Clinical and molecular biological characterization of patients with accelerated chronic lymphocytic leukemia / 中华血液学杂志

Objective: To investigate the clinical and molecular biological characteristics of patients with accelerated chronic lymphocytic leukemia (aCLL) . Methods: From January 2020 to October 2022, the data of 13 patients diagnosed with aCLL at The First Affiliated Hospital of Nanjing Medical University were retrospectively analyzed to explore the clinical and molecular biological characteristics of aCLL. Results: The median age of the patients was 54 (35-72) years. Prior to aCLL, five patients received no treatment for CLL/small lymphocytic lymphoma (SLL), while the other patients received treatment, predominantly with BTK inhibitors. The patients were diagnosed with aCLL through pathological confirmation upon disease progression. Six patients exhibited bulky disease (lesions with a maximum diameter ≥5 cm). Positron emission tomography (PET) -computed tomography (CT) images revealed metabolic heterogeneity, both between and within lesions, and the median maximum standardized uptake value (SUVmax) of the lesion with the most elevated metabolic activity was 6.96 (2.51-11.90). Patients with unmutated IGHV CLL accounted for 76.9% (10/13), and the most frequent genetic and molecular aberrations included +12 [3/7 (42.9% ) ], ATM mutation [6/12 (50% ) ], and NOTCH1 mutation [6/12 (50% ) ]. Twelve patients received subsequent treatment. The overall response rate was 91.7%, and the complete response rate was 58.3%. Five patients experienced disease progression, among which two patients developed Richter transformation. Patients with aCLL with KRAS mutation had worse progression-free survival (7.0 month vs 26.3 months, P=0.015) . Conclusion: Patients with aCLL exhibited a clinically aggressive course, often accompanied by unfavorable prognostic factors, including unmutated IGHV, +12, ATM mutation, and NOTCH1 mutation. Patients with CLL/SLL with clinical suspicion of disease progression, especially those with bulky disease and PET-CT SUVmax ≥5, should undergo biopsy at the site of highest metabolic uptake to establish a definitive pathological diagnosis.

Rapid analysis of chemical components of Xiaotan Tongfu formula based on UHPLC-Q-TOF/MS / 药学实践杂志

Objective To rapidly explore the chemical components of Xiaotan Tongfu formula, and to provide scientific basis for the basic research and clinical treatment of the formula. Methods Analysis was performed on an Agilent 1290 ultra-performance liquid chromatography system coupled with an Agilent 6530 accurate quality Q-TOF/MS system, by using a Waters ACQUITY UPLC BEH C18 column (2.1 mm × 100 mm, 1.7 μm), with a gradient elution applying 0.1% aqueous formic acid solution and acetonitrile as a mobile phase. The flow rate was 0.3 ml/min. The column temperature was 30°C. The injection volume was 1 μl, and the detection wavelength was 254 nm. Mass spectrometry (MS) data were collected in both positive and negative ESI ion modes. Components in the formula were identified by using the in-house compound database, and comparing the retention time (tR), MS1 and MS2 data with the standard compounds, and the online compound MS database. Results A total of 55 compounds were identified from Coptis coptidis, Pseudomonas solani, Rhubarb, Araceae artemisiae and Pinellia chinensis. Conclusion The established UHPLC-Q-TOF/MS method could systematically and accurately identify the chemical components from Xiaotan Tongfu formula, and provided a reference for the quality marker selection and the research on the active ingredient.

Serum metabolomic study of Shenfu decoction on adriamycin-induced cardiomyopathy in mice / 药学实践杂志

