This study explored the growth-promoting effect and mechanism of the endophytic bacterium Kocuria rosea on Rehmannia glutinosa, aiming to provide a scientific basis for the development of green bacterial fertilizer. R. glutinosa 'Jinjiu' was treated with K. rosea, and the shoot parameters including leaf length, leaf width, plant width, and stem diameter were measured every 15 days. After 120 days, the shoots and roots were harvested. The root indicators(root number, root length, root diameter, root fresh weight, root dry weight, root volume, and root vitality) and secondary metabolites(catalpol, rehmannioside A, rehmannioside D, verbascoside, and leonuride) were determined. The R. glutinosa growth-promoting mechanism of K. rosea was discussed from the effect of K. rosea on the nutrient element content in R. glutinosa and rhizosphere soil and the genome information of this plant. After application of K. rosea, the maximum increases in leaf length, leaf width, plant width, and stem diameter were 35.67%(60 d), 25.39%(45 d), 40.17%(60 d), and 113.85%(45 d), respectively. The root number, root length, root diameter, root volume, root fresh weight, root dry weight, and root viability increased by 41.71%, 45.10%, 48.61%, 94.34%, 101.55%, 147.61%, and 42.08%, respectively. In addition, the content of rehmannioside A and verbascoside in the root of R. glutinosa increased by 76.67% and 69.54%, respectively. K. rosea promoted the transformation of nitrogen(N), phosphorus(P), and potassium(K) in the rhizosphere soil into the available state. Compared with that in the control, the content of available N(54.60 mg·kg~(-1)), available P(1.83 μmol·g~(-1)), and available K(83.75 mg·kg~(-1)) in the treatment with K. rosea increased by 138.78%, 44.89%, and 14.34%, respectively. The content of N, P, and K in the treatment group increased by 293.22%, 202.63%, and 23.80% in the roots and by 23.60%, 107.23%, and 134.53% in the leaves of R. glutinosa, respectively. K. rosea carried the genes related to colonization(rbsB, efp, bcsA, and gmhC), N, P, and K metabolism(narG, narH, narI, nasA, nasB, GDH2, pyk, aceB, ackA, CS, ppa, ppk, ppk2, pstS, pstA, pstB, and pstC), and indole-3-acetic acid and zeatin synthesis(iaaH and miaA). Further studies showed that K. rosea could colonize the roots of R. glutinosa and secrete indole-3-acetic acid(3.85 μg·mL~(-1)) and zeatin(0.10 μg·mL~(-1)). In summary, K. rosea promotes the growth of R.ehmannia glutinosa by enhancing the nutrient uptake, which provides a theoretical basis for the development of plant growth-promoting microbial products.
Rehmannia/metabolism* ; Endophytes/metabolism* ; Plant Roots/growth & development* ; Micrococcaceae/genetics* ; Data Mining ; Plant Leaves/metabolism* ; Genomics ; Rhizosphere

