Pyroptosis is the programmed death of cells accompanied by an inflammatory response and is widely involved in the development of a variety of diseases, such as infectious diseases, cardiovascular diseases, and neurodegeneration. It has been shown that cellular scorching is involved in the pathogenesis of pulmonary arterial hypertension ( PAH) in cardiovascular diseases. Patients with PAH have perivascular inflammatory infiltrates in lungs, pulmonary vasculopathy exists in an extremely inflam-matory microenvironment, and pro-inflammatory factors in cellular scorching drive pulmonary vascular remodelling in PAH patients. This article reviews the role of cellular scorch in the pathogenesis of PAH and the related research on drugs for the treatment of PAH, with the aim of providing new ideas for clinical treatment of PAH.

Dihydromyricetin is a dihydroflavone compound which widely exists in ampelopsis of grapevine family. It has many pharmacological effects, such as anti-inflammatory, antibacterial, anti-tumor, antioxidant, regulating blood glucose, reducing blood lipid, liver protection and so on. In recent years, it has been found that dihydromyricetin has a good neuroprotective effect and can play a certain pharmacological role in a variety of neurological diseases, including Alzheimer' s disease, depression, Parkinson's disease and stroke. The purpose of this paper is to review the research on the neuroprotective effect of dihydromyricetin in the past decade.

Ginsenoside Rg1 is one of the most important saponins in ginseng. It has a wide range of pharmacological activities. It is considered to be a powerful neuroprotective agent. It has neuroprotective effects such as anti-neuroinflammation, anti-oxidative stress, anti-neuronal apoptosis, and enhancing memory. Rg1 shows a good application prospect in the prevention and treatment of neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease, stroke, and mental diseases such as depression. This paper reviews the research on the neuroprotective mechanism of Rg1 at home and abroad in recent years, in order to provide new research ideas for the clinical treatment of nervous system diseases.

OBJECTIVE: To observe the clinical effect of needle-knife at cervical spine area as adjunctive therapy on dry eye syndrome. METHODS: A total of 84 patients with dry eye syndrome were randomized into 3 groups, named group A, group B and group C, 28 cases in each one (1 case dropped off in the group A, 2 cases dropped off in both group B and C). In the group A, needle-knife was applied at the margo inferior of external occipital protuberance, the range of 4 cm bilateral to external occipital protuberance, the spinous process of C, the range of 3 cm bilateral to 2 cm above C spinous process, the range of 2 cm bilateral to C, C, C spinous process for once a week; acupuncture was applied at Jingming (BL 1), Cuanzhu (BL 2), Zusanli (ST 36), Sanyinjiao (SP 6), Taixi (KI 3), Yanglao (SI 6), Ganshu (BL 18), Shenshu (BL 23), etc. for once a day, 6 times a week; sodium hyaluronate eye drop was given one drop once, 5-6 times a day. Treatment of acupuncture and sodium hyaluronate eye drop was given in the group B, sodium hyaluronate eye drop was given in the group C, the acupoints selection and the manipulation of acupuncture, the dosage of sodium hyaluronate eye drop were the same as the group A. One week was as one course and 3 courses were required in the 3 groups. SchirmerⅠtest (SⅠT), break-up time (BUT), scores of corneal fluorescein staining (CFS) and eye symptom before and after treatment were observed, the clinical effect was evaluated in the 3 groups. RESULTS: SⅠT was increased, BUT was prolonged, scores of CFS and eye symptom were reduced after treatment in the group A and group B (<0.01); scores of CFS and eye symptom were reduced after treatment in the group C (<0.01). The variations of SⅠT, BUT and the scores of CFS and eye symptom in the group A were greater than those in the group B and the group C (<0.01); the variations of above indexes in the group B were greater than those in the group C (<0.05, <0.01). The total effective rate was 94.4% (51/54) in the group A, which was superior to 78.8% (41/52) in the group B and 48.1% (25/52) in the group C (<0.01), and the total effective rate in the group B was superior to the group C (<0.01). CONCLUSION Needle-knife at cervical spine area as adjunctive therapy can relieve the clinical symptoms and improve the function of lacrimal gland in patients with dry eye syndrome.
Acupuncture Points ; Acupuncture Therapy ; Combined Modality Therapy ; Dry Eye Syndromes ; therapy ; Humans ; Needles

