Lingnan Fire-needle on Inhibiting Melanocyte Apoptosis in Vitiligo Model Mice by Regulating Hippo-YAP Signaling Pathway / 中山大学学报(医学科学版)

ObjectiveTo observe the effects of fire-needle of Lingnan on the vitiligo model after hydroquinone-induced oxidative stress based on the Hippo-YAP signaling pathway. MethodsC57BL/6 mice were randomly divided into normal group （Control）， model group （HQ）， HQ+fire-needle group （FA）， and positive control group （Halometasone）， with 8 mice in each group. The vitiligo model was prepared by hydroquinone （HQ）. The skin pathological changes were observed by depigmentation score， HE staining and Masson-Fontana. Elisa was used to detect the levels of tyrosinase （TYR）， malondialdehyde （MDA） and monoamine oxidase （MAO）.Western-blot and PCR were used to detect the expression of Yap1 and Tp73 among the groups. ResultsCompared with the control group， the epidermis and dermis were significantly thicker. The number of melanocyte hair follicles， basal melanocytes， epidermal cells containing melanin granules were significantly decreased， and the depigmentation score was significantly reduced（P＜0.01）. The level of TYR decreased， and the levels of MDA and MAO increased after modeling（P＜0.01）. The expression of Yap1 and Tp73 were significantly reduced （P<0.01）. The dermis became thinner in the halometasone and FA group after treatment of 4 weeks. The number of melanocyte hair follicles， basal melanocytes， epidermal cells containing melanin granules increased （P<0.05）. Compared with that of the HQ group， the level of TYR in the halometasone group and FA group was significantly increased （P<0.01）. The levels of MDA and MAO in the FA group were decreased （P<0.05）. The expressions of Yap1 and Tp73 in the FA group were significantly increased （P<0.01）， and their effects were better than those in the Halometasone group （P<0.05）. ConclusionsFire-needle of Lingnan protects melanocytes from oxidative stress by activating the Hippo-YAP pathway. It enhances the synthesis and function of melanocytes and promotes repigmentation by reducing the content and activity of oxidative stress products.

Professor LIN Guo-hua's clinical experience in staging treatment for post-stroke dysphagia / 中国针灸

The paper summarizes professor LIN Guo-hua's clinical experience in staging treatment for post-stroke dysphagia. Professor LIN Guo-hua adheres to "essence and marrow deficiency and primary yang decline" as the pathogenesis and "conducting yin from yang " as the treating principle. By regulating the conception vessel and the governor vessel and focusing on yang meridians, in association with meridian differentiation and the location differentiation, professor LIN provides the staging treatment for post-stroke dysphagia. At the oral phase, yangming is dysfunction, manifested as facial paralysis and flaccid tongue. In treatment, reducing method is predominated at yangming meridian specially. At the pharyngeal phase, shaoyang is invaded by pathogens, manifested as pivoting dysfunction. The treatment focuses on communicating the exterior with the interior and promoting shaoyang meridian. At the esophageal phase, yangming meridian is deficiency and the turbid qi fails to descend, thus the reinforcing method is dominated to promote and tonify yangming. Additionally, the kinesiotherapy of acupuncture is assisted and the Lingnan fire needling therapy is used particularly. All of the summaries above provide the reference for the clinical treatment of post-stroke dysphagia.

Erianin Inhibits Proliferation of Bladder Cancer 5637 Cells Through Akt / 中国实验方剂学杂志

