Objective To investigate the dynamic changes of glutamic acid(Glu) levels,ATP levels,free calcium ion,mitochondrial membrane potential,apoptosis related to mitochondrial pathways of apoptosis and Na+-K+-ATPase activity,and explore the mechanism of mitochondrial pathways of apoptosis in neuron injury of rats with kainite acid(KA)-induced epilepsy.Methods KA-induced epilepsy model was induced by injection of KA into the hippocampus.Forty SD rats were randomly divided into 2 groups: control group(n=8)and KA group(6 h,1 d,3 d,7 d,n=8).The concentration of Glu in hippocampus CA3 area was detected by high performance liquid chromatography.The apoptosis of hippocampus neurons and the concentration of Ca2+ were assayed by flow cytometry.The mitochondrial membrane potential was detected by JC-1.The Na+-K+-ATPase activity was examined.Results 1.The concentration of Glu in hippocampus increased at 3 d after KA injection and reached the peak after 7 d injection.2.The concentration of Ca2+ level,mitochondrial membrane potential,and the number of apoptosis neurons were significantly increased,wherase the mitochondrial membrane potential decreased after 6 h of KA injection,7 d after KA injection,and the changes were more severe.3.In the hippocampus,the activities of the Na+-K+-ATPase significantly decreased at 1 d after KA injection,and they decreased more over at 7 d after KA injection.4.The levels of ATP,mitochondrial membrane potential,and the activity of the Na+-K+-ATPase were negatively correlated with the neuron apoptosis(Pa

Protein kinases are intimately involved in the pathogenesis of many diseases such as cancer, inflammation, and autoimmune and neurological diseases. Therefore, kinases have been widely studied as drug targets over the past three decades. As of April, 2020, the FDA had approved 59 small molecule kinase inhibitors (SMKIs) in the emerging field of targeted drug therapy. This paper focuses on the biochemistry and pharmacology of these 59 SMKIs and 121 SMKIs for which structures can be retrieved and that are now in phase Ⅱ and Ⅲ clinical trials. In addition, this paper also conducts a simple analysis of several popular targets and their inhibitors.

italic>γ-Aminobutyric acid (GABA) is a crucial inhibitory neurotransmitter found in various cells in the human body. While the GABAergic system is typically associated with the nervous system, recent research has revealed that immune cells and tumor cells also express components of this system. In the tumor microenvironment (TME), GABA is secreted to act extracellularly on other cells. GABA is metabolized via the GABA shunt and is involved in the tricarboxylic acid (TCA) cycle by generating succinate, which can provide energy for tumor cells. Activation of GABA receptors (GABARs) is a major pathway through which GABA participates in the regulation of antitumor immune responses. The activation of GABA type A receptors (GABA_ARs) can inhibit the activation and proliferation of T cells, elicit anti-inflammatory macrophages, and promote tumor cell growth and migration, while activation of GABA type B receptors (GABA_BRs) is generally considered to inhibit cancer cell migration and induce cancer cell apoptosis. In general, receptor activation inhibits immune cells, but the effect on tumor cells varies. Additionally, the downregulation of the expression levels of GABA transporters (GATs) is involved in tumor progression. Although antagonists of GABA metabolism and drugs that act on GABA receptors are considered therapeutic drugs for tumors, there have been few clinical studies conducted on them.

Objective To investigate the difference between the blood pressure readings between sitting and supine position,and to study the factors that associated with the sitting-supine blood pressure difference in patient with diabetes.Methods We measured the sitting blood pressure first then followed by the supine pressure in 356 diabetic patients,using a standard mercury sphygmomanometer.Patient's body weight,height and blood glucose levels were also measured.Results SBP and DBP were significantly higher in the supine position than in sitting position in diabetic patients(by 3.5?7.6/1.5?4.9 mm Hg,P

OBJECTIVETo compare the effect and impact of holmium laser enucleation of the prostate (HoLEP) and 120-W thulium: YAG vapoenucleation of the prostate (ThuVEP) on erectile function in the treatment of benign prostatic hyperplasia (BPH).

