BACKGROUND:Apoptosis plays an important role in secondary brain injury.Therefore,to explore the pathophysiological mechanism of promoting nerve cell survival after traumatic brain injury provides a new direction and theoretical basis for the prevention and treatment of traumatic brain injury. OBJECTIVE:To explore the expression changes of Lnx1 molecule in mammalian cortical neurons after brain injury and the possible mechanism involved in secondary brain injury. METHODS:Eighty adult SD rats were divided into 20 male and 20 female mice in sham operation group and 20 male and 20 female mice in traumatic brain injury group.The traumatic brain injury rat model was established by heavy falling method.At 6,12,24,48,and 72 hours after brain injury,the expression of related molecules in damaged cortical neurons was analyzed by RT-qPCR,western blot assay,and immunofluorescence staining. RESULTS AND CONCLUSION:(1)The brain tissue of traumatic brain injury group was bleeding and obvious tissue injury could be observed.Water content of brain tissue increased after traumatic brain injury.(2)Compared with the sham operation group,the expression of Lnx1 in cortical neurons after traumatic brain injury increased significantly at 24 hours after injury.(3)After traumatic brain injury,the expression of PBK and BCR protein decreased,and the pro-survival factor ctgf increased.(4)These findings suggest that after traumatic brain injury,the expression of Lnx1 is up-regulated in neurons,which may be due to the decrease of the expression of its target molecules PBK and BCR,and further promote the expression of living factor ctgf,which has a protective effect on the damaged neurons.

ObjectiveTo investigate the potential mechanism of Liangxue Tuizi Formula （凉血退紫方， LXTZF） in treating Henoch-Schönlein Purpura （HSP） by examining its regulatory effect on neutrophil extracellular trap （NETs） dysregulation via the rapidly accelerated fibrosarcoma kinase （RAF）/mitogen-activated protein kinase （MEK）/extracellular signal-regulated kinase （ERK） signaling pathway. MethodsSeventy Wistar rats were randomly allocated into a blank control group （n=14） and a modeling group （n=56）. Rats in the modelling group underwent an eight-week modelling period to establish HSP rat models with blood-heat syndrome via modified ovalbumin （OVA） induction method combined with oral administration of heat-property Chinese herbal medicine. Fifty successfully modeled rats were subsequently randomly divided into five groups （n=10 per group）， model group， compound glycyrrhizin group， LXTZF group， RAF inhibitor group， and LXTZF + RAF agonist group. Additionally， 10 rats were selected from the original blank control group for the final experiment. From the 11th week of modelling， rats in the blank control group and the model group received 1 ml/（100 g·d） ultrapure water via oral administration， in addition to 0.5 ml/（kg·d） 0.9% sodium chloride solution via intraperitoneal injection. The LXTZF group and the compound glycyrrhizin group received 7.5 g/（kg·d） LXTZF granule suspension via gavage， 13.5 mg/（kg·d） compound glycyrrhizin suspension via gavage， respectively. The RAF inhibitor group received 1 mg/（kg·d） GW5074 suspension via intraperitoneal injection and ultrapure water via oral administration； the LXTZF + RAF agonist group received 7.5 g/（kg·d） LXTZF granule suspension via gavage and 1 mg/（kg·d） paclitaxel suspension via intraperitoneal injection. All administrations were performed once daily for 4 weeks. After intervention， skin tissue histopathology was examined by hematoxylin and eosin （H&E） staining， immunoglobulin A （IgA） deposition was assessed via immunofluorescence， serum levels of neutrophil elastase （NE）， tumor necrosis factor-α （TNF-α）， and vascular cell adhesion molecule-1 （VCAM-1） were measured using enzyme-linked immunosorbent assay （ELISA）， serum myeloperoxidase （MPO） level was determined by a colorimetric assay； the mRNA expression levels of RAF， MEK， and ERK in skin tissue were detected by real-time quantitative polymerase chain reaction （RT-qPCR）； and the protein expression of RAF， MEK， ERK， as well as phosphorylated MEK （p-MEK） and phosphorylated ERK （p-ERK）， were analyzed by Western Blot. ResultsSkin tissue in the blank control group rats remained normal， whereas the model group exhibited neutrophil infiltration and haemorrhage with red blood cell rupture. In all drug intervention groups， neutrophil infiltration and haemorrhagic exudation reduced markedly， with LXTZF group