OBJECTIVES: Patients with heart failure with reduced ejection fraction (HFrEF) often require diuretics during hospitalization to alleviate fluid retention and improve prognosis. However, the diuretic efficacy and renal impact of dapagliflozin in this population remain unclear. This study aims to investigate the effects of dapagliflozin on diuresis and renal function in hospitalized patients with HFrEF. METHODS: This retrospective analysis included clinical data from 200 hospitalized HFrEF patients treated at Xiangya Hospital of Central South University between January 2021 and September 2022. Patients were divided into 2 groups based on whether they received dapagliflozin: a standard treatment group (n=120) and a dapagliflozin treatment group (n=80). The following were compared between the 2 groups during hospitalization: The 24-hour average difference of liquid intake and output during the first 5 days, urine output, cumulative urine output, diuretic efficiency, estimated glomerular filtration rate (eGFR), N-terminal pro B-type natriuretic peptide (NT-proBNP), hospitalization costs, drug costs, and cost-effectiveness ratio (C/E). RESULTS: 1) Primary outcome: The 24-hour average difference of liquid intake and output during the first 5 days was significantly higher in the dapagliflozin treatment group than in the standard treatment group (P<0.05). 2) Secondary outcomes: The 24-hour average urine volume, cumulative urine volume and diuretic efficiency in the first 5 days of dapagliflozin treatment group were higher than those in the standard treatment group, and the differences were statistically significant (all P<0.05). Among patients with impaired renal function on admission [eGFR between 45 and 90 mL/(min·1.73 m²)], the change in eGFR after treatment was significantly smaller in the dapagliflozin treatment group (P<0.05). For patients with normal renal function on admission [eGFR >90 mL/(min·1.73 m²)], the difference in eGFR changes between 2 groups was not significant (P>0.05). NT-proBNP decreased more in the dapagliflozin treatment group than in the standard treatment group during hospitalization (P<0.05). 3) Other indicators: The length of hospital stay was longer in the dapagliflozin treatment group. However, discharge systolic blood pressure, drug costs, and hospitalization costs were all higher in the standard group, though differences were not statistically significant (all P>0.05). The C/E was more favorable in the dapagliflozin treatment group (425.36 vs. 476.67). CONCLUSIONS In hospitalized patients with chronic HFrEF, dapagliflozin treatment increased 24-hour average difference of liquid intake and output and total urine output, reduced NT-proBNP levels, and showed a milder decline in eGFR in those with pre-existing renal impairment. Discharge blood pressure, drug costs, and hospital stay were not significantly affected. While standard therapy may offer better short-term clinical benefits, dapagliflozin demonstrated a superior short-term cost-effectiveness profile.
Humans ; Benzhydryl Compounds/pharmacology* ; Glucosides/pharmacology* ; Retrospective Studies ; Male ; Female ; Heart Failure/physiopathology* ; Hospitalization ; Middle Aged ; Aged ; Glomerular Filtration Rate/drug effects* ; Diuretics/therapeutic use* ; Kidney/drug effects* ; Natriuretic Peptide, Brain/blood* ; Stroke Volume ; Peptide Fragments/blood* ; Diuresis/drug effects*

