Objective To observe the effect of extracorporeal shockwave therapy (ESWT) in regulating endothelial cell phosphatase and tensin homolog deleted on chromosome ten (PTEN) expression on lower ex-tremity vascular lesion and its possible mechanism.Methods Twenty-four 2-month-old healthy male SD rats were randomly divided into the three groups:control group (group A),diabetes angiopathy group (group B),diabetes angiopathy+ESWT group (group C).The group B and C were fed with high fat and high sugar and intraperitoneally injected with streptozotocin 60 mg/kg to establish the rat model of diabetes vascular lesion. The group C received ESWT at 1 week (T1),2 weeks (T2),3 weeks (T3) and 4 weeks (T4) after modeling,and the blood stream velocity of rat femoral artery vascular lesion area and vascular internal diameter were measured at T4 by ultrasound.At the end of ESWT,the rats were immediately killed for taking their femoral arteries and gastrocnemius.The structures of the femoral arteries in each group were observed under electron microscopy.Western blot was used to detect the expression levels of PTEN,PI3K and Akt proteins,while qRT-PCR was used to detect the expression levels of PTEN mRNA.Immunofluorescence was used to detect the expression level of CD31 in gastrocnemius muscle .Results The peak systolic flow velocity and end-dias-tolic flow velocity of femoral artery at T4 in group B and C were significantly lower than those in group A (P<0.05),but group C was higher than group B (P<0.05).The internal diameter of femoral artery had no statistical difference among 3 groups (P>0.05).The PTEN expression level in group B and group C was sig-nificantly lower than that in group A (P<0.05),while group C was higher than group B (P<0.05).The ex-pression levels of PI3K and Akt in group B were higher than those in group A (P<0.05),and group C was lower than group B (P<0.05).The PTEN mRNA expression level in group B and group C was significantly lower than that in group A (P<0.05),but group C was higher than group B (P<0.05).Under electron mi-croscopy,it was observed that after ESWT,the endothelial cell damage in group C was obvious when com-pared with group B.The CD31 expression level in group B and group C was significantly lower than that in group A (P<0.05),but group C was higher than group B (P<0.05).Conclusion ESWT could improve the vascular function,increase the peak velocity during systolic period of femoral artery in diabetes rats and im-prove the microvessel density of gastrocnemius muscle by up-regulating PTEN in lower extremity artery and down-regulating PI3K and Akt in diabetes rats.

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::Dopamine, via its receptors, plays a vital role in the maintenance of blood pressure by modulating renal sodium transport. However, the role of the D 4 dopamine receptor (D 4 receptor) in renal proximal tubules (PRTs) is still unclear. This study aimed to verify the hypothesis that activation of D 4 receptor directly inhibits the activity of the Na +-K +-ATPase (NKA) in RPT cells. Methods::NKA activity, nitric oxide (NO) and cyclic guanosine monophosphate (cGMP) levels were measured in RPT cells treated with the D 4 receptor agonist PD168077 and/or the D 4 receptor antagonist L745870, the NO synthase inhibitor NG-nitro-L-arginine-methyl ester (L-NAME) or the soluble guanylyl cyclase inhibitor 1H-[1,2,4] oxadiazolo-[4,3-a] quinoxalin-1-one (ODQ). Total D 4 receptor expression and its expression in the plasma membrane were investigated by immunoblotting in RPT cells from Wistar-Kyoto (WKY) rats and spontaneously hypertensive rats (SHRs). Results::Activation of D 4 receptors with PD168077, inhibited NKA activity in RPT cells from WKY rats in a concentration- and time-dependent manner. The inhibitory effect of PD168077 on NKA activity was prevented by the addition of the D 4 receptor antagonist L745870, which by itself had no effect. The NO synthase inhibitor L-NAME and the soluble guanylyl cyclase inhibitor ODQ, which by themselves had no effect on NKA activity, eliminated the inhibitory effect of PD168077 on NKA activity. Activation of D 4 receptors also increased NO levels in the culture medium and cGMP levels in RPT cells. However, the inhibitory effect of D 4 receptors on NKA activity was absent in RPT cells from SHRs, which could be related to decreased plasma membrane expression of D 4 receptors in SHR RPT cells. Conclusions::Activation of D 4 receptors directly inhibits NKA activity via the NO/cGMP signaling pathway in RPT cells from WKY rats but not SHRs. Aberrant regulation of NKA activity in RPT cells may be involved in the pathogenesis of hypertension.

