Objective To evaluate the efficacy and safety of brexpiprazole in treating acute schizophrenia.Methods Patients with schizophrenia were randomly divided into treatment group and control group.The treatment group was given brexpiprozole 2-4 mg·d-1 orally and the control group was given aripiprazole 10-20 mg·d-1orally,both were treated for 6 weeks.Clinical efficacy of the two groups,the response rate at endpoint,the changes from baseline to endpoint of Positive and Negative Syndrome Scale(PANSS),Clinical Global Impression-Improvement(CGI-S),Personal and Social Performance scale(PSP),PANSS Positive syndrome subscale,PANSS negative syndrome subscale were compared.The incidence of treatment-related adverse events in two groups were compared.Results There were 184 patients in treatment group and 186 patients in control group.After treatment,the response rates of treatment group and control group were 79.50％(140 cases/184 cases)and 82.40％(150 cases/186 cases),the scores of CGI-I of treatment group and control group were(2.00±1.20)and(1.90±1.01),with no significant difference(all P＞0.05).From baseline to Week 6,the mean change of PANSS total score wese(-30.70±16.96)points in treatment group and(-32.20±17.00)points in control group,with no significant difference(P＞0.05).The changes of CGI-S scores in treatment group and control group were(-2.00±1.27)and(-1.90±1.22)points,PSP scores were(18.80±14.77)and(19.20±14.55)points,PANSS positive syndrome scores were(-10.30±5.93)and(-10.80±5.81)points,PANSS negative syndrome scores were(-6.80±5.98)and(-7.30±5.15)points,with no significant difference(P＞0.05).There was no significant difference in the incidence of treatment-related adverse events between the two group(69.00％vs.64.50％,P＞0.05).Conclusion The non-inferiority of Brexpiprazole to aripiprazole was established,with comparable efficacy and acceptability.

OBJECTIVE: To observe the safety of donor NK cell infusions in the settings of hematopoietic stem cell transplantation and after consolidation chemotherapy in elderly patients with acute myeloid leukemia (AML). METHODS: Forty patients with AML were included, in which 21 patients aged over 60 years were at the stage of complete remission (CR) and 19 patients that received allogeneic hematopoietic stem cell transplantation (allo-HSCT). Mononucleated cells were isolated from peripheral blood from the donors (for allo-HSCT) or healthy immediate family members (elderly AML). The cells were seeded into the flasks pre-coated with NK cell specific activators, and expanded in media containing recombinant human IL-15 and IL-2 for 14 days. The cells were transfused intravenously after the identification of quality control. Trypan blue exclusion test was used for the determination of cell viability and counting. Flow cytometry analysis was performed to assess the surface antigenic profile. Seventy-eight infusions of the cell products were received by the elderly patients with AML after consolidation chemotherapy, 11 infusions were received by the patients during allo-HSCT and 32 infusions 3 moths after transplantation. The safety of cell therapy, body temperature, blood pressure and other indexes were observe during and 48 hours after cell transfusion. Meanwhile, the occurrence and severity of acute graft-versus-host disease (GVHD) were documented. RESULTS: Flow cytometry analysis showed that the proportion of NK cells (CD3^-CD56⁺) in the mononucleated cells before culture was (14.10±4.22)% (n=121), and the proportion increased dramatically up to (87.29±8.75)% (n=121) after culture for 14 days, the number of NK cells increased to 753.47±140.13 times (n=121). The doses of the infused NK cells was (7.58±2.50)×10⁷/kg per infusion. Moderate fever occurred in three cases after multiple infusions, and the temperature restored to normal on the same day after treatment. Fever was observed in one patient after every infusion of four times in total. The temperature reached to 38.5-39.0 ℃ and returned to normal within 1-2 hours after adequate antipyretic treatment, and then there was no discomfort. No GVHD was observed in the elderly AML patients, while 6 cases that received allo-HSCT developed moderate acute GVHD, among them grade I in 5 cases and grade II in 1 case. No other severe toxicities were observed. CONCLUSION NK cell products with a high-purity could be obtained by ex vivo expansion with this protocol. The transfusion of these expanded cells is generally safe in the elderly patients with AML that have received chemotherapy or patients that received hematopoietic stem cell transplantation.
Aged ; Graft vs Host Disease/prevention & control* ; Hematopoietic Stem Cell Transplantation ; Humans ; Killer Cells, Natural ; Leukemia, Myeloid, Acute/therapy* ; Middle Aged ; Recurrence

