Objective:To summarize the preliminary clinical experience of utilizing ureteral balloon dilation catheter in the treatment of "difficult ureter" during ureteroscopic lithotripsy, and to discuss the efficacy and safety of the technique.Methods:Clinical data of 28 patients (30 sides) with upper urinary tract calculi admitted to Beijing Tsinghua Changgung Hospital Affiliated to Tsinghua University from April 2021 to July 2022 were retrospectively analyzed. There were 23 males (82.1%) and 5 females (17.9%), with age of (51.5±13.6) years. Among the 30 sides, 20 (66.7%) on the left and 10(33.3%) were on the right. Calculi were either located in the renal pelvis or calyxes in 7 sides (23.3%), upper ureter in 17 sides (56.7%), and lower ureter in 6 sides (20.0%). The maximum diameter of the stones was (9.4±4.2)mm, and 23 sides (76.7%) were combined with hydronephrosis before surgery. When "difficult ureter" was encountered during the procedure, that is, it was difficult to insert ureteroscope or ureteral access sheath (UAS) due to small ureteral lumen, balloon catheter was used for dilation in the first stage, in which the balloon diameter was 4 mm on 22 sides and 5mm on 8 sides. The instrument was retrogradely inserted through the working channel of F8 semi-rigid ureteroscope, and the small site of the ureteral lumen was dilated under direct endoscopic view. After a single dilation, the balloon catheter was withdrawn, and the effect of dilation was evaluated by semi-rigid ureteroscopy to determine whether to proceed with the following procedures. The intraoperative data were recorded, including surgical method, stage of "difficult ureter" occurred, site of the small part of the ureter, related data of utilizing ureteral dilatation balloon catheter, grade of ureteral injury after dilatation (according to the 0-4 grading classification of endoscopic ureteral injuries), total operation time, balloon catheter-related adverse events, stone-free rate, and time of removing ureteral stents.Results:Among the 30 sides, 29 (96.7%) had difficulty in the stage of ureteroscope insertion, and 1(3.3%) had difficulty in the stage of UAS insertion. A total of 37 small sites of ureter were involved, including 18 in the intramural segment, 10 in the lower part, 2 in the middle part, and 7 in the upper part. Each site was dilated once with a median time of 3 (0.5, 5.0) minutes and a median maximum balloon pressure of 1 215.9(1 215.9, 1 443.9)kPa[12.0(12.0, 14.3)atm]. There were 28 sites of grade Ⅰ injury, 8 sites of grade Ⅱinjury, and 1 site of grade Ⅲinjury. The total duration of unilateral procedure was (73.4±30.3) min. Ureteroscope or UAS insertion was successful in 28 sides(93.3%) after balloon dilation, and failed in 2 sides(6.7%), both of which were in the stage of inserting ureteroscope and ureteral stent was indwelled for the second-stage procedures. On the first day after surgery, the hemoglobin level was (134.1±12.9)g/L, which was significantly different from the preoperative parameters ( P<0.01), and serum creatinine level was (86.7±23.2)μmol/L, which showed no significant difference from the preoperative one ( P=0.263). The primary stone-free rate was 92.9% (26/28), and the total postoperative complication rate was 13.3% (4/30), including 3 of grade Ⅰ (lateral lower abdominal pain requiring additional analgesic drugs) and 1 of grade Ⅱ (postoperative hematuria requiring intravenous hemostatic drugs). Follow-up was conducted for 3 months. All of the 28 successful sides had their ureteral stents removed before the last follow-up, and the time of removal was (36.9±11.5) days. No hydronephrosis was found in the ipsilateral kidney by ultrasound 3 months after operation. Conclusions:Balloon dilation technique showed good efficacy and safety in the treatment of "difficult ureter" during ureteroscopic lithotripsy.

