A retrospective case series of segmental zoster paresis of limbs: clinical, electrophysiological and imaging characteristics.

BACKGROUND: Segmental zoster paresis (SZP) of limbs, characterized by focal weakness of extremity, is recognized as a rare complication of herpes zoster (HZ). The following study analyzes the clinical characteristics and data from electromyography and MRI scans in patients with motor weakness after zoster infection. METHODS: One thousand three hundred ninety-three patients from our database (Shandong Provincial Qianfoshan Hospital) suffering from HZ were retrospectively reviewed from June 2015 to July 2017. Patients who fulfilled the diagnostic criteria for SZP were included in the analysis. The clinical characteristics, as well as electromyography findings and MRI scans were analyzed. RESULTS: SZP was present in 0.57% of patients with HZ (8/1393). The average age of symptom onset in 8 SZP patients was 69 years old (SD: 13, range 47-87). The severity of muscle weakness ranged from mild to severe. The electrophysiological testing revealed the characteristics of axonopathy. Radiculopathy (2/8), plexopathy (2/8), radiculoplexopathy (3/8) and combined radiculopathy and mononeuropathy (1/8) were also identified. MRI revealed hyperintensity of the affected spinal dorsal horns, nerve roots or peripheral nerves. CONCLUSIONS: SZP is associated with obvious limb weakness, nerve axons lesions and localization to nerve roots, plexus or peripheral nerves.

Effect of Bcl-xL gene expression silenced by RNA interference on invasion of human colorectal cancer cells.

PURPOSE: To investigate the effect and possible mechanisms of Bcl-xL gene on the invasive capacity of human colon cancer cells. METHODS: HT29 human colorectal carcinoma cell line was transfected by small interfering RNA (siRNA) of Bcl-xL gene. Quantitative real-time (RT)-PCR and Western blot were used to detect the transfection, and soft agar colony culture experiments and Boyden chamber model test were used for cancer cell proliferation and invasion, respectively. Western blot was used to detect the protein changes of urokinase-type plasminogen activator (uPA) in cancer cells. RESULTS: Compared with the control group, the number of soft agar colonies and the number of penetrating membrane cells significantly reduced in the siRNA transfection group, and had dose-dependent characteristics; the uPA protein decreased significantly in the siRNA transfected cells. CONCLUSION: Bcl-xL gene may play an important role in the invasion of colon cancer cells, and the mechanism may be related to regulation of uPA expression.

[Photoinduced electron transfer between [Ru(bpy)3]2+ and copper(II) ion in composite films mediated by DNA].

An orange-red [Ru(bpy)3]2+ -DNA-CU2 composite film (bpy = 2,2'-bipyridine) was fabricated on an indium-tin (ITO) surface based on electrostatic interactions among [Ru(bpy)3]2+, DNA and Cu2+ by using self-standing cast methods. The photoinduced electron transfer (PET) properties of the resultant composite film mediated by DNA were studied by means of steady-state and time-resolved fluorescence spectroscopy, UV-visible absorption spectroscopy, fluorescence microscopic imaging and scan electron microscopy. The [Ru(bpy)3]2+ -DNA-Cu2+ composite film with molar ratio of 10:20:1 shows an obvious absorption band (450 nm) and an intense emission peak (lamda(em) = 595 nm), whose emission exhibits a single-exponential decay with tau = 188.6 ns and is quenched by Cu2+ via DNA-mediated PET mechanism, indicating that the quenching constant is 6.94 x 10(3) L x mol(-1) and quenching rate constant is 3.80 x 10(10) L x mol(-1) x s(-1). The increasing molar ratio of Cu2+ in composite films (10-fold) leads to an 11 nm blue-shift of the emission peak, which is dramatically weakened by Cu2+ via a static quenching mechanism. In addition, compared with the emission quenching of DNA-[Ru(bpy)2 (tatp)]2+ (tatp = 1, 4, 8, 9-tetra-aza-triphenylene) tuned by Cu2+, which is present either in solutions or in composite films, Cu2+ only quenches the emission of [Ru(bpy)3]2+ bound to DNA via an electrostatic interaction mode in composite films.

[Effects of penetration enhancers on curcumin transdermal drug delivery].

OBJECTIVE: To study the effects of penetration enhancers and their combinations on the curcumine transdermal drug delivery (CUR-TDDS). METHODS: The penetration rate of curcumin through rat skin in vitro was measured using Valia-Chien diffusion cells, and orthogonal design method was set up for experimental design. RESULTS: The optimum penetration enhancers were: 3% hydroxypropyl beta cyclodextrins (HP-beta-CD), 9% borneol and 3% peppermint oil. CONCLUSION: The HP-beta-CD has the most potent enhancing effect.

Altering substrate properties of thin film nanocomposite membrane by Al2O3 nanoparticles for engineered osmosis process.

