Objective To explore whether Yes-associated protein(YAP)affects occurrence and progression of liver fibrosis by regulating epithelial-mesenchymal transition(EMT).Methods In a 8-week-old C57BL/6 mouse model of CCl4-induced liver fibrosis,the effect of verteporfin(a YAP inhibitor)intervention was assessed with HE staining and by detecting liver biochemistry and expressions of YAP and EMT-related genes using immunohistochemistry and Western blotting.Transcriptome and proteomic sequencing and informatics analysis were used to investigate the main downstream pathways of YAP in liver fibrosis.Serum levels of YAP,N-cadherin,vimentin and Twist were examined in 60 healthy individuals,60 patients with chronic hepatitis B(CHB),and 60 patients with HBV-related liver cirrhosis.In another 24 C57BL/6 mice,the effects of Twist inhibitor alone or in combination with harmine(a YAP activator)on CCl4-induced liver fibrosis were evaluated by histopathological examination and Western blotting.Results The mouse models of liver fibrosis showed obvious structural damages of the liver lobes with formation of pseudolobules,and verteporfin treatment significantly improved these pathologies and lowered plasma ALT and AST levels of the mice.Transcriptome and proteomic sequencing and informatics analysis suggested that N-cadherin and Twist were differentially expressed in liver fibrosis in close correlation with YAP.Inhibition of YAP obviously downregulated hepatic N-cadherin and Twist protein expressions in the mice with liver fibrosis.In patients with CHB and liver cirrhosis,serum levels of YAP elevated obviously with the severity of liver fibrosis and were significantly correlated with N-cadherin,vimentin and Twist levels.In mice with liver fibrosis,inhibiting Twist effectively improved liver inflammation and fibrosis,while the combined treatment with YAP activator worsened hepatic collagen fiber deposition and increased hepatic YAP and α-SMA expressions.Conclusion EMT is an important pathogenic mechanism of liver fibrosis,and inhibiting YAP can alleviate liver fibrosis by reducing EMT.

Objective:To retrospectively analyze and summarize the clinical experience and therapeutic effect of anterograde Needle-perc combined with RIRS, namely N+ R (Needle perc + RIRS) technique in the treatment of complex calyceal diverticular stone.Methods:Retrospective analysis of 23 cases of complex renal caliceal diverticulum stones admitted to our hospital from January 2020 to December 2022. The complex factors mainly include the invisible cervical orifice of diverticulum, large stone volume, and special anatomical location, which makes single RIRS or PCNL treatment difficult or unsuccessful. There were 14 males and 9 females with an average age of (42.3±6.1) years. Three cases were upper calyceal diverticular stone, average size was (0.9±0.2)cm. Nine patients had diverticular stone in the middle posterior calyx, and the average size was (1.2±0.3)cm. The average size of four diverticular stone was (1.8±0.2)cm in the anterior middle calyx. Seven patients had diverticular stone with an average size of (1.3±0.1)cm in lower calyx. Among them, 12 patients underwent RIRS which were difficult or stone undiscovered, and 3 patients underwent PCNL and the operation was terminated due to failure of channel establishment. In our center, oblique supine lithotomy position (male) or prone split-leg position (female) was adopted, and the combined treatment of Needle-perc and RIRS was performed. Needle-perc puncture was completed under the guidance of full ultrasound. During the operation, methylene blue reagent or mutual guidance of two endoscopes was used to find the diverticulum neck and expand the outlet with holmium laser incision. Depending on the size and location of the stones, a single Needle-perc laser lithotripsy combined with stone removal in flexible ureteroscope was used, or dual lasers were be used simultaneously for stone removal under double endoscopes. The first stage stone free rate, operation time, hemoglobin decrease, complications, postoperative hospital stay and other conditions were analyzed.Results:All the 23 operations were completed successfully. The stone free rate within 48 hours and one month after surgery was 78.2% and 100.0% respectively. The average operation time was (61.5±12.2)min. The mean postoperative hospital stay was (2.8±0.6) days. The mean decrease of hemoglobin was (3.6±0.4)g/L. Three patients had fever and one patient had renal subcapsular effusion. After anti-inflammatory and symptomatic treatment, the patient was discharged. There was no incidence of Clavien-Dindo≥Ⅱcomplications such as blood transfusion, abdominal organ injury or urosepsis.Conclusions:Treatment of complex renal caliceal diverticulum stones using N+ R technique of anterograde needle-perc combined with RIRS can effectively improve the success rate of first-stage surgery. Overall, it is safe, efficient and feasible with the advantages of high stone free rate, lower damage, and few postoperative complications.

