Objective:To investigate the effect of low-dose ketamine on neuroinflammation and microcirculation in mice with traumatic brain injury (TBI).Methods:Sixty adult male C57BL/6 mice, weighing 22-28 g, were randomly divided into sham-operated group, TBI group, Sham+ketamine group, and TBI+ketamine group ( n=15). A controlled cortical impingement (CCI) method was used to establish TBI models in the later 2 groups. Sham+ketamine group and TBI+ketamine group were intraperitoneally injected with 30 mg/kg ketamine once daily for 3 d at 30 min after TBI; sham-operated group and TBI group were intraperitoneally injected same amount of saline at the same time points. Cerebral cortical blood flow in 6 mice from each group was measured by laser speckle contrast imaging (LSCI) before, immediately after, 30 min after, 1 d after and 3 d after modeling, respectively. Three d after modeling, immunohistochemical staining and immunofluorescent double label staining were used to detect the nuclear translocation of microglia markers, ionized calcin-antibody-1 (Iba-1) and nuclear factor (NF)-κB p65 in damaged cortical brain tissues in 6 mice from each group. The remaining 3 mice in each group were sacrificed and tissue plasma was extracted 3 d after modeling; levels of NF-κB p65, phosphorylated (p)-NF-κB p65, p-IκB and inducible nitric oxide synthase (iNOS) in cortical brain tissues were detected by Western blotting. Expressions of tumor necrosis factor-α (TNF-α), interleukin-1-β (IL-1β) and interleukin-6 (IL-6), iNOS, reactive oxygen species (ROS) and reactive nitrogen species (RNS) in cortical brain tissues were detected by ELISA. Results:LSCI indicated that, 3 d after modeling, relative blood flow in local cerebral microcirculation of TBI+ketamine group was significantly increased compared with that of TBI group ( P<0.05). Immunohistochemical staining indicated that compared with the sham-operated group and Sham+ketamine group, the TBI group and TBI+ketamine group had significantly increased number of Iba-1 positive cells in the cerebral cortex ( P<0.05); compared with the TBI group, the TBI+ketamine group had significantly decreased number of Iba-1 positive cells ( P<0.05). ELISA indicated that compared with the sham-operated group and Sham+ketamine group, the TBI group and TBI+ketamine group had significantly increased expressions of TNF-α, IL-1β, IL-6, iNOS, ROS and RNS in damaged cortical brain tissues ( P<0.05); compared with the TBI group, the TBI+ ketamine group had significantly decreased expressions of TNF-α, IL-1β, IL-6, iNOS, ROS and RNS in damaged cortical brain tissues ( P<0.05). Immunofluorescent double label staining indicated obviously inhibited NF-κB p65 nuclear translocation in TBI+ketamine group when it was compared with TBI group. Western blotting indicated that compared with the sham-operated group and Sham+ketamine group, the TBI+ketamine group had significantly increased iNOS, NF-κB p65, p-NF-κB p65 and P-IκB protein expressions in damaged cortical brain tissues ( P<0.05); compared with the TBI group, the TBI+ketamine group had significantly decreased protein expressions of iNOS, NF-κB p65, p-NF-κB p65 and p-IκB in damaged cortical brain tissues ( P<0.05). Conclusion:Low-dose ketamine reduces neuroinflammation and improves cerebral microcirculatory blood flow after open TBI, whose mechanism may be related to inhibition of microglia NF-κB/iNOS pathway.

