ObjectiveThe human angiotensin converting enzyme2 （hACE2） transgenic mouse model was used to clarify the antiviral efficacy of BD-77 against a novel coronavirus SARS-CoV-2 and explore the action mechanism of BD-77 against SARS-CoV-2. MethodSARS-CoV-2 Omicron and Delta variant strains-infected VeroE6 cell models were established and administered with BD-77 to observe the antiviral effect of BD-77 in vitro. A kit was used to detect the effect of BD-77 in vitro on the binding of spike S protein of SARS-CoV-2 virus （Delta/Omicron） to angiotensin converting enzyme2 （ACE2）. Chromatography was adopted to detect the binding of BD-77 to the S protein and N protein of the novel coronavirus. hACE2 transgenic C57BL/6 mice were divided into a blank control group， SARS-CoV-2 infection group， BD-77 administration groups of 37.5 mg·kg^-1 and 75 mg·kg^-1， with eight mice in each group. The pneumonia model of SARS-CoV-2-infected hACE2 transgenic mice was built to observe the survival of the mice， detect the virus titer of the lung tissue of the mice， and observe the lesions in the lung tissue. ResultBD-77 had a certain inhibitory effect on Omicron and Delta variant strains in vitro， with median inhibitory concentration （IC₅₀） of 526.3 mg·L^-1 and 653.0 mg·L^-1， respectively. BD-77 had no significant inhibitory effect on the binding of the S protein of WT， Omicron， and Delta variant strains of SARS-CoV-2 to ACE2 and had no binding effect with the S protein and N protein of the novel coronavirus. No mice in the blank group died， while the mortality rate of SARS-CoV-2-infected mice was 75%. There was a large amount of virus replication in the lung tissue of the mice and large areas of inflammatory infiltration in the lung tissue and interstitium. Compared with the model group， BD-77 administration groups of 37.5 mg·kg^-1 and 75 mg·kg^-1 could reduce the mortality of mice， significantly lower the virus titer in the lung tissue of mice （P<0.05）， and improve lung lesions. ConclusionBD-77 demonstrated significant inhibitory effects against SARS-CoV-2 virus in vitro and in vivo. However， its mechanism of action did not involve direct inhibition of the virus itself or intervention in the virus-host binding process. This finding suggests that the mechanism of action of BD-77 needs to be thoroughly investigated and elucidated by further experiments.

ObjectiveTo observe the therapeutic effect of BD-77 by nebulized inhalation on animal models of various respiratory viral infections and investigate the mechanism of broad-spectrum antiviral action of BD-77 using proteomics. MethodThe influenza virus H1N1/FM1 experiment used ICR mice and divided them into a normal group， model group， Tamiflu group， and BD-77 groups of 75 and 37.5 g·L^-1 for inhalation of 20 min and 25 min. Human coronavirus 229E and OC43 experiment divided the BALB/c mice into a normal group， model group， chloroquine phosphate group， and BD-77 groups of 75， 37.5， 18.75， and 9.375 g·L^-1， with 10 mice in each group. Influenza virus H1N1/FM1 and human coronaviruses 229E and OC43 infection-induced pneumonia models were used to detect mouse lung index， and real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） was used to detect the viral load in lung tissue. Enzyme-linked immunosorbent assay （ELISA） was used to detect related inflammatory factors in lung tissue， and proteomics analysis was performed on the lung tissue of OC43-infected mice. ResultCompared with that in the normal group， the lung index of mice in each infection group was significantly increased （P<0.01）， and viral nucleic acid could be detected in the lung tissue of mice infected with human coronaviruses 229E and OC43. The levels of interleukin-6 （IL-6）， IL-10， and tumor necrosis factor-α （TNF-α） in the lung tissue of mice infected with human coronavirus 229E were all significantly increased （P<0.01）. BD-77 could significantly reduce the lung index of mice infected with influenza virus H1N1/FM1 and human coronaviruses 229E and OC43 （P<0.05， P<0.01）， cut down the viral load in the lungs of mice infected with human coronaviruses 229E and OC43 （P<0.01）， and lower the contents of IL-6， IL-10， and TNF-α in the lung tissue of mice infected with human coronavirus 229E （P<0.01）. Proteomics analysis of the lung tissue of OC43-infected mice showed that BD-77 regulated the AMPK signaling pathway， TNF signaling pathway， NOD-like signaling pathway， IL-17 signaling pathway， Forkhead box protein O （FoxO） signaling pathway， transforming growth factor-β （TGF-β） signaling pathway， and other signaling pathways. ConclusionNebulized inhalation of BD-77 is effective in treating pneumonia caused by influenza virus H1N1/FM1 and human coronaviruses 229E and OC43 infection in mice and may exert its antiviral effects by regulating the balance of cellular metabolism， enhancing the immune function of the host， and attenuating inflammatory responses.