The demographic characteristics, drug use, clinical symptoms and other data of the patients treated with Huoxiang Zhengqi Oral Liquid were collected. The latent class analysis(LCA) was performed to reveal the distribution of primary symptoms, and then the doubly robust estimation was employed to analyze the efficacy of different doses of Huoxiang Zhengqi Oral Liquid in different populations. A total of 11 273 patients were enrolled in this study, including 4 347 males and 6 926 females. A total of 15 primary symptoms were included, with the top 3 being dizziness(53.9%), head heaviness(39.6%), and nausea(39.4%). According to the LCA, the population was divided into 3 groups of spleen deficiency and dampness exuberance(5 604 cases, 49.71%), upward harassing of wind-phlegm(4 955 cases, 43.96%), and spleen Qi deficiency(714 cases, 6.33%). Double robust estimation showed that the time to recovery of the patients with spleen Qi deficiency had no significant difference regarding the daily dose. Compared with the daily dose of 20 mL, the daily doses of 40, and 60 mL shortened the time to recovery by 16.67(95%CI[5.23, 28.12]) and 15.94 h(95%C1[7.45, 24.43]) in the patients with upward harassingof wind-phlegm, the daily doses of 30, 40, and 60 mL shortened the time to recovery by 4.42(95%CI[1.06, 7.77]), 13.07(95%CI[1.61, 24.54]), 13.92 h(95%CI[5.14, 22.70]) in the patients with spleen deficiency and dampness exuberance, respectively. The patients with cold due to wind-cold and dampness stagnation had more primary syndromes, and the disease locations were mainly in the head, stomach, and spleen. In clinical practice, the daily dose of Huoxiang Zhengqi Oral Liquid can be increased according to the symptoms of patients, which can shorten the time to recovery.
Humans ; Male ; Female ; Drugs, Chinese Herbal/therapeutic use* ; Middle Aged ; Adult ; Young Adult ; Aged ; Adolescent ; Administration, Oral ; Wind ; Child ; Spleen/drug effects* ; Cold Temperature ; Aged, 80 and over

OBJECTIVE: Despite the combination of Scutellaria barbata D. Don and Scleromitrion diffusum (Willd.) R.J. Wang (SB-SD) being a recognized Chinese medicinal herbal pair that is commonly used in the treatment of ovarian cancer, there is a poor understanding of their pharmacological mechanisms. This study examines the antitumor properties and potential mechanisms of SB-SD on human ovarian cancer A2780 cells through a multi-omics approach, establishing a pharmacological basis for clinical utilization. METHODS: A range of mass ratios and reagents were used in the hot reflux extraction of SB-SD. The inhibitory effect of the SB-SD extracts on A2780 cell proliferation was assessed using the cell-counting kit 8 assay. A zebrafish tumor implantation model was used to evaluate the effects of SB-SD extracts on tumor growth and metastasis in vivo. Transcriptomics and proteomics were used to investigate alterations in biological pathways in A2780 cells after treatment with different concentrations of SB-SD extract. Cell cycle, cell apoptosis, intracellular free iron concentration, intracellular reactive oxygen species (ROS) concentration, malondialdehyde (MDA), and mitochondrial membrane potential were measured. Real-time quantitative reverse transcription polymerase chain reaction and Western blotting were utilized to investigate the effects of heme catabolism and ferritinophagy on ferroptosis induced by SB-SD extract in A2780 cells. RESULTS: The 70% ethanol extract of SB-SD (a mass ratio of 4:1) inhibited A2780 cell proliferation significantly with a half maximal inhibitory concentration of 660 μg/mL in a concentration- and time-dependent manner. Moreover, it effectively suppressed tumor growth and metastasis in a zebrafish tumor implantation model. SB-SD extract induced the accumulation of free iron, ROS, MDA, and mitochondrial damage in A2780 cells. The mechanisms might involve the upregulated expression of ferritinophagy-related genes microtubule-associated protein 1 light chain 3, autophagy-related gene 5, and nuclear receptor coactivator 4. CONCLUSION SB-SD extract effectively inhibited the development of ovarian cancer both in vitro and in vivo. Its mechanism of action involved inducing ferroptosis by facilitating heme catabolism and ferritinophagy. This herbal pair holds promise as a potential therapeutic option for ovarian cancer treatment and may be utilized in combination with routine treatment to improve the treatment outcomes of ovarian cancer patients. Please cite this article as: Wang Z, Liu M, Li GX, Zhang L, Ding KY, Li SQ, Gao BQ, Chen P, Choe HC, Xia LY, Yang YT, Liu Y, Sui X, Ma JN, Zhang L. A herbal pair of Scutellaria barbata D. Don and Scleromitrion diffusum (Willd.) R.J. Wang induced ferroptosis in ovarian cancer A2780 cells via inducing heme catabolism and ferritinophagy. J Integr Med. 2024; 22(6): 666-683.
Ferroptosis/drug effects* ; Female ; Humans ; Animals ; Scutellaria/chemistry* ; Ovarian Neoplasms/genetics* ; Zebrafish ; Cell Line, Tumor ; Ferritins/genetics* ; Plant Extracts/pharmacology* ; Heme/metabolism* ; Drugs, Chinese Herbal/pharmacology* ; Cell Proliferation/drug effects* ; Reactive Oxygen Species/metabolism* ; Antineoplastic Agents, Phytogenic/pharmacology* ; Autophagy/drug effects* ; Apoptosis/drug effects*