The scarcity of energy and water resources is a major challenge for humanity in the twenty-first century. Engineered osmosis (EO) technologies are extensively researched as a means of producing sustainable water and energy. This study focuses on the modification of substrate properties of thin film nanocomposite (TFN) membrane using aluminium oxide (Al2O3) nanoparticles and further evaluates the performance of resultant membranes for EO process. Different Al2O3 loading ranging from zero to 0.10 wt% was incorporated into the substrate and the results showed that the hydrophilicity of substrate was increased with contact angle reduced from 74.81° to 66.17° upon the Al2O3 incorporation. Furthermore, the addition of Al2O3 resulted in the formation of larger porous structure on the bottom part of substrate which reduced water transport resistance. Using the substrate modified by 0.02 wt% Al2O3, we could produce the TFN membrane that exhibited the highest water permeability (1.32 L/m2.h.bar, DI water as a feed solution at 15 bar), decent salt rejection (96.89%), low structural parameter (532.44 µm) and relatively good pressure withstandability (>25 bar).

[Study on the preparation of curcumin inclusion complex and its stability].

OBJECTIVE: To prepare the curcumin inclusion complex and study its stability. METHODS: Beta-cyclodextrin (beta-CD) was chosen as inclusion material and orthogonal design method was used. UV-Vis spectrophotometer was used to determine the solubility and content of different samples. They were placed under conditions of light and the solution containing Fe(3+) to determine their stability. RESULTS: The optimum preparation procedure were : curcumin and beta-cyclodextrin feed molar ratio of 1: 1, the concentration of ethanol was 40%, 40 degrees C inclusion temperature and 1 h reaction time. CONCLUSION: Inclusion complex prepared under eptimal condition is stable.

[Preparation of curcumin solid dispersion and inclusion complex].

OBJECTIVE: To prepare the curcumin solid dispersion and the curcumin inclusion complex, evaluate its stability and the transdermal properties. METHODS: The samples were prepared with hydrophilic, or water-soluble polymers, by solvent and solvent-melting methods. The optical microscope and the melting point were used to identify the state of the drug existence in it, and UV-Vis spectrophotometer was used to determine the solubility and content of different samples. They were placed under conditions of light, phosphate buffers with different pH values and different metal ions to determine their stability. The lipid/aqueous partition coefficients and the permeation of samples were measured. RESULTS: The content and solubility of curcumin in the solid dispersion prepared with PVP k-30 as the carrier were larger than those of other solid dispersions, with 81.26% and 337.59 microg/mL, respectively. The oil-water distribution coefficient was 26.04, indicating good penetration properties. CONCLUSION: The solubilty and stability of curcumin can be improved to various degrees. The solubility and oil-water partition coefficient of the curcumin solid dispersion prepared by povidone k-30 as a carrier is the largest.

Thiol-capped CdTe quantum dots with two-photon excitation for imaging high autofluorescence background living cells.

To effectively image living cells with quantum dots (QDs), particularly for those cells containing high content of native fluorophores, the two-photon excitation (TPE) with a femto-second 800 nm laser was employed and compared with the single-photon excitations (SPE) of 405 nm and 488 nm in BY-2 Tobacco (BY-2-T) and human hepatocellular carcinoma (QGY) cells, respectively. The 405 nm SPE produced the bright photoluminescence (PL) signals of cellular QDs but also induced a strong autofluorescence(AF) from the native fluorophores like flavins in cells. The AF occupied about 30% and 13% of the total signals detected in QD imaging channel in the BY-2-T and QGY cells, respectively. With the excitation of 488 nm SPE, the PL signals were lower than those excited with the 405 nm SPE, although the AF signals were also reduced. The 800 nm TPE generated the best PL images of intracellular QDs with the highest signal ratio of PL to AF, because the two-photon absorption cross section of QDs is much higher than that of the native fluorophores. By means of the TPE, the reliable cellular imaging with QDs, even for the cells having the high AF background, can be achieved.

Clinical application of laparoscopic total mesorectal excision using the intersphincteric approach through the sacrococcygeal incision for treating patients with rectal cancer.