ObjectiveTo investigate the role of protein kinase B （Akt） overexpression in the inhibition of human bladder cancer 5637 cell proliferation by erianin and related mechanisms. MethodThe 5637 cells stably over-expressing Akt were induced using the lentivirus vector. The 5637 cells infected with the empty vector were classified into blank group. Then the Akt group， empty vector combined with erianin （62.5 μg·L-1） group， and Akt combined with erianin （62.5 μg·L-1） group were set up. The cell viability was detected by cell counting kit-8 （CCK-8） assay， and the clone formation of 5637 cells in each group was determined in the clone formation experiment. The cell cycle distribution was detected by flow cytometry. Western blot was used to assay the protein expression levels of phosphorylated （p）-Akt， Akt， p21. The glycolysis of 5637 cells was determined in glucose uptake and lactate secretion assays. ResultCompared with the blank group， erianin inhibited the proliferation of bladder cancer 5637 cells （P<0.05）. Overexpression of Akt partially reversed the inhibitory effect of erianin on the proliferation of bladder cancer 5637 cells （P<0.05）. Clone formation assay showed that erianin inhibited the clone formation of bladder cancer 5637 cells （P<0.05）， which was partially reversed by the overexpressed Akt （P<0.05）. As revealed by comparison with the blank group， erianin arrested the bladder cancer 5637 cells in G1 phase （P<0.05）， which was also reversed by the overexpressed Akt （P<0.05）. Western bolt showed that erianin promoted the expression of p21 but suppressed the expression of p-Akt and Akt （P<0.05）. By contrast， the overexpression of Akt down-regulated the elevated p21 protein expression induced by erianin （P<0.05）. Compared with the blank group， erianin inhibited the glucose uptake and lactate secretion of bladder cancer 5637 cells （P<0.05）. Overexpression of Akt weakened the inhibitory effect of erianin against the glycolysis of 5637 cells （P<0.05）. ConclusionErianin is able to inhibit the proliferation of bladder cancer 5637 cells， promote the expression of p21， and inhibit the expression of p-Akt. Overexpressed Akt reduces the inhibitory effect of erianin on the proliferation of bladder cancer 5637 cells， suggesting that Akt plays an important role in the inhibition of 5637 cell proliferation by erianin， which has provided a new target for the application of erianin in the treatment of bladder cancer.

Diffusion tensor imaging in assessment of structural brain networks in patients with anti-N-methyl-D-aspartate receptor encephalitis / 中华放射学杂志

Objective:To explore the alteration of structural network, cognitive scores in patients with anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis, as well as the relationship between cognitive impairment and changes of structural networks in patients with NMDAR encephalitis.Methods:This study was a retrospective study. A total of 39 patients with anti-NMDAR encephalitis were recruited as the autoimmune encephalitis group (AE group) from the First Affiliated Hospital of Chongqing Medical University between September 2012 to December 2019, and 32 healthy volunteers with normal results of routine head MR examinations and no history of central nervous system diseases were recruited as the health control group (HC group). There were 16 males and 23 females, aged from 13 to 66 (34±15) years, with duration of disease from 11 to 110 (31±20) days in AE group, and there were 16 males and 23 females, aged from 13 to 66 (34±15) years in HC group. All subjects underwent diffusion tensor imaging (DTI) scan and cognitive function evaluation. The brain structural networks of two groups were constructed by deterministic fiber tracking techniques, and the differences of global topological properties [clustering coefficient (C p), shortest path length (L p), local efficiency (E loc), global efficiency (E glob), normalized C p (γ), normalized L p (λ), small-worldness (σ)] and local topological properties between two groups were analyzed by the graph theory approch. The correlations between characteristics of brain structural networks and cognitive function scores were further analyzed. Results:There was no significant difference in age and gender distribution between the AE group and HC group ( P>0.05). The C p [0.005(0.004, 0.007)], γ (1.76±0.13), λ (0.51±0.03) and σ value (1.57±0.13) of AE group were decreased when compared with HC group [the values were 0.007(0.004,0.017), 2.13±0.63, 0.55±0.06 and 1.73±0.36 each] ( Z=-939.00, t=-3.58, t=-4.16, t=-2.58, P<0.05). Compared with HC group, nodal efficiencies in the left middle frontal gyrus (orbital part), left and right supplementary motor areas, left olfactory cortex, left gyrus rectus, bilateral insula, left postcentral gyrus, left paracentral lobule and right heschl gyrus were changed ( P<0.05). There were five identical hub regions which contains the left middle occipital gyrus, bilateral supplementary motor areas and precuneus in both groups. However, in the AE group, three hub regions of the left middle occipital gyrus and bilateral middle temporal gyrus were reduced, and the left precentral gyrus was increased as hub region. The nodal efficiencies of the left supplementary motor areas ( r=0.393, P=0.013), right supplementary motor areas ( r=0.384, P=0.016) and left paracentral lobule ( r=0.356, P=0.026) were positively correlated with the montreal cognitive assessment scores. Conclusion:The white matter is extensively impaired in anti-NMDAR encephalitis patients and the changes of topological properties in several brain regions are correlated with cognitive decline.