Objective To explore whether Yes-associated protein(YAP)affects occurrence and progression of liver fibrosis by regulating epithelial-mesenchymal transition(EMT).Methods In a 8-week-old C57BL/6 mouse model of CCl4-induced liver fibrosis,the effect of verteporfin(a YAP inhibitor)intervention was assessed with HE staining and by detecting liver biochemistry and expressions of YAP and EMT-related genes using immunohistochemistry and Western blotting.Transcriptome and proteomic sequencing and informatics analysis were used to investigate the main downstream pathways of YAP in liver fibrosis.Serum levels of YAP,N-cadherin,vimentin and Twist were examined in 60 healthy individuals,60 patients with chronic hepatitis B(CHB),and 60 patients with HBV-related liver cirrhosis.In another 24 C57BL/6 mice,the effects of Twist inhibitor alone or in combination with harmine(a YAP activator)on CCl4-induced liver fibrosis were evaluated by histopathological examination and Western blotting.Results The mouse models of liver fibrosis showed obvious structural damages of the liver lobes with formation of pseudolobules,and verteporfin treatment significantly improved these pathologies and lowered plasma ALT and AST levels of the mice.Transcriptome and proteomic sequencing and informatics analysis suggested that N-cadherin and Twist were differentially expressed in liver fibrosis in close correlation with YAP.Inhibition of YAP obviously downregulated hepatic N-cadherin and Twist protein expressions in the mice with liver fibrosis.In patients with CHB and liver cirrhosis,serum levels of YAP elevated obviously with the severity of liver fibrosis and were significantly correlated with N-cadherin,vimentin and Twist levels.In mice with liver fibrosis,inhibiting Twist effectively improved liver inflammation and fibrosis,while the combined treatment with YAP activator worsened hepatic collagen fiber deposition and increased hepatic YAP and α-SMA expressions.Conclusion EMT is an important pathogenic mechanism of liver fibrosis,and inhibiting YAP can alleviate liver fibrosis by reducing EMT.

Objective:To study the effects of cathepsin K(CTSK)on the healing process of tooth extraction socket and type H blood vessel angiogenesis in mice.Methods:Ctsk knockout(Ctsk-/-)mice were generated by CRISPR/Cas9 technology,and genotype sequen-cing,general observation,Micro-CT and immunohistochemistry were performed to confirm successful knockout of Ctsk.Then 8 week-old WT and Ctsk-/-mice were used to establish the tooth extraction modle by extracting the left maxillary first molars,and the mice were sac-rificed at the day 7,10,14,21,28 and 35 respectively(n=3)after tooth extraction.Then samples were subjected to stereo microscope and Micro-CT examination.Immunofluorescence staining was used to study the effect of Ctsk knockout on type H blood vessel angiogene-sis.Results:Ctsk knockout did not affect the soft tissue healing of tooth extraction socket,but significantly promoted the bone healing process,and Ctsk deficency significantly enhanced type H blood vessel angiogenesis in the tooth extraction socket.Conclusion:Ctsk knockout can enhance type H vessel angiogenesis,and promote bone healing process of tooth extraction socket in mice.

With the extension of human life expectancy, the threat of cancer to human beings has become increasingly prominent. Cancer has become the first cause of death for urban and rural residents in China. As the disease progresses, many patients have metastases in other sites besides the primary malignant tumors. Hence, it is of significance to choose effective treatment methods. Body gamma knife treatment is an accurate stereotactic radiotherapy that can render higher doses to the tumors and better protect surrounding normal tissues. A large number of clinical trials have demonstrated that body gamma knife treatment of lung metastases, liver metastases and adrenal metastases can obtain relatively high local control rates. In this article, the application of body gamma knife in the treatment of metastatic tumors was reviewed.