Objective To study the reversal effect of Shenfu decoction（SFD）on adriamycin-induced cardiomyopathy and explore its mechanism by using serum metabolomic technology. Methods The BALB/c mouse model of cardiomyopathy induced by adriamycin was established. The corresponding intervention was given. The serum lactate dehydrogenase（LDH）and creatine phosphatase isoenzyme MB（CK-MB）were measured. The ejection fraction (EF) and shortening fraction (FS) were measured by echocardiography. Mouse serum was collected for gas chromatography-mass spectrometry (GC-MS) analysis. The data obtained was analyzed by multivariate and univariate statistical analysis to compare the changes of endogenous metabolites in the serum of mice in the normal group, model group and Shenfu decoction treatment group, to find the potential biomarkers of Shenfu decoction to reverse the adriamycin-induced cardiomyopathy. Metabolic pathway analysis was used to explore the targeted metabolic pathway of Shenfu decoction. Results The levels of serum LDH and CK-MB in the model group were increased significantly, and the values of EF and FS decreased significantly, indicating that the model was successfully established. The above indicators were significantly improved after treatment with Shenfu decoction. 13 potential biomarkers of adriamycin-induced cardiomyopathy were identified by metabonomic analysis, and Shenfu decoction had significant reversal effect on 11 metabolites. Metabolic pathway analysis showed that the synthesis of phenylalanine, tyrosine and tryptophan, arachidonic acid metabolism, phenylalanine metabolism, tricarboxylic acid cycle and dicarboxylic acid metabolism were the main targeted metabolic pathways of Shenfu decoction. Conclusion Shenfu decoction can reverse adriamycin-induced cardiomyopathy by regulating the unbalanced synthesis of phenylalanine, tyrosine and tryptophan, as well as the metabolism of arachidonic acid, phenylalanine, dicarboxylic acid and tricarboxylic acid cycle.

Effect of Qigui Yishen Decoction on miR-141 regulation in UUO mice with renal fibrosis / 中成药

AIM To investigate the effect and mechanism of Qigui Yishen Decoction (QGYS,Astragali Radix,Angelicae sinensis Radix,Chuanxiong Rhizoma,Achyranthis bidentatae Radix) on regulating the expression of miR-141 in unilateral ureteral obstruction (UUO) mice with renal fibrosis.METHODS Thirty Balb/c male mice randomly divided into sham-operated group (n =6),UUO group (n =6),Lotensin (50 g/kg) group (n =6),QGYS high dose (50 g/kg) group (n =6),and QGYS low dose (10 g/kg) group (n =6) were conducted UUO surgery to promote kidney fibrosis except the six mice in the sham operation group.After a successive 10-day medication of QGYS and Lotensin to mice by oral gavage on daily basis,all mice were killed to procure renal tissue to observe its morphology and pathology changes by HE staining.The expressions of TGF-β1,ColⅣ,and MMP-9 were analyzed by immunohistochemical method,and the expressions of miR141,TGF-β1 were measured by real-time PCR.RESULTS The obviously pathological injuries including renal interstitial fibrosis were identified by HE staining among the groups intervened with UUO,but the variance in the extent due to different administrations of QGYS and Lotensin was noticed as well (P ＜ 0.05).As compared to the UUO group,high and low dose QGYS groups and Lotensin group achieved an up-regulated expression of TGF-β1 and ColⅣ,and a down-regulated expression of MMP-9 by immunohistochemistry (P ＜ 0.05),and significantly increased Mrna expression of miR-141,and decreased Mrna expression of TGF-β1 by real-time PCR (P ＜ 0.05).CONCLUSION In UUO mouse models,QGYS gives influence to TGF-β1and MMP-9 through inducing miR-141 expression change to decrease abnormal accumulation of ECM,and thus inhibits the progression of renal fibrosis.

Immunogenic apoptosis of human Caski cervical cancer cells induced by Lidamy-cin / 中国免疫学杂志

Objective:To investigate effects of Lidamycin (LDM,C-1027) on the proliferation and immunogenic transform of human Caski cervical cancer cells and to provide the basic experiment data and theoretical supports for establishment of the new immu-notherapy method mediated by LDM. Methods:MTT was used for the analysis of cell proliferation;apoptosis rate was analyzed by flow cytometry;Western blot was used to analyze the effect of LDM on the expression of Bax and Bcl-2 in Caski cells;the Flow cytometry was used to detect the expression of Calreticulin ( CRT ) on the cell surface. Results: Lidamycin inhibited proliferation of Caski cells significantly in the time-and dose-dependent manners;The apoptotic cell ratio induced by 5 μg/L Lidamycin was 11. 5% ,Comparing with the control group, Lidamycin treatment increased Bax but decreased Bcl-2 contents significantly within Caski cells, it also significantly increased the expression of CRT on the cell surface of Caski cells from 2. 31% to 67. 2%. Conclusion: Lidamycin has pharmacological activity in inhibiting proliferation of the human cervical Caski cells and the underlying mechanism is related with inducing the intrinsic mitochondrial pathway of apoptosis. In the same time,Lidamycin can increase the expression of CRT on the cell surface,so it may have the ability to promote the immunogenic apoptosis of tumor cells.

