Lignans are a powerful weapon for plants to resist stresses and have diverse bioactive functions to protect human health. Elucidating the mechanisms of stereoselective biosynthesis and response to stresses of lignans is important for the guidance of plant improvement. Here, we identified the complete pathway to stereoselectively synthesize antiviral (-)-lariciresinol glucosides in Isatis indigotica roots, which consists of three-step sequential stereoselective enzymes DIR1/2, PLR, and UGT71B2. DIR1 was further identified as the key gene in respoJanuary 2024nse to stresses and was able to trigger stress defenses by mediating the elevation in lignan content. Mechanistically, the phytohormone-responsive ERF transcription factor LTF1 colocalized with DIR1 in the cell periphery of the vascular regions in mature roots and helped resist biotic and abiotic stresses by directly regulating the expression of DIR1. These systematic results suggest that DIR1 as the first common step of the lignan pathway cooperates with PLR and UGT71B2 to stereoselectively synthesize (-)-lariciresinol derived antiviral lignans in I. indigotica roots and is also a part of the LTF1-mediated regulatory network to resist stresses. In conclusion, the LTF1-DIR1 module is an ideal engineering target to improve plant Defenses while increasing the content of valuable lignans in plants.

ObjectiveTo observe the effects of Xibining （XBN） and adipose stem cell exosome （ADSC-Exos） in the cases of separate or joint application on cartilage degeneration and mitochondrial autophagy and explore its mechanism of action to improve knee osteoarthritis （KOA）. MethodSD rats were divided into a sham operation group （sham group）， a model group， an ADSC-Exos group （Exos group）， an XBN group， and an ADSC-Exos+XBN group （Exos+XBN group）. KOA model was established by using anterior cruciate ligament transection （ACLT）. The pain sensitivity status of rats was evaluated， and the degeneration degree of the knee joint and cartilage tissue was detected by Micro-CT and pathological staining. The expression of p62 and LC3B was observed by immunofluorescence， and the serum levels of TNF-α， IL-1β， IL-6， and IL-15 in rats were detected by ELISA. The Western blot was used to detect the protein expression levels of MMP-3， MMP-13， ADAMTS5， ColⅡ， TIMP， ACAN， PINK1， Parkin， p62， and LC3A/B. ResultCompared with the sham group， rats in the model group showed decreased cold-stimulated foot-shrinkage thresholds and mechanical pain sensitivity thresholds， varying degrees of abrasion and loss of cartilage tissue， degeneration of cartilage tissue， elevated serum IL-1β， IL-6， IL-15， and TNF-α levels （P<0.01）， and increased protein expression of MMP-3， MMP-13， and ADAMTS5 in cartilage tissue. In addition， the protein expression of ColⅡ， TIMP1， and ACAN was decreased （P<0.01）. Compared with the model group， rats in each treatment group showed higher cold-stimulated foot-shrinkage thresholds and mechanical pain sensitivity thresholds， reduced cartilage tissue degeneration， lower serum levels of IL-1β， IL-6， IL-15， and TNF-α （P<0.05，P<0.01）， decreased protein expression of MMP-3， MMP-13， and ADAMTS5， and higher protein expression of Cold， TIMP1， and ACAN in cartilage tissue （P<0.05，P<0.01）. Moreover， the changes were the most obvious in the Exos+XBN group. ConclusionBoth ADSCs-Exos and XBN can increase the level of mitochondrial autophagy in chondrocytes and delay cartilage tissue degeneration by promoting the expression of the PINK1/Parkin signaling pathway， and the combination of the two can enhance the therapeutic effect.

