Analyze the changes in phenolic components and gene expression profiles of Tetrastigma hemsleyanum leaves with supplemental blue light, and screen differentially expressed genes related to phenolic metabolism, providing a basis for improving the quality of T. hemsleyanum leaves. Using the leaves of T. hemsleyanum under supplemental blue light and visible light as research materials, the content of phenolic components such as neochlorogenic acid, chlorogenic acid, and 3-O-coumaroyl quinic acid was significantly increased by supplemental blue light. A total of 102 949 unigenes were obtained from the transcriptome, including 14 564 differentially expressed unigenes. They can be divided into 52 subclasses by gene ontology (GO) function, kyoto encyclopedia of genes and genomes (KEGG) pathway enrichment analysis showed that these differentially expressed unigenes were significantly enriched in phenolic metabolic pathways such as phenylpropane biosynthesis, flavonoid biosynthesis and isoflavone biosynthesis. A total of 63 differentially expressed unigenes were identified in the pathways related to the biosynthesis of phenolic cpmponents, including 19 key enzymes such as phenylalanine ammonia-lyase (PAL), cinnamyl-alcohol dehydrogenase (CAD), flavonol synthase (FLS), and so on. This study greatly enriched the genetic data information of T. hemsleyanum and laid a foundation for analyzing the mechanism of blue light promoting the biosynthesis of phenols and molecular breeding of T. hemsleyanum.

To address the key challenges in multivariate statistical modeling,a higher-order derivative approach combined with vector space angle multiplicative error correction was proposed for establishing an acid value prediction ordinary least squares(OLS)regression model based on attenuated total reflectance-Fourier transform infrared(ATR-FTIR)spectroscopy.By using acid values measured by potentiometric titration as reference,ATR-FTIR spectroscopy was utilized for direct calibration and prediction of acid values on 96 kinds of lubricating oil samples from a wind turbine.Firstly,the simulated hyperbolic(SH)method was employed to obtain accurate fourth derivative spectrum,resolving overlapping bands and enhancing spectral selectivity.Then,from the calibration set(48 samples),informative spectral regions were identified based on correlation coefficients.Next,the sample with the highest acid value was selected as the reference and1/(1+tan(θ/2))was used as the metric relation of the spectrum to suppress the multiplicity error caused by factors such as the change of effective optical path in ATR-FTIR spectroscopy.After pretreatment of the spectrum by the method of fourth-order derivative combined with angular quantity,the number of variables decreased from 1737 to 8,and the matrix condition number decreased from 1.85×1015 to 56.34,which effectively eliminated the collinearity issue for OLS regression.Direct OLS modeling on spectral preprocessed data achieved a determination coefficient of 0.981 for 47 validation samples,with a relative error range of-8.38%-8.22%,outperforming the commonly used partial least squares(PLS)method(Determination coefficient of 0.865,relative error of-27.82%-22.38%).It was proved that effective data preprocessing significantly improved the prediction accuracy of the model.Furthermore,when the number of calibration set was compressed to 25 and the number of validation set was expanded to 70,the model retained 8 variables with a condition number of 42.60,the determination coefficient of validation set was 0.972,and the relative error ranged from-10.80%to 12.31%.Comparing with the PLS method(Determination coefficient of 0.724,relative error of-34.26%-53.84%),the improvement was more obvious,which showed that the method could still have high prediction accuracy even with fewer modeling samples as well as robustness against multiplicative error interference.