Objective::Dopamine, via its receptors, plays a vital role in the maintenance of blood pressure by modulating renal sodium transport. However, the role of the D 4 dopamine receptor (D 4 receptor) in renal proximal tubules (PRTs) is still unclear. This study aimed to verify the hypothesis that activation of D 4 receptor directly inhibits the activity of the Na +-K +-ATPase (NKA) in RPT cells. Methods::NKA activity, nitric oxide (NO) and cyclic guanosine monophosphate (cGMP) levels were measured in RPT cells treated with the D 4 receptor agonist PD168077 and/or the D 4 receptor antagonist L745870, the NO synthase inhibitor NG-nitro-L-arginine-methyl ester (L-NAME) or the soluble guanylyl cyclase inhibitor 1H-[1,2,4] oxadiazolo-[4,3-a] quinoxalin-1-one (ODQ). Total D 4 receptor expression and its expression in the plasma membrane were investigated by immunoblotting in RPT cells from Wistar-Kyoto (WKY) rats and spontaneously hypertensive rats (SHRs). Results::Activation of D 4 receptors with PD168077, inhibited NKA activity in RPT cells from WKY rats in a concentration- and time-dependent manner. The inhibitory effect of PD168077 on NKA activity was prevented by the addition of the D 4 receptor antagonist L745870, which by itself had no effect. The NO synthase inhibitor L-NAME and the soluble guanylyl cyclase inhibitor ODQ, which by themselves had no effect on NKA activity, eliminated the inhibitory effect of PD168077 on NKA activity. Activation of D 4 receptors also increased NO levels in the culture medium and cGMP levels in RPT cells. However, the inhibitory effect of D 4 receptors on NKA activity was absent in RPT cells from SHRs, which could be related to decreased plasma membrane expression of D 4 receptors in SHR RPT cells. Conclusions::Activation of D 4 receptors directly inhibits NKA activity via the NO/cGMP signaling pathway in RPT cells from WKY rats but not SHRs. Aberrant regulation of NKA activity in RPT cells may be involved in the pathogenesis of hypertension.

Objective: To evaluate the efficacy of reinforcement on duodenal stump using single purse-string suture during laparoscopic radical gastrectomy for gastric cancer in preventing duodenal stump leakage. Methods: A descriptive cohort study was conducted to retrospectively collect clinical data of 211 patients with gastric adenocarcinoma who underwent laparoscopic radical gastrectomy with Roux-en-Y or Billroth Ⅱ reconstruction and reinforcement on duodenal stump using laparoscopic single purse-string suture in Zhongshan Hospital of Fudan University between January 2013 and December 2016. Of 211 patients, 136 were male and 75 were female with mean age of (57.5±11.1)(24 to 87) years. Tumors locating at gastric upper 1/3, middle 1/3 and low 1/3 were found in 62, 68 and 81 patients respectively. Eighty-three cases underwent total gastrectomy, 128 underwent distal subtotal gastrectomy, 107 underwent Roux-en-Y reconstruction and 104 underwent Billroth II reconstruction. The procedure of reinforcement on duodenal stump using single purse-string suture during laparoscopic radical gastrectomy was as follows: (1) after cutting the duodenal stump to about 2.0 cm in length, use a 3-0 single-strand absorbable suture to make a muscle layer purse at a distance of 1.0 to 1.5 cm from the duodenal stump; (2) use the purse line to make a slipknot; (3) push the duodenum stump into the purse with a needle holder or grasper; (4) tighten the knot of the purse string, and then make 4 to 5 knots for reinforcement. Postoperative complications were defined and graded according to the Clavien-Dindo grading criteria, and the incidence of early complications was recorded. Clinicopathologic features and postoperative outcomes were analyzed. Results: All patients completed operations successfully. The mean time of laparoscopic single purse-string suture was (5.1±1.6) (3.6 to 10.2) minutes. Postoperative early complication occurred in 31 