Objective To investigate the efficacy and safety of Chinese herbal compound modified Huanglian Wendan Decoction in the treatment of hypertension complicated with sleep disorders of phlegm-heat harassing the interior type.Methods A total of 70 patients with hypertension complicated with sleep disorders of phlegm-heat harassing the interior type were randomly divided into a control group and an observation group,35 cases in each group.The patients in the control group were treated with conventional western medicine,and the patients in the observation group were treated with modified Huanglian Wendan Decoction on the basis of treatment for the control group.The course of treatment covered four weeks.The Clinical Global Impression(CGI)score,traditional Chinese medicine(TCM)syndrome score,Pittsburgh Sleep Quality Index(PSQI)score,blood pressure,and serum levels of homocysteine(Hey),interleukin 6(IL-6),interleukin 10(IL-10)and interleukin 8(IL-8)levels in the two groups were observed before and after treatment.Moreover,the safety of medication was evaluated in the two groups.Results(1)After four weeks of treatment,the CGI score of the observation group was(1.63±0.60)points,which was significantly lower than that of the control group[(2.74±0.82)points],and the difference was statistically significant(P＜0.01).(2)After treatment,the TCM syndrome score,systolic blood pressure,diastolic blood pressure and PSQI score of the two groups were significantly decreased compared with those before treatment(P＜0.01),and the decrease of TCM syndrome score,systolic blood pressure,diastolic blood pressure and PSQI score in the observation group was significantly superior to that in the control group(P＜0.05 or P＜0.01).(3)After treatment,the levels of serum Hcy,IL-6 and IL-8 in the two groups were significantly decreased compared with those before treatment(P＜0.01),and the serum IL-10 level was significantly increased compared with that before treatment(P＜0.01).The decrease of serum Hcy,IL-6 and IL-8 levels and the increase of serum IL-10 level in the observation group were significantly superior to those in the control group(P＜0.01).(4)During the treatment,no treatment-related adverse reactions or complications occurred in the two groups.Conclusion Modified Huanglian Wendan Decoction has certain efficacy on patients with hypertension complicated with sleep disorders of phlegm-heat harassing the interior type.The decoction can not only reduce the blood pressure and serum Hcy level of the patients,but also regulate the level of inflammatory factors with high safety.

Fusobacterium nucleatum (F. nucleatum) is an early pathogenic colonizer in periodontitis, but the host response to infection with this pathogen remains unclear. In this study, we built an F. nucleatum infectious model with human periodontal ligament stem cells (PDLSCs) and showed that F. nucleatum could inhibit proliferation, and facilitate apoptosis, ferroptosis, and inflammatory cytokine production in a dose-dependent manner. The F. nucleatum adhesin FadA acted as a proinflammatory virulence factor and increased the expression of interleukin(IL)-1β, IL-6 and IL-8. Further study showed that FadA could bind with PEBP1 to activate the Raf1-MAPK and IKK-NF-κB signaling pathways. Time-course RNA-sequencing analyses showed the cascade of gene activation process in PDLSCs with increasing durations of F. nucleatum infection. NFκB1 and NFκB2 upregulated after 3 h of F. nucleatum-infection, and the inflammatory-related genes in the NF-κB signaling pathway were serially elevated with time. Using computational drug repositioning analysis, we predicted and validated that two potential drugs (piperlongumine and fisetin) could attenuate the negative effects of F. nucleatum-infection. Collectively, this study unveils the potential pathogenic mechanisms of F. nucleatum and the host inflammatory response at the early stage of F. nucleatum infection.