OBJECTIVE: We have demonstrated that needle knife (acupotomy) treatment can improve knee osteoarthritis (KOA) in rabbits. The present study was designed to examine its effect on expression of phosphorylated focal adhesion kinase (p-FAK), phosphinositides 3 kinase (p-PI 3 K) and Aggrecan genes and proteins in the knee-joint cartilage tissues of KOA rabbits, so as to explore its partial molecular mechanism underlying improvement of KOA. METHODS: Forty-nine New Zealand male rabbits were randomly divided into normal control, model, model +inhibitor, needle knife, needle knife+ inhibitor, electroacupuncture (EA), EA +inhibitor groups (n=7 in each). The KOA model was established by modified Videman method (left hindlimb extension immobilization and ankle dorsal flexion 60°). Acupotomy relaxing manipulation was applied to the lateral collateral ligament and patellar ligament of the left knee-joint, two times a week for 4 weeks, and EA (2 Hz/100 Hz, 3 mA) was applied to the left "Liangmen" (ST 21), "Xuehai" (SP 10), "Neixiyan " (EX-LE 4) and "Dubi" (ST 35) for 20 min, three times a week, for 4 weeks. About 2 h before every needle-knife or EA treatment or at the corresponding time-point, intra-articular cavity injection of PF-562271(a specific antagonist of FAK, 200 μmol/L, 0.5 mL)was performed in the three inhibitor groups. The expression levels of p-FAK, p-PI 3 K, Aggrecan genes and proteins in the cartilage tissues were measured with quantitative Real-time PCR and Western blot, separately. RESULTS: After modeling, the expression levels of p-FAK and p-PI 3 K genes and proteins were significantly up-regulated (P<0.05, P<0.01), while those of Aggrecan protein and mRNA considerably down-regulated in the model group in comparison with the normal group (P<0.01). Following 4 weeks' needle-knife or EA treatment, the expression levels of p-FAK and p-PI 3 K and Aggrecan proteins in both EA and needle-knife groups, and Aggrecan mRNA in the needle knife group were significantly up-regulated (P<0.05, P<0.01). After administration of p-FAK antagonist, modeling-induced upregulation of expression of p-FAK mRNA and protein and p-PI 3 K protein, as well as modeling-induced down-regulation of Aggrecan mRNA and protein were significantly suppressed in the model+inhibitor group (P<0.05, P<0.01), and needle knife-induced and EA-induced up-regulation of expression of p-FAK, p-PI 3 K and Aggrecan mRNAs and proteins was notably suppressed respectively in comparison with the needle knife and EA groups (P<0.05, P<0.01). The effect of needle knife was significantly superior to that of EA in up-regulating p-PI 3 K and Aggrecan mRNAs as well as p-FAK, p-PI 3 K and Aggrecan proteins (P<0.05, P<0.01). CONCLUSION: Needle knife intervention can up-regulate the expression levels of p-FAK, p-PI 3 K and Aggrecan proteins and mRNAs in the cartilage tissue of the knee-joint in KOA rabbits, suggesting an involvement of FAK-PI 3 K signaling in the needle knife-induced improvement of KOA.

OBJECTIVETo explore the analgesic mechanism of small knife needle for treating transverse process syndrome of the third vertebra (TPSTV) by observing peripheral and central changesof β-endorphin (β-EP) and enkephalin (ENK) contents.

METHODSTotally 30 Japanese white big-ear rabbits of clean grade were divided into 5 groups according to random digit table, i.e., the normal control group, the model group, the small knife needle group, the electroacupunture (EA) group, and the small knife needle plus EA group, 6 in each group. The TPSTV model was established by inserting a piece of gelatin sponge into the left transverse process of 3rd lumbar vertebrae. Rabbits in the small knife needlegroup were intervened by small knife needle. Those in the EA group were intervened by EA at bilateralWeizhong (BL40). Those in the small knife needle plus EA group were intervened by small knife needleand EA at bilateral Weizhong (BL40). Contents of β-EP and ENK in plasma, muscle, spinal cord, and hypothalamus were determined after sample collection at day 28 after modeling.

