This study selected 6 529 plant-based Chinese materia medica(PCMM) from Chinese Materia Medica as research subjects and applied a random permutation test to explore the overall correlation characteristics between nature and flavor, as well as the correlation characteristics after distinguishing different medicinal parts and harvest seasons. The results showed that the overall correlation characteristics between nature and flavor in PCMM were significantly associated in the following pairs: cold and bitter, cool and bitter, cool and astringent, cool and light, neutral and sweet, neutral and astringent, neutral and light, neutral and sour, hot and pungent, and warm and pungent. When analyzing the data by distinguishing medicinal parts and/or harvest seasons, new correlation patterns emerged, characterized by the disappearance of some significant correlations and the emergence of new ones. When analyzing by medicinal parts alone, significant correlations were found in the following cases: cold and light in leaves, cold and salty in barks, cool and sweet in fruits and seeds, neutral and pungent in whole herbs, neutral and salty in stems, and warm and salty in flowers. However, no significant correlations were found between cool and bitter in stems and other types of herbs, cool and astringent in fruits, seeds, flowers, and other types of herbs, cool and light in leaves, fruits, seeds, barks, flowers and other types of herbs, neutral and sweet in barks, neutral and astringent in whole herbs and stems, neutral and light in leaves, fruits, seeds, and flowers, neutral and sour in whole herbs, stems, barks, flowers, and other types of herbs, and hot and pungent in whole herbs, stems, flowers, and other types of herbs. When analyzing by harvest season alone, significant correlations were found in the following cases: cold and salty, and cool and sour in herbs harvested in winter, and neutral and salty in herbs harvested year-round. However, no significant correlation was found between cool and light in herbs harvested in winter. When considering both medicinal parts and harvest seasons, compared to the independent influence of medicinal parts, 14 new significant correlations emerged(e.g., the correlation between cool and bitter in stems harvested in spring), while 53 previously significant correlations disappeared(e.g., the correlation between cool and bitter in barks harvested in summer). Compared to the independent influence of harvest seasons, 11 new significant correlations appeared(e.g., the correlation between cold and light in barks harvested in autumn), while 50 previously significant correlations disappeared(e.g., the correlation between hot and pungent in leaves harvested in winter). This study is the first to reveal the influence of medicinal parts and harvest seasons on the correlation between nature and flavor in PCMM, which highlights that these two factors can interact and jointly affect nature-flavor correlations. Further research is needed to explore the underlying mechanisms. This study provides a deeper understanding of the inherent scientific connotations of herbal properties and offers a theoretical foundation for the cultivation and harvesting of PCMM.
Seasons ; Plants, Medicinal/growth & development* ; Drugs, Chinese Herbal/chemistry* ; Taste

Metachromatic leukodystrophy (MLD) is an inherited disease caused by a deficiency of the enzyme arylsulfatase A (ARSA). Lentivirus-modified autologous hematopoietic stem cell gene therapy (HSCGT) has recently been approved for clinical use in pre and early symptomatic children with MLD to increase ARSA activity. Unfortunately, this advanced therapy is not available for most patients with MLD who have progressed to more advanced symptomatic stages at diagnosis. Patients with late-onset juvenile MLD typically present with a slower neurological progression of symptoms and represent a significant burden to the economy and healthcare system, whereas those with early onset infantile MLD die within a few years of symptom onset. We conducted a pilot study to determine the safety and benefit of HSCGT in patients with postsymptomatic juvenile MLD and report preliminary results. The safety profile of HSCGT was favorable in this long-term follow-up over 9 years. The most common adverse events (AEs) within 2 months of HSCGT were related to busulfan conditioning, and all AEs resolved. No HSCGT-related AEs and no evidence of distorted hematopoietic differentiation during long-term follow-up for up to 9.6 years. Importantly, to date, patients have maintained remarkably improved ARSA activity with a stable disease state, including increased Functional Independence Measure (FIM) score and decreased magnetic resonance imaging (MRI) lesion score. This long-term follow-up pilot study suggests that HSCGT is safe and provides clinical benefit to patients with postsymptomatic juvenile MLD.