Consistency in quality of traditional Chinese medicine granules is an important factor to ensure reproducible clinical efficacy. In this study rhubarb dispensing granules were utilized to construct an efficacious near-infrared spectroscopy (eNIRS) assay by combining NIRS and biopotency. A NIR method for assaying rhubarb dispensing particles was established, and information on different batches was collected. The diarrhea-inducing biopotency of rhubarb dispensing granules was determined based on a constipation model induced by diphenoxylate in mice. The animal protocol was approved by the Animal Ethic Committee​ of 302 Hospital of Chinese PLA People's Liberation Army (ID: IACUC-2019-0010). Ten anthraquinones were determined in rhubarb dispensing granules by UPLC. The correlation between NIR and biopotency was analyzed and five characteristic bands that correlated highly with bioactivity were identified, including 4 011-4 390, 4 859-5 461, 7 012-7 493, 10 992-11 312 and 11 871-12 489 cm^-1. There were some differences in the main bands of different chemical constituents. In summary, five active bands based on NIRS were identified and found to be able to achieve rapid on-line detection of rhubarb dispensing granule quality. This research model may also provide reference for quality control of other Chinese medicine dispensing granules.

Objective To evaluate the clinical application and security of percutaneous endoscopic gastrostomy (PEG) with the Introducer method using ultrathin gastroseopy in dysphagia patients. Methods Clinical data of 22 cases dysphagia patients implemented with PEG with the Introducer method using ultrathin gastroseopy or conventional gastroseopy were retrospectively analyzed, the clinical effect and the complication were observed. Results 22 patients underwent PEG with the Introducer method using conventional gastroscopy (6 cases) or ultrathin gastroscopy (16 cases). Among the 16 patients underwent PEG using ultrathin gastroseopy by transnasal or peroral approach, 2 cases with trimus by received radiotherapy for nasopharyngeal cancer and 14 cases with pharyngeal or esophagus narrowing, could not completed PEG by conventional gastroscopy. The average procedure time of PEG was (12.2 ± 2.9) min in conventional gastroscopy group and (11.8 ± 3.2) min in control group. No complications were observed in these patients, but the patients in ultrathin gastroseopy group reported less discomfort associated with the procedure. 17 patients with advanced nasopharyngeal carcinoma and esophagus cancer who received PEG could completely finished 6 cycles of concurrent chemoradiotherapy. Paired-sample t test of nutrition indicators (hemoglobin, albumin and RBC) before and after the treatment showed significant difference (P < 0.05). Conclusion PEG with the introducer method using ultrathin gastroseopy is a safe and effective method of enteral nutrition, Ultrathin gastroscopy reduces the discomfort of the procedure, especially in patients with serious trimus and pharyngeal or esophagus narrowing. For patients with advanced nasopharyngeal carcinoma, preventative PEG improved the tolerance of chemoradiotherapy,reduce the incidence of adverse events.

BACKGROUNDBone morphogenetic protein 9 (BMP9) and Wnt/β-catenin signaling pathways are able to induce osteogenic differentiation of mesenchymal stem cells (MSCs), but the role of Wnt/β-catenin signaling pathway in BMP9-induced osteogenic differentiation is not well understood. Thus, our experiment was undertaken to investigate the interaction between BMP9 and Wnt/β-catenin pathway in inducing osteogenic differentiation of MSCs.

METHODSC3H10T1/2 cells were infected with recombinant adenovirus expressing BMP9, Wnt3a, and BMP9+Wnt3a. ALP, the early osteogenic marker, was detected by quantitative and staining assay. Later osteogenic marker, mineral calcium deposition, was determined by Alizarin Red S staining. The expression of osteopotin (OPN), osteocalcin (OC), and Runx2 was analyzed by Real time PCR and Western blotting. In vivo animal experiment was carried out to further confirm the role of Wnt3a in ectopic bone formation induced by BMP9.

RESULTSThe results showed that Wnt3a enhanced the ALP activity induced by BMP9 and increased the expressions of OC and OPN, with increase of mineral calcium deposition in vitro and ectopic bone formation in vivo. Furthermore, we also found that Wnt3a increased the level of Runx2, an important nuclear transcription factor of BMP9.

CONCLUSIONCanonical Wnt/β-catenin signal pathway may play an important role in BMP9-induced osteogenic differentiation of MSCs, and Runx2 may be a linkage between the two signal pathways.

