Kai-Xin-San ameliorates Alzheimer's disease-related neuropathology and cognitive impairment in APP/PS1 mice via the mitochondrial autophagy-NLRP3 inflammasome pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Kai-Xin-San (KXS) is a classic famous prescription that has been utilized for centuries to address dementia. New investigations have shown that the anti-dementia effect of KXS is connected with improved neuroinflammation. Nevertheless, the underlying mechanism is not well elucidated. AIM OF THE STUDY: We propose to discover the ameliorative impact of KXS on Alzheimer's disease (AD) and its regulatory role on the mitochondrial autophagy-nod-like receptor protein 3 (NLRP3) inflammasome pathway. MATERIALS AND METHODS: The Y maze, Morris water maze, and new objection recognition tests were applied to ascertain the spatial learning and memory capacities of amyloid precursor protein/presenilin 1 (APP/PS1) mice after KXS-treatment. Meanwhile, the biochemical indexes of the hippocampus were detected by reagent kits. The pathological alterations and mitochondrial autophagy in the mice' hippocampus were detected utilizing hematoxylin and eosin (H&E), immunohistochemistry, immunofluorescence staining, and transmission electron microscopy. Besides, the PTEN-induced putative kinase 1 (PINK1)/Parkin and NLRP3 inflammasome pathways protein expressions were determined employing the immunoblot analysis. RESULTS: The results of behavioral tests showed that KXS significantly enhanced the AD mice' spatial learning and memory capacities. Furthermore, KXS reversed the biochemical index levels and reduced amyloid-ß protein deposition in AD mice brains. Besides, H&E staining showed that KXS remarkably ameliorated the neuronal damage in AD mice. Concurrently, the results of transmission electron microscopy suggest that KXS ameliorated the mitochondrial damage in microglia and promoted mitochondrial autophagy. Moreover, the immunofluorescence outcomes exhibited that KXS promoted the expression of protein 1 light chain 3B (LC3B) associated with microtubule and the generation of autophagic flux. Notably, the immunofluorescence co-localization results confirmed the presence of mitochondrial autophagy in microglia. Finally, KXS promoted the protein expressions of the PINK1/Parkin pathway and reduced the activation of NLRP3 inflammasome. Most importantly, these beneficial effects of KXS were attenuated by the mitochondrial autophagy inhibitor chloroquine. CONCLUSION: KXS ameliorates AD-related neuropathology and cognitive impairment in APP/PS1 mice by enhancing the mitochondrial autophagy and suppressing the NLRP3 inflammasome pathway.

Anti-hepatocellular carcinoma activity of Sorbaria sorbifolia by regulating VEGFR and c-Met/apoptotic pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Sorbaria sorbifolia (SS) is a traditional Chinese medicine (TCM) that has been employed anti-hepatocellular carcinoma (HCC) for over 2000 years; yet, its underlying mechanism is still not fully understood. AIM OF THE STUDY: In this study, we evaluated the anti-HCC effect on the freeze-dried powder of the water extract of SS (FDSS) by inhibiting tumor-induced neovascularization, and promoting apoptosis, and elucidated the underlying mechanisms. MATERIALS AND METHODS: HCC cell lines (HepG2 and Huh7 cells) and HepG2 xenograft tumors in zebrafish were employed as in vivo and in vitro models, respectively, to evaluate the anti- HCC-indued neovascularization and apoptosis. In HCC cell lines, CCK-8 assay, wound-healing assay, transwell assay, cell circle assay, apoptosis assay, transmission electron microscopy, and co-culture assay were performed in vitro; in HepG2 xenograft tumor-zebrafish, tumor growth inhibition assay, hematoxylin and eosin (HE) staining, xenograft tumor-zebrafish apoptosis assay, and HCC-indued neovascularization assay were performed to evaluate the effect of FDSS on biological behavior of tumor, HCC-indued neovascularization, and apoptosis. The expression of VEGFR and c-Met/apoptotic pathway-related proteins was detected by western blotting analysis. Assays for c-Met and VEGFR activation were conducted to assess the impact of FDSS in either agonistic or inhibitory roles on these receptor proteins. RESULTS: The findings from our study revealed that FDSS effectively suppresses the proliferation, migration, and invasion of HepG2 and Huh7 cells, as well as inhibiting tumor growth in the HepG2 xenograft zebrafish model by downregulating the expression of p-Met and p-AKT proteins. FDSS decreased the tumor growth associated with promoting apoptosis, including arresting HepG2 and Huh7 cells cycle at G0/G1phase, increasing apoptotic cell numbers and apoptotic bodies in cancer cells, and increasing the apoptotic fluorescence of xenograft tumor zebrafish by downregulating Bcl-2 proteins and upregulating Bax, caspase-9, and caspase-3 levels. We also found that FDSS can inhibit HCC-induced neovascularization and regulate VEGFR. Using an agonist or inhibitor of c-Met and VEGFR in HepG2 cells, we discovered that FDSS can downregulate c-Met and VEGFR protein expression. CONCLUSION: FDSS exerts an anti-HCC effect by inhibiting HCC-indued neovascularization and pro-apoptosis through the inhibition of the action of VEGFR and c-Met/apoptotic pathway.

