Metabolic reprogramming plays a central role in tumors. However, the key drivers modulating reprogramming of gluconeogenesis/lipogenesis are poorly understood. Here, we try to identify the mechanism by which histone acetyltransferase 1 (HAT1) confers reprogramming of gluconeogenesis/lipogenesis in liver cancer. Diethylnitrosamine (DEN)/carbon tetrachloride (CCl₄)-induced hepatocarcinogenesis was hardly observed in HAT1-knockout mice. Multi-omics identified that HAT1 modulated gluconeogenesis and lipogenesis in liver. Protein phosphatase 2 scaffold subunit alpha (PPP2R1A) promoted gluconeogenesis and inhibited lipogenesis by phosphoenolpyruvate carboxykinase 1 (PCK1) serine 90 dephosphorylation to suppress the tumor growth. HAT1 succinylated PPP2R1A at lysine 541 (K541) to block the assembly of protein phosphatase 2A (PP2A) holoenzyme and interaction with PCK1, resulting in the depression of dephosphorylation of PCK1. HAT1-succinylated PPP2R1A contributed to the remodeling of gluconeogenesis/lipogenesis by PCK1 serine 90 phosphorylation, leading to the inhibition of gluconeogenic enzyme activity and activating sterol regulatory element-binding protein 1 (SREBP1) nuclear accumulation-induced lipogenesis gene expression, which enhanced the tumor growth. In conclusion, succinylation of PPP2R1A lysine 541 by HAT1 converses the role in modulation of gluconeogenesis/lipogenesis remodeling through PCK1 S90 phosphorylation to support liver cancer. Our finding provides new insights into the mechanism by which post-translational modifications (PTMs) confer the conversion of tumor suppressor function to oncogene.

Objective:To investigate the therapeutic effect of exosomes derived from remote ischemic conditioning on neurological dysfunction after cardiopulmonary resuscitation in a rat model of cardiac arrest and the relationship with glycocalyx protection.Methods:Exosomes were isolated from the blood of healthy adult male Sprague-Dawley rats using ultracentrifugation after undergoing remote ischemic conditioning for use as intervention drugs. Nanoparticle tracking analysis technology was used for exosome detection. Thirty-six adult male Sprague-Dawley rats were randomly assigned to 3 groups ( n=12 each) :Sham group, Control group and Exosome group. Cardiac arrest was induced by asphyxia for 7 min in the Control and Exosome groups. Placebo or exosomes (1×10 10 Particles) were infused intravenously at 5 min after the rats had returned of spontaneous circulation. Neuropsychological deficit score (NDS), open field test, Y maze and Morris water maze were used to assess neurological outcomes. The levels of plasma Hyaluronic acid (HA) and syndecan-1 (Sdc-1) were detected by Elisa. The expression levels of matrix metalloproteinase-2/9 (MMP-2/9) in hippocampal CA1 region were detected by Western blot. Results:After undergoing remote ischemic conditioning, the plasma levels of exosomes were elevated in rats compared to normal rats. Compared with the control group, the behavioral experiment of rats in the exosomes group were significantly improved, as evidenced by an increase in horizontal locomotor distance (5.86±2.89 vs. 17.53±5.51, P< 0.05), an increase in the correct rate of spontaneous alternation (13.29±15.07 vs. 42.63±10.25, P< 0.05), and a shortening of avoidance latency (25.83±8.54 vs. 13.49±4.55, P< 0.05). Plasma HA and Sdc-1 levels were significantly lower 24 h after resuscitation (HA: 26.34±9.83 vs. 14.84±6.26, P< 0.05; Sdc-1: 0.05±0.03 vs. 0.02±0.02, P<0.05), along with significantly lower MMP-2/9 levels in hippocampal tissue. Conclusions:Exosomes extracted from the plasma of rats undergoing remote ischemic conditioning can improve neurological dysfunction after cardiac arrest in rats, and the mechanism may be related to the inhibition of metalloproteinases and the reduction of endothelial glycocalyx degradation.