ObjectiveMetabolomics was utilized to investigate the preventive effect of notoginseng total saponins（NTS） on aspirin（acetyl salicylic acid， ASA）-induced small bowel injury in rats. MethodFifty male SD rats were randomly divided into normal and model groups， NTS high-dose and low-dose groups（62.5， 31.25 mg·kg^-1）， and positive drug group（omeprazole 2.08 mg·kg^-1+rebamipide 31.25 mg·kg^-1）， with 10 rats in each group. Except for the normal group， rats in other groups were given ASA enteric-coated pellets 10.41 mg·kg^-1 daily to establish a small intestine injury model. On this basis， each medication group was gavaged daily with the corresponding dose of drug， and the normal group and the model group were gavaged with an equal amount of drinking water. Changes in body mass and fecal characteristics of rats were recorded and scored during the period. After 14 weeks of administration， small intestinal tissues of each group were taken for hematoxylin-eosin（HE） staining， scanning electron microscopy to observe the damage， and the apparent damage of small intestine was scored. Serum from rats in the normal group， the model group， and the NTS high-dose group was taken and analyzed for metabolomics by ultra-performance liquid chromatography-quadrupole-electrostatic field orbitrap high-resolution mass spectrometry（UPLC-Q-Exactive Orbitrap MS）， and the data were processed by multivariate statistical analysis， the potential biomarkers were screened by variable importance in the projection（VIP） value≥1.0， fold change（FC）≥1.5 or ≤0.6 and t-test P<0.05， and pathway enrichment analysis of differential metabolites was performed in conjunction with Human Metabolome Database（HMDB） and Kyoto Encyclopedia of Genes and Genomes（KEGG）. ResultAfter 14 weeks of administration， the average body mass gain of the model group was lower than that of the normal group， and the NTS high-dose group was close to that of the normal group. Compared with the normal group， the fecal character score of rats in the model group was significantly increased（P<0.05）， and compared with the model group， the scores of the positive drug group and the NTS high-dose group were reduced， but the difference was not statistically significant. HE staining and scanning electron microscopy results showed that NTS could significantly improve ASA-induced small intestinal injury， compared with the normal group， the small bowel injury score of the model group was significantly increased（P<0.01）， compared with the model group， the small bowel injury scores of the NTS low and high dose groups were significantly reduced（P<0.05， P<0.01）. Serum metabolomics screened a total of 75 differential metabolites between the normal group and the model group， of which 55 were up-regulated and 20 were down-regulated， 76 differential metabolites between the model group and the NTS groups， of which 14 were up-regulated and 62 were down-regulated. NTS could modulate three differential metabolites（salicylic acid， 3-hydroxybenzoic acid and 4-hydroxybenzoic acid）， which were involved in 3 metabolic pathways， namely， the bile secretion， the biosynthesis of folic acid， and the biosynthesis of phenylalanine， tyrosine and tryptophan. ConclusionNTS can prevent ASA-induced small bowel injury， and the underlying mechanism may be related to the regulation of bile secretion and amino acid metabolic pathways in rats.

Objective:To investigate the clinical effect of three-dimensional(3D) flap model accurately designed before the operation in repairing irregular wounds of limbs with anterolateral thigh(ALT) perforator flap.Methods:The data of patients with ALT flaps designed with 3D printing technology to repair irregular soft tissue defects of limbs in Suzhou Ruihua Orthopedic Hospital from January to October 2022 were retrospectively analyzed. After the wound was scanned by 3D scanner before surgery, the wound model was printed. The ALT flap was precisely designed and harvested for covering the wound according to the body surface projection of the perforator vessel in the anterolateral femoral region located by color Doppler ultrasound before surgery. The survival of the flap, the healing of the donor and recipient sites and the occurrence of complications were observed and followed up after the operation. The effect of wound repair was evaluated by the comprehensive efficacy evaluation scale of the skin flap. The total score was 100 points, which was divided into excellent (90-100 points), good (75-89 points), fair (60-74 points) and poor (< 60 points).Results:A total of 34 patients were enrolled, including 26 males and 8 females, aged 18-75 years, with an average age of 45.5 years. Injury sites: wrist in 17 cases, foot in 10 cases, ankle in 7 cases. The operation time was 2.0-4.5 h (mean 3.3 h), and all donor sites were sutured directly. Vascular crisis occurred in 2 cases after skin flap transplantation. After surgical exploration, the transplanted skin flap survived, and the other skin flaps survived successfully. All 34 patients were followed up for 6 to 10 months, with an average of 8 months. All the donor sites of the skin flap healed primarily, and the wound healing time of the recipient site was 10-44 days, with an average of 20 days. At the last follow-up, the skin flap was good in color and texture, and the sensation returned to S1 and S2 grades. There were scars left in the donor site, no cicatricial contracture, pain and other discomfort, and no other serious complications. The results of flap evaluation were 80-91 points, with an average of 86 points. Among them, 25 cases were excellent, 6 cases were good, 3 cases were fair, and the excellent and good rate was 91%(31/34).Conclusion:The application of 3D printing technology assisted the design of ALT perforator flap to repair irregular wounds of limbs can significantly reduce the intraoperative design time of the flap, which is in line with the concept of precise design and incision of the flap, and has good clinical effect, and can effectively reduce the trauma and complications of the donor site.