cases (14.7%), of whom 27 cases developed surgery-related complications (12.8%), including 7 cases (3.3%) of peritoneal infection, 6 (2.8%) of pancreatic leakage, 4 (1.9%) of wound infection, 4 (1.9%) of gastroplegia, 2 (0.9%) of peritoneal hemorrhage, 2 (0.9%) of intestinal obstruction, 2 (0.9%) of lymphatic leakage, and no duodenal stump leakage; while 4 cases (1.9%) developed internal non-surgical complication, including 3 cases (1.4%) of pulmonary infection and 1 (0.5%) of cardiovascular event. The patient with peritoneal hemorrhage was healed after re-operation and all other patients were discharged uneventfully after conservative treatment. Four cases (1.9%) developed complications beyond grade III a of Clavien-Dindo criteria. Conclusion Reinforcement on duodenal stump using laparoscopic single purse-string suture during laparoscopic radical gastrectomy with Roux-en-Y or Billroth II reconstruction is simple and effective, and can prevent the risk of development of duodenal stump leakage.

Objective To evaluate the efficacy of reinforcement on duodenal stump using single purse?string suture during laparoscopic radical gastrectomy for gastric cancer in preventing duodenal stump leakage. Methods A descriptive cohort study was conducted to retrospectively collect clinical data of 211 patients with gastric adenocarcinoma who underwent laparoscopic radical gastrectomy with Roux?en?Y or BillrothⅡreconstruction and reinforcement on duodenal stump using laparoscopic single purse?string suture in Zhongshan Hospital of Fudan University between January 2013 and December 2016. Of 211 patients, 136 were male and 75 were female with mean age of (57.5±11.1)(24 to 87) years. Tumors locating at gastric upper 1/3, middle 1/3 and low 1/3 were found in 62, 68 and 81 patients respectively. Eighty?three cases underwent total gastrectomy, 128 underwent distal subtotal gastrectomy, 107 underwent Roux?en?Y reconstruction and 104 underwent Billroth II reconstruction. The procedure of reinforcement on duodenal stump using single purse?string suture during laparoscopic radical gastrectomy was as follows: (1) after cutting the duodenal stump to about 2.0 cm in length, use a 3?0 single?strand absorbable suture to make a muscle layer purse at a distance of 1.0 to 1.5 cm from the duodenal stump; (2) use the purse line to make a slipknot; (3) push the duodenum stump into the purse with a needle holder or grasper; (4) tighten the knot of the purse string, and then make 4 to 5 knots for reinforcement. Postoperative complications were defined and graded according to the Clavien?Dindo grading criteria, and the incidence of early complications was recorded. Clinicopathologic features and postoperative outcomes were analyzed. Results All patients completed operations successfully. The mean time of laparoscopic single purse?string suture was (5.1±1.6) (3.6 to 10.2) minutes. Postoperative early complication occurred in 31 cases (14.7%), of whom 27 cases developed surgery?related complications (12.8%), including 7 cases (3.3%) of peritoneal infection, 6 (2.8%) of pancreatic leakage, 4 (1.9%) of wound infection, 4 (1.9%) of gastroplegia, 2 (0.9%) of peritoneal hemorrhage, 2 (0.9%) of intestinal obstruction, 2 (0.9%) of lymphatic leakage, and no duodenal stump leakage; while 4 cases (1.9%) developed internal non?surgical complication, including 3 cases (1.4%) of pulmonary infection and 1 (0.5%) of cardiovascular event. The patient with peritoneal hemorrhage was healed after re?operation and all other patients were discharged uneventfully after conservative treatment. Four cases (1.9%) developed complications beyond grade III a of Clavien?Dindo criteria. Conclusion Reinforcement on duodenal stump using laparoscopic single purse?string suture during laparoscopic radical gastrectomy with Roux?en?Y or Billroth II reconstruction is simple and effective, and can prevent the risk of development of duodenal stump leakage.

