The degeneration of monoaminergic system and the reduction of monoamine neurotransmitters(MNTs) are associated with the occurrence of a variety of neuropsychiatric diseases, becoming the key indicators for clinical diagnosis and treatment. Recent studies suggested gut microbiota could influence the occurrence, development, and treatment of neuropsychiatric diseases by directly or indirectly regulating the synthesis and metabolism of MNTs. Rich clinical experience has been accumulated in the amelioration and treatment of neuropsychiatric diseases by traditional Chinese medicines. The traditional oral administration method demonstrates obvious advantages in regulating gut microbiota. It provides a new idea for explaining the pharmacodynamic material basis and mechanism of traditional Chinese medicines in ameliorating neuropsychiatric disease by improving the levels of MNTs via gut microbiota regulation. Focusing on three common neuropsychiatric diseases including Alzheimer's disease, Parkinson's disease, and major depression, we summarized the pathways of gut microbiota in regulating the levels of MNTs and the paradigms of traditional Chinese medicines in ameliorating neuropsychiatric diseases via the "bacteria-gut-brain axis", aiming to provide ideas for the development of drugs and treatment schemes.
Humans ; Administration, Oral ; Alzheimer Disease ; Brain-Gut Axis ; Gastrointestinal Microbiome ; Neurotransmitter Agents

Objective: Systematically summarize the research progress of clinical trials of gastric cancer oncology drugs and the overview of marketed drugs in China from 2012 to 2021, providing data and decision-making evidence for relevant departments. Methods: Based on the registration database of the drug clinical trial registration and information disclosure platform of Food and Drug Administration of China and the data query system of domestic and imported drugs, the information on gastric cancer drug clinical trials, investigational drugs and marketed drugs from January 1, 2012 to December 31, 2021 was analyzed, and the differences between Chinese and foreign enterprises in terms of trial scope, trial phase, treatment lines and drug type, effect and mechanism studies were compared. Results: A total of 114 drug clinical trials related to gastric tumor were registered in China from 2012 to 2021, accounting for 3.7% (114/3 041) of all anticancer drug clinical trials in the same period, the registration number showed a significant growth rate after 2016 and reached its peak with 32 trials in 2020. Among them, 85 (74.6%, 85/114) trials were initiated by Chinese pharmaceutical enterprise. Compared with foreign pharmaceutical enterprise, Chinese pharmaceutical enterprise had higher rates of phase I trials (35.3% vs 6.9%, P=0.001), but the rate of international multicenter trials (11.9% vs 67.9%, P<0.001) was relatively low. There were 76 different drugs involved in relevant clinical trials, of which 65 (85.5%) were targeted drugs. For targeted drugs, HER2 is the most common one (14 types), followed by PD-1 and multi-target VEGER. In the past ten years, 3 of 4 marketed drugs for gastric cancer treatment were domestic and included in the national medical insurance directory. Conclusions: From 2012 to 2021, China has made some progress in drug research and development for gastric carcinoma. However, compared with the serious disease burden, it is still insufficient. Targeted strengthening of research and development of investment in many aspects of gastric cancer drugs, such as new target discovery, matured target excavating, combination drug development and early line therapy promotion, is the key work in the future, especially for domestic companies.
China ; Gastrointestinal Agents/therapeutic use* ; Gastrointestinal Neoplasms ; Humans ; Pharmaceutical Preparations ; United States ; United States Food and Drug Administration

Panax notoginseng saponins (PNS) are the major components of Panax notoginseng, with multiple pharmacological activities but poor oral bioavailability. PNS could be metabolized by gut microbiota in vitro, while the exact role of gut microbiota of PNS metabolism in vivo remains poorly understood. In this study, pseudo germ-free rat models were constructed by using broad-spectrum antibiotics to validate the gut microbiota-mediated transformation of PNS in vivo. Moreover, a high performance liquid chromatography-electrospray ionization tandem mass spectrometry (HPLC-ESI-MS/MS) was developed for quantitative analysis of four metabolites of PNS, including ginsenoside F1 (GF1), ginsenoside Rh2 (GRh2), ginsenoside compound K (GCK) and protopanaxatriol (PPT). The results showed that the four metabolites could be detected in the control rat plasma, while they could not be determined in pseudo germ-free rat plasma. The results implied that PNS could not be biotransformed effectively when gut microbiota was disrupted. In conclusion, gut microbiota plays an important role in biotransformation of PNS into metabolites in vivo.
Animals ; Anti-Bacterial Agents ; pharmacology ; Biotransformation ; Chromatography, High Pressure Liquid ; Feces ; microbiology ; Gastrointestinal Microbiome ; drug effects ; physiology ; Ginsenosides ; blood ; Male ; Panax notoginseng ; chemistry ; Rats, Sprague-Dawley ; Sapogenins ; blood ; Saponins ; administration & dosage ; metabolism ; Tandem Mass Spectrometry