Quantitative analysis of demyelination and remyelination in modified cuprizone mice model based on T 2WI combined with DTI using 7.0 T MR / 中华放射学杂志

Objective:To explore the method of establishing a modified demyelination and myelination regeneration model induced by dicyclohexanone oxalyl dihydrazone (CPZ) in mice with multiple sclerosis (MS), and to analyze the image markers of demyelination and myelination regeneration in mouse MS model.Methods:After the intragastrically administered with sodium carboxymethyl cellulose (CMCNa) for one week, a total of 30 C57BL/6 male mice were randomly divided into the control group ( n=10), the demyelination group ( n=10), and the remyelination group ( n=10). The mice of the control group were immediately performed MR scanning and pathological specimen obtaining; the mice in the demyelination group were administered with intragastrical CPZ-CMCNa once a day for 6 weeks for inducing demyelination, then received MR scanning and specimen obtaining with the same protocols used in control group; the mice in the remyelination group were administered with intragastrical CPZ-CMCNa once a day for six weeks for demyelination, then CPZ was withdrawn and normal diet was given for another four weeks. Then MR scanning and specimen obtaining were performed with the same protocols used in the other two groups. Regions of interest (ROIs) were set at the rostrum of corpus callosum (rCC), the bilateral normal appearing white matters (NAWM) of the rostrum of corpus callosum, and the bilateral cerebral cortex (Cx). The normalized T 2WI (T 2-normalized), fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD), and radial diffusivity (RD) values were compared among the three groups by one-way ANOVA. Results:The demyelination and remyelination mice model of MS were successfully established. The T 2-normalized values of rCC in control group, demyelination group and remyelination group were 0.47±0.03, 0.72±0.04, 0.54±0.04, respectively, with statistically significant difference found ( F=90.511, P<0.05). Post-hoc multiple comparisons showed significant differences among those groups ( P<0.05). There was no significant difference of T 2-normalized value in NAWM and Cx among the three groups ( P>0.05). Moreover, there were significant differences in the FA values (0.36±0.04, 0.29±0.03, and 0.32±0.05), the MD values [(0.572±0.015), (0.598±0.034), and (0.626±0.043)×10 -3 mm 2/s], the AD values [(0.79±0.04), (0.77±0.06), and (0.83±0.04)×10 -3 mm 2/s], and the RD values [(0.46±0.02), (0.51±0.03), and (0.53±0.05)×10 -3 mm 2/s] of rCC of the control group, the demyelination group, and the remyelination group (all P<0.05). Significant difference was found in FA values between the demyelination group and the control group ( P<0.05), and in MD values between the remyelination group and the control group ( P<0.05), as well as in AD values between the remyelination group and the demyelination group ( P<0.05). There were also significant differences in RD values between the remyelination group and the control group, and the demyelination group and the control group (all P<0.05). However, no significant difference was found in all diffusion tensor imaging (DTI) metrics of NAWM and Cx among the three groups (all P>0.05). The LFB-eosin staining showed that the myelin sheath of rCC was lost in the demyelination group, and the rCC was partially regenerated and repaired in the remyelination group. Conclusion:The modified CPZ-CMCNa model can selectively induce demyelination and remyelination of rCC, and the changes of demyelination and remyelination of rCC in the modified CPZ-CMCNa model can be quantitatively detected by T 2WI combined with DTI, which might provide related theoretical basis for the study on dynamic changes of MS lesions.

Discovery of a potent FKBP38 agonist that ameliorates HFD-induced hyperlipidemia

The mammalian target of rapamycin (mTOR)-sterol regulatory element-binding proteins (SREBPs) signaling promotes lipogenesis. However, mTOR inhibitors also displayed a significant side effect of hyperlipidemia. Thus, it is essential to develop mTOR-specific inhibitors to inhibit lipogenesis. Here, we screened the endogenous inhibitors of mTOR, and identified that FKBP38 as a vital regulator of lipid metabolism. FKBP38 decreased the lipid content

The Establishment and Identification of Acute Myeloid Leukemia NOD-SCID-IL2rg / 中国实验血液学杂志