Objective:To explore the independent risk factors for the occurrence and aggravation of lower back pain (LBP) in patients with Parkinson′s disease (PD), in order to provide reference for clinical diagnosis and treatment.Methods:A retrospective analysis was conducted on the case data of 309 PD patients who visited the Affiliated Yixing Hospital of Jiangsu University from June 2018 to May 2020. The KING Parkinson′s Disease Pain Scale (KPPS) was used to quantitatively evaluate the LBP of PD patients, who were divided into LBP group and Non LBP group. The general clinical data, PD related data, and imaging data of the two groups were compared and analyzed. Binary logistic regression analysis was used to evaluate independent risk factors for LBP in PD patients. Pearson correlation analysis was conducted between KPPS scores and various factors, and linear regression analysis was used to identify the relevant risk factors that exacerbate LBP in PD patients.Results:Compared with the Non LBP group, the LBP group had lower bone mineral density (BMD) and a lower proportion of patients who engaged in daily exercise. The difference between the two groups was statistically significant (all P<0.05). Compared with the Non LBP group, patients in the LBP group had a longer course of illness, higher stiffness scores, a higher proportion of patients with fluctuating symptoms, higher UPDRS-Ⅲ scores, and a higher proportion of patients with thoracolumbar fascial injury (TLFI) and lumbar sagittal imbalance. The differences between the two groups were statistically significant (all P<0.05). The results of binary logistic regression analysis showed that combined TLFI ( OR=2.773, 95% CI: 1.219-6.309, P=0.015), combined lumbar sagittal imbalance ( OR=4.835, 95% CI: 2.244-10.421, P<0.001), and lower BMD ( OR=2.818, 95% CI: 1.767-4.493, P<0.001) were risk factors for LBP in PD patients. The KPPS score was correlated with BMD and TLFI ( r=-0.146, 0.294, all P<0.05). The linear regression results showed that the merged TLFI ( B=2.271, β=0.285, P<0.001) was positively correlated with KPPS score, indicating a risk factor. Conclusions:The combination of TLFI, lumbar sagittal imbalance, and lower BMD is closely related to the occurrence of LBP in PD patients, and the combination of TLFI is an independent risk factor for exacerbating LBP symptoms. Clinical attention should be paid to the prevention and treatment of TLFI in PD patients.

Objective:To corelate thromboelastography (TEG)-related parameters and D-dimer and fibrinogen levels with the severity of preeclampsia and pregnancy outcomes in patients with preeclampsia.Methods:A case-control study was conducted involving 92 patients with preeclampsia who received treatment at Northwest Women's and Children's Hospital between March 2022 and September 2023 (patient group) and 92 healthy pregnant women who underwent routine check-ups during the same period (control group). All participants underwent TEG tests, and D-dimer and fibrinogen levels were measured. Intergroup comparisons were performed, and patients were categorized based on the severity of their condition. TEG parameters and D-dimer and fibrinogen levels were compared among patients with varying severities of preeclampsia. TEG-related parameters were correlated with D-dimer and fibrinogen levels. Adverse pregnancy outcomes in the patient group were statistically analyzed, and risk factors for these adverse outcomes in women with preeclampsia were identified.Results:In the patient group, the R and K values were (3.06 ± 0.36) minutes and (1.21 ± 0.14) minutes, respectively, both of which were significantly lower than those in the control group [(5.44 ± 0.61) minutes, (1.79 ± 0.21) minutes, t = 32.22, 22.04, both P < 0.001]. The α angle, CI value, MA value, and D-dimer and fibrinogen levels in the patient group were (71.31 ± 7.63)°, (3.89 ± 0.41), (65.71 ± 7.01) mm, (2.22 ± 0.24) mg/L, and (4.51 ± 0.49) g/L, respectively, all of which were significantly higher than those in the control group [(64.85 ± 6.79)°, (2.19 ± 0.23), (58.96 ± 6.09) mm, (1.92 ± 0.21) mg/L, (3.75 ± 0.40) g/L, t = -6.06, -34.68, -6.97, -9.02, -11.52, all P < 0.001]. In the patient group, severe cases had significantly lower R and K values compared with mild cases, while the α angle, CI value, MA value, and D-dimer and fibrinogen levels were significantly higher in severe cases than in mild cases ( t = 11.06, 7.16, -8.01, -12.05, -3.91, -13.74, -8.269, all P < 0.001). In patients with preeclampsia, the R and K values were negatively correlated with D-dimer levels, and the R value was negatively correlated with fibrinogen level ( r = -0.504, -0.612, -0.493, all P < 0.05). In addition, the MA and CI values were positively correlated with D-dimer level, and the α angle was positively correlated with fibrinogen level ( r = 0.436, 0.534, 0.492, all P < 0.05). Among the participants, 41 women experienced adverse pregnancy outcomes. In patients with adverse pregnancy outcomes, the R and K values were (2.48 ± 0.25) minutes and (1.12 ± 0.14) minutes, which were significantly lower than those in patients without adverse pregnancy outcomes [(2.75 ± 0.29) minutes, (1.28 ± 0.13) minutes, t = 4.71, 5.67; both P < 0.001]. The α angle, CI value, MA value, and D-dimer and fibrinogen levels in patients with adverse pregnancy outcomes were (76.62 ± 8.01)°, (4.42 ± 0.46), (69.77 ± 7.06) mm, (2.57 ± 0.27) mg/L, and (4.97 ± 0.51) g/L, all of which were significantly higher than those in patients without adverse pregnancy outcomes [(67.04 ± 7.01)°, (3.46 ± 0.37), (62.45 ± 6.82) mm, (1.94 ± 0.21) mg/L, (4.14 ± 0.43) g/L, t = -6.11, -5.03, -11.09, -12.25, -8.46, all P < 0.001]. Logistic regression analysis indicated that R and K values were protective factors for adverse pregnancy outcomes ( OR < 1, P < 0.05), while MA value, α angle, CI value, and D-dimer and fibrinogen levels were independent risk factors ( OR > 1, P < 0.05). Conclusion:TEG-related parameters differ significantly between patients with preeclampsia and healthy pregnant women. These parameters are correlated with the severity of preeclampsia, as well as with D-dimer and fibrinogen levels. TEG-related parameters are risk factors for adverse pregnancy outcomes in patients with preeclampsia.

