Hepatic stellate cells (HSCs) are the primary fibrogenic cells in the liver, and their activation plays a crucial role in the development and progression of hepatic fibrosis. Here, we report that retinoid X receptor-alpha (RXRα), a unique member of the nuclear receptor superfamily, is a key modulator of HSC activation and liver fibrosis. RXRα exerts its effects by modulating calcium/calmodulin-dependent protein kinase kinase β (CaMKKβ)-mediated activation of AMP-activated protein kinase-alpha (AMPKα). In addition, we demonstrate that K-80003, which binds RXRα by a unique mechanism, effectively suppresses HSC activation, proliferation, and migration, thereby inhibiting liver fibrosis in the CCl₄ and amylin liver NASH (AMLN) diet animal models. The effect is mediated by AMPKα activation, promoting mitophagy in HSCs. Mechanistically, K-80003 activates AMPKα by inducing RXRα to form condensates with CaMKKβ and AMPKα via a two-phase process. The formation of RXRα condensates is driven by its N-terminal intrinsic disorder region and requires phosphorylation by CaMKKβ. Our results reveal a crucial role of RXRα in liver fibrosis regulation through modulating mitochondrial activities in HSCs. Furthermore, they suggest that K-80003 and related RXRα modulators hold promise as therapeutic agents for fibrosis-related diseases.

Bacterial resistance and excessive inflammation are common issues that hinder wound healing.Antimicrobial peptides(AMPs)offer a promising and versatile antibacterial option compared to traditional antibiotics,with additional anti-inflammatory properties.However,the applications of AMPs are limited by their antimicrobial effects and stability against bacterial degradation.TFNAs are regarded as a promising drug delivery platform that could enhance the antibacterial properties and stability of nanodrugs.Therefore,in this study,a composite hydrogel(HAMA/t-GL13K)was prepared via the photocross-linking method,in which tFNAs carry GL13K.The hydrogel was injectable,biocompatible,and could be instantly photocured.It exhibited broad-spectrum antibacterial and anti-inflammatory properties by inhibiting the expression of inflammatory factors and scavenging ROS.Thereby,the hydrogel inhibited bacterial infection,shortened the wound healing time of skin defects in infected skin full-thickness defect wound models and reduced scarring.The constructed HAMA/tFNA-AMPs hydrogels exhibit the potential for clinical use in treating microbial infections and promoting wound healing.

Objective To investigate the effects of calcitriol intervention on PI3K/AKT signaling pathway and wound healing in rats with diabetic foot ulcer(DFU).Methods Thirty-two male SD rats were divided into normal control(Con)group,DFU group,calcitriol low dose(L)group and calcitriol high dose(H)group.A circular wound of 5 mm in diameter and deep to the fascia was made on the dorsum of the left foot of rats in each group.HE staining was used to evaluate the histopathological changes of the wounds.Immunohistochemical method was selected to compare the distribution of CD34-positive cells and the expression of p-PI3K and p-AKT in traumatic tissues of each group.ELISA was adopted in the detection of serum IL-6,IFN-γ,TNF-α and IL-7.RT-PCR was used to detect the mRNA expression of PI3K and AKT in each group,and western blot was used to detect the protein expression of PI3K,p-PI3K,AKT,p-AKT and VEGF.Results Compared with Con group,the expressions of IL-6,IFN-γ,TNF-α,IL-7,CD34,PI3K mRNA,AKT mRNA,p-AKT protein,p-PI3K protein,p-PI3K/PI3K,p-AKT/AKT increased,while PI3K protein expression decreased in DFU,L and H groups(P<0.05),VEGF and AKT protein expression decreased in DFV and L groups(P<0.05).Compared with DFU group,the expressions of VEGF,AKT and PI3K protein increased(P<0.05),while the expressions of p-PI3K/PI3K,p-AKT/AKT decreased in L and H groups(P<0.05),IL-6 decreased in L group(P<0.05),and CD34 expression increased in H group(P<0.05),while IL-6,IFN-γ,TNF-α and IL-7,PI3K mRNA,AKT mRNA,p-AKT protein and p-PI3K protein expression decreased(P<0.05).Compared with L group,the expressions of CD34,VEGF,AKT and PI3K protein increased(P<0.05),while IL-6,PI3K mRNA,AKT mRNA,p-AKT protein,p-PI3K protein,p-PI3K/PI3K and p-AKT/AKT decreased in H group(P<0.05).Conclusions Calcitriol intervention may reduce the activity of the PI3K/AKT signaling pathway,inhibit inflammation,promote neovascularization,and facilitate wound healing in rats with DFU.