Objective:To investigate the surgical methods and clinical effects of free superficial peroneal artery perforator flap in repairing small and medium-sized thermal crush injury wounds in the hand.Methods:A retrospective observational study was conducted. From August 2018 to December 2021, 12 patients (19 wounds) with small and medium-sized thermal crush injury in the hand who met the inclusion criteria were hospitalized in Suzhou Ruihua Orthopaedic Hospital, including 5 males and 7 females, aged from 30 to 54 years. The area of the wound was from 2.5 cm×2.0 cm to 14.0 cm×3.5 cm, and all the wounds were repaired by using free superficial peroneal artery perforator flaps from lower leg on one side (including single flap, multiple flaps, and multiple flaps with one pedicle resected from the same donor site). The area of the flap was from 3.5 cm×3.0 cm to 16.0 cm×4.0 cm. The wound in the donor site was sutured directly. The vascular crisis and survival of the flap were observed after operation. The texture, appearance, color, hyperpigmentation, sensation, and two-point discrimination of the flap repaired area were followed up, as well as the hyperplasia of scar and pain condition in the donor and recipient sites. At the last follow-up, the curative effect of flap repair was evaluated by the comprehensive evaluation scale, and the extension and flexion functions of the reserved digital joint were evaluated by the total active movement systematic evaluation method recommended by American Academy for Surgery of Hand.Results:One flap developed arterial crisis on the first day after operation but survived after timely exploration. The other 18 flaps survived successfully after operation. Follow-up of 4 to 24 months after operation showed good texture and appearance in the flap repaired area; the color of the flap repaired area was similar to that of the normal skin around the recipient site, without pigmentation; the protective sensation was restored in all cases, but there was no two-point discrimination; there was no obvious hypertrophic scarring or pain in the donor or recipient site. At the last follow-up, the curative effect of flap repair was evaluated with 3 flaps being excellent and 16 flaps being good; the extension and flexion functions of the reserved digital joint were also assessed, being excellent in 8 fingers, good in 9 fingers, and fair in 2 fingers.Conclusions:The blood supply of superficial peroneal artery perforator flap is sufficient and reliable, and multiple flaps of this type or multiple flaps with one pedicle can be resected from one donor site. The use of this flap to repair small and medium-sized thermal crush injury wounds in the hand results in minimal damage to the donor area, and good postoperative appearance and texture of the flap.

Objective:To summarise the clinical application and results of superficial peroneal artery perforator flaps in tiled reconstruction of thumbs and fingers.Methods:From June 2020 to June 2022, 8 patients with finger or thumb defects (4 thumbs, 2 index fingers and 2 middle fingers) received digit reconstruction in the Department of Hand Surgery, Suzhou Ruihua Orthopaedic Hospital. Two thumbs (2 patients) were reconstructed with a free partial hallux nail flap combined with a free perforator flap of superficial peroneal artery and an iliac bone graft, 1 thumb was reconstructed with a free partial hallux nail flap combined with a free perforator flap of superficial peroneal artery, 1 thumb and 2 middle fingers were reconstructed with free perforator flaps of superficial peroneal artery combined with iliac bone grafts, and 2 index fingers were reconstructed with lobulated free perforator flaps of superficial peroneal artery. The sizes of the flaps were 1.8 cm×3.2 cm-4.0 cm×10.0 cm. Lengths of iliac crest were 1.5-4.0 cm. The donor sites were directly sutured in 5 patients, skin grafts in 2 and superficial peroneal artery perforator flap reconstruction in 1 patient. Postoperative observations included survival of the digits and healing of the bone grafts. Monthly scheduled postoperative follow-ups were conducted at outpatient clinics and via telephone or WeChat reviews, covering function and appearance of the reconstructed digits, impact on the function and appearance of donor sites as well as the satisfaction of patients.Results:All 8 reconstructed digits survived in one stage and all the 5 bone grafts healed at 3 to 4 months after surgery. The mean postoperative follow-up period was 10 months, ranged 4 to 20 months. The texture of the reconstructed digits was close to that of the recipient site and good in elasticity, without purplish while in cold, nor ulceration, obvious bloating and pigmentation. Sensation of the digit pulps was recovered to S 2 to S 3, and the sensation in touch, pain and temperature were restored. TPD was not checked. There was no noticeable hyperplasia nor pain in the recipient and donor sites. There was no obvious hyperplasia or pain at the donor sites for the hallux nail flap, and the skin grafts or flaps in the donor sites survived well without ulceration or pain and the function of the donor feet were not affected. Functions of the reconstructed digits were assessed according to the Functional Assessment Criteria for Thumb and Finger Reconstruction of the Society for Evaluation Standard of Upper Limb Partial Functional of Hand Surgery of Chinese Medical Association, 4 patients achieved in excellent and 4 in good. According to the University of Michigan Hand Profile Questionnaire (MHQ), patient satisfaction was found very satisfied with 4 patients and satisfied with the other 4 patients. Conclusion:The superficial peroneal artery perforator flap has advantages of thin and large area with pleasant texture, better sensation recovery and less damage to the donor site. It is an ideal flap for reconstruction of thumbs and fingers.