Humans ; Leukodystrophy, Metachromatic/genetics* ; Pilot Projects ; Genetic Therapy/methods* ; Hematopoietic Stem Cell Transplantation ; Male ; Follow-Up Studies ; Female ; Lentivirus/genetics* ; Child ; Child, Preschool ; Hematopoietic Stem Cells/metabolism* ; Cerebroside-Sulfatase/metabolism* ; Adolescent

ObjectiveTo investigate the clinical features of patients with acute-on-chronic liver failure （ACLF）， and to construct a risk scoring table that can accurately predict the prognosis of patients in the early stage. MethodsA retrospective analysis was performed for the clinical data of 502 patients with ACLF who were admitted to Tangdu Hospital， Air Force Medical University， from January 1， 2010 to December 31， 2020 （training set）， and the influencing factors for 28-day mortality rate were identified. The 69 ACLF patients who were admitted to Tangdu Hospital， Air Force Medical University， from January 1 to December 31， 2021 were enrolled as the validation set. The independent-samples t test or the Mann-Whitney U test was used for comparison of continuous data between two groups， and the chi-square test or the Fisher’s exact test was used for comparison of categorical data between two groups. A univariate Cox regression analysis was used to obtain the early warning indicators associated with the 28-day prognosis of ACLF patients， and variance inflation factors were used to assess multicollinearity among predictors； a multivariate Cox regression analysis was used to construct a risk model for ACLF prognosis （mortality）. A risk scoring table for ACLF prognosis （mortality） was developed based on regression coefficients （β） from the model equation and weight assignments in the nomogram. Internal validation and comparison were performed for the risk model for ACLF prognosis （mortality）， the scoring table for ACLF prognosis （mortality）， and other scoring models （Child-Turcotte-Pugh ［CTP］ score， Model for End-Stage Liver Disease ［MELD］ score， MELD combined with serum sodium concentration ［MELD-Na］ score， and integrated MELD ［iMELD］ score） in the training set， while external validation and comprehensive evaluation of the scoring table and the other scoring models were performed in the validation set. The Nagelkerke’s R² test and the Hosmer-Lemeshow test were used to assess the degree of fitting of the risk model for ACLF prognosis （mortality）， the scoring table for ACLF prognosis （mortality）， and other scoring models， and fitting curves were plotted. C-index was used to assess the discriminatory ability of the scoring table for ACLF prognosis （mortality） and the other scoring models， and the Z-test was used for comparison of C-index between different models. The decision curve analysis was used to compare the clinical benefits of the scoring table for ACLF prognosis （mortality） and the other scoring models. ResultsThe multivariate Cox regression analysis showed that age （hazard ratio ［HR］=1.027， 95% confidence interval ［CI］： 1.015 — 1.039， P<0.001）， hepatic encephalopathy grade （grade 1： HR=2.928， 95%CI： 1.463 — 5.858， P=0.002； grade 2： HR=3.811， 95%CI： 2.078 — 6.988， P<0.001； grade 3： HR=3.916， 95%CI： 1.917 — 8.001， P<0.001； grade 4： HR=6.966， 95%CI： 4.559 — 10.644， P<0.001）， an increase in total bilirubin （TBil） by ≥17.1 μmol/L per day （HR=1.771， 95%CI： 1.248 — 2.513， P=0.001）， creatinine （HR=1.005， 95%CI： 1.004 — 1.006， P<0.001）， neutrophil count （HR=1.092， 95%CI： 1.060 — 1.126， P<0.001）， and international normalized ratio （HR=1.298， 95%CI： 1.187 — 1.418， P<0.001） were independent risk factors associated with the 28-day mortality rate of ACLF patients， and a risk scoring table was constructed for ACLF prognosis （mortality）. The Nagelkerke’s R² test showed that the risk scoring table for ACLF prognosis （mortality） had an R² value of 0.599 in the training set and 0.722 in the validation set， which were higher than the R² values of CTP， MELD， MELD-Na， and iMELD scores. The Hosmer-Lemeshow test showed that the risk scoring table for ACLF prognosis （mortality） had a P value of 0.280 in the training set and 0.788 in the validation set. The C-index analysis showed that the scoring table had a higher C-index than the other scoring models in the validation set （all P<0.001）， as well as a higher C-index than CTP score in the training set （P<0.001）. The decision curve analysis showed that the risk scoring table for ACLF prognosis （mortality） had higher clinical net benefits than the other scoring models. ConclusionCompared with other scoring models currently used in clinical practice， the novel risk scoring table for ACLF prognosis （mortality） constructed based on the six predictive factors of age， hepatic encephalopathy grade， an increase in TBil by ≥17.1 μmol/L per day， creatinine， neutrophil count， and international normalized ratio has a relatively high value in predicting the 28-day prognosis of ACLF patients.