Objective:To investigate the effects of anterolateral femoral perforator flaps pedicled with oblique branch of lateral circumflex femoral artery and carrying fascia lata in repairing destructive wounds and rebuilding function of hands or feet.Methods:This study was a retrospective observational study. From January 2022 to March 2023, 16 patients with destructive wounds in hands or feet combined with extensor tendon defects who met the inclusion criteria were admitted to Suzhou Ruihua Orthopedic Hospital, including 12 males and 4 females, aged 3 to 63 years. The wounds were located on the hands in 12 cases and on the feet in 4 cases. The number of defective extensor tendon ranged one to five, and the length of the defect ranged from 2.5 to 6.0 cm. The wound area was 11.0 cm×5.5 cm to 29.0 cm×9.5 cm after debridement. The wounds were repaired with anterolateral femoral perforator flaps pedicled with oblique branch of lateral circumflex femoral artery and carrying fascia lata, and the flap area was 12.0 cm×6.5 cm to 30.0 cm×11.0 cm. The fascia lata was used to repair the extensor tendon defects, and the harvesting area of fascia lata was 8.0 cm×3.0 cm to 12.0 cm×8.0 cm. The wounds in flap donor areas in 15 patients were sutured directly, and the wound in flap donor area in 1 patient was covered with medium-thickness skin graft from lower abdomen. The survival of flaps and the wound healing in donor and recipient areas of flaps were observed within 1 week after operation. The number of patients who underwent thinning and plastic surgery or tenolysis was recorded during postoperative follow-up. At the last follow-up, the recovery of sensory function of the transplanted flaps on hands or feet was evaluated, the efficacy of flap repair was evaluated according to the comprehensive flap evaluation scale, and the function of hands was evaluated according to the trial standards for evaluation of partial function of upper extremity by the Hand Surgery Society of Chinese Medical Association. The following two indexes were compared, including the measured total active motion of the injured fingers and the foot function assessed using Maryland foot function scale between before surgery and at the last follow-up.Results:Arterial crisis occurred in flaps in 2 patients after operation, and the flaps survived after timely exploration; the flaps in the rest patients survived well after operation. No obvious scar hyperplasia or ulceration was observed in donor and recipient areas of flaps after operation. All patients were followed up for 8 to 16 months, of which 6 patients underwent flap thinning and plastic surgery 6 to 7 months after operation, and 4 patients underwent tenolysis 3 to 6 months after operation. At the last follow-up, the recovery of sensory function of flaps reached S1 level in 5 cases and S2 level in 11 cases, and the two-point discrimination only had 1 point. The efficacy of flap repair scored 80 to 91, which were evaluated as excellent in 5 cases, good in 9 cases, and acceptable in 2 cases. The hand function was evaluated as excellent in 5 cases, good in 5 cases, and acceptable in 2 cases. The active extension function of the injured finger/toe was reconstructed successfully, and the total active motion of the injured finger was (225±22)° at the last follow-up, which was significantly higher than (117±20)° before surgery ( t=119.59, P<0.05); the foot function score was 86±7 at the last follow-up, which was significantly higher than 29±7 before surgery ( t=222.68, P<0.05), and the foot function was evaluated as excellent in 2 cases, good in 1 case, and acceptable in 1 case. Conclusions:The operation of harvesting the anterolateral femoral perforator flap pedicled with oblique branch of lateral circumflex femoral artery is relatively simple. After the wounds on hands or feet being repaired with the flaps, the appearance and function are good, with no obvious scar hyperplasia in donor and recipient areas of flaps. The fascia lata carried by the flap can repair the extensor tendon defect at the same time and improve the movement of the finger/toe.

