Liraglutide (Lira), a glucagon-like peptide-1 (GLP-1) receptor agonist approved for diabetes and obesity, has shown significant potential in treating metabolic dysfunction-associated steatotic liver disease (MASLD). However, its systematic molecular regulation and mechanisms remain underexplored. In this study, a mouse model of MASLD was developed using a high-fat diet (HFD), followed by Lira administration. Proteomics and glycoproteomics were analyzed using label-free liquid chromatography-tandem mass spectrometry (LC-MS/MS), while potential molecular target analysis was conducted via quantitative real-time polymerase chain reaction (qPCR) and Western blotting. Our results revealed that Lira treatment significantly reduced liver weight and serum markers, including alanine aminotransferase (ALT) and others, with glycosylation changes playing a more significant role than overall protein expression. The glycoproteome identified 255 independent glycosylation sites, emphasizing the impact of Lira on amino acid, carbohydrate metabolism, and ferroptosis. Simultaneously, proteomic analysis highlighted its effects on lipid metabolism and fibrosis pathways. 21 signature molecules, including 7 proteins and 14 N-glycosylation sites (N-glycosites), were identified as potential targets. A Lira hydrogel formulation (Lira@fibrin (Fib) Gel) was developed to extend drug dosing intervals, offering enhanced therapeutic efficacy in managing chronic metabolic diseases. Our study demonstrated the importance of glycosylation regulation in the therapeutic effects of Lira on MASLD, identifying potential molecular targets and advancing its clinical application for MASLD treatment.

Objective:To explore the effect of free transplantation of composite tissue flap from the anterior lateral aspect of the femur in repairing head skin defects with artificial dural exposure infection.Methods:A retrospective study was conducted on 13 patients admitted to the First Affiliated Hospital of Air Force Military Medical University from April 2018 to August 2020 with craniotomy complications, including craniotomy skin and soft tissue defects combined with artificial dural exposure and infection. After preoperative anti infection treatment, the neurosurgery department participated in debridement and removed the artificial dura mater as much as possible during the operation. A composite tissue flap carrying the fascia lata was designed for the anterior lateral aspect of the thigh, and the flap artery and vein were anastomosed with the superficial temporal artery and superficial temporal vein/middle temporal vein respectively. The defect of the dura mater was repaired with the fascia lata with blood supply. The flap was used to seal the wound, and the donor site was directly sutured or transplanted with autologous medium thick skin graft. The postoperative blood supply and survival of the flap, the presence of cerebrospinal fluid leakage, and the healing of the donor site were observed; The observation of dural integrity and postoperative effects of skull reconstruction using cranial magnetic resonance imaging was followed up.Results:Among the 13 patients in this group, 11 patients had their artificial dura mater completely removed, while 2 patients were not completely removed due to severe adhesion. Among them, 1 patient had a residual area of 0.8 cm×1 cm, and the other had 3 residual areas, with a maximum area of 0.5 cm×0.7 cm; All transplanted skin flaps survived, with 12 cases achieving primary healing and 1 case of partial wound rupture after suture removal, which healed after conservative dressing change; All patients had no cerebrospinal fluid leakage; There was one case of partial necrosis of the graft in the donor site, which healed after supplementing the graft; Thirteen patients underwent cranial magnetic resonance imaging at 3-6 months postoperatively, all of which showed intact dura mater; Among them, 8 patients have completed skull reconstruction surgery, and all of them have healed well after reconstruction, with a good appearance of the surgical area.Conclusions:For wounds with head skin defects and exposed artificial dura mater infection, free transplantation of the anterior lateral composite tissue flap carrying the fascia lata can effectively cover the wound and repair the dura mater defect, achieve good function and appearance, and create favorable conditions for later skull reconstruction.