Objective To investigate the feasibility of tract dilation monitored by ultrasound in percutaneous nephrolithotomy (PCNL),and the risk factors for its failure.Methods A retrospective study was conducted on patients underwent PCNL with only one access (F24) using balloon dilator and sequential dilators (Amplatz and telescopic metal dilators) from December 2014 to December 2018 in Beijing Tsinghua Changgung Hospital.A total of 231 patients (130 males and 101 females) underwent ultrasound-guided PCNL with a mean age of (52.3 ± 9.8) years were included in our study.Mean BMI was (25.8 ± 3.1) kg/m2.Mean size of stone was (3.9 ± 1.1)cm,51.1％ (118/231) of which were staghorn stones.Under ultrasound guidance,after puncture of the target calyx,the balloon dilator was advanced through the guide wire,and inflated to establish the F24 standard renal access.Patients' clinical parameters such as age,gender,BMI,stone diameter,history of open nephrolithotomy were collected.Risk factors for the failure of ultrasound guided balloon dilation were analyzed by logistic regression analysis.Results Tract dilation succeed in 89.2 ％ cases (206 succeed,25 failed) at first attempt.Median tract dilation time was 4.2 min (2.2-8.0 min).Mean operation time was 85.5 min(45.0-120.0 min).Median hemoglobin drop at the first postoperative day was 16.0 g/L (5.0-25.8 g/L).The total rate of complication was 9.1％ (21 cases),including 18 cases Clavien Ⅰ and 3 cases Clavien Ⅱ.The stone free rate was 89.6％ (207/231).Logistic regression analysis revealed that lower pole access (P =0.014) was a risk factor for the failure of access establishment,while the presence of hydronephrosis of target calyx (P ＜ 0.001) would significantly increase the success rate.Conclusions Tract dilation using balloon catheter can be safely monitored by ultrasound with high success rate and low complication rate.Lower pole puncture will make tract establishment difficulty.Patients with a hydronephrotic target calyx are more suitable for this procedure.

Primary lesion removal and lymph node dissection are the main constituents of radical gastrectomy. However, the high recurrence rate after D2 radical gastrectomy for advanced gastric cancer has not improved. Recently, studies have found that discrete tumor deposits in the mesogastrium may be an important factor affecting the prognosis of gastric cancer after surgery. With the development of laparoscopic equipment, the ever-expanding "submicroscopic vision" makes it possible to completely remove the mesogastrium. Professor Gong Jianping advocated "membrane anatomy" to optimize the concept of radical gastrectomy: D2- based complete mesenteric resection (CME), namely D2+CME procedure. To prevent the leakage of tumor cells into the surgical field, as histological barrier, the intact mesogastrium should be located. The essential difference between D2+CME and previous D2/D2+systematic mesogastrium excision (SME), en-bloc mesogastric excision (EME) is as follow: double-factor guiding (lymph nodes and discrete tumor deposits) vs. single factor guiding (lymph nodes only). After practicing dozens of radical gastrectomy (D2+CME) authors believe that its conceptual connotation (double factor guiding) and operational extension (above mesentery bed) cover D2. In D2+CME surgery, depending on the anatomical identification under the magnified field of view, the conformal space between gastric mesentery and mesenteric beds is unique operational plane with repeatability. These findings and considerations address one problem: where is the precise boundary of en bloc principle in radical gastrectomy? In author′s opinion, with laparoscopy and "sub-microsurgery" progression and detection of discrete tumor deposit metastasis, survival benefit from definition of en bloc boundary in radical gastrectomy will be widely recognized. Meanwhile, D2+CME procedure is an appropriate way for study. Although the development of the "membrane anatomy" concept for gastric cancer still requires many further clinical and basic researches, it is reasonable to foresee that D2+CME surgery will guide a concept-optimized era for gastric cancer surgery.

Primary lesion removal and lymph node dissection are the main constituents of radical gastrectomy. However, the high recurrence rate after D2 radical gastrectomy for advanced gastric cancer has not improved. Recently, studies have found that discrete tumor deposits in the mesogastrium may be an important factor affecting the prognosis of gastric cancer after surgery. With the development of laparoscopic equipment, the ever?expanding "submicroscopic vision" makes it possible to completely remove the mesogastrium. Professor Gong Jianping advocated "membrane anatomy" to optimize the concept of radical gastrectomy: D2-based complete mesenteric resection (CME), namely D2+CME procedure. To prevent the leakage of tumor cells into the surgical field, as histological barrier, the intact mesogastrium should be located. The essential difference between D2+CME and previous D2/D2+systematic mesogastrium excision (SME), en?bloc mesogastric excision (EME) is as follow: double?factor guiding (lymph nodes and discrete tumor deposits) vs. single factor guiding (lymph nodes only). After practicing dozens of radical gastrectomy (D2+CME) authors believe that its conceptual connotation (double factor guiding) and operational extension (above mesentery bed) cover D2. In D2+CME surgery, depending on the anatomical identification under the magnified field of view, the conformal space between gastric mesentery and mesenteric beds is unique operational plane with repeatability. These findings and considerations address one problem: where is the precise boundary of en bloc principle in radical gastrectomy? In author′s opinion, with laparoscopy and "sub?microsurgery"progression and detection of discrete tumor deposit metastasis, survival benefit from definition of en bloc boundary in radical gastrectomy will be widely recognized. Meanwhile, D2+CME procedure is an appropriate way for study. Although the development of the "membrane anatomy" concept for gastric cancer still requires many further clinical and basic researches, it is reasonable to foresee that D2+CME surgery will guide a concept?optimized era for gastric cancer surgery.

