Effect of Isodon ternifolius-medicated serum on hepatic stellate cells based on TLR4/NF-κB/NLRP3 signaling pathway / 中国中药杂志

The present study aimed to investigate the inhibitory effect and mechanism of Isodon terricolous-medicated serum on lipopolysaccharide(LPS)-induced hepatic stellate cell(HSC) activation. LPS-induced HSCs were divided into a blank control group, an LPS model group, a colchicine-medicated serum group, an LPS + blank serum group, an I. terricolous-medicated serum group, a Toll-like receptor 4(TLR4) blocker group, and a TLR4 blocker + I. terricolous-medicated serum group. HSC proliferation was detected by methyl thiazolyl tetrazolium(MTT) assay. Enzyme-linked immunosorbent assay(ELISA) was used to measure type Ⅰ collagen(COL Ⅰ), COL Ⅲ, transforming growth factor-β1(TGF-β1), intercellular adhesion molecule-1(ICAM-1), α-smooth muscle actin(α-SMA), vascular cell adhesion molecule-1(VCAM-1), cysteinyl aspartate-specific proteinase-1(caspase-1), and monocyte chemotactic protein-1(MCP-1). Real-time PCR(RT-PCR) was used to detect mRNA expression of TLR4, IκBα, and NOD-like receptor thermal protein domain associated protein 3(NLRP3), nuclear factor-κB(NF-κB) p65, gasdermin D(GSDMD), and apoptosis-associated speck-like protein containing a CARD(ASC) in HSCs. Western blot(WB) was used to detect the protein levels of TLR4, p-IκBα, NF-κB p65, NLRP3, ASC, and GSDMD in HSCs. The results showed that I. terricolous-medicated serum could inhibit the proliferation activity of HSCs and inhibit the secretion of COL Ⅰ, COL Ⅲ, α-SMA, TGF-β1, caspase-1, MCP-1, VCAM-1, and ICAM-1 in HSCs. Compared with the LPS model group, the I. terricolous-medicated serum group, the colchicine-medicated serum group, and the TLR4 blocker group showed down-regulated expression of p-IκBα, NLRP3, NF-κB p65, GSDMD, and ASC, and up-regulated expression of IκBα. Compared with the TLR4 blocker group, the TLR4 blocker + I. terricolous-medicated serum group showed decreased expression of TLR4, p-IκBα, NLRP3, NF-κB p65, GSDMD, and ASC, and increased expression of IκBα. In conclusion, I. terricolous-medicated serum down-regulates HSC activation by inhibiting the TLR4/NF-κB/NLRP3 signaling pathway.

Non-coding RNA-mediated TGF-β1/Smads Signaling Pathway and Liver Fibrosis， and Intervention by Active Components of Chinese Medicinal： A Review / 中国实验方剂学杂志

Liver fibrosis is a wound healing response that occurs in the setting of chronic liver injury and is caused by imbalance in the synthesis and degradation of extracellular matrix （ECM）. If left untreated， it can progress to liver cirrhosis and hepatocellular carcinoma. The activation of hepatic stellate cell （HSC） is now well established as a central driver of liver fibrosis. The activated HSC will transform into myofibroblasts that produce ECM protein. Transforming growth factor-β1 （TGF-β1） can induce the activation of hepatic stellate cell （HSC）， and TGF-β1/Smads signaling pathway is one of the important pathways to promote liver fibrosis. Non-coding RNA （ncRNA） does not encode proteins during the transcription but plays an important regulatory role in the post-transcriptional process of genes. Accumulating evidence shows that the occurrence of liver fibrosis is closely related to the abnormal expression of ncRNA which participates in the activation of HSC by regulating TGF-β1 signal transduction and then affects the process of liver fibrosis. MiRNA-mediated TGF-β1/Smads signaling pathway can not only promote liver fibrosis but also play a role in anti-fibrosis. Long non-coding RNA （lncRNA） not only promotes the development of liver fibrosis by binding to target genes but also enhances TGF-β1 signal transduction by acting as competitive endogenous RNA. circular RNA （circRNA） acts as a ''sponge'' to regulate TGF-β1/Smads pathway， thereby inhibiting HSC activation and exerting the anti-liver fibrosis effect. Chinese medicinal plays an essential part in the prevention and treatment of liver fibrosis， and the active components can inhibit TGF-β1/Smads pathway by regulating the expression of miRNA， thus alleviating liver fibrosis. This article reviews the role and mechanism of miRNA-， lncRNA- and circRNA-mediated TGF-β1/Smads signaling pathway in liver fibrosis and summarizes the anti-liver fibrosis effect of active components of Chinese medicinals by regulating miRNA-mediated TGF-β1/Smads signaling pathway， which can serve as a reference for clinical treatment of liver fibrosis and the development of new drugs.