INTRODUCTION: Colorectal cancer is the third most common cancer causing death in Western countries; laparoscopic surgery for colorectal cancer has many advantages and thus has been used widely. Laparoscopic total mesorectal excision through the sacrococcygeal incision under direct visualization to excise distal rectal cancer is an important procedure for super-low rectal carcinomas. AIM: To investigate the feasibility of mesorectal excision and super-low rectal carcinoma excision using the intersphincteric approach through the sacrococcygeal incision. MATERIAL AND METHODS: From December 2009 to June 2017, intersphincteric resection was performed through the sacrococcygeal incision; the mesentery was excised in 27 patients with rectal cancer and a contracted pelvis (the lower edge of the tumor was 4 to 7 cm to the anal verge) through laparoscopy in the Gastrointestinal Surgery Department of our hospital. RESULTS: No death was recorded during surgery. The surgical time ranged from 190 to 310 min, the bleeding volume was 50 to 150 ml, and the post-surgical length of stay was 6 to 19 days. There were three cases of anastomotic fistulas, one case of anastomotic stenosis, and one case of fecal incontinence. Follow-up visits were scheduled for 19 patients, with a mean time of 37 months, ranging from 3 to 92 months; one case of local recurrence, one case of peritoneal metastasis, and two cases of hepatic metastasis were observed. CONCLUSIONS: Laparoscopic total mesorectal excision using the intersphincteric approach through the sacrococcygeal incision is feasible for treating patients with a contracted pelvis and super-low rectal carcinoma.

Application of Natural Ingredients of Traditional Chinese Medicine in Pain Management： A Review / 中国实验方剂学杂志

Pain is one of the most prevalent health problems. Current medications for pain are mainly anticonvulsants， tricyclic antidepressants， and opioidergic drugs. However， their therapeutic effectiveness is limited during application， and some even have severe side effects. In recent years， research on natural ingredients from Chinese herbal medicine has been extensively conducted for their analgesic activities. A series of natural ingredients represented by alkaloids， coumarins， flavonoids， and terpenoids have shown great analgesic activity， and further studies on their analgesic mechanism have found that most natural products have multi-target analgesic mechanisms. It can exert analgesic effects by blocking ion channels， regulating related receptors， or inducing anti-inflammatory or antioxidant effects. In addition， many traditional Chinese medicine （TCM） formulas have shown great analgesic ability after clinical application and have multiple complex analgesic mechanisms. The drug cloud （dCloud） theory can better describe the mechanisms， and it can represent the complete therapeutic spectrum of multi-target analgesics from two dimensions， namely the "direct efficacy" that directly inhibits pain signals and the "background efficacy" that targets the root causes of pain. The authors summarized the research progress of natural ingredients with analgesic effects found in Chinese herbal medicine so far， as well as the analgesic efficacy and potential mechanisms of TCM formulas with great analgesic effects in clinical applications， so as to provide a new basis for searching for new analgesic drugs from TCM.

Astragali Radix-Salviae Miltiorrhizae Radix et Rhizoma Mitigate Renal Fibrosis： A Review / 中国实验方剂学杂志

Renal fibrosis， the final pathological outcome of end-stage chronic kidney diseases， is associated with inflammation， oxidative stress， epithelial-mesenchymal transdifferentiation （EMT）， and extracellular matrix deposition. It belongs to the categories of edema， ischuria， anuria and vomiting， and consumptive disease in traditional Chinese medicine （TCM）， with the key pathogenesis of Qi deficiency and blood stasis and the primary treatment principle of replenishing Qi and activating blood. Astragali Radix-Salviae Miltiorrhizae Radix et Rhizoma mainly contains astragalosides， polysaccharides， calycosin， salvianolic acid， and tanshinone， with the effect of tonifying Qi and activating blood. Studies have shown that this herb pair and its active components can delay the progress of renal fibrosis by regulating multiple signaling pathways. With consideration to the pathogenesis of Qi deficiency and blood stasis， this article reviews the research progress in the mitigation of renal fibrosis by Astragali Radix-Salviae Miltiorrhizae Radix et Rhizoma from the aspects of protecting glomerular filtration barrier， inhibiting EMT and mesangial cell proliferation， improving renal hemodynamics， and protecting renal function. Furthermore， the mechanisms were summarized. Specifically， Astragali Radix-Salviae Miltiorrhizae Radix et Rhizoma and its effective components can improve mitochondrial function and fatty acid metabolism， alleviate endoplasmic reticulum stress and autophagy disorders， and inhibit immune inflammation and oxidative stress by regulating nuclear factor E2-related factor 2 （Nrf2）/PTEN-induced kinase 1 （Pink1）， Nrf2/antioxidant response element （ARE）， tumor necrosis factor-α （TNF-α）/nuclear transcription factor-κB （NF-κB）， miR-21/Smad7/transforming growth factor beta （TGF-β）， Wnt/β-catenin， long non-coding RNA-taurine up-regulated gene 1 （lncRNA-TUG1）/tumor necrosis factor receptor-associated factor 5 （TRAF5）， Ras-related C3 botulinum toxin substrate 1 （Rac1）/cell division cycle protein 42 （CDC42）， Ras homolog （Rho）/Rho-associated coiled-coil containing protein kinase （ROCK）， phosphatidylinositol-3-kinase （PI3K）/protein kinase B （Akt）， Janus kinase （JAK）/signal transducer and activator of transcription （STAT）， peroxisome proliferator-activated receptor α （PPARα）/peroxisome proliferator-activated receptor γ coactivator l alpha （PGC-1α）， and p38 mitogen-activated protein kinase （p38 MAPK）. This review aims to provide references for the relevant research， give play to the role of Astragali Radix-Salviae Miltiorrhizae Radix et Rhizoma， and provide guidance for the clinical treatment of renal fibrosis.

