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

Background/Aims: Irritable bowel syndrome (IBS) is a prevalent functional gastrointestinal disease characterized by recurrent abdominal pain and bowel dysfunction. However, the majority of previous neuroimaging studies focus on brain structure and connections but seldom on the inter-hemispheric connectivity or structural asymmetry. This study uses multi-modal imaging to investigate the abnormal changes across the 2 cerebral hemispheres in patients with IBS. Methods: Structural MRI, resting-state functional MRI, and diffusion tensor imaging were acquired from 34 patients with IBS and 33 healthy controls. The voxel-mirrored homotopic connectivity, fractional anisotropy, fiber length, fiber number, and asymmetry index were calculated and assessed for group differences. In addition, we assessed their relevance for the severity of IBS. Results: Compared with healthy controls, the inter-hemispheric functional connectivity of patients with IBS showed higher levels in bilateral superior occipital gyrus, middle occipital gyrus, precuneus, posterior cingulate gyrus, and angular gyrus, but lower in supplementary motor area. The statistical results showed no significant difference in inter-hemispheric anatomical connections and structural asymmetry, however negative correlations between inter-hemispheric connectivity and the severity of IBS were found in some regions with significant difference. Conclusions The functional connections between cerebral hemispheres were more susceptible to IBS than anatomical connections, and brain structure is relatively stable. Besides, the brain areas affected by IBS were concentrated in default mode network and sensorimotor network.

Objective: To compare the efficiency of the target gene panel method and whole-exome sequencing (WES) in detecting idiopathic hypogonadotropic hypogonadism (IHH), and select a more suitable gene detection method. METHODS: We selected 24 genes closely related to the molecular pathogenesis of IHH to make up the gene panel, detected the mutation sites in 73 patients with IHH using the panel method, and verified the results of sequencing with the Sanger method. Using the key words "idiopathic hypogonadotropic hypogonadism", we searched databases for relevant literature, calculated the positive rate of IHH detected by WES and compared it with that detected with the panel method. RESULTS: Of the 73 cases of IHH detected with the panel method, 7 were found with pathogenic mutations, including 2 cases of FGFR1, 2 cases of CHD7, 2 cases of KISS1R, and 1 case of NR5A1 mutation. Sanger sequencing showed that the positive rate of the panel method was 9.7%. Of the 1 336 articles retrieved, 5 met the inclusion criteria and were included, in which WES revealed a positive rate of about 30%. CONCLUSIONS For detection of the diseases with clear mutated genes, the panel method is relatively inexpensive and has a high sequencing depth, while for detection of the diseases with complicated genetic patterns and unclear mutated genes, WES is more efficient. Further studies are needed for choice of the two methods for different purpose of detection./.
Humans ; Hypogonadism/genetics* ; Male ; Whole Exome Sequencing

The purpose of this study was to understand the pharmacodynamic effect of Valeriana jatamansi extract in diarrhea predominant irritable bowel syndrome(IBS-D) rat model induced by maternal separation combined with three kinds of stress, and observe the changes of endogenous metabolites in feces after intervention to find potential biomarkers and related metabolic pathways. The animal model of IBS-D was established by maternal separation combined with restraint, ice swimming and tail clamping. The therapeutic effect of each dose group of V. jatamansi extract was evaluated in terms of abdominal withdrawal reflex pressure threshold, fecal water content and immobility time of forced swimming test. In addition, rat feces were collected for detection of metabolic profiles of small molecular metabolites with UPLC-LTQ-Orbitrap MS platform, so as to find the biomarkers of differential metabolism with multivariate statistical analysis methods such as principal component analysis(PCA) and orthogon partial least squares discrimination analysis(OPLS-DA). The results showed that as compared with the normal group, the threshold of abdominal withdrawal reflex pressure was decreased, the fecal water content was increased, and the immobility time of forced swimming test was prolonged in the model group. The results of fecal metabonomics showed that the levels of 39 metabolites were down-regulated and those of 37 metabolites were up-re-gulated. Further analysis showed that these metabolites were related to bile acid metabolism, unsaturated fatty acid metabolism, amino acid metabolism, ceramide metabolism and other metabolic pathways. This study proved that the extract of V. jatamansi had definite pharmacodynamic effect on IBS-D model rats, and the mechanism was discussed from the perspective of fecal metabonomics.
Animals ; Chromatography, High Pressure Liquid ; Chromatography, Liquid ; Diarrhea ; Feces ; Irritable Bowel Syndrome/drug therapy* ; Maternal Deprivation ; Metabolomics ; Rats ; Tandem Mass Spectrometry ; Valerian

