Myocardial dysfunction is the most serious complication of sepsis. Sepsis-induced myocardial dysfunction (SMD) is often associated with gastrointestinal dysfunction, but its pathophysiological significance remains unclear. The present study found that patients with SMD had higher plasma gastrin concentrations than those without SMD. In mice, knockdown of the gastrin receptor, cholecystokinin B receptor (Cckbr), aggravated lipopolysaccharide (LPS)-induced cardiac dysfunction and increased inflammation in the heart, whereas the intravenous administration of gastrin ameliorated SMD and cardiac injury. Macrophage infiltration plays a significant role in SMD because depletion of macrophages by the intravenous injection of clodronate liposomes, 48 h prior to LPS administration, alleviated LPS-induced cardiac injury in Cckbr-deficient mice. The intravenous injection of bone marrow macrophages (BMMs) overexpressing Cckbr reduced LPS-induced myocardial dysfunction. Furthermore, gastrin treatment inhibited toll-like receptor 4 (TLR4) expression through the peroxisome proliferator-activated receptor α (PPAR-α) signaling pathway in BMMs. Thus, our findings provide insights into the mechanism of the protective role of gastrin/CCKBR in SMD, which could be used to develop new treatment modalities for SMD.

Objective:To clarify the clinicopathological, especially molecular, features of early-onset gastric cancer with the aim of informing analysis of treatment strategies.Methods:In this retrospective case-control study, we examined data from a dedicated gastric cancer database in Zhongshan Hospital affiliated to Fudan University. The original cohort comprised 2506 patients with gastric cancer who had undergone gastrectomy in Zhongshan Hospital Fudan University from July 2020 to October 2021, including 198 with early-onset gastric cancer (aged ≤45 years) and 2,308 with non-early gastric cancer. We used a simple random sampling method to select 396 of the 2,308 patients aged >45 years (ratio of 1:2) as the control group and then compared molecular diagnostic data and clinicopathological features of the two groups.Results:The median age was 39 years in the early-onset gastric cancer group, while 66 years in the control group. The clinicopathological features of early-onset gastric cancer included female predominance (59.1% [117/198] vs. 27.8% [110/396], χ 2=54.816, P<0.001), less comorbidity (32.3% [64/198] vs. 57.1% [226/396], χ 2=32.355, P<0.001), poorer differentiation (93.9% [186/198] vs. 74.5% [295/396], χ 2=30.777, P<0.001) and higher proportion of diffuse type (40.4% [80/198] vs. 15.9% [63/396], χ 2=69.639, P<0.001), distant metastasis (7.1% [14/198] vs. 2.8% [11/396], χ 2=6.034, P=0.014). Regarding treatment, distal gastrectomy was more commonly performed than proximal gastrectomy (55.1% [109/198] vs. 47.0% [186/396], 1.5% [3/198] vs. 8.3% [33/396], χ 2=11.644, P=0.003). Family history of gastric cancer, TNM stage, tumor size, lymph node dissection, nerve invasion, nodes harboring metastases, range of lymph node dissection, digestive tract reconstruction procedure, implementation of laparoscopic surgery, combined resection, and preoperative treatment did not differ significantly between the two groups (all P>0.05). Molecular diagnosis showed there was a smaller percentage of mismatch repair deficiency in the early-onset gastric cancer than in the control group (1.0% [2/198] vs. 10.1% [40/396], χ 2=16.301, P<0.001), and a higher rate of positivity for Claudin 18.2 (77.8% [154/198] vs. 53.0% [210/396], χ 2=5.442, P<0.001). HER-2 and Epstein–Barr virus positivity rates did not differ significantly between the two groups. Conclusion:Early-onset gastric cancer is a distinct type of gastric cancer with a high degree of malignancy, and treatment targeting Claudin 18.2 may be effective.