Relationship between intramuscular fat content in the quadriceps muscle and clinical severity in patients with knee osteoarthritis / 中国骨伤

OBJECTIVE@#To explore relationship between intramuscular fat content of quadriceps femoris and clinical severity of knee osteoarthritis (KOA).@*METHODS@#Totally 30 KOA patients were selected from February 2021 to June 2021, including 6 males and 24 females, aged with an average of (64.20±9.19) years old, and body mass index (BMI) was (24.92±3.35) kg·m-2. Patients were divided into relative severe leg (RSL) and relative moderate leg (RML) according to severity of pain on visual analogue scale(VAS). Musculoskeletal ultrasound was used to collect muscle images of quadriceps muscles on both sides of the patient, and Image J was used to analyze echo intensity (EI) of each muscle. Both VAS and Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) were used to assess pain and function. Quadriceps muscle EI on both sides of patients was compared. Pearson correlation analysis was conducted to analyze correlation between quadriceps muscle EI value between RSL and RML, and linear regression was used to analyze relationship between each muscle EI and VAS and WOMA scores of patients.@*RESULTS@#The EI of RSL lateral vastus lateralis (VL) was 123.78±36.25 and RSL vastus medialis (VM) was 109.46±30.36 which were significantly higher than those of 108.03±31.34 and 93.32±26.04 of RML (P<0.05), but there was no statistical significance in EI values of rectus femoris (RF) on both sides (P>0.05). EI values of VL and VM on both sides were significantly correlated (P<0.05). There was a significant positive correlation between VM EI value and VAS score in RSL and RML (P<0.05). VM EI values in RSL were positively correlated with total WOMAC (P<0.05), and VM VL EI values in RML were positively correlated with total WOMAC score (P<0.05).@*CONCLUSION@#Intramuscular fat content of quadriceps is closely related to severity of clinical symptoms in KOA patients, and the most obvious one is VM. Therefore, the intramuscular fat content of quadriceps may be an objective indicator to evaluate severity of KOA patients. At the same time, reducing intramuscular fat content of the quadriceps muscle of KOA patients may be a new direction for the prevention and treatment of KOA.

Experimental Study on the Mechanism of Mangiferin Inhibiting Malignant Biological Characteristics of Multiple Myeloma and Exerting Anticancer Effect / 中国实验血液学杂志

OBJECTIVE@#To investigate the effect of pure Chinese herbal extract Mangiferin on the malignant biological behaviors of multiple myeloma (MM) cells, and to analyze the molecular mechanism of the anti-myeloma effect of Mangiferin, so as to provide experimental basis for MM replacement therapy.@*METHODS@#U266 and RPMI8226 of human MM cell lines were intervened with different concentrations of Mangiferin. Cell proliferation was detected by CCK-8 method. Annexin V/PI double staining flow cytometry was used to detect cell apoptosis. Western blot was used to detect the expression of apoptosis and related signaling pathway proteins, and real-time quantitative polymerase chain reaction (qRT-PCR) was used to detect the expression of matrix metalloproteinase (MMP) and CXC chemokine receptor (CXCR) family.@*RESULTS@#Mangiferin could inhibit the proliferation activity of U266 and RPMI8226 cells and induce cells apoptosis. After Mangiferin intervened in U266, RPMI8226 cells for 48 h, the expression of Bcl-2 family pro-apoptotic protein Bax was up-regulated, while the expression of survivin and Bcl-xL proteins was down-regulated and caspase-3 was hydrolyzed and activated to promote cell apoptosis, besides, the expression of Bcl-2 protein in U266 cells was also significantly down-regulated to induce apoptosis (P<0.05). After Mangiferin intervenes in MM cells, it can not only increase the expression level of tumor suppressor p53, but also induce programmed cell death of MM cells by inhibiting the expression of anti-apoptotic molecules and down-regulating the phosphorylation levels of AKT and NF-κB. In addition, after the intervention of Mangiferin, the expressions of CXCR4, MMP2 and MMP9 in U266 cells were down-regulated (P<0.05), while there is no effect on the expressions of CXCR2, CXCR7 and MMP13 (P>0.05). However, the expressions of CXCR4, MMP9, and MMP13 in RPMI8226 cells were down-regulated (P<0.01), the expression of MMP2 was weakly affected, and the expression of CXCR2 and CXCR7 was basically not affected (P>0.05).@*CONCLUSION@#Mangiferin can inhibit the proliferation and induce apoptosis of MM cells, and its mechanism may be related to inhibiting the activation of NF-κB signaling pathway, affecting the expression of Bcl-2 family proteins, and inhibiting the expression of core members of MMP and CXCR family.