Objective:To investigate the effect of bone marrow mesenchymal stem cells(BMSCs)on the proliferation and collagen expression levels of L929 cells,and to clarify its related mechanism.Methods:The BMSCs were extracted from the 4-week-old C57BL/6 mice.The phenotypes of BMSCs were identified by immunofluorescence staining.The L929 cells were divided into control group(L929 cells),co-culture group(L929 cells and BMSCs),inhibitor of Janus kinase(JAK)WP1066 group(WP1066-treated L929 cells and BMSCs),and dimethyl sulfoxide(DMSO)group(DMSO-treated L929 cells and BMSCs).Cell counting kit-8(CCK-8)assay was used to detect the proliferation activities of the L929 cells in various groups at different time points;Western blotting method was used to detect the expression levels of type Ⅰ collagen(Col Ⅰ)and type Ⅲ collagen(Col Ⅲ)in the L929 cells in various groups;immunofluorescence staining was used to detect the expressions of Col Ⅰ and Col Ⅲ proteins in the L929 cells in various groups.Results:The fluorescence assay results of surface antigen(SA)showed that the surface markers CD29+,CD45-,CD90+and CD105+were found in the BMSCs.The CCK-8 assay results showed that compared with control group,the proliferation activities of the L929 cells in co-culture group and DMSO group were significantly increased(P＜0.01);compared with co-culture group,the proliferation activity of the L929 cells in WP1066 group was significantly decreased(P＜0.01).The Western blotting method results showed that compared with control group,the expression levels of Col Ⅰ and Col Ⅲ proteins in the L929 cells in co-culture group and DMSO group were significantly increased(P＜0.01);compared with co-culture group,the expression levels of Col Ⅰ and Col Ⅲ proteins in the L929 cells in WP1066 group were significantly decreased(P＜0.01);compared with DMSO group,the expression levels of Col Ⅰ and Col Ⅲ proteins in the L929 cells in WP1066 group were significantly decreased(P＜0.01).The immunofluorescence staining results showed that compared with control group,the fluorescence intensities of Col Ⅰ and Col Ⅲ proteins in the L929 cells in co-culture group and DMSO group were significantly increased(P＜0.01);compared with co-culture group,the fluorescence intensities of Col Ⅰ and Col Ⅲ in the L929 cells in WP1066 group were significantly decreased(P＜0.01);compared with DMSO group,the fluorescence intensities of Col Ⅰ and Col Ⅲ in the L929 cells in WP1066 group were significantly decreased(P＜0.01).Conclusion:MSCs can promote the proliferation and collagen production of the L929 cells of the mice through the JAK2/signal transducer and activator of transcription 3(STAT3)signaling pathway.

Objective To investigate the risk factors for pneumonia complicating infectious mononucleosis(IM)in adults and construct a nomogram prediction model.Methods A retrospective analysis was conducted on 198 IM patients admitted to the Second Affiliated Hospital of Air Force Medical University from January 2015 to December 2021.Patients were divided into pneumonia group(n=52)and non-pneumonia group(n=146)based on whether pulmonary infection occurred during hospitalization.The baseline data(age,gender,place of onset,etc.),clinical manifestations(maximum body temperature,lymph node enlargement,splenomegaly,etc.),and inflammatory indicators[white blood cell count(WBC),C-reactive protein(CRP),etc.]were compared between the two groups.Kaplan-Meier curves were plotted to analyze the key indicators affecting the hospital stay of IM patients.Multivariate logistic regression was used to analyze the independent risk factors for pneumonia complicating IM in adults and construct a nomogram prediction model based on the identified risk factors.The predictive efficacy of the model was evaluated using the receiver operating characteristic(ROC)curve and the consistency of the model was assessed using the calibration curve.The fit of the model was evaluated using the Hosmer-Lemeshow test.Additionally,the sensitivity,specificity,and accuracy of the model were assessed using confusion matrix.Results Compared with non-pneumonia group,the pneumonia group had a significantly higher proportion of patients from rural areas,with body mass index(BMI)≥24 kg/m2,smoking history,hepatomegaly,fever duration of≥7 d,as well as increased total hospitalization costs and average daily hospitalization costs,and prolonged hospital stay(P<0.05).The proportion of patients with a history of antibiotic use was lower in the pneumonia group(P<0.05).Kaplan-Meier survival analysis showed that patients from rural areas,with BMI≥24 kg/m2,smoking history,no prophylactic use of antibiotics,fever duration≥7 d,and hepatomegaly had significantly prolonged hospital stays(P<0.05).Multivariate logistic regression analysis revealed that living in a rural area(OR=4.089,P<0.05),hepatomegaly(OR=4.082,P<0.05),and elevated WBC(OR=1.205,P<0.05)were independent risk factors for pneumonia complicating IM in adults,while the prophylactic use of antibiotics(OR=0.142,P<0.05)was an independent protective factor.The area under the ROC curve of the constructed nomogram prediction model was 0.827(95%CI 0.762-0.892),and the slope of the calibration curve was close to 1,and the Hosmer-Lemeshow test showed χ2=5.299,P=0.725,indicating good consistency and fit of the prediction model.The results of the confusion matrix assessment showed that the sensitivity of the model was 0.669(0.624-0.773),the specificity was 0.827(0.724-0.930),and the accuracy was 0.732(0.665-0.793).Conclusion The nomogram prediction model based on place of onset,hepatomegaly,the prophylactic use of antibiotics and WBC has excellent fit and discrimination,providing an effective quantitative tool for prognosis assessment of IM.