RESULTSCompared with the normal control group, contents of β-EP and ENK in plasma and muscle increased significantly, and contents of β-EP and ENK in spinal cord and hypothalamus decreased significantly in the model group (P < 0.05, P < 0.01). Contents of β-EP and ENK approximated normal levels in the three treatment groups after respective treatment. Compared with the model group, the content of β-EP in muscle decreased, and contents of β-EP and ENK in hypothalamus increased in the three treatment groups after respective treatment (P < 0.05). There were no significant difference among the three treatment groups (P > 0.05).

CONCLUSIONSSmall knife needle treatment and EA had benign regulation on peripheral and central β-EP and ENK in TPSTV rabbits. Small knife needle treatment showed better effect than that of EA.

Acupuncture Points ; Animals ; Electroacupuncture ; Enkephalins ; metabolism ; Hypothalamus ; metabolism ; Lumbar Vertebrae ; pathology ; Muscle, Skeletal ; metabolism ; Needles ; Rabbits ; Random Allocation ; Spinal Cord ; metabolism ; Spinal Diseases ; therapy ; beta-Endorphin ; metabolism

OBJECTIVETo investigate the effects of sorafenib on human acute promyelocytic leukemia cell NB4 and its mechanism.

METHODSThe human acute promyelocytic leukemia cell NB4 was treated with different concentrations (0, 1.5, 3, 6 and 12 µmol/L) of sorafenib, the proliferation inhibitory rate of NB4 cells was assayed by MTT, the apoptosis of NB4 was determined with flow-cytomatry after treatment; after extraction of total protein, the Western blot was performed to determine the expressions of apoptosis-relatived molecules Caspase-3, Caspase-8 and MCL-1. The mRNA expressions of Caspase-3, Caspase-8 and MCL-1 were determined by RT-PCR.

RESULTSAs compared with the control group, the proliferation of NB4 significantly decreased after treatment with different concentrations of sorafenib. The sorafenib significantly induced the apopotosis of NB4 cells in time- and dose-dependent manners. Furthermore, sorafenib treatment resulted in the obvious increase of the Caspase-3 and Caspase-8 protein and mRNA expressions, and down-regulated the MCL-1 protein and mRNA expressions in NB4 cells.

CONCLUSIONSorafenib can inhibit proliferation and induce apopotosis of human acute promyelocytic leukemia cell NB4 through the expression of Caspase-3 and Caspase-8, and down-regulation of the expression of MCL-1.

Antineoplastic Agents ; Apoptosis ; Caspase 3 ; Caspase 8 ; Cell Line, Tumor ; Down-Regulation ; Humans ; Leukemia, Promyelocytic, Acute ; Niacinamide ; analogs & derivatives ; Phenylurea Compounds ; T-Lymphocytes, Helper-Inducer

The study reports the detection of neuroprotective effect of 10 kinds of coumarin derivatives and explores their possible mechanism. MTT method was used to screen the neuroprotective effect of 10 coumarin derivatives on neurotoxic agents (Aβ25-35 and rotenone) or OGD (oxygen-glucose deprivation). A compound with better protective effect was obtained. Then the effect of this compound on neurotoxic agents on PC12 was detected by the morphological observation. Furthermore, the effect of compound 3 on microglia with lipopolysaccharide (LPS) induced inflammation was detected. And the inflammatory factor was tested. Finally, direct free radical scavenging ability was detected. Compound 3 was found to be the best compound through three neurons toxic models. Not only compound 3 ameliorated cell viability reduced by three neurons toxic models, but also significantly inhibited the production of inflammatory factor (TNF-α and IL-1β). And its free radical scavenging ability is very good, especially the effect on superoxide anion, which is comparable with vitamin C. The significant scavenging effect of compound 3 on superoxide anion might be the mechanism of the neuroprotection. Compound 3 as a potential neural cell protective agent merits further investigation.
Animals ; Coumarins ; chemistry ; Free Radical Scavengers ; chemistry ; Inflammation ; Microglia ; drug effects ; Neurons ; drug effects ; Neuroprotective Agents ; chemistry ; PC12 Cells ; Rats

OBJECTIVETo explore the mechanism of acupotomy lysis in treatment of the third lumbar vertebrae transverse process syndrome.

