complicated with pulmonary embolism has been described in literature, however, hyperlipidaemic acute pancreatitis complicated with pulmonary embolism and deep vein thrombosis has rarely been reported. We reported here a rare case of hyperlipidaemic acute pancreatitis. Although he had undergone plasmapheresis and his TG level reduced to normal range with symptoms relieved, he developed pulmonary embolism and multiple deep vein thromboses. The patient was diagnosed early and successfully salvaged by interventional radiology and oral anticoagulants. The patient was a 51-year-old man, he experienced a sudden upper abdomen pain for 24 h before being admitted to a local hospital where diagnosis of acute pancreatitis was made, and he had no relief of the symptoms after treatment. The patient was a non-smoker and did not consume alcohol. He had no history of diabetes, gallstones or cholelithasis. After transferring to our unit, the patient was treated with plasmapheresis along with low molecular weight heparin, insulin, antibiotics and proton pump inhibitors and the abdomen pain was alleviated gradually. However, 8 days after admission, the patient developed a sudden chest tightness and shortness of breath. Examination revealed a high level of D-dimer (16700 ug/L), a computer tomography angiography of chest revealed pulmonary embolism. Urokinase was started intravenously. Pulmonary angiography and venography demonstrated pulmonary embolism and extensive lower limb deep vein thrombosis. Catheter directed thrombolysis and urokinase was initiated through catheter followed by an IVC filter implantation. Dyspnea of the patient got well with thrombolytic treatment and anticoagulation therapy. This is a rare case of hyperlipidaemic acute pancreatitis complicated pulmonary embolism and Deep vein thrombosis even after treated with plasmapheresis. The case we present here will aid in its early recognition, interventional radiology hence the prevention for this rare but catastrophic complication. [ABSTRACT FROM AUTHOR]

Studies have suggested that phosphatase and tensin homolog (PTEN) plays an important role in neuroprotection and neuronal regeneration. To better understand the potential role of PTEN with respect to peripheral nerve development and injury, we investigated the expression pattern of PTEN at different stages of rat peripheral nerve development and injury and subsequently assessed the effect of pharmacological inhibition of PTEN using bpV(pic) on axonal regeneration in a rat sciatic nerve crush injury model. During the early stages of development, PTEN exhibits low expression in neuronal cell bodies and axons. From embryonic day (E) 18.5 and postnatal day (P)5 to adult, PTEN protein becomes more detectable, with high expression in the dorsal root ganglia (DRG) and axons. PTEN expression is inhibited in peripheral nerves, preceding myelination during neuronal development and remyelination after acute nerve injury. Low PTEN expression after nerve injury promotes Akt/mammalian target of rapamycin (mTOR) signaling pathway activity. In vivo pharmacological inhibition of PTEN using bpV(pic) promoted axonal regrowth, increased the number of myelinated nerve fibers, improved locomotive recovery and enhanced the amplitude response and nerve conduction velocity following stimulation in a rat sciatic nerve crush injury model. Thus, we suggest that PTEN may play potential roles in peripheral nerve development and regeneration and that inhibition of PTEN expression is beneficial for nerve regeneration and functional recovery after peripheral nerve injury. [ABSTRACT FROM AUTHOR]

Recently, researchers have developed protocols for human cerebral organoids using human pluripotent stem cells, which mimic the structure of the developing human brain. Existing research demonstrated that human cerebral organoids which undergo short cultivation periods, contain astrocytes, neurons, and neural stem cells, but lacked mature oligodendrocytes, and mature, fully functional neurons. In this study, we analyzed organoids induced from H9 human embryonic stem (ES) cells that were cultivated for as long as six months. We observed mature oligodendrocytes, positive for MBP (myelin-basic protein), and mature GAD67 (glutamate decarboxylase 67 kDa isoform)-positive inhibitory neurons and VGLUT1 (vesicular glutamate transporter 1)-positive excitatory neurons via immunohistochemical analysis. These observations suggest that long-term cultivation of cerebral organoids can lead to the maturation of human cerebral organoids, which can be used as a tool to study the development of human brains. [ABSTRACT FROM AUTHOR]

Background The precise annotation and accurate identification of the topography of fascicles to the end organs are prerequisites for studying human peripheral nerves. New method In this study, we present a feasible imaging method that acquires 3D high-resolution (HR) topography of peripheral nerve fascicles using an iodine and freeze-drying (IFD) micro-computed tomography (microCT) method to greatly increase the contrast of fascicle images. Results The enhanced microCT imaging method can facilitate the reconstruction of high-contrast HR fascicle images, fascicle segmentation and extraction, feature analysis, and the tracing of fascicle topography to end organs, which define fascicle functions. Comparison with existing methods The complex intraneural aggregation and distribution of fascicles is typically assessed using histological techniques or MR imaging to acquire coarse axial three-dimensional (3D) maps. However, the disadvantages of histological techniques (static, axial manual registration, and data instability) and MR imaging (low-resolution) limit these applications in reconstructing the topography of nerve fascicles. Conclusions Thus, enhanced microCT is a new technique for acquiring 3D intraneural topography of the human peripheral nerve fascicles both to improve our understanding of neurobiological principles and to guide accurate repair in the clinic. Additionally, 3D microstructure data can be used as a biofabrication model, which in turn can be used to fabricate scaffolds to repair long nerve gaps. [ABSTRACT FROM AUTHOR]