Primary lesion removal and lymph node dissection are the main constituents of radical gastrectomy. However, the high recurrence rate after D2 radical gastrectomy for advanced gastric cancer has not improved. Recently, studies have found that discrete tumor deposits in the mesogastrium may be an important factor affecting the prognosis of gastric cancer after surgery. With the development of laparoscopic equipment, the ever?expanding "submicroscopic vision" makes it possible to completely remove the mesogastrium. Professor Gong Jianping advocated "membrane anatomy" to optimize the concept of radical gastrectomy: D2-based complete mesenteric resection (CME), namely D2+CME procedure. To prevent the leakage of tumor cells into the surgical field, as histological barrier, the intact mesogastrium should be located. The essential difference between D2+CME and previous D2/D2+systematic mesogastrium excision (SME), en?bloc mesogastric excision (EME) is as follow: double?factor guiding (lymph nodes and discrete tumor deposits) vs. single factor guiding (lymph nodes only). After practicing dozens of radical gastrectomy (D2+CME) authors believe that its conceptual connotation (double factor guiding) and operational extension (above mesentery bed) cover D2. In D2+CME surgery, depending on the anatomical identification under the magnified field of view, the conformal space between gastric mesentery and mesenteric beds is unique operational plane with repeatability. These findings and considerations address one problem: where is the precise boundary of en bloc principle in radical gastrectomy? In author′s opinion, with laparoscopy and "sub?microsurgery"progression and detection of discrete tumor deposit metastasis, survival benefit from definition of en bloc boundary in radical gastrectomy will be widely recognized. Meanwhile, D2+CME procedure is an appropriate way for study. Although the development of the "membrane anatomy" concept for gastric cancer still requires many further clinical and basic researches, it is reasonable to foresee that D2+CME surgery will guide a concept?optimized era for gastric cancer surgery.

Objective To investigate the value of iFlow color-coding technique in quantitative real-time analysis of hemodynamic changes after transarterial chemoembolization (TACE) for hepatocellular carcinoma (HCC) . Methods A total of 31 patients who were diagnosed with HCC in Shanghai Fifth People's Hospital from December 2015 to January 2017 were enrolled. No patient underwent surgical operation or ablation. All patients underwent TACE with the same contrast agent, high-pressure injector parameters, and place of angiographic catheter. The iFlow technique was used to generate two-dimensional color-coded images and time-density curve (TDC) before and after surgery and measure the opening of the angiographic catheter and the time to peak (TTP) of the starting and ending points of the major tumor feeding arteries, as well as the ratio of the areas under the curve (AUC) of TDC of tumor tissue and the opening of the angiographic catheter. The paired t-test was used for comparison of continuous data between groups. Results TTP of the major tumor feeding arteries was 4.64 ± 0. 49 s before TACE and 5. 97 ± 0. 84 s after TACE (t = 11. 57, P ＜ 0. 01), and there was a significant difference in AUC between the tumor tissue and the opening of the angiographic catheter (0. 53 ± 0. 15 vs 0. 16 ± 0. 12, t = 25. 85, P ＜ 0. 01) . There was no significant difference in TTP between the opening of the angiographic catheter and the major tumor feeding arteries before and after TACE (P＞ 0. 05) .Before TACE, the TDC of tumor feeding arteries had a shape of"rapid increase-rapid reduction"with relatively high slope and peak value, while after TACE, the TDC had a shape of "increase-flat-reduction"with reductions in slope and peak value. Conclusion The iFlow technique can perform real-time measurement of TTP and TDC of the region of interest and helps with quantitative evaluation of hemodynamic changes in HCC. Therefore, it can provide objective quantitative indices for evaluating the degree of tumor embolism.