Pulmonary blast injury has become the main type of trauma in modern warfare, characterized by externally mild injuries but internally severe injuries, rapid disease progression, and a high rate of early death. The injury is complicated in clinical practice, often with multiple and compound injuries. Currently, there is a lack of effective protective materials, accurate injury detection instrument and portable monitoring and transportation equipment, standardized clinical treatment guidelines in various medical centers, and evidence-based guidelines at home and abroad, resulting in a high mortality in clinlcal practice. Therefore, the Trauma Branch of Chinese Medical Association and the Editorial Committee of Chinese Journal of Trauma organized military and civilian experts in related fields such as thoracic surgery and traumatic surgery to jointly develop the Clinical treatment guideline for pulmonary blast injury ( version 2023) by combining evidence for effectiveness and clinical first-line treatment experience. This guideline provided 16 recommended opinions surrounding definition, characteristics, pre-hospital diagnosis and treatment, and in-hospital treatment of pulmonary blast injury, hoping to provide a basis for the clinical treatment in hospitals at different levels.

Objective:To compare the efficacy of standardized incision and conventional incision for reduction and internal fixation of multiple rib fracture.Methods:A retrospective cohort study was conducted to analyze the clinical data of 192 patients with multiple rib fracture treated in 909th Hospital of Joint Logistics Support Force (Affiliated Dongnan Hospital of Xianmen University Medical College) from January 2020 to January 2022. There were 101 males and 91 females; aged 32-94 years [(51.5±16.6)years]. The patients underwent open reduction and internal fixation with nickel-titanium shape memory alloy embracer via standard incision such as anterior axillary longitudinal incision (standard incision group, n=96) or conventional incision such as posterolateral incision (conventional incision group, n=96). The incision length, operation time, intraoperative blood loss, number of fixed fractures, indwelling time of closed thoracic drainage tube, postoperative thoracic drainage volume, postoperative spontaneous ambulation time and length of hospital stay were compared in the two groups. The visual analogue scale (VAS) was used to evaluate pain at 1 month after operation. Postoperative complications were recorded. Results:All patients were followed up for 1-16 months [4.0(3.0, 10.5)months]. The operation time, intraoperative blood loss, indwelling time of closed thoracic drainage tube, postoperative thoracic drainage volume, postoperative spontaneous ambulation time, length of hospital stay and VAS at postoperative 1 month in standard incision group [(12.1±1.6)cm, (51.4±13.0)minutes, (191.5±16.8)ml, (2.8±0.6)days, (568.9±109.0)ml, (4.1±0.7)days, (11.4±1.7)days, (2.5±0.7)points] were better than those in conventional incision group [(13.7±1.9)cm, (62.0±8.8)minutes, (248.9±65.4)ml, (4.8±1.1)days, (655.9±121.9)ml, (5.2±0.9)days, (15.3± 1.7)days, (3.5±0.7)points] ( P<0.05 or 0.01). There was no statistical difference in the number of fixed fractures between standard incision group and conventional incision group (5.1±0.8 vs. 5.4±0.9) ( P>0.05). In standard incision group, there were 3 patients with poor wound healing, 5 with pulmonary infection, 3 with atelectasis and 3 with small pleural effusion. In conventional incision group, there were 11 patients with poor wound healing, 9 with pulmonary infection, 7 with atelectasis and 7 with small pleural effusion. The incidence of postoperative complications was 14.6% (14/96) in standard incision group and 35.4% (34/96) in conventional incision group ( P<0.01). Conclusion:For multiple rib fracture, standard incision is superior to conventional incision reduction in shortening the incision length, operation time, indwelling time of drainage tube, postoperative spontaneous ambulation time and length of hospital stay, reducing the intraoperative blood loss and postoperative thoracic drainage volume, alleviating the pain and reducing the postoperative complications.