Blotting, Western ; Cell Differentiation ; genetics ; physiology ; Core Binding Factor Alpha 1 Subunit ; genetics ; metabolism ; Growth Differentiation Factor 2 ; genetics ; metabolism ; Humans ; Osteocalcin ; genetics ; metabolism ; Osteogenesis ; genetics ; physiology ; Wnt3A Protein ; genetics ; metabolism

OBJECTIVETo observe the clinical efficacy of penyan pill (PP) in treating ureaplasma urealyticum (UU) infection patients of qi deficiency blood stasis syndrome (QDBSS).

METHODSTotally 188 UU infection patients of QDBSS were randomly assigned to two groups, the treatment group and the control group. Patients in the treatment group were treated with PP (10 g each time, thrice daily, 14 consecutive days as one therapeutic course), while those in the control group took azithromycin (10 g each day, 7 consecutive days as one therapeutic course). They were continually treated for 3 therapeutic courses. The clinical symptom integrals were observed in the two groups before and after treatment. The short-term efficacy was judged. Their recurrence rates were followed-up to assess their long-term efficacies.

RESULTSThe total effective rate of the comprehensive efficacy in the treatment group was 91.4%, while it was 79. 3%in the control group, showing no statistical difference between the two groups (P > 0.05). Better effects were obtained in improving Chinese medical clinical symptoms in the treatment group (P <0.01). There was no statistical difference in the negative conversion rate between the two groups after treatment (P >0. 05). There was statistical difference in the recurrence rate between the two groups (12. 82% vs 54.76%,P <0. 05).

CONCLUSIONSPP showed equivalent effects in treating UU infection patients of QDBSS to those of azithromycin. But PP showed obvious advantages over azithromycin in improving Chinese medical syndromes.

Adult ; Azithromycin ; therapeutic use ; Drugs, Chinese Herbal ; therapeutic use ; Female ; Humans ; Medicine, Chinese Traditional ; Middle Aged ; Phytotherapy ; Ureaplasma Infections ; diagnosis ; drug therapy ; Ureaplasma urealyticum

BACKGROUNDThe preclinical experiments and studies of congener drugs show icotinib, a new epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor, can specifically bind to the tyrosine kinase domain of the EGFR, block the EGFR related signal, thereby inhibit the growth of tumor cell. The objective of this study was to investigate the safety, tolerability and dose-related biologic effects of icotinib in patients with non-small cell lung cancer (NSCLC) in a Chinese patient population.

METHODSThis was an open-label, phase I, dose escalation, safety/tolerability trial of oral icotinib (100 to 400 mg), administered twice per day for 28-continuous-day cycles until disease progression or undue toxicity.

RESULTSForty patients with stage IIIB (15%) or IV (85%) NSCLC were included in the study. They had mainly adenocarcinoma (85%), with a performance status (PS) of 0 (45%) or 1 (55%) and less than half the patients (45%) had histories of smoking and all were pretreated by at least one regimen of chemotherapy. Patients were assigned to three dose levels of 150 mg b.i.d, 200 mg b.i.d, or 125 mg t.i.d. The follow-up periods ranged from 5 to 80 weeks. Adverse events were found in 35% patients, most of which were mild and reversible. The adverse events mainly occurred in the first 4 weeks and included rash (25%), diarrhea, nausea and abdominal distention. One definite interstitial lung disease (ILD) was found in a patient in the dose of 200 mg b.i.d. According to an 8-week assessment, one (2.5%) patient receiving 150 mg gained complete response (CR) that persisted for 44 weeks, seven (17.50%) patients had partial remission (PR), and 18 (45%) patients had stable disease (SD). The objective response including CR + PR was 20%. The median time of progression-free survival for the 40 patients was 20 weeks (range: 12 to 32 weeks). The response was not affected by pathological type, history of smoking, or numbers of previous therapeutic regimens. No relationship between dose, response, adverse effect, or duration of the study was observed.

CONCLUSIONSIcotinib, given as oral twice daily, showed favorable safety and tolerability. Mild and reversible rash, diarrhea, and nausea were the main adverse events. Antitumor activity was obvious at each dose in heavily pretreated patients. Pharmacodynamic evaluations and further phase II/III trials are in progress.

Aged ; Aged, 80 and over ; Antineoplastic Agents ; therapeutic use ; Carcinoma, Non-Small-Cell Lung ; drug therapy ; mortality ; pathology ; Crown Ethers ; therapeutic use ; Disease-Free Survival ; Female ; Humans ; Male ; Middle Aged ; Quinazolines ; therapeutic use ; Receptor, Epidermal Growth Factor ; antagonists & inhibitors

OBJECTIVETo investigate a novel immunotherapy through immobilization of streptavidin-tagged hTNF-alpha on the biotinylated mucosal surface of the bladder wall for bladder cancer treatment in mice.

METHODSA total of 120 female C57BL/6j mice were randomized into 5 equal groups, namely blank control, PBS, soluble hTNF-alpha, SA-GFP, and SA-hTNF-alpha treatment groups. Twenty-four hours after establishment of a mouse model of orthotopic superficial bladder cancer, SA-hTNF-alpha fusion protein was immobilized on the biotinylated mucosal surface of the bladder wall, which was repeated every 4 days for a total of 6 sessions. Immunohistochemistry was performed to detect the retention time of SA-hTNF-alpha fusion protein in the biotinylated mouse bladder mucosa and the distribution of CD4(+) and CD8(+) lymphocytes in the mucosa and tumor tissues, with the tumor growth and mouse survival also observed. The cytotoxiciy of the tumor-specific lymphocytes was evaluated. The mice responding well to the treatment were re-challenged by MB49 and monitored for survival.

RESULTSSA-hTNF-alpha could be efficiently and stably immobilized on the bladder mucosal surface for as long as 7 days. On day 60 after MB49 implantation, 18 out of 22 SA- hTNF-alpha-treated mice survived, with 9 appearing tumor-free, but all the mice in PBS control group died. Five out of 9 tumor-free mice in SA-hTNF-alpha group showed resistance to a re-challenge with intravesical MB49. The numbers of CD4(+) and CD8(+) lymphocytes were significantly greater in SA-hTNF-alpha group than in the other groups (P<0.05). The cytotoxicity of the tumor-specific lymphocytes was significantly stronger in SA-hTNF-alpha group than in the other groups (P<0.05).

CONCLUSIONSA-hTNF-alpha immobilized on the biotinylated mucosal surface of the bladder wall can significantly inhibit the tumor growth and promote the survival of the mice bearing orthotopic superficial bladder cancer.

Administration, Intravesical ; Animals ; Biotinylation ; Carcinoma, Transitional Cell ; immunology ; therapy ; Female ; Immobilized Proteins ; therapeutic use ; Immunotherapy ; methods ; Mice ; Mice, Inbred C57BL ; Recombinant Fusion Proteins ; metabolism ; therapeutic use ; Streptavidin ; metabolism ; therapeutic use ; Tumor Necrosis Factor-alpha ; metabolism ; therapeutic use ; Urinary Bladder Neoplasms ; immunology ; therapy

BACKGROUNDThe Pringle maneuver, which has been the standard for hepatic resection surgery for a long time, has the major flaw of ischemic damage in the liver. The aim of this research was to evaluate hepatic blood inflow occlusion with/without hemihepatic artery control vs. the Pringle maneuver in hepatocellular carcinoma (HCC) resection.

METHODSTwo hundred and eighty-one cases of resection of HCC with hepatic blood inflow occlusion (with/without hemihepatic artery control) and the Pringle maneuver from January 2006 to December 2008 in our hospital were analyzed and compared retrospectively; among them 107 were in group I (Pringle maneuver), 98 in group II (hepatic blood inflow occlusion), and 76 in group III (hepatic blood inflow occlusion without hemihepatic artery control). The operation time, intraoperative blood loss, postoperative liver function and complications were used as the endpoints for evaluation.

RESULTSThe operative duration and intraoperative blood loss of three groups showed no significant difference; alanine aminotransferase, total bilirubin and incidence of postoperative complications were significantly lower in groups II and III postoperation than those in group I.

CONCLUSIONHepatic blood inflow occlusion without hemihepatic artery control is safe, convenient and feasible for resection of HCC, especially for cases involving underlying diseases such as cirrhosis.

Adult ; Aged ; Carcinoma, Hepatocellular ; surgery ; Female ; Hepatectomy ; methods ; Humans ; Liver ; blood supply ; Liver Neoplasms ; surgery ; Male ; Middle Aged ; Retrospective Studies ; Young Adult