demonstrating the most pronounced improvement. Compared with the blank control group， rats in the model group exhibited enhanced IgA fluorescence intensity in skin tissue， elevated serum levels of NE， MPO， TNF-α and VCAM-1， increased mRNA expression of RAF， MEK， ERK1 and ERK2， as well as heightened RAF protein levels and p-MEK/MEK and p-ERK/ERK ratios （P＜0.05）. Compared with the model group， the drug intervention groups exhibited reduced IgA fluorescence intensity in skin tissue， along with decreased serum levels of NE， MPO， TNF-α， and VCAM-1 （P＜0.05）. In LXTZF group and RAF inhibition groups， reduced mRNA expression of RAF， MEK， ERK1， and ERK2 was observed in rat skin tissue， alongside decreased RAF protein levels and reduced p-MEK/MEK and p-ERK/ERK ratios （P＜0.05）. Compared with LXTZF + RAF agonist group， the compound glycyrrhizin group， LXTZF group， and RAF inhibitior group exhibited reduced IgA fluorescence intensity in skin tissue， decreased serum NE， MPO， TNF-α， and VCAM-1 levels， and decreased MEK mRNA expression and p-MEK/MEK ratio （P＜0.05）. ConclusionThe potential mechanism by which LXTZF treats Henoch-Schönlein purpura with blood heat syndrome may involve blocking the RAF/MEK/ERK signaling pathway in skin tissue， and suppressing excessive formation of NETs， thereby reducing IgA deposition in dermal microvessels and attenuating systemic inflammatory responses.

Objective:To compare the clinical efficacy and analyze the surgical approach differences using CT parameters between mini-open transforaminal lumbar interbody fusion (MO-TLIF) and minimally invasive surgery of transforaminal lumbar interbody fusion (MIS-TLIF) in the treatment of degenerative lumbar diseases.Methods:A total of 68 consecutive patients with degenerative lumbar diseases undergoing surgery at the Second Affiliated Hospital of Soochow University from January 2022 to January 2023 were randomized into the MO-TLIF group (34 cases, percutaneous screw-assisted posterior midline MO-TLIF) and the MIS-TLIF group (34 cases, Wiltse approach MIS-TLIF using the Quadrant channel). Perioperative indicators (operative time, incision length, intraoperative blood loss, fluoroscopy frequency, postoperative bedrest duration, and hospital stay) and complications were compared. Visual analogue scale (VAS) and Oswestry disability index (ODI) were assessed preoperatively and at 3 days, 3 months, and 1 year postoperatively. Effective cross-sectional area (eCSA) of paraspinal muscles was evaluated on MRI preoperatively and 1 year postoperatively. CT parameters of surgical approaches, including spinous process-midline distance (SM), Wiltse-midline distance (WM), surgical approach angle, depth, and multifidus muscle displacement were compared. Pearson correlation and multivariate linear regression analyses were performed to explore associations between CT parameters, operative time, blood loss, and eCSA atrophy.Results:Baseline characteristics showed no significant differences between groups ( P>0.05). The MO-TLIF group exhibited shorter operative time (109.85±7.82 min vs. 133.82±20.22 min), reduced blood loss (77.21±21.83 ml vs. 141.18±31.44 ml), smaller incision length (6.09±0.22 cm vs. 7.00±0.43 cm), shorter bedrest duration (1.59±0.49 d vs. 2.38±0.50 d), and shorter hospital stay (8.93±1.44 d vs. 10.35±1.45 d), but higher fluoroscopy frequency (19.53±1.92 times vs. 16.29±1.78 times) compared to the MIS-TLIF group ( P<0.05). Complications included fat liquefaction (5 cases) and dural tears (2 cases). Both groups showed improved VAS and ODI postoperatively ( P<0.05). At 3 d postoperatively, the MO-TLIF group had lower VAS (2.74±0.47 points vs. 3.35±0.48 points) and ODI (27.46%±2.16% vs. 30.42%±2.52%) than the MIS-TLIF group ( P<0.05). Postoperative eCSA decreased significantly in the MIS-TLIF group ( P<0.05) but remained stable in the MO-TLIF group ( P>0.05). The MO-TLIF group demonstrated smaller SM (8.43±1.81 mm vs. 31.15±6.53 mm), approach angle, depth, and muscle displacement ( P<0.05). CT parameters in the MO-TLIF group showed no correlation with operative time, blood loss, or eCSA atrophy ( r<0.3, P>0.05), whereas parameters in the MIS-TLIF group correlated positively with these outcomes (0.3< r<0.6, P<0.05). Multivariate regression revealed a significant association between CT parameters and eCSA atrophy in the MIS-TLIF group ( R 2=0.474, P<0.05). Conclusion:Compared to MIS-TLIF, MO-TLIF reduces intraoperative blood loss, accelerates recovery, and minimizes paraspinal muscle trauma.