Clinical Features and Outcomes of the Patients with B-Cell Chronic Lymphoproliferative Disease in the New Drug Era / 中国实验血液学杂志

OBJECTIVE@#To analyze the clinical characteristics of the patients with B-cell chronic lymphoproliferative disease（B-CLPD） in the new drug era and the effect of new drug treatment on efficacy and survival.@*METHODS@#The clinical and laboratory data of 200 cases B-CLPD patients diagnosed between April 2015 and August 2021 were analyzed retrospectively. The clinical efficacy and survival of the patients under different treatments including Bruton tyrosine kinase（BTK） inhibitors， rituximab， and chemotherapy alone were analyzed. The prognostic factors affecting the survival of patients were analyzed by univarite analysis and multivariate analysis.@*RESULTS@#There were 119 male（59.5％） and 81 female（40.5%） in 200 cases B-CLPD patients， the sex ratio(male/female) was 1.5∶1 with median age of 61（30- 91） years old. The distribution of subtypes were as fallows: 51 cases (25.5%) of chronic lymphocytic leukemia/small lymphocytic lymphoma（CLL/SLL）， 64（32.0%） cases of follicular lymphoma（FL）， 40（20.0%） cases mantle cell lymphoma（MCL）， 30（15.0%） cases of marginal zone lymphoma（MZL）， 10（5%） cases of lymphoplasmacytic lymphoma/waldenstrom macroglobulinemia（LPL/WM）， 5（2.5%） cases of B cell chronic lymphoproliferative disorders unclassified（B-CLPD-U） . The main clinical manifestation of 102 patients was lymph node enlargement, 32 cases were complicated with B symptoms. Among CLL/SLL patients， there were 12（23.5%） cases in Binet A and 39（76.5%） cases in Binet B/C. There were 29 patients（20.9%） in Ann Arbor or Lugano stage I-II and 110 cases（79.1%） in stage III-IV of other subtypes. The complete remission（CR） rate was 43.1%（25/58）， 40.2%（39/97）， 7.1%（1/14）， and overaIl response rate（ORR） was 87.9%（51/58）， 62.9%（61/97）， 28.6%（4/14） in the groups of BTK inhibitors， rituximab-based therapy， and chemotherapy alone. The 3-year OS rate and PFS rate in all patients was 79.2% and 72.4% respectively. The 3-year OS rate of patient with MZL, CLL/SLL, FL,WM was 94.7%, 87.7%, 86.8% and 83.3% respectively, while the 3-year OS rate of MCL was only 40.6%, which was significantly lower than other subtypes. The median OS of patients treated with BTK inhibitors and rituximab-based therapy was 20.5 and 18.5 months respectively， and the 3-year OS rate was 97.4% and 90.7%. However， the median PFS of patients receiving chemotherapy alone was 4 months， and the 1-year OS rate was 52.7%， which was statistically significant compared with the other two groups（P<0.05）. Univarite analysis showed that anemia， elevated lactate dehydrogenase， elevated β2-microglobulin， and splenomegaly were the poor prognostic factors for OS（P<0.05）， elevated lactate dehydrogenase was also poor prognostic factors for PFS（P<0.05）. Multifactor analysis showed that anemia and elevated lactate dehydrogenase were the independent poor prognostic factors for survival（P<0.05）.@*CONCLUSION@#The clinical features of B-CLPD was various， anemia and elevated lactate dehydrogenase are the prognostic factors for poor survival. BTK inhibitors and new immunotherapy can improve the survival and prognosis of patients in the new drug era.

Analysis of Mechanism of Yishen Huashi Granules for Improving Diabetic Nephropathy Based on Metabonomics and Transcriptomics / 中国实验方剂学杂志