Objective:To clarify the clinicopathological, especially molecular, features of early-onset gastric cancer with the aim of informing analysis of treatment strategies.Methods:In this retrospective case-control study, we examined data from a dedicated gastric cancer database in Zhongshan Hospital affiliated to Fudan University. The original cohort comprised 2506 patients with gastric cancer who had undergone gastrectomy in Zhongshan Hospital Fudan University from July 2020 to October 2021, including 198 with early-onset gastric cancer (aged ≤45 years) and 2,308 with non-early gastric cancer. We used a simple random sampling method to select 396 of the 2,308 patients aged >45 years (ratio of 1:2) as the control group and then compared molecular diagnostic data and clinicopathological features of the two groups.Results:The median age was 39 years in the early-onset gastric cancer group, while 66 years in the control group. The clinicopathological features of early-onset gastric cancer included female predominance (59.1% [117/198] vs. 27.8% [110/396], χ 2=54.816, P<0.001), less comorbidity (32.3% [64/198] vs. 57.1% [226/396], χ 2=32.355, P<0.001), poorer differentiation (93.9% [186/198] vs. 74.5% [295/396], χ 2=30.777, P<0.001) and higher proportion of diffuse type (40.4% [80/198] vs. 15.9% [63/396], χ 2=69.639, P<0.001), distant metastasis (7.1% [14/198] vs. 2.8% [11/396], χ 2=6.034, P=0.014). Regarding treatment, distal gastrectomy was more commonly performed than proximal gastrectomy (55.1% [109/198] vs. 47.0% [186/396], 1.5% [3/198] vs. 8.3% [33/396], χ 2=11.644, P=0.003). Family history of gastric cancer, TNM stage, tumor size, lymph node dissection, nerve invasion, nodes harboring metastases, range of lymph node dissection, digestive tract reconstruction procedure, implementation of laparoscopic surgery, combined resection, and preoperative treatment did not differ significantly between the two groups (all P>0.05). Molecular diagnosis showed there was a smaller percentage of mismatch repair deficiency in the early-onset gastric cancer than in the control group (1.0% [2/198] vs. 10.1% [40/396], χ 2=16.301, P<0.001), and a higher rate of positivity for Claudin 18.2 (77.8% [154/198] vs. 53.0% [210/396], χ 2=5.442, P<0.001). HER-2 and Epstein–Barr virus positivity rates did not differ significantly between the two groups. Conclusion:Early-onset gastric cancer is a distinct type of gastric cancer with a high degree of malignancy, and treatment targeting Claudin 18.2 may be effective.

OBJECTIVE To provide reference for improving the dispensing accuracy of similar drugs and reducing dispensing error risk through exploring the dispensing mode of similar drugs. METHODS The effectiveness and feasibility of the similar drug dispensing management mode was explored through adjusting the traditional horizontal or vertical sorting method to a “Z” shaped cargo location sorting， implementing similar drug in different zones dispensed by different people， and combining measures such as adjusting the format of drug dispensing documents and improving inventory methods. The role of similar drug dispensing mode in drug dispensing management was evaluated comprehensively from two aspects： work quality and work efficiency. RESULTS After the implementation of similar drug dispensing mode， total number of monthly dispensing errors （18.42±8.79 vs. 28.50±6.87，P= 0.005） and the proportion of monthly dispensing errors of similar drugs （[ 4.17±5.71）% vs. （10.96±7.05）%，P＝0.017] were significantly lower than before the implementation； the monthly consistency rate between accounts and materials （[ 98.46±0.73）% vs. （97.61±0.57）%， P＝0.004] was significantly higher than before implementation； completion time of dispensing in each batch was not significantly affected， and daily work was carried out smoothly and orderly. CONCLUSIONS The similar drug dispensing mode has a significant effect in improving the accuracy of dispensing similar drugs， reducing the risk of dispensing errors， and does not affect the efficiency of dispensing work.

The incidence rate of liver cancer has been rising in recent years. Traditional cell line culture and human patient-derived tumor xenograft models, which are commonly used tools to simulate the occurrence of human liver cancer, have deepened the understanding of tumor occurrence, development, and drug resistance mechanisms. However, they cannot reflect the accurate state of cancer cells, the tumor microenvironment, or spatial structural characteristics. Recently, more in vitro-produced physiological liver organoids have been applied in the study of liver cancer. Liver organoid models have made breakthroughs in the occurrence and development mechanisms of liver cancer, personalized drug screening and biomarker identification, immunotherapy, and regenerative medicine applications. This paper mainly summarizes the progress and application of liver organoids processed in the study of liver cancer.