In order to strengthen the supervision of the use of drugs in hospitals，the Sichuan Academy of Medical Sciences· Sichuan Provincial People’s Hospital took the lead in compiling the Principles for the Rational Use of National Key Monitoring Drugs （the Second Batch） with a number of experts from multiple medical units in accordance with the Second Batch of National Key Monitoring Rational Drug Use List （hereinafter referred to as “the List”） issued by the National Health Commission. According to the method of the WHO Guidelines Development Manual， the writing team used the Delphi method to unify expert opinions by reading and summarizing the domestic and foreign literature evidence of related drugs， and applied the evaluation， formulation and evaluation method of recommendation grading （GRADE） to evaluate the quality of evidence formed， focusing on more than 30 drugs in the List about the evaluation of off-label indications of drugs， key points of rational drug use and key points of pharmaceutical monitoring. It aims to promote the scientific standardization and effective management of clinical medication， further improve the quality of medical services， reduce the risk of adverse drug reactions and drug abuse， promote rational drug use， and improve public health.

The condition of patients with severe traumatic brain injury (sTBI) complicated by corona virus 2019 disease (COVID-19) is complex. sTBI can significantly increase the probability of COVID-19 developing into severe or critical stage, while COVID-19 can also increase the surgical risk of sTBI and the severity of postoperative lung lesions. There are many contradictions in the treatment process, which brings difficulties to the clinical treatment of such patients. Up to now, there are few clinical studies and therapeutic norms relevant to sTBI complicated by COVID-19. In order to standardize the clinical treatment of such patients, Critical Care Medicine Branch of China International Exchange and Promotive Association for Medical and Healthcare and Editorial Board of Chinese Journal of Trauma organized relevant experts to formulate the Chinese expert consensus on clinical treatment of adult patients with severe traumatic brain injury complicated by corona virus infection 2019 ( version 2023) based on the joint prevention and control mechanism scheme of the State Council and domestic and foreign literatures on sTBI and COVID-19 in the past 3 years of the international epidemic. Fifteen recommendations focused on emergency treatment, emergency surgery and comprehensive management were put forward to provide a guidance for the diagnosis and treatment of sTBI complicated by COVID-19.

Single-cell or low-input multi-omics techniques have revolutionized the study of pre-implantation embryo development.However,the single-cell or low-input proteomic research in this field is rela-tively underdeveloped because of the higher threshold of the starting material for mammalian embryo samples and the lack of hypersensitive proteome technology.In this study,a comprehensive solution of ultrasensitive proteome technology(CS-UPT)was developed for single-cell or low-input mouse oocyte/embryo samples.The deep coverage and high-throughput routes significantly reduced the starting material and were selected by investigators based on their demands.Using the deep coverage route,we provided the first large-scale snapshot of the very early stage of mouse maternal-to-zygotic transition,including almost 5,500 protein groups from 20 mouse oocytes or zygotes for each sample.Moreover,significant protein regulatory networks centered on transcription factors and kinases between the MII oocyte and 1-cell embryo provided rich insights into minor zygotic genome activation.