The diagnosis and management of intestinal obstruction after pediatric liver transplantation.

BACKGROUND: The aim of this study was to analyze the risk factors, causes, and management of intestinal obstruction after pediatric liver transplantation. METHODS: Retrospective analysis was performed on pediatric liver transplantation recipients from January 1st 2013 to December 31st 2019 at Organ Transplant Center, Tianjin First Central Hospital. The cases of intestinal obstruction were analyzed. RESULTS: A total of 1034 pediatric liver transplantations were performed during the study period, 66 intestinal obstructions were diagnosed in 61 recipients. Three recipients suffered intestinal obstructions twice, and one recipient suffered three times. Forty of the 66 cases were treated with non-surgical treatment, including fasting, gastrointestinal decompression, purgation, enema, and parenteral nutrition. Surgical intervention was performed in 26 cases. Diaphragmatic hernia, intestinal inflammatory stenosis, PTLD, and intestine perforation are essential causes of intestinal obstruction in pediatric liver transplant recipients. Diaphragmatic hernia was independent risk factors for intestinal obstruction. The 1-, 2- and 3-year survival rate of the recipients with or without intestinal obstruction were 98.4%, 96.5%, 96.5% and 95.3%, 94.4%, 94.0%, respectively, without significant difference. CONCLUSIONS: Most cases of intestinal obstruction after liver transplantation in children can be remitted by non-surgical treatment, but there are still some cases need to be treated by surgery. Both measures are related to ideal outcomes, intestinal obstruction does not increase the mortality rate in pediatric liver transplantation.

[5-year follow-up to transurethral vaporesection of the prostate using the 2 micron continuous wave laser for the treatment of benign prostatic hyperplasia].