BACKGROUND/AIMS: Gastrointestinal (GI) symptoms may develop when we fail to adapt to various stressors of our daily life. Central oxytocin (OXT) can counteract the biological actions of corticotropin-releasing factor (CRF), and in turn attenuates stress responses. Administration (intracerebroventricular) of OXT significantly antagonized the inhibitory effects of chronic complicated stress (CCS) on GI dysmotility in rats. However, intracerebroventricular administration is an invasive pathway. Intranasal administration can rapidly deliver peptides to the brain avoiding stress response. The effects of intranasal OXT on hypothalamus-pituitary-adrenal axis and GI motility in CCS conditions have not been investigated. METHODS: A CCS rat model was set up, OXT 5, 10, or 20 μg were intranasal administered, 30 minutes prior to stress loading. Central CRF and OXT expression levels were analyzed, serum corticosterone and OXT concentrations were measured, and gastric and colonic motor functions were evaluated by gastric emptying, fecal pellet output, and motility recording system. RESULTS: Rats in CCS condition showed significantly increased CRF expression and corticosterone concentration, which resulted in delayed gastric emptying and increased fecal pellet output, attenuated gastric motility and enhanced colonic motility were also recorded. OXT 10 μg or 20 μg significantly reduced CRF mRNA expression and the corticosterone concentration, OXT 20 μg also helped to restore GI motor dysfunction induced by CCS. CONCLUSION: Intranasal administration of OXT has an anxiolytic effect and attenuates the hypothalamus-pituitary-adrenal axis in response to CCS, and gave effects which helped to restore GI dysmotility, and might be a new approach for the treatment of stress-induced GI motility disorders.
Administration, Intranasal ; Animals ; Anti-Anxiety Agents ; Brain ; Colon ; Corticosterone ; Corticotropin-Releasing Hormone ; Gastric Emptying ; Gastrointestinal Motility ; Models, Animal ; Oxytocin ; Peptides ; Rats ; RNA, Messenger

OBJECTIVETo investigate the factors which may influence the imatinib plasma concentration in Chinese patients with gastrointestinal stromal tumor(GIST), and to illuminate the significance of monitoring imatinib plasma concentration in adjuvant therapy for patients with GIST.

METHODSA cross-sectional study with 60 GIST patients who accepted the imatinib therapy after surgery was conducted. They were respectively administrated in 10 domestic hospitals from December 2014 to April 2016, including The First Affiliated Hospital of Nanjing Medical University(n=28), The Affiliated Hospital of Nantong University(n=9), The Affiliated Hospital of Xuzhou Medical College(n=6), Nanjing Drum Tower Hospital(n=5), The Second Affiliated Hospital of Nanjing Medical University (n=2), Jingling Hospital (n=2), The Second People's Hospital of Lianyungang(n=2), Shandong Provincial Hospital(n=2), Jiangsu Province Tumor Hospital(n=2), and The First Affiliated Hospital of Zhejiang University(n=2). Some specific time points for collecting blood sample before and after taking imatinib were determined, then liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was used for monitoring imatinib plasma concentration in patients with GIST. Linear regression analysis was used for the correlation analysis of imatinib plasma concentration with dosage, clinicopathologic feature and side effect.

RESULTSPatients who could not tolerate 400 mg imatinib per day(n=3) received 300 mg per day. There was no significant difference in imatinib plasma concentration between patients with 300 mg and those with 400 mg imatinib(n=53)(P=0.527). However, the imatinib plasma concentration in patients with 600 mg imatinib per day (n=4) was significantly higher as compared to those with 400 mg(P=0.000). Linear regression analysis indicated a negative correlation between the imatinib plasma concentration in patients with 400mg imatinib per day for 90 days continuously and body surface area(R=0.074, P=0.035), but no significant correlations of with age, creatinine clearance and serum albumin concentration were observed (all P>0.05). The differences in imatinib plasma concentration were not statistically significant between patients of different gender and those taking proton-pump inhibitor (PPI) or not (both P>0.05). Difference in imatinib plasma concentration between patients with different surgery was significant (P=0.026). Compared to patients who underwent wedge resection, enterectomy and other surgeries, the imatinib plasma concentration of patients with subtotal gastrectomy or total gastrectomy decreased significantly (all P<0.05). After 90 days of taking imatinib continuously, linear regression analysis revealed a negative correlation between imatinib plasma concentration in patients with 400 mg imatinib per day and white blood cell count (R=0.103, P=0.013), and a positive correlation with serum alanine aminotransferase (ALT) concentration (R=0.076, P=0.033).