OBJECTIVE@#To establish the in vivo traceable acute myeloid leukemia mice model with Luciferase-Expressing KG1a Cells.@*METHODS@#KG1a cells with stable luciferase gene expression (called as KG1a-Luc cells) were constructed by lentivirus transfection, then sifted out by puromycin. Eighteen male NOD-SCID-IL2rg@*RESULTS@#KG1a cells expressing luciferase stably were successfully obtained. The tumor luminescence wildly spread at day 17 captured by in vivo imaging. The KG1a-Luc tumor cells could be detected in the peripheral blood of the mice, with the average percentage of (16.27±6.66)%. The morphology and pathology result showed that KG1a-Luc cells infiltrate was detected in bone marrow, spleens and livers. The survival time of the KG1a-Luc mice was notably shorter as compared with those in the control group, the median survival time was 30.5 days (95%CI: 0.008-0.260).@*CONCLUSION@#The acute myeloid leukemia NOD-SCID-IL2rg

Drug-Resistant Mycobacterium tuberculosis Isolates from New and Previously Treated TB Patients in China, 2017-2019

Abstract INTRODUCTION: Mycobacterium tuberculosis (MTB) is a causative agent of tuberculosis (TB) that causes death worldwide. METHODS: MTB was subjected to phenotypic drug-susceptibility tests (DST), and drug-resistant genes were sequenced. RESULTS: Previously treated patients were more likely to have positive smear results and exhibit drug resistance. New patients were more likely to be mono SM-resistant and less likely to be INH- and RIF-resistant. The most common mutations were katG (S315T), rpoB (S450L), rpsL (K43R), and embB (M306V). CONCLUSIONS: The proportion of mono-SM-resistant TB among new patients was higher.

Comparison of efficacy of anterior cruciate ligament reconstruction between small-sized and normal-sized patients using grafts of different diameters / 中华创伤骨科杂志

Objective:To compare the therapeutic outcomes of anterior cruciate ligament (ACL) reconstruction between small-sized and normal-sized patients using grafts of different diameters.Methods:The data of 63 patients were selected who had undergone ACL reconstruction at Department of Joint/Sports Medicine, The Third Affiliated Hospital to Southern Medical University from January 2018 to December 2018. They were divided into 2 groups according to body size. In the observation group of 26 small-sized patients who were shorter and lighter, there were 18 males and 8 females with an age of (29.4±8.5) years and a graft of 7.5 mm in diameter was used. In the control group of 37 normal-sized patients, there were 26 males and 11 females with an age of (28.8±8.2) years and a graft of 8.0 mm in diameter was used. The 2 groups were compared in terms of failure rate, kinematic changes in the affected knee joint (taking the 63 normal knee joints in the 2 groups as controls), isokinetic muscle strength and Lysholm knee score.Results:There was no significant difference in the general data or follow-up time between the 2 groups other than height and weight ( P>0.05), indicating comparability between the 2 groups. In the control and observation groups, the failure rates were 2.7% (1/37) and 3.8% (1/26), and the Lysholm knee scores 2 years after surgery (86.6±10.1) points and (90.2±6.9) points, respectively, showing no statistical significance ( P>0.05). The range of flexion and extension was 56.30° (51.10°, 58.10°) in the observation group, significantly smaller than that in the control group [60.15°(58.95°, 63.08°)] and that for a normal knee joint [59.00° (56.45°, 63.00°]; the internal and external displacement in the observation group [7.30 (5.30, 8.30) mm] was significantly smaller than that for a normal knee joint [9.00 (7.00, 12.00) mm]; the external rotation in the observation group [0.97°(-1.59°, 3.01°)] was significantly larger than that for a normal knee joint [-1.54°(-5.30°, 2.28°)]; the knee extension muscle strength at 60°/s in the observation group was (65%±19%), significantly smaller than that in the control group (78%±18%) (all P<0.05). Conclusion:When small-sized and normal-sized patients use a 7.5 mm graft and a 8.0 mm graft respectively in ACL reconstruction, similar therapeutic outcomes can be expected.