Microvascular invasion (MVI) is an independent predictor of early recurrence and poor prognosis following hepatocellular carcinoma (HCC) resection and transplantation. As a novel non-invasive diagnostic tool, radiomics can extract the quantitative imaging features of tumors and peritumoral tissues with high throughput, providing more information on tumor heterogeneity than conventional and functional imaging of visual analysis and having a good application prospect in predicting the presence of MVI in HCC patients, thereby improving the accuracy of HCC diagnosis and prognosis. The value of the multimodal radiomics method based on various imaging methods in evaluating the possibility of MVI in HCC patients is elucidated here in combination with the latest research progress.

The protection of language function is one of the major challenges of brain surgery. Over the past century, neurosurgeons have attempted to seek the optimal strategy for the preoperative and intraoperative identification of language-related brain regions. Neurosurgeons have investigated the neural mechanism of language, developed neurolinguistics theory, and provided unique evidence to further understand the neural basis of language functions by using intraoperative cortical and subcortical electrical stimulation. With the emergence of modern neuroscience techniques and dramatic advances in language models over the last 25 years, novel language mapping methods have been applied in the neurosurgical practice to help neurosurgeons protect the brain and reduce morbidity. The rapid advancements in brain-computer interface have provided the perfect platform for the combination of neurosurgery and neurolinguistics. In this review, the history of neurolinguistics models, advancements in modern technology, role of neurosurgery in language mapping, and modern language mapping methods (including noninvasive neuroimaging techniques and invasive cortical electroencephalogram) are presented.
Brain Mapping ; Brain Neoplasms ; Humans ; Language ; Neurosurgery ; Neurosurgical Procedures

ObjectiveTo investigate the change in the activity of glucosylceramide synthase, the key enzyme in glycosphingolipid metabolism and synthesis, in Huh7 cells infected by hepatitis B virus (HBV) in vitro. MethodsBlood samples were collected from nine previously untreated patients with acute hepatitis B who attended Department of Infectious Diseases, The First Hospital of Lanzhou University, from June to August, 2019, and the blood samples collected from seven healthy individuals who underwent physical examination were established as control. Huh7 cells were inoculated with the high-copy HBV particles (＞9.9×107 IU/ml) in the serum of patients with HBV infection (infection group), and Huh7 cells co-cultured with the serum of healthy individuals were established as control group. The expression levels of HBsAg and HBV DNA in the cytoplasm of HBV-infected Huh7 cells were measured, and the correlation between GCS activity and virus was analyzed. A one-way analysis of variance was used for comparison of continuous data between multiple groups, and the least significant difference t-test was used for further comparison between two groups, and a Pearson correlation analysis was performed. ResultsCompared with the control group, the infection group had a significant reduction in the number of cells, an increase in cell volume, and cell membrane fragmentation. The infection group had a significant increase in the expression of HBsAg in cytoplasm at 4 hours, 8 hours, 2 days, and 5 days after infection (P＜0.05); the expression level of HBV DNA tended to increase significantly from 4 hours after infection to 8 hours, 2 days, and 5 days after infection (16.67±11.55 IU/ml vs 112.01±25.94 IU/ml/328.01±10350 IU/ml/101.60±49.84 IU/ml, P＜0.001), with the highest level at 2 days after infection. During HBV infection, the activity of GCS gradually increased with the increase in viral replication from 4 hours after infection (126.21±9.59 IU/ml) and reached a peak at 2 days after infection (226.53±36.27 IU/ml), with a significant difference between the infection group and the control group at 2 days after infection (226.53±36.27 IU/ml vs 136.50±1544 IU/ml, t=3.956, P=0.016 7). The activity of GCS was positively correlated with HBV DNA level (r=0.576 8, P=0047 1). ConclusionHuh7 cells are successfully infected with the high-copy HBV particles in the serum of patients with HBV infection, which mimics the characteristics of HBV infection in vitro to a certain degree. The activity of GCS may be associated with HBV infection, suggesting that glycosphingolipid synthesis and metabolism may be closely associated with HBV.