Objective To evaluate the clinical value of holographic image navigation in urological laparoscopic and robotic surgery.Methods The data of patients were reviewed retrospectively for whom accepted holographic image navigation laparoscopic and robotic surgery from Jan.2019 to Dec.2019 in Beijing United Family Hospital and other 18 medical centers,including 78 cases of renal tumor,2 cases of bladder cancer,2 cases of adrenal gland tumor,1 cases of renal cyst,1 case of prostate cancer,1 case of sweat gland carcinoma with lymph node metastasis,1 case of pelvic metastasis after radical cystectomy.All the patients underwent operations.In the laparoscopic surgery group,there were 27 cases of partial nephrectomy,1 case of radical prostatectomy,2 cases of radical cystectomy and 2 cases of adrenalectomy.In the da Vinci robotic surgery group of 54 cases,there were 51 cases of partial nephrectomy,1 case of retroperitoneal lymph node dissection,1 case of retroperitoneal bilateral renal cyst deroofing and 1 case of resection of pelvic metastasis.There were 41 partial nephrectomy patients with available clinical data for statistic,with a median age of 53.5 years (range 24-76),including 26 males and 15 females.The median R.E.N.A.L score was 7.8 (range 4-11).Before the operation,the engineers established the holographic image based on the contrast CT images and reports.The surgeon applied the holographic image for preoperative planning.During the operation,the navigation was achieved by real time fusing holographic images with the laparoscopic surgery images in the screen.Results All the procedures had been complete uneventfully.The holographic images helped surgeon in understanding the visual three-dimension structure and relation of vessels supplying tumor or resection tissue,lymph nodes and nerves.By manipulating the holographic images extracorporeally,the fused image guide surgeons about location vessel,lymph node and other important structure and then facilitate the delicate dissection.For the 41 cases with available clinical data including 23 cases of robotic-assisted partial nephrectomy and 18 cases of laparoscopic nephrectomy,the median operation time was 140 (range 50-225) min,the median warm ischemia time was 23 (range 14-60) min,the median blood loss was 80(range 5-1 200) ml.In the robotic surgery group,the median operation time was 140 (range 50-215)min,the median warm i schemia time was 21 (range 17-40)min,the median blood loss was 150(range 30-1 200)ml.In the laparoscopic surgery group,the median operation time was 160(range 80-225)min,the median warm ischemia time was 25 (range 14-60)min,the median blood loss was 50 (range 5-1 200) ml.All the patients had no adjacent organ injury during operation.There were 2 cases with Clavien Ⅱ complications.One required transfusion and the other one suffered hematoma post-operation.However,the tumors were located in the renal hilus for these 2 cases and the R.E.N.A.L scores were both 11.Conclusions Holographic image navigation can help location and recognize important anatomic structures during the surgical procedures..This technique will reduce the tissue injury,decrease the complications and improve the success rate of surgery.

Objective: To explore the diagnostic value of serum NSE, S100B protein and myocardial zymogram in premature infants with intrauterine infection. Methods: From January 2016 to December 2017, 60 preterm infants with intrauterine infection in the Integrated Chinese and Western Medicine Hospital of Wenzhou were selected in the study.According to whether brain injury occurred, they were divided into brain injury group (28 cases) and non-brain injury group (32 cases). Serum NSE content was detected by chemiluminescence method, serum S100B protein level was detected by enzyme linked immunosorbent assay (ELISA), and serum CK and HBDH levels were detected by automatic biochemical analyzer.The serum levels of NSE, S100B, CK and HBDH were compared between the two groups, the combined diagnostic efficacy of NSE+ S100B protein+ CK+ HBDH was analyzed, the correlation of serum NSE, S100B protein, CK, HBDH with brain injury wasanalyzed. Results: The levels of serum NSE [(2.43±0.54)μg/L] and S 100B [(14.36±3.21)ng/L] in the brain injury group were higher than those in the non-brain injury group [(0.97±0.27)μg/L and (8.10±1.87)ng/L] (t=13.498, 9.370, all P<0.05). The levels of serum CK [(437.64±54.12)U/L] and HBDH [(387.91±56.45)U/L] in the brain injury group were significantly higher than those in the non-brain injury group [(183.54±32.58)U/L and (174.3±26.63)U/L] (t=22.347, 19.126, all P<0.05). The sensitivity and specificity of the combined diagnosis of NSE+ S100B protein and myocardial zymogram were higher than those of each single index.Serum NSE, S100B protein, CK and HBDH were positively correlated with brain injury. Conclusion The elevation of serum NSE, S100B protein and myocardial zymogram in preterm infants with intrauterine infection after birth has certain clinical significance in judging whether brain injury occurs or not.