Humans ; Fusobacterium nucleatum/metabolism* ; NF-kappa B/metabolism* ; Periodontal Ligament/metabolism* ; Signal Transduction ; Fusobacterium Infections/pathology* ; Stem Cells/metabolism*

Objective: To investigate the efficacy and safety of liver venous deprivation (LVD) before secondary resection of primary liver cancer. Methods: 56 patients with advanced primary liver cancer who were not suitable for primary resection in Liver Surgery Department of Xinxiang Central Hospital from January 2018 to January 2019 were analyzed retrospectively. They were divided into liver vein deprivation group (LVD group: LVD+ PVE, n=26) and portal vein embolization group (PVE group, n=30). The dynamic changes of liver reserve function and future liver remnant volume (FLR-V), R0 resection rate, surgical complications, postoperative recurrence rate and overall survival rate of two groups before and after LVD/PVE were compared. Results: The success rate of puncture and embolization in LVD group and PVE group was 100%. There were no grade Ⅳ complications, and there was no significant difference of grades Ⅰ, Ⅱ and Ⅲ complications between the groups (P=0.808). The FLR-V of LVD group before embolization, 7, 14 and 21 days after embolization was (493.1±25.8), (673.2±56.1), (779.5±81.6) and (853.3±85.2) cm(3), respectively. The FLR-V of PVE group before embolization, 7, 14 and 21 days after embolization were (502.4±20.1), (688.6±43.9), (656.8±73.7) and (563.5±69.1) cm(3), respectively. There was no significant difference in FLR-V between the two groups before and 7 days after embolization (P>0.05). The FLR-V of LVD group was higher than that of PVE group at 14 and 21 days after embolization (P<0.01). The preparation time of LVD group was (20.4±6.3) days, which was shorter than that of PVE group [(31.5±8.8) days, P=0.045]. The rate of secondary hepatectomy was 92.3% (24/26), which was higher than that of PVE group [70.0% (21/30), P=0.036]. The R0 resection rate was 87.5% (21/24), which was higher than that of the PVE group [57.1% (12/21), P=0.022]. However, there were no significant differences in surgical methods, operation time, intraoperative blood loss, Clavien-Dindo complication grade and length of hospital stay between the two groups (P>0.05). After hepatectomy, the median recurrence time and median survival time of LVD group were 12.6 months and 21.3 months, respectively, which were longer than those of PVE group (9.4 months and 13.5 months, respectively, P<0.01). Conclusions: For patients with advanced liver cancer who are not suitable for primary hepatectomy, preoperative LVD can significantly increase FLR-V, improve the resection rate of secondary surgery, shorten the preparation time of two operations, and do not increase surgical complications. Moreover, patients with LVD can improve the R0 resection rate of secondary surgery. The postoperative recurrence time and overall survival rate of patients with LVD are better than those of patients with PVE, and LVD has a good long-term effect.
Humans ; Portal Vein ; Retrospective Studies ; Hepatectomy/methods* ; Liver/surgery* ; Liver Neoplasms/surgery* ; Embolization, Therapeutic/methods* ; Treatment Outcome

Aim To explore the characteristics and mechanism of resveratrol(Res)in promoting apoptosisof T lymphocytes and to investigate the therapeutic effect of Res on experimental autoimmune encephalomyelitis(EAE)in mice. Methods Annexin V/PI double staining was used to investigate the effect of Res on the apoptosis of mouse primary naïve T lymphocytes and anti-CD3/anti-CD28 activated T lymphocytes. Activation-induced cell death models were established on CD4+ T lymphocytes and Jurkat cells in vitro,and the effect of Res on activation-induced cell death was detected by PI single staining or Annexin V/PI double staining. The expression of apoptosis related proteins were detected by Western blot. EAE model in mice was induced by MOG35-55,and the therapeutic effect of Res administration was investigated. The apoptosis of CD4+ T lymphocytes from vehicle group and Res group was detected. Results Res did not affect the survival of naïve T cells,but promoted the apoptosis of activated T lymphocytes. With the increase of Res concentration,activation-induced cell death of CD4+ T cells and Jurkat cells significantly increased,and the cleavage of apoptosis related proteins PARP and Caspase-3 increased. In addition,Res delayed the onset of EAE,reduced the clinical score,and decreased the infiltration of inflammatory cells in spinal cord. The CD4+ T lymphocytes from the mice with Res administration were more sensitive to activation-induced cell death. Conclusion Res promotes activation-induced cell death of T lymphocytes and ameliorates EAE in mice.