ObjectiveTraditional Chinese medicine， namely Dahuang Zhechongwan （DHZCW） was used to treat myocardial fibrosis in model rats， observe its effect on myocardial fibrosis in rats， and explore its action mechanism. MethodThirty-six SPF male Kunming rats were divided into blank group， model group， low-， medium-， high-dose groups of DHZCW （0.056， 0.084， 0.168 g·kg^-1）， captopril group （10 mg·kg^-1）， with six rats in each group. Except for the blank group， the other groups were intraperitoneally injected isoproterenol solution of 5 mg·kg^-1 for 15 consecutive days to replicate the myocardial fibrosis model. At the beginning of modeling， the rats in each group took drugs， and they were sacrificed 28 days after administration. Serum and heart tissue were collected for the corresponding detection. Hematoxylin-eosin （HE） staining and Masson staining were used to observe tissue inflammation， cellular degeneration， necrosis， and fibrosis. The contents of hydroxyproline （HYP）， tumor necrosis factor-α （TNF-α）， interleukin-1β （IL-1β）， interleukin-6 （IL-6）， hyaluronic acid （HA）， laminin （LN）， type-Ⅲ procollagen （PC Ⅲ） in serum of rats and rats were determined by enzyme-related immunosorbent assay （ELISA）. The expression levels of key pathway proteins transforming growth factor-β₁ （TGF-β₁）， α-smooth muscle actin （α-SMA）， Smad2， Smad3， and Smad7 were detected by Western blot. The expression levels of key pathway genes TGF-β₁， α-SMA， Smad2， Smad3， Smad7， miR-29a-5p， miR-29b-2-5p， and miR-29c-5p were detected by Real-time quantitative polymerase chain reaction （Real-time PCR）. ResultCompared with the blank group， the pathological changes of fibrosis in the model group were obvious， the contents of serum HYP， TNF-α， IL-1β， IL-6， HA， LN， and PCⅢ were increased （P<0.01）， the protein expression levels of TGF-β₁， α-SMA， Smad2， and Smad3 were increased； the protein expression level of Smad7 was decreased （P<0.01）. The mRNA expression levels of TGF-β₁， α-SMA， Smad2， and Smad3 were increased （P<0.05， P<0.01）， while those of Smad7， miR-29a-5p， miR-29b-2-5p， and miR-29c-5p were decreased （P<0.01）. Compared with the model group， after 28 days of administration， serum HYP， TNF-α， IL-1β， IL-6， HA， LN， and PCⅢ in high-， medium-， and low-dose groups of DHZCW and captopril groups were decreased （P<0.01）. Except for the low-dose group， the protein contents of TGF-β₁， α-SMA， Smad2， and Smad3 were decreased， while the protein content of Smad7 was increased （P<0.01）. The mRNA expression levels of TGF-β₁， Smad2， α-SMA， and Smad3 in high-dose group of DHZCW were decreased （P<0.05，P<0.01）， while those of Smad7， miR-29a-5p， miR-29b-2-5p， and miR-29c-5p were increased （P<0.05）. The mRNA expressions of TGF-β₁， Smad2， and Smad3 in the medium-dose group of DHZCW were decreased （P<0.05， P<0.01）， while mRNA expression of Smad7 was increased （P<0.01）. The mRNA levels of TGF-β₁ and Smad2 in the low-dose group of DHZCW were decreased （P<0.01）. ConclusionDHZCW can improve myocardial fibrosis in rats， and its action mechanism may be related to the regulation of the TGF-β₁/Smads/miR-29 pathway. In addition， there is dose dependence in the range of 0.056-0.168 g·kg^-1， and the effect of the high-dose group is more stable.