To characterize human antibodies against low-calcium response V(LcrV)antigen of Yersinia pestis,the mono-clonal antibodies were screened and assayed.Antibody gene was derived from peripheral blood mononuclear cells of the vaccin-ees immunized by plague subunit vaccine in phase Ⅱb clinical trial.Human ScFv antibody library was constructed by phage dis-play.After panning library by using recombinant LcrV antigen,antibody variable genes were sequenced and converted into IgG1 format to evaluate its binding specificity and relevant parameters.An anti-plague human ScFv antibody library was estab-lished contained 7.54× 108 independent clones.After panning by LcrV antigen,3 human antibodies named as RV-B4,RV-D1 and RV-E8,respectively,were identified.Using indirect enzyme-linked immunosorbent assay(ELISA)and Western blot(WB),the specific bindings of the mAbs to LcrV antigen were confirmed.The dissociation constant(KD)of them to LcrV is 2.1 nmol/L,1.24 nmol/L and 42 nmol/L,respectively.Minor protective efficacy was found among 3 human antibodies in Y.pestis 141-infected mice.Three anti-LcrV monoclonal antibodies generated from immunized vaccinees were binding specific antibod-ies and could not block plague infection in mice.These antibodies are the potential candidate reagents for basic research of plague immunity and the application of plague diagnosis.

ObjectiveTo investigate the clinical features of patients with acute-on-chronic liver failure （ACLF） and bacterial infection and early warning indicators associated with multidrug-resistant infections. MethodsA retrospective analysis was performed for 130 patients with ACLF and bacterial infection who attended The Second Affiliated Hospital of Air Force Medical University from January 1， 2010 to December 31， 2021， and according to the drug susceptibility results， the patients were divided into multidrug-resistant （MDR） bacterial infection group with 80 patients and non-MDR bacterial infection group with 50 patients. General information and laboratory examination results were compared between the two groups to screen for the early warning indicators associated with MDR bacterial infection. The Student’s t-test was used for comparison of normally distributed continuous data with homogeneity of variance between two groups， and the Mann-Whitney U test was used for comparison of non-normally distributed continuous data or continuous data with heterogeneity of variance between two groups； the chi-square test or the Fisher’s exact test was used for comparison of categorical data between two groups. The binary logistic regression analysis and the receiver operating characteristic （ROC） curve were used to assess the predictive value of early warning indicators. ResultsAmong the 130 patients with ACLF and bacterial infection， sputum （27.7%） was the most common specimen for detection， followed by blood （24.6%）， urine （18.5%）， and ascites （17.7%）. Bacterial infections were dominated by Gram-negative bacteria （58.5%）. Of all bacteria， Escherichia coli （18.5%）， Klebsiella pneumoniae （14.6%）， and Enterococcus faecium （13.8%） were the most common pathogens. Gram-positive bacteria had a high resistance rate to the antibacterial drugs such as erythromycin （72.2%）， penicillin （57.4%）， ampicillin （55.6%）， and ciprofloxacin （53.7%）， while Gram-negative bacteria had a high resistance rate to the antibacterial drugs such as ampicillin （73.3%）， cefazolin （50.0%）， and cefepime （47.4%）. The patients with ACLF and bacterial infection had a relatively high rate of MDR bacterial infection （61.5%）. Comparison of clinical data between the two groups showed that compared with the patients with non-MDR bacterial infection， the patients with MDR bacterial infection had significantly higher levels of alanine aminotransferase （Z=2.089， P=0.037）， aspartate aminotransferase （Z=2.063， P=0.039）， white blood cell count （Z=2.207， P=0.027）， and monocyte count （Z=4.413， P<0.001）. The binary logistic regression analysis showed that monocyte count was an independent risk factor for MDR bacterial infection （odds ratio=7.120， 95% confidence interval ［CI］： 2.478‍ ‍—‍ ‍20.456，P<0.001） and had an area under the ROC curve of 0.686 （95%CI： 0.597‍ ‍—‍ ‍0.776） in predicting ACLF with MDR bacterial infection（P<0.001）， with the optimal cut-off value of 0.50×10⁹/L， a sensitivity of 0.725， and a specificity of 0.400. ConclusionACLF combined with bacterial infections is mainly caused by Gram-negative bacteria， with the common pathogens of Escherichia coli and Klebsiella pneumoniae and a relatively high MDR rate in clinical practice. An increase in monocyte count can be used as an early warning indicator to distinguish MDR bacterial infection from non-MDR bacterial infection.