Investigation on supramolecular mechanism of multi-component overall control in Chinese medicine controlled sustained-release preparation / 中国中药杂志

Controlled sustained-release preparation (CSRP) is a definitely important source of innovative medicines, however, its further researches and development are limited due to the complexity of Chinese medicine (CM) compositions, and a series of unclear key problems like the apparent properties from physical and chemical aspects. Combined with the CM characteristics of the multiple components and synergistic effect, a series of bottleneck problems in the preparation of CSRP were analyzed. Then the mechanism and influences of supermolecular chemical theory in the CSRP about the multiple-components overall-control were explored under the guideline of "overall control, synchronous dissolution" in CSRP, based on the previous explications about supramolecular chemistry theories and with the application of single component precision controlling technologies. The supermolecular mechanism of multi-component overall control and synchronous release of the CSRP was investigated, providing an useful academic reference for the research and development of the CSRP and laying the theoretical and technical foundation for the manufacturing process of CSRP.

Solubilization characteristics of licorice based on supramolecular "imprinted template" theory / 中国中药杂志

To investigate the effect of the ingredient group of traditional Chinese medicine (TCM) with different "imprinted template" on the supramolecular solubilization ability of licorice, in order to lay a theoretical foundation for explaining the solubilization phenomenon of the components of TCM. Based on the independent supramolecular "imprinted template" rules, molecular connectivity index (MCI) and the correlation of n-octanol-water partition coefficient (logP) were used to indicate hydrophilic lipophilic capacity of TCM, and the extractum rate was used to indicate the solubilization effect of licoriceon single TCM herbs or compounds. The solubilization ability of licorice was evaluated based on MCI, logP and the extractum rate. According to the results, the correlation coefficient between MCI and logP for single herbs was 0.942, and that for single herb adding licorice was 0.916. The extractum rate of most herbs was increased after adding licorice. The correlation coefficient among the extractum rate as well as MCI and logP change values before and after adding licorice were respectively 0.837, 0.405. The correlation coefficient between MCI and logP for eight compounds was 0.937. Meanwhile, licorice had a solubilization effect on the remaining 7 compound except for Huangqi decoction. Therefore, licorice shows the solubilization effect through the independent supramolecular "imprinted template", so as to improve the hydrophilic lipophilic ability. There was a high positive correlation between the MCI and logP in ingredients for TCM, which could be used as important parameters to indicate the "imprinted template" feature for components of TCM. The study on the solubilizing effect of TCM with the supramolecular "imprinted template" theory was feasible, and will lay a foundation for the reform of single-herb dosage form.

Investigation of supramolecular chemical mechanism of traditional Chinese medicine processing / 中国中药杂志

To analyze the research status of traditional Chinese medicine (TCM) processing and key scientific issues to be resolved by using characteristic of TCM biological supramolecules and reaction theories of 'Qi chromatography' to human being, and then put forward the solution countermeasures. Based on the previous explications of theories of the Chinese medicine with supramolecular chemistry as 'Qi chromatograpy', biological supramolecular chemistry theory was used to explain the root of the problem in TCM processing and form the countermeasures for supramolecular chemistry research in the processing of TCM decoction pieces. TCM is a huge complex biological supramolecular body, so the processing of TCM is in view of the processing of huge complex biological supramolecular body. In nature, it is a TCM pharmaceutical technology with chemical changes of the subject and object of biological supramolecular body with or without auxiliary materials, under the condition of high temperature and high humidity. Supramolecular chemistry was throughout the processing of TCM, so the use of supramolecular technology was appropriate in research. TCM decoction pieces were the product of subject and object molecular changes after supramolecular chemistry reaction, with changes in physical and chemical properties of the subject and object molecules, such as bound water overflow, chemical bond rupture, dehydration, carbonization, and reaction with auxiliary materials. Changes in drug property and drug efficacy after processing depended on the degree of subject and object "imprinting template" change, which can be measured by 'Qi chromatography' function of supermolecular imprinting template in human body. In this paper, the research ideas, methods, variety attribution, processing principle, quality standard and clinical application were analyzed to find out the sticking point of the problems, and form the countermeasures with supramolecular chemistry as the core. The processing of TCM is a chemical technology of biological supramolecular body based on the function of supermolecular 'imprinting template' (medical element) of human meridian-viscera, and its reaction products (decoction pieces) showed determinacy when used alone and compatibility when used together, which may constitute a compatible drug delivery system of TCM in clinical application.

