Objective To understand the frequency distribution of causes to facilitate the diagnosis and treatment of chronic cough.Methods Patients were recruited according to the inclusion criteria:chronic cough more than 8 weeks;normal X-ray appearance;coughing symptoms as the main or only symptom.Disease history was referred and physical examination was conducted,according to the diagnosis criteria of chronic cough causeoriented processes.If laboratory examination results are missing for a patient,empirical treatment will be combined as a treatment for this patient.Finally,the curative effect and the cause of disease will be analyzed.Results Seventy-nine patients were followed up.Twenty-eight,12,22,10,and 7 patients respectively were suspected of having CVA,EB,UACS,AC and GERC,among whom,23,9,14,9 and 4 were confirmed for their diagnosis,and 84.1％,75.0％,63.6％,90.0％,and 57.1％ of them received effective targeted therapies,accounting for 29.1％,11.4％,24.1％,11.4％,and 6.3％ respectively of all patients.The overall response rate was 74.7％.Conclusion The diagnosis and treatment of chronic cough with combinational cause-oriented diagnostic process and empirical therapy produce high effective rate with low cost.In addition,it could help understand the local frequency distribution of causes of chronic cough.It may be worth wide clinical application.

Objective To investigate the effect of different concentrations of rapamycin on the proliferation and apoptosis of glomerular mesangial cells(GMCs)and to investigate the mechanism. Methods GMCs were treated with different concentrations of rapamycin(1 μg/L,2 μg/L,4 μg/L,8 μg/L,16 μg/L).After treatment for 24 h,48 h and 72 h,cell proliferation was assessed bv MTT colorimetric assay and the growth curve was traced.After treatment for 72 h,the cell cycle distribution and the apoptotic rate of GMCs in different concentrations of rapamycin were analyzed bv flow cytometry.The effects of different concentrations of rapamycin on the mRNA and protein expression of p27 and p53 were detected by RT-PCR and Western blot respectivelyResult The low dose of rapamycin(1 μ/L)could signiticanfly inhibit the proliferation of GMCs and showed no effect on apoptosis.The high dose of rapamycin (8-16 μg/L)could significantly increase the apoptotic rate of GMCs.Rapamycin could increase the mRNA and protein expression of p27 and p53. Conclusion Rapamycin can inhibit GMCs proliferation and promote GMCs apoptosis by increasing the expression of p27 and p53.

ObjectiveTo investigate the changes in mammalian target of rapamyein (mTOR) with aging in rat kidneys.MethodsMale Wistar rats at the ages of 3, 12, 24 months were used for this study. Therenaltissuesandmesangialcellswereprocessedfor senescenceassociated β-galactosidase (SA-β-gal) staining. The expression and location of roTOR in kidneys and mesangial cells were studied by immunohistochemistry and immunocytochemistry, respectively. The mRNA and protein levels of the roTOR and p-roTOR were detected by Western blot assay and RT-PCR,respectively.ResultsThe expression of neutral β-galactosidase activity was increased in kidneys and mesangial cells with advancing age. Percentages of SA-β-gal staining positive ceils were (11.9±3.6)% versus ( 39.0±4.0)% versus ( 86.9±7.4) % in young, middle and aging glomerular mesangial cells (P<0.05). The mTOR staining appeared in the mesangial matrix and interstitium in kidneys, while the mTOR protein showed localization in cytoplasm and nucleus in mesangial cells. The staining intensity of mTOR in kidneys and mesangial cells in aged rats was markedly increased as compared to that in young and middle aged rats (P<0.05). The mRNA level of roTOR was significantly increased in kidneys and mesangial cells of agedrats versus young and middle aged rats,meanwhile, the roTOR and p-mTOR protein expressions were dramatically increased with advancing age (P<0.05 ).ConclusionsmTOR expression is increased with aging, which may play an important role in the aging process of kidneys.