Background/Aims: Irritable bowel syndrome (IBS) is a prevalent functional gastrointestinal disease characterized by recurrent abdominal pain and bowel dysfunction. However, the majority of previous neuroimaging studies focus on brain structure and connections but seldom on the inter-hemispheric connectivity or structural asymmetry. This study uses multi-modal imaging to investigate the abnormal changes across the 2 cerebral hemispheres in patients with IBS. Methods: Structural MRI, resting-state functional MRI, and diffusion tensor imaging were acquired from 34 patients with IBS and 33 healthy controls. The voxel-mirrored homotopic connectivity, fractional anisotropy, fiber length, fiber number, and asymmetry index were calculated and assessed for group differences. In addition, we assessed their relevance for the severity of IBS. Results: Compared with healthy controls, the inter-hemispheric functional connectivity of patients with IBS showed higher levels in bilateral superior occipital gyrus, middle occipital gyrus, precuneus, posterior cingulate gyrus, and angular gyrus, but lower in supplementary motor area. The statistical results showed no significant difference in inter-hemispheric anatomical connections and structural asymmetry, however negative correlations between inter-hemispheric connectivity and the severity of IBS were found in some regions with significant difference. Conclusions The functional connections between cerebral hemispheres were more susceptible to IBS than anatomical connections, and brain structure is relatively stable. Besides, the brain areas affected by IBS were concentrated in default mode network and sensorimotor network.

Objective:Asthma is a chronic inflammatory respiratory disease .The data show that involvement of the GATA 3-IL-13 gene in asthma is biologically plausible .The objective of this study is investigated the association of GATA 3-IL13 gene polymorphisms and IL-13 levels with asthma;assess the correlations between GATA 3-IL-13 gene SNPs polymorphisms and serum levels of IL-13 in population of Xinjiang (China).Methods:A case group of 279 patients and 277 healthy controls were genotyped to perform using the MassARRAY SNP genotyping system.In 279 asthma patients and 277 controls,IL-13 levels were measured by ELISA.Data were analyzed using the statistical package for social science (SPSS) 22.0 (IBM,NY,USA) and Graph Pad Prism 6.0.Results:Patients were found that IL-13 levels were associated with asthma in asthmatic and the IL-13 ( rs2066960 AA ) , GATA3 ( rs3781093 CC) genotype was associated with a notably increased risk of asthma compared with the CC (rs2066960),TT (rs3781093) genotype (P<0.05).Similarly,IL-13(rs2066960) C-A alleles were significantly associated with risk of asthma (P<0.05).However,the rs3781093 C-T alleles had no obvious differences (P>0.05).In addition,the patients carrying the rs2066960 AA genotype presented with higher IL-13 levels compared to the CC group .Conclusion:This result suggests that the rs 2066960 C-A variant is associated with IL-33 levels in patients with asthma .

Background:The Food and Drug Administration recently announced that the use of morcellation may cause fibroids or pelvic dissemination and metastasis of uterine sarcoma;therefore,the use of morcellation is limited in the USA.A large sample study is necessary to assess the proportion of uterine malignant tumors found in patients with laparoscopic myomectomy.Methods:A national multicenter study was performed in China.From 2002 to 2014,33,723 cases were retrospectively selected.We calculated the prevalence and recorded the clinical characteristics of the patients with malignancy after morcellation application.A total of 62 cases were finally pathologically confirmed as malignant postoperatively.Additionally,the medical records of the 62 patients were analyzed in details.Results:The proportion of postoperative malignancy after morcellation application was 0.18％ (62/33,723) for patients who underwent laparoscopic myomectomy.Nearly 62.9％ (39/62) of patients had demonstrated blood flow signals in the uterine fibroids before surgery.And,23 (37.1％) patients showed rapid growth at the final preoperative ultrasound.With respect to the pathological types,38 (61.3％) patients had detectable endometrial stromal sarcoma,13 (21.0％) had detectable uterine leiomyosarcoma,only 3 (3.2％) had detectable carcinosarcoma,and 5 (8.1％) patients with leiomyoma had an undetermined malignant potential.Conclusions:The proportion of malignancy is low after using morcellation in patients who undergo laparoscopic myomectomy.Patients with fast-growing uterine fibroids and abnormal ultrasonic tumor blood flow should be considered for malignant potential,and morcellation should be avoided.