The whole process management principles of chimeric antigen receptor T-cell therapy for lymphoma at Peking University Cancer Hospital / 白血病·淋巴瘤

Chimeric antigen receptor T (CAR-T) cell has achieved excellent efficacy in hematological tumors, especially for lymphoma. Many products have been approved to market all over the world, and 2 products targeting CD19 have been approved to treat relapsed and refractory large B-cell lymphoma in China. The current experiences of using CAR-T cells come from previous clinical studies. How to use CAR-T cells in a standardized and rationalized way is still a challenge faced by our clinicians. Based on the CAR-T cell treatment experiences from Peking University Cancer Hospital and the latest research progresses in CAR-T in China and abroad, this article will elaborate on patient screening, peripheral blood mononuclear cell collection, bridging treatment, lymphocyte depletion chemotherapy, CAR-T cell infusion, the monitoring and treatment of adverse events after infusion, and long-term follow-up after infusion, in order to guide clinicians to better use CAR-T cell and to bring maximum benefits to patients.

Advances on treatment of periprosthetic infection and antibiotic delivery system after total hip arthroplasty / 中国骨伤

Periprosthetic infection after hip replacement is a clinical catastrophic disease, which often leads to the failure of the prosthesis. It needs the combination of systemic antibiotics to cure the infection, which brings huge burden to doctors and patients. There are strict indications for debridement and one-stage revision of the prosthesis, and few cases meet the requirements. The second revision is still the gold standard for the treatment of periprosthetic infection. It is suitable for all infection conditions and has a high success rate. On the second phase of renovation, the antibiotic sustained release system plays a key role, and the carrier of antibiotic sustained-release system is the focus of current research, including classic bone cement and absorbable biomaterials. Bone cement has strong mechanical strength, but the antibiotic release shows a sharp decline trend; the absorbable biomaterials can continuously release antibiotics with high concentration, but the mechanical strength is poor, so it could not use alone. The combination of bone cement and absorbable biomaterials will be an ideal antibiotic carrier. PMMA is the most commonly used antibiotic carrier, but the antibiotic release concentration is decreased sharply after 24 hours. It will be difficult to control the infection and increase the risk of bacterial resistance if it is lower than the minimum inhibitory concentration. The biodegradable materials can release antibiotics completely, with long release time and high concentration, but low mechanical strength. Antibiotic spacer plays an important role in the control of infection. In the future, how to further extend the antibiotic release time of antibiotic sustained-release system, increase the amount of antibiotic release and maintain the mechanical strength of the material will be studied.

Analysis of adverse reactions of acupoint catgut embedding therapy / 中国针灸

OBJECTIVE@#To objectively evaluate the safety of acupoint catgut embedding therapy.@*METHODS@#A total of 331 patients who received acupoint catgut embedding therapy were enrolled and summarized through the inpatient medical record system, follow-up record and adverse reaction report card. The statistical analysis was performed from the aspects of patients' gender, age, marital status, history of allergy, history of diabetes and the time, symptoms, duration and prognosis of adverse reactions, etc.@*RESULTS@#Among 331 patients who received acupoint catgut embedding therapy, 70 patients had adverse reactions, which were divided into 9 types, including post-treatment discomfort, local hematoma or subcutaneous hemorrhage, local swelling, local induration, severe pain, thread-body rejection, local pruritus, post-treatment body temperature rising, local redness, swelling, fever and pain. The incidence rate of adverse events was 21.15%, and the incidence of serious adverse events was 0. Among the patients with adverse reactions, 58 patients (82.86%) relieved without treatment, and 12 patients (17.14%) received after symptomatic treatment; all patients had no sequelae.@*CONCLUSION@#The acupoint catgut embedding therapy is relatively safe and the incidence of adverse reactions is low.

Clinical Effect of Kangfuxin Solution Combined with Almagate Suspension on Complication of Gastroscope Biopsy / 中国实验方剂学杂志

Objective:To observe the clinical effect of Kangfuxin solution combined with Almagate suspension on the complication of gastroscope biopsy. Method:Totally 276 cases of chronic superficial gastritis gastroscope biopsy were divided into treatment group and control group randomly. Treatment group was treated by Kangfuxin solution combined with Almagate suspension，while the control group was given no precautionary measures as usual. Then the patients received the abdominal symptom score and fecal occult blood test（FOBT）after 1 week. Result:The cases with abdominal pain，burning sensation and stool occult blood in the control group were more than the treatment group significantly（P<0.05）. The patients' abdominal symptom score in control group was higher than that before the gastroscope biopsy，and that was lower in treatment group（P<0.05）. And the patients' abdominal symptom score of the control group was significantly higher than that of the treatment group after the gastroscope biopsy（P<0.05）. Compared with the Helicobacter pylori（HP）-infected subgroup，the incidences of early satiety and ventosity in the control group were higher than those of the treatment group（P<0.05）. The abdominal symptom score of the patients infected with helicobacter pylori（HP）in control group was significantly higher than that before the gastroscope biopsy and in the treatment group（P<0.05）. Conclusion:Kangfuxin solution combined with Almagate suspension is safe and effective in preventing complications of gastroscope biopsy，especially for patients infected with HP. The method could avoid exacerbating clinical symptoms.