Objective To explore the clinical efficacy and side effects of intraperitoneal perfusion of verapamil and chemotherapeutic drugs in treating patients with gastric cancer after operation.Methods Totally 184 gastric cancer patients accepted radical surgery with postoperative classification (pT1/2/3/4N2/3M0) were randomly divided into control group (n =58) and treatment group (n =126).For the post-gastrectomy chemotherapeuric treatment,1 g of 5-fluorouracil and 70 to 90 mg of cisplatin were administrated for the patients in the control group,while 1 g of 5-fluorouracil,70 to 90 mg of cisplatin and 25 mg of verapamil were given to the patients in the treatment group.Patients in both groups received intravenous administration of 20 to 30 mg of doxorubicin 3 ～ 5 hours before the intraperitoneal chemotherapy,and 0.1 g of leucovorin 30 minutes prior to the intraperitoneal chemotherapy.On the second day,intraperitoneal chemotherapy of 0.5 to 0.75 g 5-fiuorouracil was given to all patients for 3 to 5 days.The disease-free survival rate,overall survival rate,disease-free survival (DFS),overall survival (OS),peritoneal recurrence rate,liver metastasis rate,gastric remnant recurrence rate,adverse reactions were examined and recorded at the time points of 12 and 24 months after the chemotherapy treatment.Results In the treatment group,disease-free survival and overall survival rates at 12 and 24 months were significantly higher than those in the control group,and the median DFS and OS were significantly longer than the control group (P ＜ 0.05).In patients with regional lymph node staging (N2,N3),low differentiated adenocarcinoma,tumor diameter greater than 4-cm,the disease free survival rate and overall survival rate at 12 and 24-months were significantly higher than the control group,and the median DFS and OS were significantly longer than the control group (P ＜0.05).In the treatment group,intraperitoneal recurrence rate and liver metastasis rate at 12 and 24-months were significantly lower than the control group (P ＜ 0.05).There was no significant difference in recurrence rate of gastric stump between the control group and treatment group.Application of verapamil did not increase the incidence rate of adverse reactions.There were 8 patients with mild abdominal pain and 3 patients with incomplete intestinal obstruction,and all of them were cured after one week of treatment.Conclusion The intraperitoneal perfusion of verapamil and chemotherapeutic drugs can significantly increase the disease-free survival rate and overall survival rate,prolong the median DFS and OS,reduce the recurrence rate of intra-abdominal and liver metastasis rate in the gastric cancer patients at 12 and 24 months after chemotherapy.

Objective To explore the clinical efficacy and side effects of intraperitoneal perfusion of verapamil and chemotherapeutic drugs in treating patients with gastric cancer after operation.Methods Totally 184 gastric cancer patients accepted radical surgery with postoperative classification (pT1/2/3/4N2/3M0) were randomly divided into control group (n =58) and treatment group (n =126).For the post-gastrectomy chemotherapeuric treatment,1 g of 5-fluorouracil and 70 to 90 mg of cisplatin were administrated for the patients in the control group,while 1 g of 5-fluorouracil,70 to 90 mg of cisplatin and 25 mg of verapamil were given to the patients in the treatment group.Patients in both groups received intravenous administration of 20 to 30 mg of doxorubicin 3 ～ 5 hours before the intraperitoneal chemotherapy,and 0.1 g of leucovorin 30 minutes prior to the intraperitoneal chemotherapy.On the second day,intraperitoneal chemotherapy of 0.5 to 0.75 g 5-fiuorouracil was given to all patients for 3 to 5 days.The disease-free survival rate,overall survival rate,disease-free survival (DFS),overall survival (OS),peritoneal recurrence rate,liver metastasis rate,gastric remnant recurrence rate,adverse reactions were examined and recorded at the time points of 12 and 24 months after the chemotherapy treatment.Results In the treatment group,disease-free survival and overall survival rates at 12 and 24 months were significantly higher than those in the control group,and the median DFS and OS were significantly longer than the control group (P ＜ 0.05).In patients with regional lymph node staging (N2,N3),low differentiated adenocarcinoma,tumor diameter greater than 4-cm,the disease free survival rate and overall survival rate at 12 and 24-months were significantly higher than the control group,and the median DFS and OS were significantly longer than the control group (P ＜0.05).In the treatment group,intraperitoneal recurrence rate and liver metastasis rate at 12 and 24-months were significantly lower than the control group (P ＜ 0.05).There was no significant difference in recurrence rate of gastric stump between the control group and treatment group.Application of verapamil did not increase the incidence rate of adverse reactions.There were 8 patients with mild abdominal pain and 3 patients with incomplete intestinal obstruction,and all of them were cured after one week of treatment.Conclusion The intraperitoneal perfusion of verapamil and chemotherapeutic drugs can significantly increase the disease-free survival rate and overall survival rate,prolong the median DFS and OS,reduce the recurrence rate of intra-abdominal and liver metastasis rate in the gastric cancer patients at 12 and 24 months after chemotherapy.