Objective:To compare the temperature rise curve and steady-state temperature of thulium and holmium laser in lithotripsy.Methods:This study was conducted from November to December 2021. Firstly, we designed an experimental water tank(10 cm×10 cm×10 cm) that can carry out constant temperature water bath, with a 8ml simulated renal pelvis, and can carry out constant velocity perfusion in the simulated renal pelvis. A 1 cm×1 cm×1 cm cubic artificial stone was placed in the simulated renal pelvis to perform 36.5℃-37.5 ℃ water bath. The simulated renal pelvis was closed with an oak plug, the temperature measuring probe and flexible ureteroscope were placed through the hole on the oak plug and entered into the simulated renal pelvis. Flexible ureteroscope was carried out by urologists. The lithotripsy lasted a total of 180 seconds for thulium and holmium laser respectively under different parameter settings (10 Hz×1.0 J, 10 Hz×2.0 J, 10 Hz×3.0 J, 20 Hz×0.5 J, 20 Hz×1.0 J, 20 Hz×1.5 J, the corresponding gravel power is 10 W, 20 W and 30 W respectively), the constant speed water pump flow rate was separate as the high flow rate group (35 ml/min) and low flow rate group (15ml/min), and leave a temperature probe 5mm around the optical fiber. Water temperature change during the lithotripsy was recorded by probes, the average of 10 temperature values of two probes measured every 5 seconds was taken as the water temperature value of this period, with a total of 216 time points in 6 parameter settings. Under the same parameter settings, the temperature of two lasers at each time point was plotted and compared to form the corresponding temperature rise curve. The average temperature in the last 30 seconds during lithotripsy in the record was used as the steady-state temperature, which of thulium and holmium laser lithotripsy was compared under the same parameter setting and the same water flow velocity. Finally, 43℃ was taken as the safety threshold temperature to evaluate whether the temperature of the two lasers during lithotripsy exceeds the safety threshold.Results:According to the temperature rise curve, the water temperature of thulium laser during lithotripsy was higher than that of holmium laser at 77.7% (168/216)of time points. At the flow rate of 15 ml/min, thulium laser was significantly higher than that of holmium laser at 10 Hz×1.0 J[(32.43±2.19℃)vs. (30.99±0.90)℃, P<0.01], 10 Hz×2.0 J[(41.21±3.30℃) vs. (38.13±1.26)℃, P<0.01], 10 Hz×3.0 J[(49.54±2.44)℃vs. (44.91±0.65)℃, P<0.01], 20 Hz×0.5 J[(32.75±1.41)℃vs. (30.84±1.16)℃, P<0.01], 20 Hz×1.0 J[(41.67±1.76)℃vs. (37.51±1.25)℃, P<0.01], 20 Hz×1.5 J [(47.54 ± 3.48)℃vs. (46.12±1.04)℃, P<0.01]. At the flow rate of 35 ml/min, the thulium laser was significantly higher than that of holmium laser at 10 Hz×1.0 J[(28.01±0.57)℃ vs. (26.84±0.97)℃, P<0.01], 10 Hz×2.0 J[(31.31±1.07)℃vs.(30.41±1.39)℃, P<0.01], 10 Hz×3.0 J[(33.29±0.70)℃vs.(32.25±2.55)℃, P<0.01], 20 Hz×0.5 J[(28.36±0.99)℃vs.(26.22±0.66)℃, P<0.01], 20 Hz×1.0 J [(30.80±2.06)℃vs.(30.08±0.78)℃, P=0.012], and the steady-state temperature was not significant different between two laser at 20 Hz×1.5 J [(34.54±3.08)℃ and(33.93±1.49)℃, P=0.163]. In the low flow rate group, thulium laser at 10 Hz×1.0 J, 10 Hz×2.0 J, 20 Hz×0.5 J and 20 Hz×1.0 J does not exceed the safety threshold temperature, while in the high flow rate group, any combination of laser parameters of the two lasers does not exceed the safety threshold temperature. Conclusion:Under the same laser parameter setting and flow rate, the thermal eff of thulium laser is more obvious. When using thulium laser for lithotripsy, the flow rate in the process of lithotripsy being faster than that of holmium laser with the same laser setting should be ensured to avoid tissue damage.