Objective To evaluate the efficacy of reinforcement on duodenal stump using single purse?string suture during laparoscopic radical gastrectomy for gastric cancer in preventing duodenal stump leakage. Methods A descriptive cohort study was conducted to retrospectively collect clinical data of 211 patients with gastric adenocarcinoma who underwent laparoscopic radical gastrectomy with Roux?en?Y or BillrothⅡreconstruction and reinforcement on duodenal stump using laparoscopic single purse?string suture in Zhongshan Hospital of Fudan University between January 2013 and December 2016. Of 211 patients, 136 were male and 75 were female with mean age of (57.5±11.1)(24 to 87) years. Tumors locating at gastric upper 1/3, middle 1/3 and low 1/3 were found in 62, 68 and 81 patients respectively. Eighty?three cases underwent total gastrectomy, 128 underwent distal subtotal gastrectomy, 107 underwent Roux?en?Y reconstruction and 104 underwent Billroth II reconstruction. The procedure of reinforcement on duodenal stump using single purse?string suture during laparoscopic radical gastrectomy was as follows: (1) after cutting the duodenal stump to about 2.0 cm in length, use a 3?0 single?strand absorbable suture to make a muscle layer purse at a distance of 1.0 to 1.5 cm from the duodenal stump; (2) use the purse line to make a slipknot; (3) push the duodenum stump into the purse with a needle holder or grasper; (4) tighten the knot of the purse string, and then make 4 to 5 knots for reinforcement. Postoperative complications were defined and graded according to the Clavien?Dindo grading criteria, and the incidence of early complications was recorded. Clinicopathologic features and postoperative outcomes were analyzed. Results All patients completed operations successfully. The mean time of laparoscopic single purse?string suture was (5.1±1.6) (3.6 to 10.2) minutes. Postoperative early complication occurred in 31 cases (14.7%), of whom 27 cases developed surgery?related complications (12.8%), including 7 cases (3.3%) of peritoneal infection, 6 (2.8%) of pancreatic leakage, 4 (1.9%) of wound infection, 4 (1.9%) of gastroplegia, 2 (0.9%) of peritoneal hemorrhage, 2 (0.9%) of intestinal obstruction, 2 (0.9%) of lymphatic leakage, and no duodenal stump leakage; while 4 cases (1.9%) developed internal non?surgical complication, including 3 cases (1.4%) of pulmonary infection and 1 (0.5%) of cardiovascular event. The patient with peritoneal hemorrhage was healed after re?operation and all other patients were discharged uneventfully after conservative treatment. Four cases (1.9%) developed complications beyond grade III a of Clavien?Dindo criteria. Conclusion Reinforcement on duodenal stump using laparoscopic single purse?string suture during laparoscopic radical gastrectomy with Roux?en?Y or Billroth II reconstruction is simple and effective, and can prevent the risk of development of duodenal stump leakage.

The strategies for prevention and treatment of recent complications after radical gastrectomy should be of equal emphasis on both theory and technology.Systematic prevention is the fundamental strategy,and adequate preoperative assessment and preparation are the basis.A reasonable extension of the radical gastrectomy and standard and refined surgical procedures could reduce the occurrence of complications.In addition,identifying these complications timely and taking effective treatments promptly according to the clinical context are the keys to reducing the treatment cycle and decreasing the mortality.