Procalcitonin as a sensitive index of chronic infection after artificial joint replacement:a retrospective analysis / 中国骨伤

OBJECTIVE@#To study the predictive value of procalcitonin as a serum biomarker in diagnosis of late periprosthetic joint infection(PJI) for providing theoretical reference basis for diagnosis of PJI.@*METHODS@#A total of 77 cases were retrospective included from January 2015 to December 2017 for revision of total hip arthroplasty and total knee arthroplasty, according to the diagnostic criteria of Musculoskeletal Infection Society(MISI). All cases were divided into infection group and non-infection group. Infection group included 21 cases, 7 cases for male and 14 cases for female, with an average age of (60.70±8.75) years old (ranged 43 to 75 years old). Non-infection group 56 included cases, 24 cases for male and 32 cases for female, with an average age (64.40±12.14) years old (ranged 43 to 85 years old). Concentration of preoperative serum procalcitonin was examined and the chi-square test was used to compare positive rate between the two groups.@*RESULTS@#Two cases in the infection group had positive serum procalcitonin, 0.06 ng/L and 0.10 ng/L respectively, with the positive rate of 9.52%; 4 cases in non-infected group had positive serum procalcitonin, 0.05 ng/L, 0.06 ng/L, 0.06 ng/L, 0.16 ng/L respectively, with the positive rate of 7.14%. No statistically significant difference was observed between the two groups (=0.662).@*CONCLUSIONS@#Most of PJI were low toxicity infection with little systemic inflammatory response, so the concentration of serum procalcitonin was normal or slightly higher level, had little clinical significance for diagnosis of PJI. But the cases of this retrospective study are not enough, more cases are needed for further study.

Predictive factors analysis of the efficacy of cyclophosphamide combined with glucocorticoids in the treatment of idiopathic membranous nephropathy / 中华肾脏病杂志

Objective To investigate the predictive factors affecting the efficacy of cyclophosphamide (CTX) combined with glucocorticoids in the treatment of idiopathic membranous nephropathy (IMN),and to evaluate the efficacy of calcineurin inhibitor (CNI) adjustment due to poor treatment.Methods A retrospective cohort study was conducted.Two hundreds and twenty-eight patients with IMN diagnosed by renal biopsy in the People's Hospital of Guangxi Zhuang Autonomous Region from January 1,2007 to December 1,2016 were enrolled.All subjects were treated with CTX in combination with glucocorticoids.The patients were divided into two groups:remission group and no remission group.Multivariable logistic regression analysis was used to determine the baseline clinical-pathological influencing factors for the remission of IMN in the enrolled patients.Results The number of total remission (including complete and partial remission) of the first CTX combined with glucocorticoid treatment in 228 patients with IMN was 188(82.5％).Among them,141 patients (61.8％) had complete remission (CR),the median time for CR was 8(6,12) months,and the median time for partial remission (PR) was 3(1,4) months.The median follow-up time for this study was 25(13,43) months.Compared with the remission group,the serum albumin level was lower in the non-remission group,the 24-hour urine protein content,the blood complement C3 and C4 levels were higher,and the pathological stage was milder (all P ＜ 0.05).Multivariate logistic regression analysis suggested that the levels of baseline serum albumin,complement C4,and pathological stage were independent predictors of clinical remission in IMN patients.Twenty-four non-remission patients were treated with CNI.The overall response rate was 66.7％(16/24) at 6 months and 77.3％(17/22) at 12 months.Conclusions The levels of baseline albumin,blood complement C4,and pathological stage were independent predictors of clinical remission in IMN patients treated with CTX plus glucocorticoids.The non-remission patients with CTX combined with glucocorticoid therapy can still achieve a higher response rate after adjusting for CNI.