Objective To discuss the techniques and methods of surgery for brain gliomas located in eloquent areas at awake anesthesia. Methods Nineteen patients with brain gliomas in eloquent areas, admitted to our hospital from December 2014 to May 2017, were operated under awake anesthesia with neuronavigation and intraoperative ultrasonography for locating the lesions and intraoperative direct electrical stimulation for functional mapping of the eloquent areas. All patients were followed up from 3 to 18 months; the surgical efficacies were analyzed. Results Of 19 patients, 18 (94.74％) were achieved awake and alert during brain mapping and resection of the tumors;17 (89.47％) were detected the motor areas by intraoperative direct electrical stimulation, 6 (31.58％) were detected the sensory cortex and 12 (63.16％) were detected language related cortex. Of 19 patients, MR imaging 2-3 months after surgery indicated that 5 (26.32％) received total resection of lesions, 9 (47.37％) subtotal resection of lesions and 5 (26.32％) partial resection of lesions. Seven patients (36.84％) had transitory postoperative aphasia, 4 (21.05％) were with transitory postoperative dyskinesia and one (5.26％) with permanent dyskinesia. Conclusion Comprehensive applications of awake anesthesia, neuronavigation, intraoperative ultrasonography and intraoperative direct electrical stimulation technologies allow maximum safe resection of gliomas in eloquent areas and protection of brain function.

Objective:To observe the regulatory effect of p38 mitogen-activated protein kinase (p38 MAPK) on aquaporin 4 (AQP4) in rats after hydrocephalus, and to explore its significance in hydrocephalus prevention.Methods:Fifty SD rats were randomly divided into sham-operated group ( n=10), hydrocephalus group ( n=20), and hydrocephalus+inhibitor (SB203580) group (SB group, n=20). The rat models of hydrocephalus in the latter two groups were prepared by intracerebroventricular injection of kaolin suspension; rats in the sham-operated group were injected with same amount of normal saline into the lateral ventricle. The p38 MAPK specific inhibitor SB203580 (10 mg/kg) was intraperitoneally injected into the rats of SB group on the 8 th d of modeling for 7 consecutive d; same volume of dimethylsulfoxide was given to the rats of hydrocephalus group on the 8 th d of modeling for 7 consecutive d; rats in the sham-operated group did not give any treatment. The severity of hydrocephalus in these rats was observed by MRI. The inflammatory factor tumor necrosis factor (TNF)-α level in the cerebrospinal fluid was detected by enzyme-linked immunosorbent assay (ELISA). The AQP4 and TNF-α mRNA expressions were detected by real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR). The phosphorylated p38 MAPK and AQP4 expressions in the periventricular brain tissues were detected by Western blotting and immunohistochemistry. Results:No hydrocephalus developed in sham-operated group and hydrocephalus developed in the latter two groups. As compared with sham-operated group, hydrocephalus group and SB group had significantly increased lateral ventricle volume, significantly aggravated periventricular edema, significantly higher EVAN's index, and statistically increased brain water content ( P<0.05). Two weeks after modeling, the TNF-α expression levels in cerebrospinal fluid of sham-operated group, hydrocephalus group and SB group were (20.49±0.96), (42.04±3.17), and (28.00±3.71) pg/mL, respectively, with significant differences ( F=186.000, P<0.001); the TNF-α expression level in SB group was significantly higher than that in sham-operated group and significantly lower than that in hydrocephalus group ( P<0.05). Two weeks after modeling, the TNF-α and AQP4 mRNA expression levels in brain tissues of the three groups were significantly different ( P<0.05); the TNF-α and AQP4 mRNA expression levels in hydrocephalus group were significantly higher than those in sham-operated group and SB group ( P<0.05). Correlation analysis showed that there was a positive linear correlation between AQP4 mRNA expression and TNF-α mRNA expression in hydrocephalus group ( r=0.511, P=0.026), and there was a positive linear correlation between AQP4 protein expression and phosphorylated p38 MAPK protein expression in hydrocephalus group and SB group ( r=0.560, P=0.013; r=0.463, P=0.030). Immunohistochemical staining results showed that AQP4 expression was abundant in glial cells of the three groups; the p38 MAPK distribution was uniform and non-polar; the phosphorylated p38 MAPK protein expression in the hydrocephalus group was significantly higher than that in the sham-operated group, and that in the SB group returned to the level of the sham-operated group. Conclusion:The p38 MAPK pathway is involved in the positive regulation of AQP4 expression, which could be inhibited by SB203580.