Objective:To compare the clinical efficacy of extracorporeal membrane oxygenation (ECMO) and ventilation therapy in the treatment of severe blast lung injury.Methods:A retrospective cohort study was conducted to analyze the clinical data of 37 patients with severe blast lung injury admitted to 909th Hospital of Joint Logistics Support Force (Affiliated Dongnan Hospital of Xianmen University Medical College) from January 2000 to December 2021, including 23 males and 14 females; aged 26-50 years [(36.3±11.1)years]. The chest abbreviated injury score (AIS) was 3-5 points. In all, 16 patients were treated with ECMO from January 2017 to December 2021 (ECMO group) and 21 with ventilator from January 2000 to December 2016 (ventilator group). Blood gas analysis indexes [arterial pH, partial pressure of carbon dioxide (PaCO 2), partial pressure of oxygen (PaO 2), blood lactate (Lac)] and hemodynamics indexes [central venous pressure (CVP), cardiac output index (CI), pulmonary arterial systolic pressure (PASP), pulmonary capillary wedge pressure (PAWP)] were compared in the two groups at 30 minutes before treatment and at 2, 4, 6 hours after treatment. The mechanical ventilation time, ICU length of stay, acute physiology and chronic health evaluation II (APACHE II) score and mortality were measured at 7 days after treatment. Results:All patients were followed up for 24-48 months [(33.6±8.2)months]. The blood gas analysis and hemodynamic indexes were significantly improved in the two groups at 2, 4, 6 hours after treatment when compared with those at 30 minutes before treatment (all P<0.05), and the improvements were still statistically significant in ECMO group at 4, 6 hours after treatment when compared with those at 2 hours after treatment (all P<0.05), while not in ventilator group (all P>0.05). There was no significant difference in blood gas analysis indexes or hemodynamic indexes between the two groups at 30 minutes before treatment (all P>0.05). After treatment for 2, 4, 6 hours, blood gas analysis indexes and hemodynamic indexes in ECMO group were statistically different from those in ventilator group (all P<0.05). After treatment for 7 days, the mechanical ventilation time, ICU length of stay, APACHE II score and mortality were (3.2±1.2)days, (5.4±1.3)days, (14.1±3.3)points and 12.5% (2/16) in ECMO group, significantly different from (5.1±1.6)days, (7.6±1.6)days, (10.2±2.6)days and 28.6% (6/21) in ventilator group (all P<0.05). Conclusion:For severe blast lung injury, ECMO can attain rapid and continuous improvement of refractory hypoxemia and dyspnea, shorten the duration of mechanical ventilation and ICU length of stay and reduce the mortality rate when compared with ventilator therapy.

Tripterygium wilfordii is a valuable medicinal plant rich in biologically active diterpenoids, but there are few studies on the origins of these diterpenoids in its secondary metabolism. Here, we identified three regions containing tandemly duplicated diterpene synthase genes on chromosomes (Chr) 17 and 21 of T. wilfordii and obtained 11 diterpene synthases with different functions. We further revealed that these diterpene synthases underwent duplication and rearrangement at approximately 2.3-23.7 million years ago (MYA) by whole-genome triplication (WGT), transposon mediation, and tandem duplication, followed by functional divergence. We first demonstrated that four key amino acids in the sequences of TwCPS3, TwCPS5, and TwCPS6 were altered during evolution, leading to their functional divergence and the formation of diterpene secondary metabolites. Then, we demonstrated that the functional divergence of three TwKSLs was driven by mutations in two key amino acids. Finally, we discovered the mechanisms of evolution and pseudogenization of miltiradiene synthases in T. wilfordii and elucidated that the new function in TwMS1/2 from the terpene synthase (TPS)-b subfamily was caused by progressive changes in multiple amino acids after the WGT event. Our results provide key evidence for the formation of diverse diterpenoids during the evolution of secondary metabolites in T. wilfordii.