Objective: To explore the clinical characteristics of various types of infected pancreatic necrosis(IPN) and the prognosis of different treatment methods in the imaging classification of IPN proposed. Methods: The clinical data of 126 patients with IPN admitted to the Department of Pancreatic and Biliary Surgery, the First Affiliated Hospital of Harbin Medical University from December 2018 to December 2021 were analyzed retrospectively. There were 70 males(55.6%) and 56 females(44.4%), with age(M(IQR)) of 44(17)years (range: 12 to 87 years). There were 67 cases(53.2%) of severe acute pancreatitis and 59 cases (46.8%) of moderately severe acute pancreatitis. All cases were based on the diagnostic criteria of IPN. All cases were divided into Type Ⅰ(central IPN)(n=21), Type Ⅱ(peripheral IPN)(n=23), Type Ⅲ(mixed IPN)(n=74) and Type Ⅳ(isolated IPN)(n=8) according to the different sites of infection and necrosis on CT.According to different treatment strategies,they were divided into Step-up group(n=109) and Step-jump group(n=17). The clinical indicators and prognosis of each group were observed and analyzed by ANOVA,t-test,χ² test or Fisher exact test,respectively. Results: There was no significant difference in mortality, complication rate and complication grade in each type of IPN(all P>0.05). Compared with other types of patients, the length of stay (69(40)days vs. 19(19)days) and hospitalization expenses(323 000(419 000)yuan vs. 60 000(78 000)yuan) were significantly increased in Type Ⅳ IPN(Z=-4.041, -3.972; both P<0.01). The incidence of postoperative residual infection of Type Ⅳ IPN was significantly higher than that of other types (χ²=16.350,P<0.01). There was no significant difference in the mortality of patients with different types of IPN between different treatment groups. The length of stay and hospitalization expenses of patients in the Step-up group were significantly less than those in the Step-jump group(19(20)days vs. 33(35)days, Z=-2.052, P=0.040;59 000(80 000)yuan vs. 122 000(109 000)yuan,Z=-2.317,P=0.020). Among the patients in Type Ⅳ IPN, the hospitalization expenses of Step-up group was significantly higher than that of Step-jump group(330 000(578 000)yuan vs. 141 000 yuan,Z=-2.000,P=0.046). The incidence of postoperative residual infection of Step-up group(17.4%(19/109)) was significantly lower than that of Step-jump group(10/17)(χ²=11.980, P=0.001). Conclusions: Type Ⅳ IPN is more serious than the other three types. It causes longer length of stay and more hospitalization expenses. The step-up approach is safe and effective in the treatment of IPN. However, for infected lesions which are deep in place,difficult to reach by conventional drainage methods, or mainly exhibit "dry necrosis", choosing the step-jump approach is a more positive choice.
Male ; Female ; Humans ; Retrospective Studies ; Pancreatitis, Acute Necrotizing/complications* ; Acute Disease ; Intraabdominal Infections/complications* ; Necrosis/complications* ; Treatment Outcome