Correlation and Traditional Chinese Medicine Intervention of Pyroptosis and Liver Diseases / 中国实验方剂学杂志

Pyroptosis， also known as cell inflammatory necrosis， is different from apoptosis， necrosis， and other forms of cell death in morphological characteristics， occurrence， and regulatory mechanism. It is a new type of programmed cell death dependent on Caspase， which has been discovered and confirmed in recent years. Studies have shown that pyroptosis is closely related to the occurrence of liver diseases， and is critical in alcoholic liver disease （ALD）， non-alcoholic fatty liver disease （NAFLD）， liver fibrosis， and liver cancer. Pyroptosis causes inflammatory injury of hepatocytes to promote the occurrence and development of liver diseases by activating Caspase-1， cleaving the effector gasdermin-D （GSDMD）， and releasing pro-inflammatory cytokines， such as interleukin-18 （IL-18） and interleukin-1β （IL-1β） mainly through the classical NOD-like receptor protein 3 （NLRP3） inflammasome pathway. Clinically， Chinese medicine in the treatment of liver diseases has unique efficacy and low side effects. In the intervention on liver diseases， Chinese medicine blocks the pyroptosis signaling pathway to relieve the liver inflammation by inhibiting the assembly and activation of NLRP3 inflammasome multiprotein complex， blunting the activity of Caspase-1 or Caspase-4/Caspase-5/Caspase-11， and inhibiting the cleavage of GSDMD to reduce the release of pro-inflammatory cytokines such as IL-18 and IL-1β. Therefore， in-depth investigation of pyroptosis facilitates unveiling its role in the occurrence， development， and prognosis of liver diseases， and the enhancement or inhibition of pyroptosis may provide a new strategy for the prevention and treatment of liver diseases by Chinese medicine. At present， NLRP3 inflammasome， a key protein in the classic pyroptosis signaling pathway， has become an anti-liver disease target of Chinese medicine. This study briefly summarized the relationship between pyroptosis and liver diseases and reviewed the intervention of monomers， compound prescriptions， effective fractions and extracts of Chinese medicine in recent years to provide important guidance for further exploring the pathogenic mechanism of pyroptosis and the treatment of liver diseases with Chinese medicine.

Study of the optimal monochromatic image of coronary stent based on dual-layer detector spectral CT / 中华放射学杂志

Objective:To explore the optimal monochromatic level for the observation of coronary in-stent lumen by dual-layer spectral CT (DLCT).Methods:Forty-nine patients with 74 stents after percutaneous coronary intervention (PCI) who underwent coronary CTA (CCTA) examinations by a DLCT between January 2016 and September 2017 were retrospectively enrolled. A total of 12 groups of images including 60-120 keV (kilo electron voltage) images with 10 keV interval, 140-200 keV images with 20 keV interval and conventional images. In-stent lumen diameter of proximal, mid and distal portion was measured. Difference of CT values between in-stent lumen and ascending aorta was used to describe as blooming artifact, and noise of in-stent lumen as image noise. Then Likert 5-point scale was performed to evaluate images noise, enhancement of in-stent lumen, blooming artifact and diagnostic confidence. Differences of objective and subjective parameters among conventional and various monochromatic images were compared by Friedman test.Results:In the diameter measurement of the proximal, middle and distal segments of the stent, the difference between the images of each group was statistically significant (χ 2 = 427.270, 426.375, 400.981, P< 0.001). The diameter of the lumen measured by 120-200 keV single-level image was larger than that measured by 60-100 keV single-level image, and the difference was statistically significant ( P< 0.05). In the comparison of CT difference between the stent lumen and ascending aorta, the difference between the images of each group was statistically significant (χ 2 = 242.193, P< 0.001), and 100-200 keV single-level images were lower than the conventional images, the difference was statistically significant ( P< 0.05). In the comparison of noise values, the difference between the images of each group was statistically significant (χ 2 = 420.161, P< 0.001), and the difference was statistically significant ( P< 0.05). In the subjective scores of noise, enhancement, halo artifact and diagnostic confidence, there were statistically significant differences among the groups (χ2= 333.827, 455.989, 276.824, 399.497, P< 0.001). The noise score of 100-200 keV single-level image was higher than that of conventional image, the difference was statistically significant ( P< 0.05). The enhancement score of 60 keV was significantly higher than that of other images ( P< 0.05). The halo artifact score of 100-200 keV single level image was higher than that of 60-90 keV image, the difference was statistically significant ( P<0.05). The scores of 90-120 keV single-level images were higher than those of other single-level images, and the difference was statistically significant ( P< 0.05). Conclusions:CCTA examinations can be effectively performed by DLCT in patients after PCI in clinical settings, and 120 keV is recommended as the optimal monochromatic image for the observation of in-stent lumen.

