ADC189 is a novel drug of cap-dependent endonuclease inhibitor. In our study, its antiviral efficacy was evaluated in vitro and in vivo, and compared with baloxavir marboxil and oseltamivir. A first-in-human phase I study in healthy volunteers included single ascending dose (SAD) and food effect (FE) parts. In the preclinical study, ADC189 showed potent antiviral activity against various types of influenza viruses, including H1N1, H3N2, influenza B virus, and highly pathogenic avian influenza, comparable to baloxavir marboxil. Additionally, ADC189 exhibited much better antiviral efficacy than oseltamivir in H1N1 infected mice. In the phase I study, ADC189 was rapidly metabolized to ADC189-I07, and its exposure increased proportionally with the dose. The terminal elimination half-life (T_1/2) ranged from 76.69 to 98.28 hours. Of note, food had no effect on the concentration, clearance, and exposure of ADC189. It was well tolerated, with few treatment-emergent adverse events (TEAEs) reported and no serious adverse events (SAEs). ADC189 demonstrated excellent antiviral efficacy both in vitro and in vivo. It was safe, well-tolerated, and had favorable pharmacokinetic characteristics in healthy volunteers, supporting its potential for single oral dosing in clinical practice.
Humans ; Antiviral Agents/therapeutic use* ; Animals ; Male ; Adult ; Mice ; Female ; Endonucleases/antagonists & inhibitors* ; Influenza, Human/drug therapy* ; Young Adult ; Dibenzothiepins/pharmacology* ; Oseltamivir/pharmacology* ; Middle Aged ; Triazines/pharmacology* ; Thiepins/pharmacology* ; Influenza B virus/drug effects* ; Influenza A Virus, H1N1 Subtype/drug effects* ; Pyridines/pharmacology* ; Morpholines ; Pyridones

Chemotherapy-induced nausea and vomiting (CINV) is common in patients receiving moderately or highly emetogenic chemotherapy and is caused by the activation of peripheral and central nervous system pathways, with the neurokinin-1 receptor playing a central role in delayed CINV. Neurokinin-1 receptor antagonists (NK1RAs) in combination with other antiemetic agents are recommended in international and Chinese guidelines for the prevention of acute and delayed CINV. Therefore, a summary of current data for NK1RAs would be of great clinical utility. This article summarizes the available clinical and real-world data on the use of NK1RAs in CINV prophylaxis, with a focus on evidence from China, where three NK1RAs, aprepitant, fosaprepitant and netupitant, are currently approved. NK1RAs have demonstrated efficacy and favorable safety in the prevention of acute and delayed CINV. Further research is required to determine the optimal use of these drugs and to identify strategies for CINV management in specific patient populations.
Humans ; Vomiting/prevention & control* ; Neurokinin-1 Receptor Antagonists/therapeutic use* ; Nausea/prevention & control* ; Antiemetics/therapeutic use* ; Antineoplastic Agents/adverse effects* ; Aprepitant/therapeutic use* ; Morpholines/therapeutic use*

This study aims to investigate the efficacy, safety, and cost-effecctiveness of Qizhi Weitong Granules in the treatment of functional dyspepsia. Specifically, two commonly used clinical protocols for the treatment of functional dyspepsia were selected: Qizhi Weitong Granules+Mosapride vs Mosapride alone(control). Meta-analysis of previous clinical studies was performed to examine the efficacy and safety, and pharmacoeconomic evaluation was carried out according to the results of the Meta-analysis. The cost-effectiveness analysis was carried out to elucidated the incremental cost-effectiveness ratio(ICER), and the sensitivity was analyzed with tornado dia-gram and Monte Carlo simulation. The willingness-to-pay threshold of patients for functional dyspepsia was investigated and compared with the ICER to evaluate whether Qizhi Weitong Granules was cost-effective. The result showed that the effective rate of Qizhi Weitong Granules combined with Mosapride in the treatment of functional dyspepsia was 95.49%, which was higher than that of Mosapride alone(73.30%)(OR=8.52, 95%CI[4.36, 16.64])(P<0.000 1). The two groups showed no significant difference in safety. The price of Qizhi Weitong Granules+Mosapride was higher than that of Mosapride alone. The ICER was 640.29 CNY, 1 506.67 CNY lower than the willingness-to-pay threshold. The sensitivity analysis showed that the analysis results were relatively stable. Thus, Qizhi Weitong Granules+Mosapride is safe, effective, and economical in the treatment of functional dyspepsia, which should be further promoted in clinical settings.
Benzamides ; Cost-Benefit Analysis ; Dyspepsia/drug therapy* ; Economics, Pharmaceutical ; Gastrointestinal Agents/therapeutic use* ; Humans ; Morpholines ; Treatment Outcome