Objective: To explore the effects of oxidative stress on renal dopamine D₁ receptor dysfunction in offspring of diabetic rat dams. Methods: The pregnant Sprague Dawley (SD) rats (n=10) were randomly divided into the diabetic group (a single intraperitoneal injection of 35 mg/kg streptozotocin on day 0 of gestation) and control group (injected with the equal volume of 0.9% saline on day 0 of gestation) according to the random number table (n=5 each group). The offspring rats were divided into 4 groups including offspring of control dams treated with vehicle, offspring of control dams treated with antioxidant, offspring of diabetic dams treated with vehicle and offspring of diabetic dams treated with antioxidant (n=10 each group). After birth, the offspring rats were treated with normal drinking water or antioxidant (tempol, 1.0 mmol/L) from the age of 4 weeks until the end of the study (20 weeks). The blood pressure was monitored continuously by non-invasive tail-cuff method. The renal oxidative markers including superoxide dismutase (SOD) and malondialdehyde (MDA) activity and D₁ receptor agonist (fenoldopam)-mediated urinary and sodium excretion were detected. Furthermore, the protein expression of renal G protein-coupled receptor kinase 2 (GRK2), GRK4, dopamine D₁ receptor and the phosphorylation level of D₁ receptor were detected. Results: The mean arterial pressure of offspring from the diabetic dams treated with vehicle was significantly higher than that of offspring from control dams treated with vehicle (P=0.013), while the mean arterial pressure of offspring from diabetic dams treated with antioxidant was significantly lower than that of offspring from the diabetic dams treated with vehicle (P=0.038). The fenoldopam-mediated urinary flow and urinary sodium excretion rate were significantly lower in offspring of diabetic dams treated with vehicle than those in offspring of control dams treated with vehicle (P<0.01), which were significantly higher in offspring of diabetic dams treated with antioxidant as compared to offspring of diabetic dams treated with vehicle (both P<0.01). There was no significant difference in fenoldopam-mediated urinary flow and urinary sodium excretion rate in offspring of control dams treated with antioxidant or vehicle (urinary flow: P=0.772; urinary sodium excretion rate: P=0.716). Compared with offspring of control dams treated with vehicle, the renal MDA activity was significantly increased, while the SOD activity was significantly decreased in offspring of diabetic dams treated with vehicle (MDA: P<0.01; SOD: P=0.013). The renal MDA activity was significantly decreased, while the SOD activity was significantly increased in offspring of diabetic dams treated with antioxidant in comparison with offspring of diabetic dams treated with vehicle (MDA: P<0.01; SOD: P=0.035).The renal GRK2 and GRK4 protein expression in offspring of diabetic dams treated with vehicle were significantly higher than those in offspring of control dams treated with vehicle (P<0.01), while the expression levels of renal GRK2 and GRK4 in offspring of diabetic dams treated with antioxidant were significantly downregulated compared with offspring of diabetic dams treated with vehicle (P<0.01). There was no significant difference in the protein expression of dopamine D₁ receptor among 4 groups (P=0.735). The level of dopamine D₁ receptor phosphorylation in offspring of diabetic dams treated with vehicle was significantly higher than that in offspring of control dams treated with vehicle (P<0.01), while the dopamine D₁ receptor phosphorylation level was significantly lower in offspring of diabetic dams treated with antioxidant compared to that in offspring of diabetic dams treated with vehicle (P<0.01). Conclusion Oxidative stress is involved in the dopamine D₁ receptors dysfunction in the offspring of diabetic dams.

Brachythrapy is a technique to implant radioactive isotype into or near tumors.The obvious properties of brachytherapy are a very high dose distribution of center,and rapid dose attenuation with the increasing of distance.Brachytherapy generally includes three major categories:low dose rate,high dose rate and pulse dose rate.The most significant clinical value of brachytherapy is that it could create dose distribution to tumor tissues,but decreased radiation injury of normal tissues close to tumor.The development of the clinical brachytherapy technique is always involved in the radiobiological characteristics.The basic concepts involving clinical brachytherapy radiobiology mainly includes:dose-rate effect,repair of radiation injury,re-oxygenation,cell cycle redistribution and repopulation.An amount of translational medical approach is needed to guide the application of clinical brachytherapy by exploring the interaction between brachytherapy radiobiology and clinical brachytherapy effect,as well as taking advantage of brachytherapy radiobiological characteristics.The ultimate goal is to improve tumor local control rate,reduce the occurrence of adverse reactions,and improve patients' overall survival.