METHODSWe retrospectively analyzed 93 cases of symptomatic BPH treated by HoLEP or 120 W ThuVEP. We made comparisons between the two groups of patients in the baseline and postoperative clinical and surgical indexes as well as their IPSS, quality of life (QOL), maximum flow rate (Qmax), postvoid residual urine volume (PVR), and IIEF-EF scores before surgery and during the 12-month follow-up.

RESULTSThuVEP, in comparison with HoLEP, achieved a significantly shorter operation time ([57.6 +/- 12. 8] vs. [70.4 +/- 21.8] min, P = 0.001) and a higher laser efficiency ([0.71 +/- 0.18] vs. [0.62 +/- 0.19] g/min, P = 0. 021). At 1, 6, or 12 months of follow-up, no significant differences were observed in IPSS, OOL, Omax, and PVR between the two groups (P > 0.05). Both the HoLEP and ThuVEP groups showed low incidences of complications and remarkably improved IIEF-EF scores at 12 months postoperatively, but with no significant differences (both P > 0.05). However, in those with relatively normal erectile functions before operation, the mean IIEF-EF score was reduced from 22.8 +/- 2.2 preoperatively to 21.0 +/- 2.7 after HoLEP, (P = 0.036).

CONCLUSIONBoth HoLEP and 120W ThuVEP are effective and safe in the treatment of BPH. Compared with HoLEP, 120 W ThuVEP has even a higher laser efficiency. However, neither can significantly improve erectile function, and HoLEP may have a short-term negative impact on the relatively normal erectile function of the patient.

Aged ; Holmium ; Humans ; Laser Therapy ; adverse effects ; methods ; Lasers, Solid-State ; therapeutic use ; Male ; Middle Aged ; Penile Erection ; Prostatectomy ; adverse effects ; methods ; Prostatic Hyperplasia ; surgery ; Quality of Life ; Retrospective Studies ; Thulium ; Transurethral Resection of Prostate ; Treatment Outcome ; Urine

Objective To study the effect of antiapoptosis factors PED/PEA-15 and XIAP on prostate cancer cells(PC-3)apoptosis.Methods The expressions of XIAP and PED/PEA-15 in prostate cancer cells(PC-3)were respectively assayed using the RT-PCR technique.XIAP and PED/ PEA-15 specific siRNA vectors were designed and constructed and then were transiently cotransfected into PC-3 cells under induction of liposome.The effects of siRNA vectors on PED/PEA-15 and XIAP transcription were assayed by RT-PCR technique,and the effect of XIAP and PED/PEA-15 on cancer cell apoptosis were determined by flow cytometry and microscope observation.Results PED/PEA- 15 and XIAP were both highly expressed in PC-3 cells.Enzyme digestion analysis and DNA sequencing confirmed that the PED/PEA-15 and XIAP-specific siRNA expression vectors were constructed successfully.The designed siRNA sequences of PED/PEA-15 and XIAP could specifically inhibit their transcription.The PC-3 cells which were cotransfected with PED/PEA-15 and XIAP- specific siRNA vectors were more sensitive to doxorubicin.The apoptosis rate of cotransfected cells was significantly increased.Conclusions PED/PEA-15 and XIAP might be involved in the development of prostate cancer.