Growing human organs in animals sounds like something from the realm of science fiction, but it may one day become a reality through a technique known as interspecies blastocyst complementation. This technique, which was originally developed to study gene function in development, involves injecting donor pluripotent stem cells into an organogenesis-disabled host embryo, allowing the donor cells to compensate for missing organs or tissues. Although interspecies blastocyst complementation has been achieved between closely related species, such as mice and rats, the situation becomes much more difficult for species that are far apart on the evolutionary tree. This is presumably because of layers of xenogeneic barriers that are a result of divergent evolution. In this Review, we discuss the current status of blastocyst complementation approaches and, in light of recent progress, elaborate on the keys to success for interspecies blastocyst complementation and organ generation., Competing Interests: Competing interests The authors declare no competing or financial interests., (© 2021. Published by The Company of Biologists Ltd.)

Dynamic pluripotent stem cell (PSC) states are in vitro adaptations of pluripotency continuum in vivo. Previous studies have generated a number of PSCs with distinct properties. To date, however, no known PSCs have demonstrated dual competency for chimera formation and direct responsiveness to primordial germ cell (PGC) specification, a unique functional feature of formative pluripotency. Here, by modulating fibroblast growth factor (FGF), transforming growth factor β (TGF-β), and WNT pathways, we derived PSCs from mice, horses, and humans (designated as XPSCs) that are permissive for direct PGC-like cell induction in vitro and are capable of contributing to intra- or inter-species chimeras in vivo. XPSCs represent a pluripotency state between naive and primed pluripotency and harbor molecular, cellular, and phenotypic features characteristic of formative pluripotency. XPSCs open new avenues for studying mammalian pluripotency and dissecting the molecular mechanisms governing PGC specification. Our method may be broadly applicable for the derivation of analogous stem cells from other mammalian species., Competing Interests: Declaration of Interests L.Y. and J.W. are inventors on a patent application arising from this work. The other authors declare no competing interests., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Acute pancreatitis complicated with pulmonary embolism has been described in literature, however, hyperlipidaemic acute pancreatitis complicated with pulmonary embolism and deep vein thrombosis has rarely been reported. We reported here a rare case of hyperlipidaemic acute pancreatitis. Although he had undergone plasmapheresis and his TG level reduced to normal range with symptoms relieved, he developed pulmonary embolism and multiple deep vein thromboses. The patient was diagnosed early and successfully salvaged by interventional radiology and oral anticoagulants. The patient was a 51-year-old man, he experienced a sudden upper abdomen pain for 24 h before being admitted to a local hospital where diagnosis of acute pancreatitis was made, and he had no relief of the symptoms after treatment. The patient was a non-smoker and did not consume alcohol. He had no history of diabetes, gallstones or cholelithasis. After transferring to our unit, the patient was treated with plasmapheresis along with low molecular weight heparin, insulin, antibiotics and proton pump inhibitors and the abdomen pain was alleviated gradually. However, 8 days after admission, the patient developed a sudden chest tightness and shortness of breath. Examination revealed a high level of D-dimer (16700 ug/L), a computer tomography angiography of chest revealed pulmonary embolism. Urokinase was started intravenously. Pulmonary angiography and venography demonstrated pulmonary embolism and extensive lower limb deep vein thrombosis. Catheter directed thrombolysis and urokinase was initiated through catheter followed by an IVC filter implantation. Dyspnea of the patient got well with thrombolytic treatment and anticoagulation therapy. This is a rare case of hyperlipidaemic acute pancreatitis complicated pulmonary embolism and Deep vein thrombosis even after treated with plasmapheresis. The case we present here will aid in its early recognition, interventional radiology hence the prevention for this rare but catastrophic complication.

Acellular nerve allografts (ANAs) behave in a similar manner to autografts in supporting axonal regeneration in the repair of short peripheral nerve defects but fail in larger defects. The objective of this article is to evaluate the effect of ANA supplemented with platelet-rich plasma (PRP) to improve nerve regeneration after surgical repair and to discuss the mechanisms that underlie this approach. Autologous PRP was obtained from rats by double-step centrifugation and was characterized by determining platelet numbers and the release of growth factors. Forty-eight Sprague-Dawley rats were randomly divided into 4 groups (12/group), identified as autograft, ANA, ANA loaded with PRP (ANA+PRP), and ANA loaded with platelet-poor plasma (PPP, ANA+PPP). All grafts were implanted to bridge long-gap (15 mm) sciatic nerve defects. We found that PRP with a high platelet concentration exhibited a sustained release of growth factors. Twelve weeks after surgery, the autograft group displayed the highest level of reinnervation, followed by the ANA+PRP group. The ANA+PRP group showed a better electrophysiology response for amplitude and conduction velocity than the ANA and ANA+PPP groups. Based on histological evaluation, the ANA+PRP and autograft groups had higher numbers of regenerating nerve fibers. Quantitative real-time polymerase chain reaction (qRT-PCR) demonstrated that PRP boosted expression of neurotrophins in the regenerated nerves. Moreover, the ANA+PRP and autograft groups showed excellent physiological outcomes in terms of the prevention of muscle atrophy. In conclusion, ANAs loaded with PRP as tissue-engineered scaffolds can enhance nerve regeneration and functional recovery after the repair of large nerve gaps nearly as well as autografts.