OBJECTIVE: To summarize the 5-year follow-up to 2 micron continuous wave laser vaporesection for the treatment of patients with low urinary tract symptoms (LUTS) secondary to benign prostatic hyperplasia (BPH), and evaluate the safety and clinical effects of the treatment. METHODS: From October 2006 to September 2007, 236 cases with low urinary tract symptom secondary to BPH were treated transurethrally under epidural or general anesthesia using the 70 Watt 2 micron laser system. Vaporesection of the prostate was performed with the traditional "U" or the "dividing" method. The 210 cases who met the inclusion criteria in this study were selected for further observation. Baseline and perioperative data were recorded and evaluated in resection time, transfusion rate, catheter-time, improvements in maximal urinary flow rate (Qmax), international prostate symptom scores (IPSS), quality of life (QoL), and post voiding residual volume (PVR). RESULTS: Out of the 210 cases, 179 cases were followed up to 5 years finally. All the surgical procedures were successfully conducted under epidural or general anesthesia. Mean operation time was (80 ± 22) minutes, and mean retrieved prostatic tissue was (24.9 ± 4.2) g. Resected prostatic tissues could be easily flashed out of the bladder. There were no significant differences in serum sodium concentrations and hemoglobin levels before and after the surgery. Mean catheter time and hospital stay was (114 ± 35) hours and (5.7 ± 1.9) days respectively. Only one postoperative secondary hemorrhage was found and treated with blood transfusion. During the 5-year follow-up, Qmax increased from (8.6 ± 3.5) ml/s preoperatively to (23.6 ± 4.2) ml/s by the end of the follow-up (P < 0.01), IPSS and QoL-Score improved from 25.3 ± 5.2 and 4.1 ± 1.3 to 6.1 ± 3.0 and 1.4 ± 0.8 respectively (P < 0.01), and PVR decreased from (248 ± 89) ml to (15 ± 13) ml. The 3 patients developed urinary incontinence and recovered 3 months later through functional exercises with the help of acupuncture. Five patients were found to have urethral stricture 3 months after the surgery and recovered with the treatment of urethral dilatation (3 cases) or internal urethrotomy (2 cases) respectively. CONCLUSIONS: Transurethral vaporesection of prostate using the 2 micron continuous wave laser system is a safe and effective treatment for benign prostatic hyperplasia with obvious improvements in subjective and objective voiding parameters, which were evident at 3 months after the surgery and were sustained throughout the 5-year long-term follow-up.

5-year follow-up to transurethral vaporesection of the prostate using the 2 micron continuous wave laser for the treatment of benign prostatic hyperplasia / 中华外科杂志

<p><b>OBJECTIVE</b>To summarize the 5-year follow-up to 2 micron continuous wave laser vaporesection for the treatment of patients with low urinary tract symptoms (LUTS) secondary to benign prostatic hyperplasia (BPH), and evaluate the safety and clinical effects of the treatment.</p><p><b>METHODS</b>From October 2006 to September 2007, 236 cases with low urinary tract symptom secondary to BPH were treated transurethrally under epidural or general anesthesia using the 70 Watt 2 micron laser system. Vaporesection of the prostate was performed with the traditional "U" or the "dividing" method. The 210 cases who met the inclusion criteria in this study were selected for further observation. Baseline and perioperative data were recorded and evaluated in resection time, transfusion rate, catheter-time, improvements in maximal urinary flow rate (Qmax), international prostate symptom scores (IPSS), quality of life (QoL), and post voiding residual volume (PVR).</p><p><b>RESULTS</b>Out of the 210 cases, 179 cases were followed up to 5 years finally. All the surgical procedures were successfully conducted under epidural or general anesthesia. Mean operation time was (80 ± 22) minutes, and mean retrieved prostatic tissue was (24.9 ± 4.2) g. Resected prostatic tissues could be easily flashed out of the bladder. There were no significant differences in serum sodium concentrations and hemoglobin levels before and after the surgery. Mean catheter time and hospital stay was (114 ± 35) hours and (5.7 ± 1.9) days respectively. Only one postoperative secondary hemorrhage was found and treated with blood transfusion. During the 5-year follow-up, Qmax increased from (8.6 ± 3.5) ml/s preoperatively to (23.6 ± 4.2) ml/s by the end of the follow-up (P < 0.01), IPSS and QoL-Score improved from 25.3 ± 5.2 and 4.1 ± 1.3 to 6.1 ± 3.0 and 1.4 ± 0.8 respectively (P < 0.01), and PVR decreased from (248 ± 89) ml to (15 ± 13) ml. The 3 patients developed urinary incontinence and recovered 3 months later through functional exercises with the help of acupuncture. Five patients were found to have urethral stricture 3 months after the surgery and recovered with the treatment of urethral dilatation (3 cases) or internal urethrotomy (2 cases) respectively.</p><p><b>CONCLUSIONS</b>Transurethral vaporesection of prostate using the 2 micron continuous wave laser system is a safe and effective treatment for benign prostatic hyperplasia with obvious improvements in subjective and objective voiding parameters, which were evident at 3 months after the surgery and were sustained throughout the 5-year long-term follow-up.</p>

Transurethral dividing vaporesection for the treatment of large volume benign prostatic hyperplasia using 2 micron continuous wave laser.

BACKGROUND: The safety and efficiency of transurethral laser resection of the prostate to treat benign prostatic hyperplasia have been verified. However, this method does still not manage large volume prostates efficiently. To tackle this problem, we have designed a method of "transurethral dividing vaporesection of prostate" using a 2 micron continuous wave laser. The aim of this study was to evaluate the safety and efficiency of this method in the management of large prostates (> 80 ml). METHODS: In this study, 45 cases of benign prostatic hyperplasia with a median prostatic volume of (123.7 ± 26.7) ml (range, 80.2-159.8 ml) were treated by the same surgeon under epidural anesthesia. During the surgery, superapubic catheters were needed, and saline solution was used for irrigation. First, the prostate was divided longitudinally into several parts from the bladder neck to the prostatic apex, and then gradually incised transversely chip by chip. Intraoperative blood transfusion rate, postoperative complications, maximum urinary flow rate, International Prostate Symptom Score and quality of life scores were recorded for statistical analysis using SPSS 16.0 software. RESULTS: Intraoperatively, no transurethral resection syndrome was observed, and no blood transfusions were needed. The resected prostatic chips were easily flushed out of the bladder through the resectoscope sheath without the use of a morcellator. Median vaporesection time was (95.0 ± 13.2) minutes (range, 75-120 minutes), and the median retrieved and removed prostatic tissue were (25.2 ± 5.1) g (range, 15.5-34.7 g) and (75.4 ± 16.4) g (range, 43.8-106.1 g), respectively. Median catheter time and hospital stay were (3.3 ± 0.9) days (range, 3-5 days) and (4.8 ± 1.8) days (range, 3-9 days), respectively. After a follow-up of 6 to 12 months, two patients had stress urinary incontinence and three had anterior urethral strictures. Satisfactory improvement was seen in maximum urinary flow rate, International Prostate Symptom Score and quality of life scores. CONCLUSIONS: This study showed that 2 micron laser vaporesection is a safe treatment for benign prostatic hyperplasia patients with large prostates, and the method of "dividing vaporesection" may help improve both surgical efficiency and patient outcomes.

[An ex vivo study on the vaporization ratio of the prostatic tissue lased by the 2 micron laser].

OBJECTIVES: To observe the vaporesection efficiency of the 2 micron laser to the prostatic gland in benign prostatic hyperplasia, and investigate the method of estimating the amount of the vaporesected prostatic tissues during transurethral vaporesection of the prostate using the 2 micron laser system in the treatment of benign prostatic hyperplasia. METHODS: Total 9 fresh prostatic gland specimens were obtained from patients with BPH under open surgical procedures, and vaporesected under a simulated transurethral environment with the 2 micron laser system immediately after weighted. Energies and time consumptions were noted, collections of vaporesected tissue specimens and the remnants of the prostatic glands were weighted after the procedures. The ratios of the vaporized tissues and the collected tissues to the whole vaporesected tissues were calculated respectively. The vaporesection efficiency of the 2 micron laser to the prostatic tissues was also calculated. RESULTS: Among the total lost tissues, about (65.6 +/- 1.5) percent of which were that of vaporized, and nearly (34.5 +/- 1.5) percent were resected. Linear correlation between the weight of collected prostatic tissue(x) and the weight of prostatic gland specimens(y) could be defined as a formula of [y = 3.245x - 6.475 (t = 15.097, P = 0.000)]. CONCLUSION: The amounts of the whole prostatic tissues removed by the 2 micron laser could be calculated from the collected resected prostatic specimens under a simulated transurethral surgical procedure.