ObjectiveIn this study， based on ultra-high performance liquid chromatography-mass spectrometry（UHPLC-MS/MS） and high-throughput transcriptome sequencing technology（RNA-seq）， we investigated the mechanism of Yishen Huashi granules in regulating serum metabolites and renal messenger ribonucleic acid（mRNA） expression to improve diabetic kidney disease（DKD）. MethodSD rats were randomly divided into normal group ， model group and Yishen Huashi granules group， with 8 rats in each group. The rat model of DKD was established by intraperitoneal injection of streptozotocin. Yishen Huashi granules group was given 5.54 g·kg-1·d-1 of Yishen Huashi granules by gavage， and the normal group and the model group were given the same amount of normal saline for 6 weeks. During the experiment， the body weight and blood glucose of rats were monitored， and the rats were anesthetized 24 hours after the last administration， blood was collected from the inferior vena cava， serum was separated， and renal function， blood lipid， and inflammatory indicators were detected. Kidney tissue of rats was fixed in neutral paraformaldehyde， and stained with hematoxylin-eosin（HE）， Masson and periodic acid-Schiff（PAS） to observe the renal pathological changes. UHPLC-MS/MS and RNA-seq were used to identify the changes of serum metabolism and the differences of renal mRNA expression， and real time fluorescence quantitative polymerase chain reaction（Real-time PCR） and Western blot were used to detect the differential mRNA and protein expression in renal tissue to explore the common expression mechanism. ResultCompared with the normal group， rats in the model group showed a decrease in body weight， a significant increase in blood glucose， urinary microalbumin to urinary creatinine ratio（UACR）， blood urea nitrogen（BUN）， cystatin-C（Cys-C）， β2-microglobulin（β2-MG）， interleukin-6（IL-6）， triglyceride（TG） and total cholesterol（TC）， and a significant decrease in total superoxide dismutase（T-SOD）（P<0.01）. After the intervention of Yishen Huashi granules， all the indexes were improved to different degrees in rats（P<0.05， P<0.01）. Compared with the normal group， the model group showed renal mesangial stromal hyperplasia， fibrous tissue hyperplasia and tubular vacuolar degeneration. Compared with the model group， the renal pathology of rats in Yishen Huashi granules group was improved to a certain extent. A total of 14 target metabolites and 96 target mRNAs were identified， the target metabolites were mainly enriched in 20 metabolic pathways， including sphingolipid metabolism， glycerophospholipid metabolism， and the biosynthesis of phenylalanine， tyrosine and tryptophan. The target mRNAs were enriched to obtain a total of 21 differential mRNAs involved in the TOP20 pathways closely related to glycolipid metabolism. A total of 6 pathways， glycerophospholipid metabolism， arachidonic acid metabolism， purine metabolism， primary bile acid biosynthesis， ascorbic acid and uronic acid metabolism， and galactose metabolism， were enriched by serum differential metabolites and renal differential mRNAs， among them， there were 7 differential metabolites such as phosphatidylethanolamine（PE） and 7 differential mRNAs such as recombinant adenylate cyclase 3（ADCY3）. Seven differential metabolites had high predictive accuracy as verified by receiver operating characteristic（ROC） curve， and the results of Real-time PCR and Western blot were highly consistent with the sequencing results. ConclusionYishen Huashi granules can reduce UACR， BUN and other biochemical indexes， correct the disorder of glucose and lipid metabolism， and improve renal function of DKD rats. And its mechanism may be related to the regulation of the level of PE and other blood metabolites， and expression of Phospho1 and other mRNAs in the kidney， of which six pathways， including glycerophospholipid metabolism， may play an important role.

The Effects and Regulatory Mechanism of Targeting CXC Chemokine Receptor 1/2 Combined with Ara-C on the Malignant Biological Behaviors of U937 Cells of Acute Myeloid Leukemia / 中国实验血液学杂志

OBJECTIVE@#To investigate and analyze the effect of CXC chemokine receptor 1/2 (CXCR1/2) targeting inhibitor Reparixin combined with cytarabine (Ara-C) on the malignant biological behaviors of acute myeloid leukemia cells and its effect on the expression of the CXCR family, while exploring the accompanying molecular mechanism, providing scientific basis and reference for new molecular markers and targeted therapy for AML.@*METHODS@#Acute myeloid leukemia U937 cells were treated with different concentrations of Reparixin, Ara-C alone or in combination, and the cell morphology was observed under an inverted microscope; Wright-Giemsa staining was used to detect cell morphological changes; CCK-8 method was used to detect cell proliferation; the ability of cell invasion was detected by Transwell chamber method; the ability of colony formation was detected by colony formation assay; cell apoptosis was detected by Hoechst 33258 fluorescent staining and Annexin V/PI double-staining flow cytometry; monodansylcadaverine(MDC) staining was used to detect cell autophagy; the expression of apoptosis, autophagy and related signaling pathway proteins was detected by Western blot and the expression changes of CXCR family were detected by real-time quantitative polymerase chain reaction (qRT-PCR).@*RESULTS@#Reparixin could inhibit the proliferation, invasion, migration and clone formation ability of U937 cells. Compared with the single drug group, when U937 cells were intervened by Reparixin combined with Ara-C, the malignant biological behaviors such as proliferation, invasion and colony formation were significantly decreased, and the levels of apoptosis and autophagy were significantly increased (P<0.01). After Reparixin combined with Ara-C intervenes in U937 cells, it can up-regulate the expression of the pro-apoptotic protein Bax and significantly down-regulate the expression of the anti-apoptotic protein Bcl-2, and also hydrolyze and activate Caspase-3, thereby inducing cell apoptosis. Reparixin combined with Ara-C could up-regulate the expressions of LC3Ⅱ and Beclin-1 proteins in U937 cells, and the ratio of LC3Ⅱ/LC3Ⅰ in cells was significantly up-regulated compared with single drug or control group (P<0.01). MDC result showed that the green granules of vesicles increased significantly, and a large number of broken cells were seen (P<0.01). Reparixin combined with Ara-C can significantly inhibit the phosphorylation level of PI3K, AKT and NF-κB signaling molecule, inhibit the malignant biological behavior of cells by inhibiting the activation of PI3K/AKT/NF-κB pathway, and induce programmed cell death. Ara-C intervention in U937 cells had no effect on the expression of CXCR family (P>0.05). The expression of CXCR1, CXCR2, and CXCR4 mRNA could be down-regulated by Reparixin single-agent intervention in U937 cells (P<0.05), and the expression of CXCR2 was more significantly down-regulated than the control group and other CXCRs (P<0.01). When Reparixin and Ara-C intervened in combination, the down-regulated levels of CXCR1 and CXCR2 were more significant than those in the single-drug group (P<0.01), while the relative expressions of CXCR4 and CXCR7 mRNA had no significant difference compared with the single-drug group (P>0.05).@*CONCLUSION@#Reparixin combined with Ara-C can synergistically inhibit the malignant biological behaviors of U937 cells such as proliferation, invasion, migration and clone formation, and induce autophagy and apoptosis. The mechanism may be related to affecting the proteins expression of Bcl-2 family and down-regulating the proteins expression of CXCR family, while inhibiting the PI3K/AKT/NF-κB signaling pathway.