italic>O-methyltransferases (OMTs) are one of the key tailoring enzymes in the biosynthesis of many natural products, O-methylation can not only reduce the reactivity of natural products, but also alter their solubility, stability and biological activities. Based on the transcriptome data of Ardisia japonica, a full-length cDNA sequence of candidate OMT (termed as AjOMT1) was cloned by reverse transcription-polymerase chain reaction (RT-PCR) and expressed in Escherichia coli (E. coli) for the first time. In vitro enzyme catalytic activity assay showed that the recombinant AjOMT1 could effectively catalyze quercetin to form O-methylated products. Most importantly, AjOMT1 showed unprecedented substrate promiscuity towards structurally various compounds including flavonoids, stilbenes, coumarins, alkaloids and phenylpropanoids, especially preferring to the compounds with adjacent phenolic hydroxyl groups, and showed regio-selectivity. These results suggested that AjOMT1 could be used as the tool enzyme to conduct O-methylation of different types of compounds to produce diverse active methylated products, and provide a new method for drug discovery, even universal part for synthetic biology of natural products.

ObjectiveTo investigate the expression of diabetes related microRNA （miRNA） in plasma exosomes of pregnant women complicated with gestational diabetes mellitus （GDM） and to study their association with the pathogenesis of GDM. MethodsIn this study， diabetes related miRNAs microarray data sets were searched through Gene Expression Omnibus （GEO） database， and screened by GEO2R to determine the candidate miRNAs. Differentially expressed miRNAs were selected if the change is consistent in more than one microarray data sets. Singleton pregnant women within 10-16 gestational weeks （gws） were included and their plasma was obtained for further analysis. In 24~28 gws， oral glucose tolerance tests （OGTT） were performed to diagnose GDM or normal glucose tolerance （NGT）. Diabetes related miRNAs expression in plasmatic exosomes was compared between GDM and NGT groups by RT-PCR. Receiver operating characteristic （ROC） curve was applied to assess the predictive efficiency of miRNAs. Finally， Kyoto Encyclopedia of Genes and Genomes （KEGG） pathway analysis was used to reveal the function of miRNAs. ResultsFive diabetes related microarray datasets were downloaded from GEO database， including GSE94649， GSE21321， GSE98043， GSE148961 and GSE27645. Ten differentially expressed miRNAs were found， among which seven were up-regulated and three were down-regulated. RT-PCR results showed that， compared with NGT group， hsa-miR-188-5p， hsa-miR-663a， hsa-miR-135a-5p and hsa-miR-4707-5p in plasma exosomes of GDM pregnant women were up-regulated. The area under the ROC curve （AUC） of these four miRNAs for GDM prediction was 0.839 （95%CI：0.724~0.954）. The target genes of miR-135a-5p were involved in insulin signaling pathways. ConclusionsDifferentially expressed exosomal miRNAs in GDM plasma act as potential predictors of GDM. Among them， miR-135a-5p mainly participates in insulin signaling pathways.

Objective:To summarize the patient profiles and therapeutic efficacies of ABO-incompatible living-related kidney transplantations at 19 domestic transplant centers and provide rationales for clinical application of ABOi-KT.Methods:Clinical cases of ABO-incompatible/compatible kidney transplantation (ABOi-KT/ABOc-KT) from December 2006 to December 2009 were collected. Then, statistical analyses were conducted from the aspects of tissue matching, perioperative managements, complications and survival rates of renal allograft or recipients.Results:Clinical data of 342 ABOi-KT and 779 ABOc-KT indicated that (1) no inter-group differences existed in age, body mass index (BMI), donor-recipient relationship or waiting time of pre-operative dialysis; (2) ABO blood type: blood type O recipients had the longest waiting list and transplantations from blood type A to blood type O accounted for the largest proportion; (3) HLA matching: no statistical significance existed in mismatch rate or positive rate of PRA I/II between two types of surgery; (4) CD20 should be properly used on the basis of different phrases; (5) hemorrhage was a common complication during an early postoperative period and microthrombosis appeared later; (6) no difference existed in postoperative incidence of complications or survival rate of renal allograft and recipients at 1/3/5/10 years between ABOi-KT and ABOc-KT. The acute rejection rate and serum creatinine levels of ABOi-KT recipients were comparable to those of ABOc-KT recipients within 1 year.Conclusions:ABOi-KT is both safe and effective so that it may be applied at all transplant centers as needed.