Given the increasing concern regarding antibacterial resistance, the antimicrobial properties of naphthoquinones have recently attracted significant attention. While 1,4-naphthoquinone and its derivatives have been extensively studied, the antibacterial properties of 5,8-dihydroxy-1,4-naphthoquinone derivatives remain relatively unexplored. This study presents a comprehensive in vitro and in vivo analysis of the antibacterial activity of 35 naturally sourced and chemically synthesized derivatives of 5,8-dihydroxy-1,4-naphthoquinone. Kirby-Bauer antibiotic testing identified three compounds with activity against methicillin-resistant Staphylococcus aureus (MRSA), with one compound (PNP-02) demonstrating activity comparable to vancomycin in minimum inhibitory concentration, minimum bactericidal concentration (MBC), and time-kill assays. Microscopic and biochemical analyses revealed that PNP-02 adversely affects the cell wall and cell membrane of MRSA. Mechanistic investigations, including proteomic sequencing analyses, Western blotting, and RT-qPCR assays, indicated that PNP-02 compromises cell membrane integrity by inhibiting arginine biosynthesis and pyrimidine metabolism pathways, thereby increasing membrane permeability and inducing bacterial death. In an in vivo mouse model of skin wound healing, PNP-02 exhibited antibacterial efficacy similar to vancomycin. The compound demonstrated low toxicity to cultured human cells and in hemolysis assays and remained stable during serum incubation. These findings suggest that PNP-02 possesses promising bioactivity against MRSA and represents a potential novel antibacterial agent.
Methicillin-Resistant Staphylococcus aureus/genetics* ; Anti-Bacterial Agents/chemistry* ; Naphthoquinones/administration & dosage* ; Animals ; Microbial Sensitivity Tests ; Mice ; Humans ; Staphylococcal Infections/microbiology* ; Molecular Structure

Objective:To compare the clinical efficacy and analyze the surgical approach differences using CT parameters between mini-open transforaminal lumbar interbody fusion (MO-TLIF) and minimally invasive surgery of transforaminal lumbar interbody fusion (MIS-TLIF) in the treatment of degenerative lumbar diseases.Methods:A total of 68 consecutive patients with degenerative lumbar diseases undergoing surgery at the Second Affiliated Hospital of Soochow University from January 2022 to January 2023 were randomized into the MO-TLIF group (34 cases, percutaneous screw-assisted posterior midline MO-TLIF) and the MIS-TLIF group (34 cases, Wiltse approach MIS-TLIF using the Quadrant channel). Perioperative indicators (operative time, incision length, intraoperative blood loss, fluoroscopy frequency, postoperative bedrest duration, and hospital stay) and complications were compared. Visual analogue scale (VAS) and Oswestry disability index (ODI) were assessed preoperatively and at 3 days, 3 months, and 1 year postoperatively. Effective cross-sectional area (eCSA) of paraspinal muscles was evaluated on MRI preoperatively and 1 year postoperatively. CT parameters of surgical approaches, including spinous process-midline distance (SM), Wiltse-midline distance (WM), surgical approach angle, depth, and multifidus muscle displacement were compared. Pearson correlation