ObjectiveTo investigate the effect and mechanism of Dahuang Zhechongwan （DHZCW） on adenine-induced renal fibrosis in rats from the perspective of intestinal flora. MethodThirty-six SD rats were randomly divided into a blank group， a model group， and high-， medium- and low-dose DHZCW groups （0.168， 0.084， 0.042 g·kg^-1）， and a pirfenidone group （200 mg·kg^-1）， with 6 rats in each group. Except for those in the blank group， rats in other groups were treated with adenine suspension （250 mg·kg^-1） by gavage for 28 days for renal fibrosis model induction. Subsequently， they received drug intervention for 4 weeks. Urine samples were collected from rats in metabolic cages， and renal function indicators including blood urea nitrogen （BUN）， urea， creatinine （Crea）， cystatin C （Cys C）， and 24-hour urine protein （24 h TP） were measured. Kidney samples were collected and subjected to hematoxylin-eosin （HE） staining and Masson's trichrome staining to observe the pathological changes in rat renal tissues. Western blot was used to detect the expression levels of key effector proteins α-smooth muscle actin （α-SMA）， type Ⅰ collagen （ColⅠ）， and type Ⅲ collagen （ColⅢ） in the kidneys. High-throughput sequencing of 16S rDNA was used to analyze the species diversity of rat intestinal flora. ResultCompared with the blank group， the model group showed increased BUN， urea， Crea， Cys C， and 24 h TP levels （P<0.01）. Compared with the model group， the high-， medium-， and low-dose DHZCW groups， as well as the pirfenidone group， showed significant reductions in BUN， urea， Crea， Cys C， and 24 h TP levels （P<0.01）， indicating that DHZCW intervention significantly improved renal function. In the model group， renal tissues exhibited significant fibrotic changes， and the protein levels of α-SMA， ColⅠ， and ColⅢ were significantly increased （P<0.01） compared to those in the blank group. Compared with the model group， the high-dose DHZCW group and the pirfenidone group had relatively normal tissue structure， with no significant pathological damage observed. However， fibrotic changes were observed in the medium- and low-dose DHZCW groups， with the changes being more significant in the low-dose group. The protein levels of α-SMA， ColⅠ， and ColⅢ were significantly decreased in the high-， medium-， and low-dose DHZCW groups， as well as the pirfenidone group （P<0.01）， indicating that DHZCW effectively reduced abnormal collagen deposition and inhibited renal fibrosis. From the perspective of intestinal flora， at the phylum level， compared with the blank group， the model group showed a significant increase in the abundance of Firmicutes and a decrease in Bacteroidetes， leading to a significant imbalance in their ratio. At the family level， the model group decreased the abundance of Lachnospiraceae， Prevotellaceae， and Bacteroidota_unclassified， and increased the abundance of Ruminococcaceae， Lactobacillaceae， and Oscillospiraceae. At the genus level， the model group showed significantly reduced abundance of Firmicutes_unclassified， Bacteroidota_unclassified， and Prevotellaceae_UCG-001， etc.， and increased abundance of UCG-005， Clostridia_UCG-014_unclassified， etc. Compared with the model group， DHZCW effectively reduced the abundance of potential pathogenic bacteria and increased the abundance of beneficial bacteria， regulating the intestinal flora. ConclusionDHZCW can effectively improve renal function and inhibit renal fibrosis， and its mechanism of action may be related to the regulation of intestinal flora.

The deep tissue defects of extremities are prone to cause the exposure of tendons, blood vessels, nerves, and bones, which are commonly repaired with free flaps in clinical practice. However, for special parts such as fingers, toes, posterior ankles, anterior tibias, and dorsum of feet, the appearances are usually bulky after being repaired with free flaps and need lipectomy operations, which bring great physiological, psychological, and economic burden to patients. As the fascia flap is soft and thin with reliable blood supply and strong anti-infection ability, the free fascia flap combined with skin grafting offers some advantages in repairing the above-mentioned wounds. However, its clinical application is severely limited due to the complexity of surgical operation and the difficulty in observing blood supply after operation. In recent years, our team has carried out a lot of work and accumulated rich experience in repairing deep tissue defects of special parts of extremities with free superficial temporal fascia flap/anterolateral femoral fascial flap combined with skin grafting. From the clinical perspective, this paper mainly introduces the anatomy and harvesting method of free superficial temporal fascia flap/anterolateral femoral fascial flap, as well as the advantages, difficulties, and precautions of clinical application, for reference of peers.

Objective:To systematically review the efficacy and safety of electrostimulation of the posterior tibial nerve and antimuscarinic drugs in the treatment of overactive bladder.Methods:The literature search was conducted using the PubMed, The Cochrane Library, EMbase, Medline, CNKI, CQVIP, Wanfang databases.The retrieval period was from the establishment of the database to February 2021. Literature was screened and evaluated independently by two investigators to compare the safety and efficacy of electrostimulation of the posterior tibial nerve and antimuscarinic drugs in the treatment of overactive bladder. Meta-analysis was performed using Review Manager 5.4 software.Results:A total of 11 clinical trials, including 10 randomized controlled trials and 1 cross-over study were included, involving 605 patients, including 309 in the experimental group (nerve stimulation group) and 296 in the control group(antimuscarinic drugs group). The results of meta-analysis showed as follow. For patients with non-neurogenetic overactive bladder, there was no statistically significant differences between electrostimulation of the posterior tibial nerve therapy and antimuscarinic drugs in the improvement of 24h urination frequency( MD=-0.06, 95% CI -1.67-1.54, P>0.05), 24h urge incontinence frequency( MD=0.04, 95% CI -0.46-0.54, P>0.05), symptoms scores of OAB-q questionnaire( MD=0.37, 95% CI -0.02-0.76, P>0.05)and quality of life scores( SMD=0.32, 95% CI-0.06-0.69, P>0.05). However, compared with antimuscarinic drugs, posterior tibial nerve stimulation had better efficacy satisfaction rate ( OR=1.97, 95% CI 1.16-3.36, P<0.05) and lower side effect rate ( OR=0.24, 95% CI 0.12-0.48, P<0.0001). And the results have significant statistical differences. Conclusions:Electrostimulation of the posterior tibial nerve was almost as effective as antimuscarinic drugs in improving symptoms and quality of life in patients with non-neurogenic OAB. However, compared with antimuscarinic drugs, electrostimulation of the posterior tibial nerve had a higher efficacy satisfaction rate and a lower incidence of side effects. Due to limited quality and quantity of the included studies, more high quality studies are required to verify above conclusions.