Objective:To observe the clinical value of intracranial pressure (ICP) monitoring combined with target temperature management (TTM) in patients with acute anterior circulation ischemic stroke after mechanical thrombectomy.Methods:A prospective analysis was performed. Ninety-two patients with acute anterior circulation ischemic stroke who received mechanical thrombectomy from March 2019 to June 2022 in Department of Neurosurgery, He'nan Provincial People's Hospital were enrolled. Within 1-5 d of mechanical thrombectomy, these patients were randomly divided into observation group ( n=46) and control group ( n=46). The patients in observation group received comprehensive management for neurological critical illness through multimodal monitoring such as ICP real-time monitoring combined with TTM (controlling the core temperature at 33℃-35℃), while patients in control group received simple ICP real-time monitoring. ICP monitoring for both groups lasted for 5-7 d, and routine symptomatic support treatment was given. Stepwise treatment was adopted based on real-time changes of ICP. The differences in clinical data, ICP at different times, incidence of adverse events, length of hospital stay, mortality rate, and prognoses were compared between the 2 groups. Results:On the 2 nd, 3 rd, 4 th, and 5 th d of monitoring, the observation group had significantly decreased ICP compared with the control group ( P<0.05). Both observation group and control group had significantly increased ICP on the 2 nd, 3 rd, 4 th, and 5 th d of monitoring compared with that on the 1 st d of monitoring ( P<0.05). Compared with the control group, the observation group had statistically higher incidences of shivers and electrolyte disorders, and statistically lower incidences of unstable blood pressure, cerebral heart syndrome, septic shock, and cerebral hernia during hospitalization ( P<0.05). Compared with the control group, the observation group had significantly shortened hospital stay, and statistically lower modified Rankin scale (mRS) scores, higher Glasgow outcome scale-extended (GOS-E) scores, higher good prognosis rate, and lower mortality rate 6 months after mechanical thrombectomy ( P<0.05). Compared with the control group, the observation group had statistically lower incidences of postoperative cerebral hemorrhage conversion and recurrent cerebral infarction ( P<0.05). Kaplan-Meier survival analysis showed that the survival rate in the observation group was significantly higher than that in the control group ( P<0.05). Conclusion:ICP monitoring combined with TTM can reduce early complications, shorten hospital stay, reduce mortality, and improve long-term prognosis in patients with acute anterior circulation ischemic stroke after mechanical thrombectomy.

Objective:To explore the surgical method and clinical effect of harvesting 2 ipsilateral free pedicled perforator flaps from a single donor site of superficial peroneal artery in reconstruction of 2 defects in same or adjacent digits.Methods:From November 2017 to August 2021, 12 patients with 2 defects in same or adjacent digits were treated in the Department of Hand Surgery, Suzhou Ruihua Orthopaedic Hospital with 2 ipsilateral free pedicled perforator flaps from a single donor site of superficial peroneal artery. Among the patients, 1 had the defect in dorsal and palmar of index finger, 1 in thumb and index finger, 6 in index and middle fingers, 3 in middle and ring fingers, and 1 in ring and little fingers. The size of digit defects was 1.5 cm×0.8 cm-6.0 cm×3.5 cm. The size of flaps was 2.0 cm× 1.2 cm-8.0 cm×4.0 cm. All the patients were included in postoperative monthly follow-up to assess the recovery of recipient and donor sites at outpatient service, by telephone or WeChat.Results:All 24 flaps in 12 patients survived without vascular compromise and achieved 100% of survival rate. The follow-up period ranged from 4 to 18 months, with an average of 10 months. Six patients were treated with additional flap thinning and plastic surgery at 4 months after the primary surgery due to slightly bloated flaps. Otherwise, all the flaps in the recipient site had neither pigmentation, obvious hyperplasia nor scar pain. All flaps gained the protective sensations, however the assessment of TPD was not conducted. The flaps were wear-resist and had no ulceration. The texture of the flaps was soft with good elasticity, and the flap did not turn to purple or swelling when in cold. The functional recovery of 23 digits in 12 patients was evaluated according to the total active mobility (TAM) of the digits. It achieved excellent in 3 digits, good in 15 digits, and fair in 5 digits, with an excellent and good rate of 78.26%. A linear scar appeared at the donor site without obvious hyperplasia or scar pain. There were normal sensations around the scar and at the digit-tips. The blood supply to the digit-tips was normal.Conclusion:Harvest of multiple free pedicled perforator flaps from a single donor site of superficial peroneal artery is an effective method in reconstruction of 2 defects in same or adjacent digits at the same time. It has advantages of being a simple surgery procedure by sacrificing only one donor site. It achieves a minimal damage to the donor site and a reliable blood supply of the flap.