Objective:To investigate the clinical effect of three-dimensional(3D) flap model accurately designed before the operation in repairing irregular wounds of limbs with anterolateral thigh(ALT) perforator flap.Methods:The data of patients with ALT flaps designed with 3D printing technology to repair irregular soft tissue defects of limbs in Suzhou Ruihua Orthopedic Hospital from January to October 2022 were retrospectively analyzed. After the wound was scanned by 3D scanner before surgery, the wound model was printed. The ALT flap was precisely designed and harvested for covering the wound according to the body surface projection of the perforator vessel in the anterolateral femoral region located by color Doppler ultrasound before surgery. The survival of the flap, the healing of the donor and recipient sites and the occurrence of complications were observed and followed up after the operation. The effect of wound repair was evaluated by the comprehensive efficacy evaluation scale of the skin flap. The total score was 100 points, which was divided into excellent (90-100 points), good (75-89 points), fair (60-74 points) and poor (< 60 points).Results:A total of 34 patients were enrolled, including 26 males and 8 females, aged 18-75 years, with an average age of 45.5 years. Injury sites: wrist in 17 cases, foot in 10 cases, ankle in 7 cases. The operation time was 2.0-4.5 h (mean 3.3 h), and all donor sites were sutured directly. Vascular crisis occurred in 2 cases after skin flap transplantation. After surgical exploration, the transplanted skin flap survived, and the other skin flaps survived successfully. All 34 patients were followed up for 6 to 10 months, with an average of 8 months. All the donor sites of the skin flap healed primarily, and the wound healing time of the recipient site was 10-44 days, with an average of 20 days. At the last follow-up, the skin flap was good in color and texture, and the sensation returned to S1 and S2 grades. There were scars left in the donor site, no cicatricial contracture, pain and other discomfort, and no other serious complications. The results of flap evaluation were 80-91 points, with an average of 86 points. Among them, 25 cases were excellent, 6 cases were good, 3 cases were fair, and the excellent and good rate was 91%(31/34).Conclusion:The application of 3D printing technology assisted the design of ALT perforator flap to repair irregular wounds of limbs can significantly reduce the intraoperative design time of the flap, which is in line with the concept of precise design and incision of the flap, and has good clinical effect, and can effectively reduce the trauma and complications of the donor site.

OBJECTIVE: To investigate the effectiveness of osteotomy of non-core weight-bearing area of the lateral tibial plateau, reduction, and internal fixation in the treatment of tibial plateau fractures involving posterolateral column collapse. METHODS: A clinical data of 23 patients with tibial plateau fractures involving posterolateral column collapse, who had undergone osteotomy of non-core weight-bearing area of the lateral tibial plateau, reduction, and internal fixation between January 2015 and June 2021, was retrospectively analyzed. There were 14 males and 9 females with an average age of 42.6 years ranging from 26 to 62 years. The causes of injury included traffic accident in 16 cases, falling from height in 5 cases, and other injuries in 2 cases. According to Schatzker classification, there were 15 cases of type Ⅴ and 8 cases of type Ⅵ. The time from injury to operation was 4-8 days with an average of 5.9 days. The operation time, intraoperative blood loss, fracture healing time, and complications were recorded. The depth of articular surface collapse of posterolateral column and posterior inclination angle (PSA) of the tibial plateau were compared before operation and at 2 days and 6 months after operation; fracture reduction of tibial plateau fracture was evaluated by Rasmussen anatomic score. The recovery of knee function was evaluated by Hospital for Special Surgery (HSS) score at 2 days and 6 months after operation. RESULTS: All 23 patients were completed the operation successfully. The operation time was 120-195 minutes, with an average of 152.8 minutes; the intraoperative blood loss was 50-175 mL, with an average of 109.5 mL. All patients were followed up 12-24 months, with an average of 16.7 months. One patient had superficial wound infection after operation, and the incision healed after dressing change; primary healing of incision of other patients was obtained. The fracture healing time was 12-18 weeks, with an average of 13.7 weeks. No failure of internal fixation, varus and valgus deformity of the knee joint, and instability of the knee joint was found at last follow-up. One patient developed joint stiffness and the range of motion of the knee joint was 10°-100°; the range of motion of the knee joint of other patients was 0°-125°. At 2 days and 6 months after operation, the depth of articular surface collapse of posterolateral column, PSA, and Rasmussen anatomic scores significantly improved when compared with those before operation ( P<0.05). There was no significant difference between the two postoperative time points ( P>0.05). The HSS score at 6 months after operation was significantly higher than that at 2 days after operation ( P<0.05). CONCLUSION For tibial plateau fractures involving posterolateral column collapse, reduction and internal fixation through osteotomy of non-core weight-bearing area of the lateral tibial plateau has the advantages of fully expose the posterolateral column fragment, good articular surface reduction, sufficient bone grafting, and fewer postoperative complications. It is beneficial to restore knee joint function and can be widely used in clinic.