There were vivax malaria, falciparum malaria, and malariae malaria epidemic in Jiangsu Province, and vivax malaria was the dominant disease. Anopheles sinensis and An. anthropophagus were malaria-transmitted vectors. Since the founding of People’s Republic of China, there have been two major malaria outbreaks in Jiangsu Province, when the highest annual malaria incidence reached up to 24.95%. According to prevention and control principles of “adjusting measures to local conditions, giving different guidance to different categories and highlighting key points”, during the epidemic outbreak stage, the largescale malaria prevention and control measures were implemented for all the residents who were target population in Jiangsu malaria-endemic areas. During the basic eradication stage, the targeted prevention and control measures had been carried out according to the different epidemic features to gradually consolidate the achievement of prevention and control in Jiangsu Province. In the malaria elimination stage, Jiangsu Province focused on controlling of the source of infection and malaria surveillance. According to the “1-3-7 targeted elimination” work model, the management of infectious sources and investigation and disposal of foci were carried out for each epidemic focus to block the malaria transmission. By the end of 2017, there had been no indigenous malaria cases for the six consecutive years in Jiangsu Province. All the 13 cities have passed the assessment of malaria elimination of Jiangsu Province. Although Jiangsu Province has achieved the goal of malaria elimination, it is urgent and necessary to maintain and improve malaria surveillance capabilities to prevent malaria reintroduction.

OBJECTIVESTo investigate the safety and efficacy of yangxinkang tablets in patients with chronic heart failure (CHF) and syndrome of qi and yin deficiency, blood stasis, and water retention.

METHODSIn a double-blinded, randomized, placebo-controlled, multicenter clinical trail, 228 patients with CHF New York Heart Association (NYHA) class II or III in stage C were assigned by randomized block method to two groups in a 1:1 ratio to undergo either conventional Western treatment or conventional treatment plus yangxinkang tablets for 4 weeks. The outcome measure were effect of cardiac function, Chinese medicine (CM) syndromes, scores of symptoms, signs, and quality of life measured by Minnesota Living with heart failure questionnaire (MLHFQ) before and after the treatment.

RESULTSTotally 112 patients were analyzed in the treatment group and 109 in the control group. They were comparable in NYHA functional class, basic parameters and primary diseases before treatment. Cardiac function and CM syndromes were greatly ameliorated in both groups after treatment. Total effective rates of cardiac function and CM syndrome in the treatment group were significantly higher than those in the control group (P<0.05). Total symptom score and sign score in the treatment group decreased significantly after treatment (P<0.01), which were significantly lower than those in the control group (P<0.05). There were statistically significant differences in post-treatment scores of gasp, cough with phlegm, pulmonary rales and jugular vein engorgement between the two groups (P<0.05 or P<0.01). Three MLHFQ scores decreased significantly in both groups after treatment (P<0.01). Post-treatment total scale score and physical subscale score in the treatment group and the reduction of them showed statistically significant differences (P<0.05) as compared with the control group. There was no significant difference between the two groups in emotional subscale score and the reduction after treatment (P>0.05). There was no obvious adverse reaction in either group noted during the study.

CONCLUSIONSYangxinkang tablets were safe and efficacious in improving cardiac function, CM syndromes, symptoms, signs, and quality of life in patients with CHF class II or III in stage C on the base of conventional treatment.

Aged ; Chronic Disease ; Double-Blind Method ; Drugs, Chinese Herbal ; administration & dosage ; Female ; Heart Failure ; drug therapy ; physiopathology ; Humans ; Male ; Quality of Life ; Surveys and Questionnaires ; Tablets

Animals ; Cellular Reprogramming ; Dentate Gyrus ; cytology ; Fibroblasts ; cytology ; Mice ; Neural Stem Cells ; cytology ; transplantation ; Swine