Objective:To investigate the influence of bacterial outer membrane vesicles (OMVs) tumor vaccine on tumor cell proliferation and CD8 + T cell infiltration of mouse with pancreatic cancer. Methods:The experimental study was conducted. The ovalbumin (OVA) lentivirus vector plasmid pLV-EF1a-hluc-P2A-mNeongreen-CMV-OVA-3Xflag-P2A-puro was used to construct the mouse pancreatic cancer Pan02-OVA cells. The ClyA-Catchers-OMVs (CC-OMVs) originated from Escherichia coli and labeled antigenic peptide SpyTag-OVA were used to construct the OMVs tumor vaccine. Mouse CD8 + T cells were stimulated by OMVs tumor vaccine, and the effects of OMVs tumor vaccine on inhibiting pancreatic cancer cells proliferation and stimulating CD8 + T cell infiltration were analy-zed by in vitro cell killing assay, including the OMVs tumor vaccine stimulated T cell group and the control T cell group, subcutaneous pancreatic cancer model, including the OMVs tumor vaccine group and the control group, and immunohistochemical staining. Observation indicators: (1) identification of mouse pancreatic cancer Pan02-OVA cells; (2) morphological observation of CC-OMVs; (3) inhibi-tion of mouse pancreatic cancer Pan02-OVA cells by OMVs tumor vaccine specific T cells; (4) inhibi-tion of mouse pancreatic cancer by OMVs tumor vaccine; (5) CD8 + T cell infiltration in pancreatic cancer tissue of mouse stimulated by OMVs tumor vaccine. Measurement data with normal distribu-tion were represented as Mean± SD, and comparison between groups was analyzed using the t test. Count data were described as absolute numbers or percentages. Results:(1) Identification of mouse pancreatic cancer Pan02-OVA cells. Results of laser scanning confocal microscopy showed that the mNeongreen fluorescence was expressed in Pan02-OVA cells infected with the OVA lentivirus vector plasmid of pLV-EF1a-hluc-P2A-mNeongreen-CMV-OVA-3Xflag-P2A-puro. Results of Flow cytometry showed that using the mouse pancreatic cancer Pan02 cells as references, the protein expression rate of Flag on the Pan02-OVA cells was 90.7%. (2) Morphological observation of CC-OMVs. Results of transmission electron microscopy analysis showed that the CC-OMVs were in spherical shape, with a diameter <50 nm. (3) Inhibition of mouse pancreatic cancer Pan02-OVA cells by OMVs tumor vaccine specific T cells. Results of cell proliferation toxicity test showed that the absorbance at 450 nm of mouse pancreatic cancer Pan02-OVA cells was 0.41±0.12 and 1.05±0.15 in the OMVs tumor vaccine-stimulated T cell group and the control T cell group, respectively, showing a significant difference between the two groups ( t=9.54, P<0.05). (4) Inhibition of mouse pancreatic cancer by OMVs tumor vaccine. The weight of subcutaneous tumor tissue in the back of mouse was (81±10)g and (153±17)g in the OMVs tumor vaccine group and the control group, respectively, showing a significant difference between the two groups ( t=8.26, P<0.05). (5) CD8 + T cell infiltration in pancreatic cancer tissue of mouse stimulated by OMVs tumor vaccine. Results of immuno-histochemical staining showed that the numbers of CD8 + T cells staining in the mouse back subcu-taneous tumor tissues was 28.7±3.5 and 9.3±1.5 in the OMVs tumor vaccine group and the control group, respectively, showing a significant difference between the two groups ( t=8.74, P<0.05). Conclusion:Bacterial OMVs tumor vaccine can inhibit proliferation of pancreatic cancer cells and increase the numbers of CD8 + T cells infiltrated in pancreatic cancer tissue of mouse.