Traditional Chinese Medicine (TCM) exerts anti-tumor effects by intervening in A549 cells of human lung adenocarcinoma, mainly including activating or inhibiting downstream target proteins of Bcl-2 and Bax, or forming RIP1/RIP3/MLKL complex bodies by affecting pathways such as PI3K/Akt, thereby inducing apoptosis in A549 cells of lung adenocarcinoma; blocks the cell growth phase, thereby inhibiting the proliferation of lung adenocarcinoma A549 cells; inhibits invasion and metastasis of A549 cells by affecting the MMPs pathway, STAT3 pathway, and regulating epithelial mesenchymal transition related factors; suppresses or activates the expression of related proteins or affect related signaling pathways, thereby reversing the resistance of lung cancer A549/DDP cell lines to cisplatin and paclitaxel.

Immune checkpoint inhibitors (ICIs) have demonstrated unparalleled clinical responses and revolutionized the paradigm of tumor treatment, while substantial patients remain unresponsive or develop resistance to ICIs as a single agent, which is traceable to cellular metabolic dysfunction. Although dysregulated metabolism has long been adjudged as a hallmark of tumor, it is now increasingly accepted that metabolic reprogramming is not exclusive to tumor cells but is also characteristic of immunocytes. Correspondingly, people used to pay more attention to the effect of tumor cell metabolism on immunocytes, but in practice immunocytes interact intimately with their own metabolic function in a way that has never been realized before during their activation and differentiation, which opens up a whole new frontier called immunometabolism. The metabolic intervention for tumor-infiltrating immunocytes could offer fresh opportunities to break the resistance and ameliorate existing ICI immunotherapy, whose crux might be to ascertain synergistic combinations of metabolic intervention with ICIs to reap synergic benefits and facilitate an adjusted anti-tumor immune response. Herein, we elaborate potential mechanisms underlying immunotherapy resistance from a novel dimension of metabolic reprogramming in diverse tumor-infiltrating immunocytes, and related metabolic intervention in the hope of offering a reference for targeting metabolic vulnerabilities to circumvent immunotherapeutic resistance.
Humans ; Neoplasms/pathology* ; Immunotherapy/methods* ; Immune Checkpoint Inhibitors/therapeutic use*

【Objective】 The thermal effects of super-pulsed thulium fiber laser (TFL) at different powers,lithotripsy modes and irrigation rates were studied using a 3D kidney model to simulate ureteral lithotripsy in vivo. 【Methods】 A thermal effect model was established in vitro. Under the same conditions of laboratory temperature and equipment,the temperature around the optical fiber was measured and compared when different optical fiber diameters,powers,lithotripsy modes and irrigation rates were used to simulate lithotripsy by TFL. 【Results】 There was significant difference in the temperature around the optical fiber caused by two fibers with different diameters under the same conditions (P<0.05). Under the same conditions,different lithotripsic modes produced different temperatures,and the temperature of "high energy and low frequency" was lower than that of "low energy and high frequency" (P<0.05). When the power was 10 W and the minimum irrigation rate was 10 mL/min,the plateau temperature did not reach the safety threshold (43 ℃). When the power was 20 W and the minimum irrigation rate was 10 mL/min,the platform temperature exceeded the safety threshold. When the irrigation rate was 20 mL/min,the platform temperature did not reach the safety threshold. 【Conclusion】 In the study of ureteral lithotripsy in vitro,the power,mode,irrigation rate and optical fiber diameter are factors affecting the thermal effects of TFL. No matter what kind of lithotripsy mode and fiber diameter,the temperature around the fiber is safe when the lithotripsy power is ≤10 W and the irrigation rate is ≥10 mL/min;when the lithotripsy power is ≤20 W and the irrigation rate is ≥20 mL/min,the temperature around the fiber is safe.