Objective:To explore the application value of simultaneous monitoring of voriconazole(VRCZ)and voriconazole N-oxide(VNO)in efficacy and safety of VRCZ in the prevention and treatment of fungal infections in allogeneic hematopoietic stem cell transplantation(allo-HSCT)patients before engraftment(i.e.,days+1 to+30 after transplantation).Methods:The influencing factors of VRCZ,VNO concentration and MR(CVNO/CVRCz)and the difference of VRCZ in the prevention and treatment of fungal infection and liver and kidney injury were analyzed.The receiver operating characteristic curve(ROC)was used to analyze the differences(the corresponding to the maximum of the Youden index on the curve was set as the cut-off value)to confirm the critical value.Results:The factors affecting VRCZ concentration(CVRCZ),VNO concentration(CVNO)and MR were patient weight,VRCZ daily dose,and transplantation type(all P＜0.05).CVRCZ and CVNO in the effective group were higher than those in the ineffective group(P＜0.001),the opposite of MR(P＜0.001);the liver and renal injury group had lower MR than the normal group(P＜0.05).ROC showed that CVRCZ,CVNO and MR had important value in predicting VRCZ in the prevention and treatment of invasive fungal infections in allo-HSCT patients before engraftment,and their cutoff of concentrations were 0.95 μg/ml,1.35 μg/ml and 1.645,respectively(AUC:0.9677,0.7634,0.9564).CVRCZ and MR can assist in indicating liver[cutoff values:0.65 μg/ml,1.96(AUC:0.5971,0.6663)]and renal injury[cutoff values:0.95 μg/ml,1.705(AUC:0.6039,0.6164)].Conclusion:The great value of simultaneous monitoring of VRCZ,VNO and MR can predict in the efficacy and safety of VRCZ in allo-HSCT patients before engraftment.The prediction accuracy of CVRCZ was higher than that of MR,followed by that of CVNO.Increased CVRCZ and decreased MR increase the risk of liver and kidney injury.

Methamphetamine abuse is a major public health problem in the world,and in recent years,methamphetamine is also the most abused synthetic drug in China.The neurotoxic or addiction mechanism of methamphetamine has not been fully clarified,and there is still a lack of specific withdrawal methods and drugs for methamphetamine abuse.Mitochondria are not on-ly the organelles to which methamphetamine directly produces toxic effects,but also participate in regulating the neurotoxic damage process of methamphetamine.Mitochondrial quality is the regulatory basis for maintaining mitochondrial homeostasis and is regulated by three main mechanisms,which are mitochon-drial biogenesis,mitochondrial dynamic,and mitophagy.This review summarizes the research progress of mitochondrial quality control in methamphetamine-induced neurotoxicity,which may provide theoretical support for further research on the mechanism of methamphetamine neurotoxicity and development the mito-chondria-targeting drugs.

Aim To investigate the effect of polyphyl-lin Ⅱ(PP Ⅱ)on autophagy of osteosarcoma(OS)cells and its related molecular mechanism.Methods U2OS and HOS cells were cultured in vitro and treated with different concentrations of PP Ⅱ(5,10,15,20 μmol·L-1)for 24 h.The changes of acid vesicles were detected by AO staining,the autophagosomes was ob-served by transmission electron microscopy,the ex-pressions of LC3B-Ⅱ/LC3B-Ⅰ,p62,caspase-3,cleaved caspase-3 were detected by Western blot,the intracellular reactive oxygen species(ROS)was detec-ted by DCFH-DA fluorescence probe,cell viability was detected by CCK-8,cell apoptosis rate was detected by Annexin V-FITC/PⅠ staining.Results PP Ⅱ signifi-cantly increased the number of acidic vesicles(P＜0.05,P＜0.01)and autophagosomes.PP Ⅱ signifi-cantly up-regulated the ratio of LC3B-Ⅱ/LC3B-Ⅰ,and down-regulated the expression level of p62 protein in a concentration-and time-dependent manner(P＜0.05,P＜0.01).PP Ⅱ significantly increased intra-cellular ROS levels(P＜0.01).Autophagy inhibitor 3-MA and CQ could reverse the regulation of cell via-bility,autophagy and apoptosis related proteins by PP Ⅱ in U2OS cells,endoplasmic reticulum stress inhibi-tor 4-PBA could also reverse the regulation of autoph-agy related proteins by PP Ⅱ in U2OS cells.Conclu-sion PP Ⅱ promotes OS cell autophagy by mediating ROS and endoplasmic reticulum stress.