italic>Lamiophlomis rotata is an important medicinal plant species endemic to the Tibetan Plateau, which is prone to strong climate change impacts on its habitable range due to the high sensitivity of the Tibetan Plateau to climate change. Accurate quantification of species vulnerability to climate change is essential for assessing species extinction risk and developing effective conservation strategies. Therefore, we carried out the α-shape analysis to determine the habitat of L. rotata. We then carried out the climate-niche factor analysis (CNFA) to assess the vulnerability of L. rotata to climate change based on five climate variables (i.e., mean diurnal range, temperature seasonality, mean temperature of warmest quarter, precipitation of driest month and precipitation of warmest quarter) in the context of two shared socioeconomic pathways (i.e., SSP126 and SSP585) and three global climate models (CMCC-ESM2: Centro Euro-Mediterraneo sui Cambiamenti Climatici-Earth System Model version 2; HadGEM3-GC31-LL: Hadley Global Environment Model version 3-Global Coupled configuration 3.1; IPSL-CM6A-LR: Institut Pierre Simon Laplace-Climate Model version 6) during two different periods (2041-2060 and 2081-2100). The vulnerability of L. rotata to climate change was calculated by integrating the sensitivity and exposure indices of L. rotata to five climate variables. The results showed that L. rotata had the highest vulnerability to the precipitation of warmest quarter. Its vulnerability within its habitat range generally showed a spatial pattern of high value in the southern region and low in the northern region, high in the western region and low in the eastern region. In general, the vulnerability of L. rotata under the SSP585 scenario was higher than that under the SSP126 scenario. The climate data of different global climate models have some influence on the results, while the resulted uncertainty can be reduced by data integration methods. As a result of climate change, the pressure on the survival of L. rotata in the future will be intensified in the low-altitude areas such as the Yarlung Zangbo River, Yigongzangbu River, Zayu River, and Jiaomuzu River, etc., while the highly weathered scree flats or stony alpine meadows in the high-altitude zones, such as the eastern Tanggula Mountain Range, the northern part of Hengduan Mountain Range, and the western part of the Qinling Mountains, may become its refuge. It is necessary to focus on and strengthen the protection and management of L. rotata resources in these vulnerble and critical areas.

An integrated evaluation model based on the combination of traditional trait identification and modern chemical analysis was used for the identification of key indexes of grade classification and the establishment of grade quality standard of Lycium barbarum fruits (LBF) from Ningxia genuine producing area. Under the guidance of herbal examination and market survey, particle size, skin color and imperfection were taken as the external trait indicators; focusing on the comprehensiveness and validity of the quality evaluation, 2-O-β-D-glucopyranosyl-L-ascorbic acid (AA-2βG), zeaxanthin dipalmitate (ZD) and volatile ether extractives were used as important parameters involving in quality evaluation in addition to the pharmacopoeia test items and determination indicators such as moisture, ash, water-soluble extractives, Lycium barbarum polysaccharide (LBP) and betaine. The quality differences between different traits and grades of LBF as well as the relevance between character and quality were further investigated by mathematical and statistical means such as t-test analysis, correlation analysis and principal component analysis (PCA). Furthermore, the activities of extractives from different grades of LBF were compared at cellular level. The results showed that LBF were mainly preferred for large and red ones; except for betaine, the other index components were relatively high (moisture and ash were low) in the first-grade and samples with bright-red skin color. Besides, there was a significant correlation between skin color and moisture, water-soluble extractives, LBP, AA-2βG and ZD contents. Considering the results of the study and the market situation, the present study took the grain size and skin color of LBF as the core of evaluation, and at the same time introduced the multi-indicator components including LBP, AA-2βG, ZD, water-soluble extractives and moisture to further guide the grading, and established the quality standard of LBF grades combining the trait indexes and the chemical composition. More importantly, in vitro cell models both preliminarily confirmed that the first-grade LBF played a more significant "nourishing liver and kidney" effect, which provided an experimental basis for the quality control of LBF and promoted the realization of high quality and good price.