Objective:To investigate the application value of three-dimensional (3D) printing technology assisted laparoscopic anatomic liver resection of segment 8 (Lap-S8).Methods:The retrospective and descriptive study was conducted. The clinicopathological data of 8 liver cancer patients including 7 cases with hepatocellular carcinoma and 1 case with intrahepatic cholangio-carcinoma who underwent 3D printing technology assisted Lap-S8 in the Hunan Provincial People′s Hospital from January 2019 to December 2020 were collected. There were 7 males and 1 female, aged from 49.0 to 80.0 years, with a median age of 56.5 years. Of the 8 patients, 6 cases underwent laparoscopic anatomic liver resection of the entire segment 8, 1 case underwent laparoscopic anatomic liver resection of ventral subsegmental of the segment 8 and 1 case underwent laparoscopic anatomic liver resection of dorsal subsegmental of the segment 8. 3D printing technology was used to assist preoperative evaluation and intraoperative navigation for all 8 patients. Observation indicators: (1) surgical situations; (2) postoperative situations; (3) follow-up. Follow-up was conducted using outpatient examination, internet or telephone interview to detect survival and tumor recurrence of patients after operation up to March 2021. Measurement data with normal distribution were represented as Mean±SD, and measurement data with skewed distribution were represented as M(range). Count data were described as absolute numbers. Results:(1) Surgical situations: all the 8 patients underwent 3D printing technology assisted Lap-S8 successfully, without conversion to open surgery. The operation time, hepatic portal occlusion time and volume of intraoperative blood loss of the 8 patients were (216±41)minutes, (56±11)minutes and 75 mL(range, 50 to 300 mL), respectively. There was no intraoperative blood transfusion in 8 patients, and the surgical margin of the 8 patients was negative. (2) Postoperative situations: the duration of postoperative hospital stay of the 8 patients were (9±3)days. There was no complication such as postoperative hemorrhage, biliary fistula, liver abscess or abdominal infection occurred. (3) Follow-up: all the 8 patients were followed up for 3.0?24.0 months, with a median follow-up time of 12.5 months. During the follow-up, 1 of 8 patients with preoperative diagnosis of recurrent hepatocellular carcinoma developed tumor recurrence at 5 months after operation. The patient underwent laparoscopic surgery followed with the transcatheter arterial chemoembolization and target therapy, and survived with tumor. There was no tumor recurrence in the other 7 patients.Conclusion:3D printing technology assisted Lap-S8 is safe and feasible.

Objective: To investigate the safety and feasibility of longitudinal transpancreatic U-sutures invaginated pancreatojejunostomy (Chen′s pancreaticojejunostomy technique) in laparoscopic pancreaticoduodenectomy (LPD) . Methods: Clinical data of 116 consecutive patients who underwent LPD using Chen′s pancreaticojejunostomy technique in Hunan Provincial People′s Hospital from May 2017 to December 2018 were retrospectively analyzed. Among these patients, 66 were males and 50 were females. The median age was 58 years old (32-84 yeas old). All 116 patients underwent pure laparoscopic whipple procedure with Child reconstruction method, using Chen′s pancreaticojejunostomy technique. The intraoperative and postoperative data of patients were analyzed. Results: All 116 patients underwent LPD successfully. The mean operative time was (260.3±33.5) minutes (200-620 minutes). The mean time of pancreaticojejunostomy was (18.2±7.6) minutes (14-35 minutes) . The mean time of hepaticojejunostomy was (14.6±6.3) minutes (10-25 minutes). The mean time of gastrojejunostomy was (12.0±5.5) minutes (8-20 minutes). The mean estimated blood loss was (106.0±87.6) ml (20-800 ml). Postoperative complications were: 11.2% (13/116) of cases had postoperative pancreatic fistula (POPF) , including 10.3% (12/116) of biochemical fistula and 0.9% (1/116) of grade B POPF, no grade C POPF occurred; 10.3% (12/116) had gastrojejunal anastomotic bleeding; 3.4% (4/116) had hepaticojejunal anastomotic fistula; 3.4% (4/116) had delayed gastric emptying; 4.3% (5/116) had localized abdominal infection; 12.1% (14/116) had pulmonary infection; postoperative mortality were 0(0/116) and 1.7% (2/116) within 30 days and 90 days, respectively. One patient died of massive abdominal bleeding secondary to Gastroduodenal artery pseudoaneurysm rupture, the other patient died of extensive tumor recurrence and metastasis after surgery. Conclusions Chen′s pancreaticojejunostomy technique is safe and feasible for LPD.It is an option especially for surgeons who have not completed the learning curve of LPD.

