Objective To observe the effects of Yiqi Huoxue Tuodu Prescription on Keap1Nrf2/HO-1 signaling pathway in rats with chronic nonbacterial prostatitis(CNP);To explore its mechanism for the treatment of CNP.Methods CNP rat model was prepared using castration combined with estrogen induction method.Totally 48 SD rats were divided into blank group,model group,celecoxib group and Yiqi Huoxue Tuodu Prescription group according to the random number table method,with 12 rats in each group.In the celecoxib group,celecoxib suspension was instilled 0.035 g/kg,and in the Yiqi Huoxue Tuodu Prescription group,Yiqi Huoxue Tuodu Prescription water decoction was instilled 8.64 g/kg,and the blank group and the model group were instilled with equal volume of normal saline for 28 days.Mechanical pain threshold in rats was measured using Von Frey fiber optic pain gauge,HE staining was used to observe pathological changes in prostate tissue and pathological scoring,the content of reactive oxygen species(ROS)in prostate tissue were detected by chemical fluorescence method and the glutathione peroxidase(GSH-Px)activity and malondialdehyde(MDA)content in prostate tissue were detected by colorimetric method,Western blot was used to detect the expressions of Kelch like ECH related protein 1(Keap1),nuclear factor E2 related factor 2(Nrf2),and heme oxygenase-1(HO-1)protein in prostate tissue.Results Compared with the blank group,rats in the model group had significantly lower mechanical pain threshold and significantly decreased prostate index(P<0.01);the size of the glandular cavity in prostate tissue varied,with the disappearance of secretions in the cavity,interstitial looseness and edema,a large amount of fibrous tissue hyperplasia and inflammatory cell infiltration,and a significant increase in pathological scores(P<0.01);the contents of ROS and MDA in prostate tissue significantly increased,the activity of GSH-Px significantly decreased(P<0.01),the expression of Keap1 and Nrf2 proteins significantly decreased,and the expression of HO-1 protein significantly increased(P<0.01,P<0.05).Compared with the model group,the mechanical pain threshold of the rats in the Yiqi Huoxue Tuodu Prescription group was significantly higher(P<0.01);there was mild damage to prostate tissue,with a small amount of fibrous hyperplasia and inflammatory cell infiltration,and a significant decrease in pathological scores(P<0.01,P<0.05);the contents of ROS and MDA in prostate tissue significantly decreased,and the GSH-Px activity significantly increased(P<0.01),the Keap1 and Nrf2 protein expressions significantly increased and HO-1 protein expression significantly decreased in prostate tissue(P<0.01,P<0.05).Conclusion Yiqi Huoxue Tuodu Prescription can effectively improve the histopathological morphology and increase the pain threshold of the prostate gland in CNP rats,and its mechanism of action may be related to the regulation of Keap1/Nrf2/HO-1 signaling pathway and reduction of oxidative stress damage in prostate tissue of rats.

Glioblastoma (GBM) is the most common and aggressive malignant brain tumor in adults and is poorly controlled. Previous studies have shown that both macrophages and angiogenesis play significant roles in GBM progression, and co-targeting of CSF1R and VEGFR is likely to be an effective strategy for GBM treatment. Therefore, this study developed a novel and selective inhibitor of CSF1R and VEGFR, SYHA1813, possessing potent antitumor activity against GBM. SYHA1813 inhibited VEGFR and CSF1R kinase activities with high potency and selectivity and thus blocked the cell viability of HUVECs and macrophages and exhibited anti-angiogenetic effects both in vitro and in vivo. SYHA1813 also displayed potent in vivo antitumor activity against GBM in immune-competent and immune-deficient mouse models, including temozolomide (TMZ) insensitive tumors. Notably, SYHA1813 could penetrate the blood-brain barrier (BBB) and prolong the survival time of mice bearing intracranial GBM xenografts. Moreover, SYHA1813 treatment resulted in a synergistic antitumor efficacy in combination with the PD-1 antibody. As a clinical proof of concept, SYHA1813 achieved confirmed responses in patients with recurrent GBM in an ongoing first-in-human phase I trial. The data of this study support the rationale for an ongoing phase I clinical study (ChiCTR2100045380).