and multivariate linear regression analyses were performed to explore associations between CT parameters, operative time, blood loss, and eCSA atrophy.Results:Baseline characteristics showed no significant differences between groups ( P>0.05). The MO-TLIF group exhibited shorter operative time (109.85±7.82 min vs. 133.82±20.22 min), reduced blood loss (77.21±21.83 ml vs. 141.18±31.44 ml), smaller incision length (6.09±0.22 cm vs. 7.00±0.43 cm), shorter bedrest duration (1.59±0.49 d vs. 2.38±0.50 d), and shorter hospital stay (8.93±1.44 d vs. 10.35±1.45 d), but higher fluoroscopy frequency (19.53±1.92 times vs. 16.29±1.78 times) compared to the MIS-TLIF group ( P<0.05). Complications included fat liquefaction (5 cases) and dural tears (2 cases). Both groups showed improved VAS and ODI postoperatively ( P<0.05). At 3 d postoperatively, the MO-TLIF group had lower VAS (2.74±0.47 points vs. 3.35±0.48 points) and ODI (27.46%±2.16% vs. 30.42%±2.52%) than the MIS-TLIF group ( P<0.05). Postoperative eCSA decreased significantly in the MIS-TLIF group ( P<0.05) but remained stable in the MO-TLIF group ( P>0.05). The MO-TLIF group demonstrated smaller SM (8.43±1.81 mm vs. 31.15±6.53 mm), approach angle, depth, and muscle displacement ( P<0.05). CT parameters in the MO-TLIF group showed no correlation with operative time, blood loss, or eCSA atrophy ( r<0.3, P>0.05), whereas parameters in the MIS-TLIF group correlated positively with these outcomes (0.3< r<0.6, P<0.05). Multivariate regression revealed a significant association between CT parameters and eCSA atrophy in the MIS-TLIF group ( R 2=0.474, P<0.05). Conclusion:Compared to MIS-TLIF, MO-TLIF reduces intraoperative blood loss, accelerates recovery, and minimizes paraspinal muscle trauma.

BACKGROUND:Previous brain studies have mostly focused on adults and fetuses,and the developmental characteristics of young children's brainstems have rarely been studied. OBJECTIVE:To observe the brainstem development characteristics of healthy young children and to explore the age-related differences and their correlation with sex. METHODS:From January 2019 to April 2022,a retrospective study of 3.0T MRI images of 174 children aged 2 to 6 years in the Affiliated Hospital of Inner Mongolia Medical University was conducted,and the median sagittal diameter,area and angle of the brainstem(including midbrain,pons and medulla oblongata)were measured. RESULTS AND CONCLUSION:There is an age-related increase in the anterior and posterior diameters of the midbrain,pons and medulla oblongata in the 2-5 years old group as well as in the longitudinal diameter and area of the midbrain,pons and medulla oblongata in the 2-6 years old group.Except for the longitudinal diameter of the medulla oblongata,all others show a positive correlation with age(r>0,P<0.05).In the 2-3 years old group and 4-5 years old group,the children are in the rapid growth and development stage,and these two age groups can be used as the key observation indicators for the development of young children.The anterior-posterior diameter,longitudinal diameter,area of the pons and total brainstem area are strongly correlated with age,which can be used as the key observation indicators for the brainstem development in young children.