Male ; Female ; Humans ; Adult ; Retrospective Studies ; Blood Loss, Surgical ; Tibial Plateau Fractures ; Treatment Outcome ; Bone Plates ; Tibial Fractures/surgery* ; Knee Joint ; Fracture Fixation, Internal ; Osteotomy ; Weight-Bearing

Objective To investigate whether Andrographolide(AG)can alleviate intestinal injury in sepsis by ac-tivating the SLC7A11/GPX4 axis in ferroptosis.Methods Forty rats were randomly divided into sham group(sham group),sepsis group(CLP group),AG low,medium and high dose groups(5,10 and 20 mg/kg).HE staining was used to observe the pathological changes of Intestinal tract.ELISA method was used to determine Inter-leukin 6(IL-6),tumour necrosis factor α(TNF-α),intestinal fatty acid binding protein(I-FABP),D-lactate content.The mechanism of ferroptosis was explored with AG high dose group(AG20 group),forty rats were ran-domly divided into sham group,CLP group,ferroptosis inhibitor(Fer-1)group,AG20+Fer-1 group.HE staining and transmission electron microscopy were used to observe the pathological changes of Intestinal tract.The kits were used to determine oxidative stress MDA,GSH levels and Fe3+content.Western blot was used to detect the protein levels of solute carrier family 7 member 11(SLC7A11),glutathione peroxidase 4(GPX4),and ferritin heavy poly-peptide 1(FTH-1).Results Compared with the sham group,the CLP group showed severe morphological damage to the small intestine,with significantly higher levels of inflammation,I-FABP and D-lactate(all P＜0.05),the AG group reversed these changes in a concentration-dependent manner(all P＜0.05).Compared with the CLP group,the AG20 and Fer-1 groups showed improved pathological damage to the small intestine,with lower levels of MDA and Fe3+and higher levels of GSH,SLC7A11,GPX4 and FTH-1 protein expression increased(all P＜0.05),and pathological injury and oxidative stress were reduced in the AG20+Fer-1 group,and SLC7A11,GPX4 and FTH-1 protein expression increased more significantly(all P＜0.05).Conclusion The mechanism by which AG attenuates intestinal injury in sepsis may be related to SLC7A11/GPX4 axis activation in ferroptosis.

Chronic refractory wound (CRW) is one of the most challengeable issues in clinic due to complex pathogenesis, long course of disease and poor prognosis. Experts need to conduct systematic summary for the diagnosis and treatment of CRW due to complex pathogenesis and poor prognosis, and standard guidelines for the diagnosis and treatment of CRW should be created. The Guideline forthe diagnosis and treatment of chronic refractory wounds in orthopedic trauma patients ( version 2023) was created by the expert group organized by the Chinese Association of Orthopedic Surgeons, Chinese Orthopedic Association, Chinese Society of Traumatology, and Trauma Orthopedics and Multiple Traumatology Group of Emergency Resuscitation Committee of Chinese Medical Doctor Association after the clinical problems were chosen based on demand-driven principles and principles of evidence-based medicine. The guideline systematically elaborated CRW from aspects of the epidemiology, diagnosis, treatment, postoperative management, complication prevention and comorbidity management, and rehabilitation and health education, and 9 recommendations were finally proposed to provide a reliable clinical reference for the diagnosis and treatment of CRW.