Research Progress of Blood Brain Barrier Model and Effect of Traditional Chinese Medicine on Its Permeability / 中国实验方剂学杂志

Blood brain barrier (BBB), as barrier between plasma and brain cells formed by brain capillary wall and glial cells and barrier between plasma and cerebrospinal fluid formed by choroid plexus, can prevent some brain tissues (mostly harmful substances), so as to maintain a stable internal environment of brain tissues, while stopping most drugs from the intracranial and causeing difficulties to cerebral diseases. The establishment of experimental model of BBB is a key technique for drug treatment of craniocerebral diseases. Therefore, the establishment of the BBB model and the study of its permeability change will deepen the understanding of the neuro-vascular interaction and provide an important theoretical basis for the diagnosis and treatment of central nervous system diseases. Traditional Chinese medicine(TCM) can affect brain tissue superoxide dismutase (SOD) activity, inhibit myeloperoxidase (MPO) activity and tumor necrosis factor-α (TNF-α) content, so as to affect the expression of zonula occluden-1 (ZO-1) or up-regulate the expression of Claudin-5, inhibit BBB permeability under pathological conditions, and play a protective role in BBB. TCM can also promote the changes in BBB permeability by affecting the expressions of cell adhesion factor-1 (CAM-1), ZO-1, filamentous actin(F-actin), P-glycoprotein(P-gp)and 5-hydroxytryptamine (5-HT), or increase drug permeability through co-delivery with other drugs. In this paper, the methods, advantages and disadvantages of the establishment of experimental models of the BBB in recent years, as well as the effects of TCM monomers, effective components and TCM compounds on the permeability of the BBB were summarized, so as to provide important guidance and direction for the future treatment of intracranial diseases by traditional Chinese and western medicine.

Clinical observation of warm moxibustion therapy to improve quadriceps weakness after total knee arthroplasty / 中国针灸

OBJECTIVE@#To evaluate the clinical efficacy of warm moxibustion therapy in the recovery of quadriceps muscle strength in patients undergoing total knee arthroplasty (TKA) with analgesia of the femoral nerve block (FNB).@*METHODS@#A total of 174 patients with KOA were randomized into a warm moxibustion group and a rehabilitation group, 87 cases in each group. In the warm moxibustion group, warm moxibustion combined with conventional quadriceps strength training were used. In the rehabilitation group, conventional quadriceps strength training was given. The warm moxibustion was applied at Liangqiu (ST 34) and Zusanli (ST 36), the treatment was given twice a day, 7 days for one course, with a total of 2 courses.The quadriceps muscle strength of the two groups was recorded and compared at 24 h before FNB, 24, 48, 72 and 96 h after surgery, and the resting and exercise VAS pain scores were also recorded at the same time point. And the first time for standing up and the first straight raising time in the two groups were compared, and the occurrence of adverse reactions in the two groups were observed.@*RESULTS@#At 24, 48, 72 and 96 h after FNB, the quadriceps muscle strength in the warm moxibustion group was better than that in the rehabilitation group (<0.05, <0.01). At 72 h and 96 h after FNB, the resting and exercise VAS scores of the warm moxibustion group were lower than those of the rehabilitation group (both <0.001). The average first straight leg raising time in the warm moxibustion group was postoperative (31.03±10.78) h, and the time in the rehabilitation group was postoperative (47.23±15.78) h. The difference was statistically significant (<0.001). The average time of the first time for standing up in the warm moxibustion group was postoperative (25.76±7.00) h, and postoperative (33.12±11.18) h in the rehabilitation group. The difference was also statistically significant (<0.001). No adverse reactions occurred in both groups.@*CONCLUSION@#Warm moxibustion combined with conventional quadriceps strength training can improve the symptoms of quadriceps weakness in patients with femoral nerve block after total knee arthroplasty, and accelerate the recovery of joint function, which is superior to conventional quadriceps strength training.