Objective:To investigate the risk factors of moderately severe acute pancreatitis (MSAP) and severe acute pancreatitis (SAP) complicated with pancreatogenic portal hypertension (PPH) and to establish a prediction model.Methods:From January 1, 2016 to December 31, 2022, a total of 1 095 patients diagnosed with MSAP or SAP at the First Affiliated Hospital of Kunming Medical University were enrolled and divided into PPH group (145 cases) and non-PPH group (950 cases) according to the presence or absence of concomitant PPH. The general data (gender, etiology of acute pancreatitis, days of hospitalization, etc.), complications (portal vein thrombosis, pancreatic pseudocyst, pancreatic encapsulated necrosis, etc.), laboratory indicators (albumin, D-dimer, etc.), and scores of modified computed tomography severity index (MCTSI) were collected in the two groups. The least absolute shrinkage and selection operator(LASSO) and multivariate logistic regression analysis were performed to analyze the independent risk factors of MSAP and SAP complicated with PPH, and the nomogram prediction model was established. The area under the curve of the receiver operating characteristic curve was calculated to evaluate the discrimination of the calibration curve and Hosmer-Lemeshow goodness of fit test were used to assess the predictive accuracy of the model, and clinical decision curve analysis (DCA) was used to evaluate the clinical practicability of the model.Results:The results of LASSO and multivariate logistic regression analysis showed that portal vein thrombosis, pancreatic pseudocyst, pancreatic encapsulated necrosis, days of hospitalization, MCTSI and decreased albumin were independent risk factors of MSAP and SAP complicated with PPH ( OR=7.013, 2.085, 1.846, 1.030, 1.235 and 0.955; 95% confidence interval 4.061 to 12.112, 1.255 to 3.463, 1.066 to 3.199, 1.013 to 1.047, 1.123 to 1.357 and 0.927 to 0.983; all P<0.05). The area under the curve of the model was 0.820 (95% confidence interval 0.780 to 0.859), the calibration curve was close to the reference curve, and the Hosmer-Lemeshow goodness-fit test showed that the model had a good fit ( χ2=9.82, P=0.278). The result of DCA indicated that the model had a high net benefit in a wide range of risk threshold (threshold probability 0.1 to 0.9), and had certain clinical practicability. Conclusions:Portal vein thrombosis, pancreatic pseudocyst, pancreatic encapsulated necrosis, days of hospitalization, MCTSI and decreased albumin are the independent risk factors of MSAP and SAP complicated with PPH. The established nomogram model has good differentiation, calibration and clinical practicability.

Objective:To investigate the risk factors of moderately severe acute pancreatitis (MSAP) and severe acute pancreatitis (SAP) complicated with pancreatogenic portal hypertension (PPH) and to establish a prediction model.Methods:From January 1, 2016 to December 31, 2022, a total of 1 095 patients diagnosed with MSAP or SAP at the First Affiliated Hospital of Kunming Medical University were enrolled and divided into PPH group (145 cases) and non-PPH group (950 cases) according to the presence or absence of concomitant PPH. The general data (gender, etiology of acute pancreatitis, days of hospitalization, etc.), complications (portal vein thrombosis, pancreatic pseudocyst, pancreatic encapsulated necrosis, etc.), laboratory indicators (albumin, D-dimer, etc.), and scores of modified computed tomography severity index (MCTSI) were collected in the two groups. The least absolute shrinkage and selection operator(LASSO) and multivariate logistic regression analysis were performed to analyze the independent risk factors of MSAP and SAP complicated with PPH, and the nomogram prediction model was established. The area under the curve of the receiver operating characteristic curve was calculated to evaluate the discrimination of the calibration curve and Hosmer-Lemeshow goodness of fit test were used to assess the predictive accuracy of the model, and clinical decision curve analysis (DCA) was used to evaluate the clinical practicability of the model.Results:The results of LASSO and multivariate logistic regression analysis showed that portal vein thrombosis, pancreatic pseudocyst, pancreatic encapsulated necrosis, days of hospitalization, MCTSI and decreased albumin were independent risk factors of MSAP and SAP complicated with PPH ( OR=7.013, 2.085, 1.846, 1.030, 1.235 and 0.955; 95% confidence interval 4.061 to 12.112, 1.255 to 3.463, 1.066 to 3.199, 1.013 to 1.047, 1.123 to 1.357 and 0.927 to 0.983; all P<0.05). The area under the curve of the model was 0.820 (95% confidence interval 0.780 to 0.859), the calibration curve was close to the reference curve, and the Hosmer-Lemeshow goodness-fit test showed that the model had a good fit ( χ2=9.82, P=0.278). The result of DCA indicated that the model had a high net benefit in a wide range of risk threshold (threshold probability 0.1 to 0.9), and had certain clinical practicability. Conclusions:Portal vein thrombosis, pancreatic pseudocyst, pancreatic encapsulated necrosis, days of hospitalization, MCTSI and decreased albumin are the independent risk factors of MSAP and SAP complicated with PPH. The established nomogram model has good differentiation, calibration and clinical practicability.