Objective:To explore the clinical efficacy of microsurgical technique combined with cosmetic suture technique in situ replantation of total scalp avulsion.Methods:The clinical data of patients with total scalp avulsion admitted to the Department of Burn and Plastic Surgery of General Hospital of Northern Theatre Command from January 2015 to December 2020 were collected. All patients were treated by microsurgical technique combined with cosmetic suture technique. Thorough debridement was performed during the operation. Active anti-shock treatment was given to the patient with hemorrhagic shock. The vascular was explored and labeled. The vascular anastomosis was conducted by microsurgical technique. The venous anastomosis was performed in the first place. The arterial anastomosis was performed according to the patient's condition. Symptomatic treatment, such as routine anti-coagulation, was given to patients after the operation. An infection prevention strategy was performed in patients. The recovery of patients was observed.Results:A total of six patients were involved in this study. All patients were females, aged from 36 to 55 years old. Various degrees of wound contamination can be seen, and one patient with hemorrhagic shock. The superficial temporal vein, supraorbital vein and sentinel vein were anastomosed in two patients, and the superficial temporal vein and sentinel vein were anastomosed in four patients. The superficial temporal artery and supratrochlear artery were anastomosed in two patients, and the superficial temporal artery was anastomosed in four patients. All patients were followed up for 3 months to 2 years, averaging 13.71 months. More than 90% of the scalp survived in three patients, 80% in two patients, and 50% in one patient. The necrotic area survived after replantation of a split-thickness skin graft. The sensory function of surviving scalp after replantation was slightly regressed. The hair growth was normal. Only superficial linear scar left. All patients were satisfied with the efficacy.Conclusions:The application of the microsurgical technique for vascular anastomosis combined with cosmetic suture technique for repair can achieve good clinical efficacy in situ replantation of total scalp avulsion.

Objective:To explore the clinical efficacy of microsurgical technique combined with cosmetic suture technique in situ replantation of total scalp avulsion.Methods:The clinical data of patients with total scalp avulsion admitted to the Department of Burn and Plastic Surgery of General Hospital of Northern Theatre Command from January 2015 to December 2020 were collected. All patients were treated by microsurgical technique combined with cosmetic suture technique. Thorough debridement was performed during the operation. Active anti-shock treatment was given to the patient with hemorrhagic shock. The vascular was explored and labeled. The vascular anastomosis was conducted by microsurgical technique. The venous anastomosis was performed in the first place. The arterial anastomosis was performed according to the patient's condition. Symptomatic treatment, such as routine anti-coagulation, was given to patients after the operation. An infection prevention strategy was performed in patients. The recovery of patients was observed.Results:A total of six patients were involved in this study. All patients were females, aged from 36 to 55 years old. Various degrees of wound contamination can be seen, and one patient with hemorrhagic shock. The superficial temporal vein, supraorbital vein and sentinel vein were anastomosed in two patients, and the superficial temporal vein and sentinel vein were anastomosed in four patients. The superficial temporal artery and supratrochlear artery were anastomosed in two patients, and the superficial temporal artery was anastomosed in four patients. All patients were followed up for 3 months to 2 years, averaging 13.71 months. More than 90% of the scalp survived in three patients, 80% in two patients, and 50% in one patient. The necrotic area survived after replantation of a split-thickness skin graft. The sensory function of surviving scalp after replantation was slightly regressed. The hair growth was normal. Only superficial linear scar left. All patients were satisfied with the efficacy.Conclusions:The application of the microsurgical technique for vascular anastomosis combined with cosmetic suture technique for repair can achieve good clinical efficacy in situ replantation of total scalp avulsion.