Objective:To explore the feasibility of early oral nutrition for gastric cancer patients after total gastrectomy based on propensity score matching.Methods:Using convenience sampling method, a retrospective analysis was conducted on the medical records of 755 patients who underwent total gastrectomy for gastric cancer at Jiangsu Subei People's Hospital from 2012 to 2020. A total of 454 patients who received early oral nutrition after surgery were included in the study group, while 301 patients who received conventional nutrition were included in the control group. The study group patients began eating orally on the first day after surgery, while the control group patients began eating orally after anal exhaust. The propensity score matching method was used to balance confounding factors between two groups.Results:A total of 203 pairs (406 cases) of patients were matched. After matching, there was no statistically significant difference in general data between the two groups ( P>0.05). The study group had lower dietary intake time, first anal exhaust time, hospital stay, incidence of abdominal infection, and incidence of anastomotic fistula compared to the control group, with statistically significant differences ( P<0.05) . Conclusions:Early oral nutrition for gastric cancer patients after total gastrectomy can promote intestinal function recovery, shorten hospital stay, and do not increase the risk of complications, including anastomotic fistula. It has the same acceptable tolerance as conventional nutrition, indicating that early oral nutrition after total gastrectomy is safe and feasible.

Objective: To investigate the effect of blocking the B7/CD28 pathway on rheumatoid arthritis mice and its possible mechanism. Methods: 40 DBA/1 mice were randomly divided into normal control group, model group, CTLA4-Ig low-dose group and cytotoxic T lymphocyte antigen-4 immunolobulin(CTLA4-Ig) high-dose group. Except for the normal control group, the other three groups were prepared for rheumatoid arthritis models. At 0, 5 and 10 days after the second immunization, the CTLA4-Ig low-dose group and CTLA4-Ig high-dose group were intraperitoneally injected with 50 mg/kg and 100 mg/kg CTLA4-Ig, respectively, the normal control group and the model group were injected with the same amount of saline. Vernier calipers were used to measure the thickness of the ipsilateral hindfoot of the mouse for arthritis score; the serum levels of tumor necrosis factor-α(TNF-α), interleukin-1β(IL-1β), interleukin-6(IL-6) and interleukin-17(IL-17) were detected by ELISA, images were acquired and bone tissue morphometric parameters were measured through Micro-CT scanning, HE staining observed the pathological changes of the knee joint, TRAP staining detected osteoclasts in knee joint tissues, real-time fluorescent quantitative PCR and Western blot detected osteoprotegerin(OPG), receptor activator of NF-κB(RANK), receptor activator of NF-κB ligand(RANKL) mRNA and protein expression, immunohistochemical staining detected nuclear factor κB(NF-κB) expression. Western blot was used to detect the expression of related proteins in the NF-κB signaling pathway. Results: Compared with the model group, after high-dose CTLA4-Ig treatment, RA mouse foot swelling and arthritis scores were reduced, the levels of TNF-α, IL-1β, IL-6 and IL-17 in serum were reduced, the knee joint damage was significantly reduced, bone mineral density(BMD), trabecular thickness(Tb.Th), bonevolume(BV) and bone volume fraction(BV/TV) increased, the number of TRAP positive cells decreased, the relative expression of OPG mRNA and protein in the tissue was up-regulated, while the relative expression of RANK, RANKL mRNA and protein were down-regulated. At the same time, the relative expression of p-p65 and p-IκBα protein decreased, the positive expression area of NF-κB decreased, and the difference were statistically significant(P<0.01); After CTLA4-Ig low-dose treatment, the serum levels of TNF-α, IL-1β, IL-6 and IL-17 in RA mice were significantly lower than those in the model group, and the area of NF-κB positive expression in the tissue was reduced, the difference were statistically significant(P<0.01). Conclusion CTLA4-Ig to block the B7/CD28 pathway has a significant therapeutic effect on mouse rheumatoid arthritis, which can inhibit the inflammatory response, reduce bone destruction and prevent the activation of the NF-κB signaling pathway.