OBJECTIVE: To investigate the effect of NBI assisted white light transurethral resection of bladder tumor (TURBT) in the treatment of bladder urothelial carcinoma and to summarize the experience of narrow band imaging (NBI) operation. METHODS: Patients with bladder urothelial carcinoma were selected, and TURBT was performed after anesthesia. First of all, the bladder tumor was found and resected under white light. Then we replaced with NBI, looked for suspicious lesions and resected them, The specimens excised under white light and NBI were collected separately. The number, location and pathological results of the lesions under white light were recorded, and the residual lesions under NBI were also recorded. To evaluate the effect of NBI, the ratio of residual bladder tumor was calculated. The cases were divided into three groups according to the time sequence. The clinical data of each group were collected and the learning curve of TURBT under NBI assisted white light was observed. RESULTS: A prospective study of 45 patients with bladder tumor from April 2018 to January 2020, including 32 males and 13 females, aged from 23 to 89 years, with an average age of 65.2 years. All the operations were successfully completed, without obvious complications after operation. Nine cases were single and 36 cases were multiple. The maximum diameter of the tumors was 0.5 to 4.0 cm, with an average of 2.2 cm. The histopathology of the resected tissue under white light was urothelial carcinoma, and 19 cases (42.2%) were pathologically positive by NBI resection. The 45 cases were divided into three groups according to the time sequence, 15 cases in each group. The true positive rate of NBI was 33.3%, 46.7% and 46.7%, respectively, and the false positive rate was 60.0%, 46.7% and 26.7%, respectively in the three groups. CONCLUSION TURBT is an effective way to treat bladder urothelial cancer, NBI is an effective supplement of white light, which can increase the detection rate of bladder cancer and reduce post-operative recurrence. The NBI light source has a certain learning curve. With the increase of cases, the false-positive rate of NBI is gradually reduced. After the NBI operator has rich experience, the recognition degree of flat tumor is gradually improved under white light, and the residual rate of NBI is reduced after the removal under white light.
Adult ; Aged ; Aged, 80 and over ; Cystoscopy ; Female ; Humans ; Male ; Middle Aged ; Narrow Band Imaging ; Neoplasm Recurrence, Local ; Prospective Studies ; Self-Control ; Urinary Bladder Neoplasms/surgery* ; Young Adult

Objective To evaluate dendritic cell vaccine immunotherapy in postoperative colorectal cancer patients. Methods 40 colorectal cancer patients were divided into two groups. Group A was not treated with the dendritic cell vaccine after chemotherapy, Group B was treated with four courses of autologous dendritic cell vaccine. The level of cytokines was tested before and after the therapy in both groups. DTH were tested after the last course of treatment. Results The levels of cytokines significantly increased in group B after vaccination compared with that in group B before vaccination and that in group A.8 patients were DTH positive in 15 patients that were tested after the vaccination. The PTS (progression-free survival) was 22 months in group B compared with 17 months in group A. The recurrence of the disease was not observed in patients with DTH positive. Conclusion DC vaccine in postoperative colorectal cancer patients improves the immune status and elicits tumor-specific response.

Objective:To observe the clinical efficacy of auricular point sticking at different points to relieve the pain in arteriovenous fistula puncture. Methods: A total of 42 patients with arteriovenous fistula were randomized into a Shenmen (TF4) group and an Elbow (SF3) group by the random number table method, with 21 cases in each group. After enrolled into different groups, before the dialysis, patients were given auricular point sticking with Wang Bu Liu Xing ( Semen Vaccariae) seeds at Shenmen (TF4) and Elbow (SF3), respectively. Patients were asked to press the seeds themselves for 2 min each time, four times a day, and an additional 5-15 min before the arteriovenous fistula puncture. Intensive pressing was offered during the puncture, 15-20 presses for each time, and the plasters were changed every 2-3 d. The numerical rating scale (NRS) was used to score the pain level one week before and after auricular point sticking. The NRS score was then compared and analyzed. Results: The intra-group comparison showed that the changes of NRS score in both groups were statistically significant after auricular point sticking (both P＜0.05). After the treatment, there was no significant difference in NRS score between the two groups (P＞0.05). Conclusion: Auricular point sticking at Shenmen (TF4) or Elbow (SF3) can effectively relieve the pain of arteriovenous fistula puncture, and these two points have equivalent analgesic effect.

Response Surface Methodology was applied to optimize the culture components for lipopeptide production by Bacillus natto TK-1. In the first step, two level factorial design of Plackett-Burman was used to evaluate the influence of six related factors. It showed that three factors playing the important roles in the medium, including peptone, yeast extract powder and CaCl_2. The path of steepest ascent was used to approach the optimal region of the fermentation conditions subsequently. In the third step, the concentrations of those three main factors were further optimized by using Box-Behnken and Response Surface Analysis. By solving the quadratic regression model equation, the optimal concentrations of the variables were determined as: peptone 1.73%, yeast extract powder 0.063 %, CaCl_2 1.385?10-4mol/L. Under the optimal culture conditions, the diameter of haemolysis zone increased 29.3 % than before. HPLC analysis showed the precise production of lipopeptide was 30.2% higher than preliminary culture. Furthermore, at three batches cultivation, the experiment values under the optimal conditions agreed with the predictive values. It showed that Response Surface Methodology was proper and a good choice for optimization.