Fibroblast growth factor receptors (FGFRs) have emerged as promising targets for anticancer therapy. In this study, we synthesized and evaluated the biological activity of 66 pyrazolo[3,4-

Objective:To investigate the predicting value of high sensitivity C-reactive protein (hs-CRP) and albumin (Alb) ratio on prognosis of patients with in-hospital cardiac arrest (IHCA).Methods:A total of 107 patients with IHCA and spontaneous circulation recovery (ROSC) after cardiopulmonary resuscitation (CPR) in the Affiliated Hospital of Xuzhou Medical University during January 1, 2017 and September 30, 2020 were selected as the subjects and divided into the survival group and death group according to the survival condition on day 14 after IHCA. The correlation between ratio of high sensitivity C-reactive protein/albumin (hs-CRP/Alb) and the prognosis of patients was analyzed.Results:No statistical significant differences were found between the survival and death groups in sex, age, medical history, ECG monitoring, recovery ventilation mode, percentage of first monitoring of heart rate and pre-resuscitation Alb (all P > 0.05). However, there were significant differences in the percentage of non-cardiogenic CA and adrenaline dose > 5 mg, time of CPR, concentrations of blood lactic acid, Alb, hs-CRP, and ratio of hs-CRP/Alb (all P < 0.05). Logistic regression analysis showed that percentage of adrenaline dose > 5 mg, concentration of blood lactic acid, time of CPR, and ratio of hs-CRP/Alb were independent risk factors for predicting death. ROC curve analysis showed that hs-CRP/Alb ratio, and concentration of hs-CRP and Alb had predictive value on the death of patients with IHCA; the areas under the curves of hs-CRP/Alb ratio, hs-CRP and Alb concentration were 0.876, 0.864 and 0.745, respectively. The predictive efficiency of hs-CRP/Alb ratio was better than that of hs-CRP concentration or Alb concentration. Conclusions:hs-CRP/Alb ratio has predictive value for the prognosis of patients with IHCA and the predictive value is superior to that of hs-CRP and Alb concentration.

Objective:To explore the surgical procedure and clinical effect of the free Flow-through superficial peroneal artery flap for repairing the digit injury with defect of proper palmar digital artery.Methods:From June, 2015 to December, 2019, free Flow-through superficial peroneal artery flap was used to repair the digit injury and to bridge the proper digital artery in 7 digits of 7 patients. There were 2 thumbs, 3 index fingers and 2 middle fingers. The size of defects on digits ranged from 2.5 cm×3.0 cm to 5.0 cm×7.0 cm. The defects of digit proper artery were 1.0 to 3.0 cm. The size of flaps was from 3.0 cm×3.5 cm to 5.5 cm×8.0 cm. The donor areas of the flap were directly sutured or covered with skin graft. Postoperative supportive treatments were given, such as infection prevention, antispasmodic, anticoagulant, analgesia and fluid infusion. The patients were kept in bed for 1 week after surgery. Monthly follow-up review were conducted and the patients were kept with the rehabilitation exercises under medical guidance.Results:All the patients entered postoperative followed-up for 6 to 18 months, with an average of 8 months. All flaps survived without any adverse event. All wounds achieved stage-one-healing. The flaps appeared in good colour, texture, elasticity and the plumps of the digit without obvious bloating. There was no obvious swelling and atrophy of the digits. The skin temperature was normal. According to the Standard for Evaluation of Upper Limb Function by the Hand Surgery Society of Chinese Medical Association, 3 digits were excellent and 4 were good. There was no obvious scar at the donor site of shank. The donor site had a good appearance and the limb function was not affected.Conclusion:The free Flow-through superficial peroneal artery flap is an ideal material to repair the defect of digit with the defect of proper digital artery. It has the advantages of simple surgical procedure, reliable blood supply and satisfactory appearance. The defect of proper digit artery can be repaired at the same time of the surgical procedure. The blood supply, appearance and function of the digits could be well recovered and the donor site is not affected.