Objective:To observe the effect of Lingshao-Zaoren Decoction on urodynamics and the expression of Piezo1 if overactive bladder (OAB) rats. Methods:Thirty SPF grade female SD rats were randomly divided into blank group, model group, Tolterodine control group, low-dose and high-dose Lingshao-Zaoren Decoction groups, with 6 rats in each group. The OAB rats were modeled by intraperitoneal injection of Cyclophosphamide. After the successful modeling, Tolterodine control group was given 0.36 mg/kg Tolterodine tartrate, the low-dose and high-dose Lingshao-Zaoren Decoction groups were given 1.59 and 3.18 g/kg Lingshao-Zaoren Mianjian granules by gavage, the blank group and model group were given the same amount of distilled water, once a day for 14 days. After 14 days, the urodynamics of rats in each group were detected. The bladder volume and maximum bladder pressure were observed respectively. The pathological changes of bladder tissue were observed by HE staining. The expression of Piezo1 protein in bladder tissue was detected by immunohistochemistry and Western blot. The expression of Piezo1 mRNA in bladder tissue was detected by qPCR. Results:Compared with the blank group, the body weight, bladder volume and maximum bladder pressure of the model group were significantly reduced ( P<0.01). HE staining result showed that the model group had hyperplasia of urinary tract epithelium, degeneration, necrosis and abscission of epithelial cells, infiltration of a large number of inflammatory cells in stroma, vascular proliferation, thickening of vascular wall, hyperplasia of mucosal smooth muscle, disorder of arrangement, and significant up regulation of Piezo1 protein expression ( P<0.01). Compared with the model group, the weight [(244.83 ± 6.05) g, (233.33 ± 11.76) g vs. (219.00 ± 9.70) g] of rats in the Tolterodine control group and high-dose group of Lingshao-Zaoren Decoction significantly increased ( P<0.01), and the bladder volume [(0.93 ± 0.31) ml, (1.17 ± 0.17) ml, (1.21 ± 0.23) ml vs. (0.50 ± 0.16) ml] and maximum bladder pressure [(42.00 ± 3.03) cmH 2O, (45.83 ± 7.19) cmH 2O, (46.83 ± 8.23) cmH 2O vs. (30.50 ± 5.47) cmH 2O] of rats in the Tolterodine control group, low-dose and high-dose Lingshao-Zaoren Decoction groups were significantly increased ( P<0.01); the bladder epithelial hyperplasia and degeneration degree, interstitial inflammatory cell infiltration degree and vascular hyperplasia degree of rats in the Tolterodine control group, low-dose and high-dose Lingshao-Zaoren Decoction groups significantly increased. The expression of Piezo1 mRNA (1.50 ± 0.04, 2.05 ± 0.08, 1.44 ± 0.10 vs. 2.56 ± 0.11) and protein in the Tolterodine control group, low-dose and high-dose Lingshao-Zaoren Decoction groups were significantly decreased ( P<0.01). Conclusion:Lingshao-Zaoren Decoction can increase the bladder volume and maximum bladder pressure of urinary incontinence caused by detrusor overactivity in rats with overactive bladder, which may be related to reduction of Piezo1 expression.

Objective:To investigate the infection status of Yersinia in the main host animals of plague in Xiahe and Luqu counties, the Himalayan marmot plague foci of Gansu Province, and to provide a basis for exploring the epidemic status of plague in these foci. Methods:Samples of the ileocecal region and contents, pharyngeal swabs (or tongue roots), and blood of the main host animals of plague in Xiahe County and Luqu County where the plague were active in the 1950s and 1960s were collected from 2014 to 2018. The Yersinia isolation, virulence determination and F1 antibody detection were performed, respectively. Results:Totally 24 strains of Yersinia were detected in 958 samples of ileocecal region and contents with a bacterial detection rate of 2.51%, which were 13 strains of Yersinia enterocolitia (Y.e), 1 strain of Yersinia kristensenii (Y.k), 2 strains of Yersinia frederiksenii/ intermedia (Y.f/i), 6 strains of Yersinia intermedia (Y.i), 1 strain of Yersinia aldouae (Y.a) and 1 strain of Yersinia massiliensis (Y.m). Totally 19 strains of Yersinia were detected in 958 samples of pharyngeal swabs (or tongue roots), and the detection rate was 1.98%, which were 8 strains of Y.e, 1 strain of Yersinia pseudotuberculosis (Y.p), 4 strains of Y.k, 1 strain of Y.f/i, 4 strains of Y.i, and 1 strain of Yersinia ruckeri (Y.r). The virulence types of 21 strains of Y.e were ail -ystA -ystB +yadA -virF -rfbc -, ail -ystA -ystB -yadA -virF -rfbc -, respectively, accounting for 9.52% (2/21) and 90.48% (19/21), none were pathogenic. The results of F1 antibody in 1 079 serum samples were all negative. Conclusions:Yersinia are widely found in the pharynx and intestines of the main host animals of plague in Xiahe and Luqu counties, and the Y.e detected are all non-pathogenic strains. The results of this investigation can provide clues for further study on the preservation of Yersinia pestis in host animals and their living environment.

Objective: To evaluate the efficacy of Fufang-Xuanju capsule combined with levofloxacin mesylate tablets in the treatment of chronic epididymitis. Methods: A total of 76 patients in the Urology Department of Xiyuan Hospital of China Academy of Chinese Medical Sciences who met the inclusion criteria from December 2016 to February 2019, were divided into treatment group (43 cases) and control group (33 cases). The control group was given levofloxacin mesylate tablets orally. The treatment group was given Fufang-Xuanju capsule based on the control group. Both groups were treated for 4 weeks. Chronic epididymitis symptom index (CESI) was used to evaluate the clinical efficacy by pain score and quality of life score. Results: The total effective rate was 83.7% (36/43) in the treatment group and 63.6% (26/33) in the control group. There was statistically significant difference between the two groups (χ²=4.020, P=0.045). Compared with baseline, the pain scores, quality of life scores and total scores of both groups at 2, 4 weeks after treatment were significantly lower (P<0.01). Two weeks after the treatment, the pain scores, quality of life scores and total scores in the treatment group were significantly lower than those of the control group (F value were 16.132, 9.134 and 23.681, respectively, all Ps<0.01). And 4 weeks after the treatment, the pain scores, quality of life scores and total scores of the treatment group were significantly lower than that of the control group (F value were 28.741, 74.049, 72.483, respectively, all Ps<0.01). Conclusions Fufang-Xuanju capsule combined with levofloxacin mesylate tablets can alleviate the pain of patients with chronic epididymitis, improve the quality of life and improve the clinical efficacy.