Objective To investigate the effect of verapamil on chemosensitivity and apoptosis of esophageal cancer cells.Methods The IC50 values (IC501) of three kinds of chemotherapy drugs:paclitaxel,cisplatin,and 5-fluorouracil were detected by CCK-8 method in 4 kinds of esopha geal cancer cell lines (EC109,EC9706,KYSE-450,TE-1).Each cell was processed by verapamil (4.91 μg/mL) combined with the chemotherapy treatment above,IC50 (IC502) value was detected by CCK8 assay combined with chemotherapy for the verapamil of the 4 esophageal carcinoma cell lines (EC109,EC9706,KYSE-450 and TE-1).A pair of esophageal cancer cells with the most significant reversal of the resistance to chemotherapy by VER detected by the previous experiments were included as research objects,and Annexin V-PI double staining method was used to detect the apoptosis of esophageal cancer cells.Results The IC50 values of paclitaxel in KYSE-450 and EC9706 cell lines were significantly higher than that in EC109 and TE-1.The IC50 values of cisplatin in TE-1 cells were significantly less than those in the other three cells,while the IC50 values of 5-fluorouracil in EC109 were significantly higher than that in other three cell lines.After adding verapamil,the IC50 values of paclitaxel,cisplatin and 5-fluorouracil in four esophageal cancer cell lines (EC109,EC9706,KYSE-450 and TE-1) all decreased to different degrees,and the above three kinds of chemotherapeutic drugs had increased their sensitivity to varying degrees.Among them,the cisplatin group before adding verapamil had different degrees of resistance compared with EC109,EC9706,KYSE-450,TE-1.After joining verapamil,IC50 value change for the EC9706 multiplied for 15.2 times,suggesting that the reversal was sensitive;IC50 value change for EC109 was 1.6 times smaller,suggesting that the reversal was tolerant.Conclusion Verapamil reversal of EC9706 adriamycin has highest efficiency index (15.2 times),there was significant difference compared with the EC109 cells (1.6 times).Tipthe EC9706 (DDP) sensitivity to the reversal of verapamil,and EC109 (DDP) reverse resistance of verapamil.Verapamil may enhance the ability to reverse chemotherapy tolerance by promoting cell apoptosis,thereby enhancing the sensitivity of chemotherapeutic drugs.

Objective To investigate the effect of verapamil on chemosensitivity and apoptosis of esophageal cancer cells.Methods The IC50 values (IC501) of three kinds of chemotherapy drugs:paclitaxel,cisplatin,and 5-fluorouracil were detected by CCK-8 method in 4 kinds of esopha geal cancer cell lines (EC109,EC9706,KYSE-450,TE-1).Each cell was processed by verapamil (4.91 μg/mL) combined with the chemotherapy treatment above,IC50 (IC502) value was detected by CCK8 assay combined with chemotherapy for the verapamil of the 4 esophageal carcinoma cell lines (EC109,EC9706,KYSE-450 and TE-1).A pair of esophageal cancer cells with the most significant reversal of the resistance to chemotherapy by VER detected by the previous experiments were included as research objects,and Annexin V-PI double staining method was used to detect the apoptosis of esophageal cancer cells.Results The IC50 values of paclitaxel in KYSE-450 and EC9706 cell lines were significantly higher than that in EC109 and TE-1.The IC50 values of cisplatin in TE-1 cells were significantly less than those in the other three cells,while the IC50 values of 5-fluorouracil in EC109 were significantly higher than that in other three cell lines.After adding verapamil,the IC50 values of paclitaxel,cisplatin and 5-fluorouracil in four esophageal cancer cell lines (EC109,EC9706,KYSE-450 and TE-1) all decreased to different degrees,and the above three kinds of chemotherapeutic drugs had increased their sensitivity to varying degrees.Among them,the cisplatin group before adding verapamil had different degrees of resistance compared with EC109,EC9706,KYSE-450,TE-1.After joining verapamil,IC50 value change for the EC9706 multiplied for 15.2 times,suggesting that the reversal was sensitive;IC50 value change for EC109 was 1.6 times smaller,suggesting that the reversal was tolerant.Conclusion Verapamil reversal of EC9706 adriamycin has highest efficiency index (15.2 times),there was significant difference compared with the EC109 cells (1.6 times).Tipthe EC9706 (DDP) sensitivity to the reversal of verapamil,and EC109 (DDP) reverse resistance of verapamil.Verapamil may enhance the ability to reverse chemotherapy tolerance by promoting cell apoptosis,thereby enhancing the sensitivity of chemotherapeutic drugs.

Objective To verify the safety and advantages of total transperitoneal laparoscopic nephroureterectomy (ttLNU) in the treatment of upper urinary tract urothelial carcinoma (UTUC).Methods From Jun.2013 to Jun.2014,there were 13 UTUC patients treated with ttLNU,including 7 males and 6 females.The mean age was 70.4 ± 8.3 yrs,and BMI was 23.3±4.1.Of them,11 cases were diagnosed with renal pelvis carcinoma,6 in the left and 5 in the right.2 cases were diagnosed with left ureteral carcinoma.TNM stages were T1-T3N0M0.Patients were put on lateral position and the position was not changed during the operation.A ttLNU was performed,and the specimen was removed from the middle extended inferior umbilical incision.Results The mean operative time was 188±33 (150-240) min,the intraoperative blood loss was 150.5±60.1 (50-700) ml,and the time of out-of-bed activity was between 1 and 4 d.The mean postoperative drainage time was 6.8±4.6 (3-6) d.The mean postoperative bowel function recovery time was 1.5± 1.0 (2-4) d and postoperative hospital stay was 12.8±7.0 (3-27) d.The ttLNU procedures were successfully performed in all cases without conversion to open surgery.Pathological results showed urothelial carcinoma in all cases,including 8 high grade and 5 low grade.All the surgical margins were negative.The followed up was from 2 to 12 mon,and there was no tumor recurrence and metastasis found.Conclusions Total transperitoneal laparoscopic nephroureterectomy in the treatment of upper urinary tract urothelial carcinoma is characterized by short operative time,low blood loss,decreased trauma and quick recovery.This is a safe and effective treatment option for the treatment of upper urinary tract urothelial carcinoma.

Objective To explore the effects of baicalin on the expression of TAFI,NF-κB,and ACE2 in the atherosclerotic rats and discuss the anti-atherosclerosis mechanisms of baicalin.Methods The subjects were healthy male Wistar rats.The rats were divided into sham operation group,model group,baicalin high dose group (1 50 mg·kg-1 ·d-1 )and baicalin low dose group (100 mg·kg-1 ·d-1 ).Plasma TAFI activity were detected with enzymatic assays.The expression of NF-κB and ACE2 were detec-ted with immunohistochemical staining.Results Compared with sham group,the rest groups of TAFI and ACE2 activity were sig-nificantly higher (P <0.05),and the expression of NF-κB,had significant decreased (P <0.05).Compared with the model group, the level of TAFI and ACE2 in baicalin drug group was significantly lower than the model group (P <0.05),and the expression of NF-κB,had significant increased.Conclusion Baicalin can reduce TAFI and ACE2 level,and upregulate the expression of NF-κB to play its role in anti atherosclerosis.

Objective: To test the feasibility of drag-reducing polymers (DRP) for improving coronary microcirculation in a canine model in order to provide the experimental basis for treating myocardial microcirculation dysfunction. Methods: A total of 8 dogs received open-chest surgery and they had intravenous injections, in turn, with adenosine (ADN), DRP 250 mg/L and DRP+ADN. The function y=A × (1-e-βt) was used to calculate the myocardium capillary volume (A value), capillary velocity (β value) and myocardial blood lfow (A ? β value) by myocardial contrast echocardiography. Results: With DRP infusion, the A value in experimental canine was similar to the baseline condition,P>0.05; while theβ value and A ? β value were signiifcantly increased as (0.57 ± 0.10) 1/s vs (0.23 ± 0.03) 1/s,P<0.01 and (11.51 ± 1.96) VI/s vs (5.15 ± 0.86) VI/s,P <0.05 respectively. With combined infusion of DRP+ADN, the β value and A ? β value were similar to the baseline condition, bothP>0.05. Conclusion: DRP improved coronary microcirculation primarily by modulating the β value in experimental canine model, and hopefully, this unique hemodynamics could provide a new approach for treating myocardial microcirculation dysfunction.