Objective : To establish a laboratory model of heroin addiction in C57BL /6 mice based on associative learning mechanisms． Methods: The black box and white box were selected as the memory training environment， and three behavioral training paradigms were studied : ① Pavlovian conditional position preference ( CPP) training paradigm，mice were placed in the white box for memory reinforcement training for 30 min after intraperitoneal injection of 0. 1 ml of corresponding concentrations (5. 0，10. 0，20. 0 mg / kg) of heroin at 9 :00 a．m．，and 24 h later 0. 1 ml of 0. 9% NaCl solution was injected intraperitoneally into the black box for training，and after the training，the mice were tested for their memory preference for the black and white boxes (movement time of different boxes) . ② A naloxone conditional position aversion ( CPA) training paradigm was conductedbased on the results of the CPP training paradigm. ③ Behavioral sensitization training paradigm，heroin addiction rating scale was established based on the statistical results of 3 behavioral experiments and the lethality of experimental animal disease mice after drug administration．Three different doses of heroin (5. 0，10. 0，20. 0 mg / kg) were selected to induce heroin addiction，and the most appropriate heroin concentration was selected by the results on the rating scale. Results: In the CPP training paradigm，CPP was observed in all heroin groups (P＜0. 05，P＜0. 001，P＜0. 05) ．In the CPA training paradigm，the CPA induction rate was highest in the 10. 0 mg / kg heroin group compared to the control group (P ＜0. 01 ) ．In the behavioral sensitization training paradigm ，all heroin groups caused behavioral sensitization changes (P＜0. 001) ; but the 5. 0 and 10. 0 mg / kg heroin groups did not cause animal mortality．Overall，the 10. 0 mg / kg heroin group had the highest dose score on the rating scale．It could be used as a concentration to establish a stable experimental animal model of heroin addiction． Conclusion The study was effective in establishing a heroin addiction model in mice，and it was suitable for modeling drug concentration screening，with high animal survival rate and simple and practical．The combined learning mechanism can effectively shorten the model establishment period.

Objective: To establish a rat model of preeclampsia (PE) in early pregnancy and to observe the changes in phenotype，pregnancy outcome and cognitive ability of offspring． Methods : The pregnant rats were randomly divided into model group and control group．Ultra-low dose lipopolysaccharide (LPS) (0. 5 μg / kg) and an equal volume of normal saline were injected into the tail vein of pregnant rats on the fifth day of pregnancy．The levels of blood pressure ，12-hour urinary protein ，peripheral blood coagulation factors and placental cytokines in the two groups were measured．Furthermore，placental pathology，pregnancy outcomes，and cognitive abilities of offspring were observed. Results: Blood pressure and urinary protein levels of model group were significantly higher than those of control group levels．Compared with the control group，the levels of platelet and antithrombin Ⅲ (AT Ⅲ) in the peripheral blood of pregnant rats in the model group were lower than those in the control group，while D-dimer was higher than that in the control group，the weight of the fetus and placenta in the model group decreased (P ＜0. 001) ，the expression levels of interleukin ( IL) -6，tumor necrosis factor α ( TNF-α) and interferon gamma (INF-γ) in peripheral blood increased，while the expression level of transforming growth factor β1 (TGF-β1) decreased(P＜0. 001) ．The water maze test showed that the latency of the offspring of the model group to the plat- form was longer than that of the control group (P＜0. 05) ，while the frequency of crossing the platform quadrant and the time of staying in the platform quadrant of the model group were lower than those of the control group (P < 0. 05 ) ．HE and PAS staining showed that there were infiltration of inflammatory cells in the basal layer of placenta， obvious decrease of blood vessels in labyrinthine area，slight edema of renal interstitium and degeneration of local renal tubular epithelial cells in the model group，while there were no above pathological changes in placenta and kidney in the control group． Conclusion A single injection of LPS in early pregnancy can successfully induce PE- related symptoms and adverse pregnancy outcomes such as fetal growth restriction and lead to the decline of cogni- tive ability of offspring.