OBJECTIVE: To observe the effects of "" acupuncture on cerebral blood flow in high-risk patients of cerebral ischemic stroke based on arterial spin labeling (ASL) and perfusion-weighted imaging (PWI), and to evaluate the clinical efficacy. METHODS: A total of 180 patients with transient ischemic attacks (TIA) / minor ischemic stroke (MIS) were randomly divided into an acupuncture A group, an acupuncture B group and a medication group, 60 cases in each group. The patients in the acupuncture A group were treated with "" acupuncture at Baihui (GV 20), Fengfu (GV 16), Yamen (GV 15), Dazhui (GV 14), Shenzhu (GV 12), Zhiyang (GV 9), Mingmen (GV 4), Yaoyangguan (GV 3) and Jingjiaji (EX-B 2), once a day; the patients in the acupuncture B group were treated with identical acupoints but was given once every other day; the patients in the medication group were treated with oral administration of nimodipine tablets, 30 mg, three times daily. All the three groups were treated for four weeks. ASL and PWI, including relative cerebral blood volume (rCBV), relative cerebral blood flow (rCBF), relative mean transit time (rMTT) and relative time to peak (rTTP), were conducted before and after treatment; the changes of the test indexes were compared before and after treatment. The clinical efficacy of the three groups was compared. RESULTS: Compared before treatment, the numbers of ASL normal perfusion in the 3 groups were significantly increased after treatment (all <0.01); the number of ASL normal perfusion in the acupuncture A group was higher than that in the acupuncture B group (<0.05), but was not significantly different from that in the medication group (>0.05). Compared before treatment, rCBV and rCBF in the 3 groups were significantly increased after treatment (all <0.01), and rMTT and rTTP were significantly reduced (all <0.01). After treatment, rCBV and rCBF in the acupuncture A group were higher than those in the acupuncture B group (all <0.05); the rMTT and rTTP in the acupuncture A group were lower than those in the acupuncture B group (all <0.05); the differences of PWI parameters after treatment were not statistically significant between the acupuncture A group and medication group (all >0.05). The total effective rate was 88.3% (53/60) in the acupuncture A group, 73.3% (44/60) in the acupuncture B group and 90.0% (54/60) in the medication group; the total effective rate in the acupuncture A group was superior to that in the acupuncture B group (<0.05), but was not significantly different from that in the medication group (>0.05). CONCLUSION "" acupuncture could effectively improve the hypoperfusion of cerebral blood flow in patients with high risk of cerebral ischemic stroke, reduce the incidence of severe CIS; acupuncture for once a day is better than once every other day.
Acupuncture Therapy ; Brain Ischemia ; prevention & control ; Cerebrovascular Circulation ; Humans ; Risk Factors ; Stroke

The first rate-limiting enzyme of the serine synthesis pathway (SSP), phosphoglycerate dehydrogenase (PHGDH), is hyperactive in multiple tumors, which leads to the activation of SSP and promotes tumorigenesis. However, only a few inhibitors of PHGDH have been discovered to date, especially the covalent inhibitors of PHGDH. Here, we identified withangulatin A (WA), a natural small molecule, as a novel covalent inhibitor of PHGDH. Affinity-based protein profiling identified that WA could directly bind to PHGDH and inactivate the enzyme activity of PHGDH. Biolayer interferometry and LC-MS/MS analysis further demonstrated the selective covalent binding of WA to the cysteine 295 residue (Cys295) of PHGDH. With the covalent modification of Cys295, WA blocked the substrate-binding domain (SBD) of PHGDH and exerted an allosteric effect to induce PHGDH inactivation. Further studies revealed that with the inhibition of PHGDH mediated by WA, the glutathione synthesis was decreased and intracellular levels of reactive oxygen species (ROS) were elevated, leading to the inhibition of tumor proliferation. This study indicates WA as a novel PHGDH covalent inhibitor, which identifies Cys295 as a novel allosteric regulatory site of PHGDH and holds great potential in developing anti-tumor agents for targeting PHGDH.