Effect of autophagy inhibitor chloroquine on acute alcoholinduced liver disease / 中国应用生理学杂志

OBJECTIVES@#To investigate the role of autophagy inhibitor chloroquine (CQ) in acute ethanol-induced liver injury and its mechenism.@*METHODS@#Twenty-one C57BL/6 male mice were randomly divided into three groups:control group, ethanol group, CQ + ethanol group (=7). Mice in ethanol group were administered 33% (v/v) ethanol at a dose of 4.5 g/kg body weight. Ethanol-induced liver steatosis in each group was detected by hematoxylin and eosin staining. Hepatic lipid accumulation was detected by staining with Oil red O. Hepatic tissue triglyceride (TG) levels, serum aspartate aminotransferase(AST) and alanine aminotransferase(ALT) were determined by biochemical assays. Protein expression of microtubule-associated protein 1 light chain 3(LC3) and nuclear factorκB p65(NF-κB p65) were measured by Western blot and immunofluorescence. Pro-inflammatory factors tumor necrosis factor-α(TNF-α)、interleukin 6(IL-6) were detected by ELISA.@*RESULTS@#Compared with control group, ethanol induced liver injury proved by accumulation of hepatic lipids, TG levels, AST and ALT activities were significantly increased by ethanol, protein expression of LC3-Ⅱ was also markedly increased by ethanol. Compared with ethanol group, addition of CQ increased furtherthe level of LC3-Ⅱexpression, and TG amount, serum AST and ALT activities, and the expression of NF-κB p65, TNF-αand IL-6.@*CONCLUSIONS@#Acute ethanol-intake could induce liver steatosis and inflammation, and autophagy inhibitor CQ exacerbatedethanol-induced liver injury, suggested that autophagy might be protective effect in acute ethanol-induced liver disease.

Pharmacokinetics mechanism of ABC efflux proteins-mediated seven features of compatibility / 中国中药杂志

ABC efflux proteins are a kind of transporters mediating diversified endogenous and exogenous efflux protein substrates across the plasma membrane by depending on the chemical energy released by ATP hydrolysis. As a vitally important functional membrane, it is widely found in various tissues and organs. The drug changes the expressions and/or functions of the transport proteins, which will affect the disposal process of substrate drugs corresponding to transporters , and finally lead to the pharmacokinetic interactions. The efflux proteins take part in the absorption, distribution, metabolism and excretion of drugs, and mainly consist of P-glycoprotein(P-gp), multidrug resistance associated protein(MRP) and breast cancer resistance protein(BCRP). The induction effect or inhibition effect of drugs on efflux protein plays a greatly significant role in the drug interaction produced by the compatibility of traditional Chinese medicine, which may be one of the important mechanisms of the theory of seven features of compatibility. In this article, the effects of seven features of compatibility on the ABC efflux transporters were reviewed, in order to reveal the roles of efflux protein in the herb-pairs compatibility, and provide new ideas for the mechanism and rationality of herb compatibility.

Cellular Uptake and Metabolism of Soluplus-based Scopoletin Micelles in Caco-2 Cells / 中国药学杂志

OBJECTIVE: To develop an analytical method for the quantification of scopoletin (Sco) and investigate the cellular uptake and metabolism of polyvinylcaprolactam-polyvinyl acetate-polyethylene glycol (soluplus)-based Sco micelles (Sco-Ms) in Caco-2 cells, as well as exploring the possible mechanisms involved in the oral absorption of Sco-Ms.METHODS: Combined with enzymatic hydrolysis for pretreatment, a liquid chromatography-electrospray ionization-tandem mass spectrometric (LC-MS/MS) method was developed for the quantification of Sco and its corresponding metabolite. Then, cellular uptake efficiency and metabolic rate of Sco were calculated.RESULTS: This method was proven to be linear over the concentration range of 5-1 000 ng•mL-1. Cellular uptake of Sco-Ms increased significantly compared with that of free Sco at various time points. Meanwhile, Sco-Ms inhibited the enzymatic degradation of Sco. Sco-Ms were primarily internalized into enterocytes via macropinocytosis and clathrin-dependent pathways.CONCLUSION: Enhanced cellular uptake and decreased metabolic rate are pivotal mechanisms by which Sco-Ms promotes oral absorption of Sco.