Objective To investigate the influence of single agent and combined medication chemotherapy on elderly patients with gastric cancer. Methods One hundred and twenty elderly inpatients with gastric cancer in the general surgery department of the Nanyang Municipal Central Hospital from January 2009 to October 2014 were divided into the single agent chemotherapy group (n=60) and combined medication chemotherapy group(n=60). The adverse reactions and survival time were compared between the two groups. Results The occurrence rates of nausea, vomiting, diarrhea, constipation, leukopenia, oral mucositis and peripheral neuropathy in the single agent group were lower than those in the combined chemotherapy group, the difference between the two groups was statistically significant (P<0.05) ; the occurrence rates of Hb decrease, thrombocytopenia and transaminase elevation in the single agent group were lower than those in the combined chemotherapy group,but the difference was not statistically significant(P>0. 05);the survival time in the combined chemotherapy group was longer than that in the single agent chemotherapy group,but the difference between them was not statistically significant(P>0.05). Conclusion Single agent chemotherapy may be considered as the first-line chemotherapy scheme for elderly patients with gastric cancer.

Objective To investigate the impact of neoadjuvant chemotherapy on surgery and prognosis in patients with stage Ⅲ gastric cancer.Methods The 90 cases staging Ⅲ gastric cancer were randomly divided into neoadjuvant chemotherapy group and surgery group.Both surgical complications and prognosis were compared.Results The overall effective rate of neoadjuvant chemotherapy was 53％ (24/45),disease control rate of neoadjuvant chemotherapy was 91％ (41/45).Blood loss (t =4.102,P =0.037),local adhesions surgery (x2 =19.756,P =0.000),local tissue necrosis (x2 =13.512,P =0.000),tissue fragility (x2 =12.870,P =0.000) number of cases found in neoadjuvant chemotherapy group were higher than surgery group,and the data were statistically significant.There were no statistically significance between two groups about operation time (t =2.391,P =0.129),tissue congestion (x2 =0.865,P =0.352),postoperative bleeding(x2 =0.720,P =0.396),postoperative fistula (x2 =1.047,P =0.306).The survival time of neoadjuvant chemotherapy group was longer than surgery group,but it was not statistically significant(t =1.086,P =0.372).Conclusions Neoadjuvant chemotherapy could reduce the stage of the gastric cancer and increase the complexity of surgery.Thus preoperative evaluation should be prepared before the surgery.

This study was aimed to observe the effect ofJian-Zhong-Li-Lao(JZLL) decoction-mediated serum on the TGF-β1-induced proliferation of HBZY-1 cells, the expression of matrix metalloproteinases and its inhibitory enzyme, in order to investigate the mechanisms of JZLL decoction in treatment of the renal fibrosis of chronic renal failure. HBZY-1 cells were culturedin vitro. JZLL decoction-mediated serum was prepared. The experiment contained the blank control group, TGF-β1-induced group, control serum group, low-dose JZLL decoction group, high-dose JZLL decoction group, and theNiao-Du-Qinggroup. The cytotoxic effects of JZLL decoction-mediated serum on HBZY-1 cells were assessed by LDH assay. The morphology and proliferation of HBZY-1 cells were examined by CCK8 assay. The expression of matrix metalloproteinases (MMP-2, MMP-9) and its inhibitory enzymes (TIMP-1, TIMP-2) were examined by ELISA assay. The results showed that there was no cytotoxic effect of JZLL decoction-mediated serum on HBZY-1 cells (P > 0.05). Compared with the model group, JZLL decoction can obviously inhibit TGF-β1-induced proliferation of HBZY-1 cells (P < 0.05). JZLL decoction can obviously increase the expressions of MMP-2 and MMP-9 (P < 0.05), and inhibit the expressions of TIMP-1 and TIMP-2 (P < 0.05). It was concluded that JZLL decoction-mediated serum significantly inhibited TGF-β1-induced proliferation of HBZY-1 cells, relieved the renal fibrosis of chronic renal failure through affecting the expression of matrix metalloproteinases and its inhibitory enzymes.