Objective To discuss the dosimetric advantage of computed tomography-guided interstitial brachytherapy compared with the conventional intracavitary brachytherapy for locally advanced cervical cancer,offering a more advantageous clinical treatment approach. Methods Twenty-eight locally advanced cervical cancer patients with bulky tumors ( tumor size>5 cm) after external beam radiotherapy received computed tomography-guided interstitial brachytherapy. Dosimetric outcomes of the current study, including the total dose ( external beam radiotherapy+ brachytherapy ) D90 for the HR-CTV and D2cc for the bladder,rectum, and sigmoid, were compared with a former patient group consisting of 30 patients who received the conventional intracavitary brachytherapy ( uterine tandem+ ovoid pairs ) . Results The mean D90 value for HR-CTV in the intracavitary brachytherapy group and interstitial brachytherapy group were (76.9±5. 7) and ( 88.1± 3. 3) Gy, respectively. The D2cc for the bladder, rectum, and sigmoid in the intracavitary brachytherapy group and interstitial brachytherapy group were (84.7±6. 8) Gy,(69.2±4. 2) Gy,(67.8±4. 5) Gy and (81.8±6. 5) Gy,(6.8±4. 0) Gy,(64.8±4. 1) Gy,respectively.1-year local tumor control rate in the intracavitary brachytherapy group and interstitial brachytherapy group were 59. 3％ and 85. 2％, respectively. Conclusions CT-guided interstitial brachytherapy shows a significant dosimetric advantage compared with the conventional intracavitary brachytherapy, and is, thereby, clinically possible feasible. However,the long term curative effect and toxicity need to be further investigated.

Objective To analyze the dosimetric advantages of CT-guided interstitial brachytherapy for recurrent cervical cancer. Methods A total of 16 patients with recurrent cervical cancer after radical surgery and adjuvant external beam radiotherapy received interstitial brachytherapy with CT-guided implantation of metal needles. The high-risk clinical target volume (HR-CTV) was given 36 Gy in 6 fractions.D90for HR-CTV in the brachytherapy and the cumulative D2 cm3values for the bladder,rectum,and sigmoid colon in the previous external beam radiotherapy and the brachytherapy were analyzed.Results The mean D90value for HR-CTV was 52.5±3.3 Gy. The cumulative D2 cm3values for the bladder, rectum, and sigmoid colon were 85.6±5.8 Gy,71.6±6.4 Gy,and 69.6±5.9 Gy,respectively.The mean number of metal needles was 6.1±1.5 in each brachytherapy. The actual 1-year overall survival and local control were 81% and 69%, respectively. Conclusions CT-guided interstitial brachytherapy for recurrent cervical cancer shows good dose-volume histogram parameters and few complications, so it may be clinically feasible. However,its long-term clinical efficacy needs further observation.

Objective To investigate the dosimetric difference between inverse planning simulated annealing(IPSA)and manual optimized plan for isodose line in interstitial brachytherapy for locally advanced cervical cancer and to provide a better optimization method for clinical application. Methods A total of 104 patients with cervical cancer were enrolled in this study. They received pelvic external beam radiotherapy and interstitial brachytherapy in five fractions. Both IPSA and manual optimized plan for isodose line were used to optimize the dose in each fraction. Dose volume parameters of the two plans were compared to analyze the dosimetric outcome by paired t-test. Results There were no significant differences in mean D 90and D 100for high-risk clinical target volume(HR-CTV)and D 90for intermediate-risk clinical target volume(IR-CTV)between the two groups(P>0.05). The IPSA group had a significantly higher D 100for IR-CTV than the manual optimized group(58.36±2.06 Gy vs. 53.99±2.17 Gy, P=0.025). For organs at risk,the IPSA group had a significantly lower mean rectum D 2ccand a significantly higher bladder D 2ccthan the manual optimized group(68.53± 2.85 Gy vs. 71.77± 1.79 Gy, P=0.002;80.49± 3.36 Gy vs. 78.71± 2.64 Gy,P=0.034). There was no significant difference in sigmoid D 2ccbetween the two groups(P>0.05). The IPSA group had significantly higher relative dose homogeneity index(HI)and conformity index (CI)of radiation dose for target volume than the manual optimized group(P<0.05), and there was no significant difference in overdose volume index(OI)between the two groups(P= 0. 1 0 7).Conclusions Compared with manual optimized plan for isodose line, IPSA can improve the dose distribution of tumor tissue,reduce mean rectum D 2cc,and increase CI and HI,so it is a preferable optimized treatment planning method in clinical application.