METHODSOne hundred and eighty patients were randomly assigned into an acupotomy group and an electroacupuncture (EA) group, 90 cases in each group. The acupotomy group was treated with acupotomy on the tip of the 3rd lumbar vertebrae transverse process (tender point) combination with massage manipulation of hyperflexion and hyperextension on the waist, once a week for 3 weeks. The EA group was treated with EA at bilateral Shenshu (BL 23), Yaoyangguan (GV 3), Ashi point (local tender point) and ipsilateral Weizhong (BL 40), 3 times a week for 3 weeks. The 500 g pressure displacement and the energy absorption ratio were measured by JZL-II soft tissue tension meter and the clinical effect was evaluated by JOA low back pain scale before treatment, after treatment and 6 months after treatment.

RESULTSAfter treatment and at follow-up visit, the 500 g pressure displacement in the acupotomy group increased significantly (both P < 0.01), but it was decreased significantly in the EA group (P < 0.05, P < 0.01). The energy absorption ratio in the acupotomy group after treatment and at follow-up visit increased significantly (both P < 0.01), and in the EA group, there was no significant difference after treatment as compared with that before treatment (P > 0.05), but it was increased significantly at follow-up visit (P < 0.01). The total therapeutic level distribution in the acupotomy group was better than that in the EA group after treatment and 6 months after treatment (P < 0.05, P < 0.01).

CONCLUSIONAcupotomy therapy can significantly increase the 500 g pressure displacement and the energy absorption ratio of the local soft tissue around the third lumbar vertebrae transverse process, decrease the local soft tissue tension so as to alleviate pain. The clinical effect of the acupotomy is superior to that of electroacupuncture.

Acupuncture Points ; Acupuncture Therapy ; methods ; Adult ; Aged ; Electroacupuncture ; Humans ; Lumbar Vertebrae ; Middle Aged ; Spinal Diseases ; physiopathology ; therapy ; Syndrome

OBJECTIVETo study the analgesia mechanism of needle-knife lysis in spinal cord and other parts of central nervous system by comparing the changes of Leu-Enkephalin (L-ENK) content in different parts of centrium of rats undergone needle-knife lysis and electro-acupuncture respectively.

METHODSSixty healthy SD rats were randomly devided into normal control group, model group, needle-knife lysis (NKL) group and electro-acupuncture (EA) group. 4% papain solution mixed with 0.3 mol/L cysteine solutin in the ratio of 1:1, paused for 0.5 h,injected the mixture, 20 microl each time,into the left knee joint cavities of rats in model, NKL, EA groups at the 1st, 4th, 7th day. After 4 weeks in NKL group and EA group were treated with needle-knife lysis and electro-acupuncture, respectively. Three weeks after treatment, samples of spinal cord of the swollen part of rat waists and rat brains were taken from and the content of L-ENK of medulla oblongata, midbrain, pituitary gland, and hippocampus were measured.

RESULTSL-ENK content of model group increased higher than that of normal control group in spinal cord, hippocampus and midbrain (P < 0.01); there were no significant difference between normal control group and modle group on L-ENK in medulla oblongata and thalamus (P > 0.05). After intervening of NKL or EA, L-ENK content of NKL group increased higher in hippocampus than that of model group and EC group (P < 0.05); but L-ENK content of NKL group in midbrain was lower than that of model group (P < 0.05).

CONCLUSIONNeedle-knife lysis has characteristic of regulation for the L-ENK content in different parts of central nervous system of rats with knee osteoarthritis, and analgesic effect of needle-knife was possibly related with regulation of center L-ENK.

Acupuncture Therapy ; methods ; Animals ; Central Nervous System ; chemistry ; Electroacupuncture ; Enkephalin, Leucine ; analysis ; Female ; Male ; Osteoarthritis, Knee ; metabolism ; therapy ; Rats ; Rats, Sprague-Dawley