Objective:To explore the clinical efficacy and safety of different surgical procedures of Mayo level Ⅳ inferior vena cava tumor thrombus(IVC-TT).Methods:The clinical and pathological data of 36 patients with Mayo level Ⅳ tumor thrombus were collected in three large clinical centers in China, including 18 cases in PLA General Hospital, 7 cases in Nanfang Hospital, and 11 cases in Renji Hospital. There were 25 males and 11 females.The median age was 56.5 years (53-67 years old). The average body mass index was 24.18±2.55 kg/m 2. The average diameter of renal tumors was 8.24±3.25 cm. The average length of inferior vena cava tumor thrombus was 12.89±2.50 cm. Mayo level Ⅳ tumor thrombus were divided into level Ⅳa and level Ⅳb (301 classification) based on the criterion of whether the proximal end of the thrombus has invaded the right atrium. Among them, level Ⅳa patients underwent robot-assisted inferior vena cava thrombectomy without cardiopulmonary bypass(CPB-free group, 6 cases). Level Ⅳb patients underwent robot-assisted inferior vena cava thrombectomy with cardiopulmonary bypass(CPB group, 12 cases) or cardiopulmonary bypass with deep hypothermic circulatory arrest assisted inferior vena cava thrombectomy(CPB/DHCA group, 18 cases). The baseline data of the three groups of patients were comparable. The perioperative results and long-term survival data after surgery were compared with different surgical methods for grade Ⅳcancer thrombosis. Results:All operations were successfully completed. Compared with the CPB group, the CPB-free group had a shorter first portal blocking time[17.5(15-36)min vs. 36.5(12-102)min, P=0.044], less intraoperative bleeding [2 350(1 000-3 000)ml vs. 3 500 (1 500-12 000)ml, P=0.043] and a lower allogeneic blood transfusion [1 250(500-2 000)ml vs. 2 185(700-5 800)ml, P=0.049]. Compared with the CPB/DHCA group, the CPB-free group had an advantage in reducing intraoperative allogeneic blood transfusion [1 250(500-2 000)ml vs. 2 700(1 200-10 000)ml, P=0.003]. There were no significant differences between groups in terms of duration of surgery and postoperative hospital stay. Among the 36 patients in this group, 23(64%) developed major complications (level Ⅲ or above), including 9 (25%) grade Ⅲ, 12 (33%) grade Ⅳ, and 2 (6%) grade Ⅴ. The CPB-free group had a relatively low complication rate of grade Ⅳ or above [ 17% (1/6) vs.42% (5/12) vs.44% (8/18)]. There were no statistical differences in median progression-free survival (16.4 vs.12.3 vs.18.0 months, P=0.695) and overall survival (30.1 vs.30.2 vs.37.7 months, P=0.674) between the groups. Conclusions:Robot-assisted inferior vena cava thrombectomy without cardiopulmonary bypass has the advantages of short ischemia time of organs, less intraoperative bleeding, and low incidence of major complications, which can be used as a safe and feasible surgical strategy for selected level Ⅳ tumor thrombus.

Cyclin-dependent kinase 9 (CDK9) activity is correlated with worse outcomes of triple-negative breast cancer (TNBC) patients. The heterodimer between CDK9 with cyclin T1 is essential for maintaining the active state of the kinase and targeting this protein-protein interaction (PPI) may offer promising avenues for selective CDK9 inhibition. Herein, we designed and generated a library of metal complexes bearing the 7-chloro-2-phenylquinoline CˆN ligand and tested their activity against the CDK9-cyclin T1 PPI. Complex 1 bound to CDK9 via an enthalpically-driven binding mode, leading to disruption of the CDK9-cyclin T1 interaction in vitro and in cellulo. Importantly, complex 1 showed promising anti-metastatic activity against TNBC allografts in mice and was comparably active compared to cisplatin. To our knowledge, 1 is the first CDK9-cyclin T1 PPI inhibitor with anti-metastatic activity against TNBC. Complex 1 could serve as a new platform for the future design of more efficacious kinase inhibitors against cancer, including TNBC.