Eficacy of levothyroxine replacement therapy in children with hypothyroidism / 中华内分泌外科杂志

Objective To investigate the clinical efficacy of levothyroxine replacement therapy in children with hypothyroidism.Methods 45 children with hypothyroidism admitted from Apr.2015 to Dec.2016 were selected as observation group,and 45 healthy children in the same period were selected as the control group.Children in the control group received regular diet and were paid attention to nutritional balance.Children in the observation group were given levothyroxine sodium on the basis of dietary guidance.The two groups were treated continuously for 6 months.The levels of thyroid function,insulin-like growth factor,indicators for growth and development and inflammatory factors were measured before and after treatment in both groups.Results After treatment for 3 months and 6 months,the levels of FT3,FT4,IGF-1,IGFBP-3 and IGF-1/IGFBP-3 in the observation group increased significantly compared with those before treatment,and the levels of TSH in the observation group decreased significantly(P＜0.05).The levels of FT3,lFT4,TSH,IGF-1,IGFBP-3 and IGF-1/IGFBP-3 in the observation group after treatment for 6 months were (7.17±0.06)pmol/L,(2.74±0.07)mU/L,(207.67±9.06)μg/L,(0.46±0.02) mg/L and(34.59±1.97).The difference was not statistically significant (P＞0.05).After 3 months and 6 months of treatment,the height,body weight,osteocalcin and 25-(OH)2D3 levels in the observation group were significantly higher than those in the control group (P＜0.05),and there was no significant difference between the two groups after 6 months (P＞0.05).The difference was statistically significant (P＜0.05).Conclusion Left thyroid hormone replacement therapy can significantly improve the thyroid function of children with hypothyroidism,increase the level of thyroid-associated hormone and insulin-like growth factor,promote the growth and development of children,which is worthy of clinical application.

Quality standard for Pogostemon auricularius / 中成药

AIM To establish the quality standard for Pogonostemon auricularius (L.) Hassk..METHODS The original,characteristic and microscopic features of P.auricularius were identified,after which TLC was used for qualitative identification,HPLC was adopted in the content determination of verbascoside,and the contents of water,total ash,acid-insoluble ash,extract were determined by Chinese Pharmacopoeia methods.RESULTS The clear TLC plots displayed good reproducibility.Verbascoside showed a good linear relationship within the range of 0.102-2.04 μg (r =0.999 98),whose average recovery was 97.99％ with the RSD of 2.02％.In four-teen batches of samples,the content ranges of water,total ash,acid-insoluble ash,extract were 6.47％-12.07％,7.59％-12.35％,0.23％-3.55％,13.28％-26.82％,respectively.CONCLUSION This stable and reliable method can be used for the quality control of P.auricularius

Value of CT in the postoperative evaluation of patellar dislocation triple surgery / 实用放射学杂志