Objective:To retrospectively summarize disease characteristics and the clinical experience of minimally invasive endoscopy in the treatment of upper urinary tract obstruction caused by ureteropelvic encrusted inflammatory disease.Methods:Three patients with bilateral ureteropelvic encrusted inflammatory disease admitted to our hospital from March 2018 to July 2021 were involved. Case 1, male, 45 years old, admitted due to bilateral hydronephrosis for 5 months. The preoperative diagnosis were bilateral ureteropelvic stones (encrustation), right ureteral atresia, left ureteral stenosis, and systemic vasculitis. Left double J tube insertion and right nephrostomy were performed in another hospital. We conducted antegrade percutaneous nephroscopy combined with retrograde ureteroscopy surgery and assisted balloon dilation to treat bilateral lesions stage by stage. Case 2, Male, 12 years old, admitted due to bilateral abdominal pain for 6 weeks. The preoperative diagnosis were bilateral ureteral stones, bilateral hydronephrosis, and dermatomyositis. After the failure of double J tube insertion in another hospital, double nephrostomy was performed instead. We performed left percutaneous nephroscopy and right percutaneous nephroscopy combined with ureteroscopy for the treatment of bilateral lesions. Case 3, female, 32 years old, was admitted because of pain in the left lower back and abdomen for over 6 months. The preoperative diagnosis were bilateral ureteral stones, bilateral ureteral stenosis, and dermatomyositis. She underwent three times of ESWL and once URS before. We performed ureteroscopic surgery for bilateral lesions. During the surgery, various degrees of crusting in the renal pelvis or ureter were observed in all 3 cases, and the lesions were removed using pneumatic lithotripsy combined with forceps or baskets. After surgery, oral antibiotics were continuously used for 1-3 months. The efficacy and prognosis were evaluated based on the follow-up of urine, imaging, and endoscopic examinations at 3, 6, and 12 months after surgery.Results:All 3 surgeries were successfully completed. At 3, 6, and 12 months after surgery, follow-up CT showed no crusting in the left ureter, and endoscopy showed good mucosal wound healing and unobstructed lumen in case 1. There were still some crusting lesions and lumen stenosis in the right renal pelvis, and the right ureter reconstruction surgery was ultimately performed. There were no crusting on both sides and the urinary tract was unobstructed after 3, 6, and 12 months of follow-up in case 2 and case 3. Postoperative pathological examination showed chronic inflammation of urothelial mucosal tissue, small pieces of proliferative fibrous tissue with peripheral calcification. Calcification layer composition analysis showed magnesium ammonium phosphate and carbonate apatite. No related complications occurred in case 2 and case 3.Conclusions:Urothelial crusted inflammatory disease is rare clinically, and the diagnosis and treatment strategies are rarely reported domestically and internationally. Preoperative imaging examination, intraoperative findings and postoperative pathology or calcification composition analysis are of instruction for the diagnosis and treatment of this disease. Minimally invasive endoscopy treatment for upper urinary tract obstruction caused by ureteropelvic encrusted inflammatory disease has a good effect. Long-term efficacy and other adjuvant treatment need long-term follow-up and clinical practice.