BACKGROUNDNonanesthetic colonoscopy is popular in clinical practice in China. However, intestinal spasms often result in a prolonged examination time, increased operating difficulties, decreased polyp detection rate, and failure to complete the procedure clinically. Therefore, exploring alternative approaches that can reduce the pain in patients during colonoscopy is of utmost importance, and finding the optimal preoperative administration to improve the quality of nonanesthetic colonoscopy is also necessary. This study aimed to investigate the effects of the prophylactic administration of pinaverium bromide before colonoscopy and the effects of pinaverium bromide alone at different time points or combined with scopolamine butylbromide.

METHODSA randomized controlled trial was performed on a cohort of 1000 patients who underwent colonoscopy in outpatient clinic of Wuhan Union Hospital. The patients were randomly assigned to the following groups: Group A, given oral pinaverium bromide (100 mg, three times a day) one day before examination combined with intramuscular injection of scopolamine butylbromide (20 mg) 10 min before colonoscopy; Group B0, given pinaverium bromide alone on the day of colonoscopy (100 mg, three times a day); Group B1, given pinaverium bromide alone (100 mg, three times a day) one day before colonoscopy; Group B2, given pinaverium bromide alone (100 mg, three times a day) two days before colonoscopy; and Group C, given scopolamine butylbromide alone (20 mg) before colonoscopy. The successful rate of colonoscopy, procedure time, degree of abdominal pain, and polyp detection rate were recorded and compared among all groups.

RESULTSThe successful rate of colonoscopy in Group B1(82.0%) and Group B2(83.0%) was significantly higher than that in Group B0(62.0%, all P < 0.01). The time to reach the ileocecal region in Group B1and Group B2were lower than those in Group B0(all P < 0.05). However, no significant differences were observed in polyp detection rate between Group B1(24.0%) or Group B2(26.0%), and Group B0(22.4%, all P > 0.05). Furthermore, there were no significant differences in the various parameters examined between Group B1and Group B2(P > 0.05). The successful rate of colonoscopy in Group A (92.0%) was significantly higher than that in Group B1(82.0%) and Group C (80.0%; both P < 0.05). Moreover, the time for the colonoscope to reach the ileocecal region in Group A were markedly shorter as compared to those in Group B1 and Group C (P < 0.05). The polyp detection rate in Group A was 32.0%, significantly higher than that in Group B1(24.0%, P < 0.05) and Group C (24.2%, P < 0.05).

CONCLUSIONAdministration of pinaverium bromide alone one day before examination was beneficial to relieve symptoms of abdominal pain during nonanesthetic colonoscopy. In addition, therapeutic effects were improved when pinaverium bromide administration was combined with intramuscular injection of scopolamine butylbromide. Therefore, the combined use of pinaverium bromide with scopolamine butylbromide might have great application value to improve the quality of nonanesthetic colonoscopy in the preoperative preparation.

Abdominal Pain ; prevention & control ; Adult ; Colonoscopy ; methods ; Double-Blind Method ; Female ; Humans ; Male ; Middle Aged ; Morpholines ; administration & dosage ; therapeutic use ; Preoperative Period

Advanced prostate cancer, especially at the castration-resistant stage, remains incurable clinically and, therefore, urgently requires new therapeutics for the patients. PI3K is a family of critical cell signal transduction molecules and their over-activation is an important factor in cancer development and progression. It has been demonstrated that class IA PI3K p110 is drastically overexpressed in prostate cancer and involved in androgen receptor-mediated gene expression and castration-resistant progression and regarded as a potential therapeutic target for prostate cancer. Several p110-specific inhibitors have been reported recently and two of them, GSK2636771 and AZD8186, are being tested in clinical trials.
Aniline Compounds ; therapeutic use ; Chromones ; therapeutic use ; Humans ; Imidazoles ; therapeutic use ; Male ; Morpholines ; therapeutic use ; Neoplasm Proteins ; antagonists & inhibitors ; Phosphatidylinositol 3-Kinases ; metabolism ; Phosphoinositide-3 Kinase Inhibitors ; Prostatic Neoplasms, Castration-Resistant ; drug therapy ; enzymology ; Protein Kinase Inhibitors ; therapeutic use

Cancer stem cells (CSCs) have tumor initiation, self-renewal, metastasis and chemo-resistance properties in various tumors including colorectal cancer. Targeting of CSCs may be essential to prevent relapse of tumors after chemotherapy. Phosphatidylinositol-3-kinase (PI3K) and mammalian target of rapamycin (mTOR) signals are central regulators of cell growth, proliferation, differentiation, and apoptosis. These pathways are related to colorectal tumorigenesis. This study focused on PI3K and mTOR pathways by inhibition which initiate differentiation of SW620 derived CSCs and investigated its effect on tumor progression. By using rapamycin, LY294002, and NVP-BEZ235, respectively, PI3K and mTOR signals were blocked independently or dually in colorectal CSCs. Colorectal CSCs gained their differentiation property and lost their stemness properties most significantly in dual-blocked CSCs. After treated with anti-cancer drug (paclitaxel) on the differentiated CSCs cell viability, self-renewal ability and differentiation status were analyzed. As a result dual-blocking group has most enhanced sensitivity for anti-cancer drug. Xenograft tumorigenesis assay by using immunodeficiency mice also shows that dual-inhibited group more effectively increased drug sensitivity and suppressed tumor growth compared to single-inhibited groups. Therefore it could have potent anti-cancer effects that dual-blocking of PI3K and mTOR induces differentiation and improves chemotherapeutic effects on SW620 human colorectal CSCs.
AC133 Antigen/genetics/metabolism ; Animals ; Antineoplastic Agents/pharmacology/therapeutic use ; Cell Differentiation/*drug effects ; Cell Line, Tumor ; Cell Survival/drug effects ; Chromones/pharmacology/therapeutic use ; Colorectal Neoplasms/drug therapy/metabolism/pathology ; Humans ; Imidazoles/pharmacology/therapeutic use ; Male ; Mice ; Mice, Inbred BALB C ; Mice, Nude ; Morpholines/pharmacology/therapeutic use ; Neoplastic Stem Cells/cytology/drug effects/metabolism ; Paclitaxel/pharmacology/therapeutic use ; Phosphatidylinositol 3-Kinases/*antagonists & inhibitors/metabolism ; Quinolines/pharmacology/therapeutic use ; SOXB1 Transcription Factors/genetics/metabolism ; Signal Transduction/*drug effects ; Sirolimus/pharmacology/therapeutic use ; TOR Serine-Threonine Kinases/*antagonists & inhibitors/metabolism ; Xenograft Model Antitumor Assays

OBJECTIVE: To explore the relevance between nasal symptoms and laryngopharyngeal reflux disease in patients with allergic rhinitis. METHOD: Thirty patients of laryngopharyngeal reflux disease were diagnosed in ENT outpatient department in our hospital. All patients have symptoms of sneeze, nasal discharge as chief complaint and they responded no effect for other normal treatment for nasal-sinusitis at least three months. Orally before meals, a dose of 5 mg Mosapride citrate each time, three times a day for 7 days. Orally before meals, a dose of 20 mg Esomeprazole each time, two times a. day for 2-3 months. Nasal spray, one spray of azelastine hydrochloride once, two times a day for 2 month. RESULT: Laryngopharyngeal reflux symptom scores at four time points (the first visit, post treatment 15 days, 45 days, 75 days) were analyzed by repeated measures analysis of variance. There is a significant difference in four time points. CONCLUSION Laryngopharyngeal reflux disease has a strong association with allergic rhinitis. Patients who has allergic rhinitis nasal symptoms as chief complaint must be exclude, the laryngopharyngeal reflux disease first.
Benzamides ; therapeutic use ; Esomeprazole ; therapeutic use ; Humans ; Laryngopharyngeal Reflux ; complications ; drug therapy ; Morpholines ; therapeutic use ; Phthalazines ; therapeutic use ; Pilot Projects ; Rhinitis, Allergic ; drug therapy ; etiology

OBJECTIVETo explore clinical short and long-term effect of combining dalitong granule (DG) and electroacupuncture group (EA) in the treatment of functional dyspepsia.

METHODSTotally 640 patients with confirmed functional dyspepsia were randomly divided into 4 groups using a randomized digital table: the DG group, the EA group, the combined group and the control group, 160 cases in each group. The DG group was treated with 6 g DG 3 times daily; the EA group was treated with puncture of points Zusanli (ST36), Zhongwan (CV12), Neiguan (PC6), Taichong (LR3) and Gongsun (SP4) twice daily; the combined group with above-mentioned DG and EA; and the control group with 5 mg mosapride 3 times, 20 mg pantoprazole and 25 mg amitriptylines twice daily. The treatment course was 4 weeks for all groups. The symptom score, quality of life score by Short Form 36 Health Survey Questionnaires (SF-36), plasma motilin by radioimmunoassay, electrogastrographic frequencies by electrogastrogram (EGG) and gastric emptying by B-sonography were examined, and adverse reactions were observed before, at the end of treatment and 60 weeks post-treatment.

RESULTSIn the DG group 1 case dropped out for not taking medicine strictly and 1 case was lost to follow-up, while 1 case in the EA group and 2 cases in the combined therapy group were lost to follow-up. Compared with pre-treatment, quality of life score, plasma motilin, electrogastrographic frequencies and gastric emptying were all increased significantly, while symptom score was decreased significantly at the end of treatment in each group (P<0.01); in the combined group quality of life score, plasma motilin, electrogastrographic frequencies and gastric emptying were all significantly higher than those in the other groups, while symptom score was significantly lower than in the other groups (P<0.05). Compared with at the end of treatment, these indices changed insignificantly in the combined group and the EA group 60 weeks post-treatment (P>0.05), but the 4 increased indices were all decreased significantly, and symptom score was increased significantly in the DG and the control groups (P>0.05). The short and long-term total effective rates in the combined group were all significantly higher than those in the other treatment groups (P<0.05 or P<0.01). No serious adverse reaction occurred in the four groups.

CONCLUSIONCombined treatment of DG and EA could increase both plasma motilin and electrogastrographic frequencies, promote gastric emptying, alleviate the symptom of dyspepsia so as to increase quality of life, with better safety and long-term effect.

Adult ; Amitriptyline ; administration & dosage ; Benzamides ; administration & dosage ; Combined Modality Therapy ; Drugs, Chinese Herbal ; administration & dosage ; therapeutic use ; Dyspepsia ; therapy ; Electroacupuncture ; Electrophysiology ; Female ; Gastric Emptying ; drug effects ; Gastrointestinal Agents ; administration & dosage ; Humans ; Male ; Morpholines ; administration & dosage ; Motilin ; blood ; Quality of Life ; Radioimmunoassay ; Sound Spectrography ; Stomach ; diagnostic imaging ; Ultrasonography

OBJECTIVETo evaluate the efficacy and safety of wuling Capsule combined with Pinaverium Bromide in treatment of irritable bowel syndrome (IBS).

METHODSSixty-four IBS patients were randomized into two groups, the treatment group and the control group, 32 in each group. Patients in the treatment group took wuling Capsule (0. 33 g/capsule, 3 times per day) and Pinaverium Bromide (50 mg/tablet, one tablet each time, 3 times per day) , while those in the control group only took Pinaverium Bromide (50 mg/tablet, one tablet each time, 3 times per day). The therapeutic course for all was 6 weeks. IBS symptom score questionnaire, IBS-Quality of Life (IBS-QOL) , Self-Rating Depression Scale (SDS) , and Self-Rating Anxiety Scale (SAS) were assessed before and after treatment. Adverse reactions were also observed.

RESULTSThe improvement of abdominal pain, stool frequency, and stool properties, as well as changing rates of integrals were significantly higher in the treatment group than in the control group (P <0. 05). The improvement of dysphoria, body image, concerns for health, and dietary restriction of IBS-QOL, as well as changing rates of integrals were significantly higher in the treatment group than in the control group (P <0. 05). The improvement of SDS and SAS, as well as changing rates of integrals were significantly higher in the treatment group than in the control group (P <0. 05). No severe adverse reaction occurred in either group.

CONCLUSIONCombination therapy of wuling Capsule and Pinaverium Bromide could improve abdominal pain and defecation, attenuate depression and anxiety of IBS patients with higher safety.

Anxiety ; Anxiety Disorders ; Biomedical Research ; Capsules ; Defecation ; Depression ; Depressive Disorder ; Drugs, Chinese Herbal ; therapeutic use ; Humans ; Irritable Bowel Syndrome ; drug therapy ; Morpholines ; therapeutic use ; Quality of Life ; Surveys and Questionnaires

OBJECTIVETo evaluate the efficacy and safety of Yigan Fupi Decoction (YFD) in the treatment of irritable bowel syndrome with diarrhea (IBS-D) patients.

METHODSA randomized controlled clinical trail was carried out in patients with IBS-D. All patients were randomly assigned to the treatment group (58 cases, treated with YFD) and the control group (58 cases, treated with Pinaverium Bromide Tablet). The treatment course was 4 weeks for all patients. The total effective rate, the stool property and state, the quality of life (QOL), and TCM syndrome efficacy were assessed by IBS bowel symptom severity scale (IBS-BSS), IBS defecation state questionnaire (IBS-DSQ), IBS quality of life questionnaire (IBS-QOL), and traditional Chinese medicine pattern curative effect scoring system (TCM-PES) before and after treatment.

RESULTSThere was no statistical difference in the total effective rate between the two groups (82.76% vs. 77.59%, P > 0.05). The treatment group was superior in the total IBS-BSS integral to the control group (P < 0.05). The total effective rate of improving the stool property was better in the treatment group than in the control group (81.03% vs. 72.41%, P < 0.05). Besides, the number of days for emergent defecation among 10 days was less in the treatment group than in the control group (P < 0.05). The improvement of the total IBS-QOL integral and the total integral of TCM syndrome were better in the treatment group than in the control group (P < 0.01). The total effective rate of TCM-PES was better in the treatment group than in the control group (84.48% vs. 70.69%, P < 0.05).

CONCLUSIONYFD was effective in the treatment of IBS-D patients of Gan-qi invading Pi syndrome, and could effectively relieve bowel symptoms, improve the stool property and the defecation frequency, elevate their QOL, and attenuate Gan-qi invading Pi syndrome with favorable safety and compliance.

Adult ; Diarrhea ; drug therapy ; Drugs, Chinese Herbal ; therapeutic use ; Female ; Humans ; Irritable Bowel Syndrome ; drug therapy ; Male ; Middle Aged ; Morpholines ; therapeutic use ; Quality of Life ; Treatment Outcome