Alzheimer's disease （AD） is a neurodegenerative disorder characterized by progressive decline in memory and cognitive function. Despite some achievements in AD research over the past few decades， its exact etiology remains elusive， with no reliable treatment currently available. This has spurred an urgent need for novel therapeutic strategies， particularly for neuroprotective agents with minimal side effects and high efficacy. Natural plant extracts contain a class of steroidal or triterpenoid saponin compounds， exhibiting various pharmacological activities， and they are believed to hold immense potential in the prevention and treatment of AD. Studies have indicated that natural saponins may exert their effects through multiple pathways， including reducing amyloid-β peptide deposition， inhibiting abnormal phosphorylation of Tau protein， modulating oxidative stress， decreasing inflammatory responses， and suppressing cell apoptosis. Particularly， certain traditional Chinese medicine （TCM） formulations containing natural saponin components have demonstrated promising advantages in AD treatment， offering significant clinical prospects. This review summarized the research progress on saponin compounds extracted from natural plants in the prevention and treatment of AD and delved into their mechanisms of action. Through comprehensive analysis of these studies， the potential mechanisms of saponins in AD treatment were elucidated， aiming to provide valuable insights for the development of novel therapeutic drugs， and the review hopes that future research and clinical experiments will fully explore their potential in AD treatment， offering more effective therapeutic options for patients.

Sepsis is a life-threatening organ dysfunction caused by a dysregulated host response to infection. Sepsis-induced cell lysis and necrosis lead to the passive release of mitochondrial DNA (mtDNA) and nuclear DNA (nDNA) into circulation. These DNAs bind to pattern recognition receptor (PRR), triggering excessive inflammatory cytokines production and increasing mortality. Three prime repair exonuclease 1 (TREX1) is a 3' to 5' exonuclease that rapidly degrades single-stranded DNA (ssDNA) and double-stranded DNA (dsDNA) by cleaving phosphodiester bonds. This process can prevent the accumulation of damaged DNA in the cytoplasm, thereby averting abnormal inflammation and pathological immune responses. TREX1 thus plays a significant role in regulating DNA-related damage caused by sepsis. However, the role and underlying mechanisms of TREX1 in sepsis have not been thoroughly discussed. This review aims to elucidate the structure and function of TREX1 and its mediated immune regulatory mechanisms, with the hope of clarifying the potential role of TREX1 in the field of sepsis.

Chronic cerebral hypoperfusion leads to white matter injury (WMI), which subsequently causes neurodegeneration and even cognitive impairment. However, due to the lack of treatment specifically for WMI, novel recognized and effective therapeutic strategies are urgently needed. In this study, we found that honokiol and magnolol, two compounds derived from Magnolia officinalis, significantly facilitated the differentiation of primary oligodendrocyte precursor cells (OPCs) into mature oligodendrocytes, with a more prominent effect of the former compound. Moreover, our results demonstrated that honokiol treatment improved myelin injury, induced mature oligodendrocyte protein expression, attenuated cognitive decline, promoted oligodendrocyte regeneration, and inhibited astrocytic activation in the bilateral carotid artery stenosis model. Mechanistically, honokiol increased the phosphorylation of serine/threonine kinase (Akt) and mammalian target of rapamycin (mTOR) by activating cannabinoid receptor 1 during OPC differentiation. Collectively, our study indicates that honokiol might serve as a potential treatment for WMI in chronic cerebral ischemia.
Magnolia ; White Matter ; Brain Ischemia/metabolism* ; Oligodendroglia/metabolism*