Objective: To explore the efficacy of adjuvant programmed cell death 1 (PD-1) monoclonal antibody immunotherapy in Chinese patients with resected stage Ⅱ-Ⅲ melanoma. Methods: A total of 296 patients who underwent radical surgery for stage Ⅱ-Ⅲ cutaneous orlimb melanoma at Fudan University Shanghai Cancer Center and Shanghai Electric Power Hospital between 2017 and 2021 and received adjuvant PD-1 monoclonal antibody immunotherapy, low-dose interferon (IFN), or observational follow-up were enrolled in this study. Patients were divided into the PD-1 monoclonal antibody group (164 cases) and the IFN or observation group (IFN/OBS group, 132 cases) based on postoperative adjuvant treatment methods. Patients' disease recurrence and survival were observed. Results: Among the 296 patients, 77 had cutaneous melanoma and 219 had limb melanoma; 110 were stage Ⅱ and 186 were stage Ⅲ. Among stage Ⅱ patients, the median recurrence-free survival (RFS) in the PD-1 monoclonal antibody group (46 cases) did not reach, while the median RFS in the IFN/OBS group (64 cases) was 36 months. The 1-year RFS rates were 85.3% and 92.1% and the 2-year RFS rates were 71.9% and 63.7% in the PD-1 monoclonal antibody group and the IFN/OBS group, respectively, with no statistically significant difference (P=0.394). Among stage Ⅲ patients, the median RFS rates in the PD-1 monoclonal antibody group (118 cases) and the IFN/OBS group (68 cases) were 23 and 13 months, respectively. The 1-year RFS rates were 70.0% and 51.8% and the 2-year RFS rates were 51.8% and 35.1%in the PD-1 monoclonal antibody group and the IFN/OBS group, respectively, with a statistically significant difference (P=0.010). Stratified analysis showed that the advantage of PD-1 monoclonal antibody adjuvant therapy in improving RFS persisted in the subgroups of primary ulceration (HR=0.558, 95% CI: 0.348-0.893), lymph node macroscopic metastasis (HR=0.486, 95% CI: 0.285-0.828), stage ⅢC (HR=0.389, 95% CI: 0.24-0.63), and the subgroup without BRAF/c-Kit/NRAS gene mutations (HR=0.347, 95% CI: 0.171-0.706). In terms of recurrence patterns, in stage Ⅱ patients, the recurrence and metastasis rate was 15.2% (7/46) in the PD-1 monoclonal antibody group, significantly lower than the IFN/OBS group [43.8% (28/64), P=0.002]. In stage Ⅲ melanoma patients, the recurrence and metastasis rate was 42.4% (50/118) in the PD-1 monoclonal antibody group, also lower than the IFN/OBS group [63.2% (43/68), P=0.006]. Conclusions: In real-world settings, compared with patients receiving low-dose IFN adjuvant therapy or observational follow-up, PD-1 monoclonal antibody immunotherapy can reduce the recurrence and metastasis rate of cutaneous and limb melanoma, and prolong the postoperative RFS of stage Ⅲ cutaneous and limb melanoma patients. Patients with a heavier tumor burden benefit more from immunotherapy.
Humans ; Antibodies, Monoclonal/therapeutic use* ; Apoptosis ; China ; Disease-Free Survival ; East Asian People ; Immunotherapy ; Interferon-alpha/therapeutic use* ; Lymphatic Metastasis ; Melanoma/pathology* ; Programmed Cell Death 1 Receptor/therapeutic use* ; Skin Neoplasms/pathology* ; Melanoma, Cutaneous Malignant

AIM: To observe the effect of soluble glycoprotein 130(sgp130)on expression of p-STAT3 and vascular endothelial growth factor(VEGF)-A in retina of mice with diabetes mellitus(DM), and explore the possibility of sgp130 in interfering with inflammatory damage of diabetic retinopathy(DR).METHODS: A total of 45 mice were randomly divided into normal group, DM group and sgp130 group. DM models were made in DM group and sgp130 group with streptozotocin. No special intervention was given to normal group and DM group, but sgp130 group was given intravitreal injection of 1.5mg/mL sgp130 2μL at the 1 and 5wk. After 10wk, all the mice were sacrificed to assess the protein expression of interleukin 6(IL-6), p-STAT3 and VEGF-A in the retina.RESULTS: The expressions of IL-6, p-STAT3 and VEGF-A in retina of DM group were higher than those of normal group at 10wk(all P<0.01). The expression of p-STAT3 and VEGF-A in sgp130 group were lower than those in DM group(all P<0.01).CONCLUSION: The sgp130 can selectively antagonize the trans signal transduction pathway of IL-6, down-regulate the expression of downstream inflammatory factors VEGF-A, and it may be used in the intervention of retinal inflammatory damage related with IL-6 in DM.

AIM To optimize the TLC identification method for Cirsii Herba and to study the changes in quality properties"carbonizing retains characteristics"of Cirsii Herba Carbonisata.METHODS After the improvement of thin layer plate and solvent in the TLC identification based on the Chinese Pharmacopoeia 2020 Edition for Cirsii Herba,Cirsii Herba Carbonisata had its TLC identification method and UPLC fingerprint established for the determination of its content of buddleoside and acacetin as well.RESULTS We used silica gel G plate,and the solvent of toluene-acetone-formic acid-methanol(6 ∶ 3 ∶ 0.5 ∶ 2.5)for TLC identification of Cirsii Herba.The content variations of buddleoside and acacetin in Cirsii Herba and its differently charred products were consistent with the result of the TLC identification.CONCLUSION The improved TLC identification method for Cirsii Herba is of lower cost and less solvent toxicity compared to the method in the Chinese Pharmacopoeia 2020 Edition,and can identify the changes in quality properties"carbonizing retains characteristics"of differently charred Cirsii Herba,therefore it can be used to control the quality of Cirsii Herba Carbonisata in the market.

OBJECTIVE: To analyze the factors related to pregnancy of endometriosis and whether Chinese herbal medicines (CHMs) can improve pregnancy outcomes in patients with endometriosis in long-term management. METHODS: This multicenter cohort study retrospectively analyzed the clinical data of endometriosis patients with fertility needs from January 2019 to November 2019. A total of 252 patients with endometriosis from 5 level-III Grade A hospitals in Beijing were included in this study. Univariate and multivariate logistic regression analysis were performed for the relevant factors. The propensity score matching (PSM) function of SPSS software was used to match the CHMs group with the non-CHMs group. The pregnancy rate and live birth rate were analyzed. RESULTS: The results of univariate analysis showed that age, disease course, presence of infertility, presence of adenomyosis, time after surgery or use of gonadotropin-releasing hormone agonist (GnRH-a), use of CHMs and follow-up time were influencing factors of pregnancy in endometriosis patients (P<0.05). The results of multivariate analysis showed that age, presence of adenomyosis, time after surgery or use of GnRH-a, use of CHMs and follow-up time were independent factors affecting pregnancy in endometriosis patients, among which, age ⩾35 years old, presence of adenomyosis and follow-up time >6 months were independent risk factors (OR=0.445, 0.348, 0.140, respectively, P<0.05), time after surgery or use of GnRH-a ⩽6 months and use of CHMs were independent protective factors (OR=3.839, 3.842, respectively, P<0.05). After PSM, 99 pairs of two groups were matched successfully. The pregnancy rate of the CHMs group was higher than that of the non-CHMs group [55.56% (55/99) vs. 36.36% (36/99), P<0.05]. The live birth rate of the CHMs group was higher than that of the non-CHMs group [49.49% (49/99) vs. 35.35% (35/99), P<0.05]. CONCLUSION CHMs can effectively improve clinical pregnancy rate and live birth rate of patients with endometriosis in the chronic disease management.
Pregnancy ; Female ; Humans ; Adult ; Pregnancy Outcome ; Endometriosis/surgery* ; Retrospective Studies ; Cohort Studies ; Adenomyosis ; Gonadotropin-Releasing Hormone ; Plant Extracts ; Fertilization in Vitro