Preparation of Zoledronate liposome and its impact on apoptosis of Kupffer cells in rat liver.

PURPOSE: To establish a method for the preparation of zoledronate liposome and to observe its effect on inducing the apoptosis of rat liver Kupffer cells. METHODS: Zoledronate was encapsulated in liposomes, and then the entrapment rate was detected on a spectrophotometer. The prepared Zoledronate liposome (0.01 mg/mL) was injected into the tail vein of SD rats. Three days later, the number of Kupffer cells (CD68 positive) in rat liver tissue was detected by immunohistochemistry. Flow cytometry was used to detect the apoptosis rate of the isolated liver Kupffer cell cultured in vitro. RESULTS: The entrapment rate of Zoledronate was 43.4±7.8%. Immunohistochemistry revealed that the number of Kupffer cells was 19.3±2.1 in PBS group and 5.5±1.7 in Zoledronate liposome group, with a significant difference (P<0.05). The apoptosis rate of Kupffer cells was 4.1±0.8% in PBS group, while it was 9±2.2% and 23.3±5.9% in Zoledronate liposomes groups with different concentrations of Zoledronate liposome (P<0.05). CONCLUSIONS: Zoledronate liposomes can effectively induce the apoptosis of Kupffer cells in vivo and in vitro, and the apoptosis rate is related to the concentration of Zoledronate liposome. To establish a rat liver Kupffer cell apoptosis model can provide a new means for further study on Kupffer cell function.

Protective Effects of Apoptosis of Kupffer Cells Induced by Zoledronate Liposomes Following Hepatic Ischemia-Reperfusion Injury.

BACKGROUND The goal of this study was to observe the effect of the apoptosis of Kupffer cells (KCs) selectively induced by zoledronate liposomes following the hepatic ischemia-reperfusion injury (IRI) in the rat liver transplantation model and to explore its mechanisms. MATERIAL AND METHODS The rat liver transplantation model was established using the improved Kamada method. Male Sprague Dawley rats were randomly divided into 3 groups: no liver transplantation or drug treatment (Group A); donor rats were injected with 1 mL normal saline through the tail vein for 3 continuous days before transplantation, and the donor liver was preserved in cold for 2 hours (Group B); donor rats were injected with 1 mL zoledronate liposomes (0.001 mg/mL) through the tail vein for 3 continuous days before transplantation, and the donor liver was preserved in cold for 2 hours (Group C). At 24 hours after transplantation, the receiving rats were sacrificed for sampling. RESULTS Compared with Group C and Group A, the bile secretion flow was dramatically decreased in Group B, whereas the serum liver function index [alanine aminotransferase (ALT), glutamate aminotransferase (AST), and γ-glutamyl transpeptidase (γ-GT)] was significantly increased (P<0.01), and the pathological injury area was obviously increased. Compared with Group B, the levels of serum interleukin1 (IL-1), tumor necrosis factor-α (TNF-α), and the apoptotic index in Group C were significantly decreased (P<0.05), and Suzuki scores of congestion, vacuolar degeneration, and necrosis were all reduced (P<0.05). CONCLUSIONS The apoptosis of KCs selectively induced by zoledronate liposomes inhibited the inflammatory cascade reaction induced by KC activation and reduced the release of cytokines and decreased the extent of IRI in the liver transplantation in animal model.