Objective:To compare the consistency of tomographic infrared spectrum analysis with conventional infrared spectrum analysis for the composition analysis of large-volume of urinary stones in vitro.Methods:Postoperative urinary stone specimens collected from 105 patients admitted to Beijing Tsinghua Changgung Hospital from January 2019 to June 2021 were analyzed, including 81 (77.14%) kidney stones, 16 (15.24%) ureteral stones, and 8 (7.62%) bladder stones. All stones measured ≥0.8 cm in maximum diameter on preoperative imaging. Eighty-four specimens, which were mainly stone fragments, were collected from percutaneous nephrolithotomy and ureteroscopic lithotripsy. These 84 specimens were analyzed and retested for stone composition using conventional infrared spectrum analysis by random multiple sampling. Other 21 renal stone specimens were obtained by laparoscopic lithotomy or standard percutaneous nephrolithotomy after November 1, 2020. These 21 specimens had a maximum diameter of ≥0.8 cm measured postoperatively. Based on intraoperative observation, stone specimens with typical layered structures were chosed. Then, all 21 samples were analyzed and retested by conventional infrared spectrum analysis and tomographic infrared spectrum analysis, respectively. When using tomographic infrared spectrum analysis, we need to take two maximum cross sections with a vertical spacing of these sections >2 mm, then perform multiple points sampling according to the morphological stratification of the first section. If the section's structure was homogeneous, we equidistantly took 2 to 3 samples from the center to the periphery. Otherwise, every layer needed to take a stone sample according to the stratification. Putting all the results of one section together, we obtained complete tomographic infrared spectrum analysis data. Take another coaxial cross-section of the same specimen for retesting. We recorded the characteristics of the three-dimensional distribution of stone composition in 21 stone specimens. Meanwhile, we compared the consistency of the results of conventional infrared spectrum analysis and tomographic infrared spectrum analysis for the same sample.Results:The consistency rate of the conventional infrared spectrum analysis was 56.19% (59/105), and that of tomographic infrared spectrum analysis was 80.95% (17/21). The difference in consistency between two methods was statistically significant ( χ2=4.447, P=0.035). Among 21 specimens, the consistency rate of conventional infrared spectrum analysis was 38.10% (8/21), which was significantly lower than that of tomographic infrared spectrum analysis ( χ2=7.814, P=0.005). Regarding the characteristics of the three-dimensional distribution of the components, the color and crystal morphology of five common types of stone components were different, and layered structure in the cross-section of the stones were observed. When the calculi were of the same composition, they were displayed in different morphology. We observed a trending change in the composition ratio between sublayers from the center to the edge in some compound-composition stones. Conclusions:For the composition analysis of larger-volume urinary stones, tomographic infrared spectrum analysis showed a higher consistency of retesting than conventional infrared spectrum analysis, and the three-dimensional distribution of stone composition had some characteristic features.

Objective: To summarize our preliminary clinical experience of ultrasound-guided needle-perc combined with standard percutaneous nephrolithotomy (PCNL) in the treatment of staghorn stones, and to analyze its safety and efficacy. Methods: The clinical data of 65 patients with staghorn stones treated by ultrasound-guided needle-perc combined with standard PCNL under general anesthesia with the patient in prone position from December 2017 to June 2019 were retrospectively reviewed. A total of 41 males and 24 females were included. The mean age was (53.5+ 8.9) years. The mean body mass index (BMI) was (25.1±2.9) kg/m², and the mean stone diameter was (10.9±3.1) cm. Among them, there were 3 cases with bilateral staghorn stones, 38 cases with complete staghorn calculi, 36 cases with non- or mild preoperative hydronephrosis, 12 cases with previous ipsilateral renal surgery, and 9 cases with solitary kidneys. Ultrasound-guided renal access and tract dilation were used to establish F24 standard channel. Pneumatic combined with ultrasonic lithotripsy with suction system was used to treat staghorn stones under nephroscope. Needle-perc consists of F4.2 needle-like metal sheath connected with a three-way tube. A 0.6 mm diameter video fiber, 200 um holmium laser fiber and liquid perfusion device can be connected through the three-way tube respectively. The residual stone in the parallel calyx after standard PCNL were punctured by needle-perc under ultrasound guidance, and then the holmium laser fiber was used for lithotripsy. Results: In this study, a total of 68 renal units were included. The median operative time was 79.8 minutes, ranging 45-129 minutes. The median decrease of hemoglobin on postoperative day 1 was 10.6 g/L, ranging 0-25.9 g/L. The median length of postoperative hospital stay was 5.5 days, ranging 4-7 days and the median time of tract establishment was 4.8 minutes, ranging 2.5-9.6 minutes. The median number of standard tract established was 1.5, ranging 1-3 and the median number of needle-perc punctured was 1.0, ranging 1-3. The total complication rate was 10.3% (7 cases), including 5 cases of Clavien grade Ⅰ, 2 cases of postoperative fever, 3 cases of analgesic use. There were 2 cases of Clavien grade Ⅱ. All of them were blood transfusion. The initial stone free rate was 79.4%(54/68). