Gastric cancer has high incidence and mortality rate. Chemotherapy is the first-line treatment for gastric cancer and has achieved considerable success. However, due to genetic variations and tumor heterogeneity, the effectiveness of chemothrapy drugs varies among different patients. Therefore, accurate assessment of patient’s sensitivity to chemotherapy drugs is crucial for personalized treatment. Gastric cancer organoids serve as effective tools for predicting patient’s sensitivity to chemotherapy drugs. This review summarizes the applications and related research progress of gastric cancer organoids in determining chemotherapy drug sensitivity, discusses the strengths and limitations of organoid models, and proposes outlooks for future research directions, hoping that organoids can provide more effective personalized treatment options and a greater range of drug choices for gastric cancer treatment.

Maternal health during pregnancy has a direct impact on the risk and severity of neurodevelopmental disorders (NDDs) in the offspring, especially in the case of drug exposure. However, little progress has been made to assess the risk of drug exposure during pregnancy due to ethical constraints and drug use factors. We collected and manually curated sub-pathways and pathways (sub-/pathways) and drug information to propose an analytical framework for predicting drug candidates. This framework linked sub-/pathway activity and drug response scores derived from gene transcription data and was applied to human fetal brain development and six NDDs. Further, specific and pleiotropic sub-/pathways/drugs were identified using entropy, and sex bias was analyzed in conjunction with logistic regression and random forest models. We identified 19 disorder-associated and 256 regionally pleiotropic and specific candidate drugs that targeted risk sub-/pathways in NDDs, showing temporal or spatial changes across fetal development. Moreover, 5443 differential drug-sub-/pathways exhibited sex-biased differences after filling in the gender labels. A user-friendly NDDP visualization website ( https://ndd-lab.shinyapps.io/NDDP ) was developed to allow researchers and clinicians to access and retrieve data easily. Our framework overcame data gaps and identified numerous pleiotropic and specific candidates across six disorders and fetal developmental trajectories. This could significantly contribute to drug discovery during pregnancy and can be applied to a wide range of traits.
Humans ; Female ; Pregnancy ; Neurodevelopmental Disorders/metabolism* ; Male ; Prenatal Exposure Delayed Effects ; Fetal Development/drug effects* ; Drug Discovery/methods* ; Brain/metabolism*

BACKGROUND:Postoperative adjuvant chemotherapy is a common method for the treatment of gastric cancer,but the curative effect of chemotherapy in different patients varies considerably.A new pre-clinical treatment model is needed to guide personalized drug therapy for patients with gastric cancer.OBJECTIVE:To construct organoid model based on gastric cancer tissue and investigate its application in personalized drug screening.METHODS:The tissue samples of 20 patients with gastric cancer were collected,digested and decomposed,mixed with matrix glue,and cultured with organoid medium containing epidermal growth factor and fibroblast growth factor 10.Hematoxylin-eosin staining and immunohistochemical method were used to verify the homogeneity of pathological morphology and immune molecular markers of gastric cancer organoids and original tumor tissues.The feasibility of the established gastric cancer organoid model for drug screening was evaluated through drug sensitivity screening of six drugs including carboplatin,irinotecan,fluorouracil,oxaliplatin,paclitaxel,and epirubicin.RESULTS AND CONCLUSION:Fourteen organoids of gastric cancer cases were successfully cultured.There were individual differences in morphology and growth characteristics of organoids.All organoids could be stably passed through,froze and resuscitated.Gastric cancer organoids retained the same morphological features and immunomolecular expression as primary tumor tissues.Six organoids showed different drug sensitivities to six chemotherapy drugs,which initially confirmed the feasibility of gastric cancer organoids as a drug screening model in vitro.

BACKGROUND:Postoperative adjuvant chemotherapy is a common method for the treatment of gastric cancer,but the curative effect of chemotherapy in different patients varies considerably.A new pre-clinical treatment model is needed to guide personalized drug therapy for patients with gastric cancer.OBJECTIVE:To construct organoid model based on gastric cancer tissue and investigate its application in personalized drug screening.METHODS:The tissue samples of 20 patients with gastric cancer were collected,digested and decomposed,mixed with matrix glue,and cultured with organoid medium containing epidermal growth factor and fibroblast growth factor 10.Hematoxylin-eosin staining and immunohistochemical method were used to verify the homogeneity of pathological morphology and immune molecular markers of gastric cancer organoids and original tumor tissues.The feasibility of the established gastric cancer organoid model for drug screening was evaluated through drug sensitivity screening of six drugs including carboplatin,irinotecan,fluorouracil,oxaliplatin,paclitaxel,and epirubicin.RESULTS AND CONCLUSION:Fourteen organoids of gastric cancer cases were successfully cultured.There were individual differences in morphology and growth characteristics of organoids.All organoids could be stably passed through,froze and resuscitated.Gastric cancer organoids retained the same morphological features and immunomolecular expression as primary tumor tissues.Six organoids showed different drug sensitivities to six chemotherapy drugs,which initially confirmed the feasibility of gastric cancer organoids as a drug screening model in vitro.

ObjectiveTo investigate the efficacy and safety of N-acetylcysteine （NAC） in the treatment of severe alcoholic hepatitis （SAH）， and to provide a basis for clinical medication for SAH. MethodsA prospective randomized controlled trial was conducted among 172 SAH patients with a Maddrey discriminant function score of >32 points who were recruited by The Fifth Medical Center of Chinese PLA General Hospital from June 2015 to June 2018， and these patients were divided into NAC group with 84 patients and control group with 86 patients. NAC （8 g/day， 28 days） was assessed in terms of its safety in SAH patients， its impact on 28-day biochemical parameters， and its role in improving 28- and 180-day survival rates. A further analysis was performed to investigate the effect of NAC on the 28- and 180-day survival rates of SAH patients with acute-on-chronic liver failure （ACLF-SAH patients） and those without acute-on-chronic liver failure （non-ACLF-SAH patients）. The independent-samples t test was used for comparison of normally distributed continuous data between two groups， and the Mann-Whitney U test was used for comparison of non-normally distributed continuous data between two groups. The Kaplan-Meier method was used to plot survival curves， and the Log-rank test was used for comparison of survival curves. Univariate and multivariate Cox proportional-hazards regression model analyses were used to investigate independent influencing factors. ResultsNo serious adverse events were observed during NAC treatment， suggesting that NAC had a good safety profile. Compared with the control group， NAC did not significantly improve the 28-day biochemical parameters （all P>0.05） and survival rate of SAH patients （P=0.081）， but it could improve the 180-day survival rate of SAH patients （67.4% vs 81.0%， χ²=4.280， P=0.039）. NAC did not improve the 28- and 180-day survival rates of ACLF-SAH patients （both P>0.05）； NAC did not improve the 28-day survival rate of non-ACLF-SAH patients （P>0.05）， but it could improve the 180-day survival rate of these patients （68.4% vs 88.9%， χ²=4.883， P=0.027）. The multivariate Cox regression survival analysis showed that NAC treatment （hazard ratio ［HR］=2.530， 95% confidence interval ［CI］： 1.334‍ ‍— 4.796， P=0.004，）， Maddrey discriminant function score （HR=3.852， 95%CI： 2.032 — 7.304， P<0.001）， and serum sodium level （HR=1.948， 95%CI： 1.079‍ ‍—‍ ‍3.517， P=0.027） were independent influencing factors for 180-day survival rate in SAH patients. ConclusionNAC has a good safety profile in the treatment of SAH and can improve the 180-day survival rate of SAH patients， and in particular， non-ACLF-SAH patients can benefit from NAC treatment in terms of middle- and long-term survival rates.

Objective:To analyze the epidemiological characteristics of pneumoconiosis in Hunan Province.Methods:In November 2018, we collected the type of work, pneumoconiosis type, pneumoconiosis stage, length of service, age of onset and complications of pneumoconiosis cases diagnosed by Hunan occupational disease prevention and control hospital from January 2017 to October 2018. A total of 3 325 cases of pneumoconiosis were collected, including 651 cases (19.58%) of occupational pneumoconiosis and 2674 cases (80.42%) of clinically diagnosed pneumoconiosis. The measurement data were expressed by ± s. The comparison between groups was performed by independent sample t test and one-way ANOVA. Results:The age of 651 patients with occupational pneumoconiosis was 35.59-85.15 years old, the average age of onset was (54.27±8.29) years, and the average exposure to dust was (14.74±8.60) years. 2 674 cases of clinically diagnosed pneumoconiosis were 26.85~87.02 years old. The average age of onset was (55.26±7.38) years, and the average exposure time was (18.83±9.35) years. Compared with silicosis patients, coal workers' pneumoconiosis patients had longer exposure time, the difference was statistically significant ( P<0.05) , and the difference was statistically significant ( F=3.678, P<0.05) . There were no complications in 651 cases of occupational pneumoconiosis. Among 2 674 cases of clinically diagnosed pneumoconiosis, 710 cases (26.55%) had complications. Conclusion:Further attention should be paid to the clinical diagnosis of pneumoconiosis in Hunan Province.

Objective:To analyze the epidemiological characteristics of pneumoconiosis in Hunan Province.Methods:In November 2018, we collected the type of work, pneumoconiosis type, pneumoconiosis stage, length of service, age of onset and complications of pneumoconiosis cases diagnosed by Hunan occupational disease prevention and control hospital from January 2017 to October 2018. A total of 3 325 cases of pneumoconiosis were collected, including 651 cases (19.58%) of occupational pneumoconiosis and 2674 cases (80.42%) of clinically diagnosed pneumoconiosis. The measurement data were expressed by ± s. The comparison between groups was performed by independent sample t test and one-way ANOVA. Results:The age of 651 patients with occupational pneumoconiosis was 35.59-85.15 years old, the average age of onset was (54.27±8.29) years, and the average exposure to dust was (14.74±8.60) years. 2 674 cases of clinically diagnosed pneumoconiosis were 26.85~87.02 years old. The average age of onset was (55.26±7.38) years, and the average exposure time was (18.83±9.35) years. Compared with silicosis patients, coal workers' pneumoconiosis patients had longer exposure time, the difference was statistically significant ( P<0.05) , and the difference was statistically significant ( F=3.678, P<0.05) . There were no complications in 651 cases of occupational pneumoconiosis. Among 2 674 cases of clinically diagnosed pneumoconiosis, 710 cases (26.55%) had complications. Conclusion:Further attention should be paid to the clinical diagnosis of pneumoconiosis in Hunan Province.

Objective To investigate the safety of young recipients undergoing living donor renal transplantation from elderly relative donors through long-term follow-up of the pathological changes. Methods According to the age of donors, 28 young recipients were divided into the observation group (n=14, elderly donors) and control group (n=14, young and middle-aged donors). The 7-year survival after renal transplantation, the serum creatinine (Scr) levels at various postoperative time points were compared between two groups. The chronic pathological injury scores of renal allograft biopsy at time-zero, postoperative 6-month and 7-year were compared between two groups. The expression levels of renal interstitial fibrosis indicators connective tissue growth factor (CTGF), transforming growth factor (TGF)-β, laminin (LN), fibronectin (FN), cell senescence indicators intercellular connexin (Cx)-43 and mammalian target of rapamycin (mTOR) at postoperative 6-month and 7-year were compared between two groups. Results The 7-year survival rates in the observation and control groups were 78.5% and 92.8% with no statistical significance (P > 0.05). In the observation and control groups, the levels of Scr were 190 and 160 μmol/L at the postoperative 7 d, and 170 and 125 μmol/L at postoperative 1 month. At each postoperative time point, the levels of Scr in the observation group were significantly higher than those in the control group (all P > 0.05). The total chronic pathological injury scores of renal transplant biopsy at time-zero in the observation group was significantly higher than that in the control group (P > 0.05), whereas the total chronic pathological injury scores at postoperative 7-year did not significantly differ between two groups (P > 0.05). Within either group, the total chronic pathological injury scores at postoperative 7-year was remarkably higher than those at time-zero and postoperative 6-month (both P < 0.05). The expression levels of CTGF, TGF-β, LN, FN, mTOR, Cx43 of renal transplant tissue at postoperative 7-year did not significantly differ between two groups (all P > 0.05). Conclusions The long-term follow-up outcomes demonstrate that the pathological changes of young recipients undergoing renal transplantation from elderly donors are similar to those from young and middle-aged donors. It is safe and feasible for young recipients to undergo renal transplantation from elderly donors in the pathological perspective.

Objective To compare different drainage methods after right hepatectomy. Methods From April 2017 to February 2018, 90 patients who underwent right hepatectomy at Zhongshan Hospital of Fudan University were prospectively randomized to the latex tube group (right subphrenic drain with a latex tube connecting to a collection bag, n=30), the silicone tube group (right subphrenic drain with a silicone tube connecting to a closed-suction, n=30) or the combination group ( right subphrenic drain with a latex tub, combined with a silicone tube, n=30). The amount of fluid collection after the operation, complications after surgery, recovery of liver function, and length of hospital stay after operation were compared. Results There were no significant differences in the clinicopathological features among the 3 groups, including gender, age, cirrhosis status, extent of hepatectomy, and blood loss (P＞0. 05). There were no significant differences among the three groups on the incidences of postoperative complications [ the latex tube group, 20. 0% (6/30); the silicone tube group, 23. 3% (7/30); the combination group, 16. 7% (5/30); P＞0. 05]. Ultrasonography showed significantly lower rates of subphrenic collection in the combination group compared with the latex tube group and the silicone tube group [16. 7% (5/30) vs. 63. 3% (19/30) vs. 53. 3% (16/30); P＜0. 05]. The rates of postoperative fever, serum total bilirubin, ALT and postoperative hospital stay were similar among the three groups (P＞0. 05). Conclusions Drainage using the combina-tion of a latex tube connecting to a collection bag and a silicone tube connecting to closed-suction after right hepatectomy significantly reduced postoperatively subphrenic collection and prevented infection of the collec-tion. However, the treatment strategy did not delay liver function recovery, prolong hospital stay nor increase post-operative infection rate.