Construction of prokaryotic expression vector, expression and purification of ginseng Cu/Zn superoxide dismutase / 中国中药杂志

The total RNA was extracted from ginseng leaves of Panax ginseng. The Cu/Zn-SOD gene was amplified via RT-PCR and the pET-28(a)-Cu/Zn-SOD expression vector was constructed. The pET-28 (a)-Cu/Zn-SOD recombinant plasmid was transformed into Escherichia coli BL21 (DE3) competent cells and was induced by IPTG in order to select optimal induction of expression conditions. The target protein was purified by the nickel ions (Ni ) affinity chromatography and the target protein enzyme activity was determinated by the xanthine oxidase method. The similarity of the Cu/Zn-SOD gene sequences and the Cu/Zn-SOD gene sequences of Korean ginseng in NCBI was 99. 00%. The target protein expression level was about 44.42%, and the molecular weight was 16.30 kDa after the pET-28(a)-Cu/Zn-SOD recombinants were induced by IPTG. The purified Cu/Zn-SOD protease activity reached 10,596.69 U x mg(-1). The P. ginseng pET-28(a)-Cu/Zn-SOD prokaryotic expression vector was built by the method of molecular biology, which provided the foundation for studying the Cu/Zn-SOD biology function.

Nicotinamide phosphoribosyltransferase inhibitors in cancer therapy: An advance / 第二军医大学学报

Nicotinamide adenine dinucleotide (NAD) plays a crucial role in many cellular processes. It functions as a cofactor in more than 200 oxidation-reduction reactions in humans. As the rate-limiting enzyme of the predominant NAD biosynthesis pathway in mammals, nicotinamide phosphoribosyltransferase (Nampt) regulates the cellular NAD level. Nampt is a key protein in biochemical processes and energy metabolism and has various biological activities. Tumor cells are more sensitive to the NAD levels, making them more susceptible to Nampt inhibition than normal cells. Experimental evidence indicates that Nampt has proangiogenic activity and supports the growth of some tumors. These findings make Nampt attractive for pharmaceutical research during recent years, and Nampt inhibitors might be used for tumor chemotherapy. Currently 4 Nampt inhibitors have been reported: FK866, CHS828, CB30865, and ISOOl. Here we review the recent progress of Nampt inhibitors in cancer therapy, providing evidence for the development and application of Nampt regulating agents.

Effects of warming needle moxibustion on improvement of gastrointestinal and immune function in patients with postoperation of colorectal cancer / 中国针灸

<p><b>OBJECTIVE</b>To verify the clinical therapeutic effect of warming needle moxibustion on improvement of the gastrointestinal and immune function in patients with postoperation of colorectal cancer.</p><p><b>METHODS</b>One hundred and five patients with postoperation of colorectal cancer were randomly divided into an acupuncture and moxibustion group, a Chinese medicine group and a routine treatment group, 35 cases in each group. They were all treated with gastrointestinal decompression and fluid replacement after operation. The acupuncture and moxibustion group was also treated with warming needle moxibustion on the 1st day after operation, and Zusanli (ST 36), Shangjuxu (ST 37) and Xiajuxu (ST 39) etc. were selected, once a day for 10 days, and the Chinese medicine group with Simo Decoction oral solution, three times daily for 10 days. The gastrointestinal function, peripheral blood components and changes of T lymphocyte and NK cells in postoperative patients were observed.</p><p><b>RESULTS</b>The time of the first bowel sound, exhaust and defecation in the acupuncture and moxibustion group were all shorter than those in the Chinese medicine group and the routine treatment group (P<0.05, P<0.01). On the 10th day after operation, the percentages distribution of lymphocyte and neutrophil in the acupuncture and moxibustion group were better than those in the Chinese medicine group and the routine treatment group (all P<0.05). The acupuncture and moxibustion group was also superior to the Chinese medicine group and the routine treatment group in improving the subgroup of T lymphocyte, NK cells and the digestive system symptoms (all P<0.05).</p><p><b>CONCLUSION</b>Warming needle moxibustion has a good therapeutic effect on gastrointestinal function and can regulate bidirectionally peripheral blood lymphocyte and neutrophile granulocyte and improve the T lymphocyte subgroup and NK cells so as to promote the recovery of immune function in patients with colorectal cancer after operation.</p>