Objective To study the role of CT in the evaluation after patellar dislocation triple surgeries.Methods Retrospectively analysed the CT measurements of 60 recurrent patellar dislocation patients (61 knees),who had undergone patellar dislocation triple surgeries,within one month before and after procedures.The measurements included patellar tilt angle,lateral patellar displacement,trochlear con-gruence angle,Tibial Tuberosity-Trochlear Groove distance,Insall-Salvati Ratio and Caton-Deschamps Index.Moreover,the troch-lear dysplasia classifications of all patients were evaluated.In addtion,an analysis has also been completed for 40 (41 knees)of 60 patients who had second postoperative CT examinations as follow-up assessment 3 to 6 months after surgeries.Results All one-month postoperative measurements decreased obviously with statistical significance(P <0.05 ).Furthermore,one case of subluxa-tion,1 1 cases of abnormal Tibial Tuberosity-Trochlear Groove distance,13 cases of abnormal Insall-Salvati Ratio and 14 cases of Ca-ton-Deschamps Index abnormities were also observed.Besides that,it was also found that all patients had trochlear dysplasia and 5 cases were diagnosed with patellar subluxation or dislocation at the second postoperative follow-up assessment.Conclusion The patients with redislocation or risks for patellar instability can be detectecd by CT which provides objective evidence for postoperative evaluation and further treatments.

Histological evaluation of cervical carcinomas in FIGO stage Ib2/IIa after neoadjuvant chemotherapy / 中华病理学杂志

<p><b>OBJECTIVE</b>To investigate the histological changes of cervical cancer after neoadjuvant chemotherapy (NACT) and to establish histological criteria for interpretation of chemotherapeutical effects.</p><p><b>METHODS</b>Fifty-six patients with FIGO stage Ib2-IIa cervical cancers treated by NACT and subsequent radical surgery were retrospectively analyzed, in which the pre- and post-chemotherapeutic histopathological changes were assessed.</p><p><b>RESULTS</b>The post-chemotherapeutic histopathological changes of 56 cases included grade 3 effects in 11 cases (19.6%), grade 2 in 24 cases (42.9%), grade 1 in 13 cases (23.2%) and no response in only 8 cases (14.3%). The histologic response rate was 62.5% (35/56) and the overall clinical response rate was 67.9% (38/56). The overall coincidence by both criteria was 78.6% (44/56). Four cases (7.1%, 4/56) had only histological response and 8 cases (14.3%, 8/56) had response by imaging. In comparison with the pre-chemotherapy specimens, the chemotherapy-associated histological changes included shrinkage and scattering of tumor nests,decrease of tumor cellularity,tumor cell degeneration and necrosis.</p><p><b>CONCLUSIONS</b>The histological changes in locally advanced cervical cancers induced by NACT are significant, which may challenge the diagnosis in the final specimens. There are some discreqancies between the histological criteria and imaging/gynecological ones for the therapeutic evaluation of cervical cancers,and it is thus recommended to use the pathological criteria for clinic practice.</p>

Rapid detection of the hot spot gene mutations in Chinese patients with nonsyndromic hearing loss by polymerase chain reaction-restrictive fragment length polymorphism / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To develop a rapid genetic diagnosis technique for the patients with hereditary hearing loss by screening hot spots of mutations, namely 235delC of the GJB2 gene, IVS7-2A>G of the SLC26A4 gene, and 1555A>G of mitochondrial 12S rRNA.</p><p><b>METHODS</b>Multiple PCR amplification of the three fragments covering the expected mutations in GJB2, SLC26A4 and 12S were carried out and the amplified products were analyzed by restriction fragment length polymorphism (RFLP).</p><p><b>RESULTS</b>Eighteen homozygous and 18 heterozygous 235delC, 2 homozygous and 13 heterozygous IVS7-2A>G, and 8 homogeneous 1555A>G were detected in the 200 patients with hearing loss. All the results were confirmed by sequencing. The detection rate of the three mutant alleles was 21.7% (71/400 + 8/200 = 0.217) and the genetic diagnosis rate was 14% [(18+2+8)/200 = 0.14].</p><p><b>CONCLUSION</b>It is a convenient, efficient and economical method to screen the hot spots of mutation in the patient with hereditary hearing loss by using PCR-RFLP.</p>

Study on graded therapy of hemophilic arthritis by integrative traditional Chinese and Western medicine / 中国结合医学杂志