Objective: To explore the safety and feasibility of laparoscopic liver resection in the treatment of intrahepatic cholangiocarcinoma (ICC). Methods: The retrospective study was adopted. The clinical data of 58 patients with ICC who underwent laparoscopic liver resection in the Department of Hepatobiliary Minimally Invasive Surgery of the First Affiliated Hospital of Hu′nan Normal University were collected From January 2016 to December 2018. Among them, 34 patients were males and 24 were females, aged from 34 to 71 years with a median age of 54 years. Observation indicators: (1) Surgical treatment: surgical methods, operation time, intraoperative blood loss, intraoperative blood transfusion rate, intraoperative hepatic portal blocking time, conversion rate, postoperative complications, postoperative hospital stay. (2) Postoperative pathological conditions. (3) Follow-up.Follow-up visits were conducted using an outpatient clinic and telephone to understand patient survival after surgery. The follow-up period was until June 2019. Measurement data with normal distribution were expressed as (Mean±SD), count data was expressed as frequency and percentage. Results: A total of 58 patients were included in this study, of which 48 patients underwent laparoscopic radical surgical resection of intrahepatic cholangiocarcinoma and 10 patients underwent laparoscopic conversion to laparotomy. (1) Surgical treatment: laparoscopic resection of the left liver (segments Ⅱ, Ⅲ and Ⅳ), laparoscopic resection of the right liver (segments Ⅴ, Ⅵ, Ⅶ and Ⅷ), laparoscopic resection of the right posterior lobe (segments Ⅵ and Ⅶ), laparoscopic extended resection of the right posterior lobe, laparoscopic resection of the middle lobe (Ⅳ, Ⅴ and Ⅷ), laparoscopic resection of the V and Ⅵ, laparoscopic resection of the left liver (segments Ⅱ, Ⅲ and Ⅳ) combined with the caudate lobe (segments I and Ⅸ), laparoscopic extended left hemihepatectomy, laparoscopic resection of the VI, laparoscopic resection of the Ⅶ and Ⅷ, laparoscopic resection of the left lateral lobe (segments Ⅱ and Ⅲ) and laparoscopic resection of the right hepatic mass; operation time: (320.38±107.68) min; intraoperative blood loss: (262.34±76.06); intraoperative blood loss: 0 (0/58); Intraoperative hepatic portal occlusion time: (48±15) min, the conversion rate was 17.2% (10/58); the incidence of postoperative biliary fistula was 6.8% (4/58), and the patient was discharged after conservative treatment and unobstructed drainage (T-tube vacuum suction); the postoperative gastrointestinal recovery time was (1.84±0.57) d; no other serious complications occurred.Postoperative hospital stay: (9.34±3.39) d; there were no deaths and unplanned surgeries during the perioperative period. (2) Pathological conditions: 32 cases received lymph node dissection during the operation, and 26 cases showed cholangiocarcinoma without lymph node dissection; pathological examination showed that the pathological reports of all tumor margins were negative, and 4 cases showed lymph node dissection and positive lymph node metastasis. (3) Follow-up results: of the 58 patients with ICC, 49 were followed up for 6 to 36 months. The tumor survival time was (4 to 36) months. 28 patients survived without tumor. 17 patients had intrahepatic metastasis with multiple lymph node metastasis. 4 patients were treated with microwave ablation after intrahepatic metastasis was found. 9 patients were lost to follow-up. Conclusion Laparoscopic treatment of intrahepatic cholangiocarcinoma is safe and feasible in experienced centers.