Clinical study on acupuncture combined with medication in restoration of gastrointestinal functions for postoperative patients with gastric cancer / 中国针灸

<p><b>OBJECTIVE</b>To observe clinical therapeutic effects of acupuncture combined with medication in restoration of gastrointestinal functions for postoperative patients with gastric cancer.</p><p><b>METHODS</b>Ninety patients undergoing radical surgeries for gastric cancer were randomly, according to the sequence of their operations, divided into three groups: a control group treated conventionally after their surgeries (group CONT, 30 cases), a Chinese medicine group treated by Simo Decoction administered by way of a nutrient canal in addition to the conventional treatment (group CM, 30 cases), and an acupuncture plus Chinese medicine group treated by warming needling in addition to those given in the Chinese medicine group (group ACUP+CM, 30 cases). Therapeutic effects were estimated 10 days after their operations.</p><p><b>RESULTS</b>The time for restoration of gastrointestinal functions was obviously shortened, and the problems of poor appetite and difficulty in defecation were more markedly improved in group ACUP+CM than those in both group CONT and group CM (P < 0.01, P < 0.05). Ten days after operations, the number of patients with normal lymphocytes and normal percentage rate of lymphocytes to neutrophile granulocytes was obviously more in group ACUP+CM than those in both group CONT and group CM (P < 0.01, P < 0.05).</p><p><b>CONCLUSION</b>Acupuncture combined with Chinese medicine is favorable in accelerating early air exhaustion and defecation, improving clinical symptoms, as well as in bi-directional regulating peripheral white blood cells.</p>

Effect of tacrolimus on the growth cycle of murine hair follicles / 中国医学科学院学报

<p><b>OBJECTIVE</b>To explore the effect of tacrolimus on murine hair follicle cycle.</p><p><b>METHOD</b>Hematoxylin-eosin dyeing and reverse transcription-polymerase chain raction techniques were used.</p><p><b>RESULTS</b>Five days after depilation, the hair follicles in both the tacrolimus group and the minoxidil group was in anagen V, while that in the vaseline group was in anagen III. vascular endothelial growth factor (VEGF) and hepatocyte growth factor (HGF) were detected in back skin in both the tacrolimus group and the minoxidil group, but not in the vaseline group.</p><p><b>CONCLUSION</b>Tacrolimus can promote the growth of hair by stimulating the hair follicle to enter anagen V in mice, which may be explained by the effects of VEGF and HGF.</p>

Effect of hypoxia inducible factor-1alpha on cells of hair follicle / 中国医学科学院学报

<p><b>OBJECTIVE</b>To investigate the feasibility of stable transfection of human hypoxia inducible factor-1alpha (HIF-1alpha) gene into fibroblasts cells and the effects of supernatant from the transfected cell culture on hair follicle cells.</p><p><b>METHODS</b>PcDNA-HIF1alpha was stably transfected into fibroblasts cells with lipofectamine 2000. Expression of HIF-1alpha was observed by reverse transcription-polymerase chain reaction (RT-PCR) and Western blot. The supernatant was obtained to detect the expression of vascular endothelial growth factor (VEGF) by ELISA. The mRNA expression of basic fibroblast growth factor (bFGF) was detected by RT-PCR. MTT was used to detect the activity of fibroblasts cells and dermal sheath cells added with supernatant.</p><p><b>RESULTS</b>PcDNA-HIF1alpha was successfully transfected into fibroblasts cells. HIF-1alpha could be detected by RT-PCR and Western blot. The expression of VEGF in the supernatant of cells transfected with PcDNA-HIF1alpha was detected. The mRNA expression of bFGF was significantly higher than in the control group (P < 0.01). MTT showed the activity of cells added with supernatant was enhanced (P < 0.05).</p><p><b>CONCLUSION</b>PcDNA-HIF1alpha can stably transfected into fibroblasts cells, and the expressed HIF-1alpha induces the expression of VEGF and bFGF, and the expressed VEGF enhances the activity of cells.</p>