ObjectiveTo investigate the effect of modified Weijingtang on the pyroptosis of RAW264.7 macrophages via the cysteinyl aspartate-specific protease-1 （Caspase-1）/gasdermin D （GSDMD） pathway. MethodLipopolysaccharide （LPS） was used to induce pyroptosis of RAW264.7 cells. The blank group was treated with the blank serum， and the intervention groups were treated with the sera containing different doses of modified Weijingtang. After 24 h， the viability of cells in different groups was examined by the cell counting kit-8 （CCK-8）. The pyroptosis and morphology of cells in each group were observed by a scanning electron microscope and a phase-contrast microscope， respectively. The mRNA and protein levels of nucleotide-binding oligomerization domain-like receptor protein 3 （NLRP3）， Caspase-1， and GSDMD in each group were determined by real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） and Western blot， respectively. The levels of interleukin （IL）-18 and IL-1β in each group were measured by enzyme-linked immunosorbent assay. ResultUnder the electron microscope， RAW264.7 cells presented the best morphology and structure in the blank group and obvious pyroptosis and leakage of cell contents in the model （LPS） group. Compared with the model group， the intervention groups showed reduced pyroptosis to varying degrees， and the high-dose group had the closest cell morphology and structure to the blank group. Under the optical microscope， RAW264.7 cells were spherical in the blank group and irregular with protrusions in the model group. Compared with the model group， the intervention groups showed improved cell morphology， and the cell morphology in the group with the dose of 20% was the closest to that in the blank group. The mRNA and protein levels of NLRP3， Caspase-1， and GSDMD in the model group were higher than those in the blank group （P<0.05）. Compared with the model group， each intervention group showed down-regulated expression of the above indicators （P<0.05）. Compared with the blank group， the model group presented elevated levels of IL-18 and IL-1β （P<0.05）， which were lowered in the intervention （10%， 20%） groups （P<0.01）. ConclusionModified Weijingtang inhibits the pyroptosis of macrophages by down-regulating the Caspase-1/GSDMD pathway and reducing the release of proinflammatory cytokines.

Objective:To observe the mechanism of electroacupuncture on nerve repair in mice with neuropathic pain based on the protein kinase C(PKC)-purinergic receptor P2X ligand-gated ion channel 3(P2X3)signal pathway.Methods:A total of 48 mice were randomly divided into sham group,model group,acupuncture group and electroacupuncture group,with 12 mice in each group.Except the sham group,the other mice were constructed with chronic constriction injury(CCI)model.On the 8th day after operation,acupuncture group and electroacupuncture group received acupuncture and electroacupuncture interventions for 7 days.Mechanical withdrawal threshold(MWT)and thermal withdrawal latency(TWL)were measured before operation and 3rd,5th,7th,10th,12th and 14th day after operation.All mice were killed 15 days after operation.The histomorphology of sciatic nerve was ob-served by HE staining.The levels of IL-1β and TNF-α in spinal cord were detected by ELISA.PKC and P2X3 levels in spinal cord tis-sue were detected by Western blot.PKC and P2X3 expressions in spinal cord neurons were detected by Immunofluorescence.Results:In the sham group,the neuronal cells were of different sizes,the cell membrane was intact,the cytoplasm was fine and granular,the nucleus was large and round,and the nucleolus was clearlyvisible in the middle.Atrophic neurons could be seen in the model group,myelinated nerve fibers were disordered,axons were swollen,and spaces were formed between neurons.Compared with the model group,the number of atrophic neurons decreased in the acupuncture group and the electroacupuncture group(P<0.05),the arrange-ment of myelinated nerve fibers improved and the improvement in the electroacupuncture group was more obvious than that in the acu-puncture group.Compared with the sham group at the same time point,on the 3rd,5th,7th,10th,12th and 14th day after opera-tion,the MWT and TWL values of the model group,acupuncture group and electroacupuncture group decreased significantly(P<0.05),while the expressions of IL-1β,TNF-α,PKC,P2X3,the numbers of PKC and P2X3 positive cells and the average optical den-sity increased(P<0.05).Compared with the model group,the values of MWT and TWL in the acupuncture group and electroacupunc-ture group increased significantly on the 10th,12th and 14th day after operation(P<0.05),while the expression of IL-1β,TNF-α,PKC,P2X3,the number of PKC and P2X3 positive cells and the average optical density decreased(P<0.05).Compared with the acu-puncture group,the values of MWT and TWL in the electroacupuncture group increased significantly on the 10th,12th and 14th day after operation(P<0.05),while the expressions of IL-1β,TNF-α,PKC,P2X3,the numbers of PKC and P2X3 positive cells and the average optical density decreased(P<0.05).Conclusion:Electroacupuncture can reduce the neuroinflammatory reaction of CCI model mice,reduce the expression levels of PKC and P2X3,improve the morphology of sciatic nerve cells and the arrangement of myelinated nerve fibers,reduce the gap between neurons,increase the values of MWT and TWL,and relieve the degree of neuropathic pain.

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*

Lipid Droplets/metabolism* ; Bacteria ; Lipid Metabolism

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 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 evaluate the curative effect of microwave ablation (MWA) for solitary hepatocellular carcinoma (HCC) sized less than 5 cm,and to discuss the prognosis and its influence factors.Methods The clinical data of 603 HCC patients,who were admitted to authors' hospital during the period from 2011 to 2013 to receive MWA,were retrospectively analyzed.The patients were followed up till March 2016.Results According to the inclusion criteria,a total of 603 patients were enrolled in this study.Complete ablation of HCC lesions was obtained in 5.8％ of patients (35/603).No statistically significant difference in complete ablation rate existed between each other among groups of different tumor diameter (P=0.056).The incidence of severe complications was 1.7％ (10/603).The median survival time was (59.6±1.9)months,while the 1-,2-and 3-year overall survival rates were 94.7％,81.9％ and 71.8％ respectively.In terms of overall survival rate,no statistically significant difference existed between groups of different age as well as between groups of different tumor diameter (P=0.225 and P=0.777 respectively),but statistically significant difference existed between groups of different sex as well as between groups of different recurrence interval (P=0.029 and P＜0.001 respectively).Univariate and multivariate analysis showed that gender,preoperative albumin level and recurrence interval were the factors influencing overall survival rate (P=0.035,P=0.006 and P＜0.001 respectively).Conclusion For the treatment of solitary HCC sized less than 5 cm,MWA has reliable curative effect,it is a safe and minimally-invasive therapy for HCC.The overall survival rate between patients with different age or between patients with different HCC size is not obviously different.The gender,preoperative albumin level and recurrence interval are independent factors that affect the overall survival rate.