To observe the effect of geniposide on non-alcoholic fatty liver disease (NAFLD), and discuss the mechanism of geniposide for NAFLD from the aspect of free fatty acid, forty healthy Wistar male rats were randomly divided into normal group, model group, geniposide and Xuezhikang group. The rats in normal group were fed with normal diets, and the rats in other 3 groups were given with high-fat diet for 8 weeks to induce the NAFLD models. From the week 5 to end of week 8, the rats in geniposide and Xuezhikang group were intervened with corresponding medicines. The body weight, liver wet weight, and fat weight of the rats were recorded. Visual and pathological changes in hepatic tissues were observed with HE staining. The contents of TG, FFA, FAS, AMPK, ACCase and Malonyl-CoA in hepatic tissue, contents of CHO and LDL-C in serum and activities of AST and ALT in serum were detected by using corresponding methods. The results showed that the body weight, liver wet weight, and fat weight of the rats, CHO, LDL-C, ALT and AST levels in serum, TG, FFA, FAS, ACCase and Malonyl-CoA levels in hepatic tissues of the rats in model group were significantly higher than those in normal group (P<0.01), while AMPK activity was significantly lower than that of the normal group (P<0.01), with obvious visual and pathological steatosis in hepatic tissues, and inflammatory injury occurred in model group. Compared with the model group, body weight of the rat, fat weight, levels of FFA in hepatic tissues, ALT and AST activities in serum, liver wet weight, TG, FAS, ACCase and Malonyl-CoA levels were significantly decreased in geniposide group (P<0.01), while the AMPK activity in hepatic tissues was significantly increased (P<0.05),with improvement in visual and pathological performance. Compared with the model group, liver wet weight, fat weight, TG and FFA levels in hepatic tissues, and LDL-C level in serum were significantly decreased in Xuezhikang group (P<0.05). Compared with Xuezhikang group, the body weight of rat, fat weight and FFA level in hepatic tissues were significantly lower in geniposide group (P<0.01), but with no significant difference in other aspects. These findings indicated that geniposide was highly effective in improving the pharmacological effect of NAFLD induced by high-fat diet, and the mechanism was achieved through AMPK-ACCase-Malonyl-CoA-FFA axis.

Objective To observe the effect of different needling retaining times in clinical curative effect of acupuncture on the treatment of periarthritis humeroscapularis.Methods A total of 60 patients, who met the inclusion criteara, were randomly divided into 2 groups according to random number table method, 30 patients in each group. Both groups were treated with the same acupuncture therapy for 20 times, but the needling retaining times were different as 20 minutes and 40 minutes. The curative effect rates, Visual Analog Scale (VAS) and Constant-Murley Score (CMS) were evaluated.Results After the treatment, the VAS scoresin 40mins group was significantly lower than that in the 20 mins group (2.67 ± 1.03vs.3.60 ± 1.48,t=-3.251, P<0.01); the CMSin 40 mins group was significantly higher than the 20 mins group (73.20 ± 10.88vs.66.47 ± 12.62,t=-2.199,P<0.05). The curative effect rates of the 40 mins group was 26.7% (8/30), which was significantly higher than 3.3% (1/30) in the 20 mins group (χ2=4.706,P=0.030). The total effective rates in the 40 mins group was 90.0% (27/30), which was significantly higher than 96.7% (29/30) in the 20 mins group (χ2=0.268,P=0.605).Conclusions Acupuncture treatment for the patients with periarthritis humeroscapularis showed that the 40 minutes of needling retaining times had better symptom improvement and restore function effects than 20 minutes, however the total effective rate was no significant difference.