Advances in clinical and safety studies of phosphodiesterase 4 inhibitors / 药学学报

Phosphodiesterase 4 (PDE4) is an important member of the phosphodiesterase enzyme family that specifically catalyzes the hydrolysis of cyclic adenosine monophosphate (cAMP), activates the downstream phosphorylation cascade pathway by altering cAMP concentration, and is strongly associated with multiple diseases. Inhibition of PDE4 is clinically investigated as a therapeutic strategy in a broad range of disease areas, including respiratory system diseases, autoimmune disorders, central nervous system diseases, and dermatological conditions. However, the incidence of adverse reactions such as nausea and vomiting is relatively high in the marketed PDE4 inhibitors, which has stalled their clinical development. In this review, we provide an overview of the clinical progression and safety issues of the marketed PDE4 inhibitors. We also review the main causes underlying PDE4-mediated adverse effects by combining the structural analysis of the PDE4 protein, the mechanism of action of PDE4 inhibitors, and the related side effect mechanism research, aiming to provide a reference for the development of safe and effective PDE4 inhibitors.

Efficacy of omeprazole and sodium bicarbonate suspension in the treatment of peptic ulcer: a multicenter clinical trial / 中华消化杂志

Objective:To evaluate the efficacy and safety of omeprazole and sodium bicarbonate suspension in the treatment of peptic ulcer.Methods:This present study was a multicenter, randomized, double-blind, double-dummy, positive drug parallel controlled phase Ⅱ clinical trial. According to different indications, the trial was divided into gastric ulcer (GU) and duodenal ulcer (DU) studies. Patients were stratified-block randomly divided with a 1∶1 ratio into experimental group and control group. The patients in the experimental group were administrated with omeprazole and sodium bicarbonate suspension omeprazole (20 mg for DU or 40 mg for GU, and 1 680 mg sodium bicarbonate) once a day. The patients in the control group received omeprazole magnesium enteric-coated tablet20 mg for DU or 40 mg for GU once a day. The treatment period was 4 weeks for DU and 8 weeks for GU. The main efficacy indicator was ulcer healing rate under endoscopy. The time of pain disappearance and the total effective rate of clinical symptom relief were used as the secondary efficacy indicators, and the incidence of adverse reactions was used as the safety indicator. The data set included full analysis set (FAS), per-protocol set (PPS) and safety set (SS). Independent sample t test, Wilcoxon rank sum test, chi square test, Fisher exact test method and non-inferiority test were used for statistical analysis. Results:Two hundred and seventy two DU patients and 237 GU patients were included in the FAS, 247 DU patients and 201 GU patients were included in the PPS, and 272 DU patients and 235 GU patients were included in the SS. The results of FAS analysis showed that after 4 weeks treatment, the healing rate of DU under endoscopy in the experimental group was 91.91% (125/136) and that in the control group was 94.85% (129/136), and the difference was not statistically significant ( P>0.05). After 8 weeks treatment the healing rate of GU under endoscopy in the experimental group was 86.44% (102/118) and that in the control group was 87.39% (104/119), and the difference was not statistically significant ( P>0.05). The results of non-inferiority analysis showed the lower limit of 95% confidence interval of difference in effective rate between the two groups was over -10% (-8.84% for DU and -9.54% for GU), which indicated that the effective rate of experimental group was not inferior to that of the control group. The results of PPS analysis were consistent with the results of FAS. The results of FAS analysis showed the median time of abdominal pain disappearance of DU patients in the experimental group and the control group was both 6 d, and the difference was not statistically significant ( P>0.05). The median time of abdominal pain disappearance of GU patients in the experimental group and the control group was both 8 d, and the difference was not statistically significant ( P>0.05). After 4 weeks of treatment, the total effective rates of clinical symptom relief of DU of the trial group and the control group were 95.59% (130/136) and 97.79% (133/136), respectively, and the difference was not statistically significant ( P>0.05). After 8 weeks of treatment, the total effective rates of clinical symptom relief of GU of the experimental group and the control group were 95.76% (113/118) and 93.28% (111/119), respectively, and the difference was not statistically significant ( P>0.05). The results of SS analysis showed that the incidence of adverse reactions of DU patients in the trial group and the control group was 5.15% (7/136) and 2.21% (3/136), respectively, and the difference was not statistically significant ( P>0.05). The incidence of adverse reactions of GU patients in the experimental group and the control group was 12.71% (15/118) and 6.84% (8/117), respectively, and the difference was not statistically significant ( P>0.05). Conclusions:Omeprazole and sodium bicarbonate suspension is not inferior to omeprazole magnesium enteric-coated tablet in healing efficacy under endoscopy in peptic ulcer, and has a good safety.