BACKGROUND: Bendamustine was approved in China on May 26th, 2019 by the National Medical Product Administration for the treatment of indolent B-cell non-Hodgkin lymphoma (NHL). The current study was the registration trial and the first reported evaluation of the efficacy, safety, and pharmacokinetics of bendamustine in Chinese adult patients with indolent B-cell NHL following relapse after chemotherapy and rituximab treatment. METHODS: This was a prospective, multicenter, open-label, single-arm, phase 3 study (NCT01596621; C18083/3076) with a 2-year follow-up period. Eligible patients received bendamustine hydrochloride 120 mg/m2 infused intravenously on days 1 and 2 of each 21-day treatment cycle for at least six planned cycles (and up to eight cycles). The primary endpoint was the overall response rate (ORR); and secondary endpoints were duration of response (DoR), progression-free survival (PFS), safety, and pharmacokinetics. Patients were classified according to their best overall response after initiation of therapy. Proportions of patients in each response category (complete response [CR], partial response [PR], stable disease, or progressive disease) were summarized along with a two-sided binomial exact 95% confidence intervals (CIs) for the ORR. RESULTS: A total of 102 patients were enrolled from 20 centers between August 6th, 2012, and June 18th, 2015. At the time of the primary analysis, the ORR was 73% (95% CI: 63%-81%) per Independent Review Committee (IRC) including 19% CR and 54% PR. With the follow-up period, the median DoR was 16.2 months by IRC and 13.4 months by investigator assessment; the median PFS was 18.6 months and 15.3 months, respectively. The most common non-hematologic adverse events (AEs) were gastrointestinal toxicity, pyrexia, and rash. Grade 3/4 neutropenia was reported in 76% of patients. Serious AEs were reported in 29 patients and five patients died during the study. Pharmacokinetic analysis indicated that the characteristics of bendamustine and its metabolites M3 and M4 were generally consistent with those reported for other ethnicities. CONCLUSION: Bendamustine is an active and effective therapy in Chinese patients with relapsed, indolent B-cell NHL, with a comparable risk/benefit relationship to that reported in North American patients. CLINICAL TRIAL REGISTRATION ClinicalTrials.gov, No. NCT01596621; https://clinicaltrials.gov/ct2/show/NCT01596621.
Adult ; Antineoplastic Combined Chemotherapy Protocols ; Bendamustine Hydrochloride/therapeutic use* ; China ; Humans ; Lymphoma, Non-Hodgkin/drug therapy* ; Neoplasm Recurrence, Local/drug therapy* ; Prospective Studies ; Rituximab/therapeutic use*

Objective:To investigate the effect of the production process of Zushima Guanjie Zhitong Gao from solvent method to hot-pressed method on in vitro kinetic behavior of this preparation. Method:Solvent and hot-pressed methods were used to prepare three batches of samples above pilot scale， and in vitro release and percutaneous penetration of the index components （7，8-dihydroxycoumarin and methyl salicylate） in Zushima Guanjie Zhitong Gao were investigated by modified Franz diffusing cells. Result:The contents of 7，8-dihydroxycoumarin and methyl salicylate in Zushima Guanjie Zhitong Gao prepared by solvent method were 73.72， 494.67 μg/patch， and their contents in hot-pressed method samples were 159.21， 2 638.99 μg/patch， respectively. In the solvent method samples， the average cumulative release amounts of 7，8-dihydroxycoumarin and methyl salicylate in 24 h were 2.04， 12.21 μg， and their average cumulative release amounts in 24 h of hot-pressed method samples were 2.16， 36.24 μg， respectively. In the solvent method samples， the average cumulative permeation amounts of 7，8-dihydroxycoumarin and methyl salicylate in 24 h were 0.38， 2.79 μg， and they were 0.40， 7.49 μg in hot-pressed method samples. The cumulative release and permeation amounts in 24 h of 7，8-dihydroxycoumarin in the hot-pressed method samples were basically the same as those of the solvent method samples， but the cumulative release and permeation amounts in 24 h of methyl salicylate in the hot-pressed method samples were significantly higher than those of the solvent method samples （P<0.05）. Conclusion:The retention of 7，8-dihydroxycoumarin and methyl salicylate by hot-pressed method is better than that of the solvent method. The process change has no significant effect on the in vitro kinetics of 7，8-dihydroxycoumarin in Zushima Guanjie Zhitong Gao， however， after the change from the solvent method to the hot-pressed method， the methyl salicylate in this preparation has a higher cumulative release and permeation amounts.