Transurethral dividing vaporesection for the treatment of large volume benign prostatic hyperplasia using 2 micron continuous wave laser / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>The safety and efficiency of transurethral laser resection of the prostate to treat benign prostatic hyperplasia have been verified. However, this method does still not manage large volume prostates efficiently. To tackle this problem, we have designed a method of "transurethral dividing vaporesection of prostate" using a 2 micron continuous wave laser. The aim of this study was to evaluate the safety and efficiency of this method in the management of large prostates (> 80 ml).</p><p><b>METHODS</b>In this study, 45 cases of benign prostatic hyperplasia with a median prostatic volume of (123.7 ± 26.7) ml (range, 80.2-159.8 ml) were treated by the same surgeon under epidural anesthesia. During the surgery, superapubic catheters were needed, and saline solution was used for irrigation. First, the prostate was divided longitudinally into several parts from the bladder neck to the prostatic apex, and then gradually incised transversely chip by chip. Intraoperative blood transfusion rate, postoperative complications, maximum urinary flow rate, International Prostate Symptom Score and quality of life scores were recorded for statistical analysis using SPSS 16.0 software.</p><p><b>RESULTS</b>Intraoperatively, no transurethral resection syndrome was observed, and no blood transfusions were needed. The resected prostatic chips were easily flushed out of the bladder through the resectoscope sheath without the use of a morcellator. Median vaporesection time was (95.0 ± 13.2) minutes (range, 75-120 minutes), and the median retrieved and removed prostatic tissue were (25.2 ± 5.1) g (range, 15.5-34.7 g) and (75.4 ± 16.4) g (range, 43.8-106.1 g), respectively. Median catheter time and hospital stay were (3.3 ± 0.9) days (range, 3-5 days) and (4.8 ± 1.8) days (range, 3-9 days), respectively. After a follow-up of 6 to 12 months, two patients had stress urinary incontinence and three had anterior urethral strictures. Satisfactory improvement was seen in maximum urinary flow rate, International Prostate Symptom Score and quality of life scores.</p><p><b>CONCLUSIONS</b>This study showed that 2 micron laser vaporesection is a safe treatment for benign prostatic hyperplasia patients with large prostates, and the method of "dividing vaporesection" may help improve both surgical efficiency and patient outcomes.</p>

An ex vivo study on the vaporization ratio of the prostatic tissue lased by the 2 micron laser / 中华外科杂志

<p><b>OBJECTIVES</b>To observe the vaporesection efficiency of the 2 micron laser to the prostatic gland in benign prostatic hyperplasia, and investigate the method of estimating the amount of the vaporesected prostatic tissues during transurethral vaporesection of the prostate using the 2 micron laser system in the treatment of benign prostatic hyperplasia.</p><p><b>METHODS</b>Total 9 fresh prostatic gland specimens were obtained from patients with BPH under open surgical procedures, and vaporesected under a simulated transurethral environment with the 2 micron laser system immediately after weighted. Energies and time consumptions were noted, collections of vaporesected tissue specimens and the remnants of the prostatic glands were weighted after the procedures. The ratios of the vaporized tissues and the collected tissues to the whole vaporesected tissues were calculated respectively. The vaporesection efficiency of the 2 micron laser to the prostatic tissues was also calculated.</p><p><b>RESULTS</b>Among the total lost tissues, about (65.6 +/- 1.5) percent of which were that of vaporized, and nearly (34.5 +/- 1.5) percent were resected. Linear correlation between the weight of collected prostatic tissue(x) and the weight of prostatic gland specimens(y) could be defined as a formula of [y = 3.245x - 6.475 (t = 15.097, P = 0.000)].</p><p><b>CONCLUSION</b>The amounts of the whole prostatic tissues removed by the 2 micron laser could be calculated from the collected resected prostatic specimens under a simulated transurethral surgical procedure.</p>