<p><b>OBJECTIVE</b>To study the effect and safety of graded therapy featuring integrative traditional Chinese and Western medicine for the treatment of hemophilic arthritis.</p><p><b>METHODS</b>Forty patients with hemophilic arthritis were hospitalized randomly, with their blood coagulation factor activity determined by one-stage method and their arthritis classified into 4 stages. The treatment was applied according to the stage of arthritis and finding of intra-articular cavity puncture. For stage I, based on the principle of RICE (rest, ice, compression and elevation), 1.8 g of Xuefuda was medicated orally once per day, intravenous dripping of 250 mL of hemostasis mixture twice a day and 1.2 g of clindamycin per day were also given for hemostasis and anti-inflammation. For stage II-III, Kangyanling was additionally administered via intra-articular cavity injection twice a week, 2 mL every time, for 5-6 times in total. For stage IV, the drug for intra-articular cavity injection was replaced with 25 mg of sodium hyaluronate and the frequency of injection reduced to every two weeks, for 5-6 times in total. Coagulation factors III and IV as well as blood plasma were not given in the whole treatment course. Short-term therapeutic effects and adverse reaction in patients were evaluated, and the long-term effects were followed-up after patients left the hospital with 6-month consolidation therapy by Xuefuda.</p><p><b>RESULTS</b>After a 3-week treatment, 33 patients (82.5%) were completely remitted; 5 (12.5%) were partially remitted and 2 (5.0%) un-remitted, setting the short-term effective rate at 95.0% (38 cases). The 6-month follow-up showed that except for a relapse in 2 and 4 patients of stage III and IV respectively, long-term remission displayed in all the other 34 patients, with the remission sustaining rate being 85.0%. No complication such as an infection, bleeding or aggravating pain occurred in the 215 times intra-articular puncturing conducted in the 40 patients. Normal figures were shown in liver and kidney function, electrolytes, ECG, blood glucose and routine test of blood and urine throughout the course.</p><p><b>CONCLUSION</b>The graded treatment of integrative medicine for hemophilia with non-blood preparation has a favorable effect and is safe or without any adverse reaction, which opens a high efficacy and new safe path and thinking for the treatment of and deformity prevention in the hemophilic patients.</p>

Observation on therapeutic effects of scraping therapy and warming acupuncture-moxibustion on 50 cases of fasciitis of back muscles / 中国针灸

<p><b>OBJECTIVE</b>To search for the best method for treatment of fasciitis of back muscles.</p><p><b>METHODS</b>One hundred cases of fasciitis of back muscles were randomly divided into two groups. The treatment group of 50 cases were treated with scraping and warming acupuncture and moxibustion at Fengmen (BL 12), Feishu (BL 13), Quyuan (SI 13), Bingfeng (SI 12), Jiafeng, local pressure pain points, and cord-like node; and the control group of 50 cases with simple acupuncture.</p><p><b>RESULTS</b>In the treatment group, 40 cases were cured and 10 cases improved with a total effective rate of 100.0%; in the control group, 26 cases were cured and 16 cases improved, 8 cases were ineffective with a total effective rate of 84.0%. The treatment group in improvement of pressure pain and pain was better than the control group, with scores significantly decreased (P < 0.01).</p><p><b>CONCLUSION</b>Scraping therapy and warming acup-moxibustion have obvious effect on fasciitis of back muscles, and it is a better therapy for this disease.</p>

Novel quantitative method for evaluating oxygen/glucose deprivation-induced injury of hippocampal slices / 浙江大学学报·医学版

OBJECTIVE: To establish a simple, sensitive in vitro method to evaluate oxygen/glucose deprivation (OGD)-induced injury of brain hippocampal slices in rats. METHODS: Rat hippocampal slices were incubated in 2% 2, 3, 5-triphenyltetrazolium chloride (TTC) solution after oxygen/glucose deprivation. They were then soaked in a measured volume of ethanol and dimethylsulfoxide (50:50) to extract the TTC formazan Product which was then measured by spectrophotometry. OGD induced LDH release was simultaneously measured. RESULTS: Progressive prolongation of OGD induced hippocampal injury resulted in decreased formazan coloration as determined by spectrophotometry. There was a parallel increase in LDH release, thus a negative correlation in these two products was noted. (r=-0.933,P <0.01). The injury was attenuated in the brain slices pre-treated with nimodipine, dexamethasone, and ketamine, but not ONO-1078. CONCLUSION: Solvent extraction and spectrophotometric quantification of formazan represents an objective measurement of OGD-induced injury of rat hippocampal slices.