Objective:To explore the curative effect of robotic intracorporeal studer orthotopic neobladder (RISON).Methods:The clinical data of 40 patients who underwent RISON in our hospital from April 2018 to March 2020 were analyzed retrospectively, including 39 males and 1 female with an average age of (56.4±9.9)years, an average body mass index of (25.5±3.1) kg/m 2. Four patients received preoperative neoadjuvant chemotherapy. Comorbidity component index score was 0-2 points in 6 cases, 3-5 points in 33 cases, 6-8 points in 1 case. All patients had definite pathological diagnosis for the high grade urothelial carcinoma or recurrent bladder tumors, and the tumor staging forecast within T 2 stage. Biopsy of the posterior urethra and bladder neck revealed negative result of tumor invasion. The patients had normal kidney function and without any clear bowel disease history. All patients underwent robotic radical intracorporeal studer orthotopic neobladders and standard lymphadenectomy. About 30 to 40 cm from terminal ileum was selected as the new bladder neck and 50 cm ileum as neobladder. Restore intestinal continuity with EndoGIA. The intestinal canal was cut off along the offside of mesentery except for proximal 10 cm. After U-shape suture of the new bladder back wall, the new anterior bladder wall was sutured with barbs line further in pulp muscularis. "Wallace" was performed bilateral ureteral anastomosis and closing the proximal end of the anterior wall of the new bladder. Further follow-up results were also collected to evaluate the clinical treatment effect, including pathological results of tumor, bladder capacity, urine control (usage of pads), sexual function, short-term(≤30 d) and long-term(>30 d) complications. Results:All the RISONs were successfully performed without conversion to open operation. Median operation time was 360(300.0, 442.5) min, blood loss was 200(200.0, 337.5) ml, indwelling time of gastric tube was 3(3, 4)d, full tolerance time was 3(3, 5)d, and postoperative hospital stay was 9(8, 10)d. Postoperative pathological results showed 39(97.5%) cases were no more than T 2N 0M 0, 1 case was confirmed T 3aN 0M 0 pathologically, 1 case was positive in surgical margin, 1 case was diagnosed as incidental prostate cancer, 15(12, 20) lymph nodes were dissected and no lymph node metastasis was found. Short-term (within 30 days) complications occurred in 12 patients, including Clavien grade Ⅰ 7 cases, Clavien grade Ⅱ 5 cases. Long-term (out of 30 days) complications occurred in 18 patients, including Clavien grade Ⅰ 10 cases, Clavien grade Ⅱ 7 cases, Clavien grade Ⅲ 1 case. And the follow-up time was 1 to 24 months. The median bladder volume 300 (0, 400)ml of 25 patients who were followed up for more than one year and 1 in 34 female patient developed incontinence. Other 33 patients had continence rate of 93.9% (0 pad) during the day, and needed regular urination at night (1-3 times), with an average of 2 pads. All 11 patients with nerve-sparing achieved satisfactory erectile function after operation, with an average IIEF-6 score of (21.5±2.7). No tumor recurrence or death occurred in all patients during the follow-up period. Conclusions:Robotic intracorporeal studer orthotopic neobladder is a safe and feasible urinary diversion operation. The patients achieved good clinical efficacy in tumor control, bladder volume, daytime and nighttime continence, sexual function recovery.