Objective:To investigate the effects of Xiangshao granules on behavior and oligodendrocyte precursor cells (OPCs) and oligodendrocytes (OLs) in the medial prefrontal cortex (mPFC) of post-stroke depression (PSD) mice.Methods:Eighty C57BL/6 mice were divided into sham-operated group, middle cerebral artery occlusion (MCAO) group, PSD+PBS group, and PSD+Xiangshao group ( n=20). PSD models were constructed using mild chronic unforeseeable stress (CUMS) and solitary feeding after MCAO. MCAO models were evaluated by laser speckle contrast imaging (LSCI), modified neurological severity score (mNSS) and TTC staining. PSD models were evaluated by body mass, sugar and water preference test and tail suspension test. After PSD modeling, mice in the sham-operated group, MCAO group, and PSD+PBS group were given 0.2 mL PBS, while mice in the PSD+Xiangshao group was given Xiangshao granules at dosage of 60 mg/kg (dissolved in 0.2 mL PBS); all were given via intragastric administration once a d for 28 d. Number of OPCs and OLs in mPFC was detected by immunofluorescence. Expressions of myelin basic protein (MBP) and phosphatidylinositol 3-kinase/serine/threonine kinase/mammalian target of rapamycin (PI3K/AKT/mTOR) pathway proteins in mPFC were detected by Western blotting. Results:(1) Model verification results: LSCI showed obvious changes of cerebral blood flow in the middle cerebral artery supply area before, during and after MCAO; TTC staining showed typical red non-infarct area and white infarct area in MCAO group, PSD+PBS group and PSD+ Xiangshao group; mNSS scores in MCAO group, PSD+PBS group and PSD+ Xiangshao group were all >4, without significant differences ( P>0.05); the MCAO model was successfully constructed. After PSD and before treatment, the PSD+PBS group and PSD+Xiangshao group had significantly decreased body weight and sugar-water preference, and statistically prolonged tail suspension immobilization time compared with sham-operated group and MCAO group ( P<0.05); the PSD model was successfully constructed. (2) Results of mouse behavior experiment after treatment: significant differences in body weight, sugar-water preference and tail suspension time were noted in mice of the 4 groups 28 d after treatment ( P<0.05); PSD+Xiangshao group had significantly increased body weight and sugar-water preference and decreased tail suspension immobilization time compared with PSD+PBS group ( P<0.05). (3) Number of OPCs (Olig2 +PDGFRa +), proliferative OPCs (Ki-67 +PDGFRa +, EdU +PDGFRa +) and OLs (Olig2 +CC1 +), and relative MBP, p-PI3K, p-AKT and p-mTOR protein expressions in mPFC of the 4 groups were significantly different ( P<0.05); compared with those in PSD+PBS group, the above cell number and relative protein expressions in PSD+Xiangshao group were significantly increased ( P<0.05). Conclusion:Xiangshao granules can promote the OPCs proliferation and OLs maturation by activating PI3K/AKT/mTOR signaling pathway in mPFC, thus playing a role in PSD.

Objective:To explore the incidence and morphology of the posterolateral fracture fragment affecting the fibular notch in posterior pilon fracture.Methods:A retrospective analysis was conducted of the CT and clinical data of the 31 patients with posterior pilon fracture who had been treated at Department of Orthopaedic, China-Japan Friendship Hospital from May 2013 to May 2018. They were 17 men and 14 women, aged from 20 to 68 years (average, 42 years). The injury affected the left side in 13 cases and the right side in 18 ones. The incidence of the posterolateral fracture fragments affecting the fibular notch was counted. The morphologic indexes of the fragments were measured like axial angle of their fracture line, fragment area, fragment height, and sagittal angle of their fracture line.Results:A posterolateral fracture fragment affecting the fibular notch was found in all the 31 posterior pilon fractures, giving an incidence of 100% in the posterior pilon fracture. The fracture line of the fragments tended to be in the coronal plane. The axial angle of the fracture line was 20.25°±9.48°; the ratio of the fragment area to the distal tibial articular area was 15.78%±6.75%; the fragment height was 36.59 mm ± 10.70 mm; the sagittal angle of the fracture line was 18.37°±5.45°.Conclusions:A posterolateral fracture fragment affecting the fibular notch can be found in all the posterior pilon fractures. It does not affect a large articular area and its fracture line is usually located in the coronal plane. These data may help choose appropriate surgical approach and internal fixation.