Objective: To analyze the prevalence and the risk factors of fungal sepsis in 25 neonatal intensive care units (NICU) among preterm infants in China, and to provide a basis for preventive strategies of fungal sepsis. Methods: This was a second-analysis of the data from the "reduction of infection in neonatal intensive care units using the evidence-based practice for improving quality" study. The current status of fungal sepsis of the 24 731 preterm infants with the gestational age of <34⁺⁰ weeks, who were admitted to 25 participating NICU within 7 days of birth between May 2015 and April 2018 were retrospectively analyzed. These preterm infants were divided into the fungal sepsis group and the without fungal sepsis group according to whether they developed fungal sepsis to analyze the incidences and the microbiology of fungal sepsis. Chi-square test was used to compare the incidences of fungal sepsis in preterm infants with different gestational ages and birth weights and in different NICU. Multivariate Logistic regression analysis was used to study the outcomes of preterm infants with fungal sepsis, which were further compared with those of preterm infants without fungal sepsis. The 144 preterm infants in the fungal sepsis group were matched with 288 preterm infants in the non-fungal sepsis group by propensity score-matched method. Univariate and multivariate Logistic regression analysis were used to analyze the risk factors of fungal sepsis. Results: In all, 166 (0.7%) of the 24 731 preterm infants developed fungal sepsis, with the gestational age of (29.7±2.0) weeks and the birth weight of (1 300±293) g. The incidence of fungal sepsis increased with decreasing gestational age and birth weight (both P<0.001). The preterm infants with gestational age of <32 weeks accounted for 87.3% (145/166). The incidence of fungal sepsis was 1.0% (117/11 438) in very preterm infants and 2.0% (28/1 401) in extremely preterm infants, and was 1.3% (103/8 060) in very low birth weight infants and 1.7% (21/1 211) in extremely low birth weight infants, respectively. There was no fungal sepsis in 3 NICU, and the incidences in the other 22 NICU ranged from 0.7% (10/1 397) to 2.9% (21/724), with significant statistical difference (P<0.001). The pathogens were mainly Candida (150/166, 90.4%), including 59 cases of Candida albicans and 91 cases of non-Candida albicans, of which Candida parapsilosis was the most common (41 cases). Fungal sepsis was independently associated with increased risk of moderate to severe bronchopulmonary dysplasia (BPD) (adjusted OR 1.52, 95%CI 1.04-2.22, P=0.030) and severe retinopathy of prematurity (ROP) (adjusted OR 2.55, 95%CI 1.12-5.80, P=0.025). Previous broad spectrum antibiotics exposure (adjusted OR=2.50, 95%CI 1.50-4.17, P<0.001), prolonged use of central line (adjusted OR=1.05, 95%CI 1.03-1.08, P<0.001) and previous total parenteral nutrition (TPN) duration (adjusted OR=1.04, 95%CI 1.02-1.06, P<0.001) were all independently associated with increasing risk of fungal sepsis. Conclusions: Candida albicans and Candida parapsilosis are the main pathogens of fungal sepsis among preterm infants in Chinese NICU. Preterm infants with fungal sepsis are at increased risk of moderate to severe BPD and severe ROP. Previous broad spectrum antibiotics exposure, prolonged use of central line and prolonged duration of TPN will increase the risk of fungal sepsis. Ongoing initiatives are needed to reduce fungal sepsis based on these risk factors.
Infant ; Infant, Newborn ; Humans ; Birth Weight ; Intensive Care Units, Neonatal ; Retrospective Studies ; Tertiary Care Centers ; Infant, Extremely Low Birth Weight ; Gestational Age ; Infant, Extremely Premature ; Sepsis/epidemiology* ; Retinopathy of Prematurity/epidemiology* ; Bronchopulmonary Dysplasia/epidemiology*