OBJECTIVE: To explore the mechanisms of angiogenesis in chronic myeloid leukemia (CML) through detecting the levels of angiogenesis-related factors secreted from K562 cells after overexpression and interference of HIF-1α gene in K562 cells. METHODS: The K562 cells were transfected by lentiviruses carried and interfered HIF-1α gene, then the transtected K562 cells with carried and interfered with HIF-1α gene were enrolled in overexpression and interference groups respectively, at the same time the K562 cells transfected by the empty virus were enrolled in control group. The cells were harvested after culture for 72 hours under normoxid condition. The transfection efficient in 3 groups was detected by fluorescence microscopy; the mRNA expression of HIF-1α gene and angiogenesis-related factors was detected by RT-PCR; the concentration of angiogenesis-related factors in the caltured supernatant was detected by ELISA. RESULTS: The optimal MOI of K562 cells transfected with lentivirus was 10 and the transfection efficiency was about 50%. The positive rate of transfection after screening by puromycin was more than 90%. The mRNA expression of ANG-I, ANG-II, TGF-α and VEGF in the interference group was lower than that in the over-expression group, and the TGF-β1 mRNA expression in the interference group was higher than in the over-expression group. The mRNA expression of ANG-I and VEGF in the interference group was lower than that in the control group. TGF-αdid not could be detected, and the culture supernatant concentration of ANG-I and TNF-α in the interference group was lower than in the over-expression group, while the VEGF concentration in the interference group was higher than that in the over-expression group. All of the above-mentioned differences were statistically significant (P＜0.05). CONCLUSION The positive K562 cells transfected with leutivirus have been harvested by screening with puromycin. The HIF-1α mRNA positively regulates the mRNA expression of ANG-1, ANG-2, TGF-α, VEGF in K562 cells, promotes the antocrine ability of ANG-1 and TNF-α, moreover not stimulates the autocrine of TGF-α, the up-regulation of HIF-1α expression can inhibit the expression TGF-β1 in K562 cells and the autocrine of TGF-β1.
Humans ; Hypoxia-Inducible Factor 1, alpha Subunit ; metabolism ; K562 Cells ; RNA, Messenger ; Vascular Endothelial Growth Factor A

Ziziphi Spinosae Semen (ZSS) has been used for treatment of insomnia in China for centuries. To reveal the influence of insomnia on the levels of the neurotransmitters including serotonin (5-HT), glutamic acid (Glu), γ-aminobutyric acid (GABA), noradrenaline (NE) and dopamine (DA), and to study the role of ZSS aqueous extract in the treatment of insomnia, an UPLC-ESI- MS/MS method was developed and validated for simultaneous determination of five neurotransmitters in the rat brain. The brain samples were pretreated by one-step direct protein precipitation with acetonitrile. The analytes were detected in positive mode with multiple reaction monitoring (MRM) and the procedure was completed in less than 10 min. The method showed a good linearity (R > 0.9967) with the other validation parameters were within acceptance range. The results indicated that the concentration of 5-HT, GABA and DA is significantly lower (P < 0.01) in para-chlorophenylalanine (PCPA)-induced insomnia rat model group, while Glu and NE significantly higher than those in control group (P < 0.01). Treatment with ZSS aqueous extract (4 or 8 g·kg·d for seven days) could ameliorate the symptoms of insomnia by significantly changing the levels of the neurotransmitter parameters mentioned above. The data obtained in this study demonstrate that ZSS aqueous extract could ameliorate the symptoms of insomnia by modulating the levels of monoamines and amino acid neurotransmitters in the brain.