CAR-T cell therapy that targets surface antigens to kill tumor cells specifically has recently become another cornerstone in tumor immunotherapy. In this study, a lentiviral expression plasmid of CAR targeting human epidermal growth factor receptor 2 (HER2) was constructed by genetic engineering. The recombinant plasmid was co-transfected with other packaging plasmids into HEK293T cells by calcium phosphate precipitation to generate lenti-car, which are CAR lentiviral particles. HER2-specific CAR-T cells were obtained by transducing human peripheral blood mononuclear cells with lenti-car. Their specific inhibitory effects on HER2-positive and HER2-negative tumor cells were analyzed in vitro. The constructed CAR-T cells were specifically activated by HER2-expressing tumor cells as indicated by secretion of IFN-γ and IL-2. The inhibitory rate on HER2-positive SK-OV-3 cell line was (58.47±1.72)%, significantly higher than that on the mock-treated control group (P<0.05). The inhibitory rate on HER2-negative K562 cell lines was (11.74±2.37)%, which was not significantly different from that on the control group (P>0.05). Furthermore, when we transfected a HER2-expressing vector into K562, the inhibitory rate increased to (30.41±7.59)%, which was higher than that on HER2-negative K562 (P<0.05). Thus, the constructed second-generation HER2-specific CAR-T cells specifically suppressed growth of tumor cells overexpressing HER2 protein, suggesting that HER2-specific CAR-T cells might prove useful for immunotherapy of HER2-positive cancer.

Objective To investigate the effect of intraoperative dripping of intravenous tranexamic acid (TXA) on the perioperative blood loss in elderly patients undergoing hip arthroplasty for femoral neck fracture.Methods From January 2016 to August 2017,118 elderly patients with femoral neck fracture were treated with hip arthroplasty at Department of Orthopaedics,China-Japan Friendship Hospital.They were 45 males and 73 females,with an average age of 77.1 years.Of them,60 (TXA group) were subjected to intravenous TXA dripping over 10 minutes by 2 doses (15 mg/kg TXA dissolved in 100 mL of saline) with the first dose before incision and the second one at wound closure;58 (control group) were subjected to intravenous administration of 100 mL of saline solution in a similar fashion.Blood routine tests were carried out one day before operation,and the first and third days after operation.The transfusion rate and volume,and surgical blood loss were recorded.The total blood loss on postoperative 1-day and 3-day were calculated according to hemoglobin balance method.The 2 groups were compared in terms of blood loss and complications.Results The blood transfusion rate (21.7％),blood transfusion volume (310.8 ± 85.7 mL),surgical blood loss (424.3 ± 87.6 mL),total blood loss on postoperative 1-day (1,284.6 ±288.7 mL) and total blood loss on postoperative 3-day (1,501.2 ± 337.1 mL) in the TXA group were all significantly lower than those in the control group (41.4％,379.8 ± 110.2 mL,526.7 ± 113.8 mL,1,534.8 ± 279.2 mL and 1,887.4 ± 431.8 mL,respectively) (P ＜ 0.05).There was no significant difference between the 2 groups in postoperative complications (P ＞ 0.05).Conclusion In elderly patients undergoing hip arthroplasty for femoral neck fracture,intravenous TXA administration may lower transfusion rate,reduce transfusion volume,and decrease surgical blood loss and postoperative total blood loss without increasing the risks of surgery-related complications like thrombosis.

Objective To analyze the risk factors associated with periprosthetic femoral fracture following hemiarthroplasty (HA) for displaced femoral neck fracture in aged patients.Methods From January 2013 to June 2016,120 patients over 80 years old were treated by HA for displaced femoral neck fractures.They were 45 males and 75 females,with an average age of 85.2 years (from 80 to 97 years).Their fractures were Garden type Ⅲ (72 cases) and Garden type Ⅳ (48 cases).The time from injury to operation averaged 5.1 days.The patients were divided into a fracture group and a non-fracture group according to the presence or absence of the periprosthetic fracture.The general data of the 2 groups were compared;multivariate logistic regression analyses were done to indentify the influencing factors associated with periprosthetic femoral fracture.Results The 120 patients obtained a mean follow-up of 26.1 months (from 13 to 48 months).Periprosthetic femoral fracture occurred in 11 cases,giving an overall incidence of 9.2％ (11/120).Compared with the non-fracture group,the average age was significantly older,the incidence of past fractures was significantly higher,significantly more types of uncemented stem were used,and American Society of Anesthesiologists (ASA) grading was significantly more severe for the fracture group (P ＜ 0.05).There were no significant differences between the 2 groups concerning the general data (P ＞ 0.05).Multivariate Logistic regression analyses revealed that age [OR =1.268,95％ CI (1.059,1.517),P =0.010] and type ofuncemented stem [OR =0.072,95％ CI (0.008,0.625),P =0.017] were independent risk factors for periprosthetic fracture.Conclusions The incidence of periprosthetic femoral fracture in the elderly patients may be high following HA for femoral neck fractures.Since age and uncemented stem may be independent risk factors for periprosthetic femoral fracture,surgeons should pay enough attention to them in clinic.