Objective:To investigate the role of NIMA-related kinase-7 (NEK7) in breast cancer (BC) and its potential molecular mechanism.Methods:Quantitative real-time reverse-transcription (RT-qPCR) was used to detect the expression of NEK7 in BC tissue and cell lines. The effect of NEK7 on BC cell proliferation was examined by CCK-8. Proteins interacted with NEK7 were screened in Biological database. The effect of overexpression of NOD-like receptor protein 3 (NLRP3) on BC cell proliferation was evaluated. Western blot was used to detect NLRP3 protein expression, and ELISA was employed to evaluate IL-1β and IL-18 expression level.Result:NEK7 was upregulated in BC tissues and cells, and enforced-expression of NEK7 promoted BC cell proliferation[NEK7 over-expression group: 24 h: (0.33±0.02) , 48 h: (0.59±0.02) , 72 h: (0.76±0.02) ; Blank group: 24 h: (0.30±0.02) , 48 h: (0.45±0.02) , 72 h: (0.62±0.03) ; NEK7 empty vector group: 24 h: (0.32±0.02) , 48 h: (0.46±0.02) , 72 h: (0.63±0.03) ]. There was a positive correlation between NEK7 and NLRP3 ( R=0.13) . Overexpression of NLRP3 increased the proliferation ability of BC cell[NLRP3 over-expression group: 24 h: (0.35±0.02) , 48 h: (0.65±0.02) , 72 h: (0.80±0.03) ; Blank group: 24 h: (0.33±0.02) , 48 h: (0.51±0.02) , 72 h: (0.66±0.03) ; NLRP3 empty vector group: 24 h: (0.34±0.02) , 48 h: (0.52±0.03) , 72 h: (0.66±0.03) ]. NEK7 could positively regulate NLRP3 protein and up-regulate IL-1β (NEK7 over-expression group: 129.96±7.62 pg/ml, Blank group: 19.80±2.42pg/ml, NEK7 empty vector group: 21.30±1.77 pg/ml) and IL-18 (NEK7 over-expression group: 144.08±17.20 pg/ml, Blank group: 16.84±2.34pg/ml, NEK7 empty vector group: 17.64±1.94 pg/ml) expression. Conclusion:The upregulation of NEK7 was involved in the process of BC progression by inducing NLRP3 inflammasome activation, suggesting that NEK7 might be a promising therapeutic target for BC.

Objective To investigate the clinical characteristics of DCD donor-derived CRKP infection and bleeding in kidney transplantation,and to summarize the experience of diagnosis,treatment and prevention.Methods A retrospective analysis was carried out from July 2016 to December 2017 in hospital,containing clinical data of 4 cases of CRKP-infected DCD donors and 7 cases of kidney transplantation recipients.Results In the CRKP culture of 4 cases of DCD donors,1 case was positive for blood culture,1 case was positive for urine culture,1 case was positive for sputum culture,and 1 case was negative for blood,urine and sputum culture.The corresponding 7 recipients were all positive for blood culture after renal transplantation,4 cases were positive for urine culture,3 cases were positive for sputum culture,and 5 cases were positive for perirenal drainage.Of the 7 patients,4 cases had renal artery hemorrhage,1 of them was died.The average bleeding time was 17.75 days after operation (14-19 days).In 7 patients with renal transplantation,CRP increasd.And in 3 cases of deaths,CRP was stably higher than normal.Meanwhile,CRP in 4 surviving patients gradually decreased to the normal range after effective anti-infection treatment.All 7 patients were treated with carbapenems;2 patients were dead without avibactam therapy;and 5 cases were treated with avibactam and carbapenems and survived,1 case died and 1 case had good renal function recovery.Conclusion Positive CRKP in blood,urine and sputum of DCD donors can lead to CRKP infection in kidney transplant recipients.Even if the body fluids of donors are all negative,the false negative results could not be excluded.Persistent or increased high-level CRP after operation is an early warning on CRKP infection.And CRP can be used as an indicator for evaluating the effectiveness of anti CRKP therapy.The combination of avibactam and carbapenem antibiotics is an effective regimen in the treatment of DCD donor-derived CRKP.