CONCLUSIONSThe imatinib plasma concentration in patients with larger body surface area, subtotal gastrectomy or total gastrectomy may be lower. For these patients, dosage of imatinib should be considered to increase in order to achieve effective plasma concentration. Excessive imatinib plasma concentration can result in some side effects, such as decrease of white blood cells and liver damage. Therefore, it is significant for receiving optimal clinical therapeutic efficacy to monitor imatinib plasma concentration, adjust imatinib dosage timely and keep imatinib plasma concentration in effective and safe range.

Adult ; Antineoplastic Agents ; administration & dosage ; pharmacokinetics ; Benzamides ; Combined Modality Therapy ; Cross-Sectional Studies ; Female ; Gastrectomy ; Gastrointestinal Stromal Tumors ; drug therapy ; surgery ; Humans ; Imatinib Mesylate ; administration & dosage ; pharmacokinetics ; Male ; Middle Aged ; Piperazines ; Pyrimidines ; Tandem Mass Spectrometry

BACKGROUND/AIMS: Functional dyspepsia (FD) is a gastrointestinal disorder in which the patient suffers from chronic abdominal symptoms despite the absence of organic disease. Benachio Q solution (soln.)(R) is a new prokinetic herbal medicine. The aim of the present study is to determine the efficacy and safety of Benachio Q soln.(R) in patients with postprandial distress syndrome (PDS) subtype in FD. METHODS: A single-center, randomized, double-blind, placebo-controlled pilot study was performed in 20 patients with PDS. Patients were assigned to receive either Benachio Q soln.(R) or placebo three times a day. After 4 weeks of treatment, the data on response rates, symptoms severity of PDS and gastric emptying time were analyzed to evaluate its efficacy. Adverse events, laboratory tests and vital sign were analyzed to assess its safety. RESULTS: Nine patients were assigned to Benachio group and 10 patients to placebo group. The response rate after 4 weeks was 44.4% and 20.0% in Benachio and placebo group, respectively (p=0.350). The response rate during the first week in Benachio group was better compared to that of placebo group with marginal difference (33.3% vs. 0.0%, p=0.087). Changes of severity score in early satiety on second and third week were -1.8+/-0.6, -1.9+/-0.4 and -1.3+/-0.5, -1.4+/-0.6 in Benachio and placebo group, respectively (p=0.059 vs. p=0.033). No adverse event was observed. CONCLUSIONS: The new herbal drug, Benachio Q soln.(R) seems to improve the symptoms of PDS subtype in FD and could be used safely. Further larger trial is needed in the future.
Adult ; Double-Blind Method ; Drug Administration Schedule ; Dyspepsia/*drug therapy/pathology ; Female ; Gastrointestinal Agents/*therapeutic use ; *Herbal Medicine ; Humans ; Male ; Middle Aged ; Pilot Projects ; Placebo Effect ; Postprandial Period ; Severity of Illness Index ; Treatment Outcome

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 assess the effectiveness of multiple cleaning and disinfection interventions in the homes and kindergartens, in reducing gastrointestinal and respiratory illnesses of children.

METHODSFrom October 2010 to September 2011, we performed a prospective, controlled study in China. 408 children under 5 years old were recruited and group randomized into intervention and control groups. Families and kindergartens in the intervention group were provided with antibacterial products for hand hygiene and surface cleaning or disinfection for one year. Each child's illness symptoms and sick leave were recorded every day.

RESULTSA total of 393 children completed the study, with similar baseline demographics in each of the 2 groups. Except for abdominal pain, the odds of symptoms (fever, cough and expectoration, runny nose and nasal congestion, diarrhea), illness (acute respiratory illness and gastrointestinal illness), and sick leave per person each month were significantly reduced by interventions. The rates of fever, diarrhea, acute respiratory illness, gastrointestinal illness and sick leave per person per year were significantly decreased as well.

CONCLUSIONNot only the acute respiratory and gastrointestinal illness but the sick leave rate in children were significantly reduced by multiple interventions.

Administration, Cutaneous ; Anti-Bacterial Agents ; administration & dosage ; Child, Preschool ; China ; epidemiology ; Disinfection ; Female ; Gastrointestinal Diseases ; epidemiology ; prevention & control ; Hand Hygiene ; Humans ; Incidence ; Male ; Prevalence ; Respiratory Tract Infections ; epidemiology ; prevention & control

Small intestinal bacterial overgrowth (SIBO) can partly explain irritable bowel syndrome (IBS), and rifaximin has been observed to improve abdominal symptoms in nonconstipated IBS patients. However, there are few reports on the association of the rifaximin treatment periods with the results of a lactulose breath test (LBT). Therefore, we performed a retrospective review of patient charts to investigate the relation between the rifaximin treatment periods with LBT results in nonconstipated IBS patients. We also evaluated the time to achieve a symptomatic improvement in the IBS patients as compared to the changes in the LBT. We reviewed the charts for patients who showed IBS symptoms with documented positive results for LBT during their initial visit and who had a follow-up LBT after treatment with rifaximin. The LBT values were compared to the subjects' symptom scores. A total of 102 subjects had a follow-up LBT to assess LBT normalization. The subjects were divided into groups according to treatment periods of 4 weeks (n = 36), 8 weeks (n = 43), and 12 weeks (n = 23). The groups with a longer treatment exhibited an increase in the hydrogen gas value at 90 min and its sum during 90 min at the initial LBT. There were significant differences in hydrogen gas value at 90 min and in its sum during 90 min at the initial LBT between the groups treated for 4 and 12 weeks. The most significant treatment response was observed during the first 4 weeks for all treatment groups. Symptomatic improvement occurred earlier than LBT normalization in the treatment period over 4 weeks. The results indicate that different rifaximin treatment periods are needed in accordance with LBT levels to effectively eradicate SIBO.
Biomarkers/analysis ; Breath Tests/*methods ; Constipation ; Drug Administration Schedule ; Drug Monitoring/*methods ; Female ; Gastrointestinal Agents/administration & dosage ; Humans ; Irritable Bowel Syndrome/*diagnosis/*drug therapy ; Lactulose/*analysis ; Male ; Middle Aged ; Reproducibility of Results ; Rifamycins/*administration & dosage ; Sensitivity and Specificity ; Treatment Outcome

BACKGROUND/AIMS: The eradication rates of Helicobacter pylori infection have been reported to have decreased over the years due to antibiotics resistance. The aim of this study is to investigate the trend of eradication rates of first-line triple therapy for H. pylori over the past 13 year period, and to evaluate factors affecting H. pylori eradication in Daegu and Gyeongsangbuk-do, Korea. METHODS: A total of 2,982 patients with H. pylori infection who were treated with either 1 week or 2 weeks first-line therapy (proton pump inhibitor [PPI], amoxicillin, and clarithromycin) from January 1999 through December 2011 were included in this study. Data were collected by retrospectively reviewing the medical records. RESULTS: The overall H. pylori eradication rate was 87.2%. The eradication rates from 1999 to 2011 fluctuated between 78.0% and 95.7%, but no definite evidence of a decreasing tendency was seen over the 13 year period (p=0.113). Furthermore, there was no significant difference in the eradication rate according to the duration of therapy (p=0.592). However, there was a significant difference in the eradication rate among various PPIs (p<0.01). CONCLUSIONS: There was no decreasing trend in the H. pylori eradication rate over the past 13 years in Daegu and Gyeongsangbuk-do, Korea. There also was no difference in the eradication rates depending on duration of therapy. However, a significant difference was noted among various PPIs.
Adult ; Aged ; Amoxicillin/therapeutic use ; Anti-Bacterial Agents/*therapeutic use ; Clarithromycin/therapeutic use ; Disease Eradication/*trends ; Drug Administration Schedule ; Drug Therapy, Combination ; Endoscopy, Gastrointestinal ; Esomeprazole/therapeutic use ; Female ; Helicobacter Infections/*drug therapy/pathology ; *Helicobacter pylori ; Humans ; Logistic Models ; Male ; Middle Aged ; Omeprazole/therapeutic use ; Proton Pump Inhibitors/*therapeutic use ; Rabeprazole/therapeutic use ; Republic of Korea ; Retrospective Studies ; Treatment Outcome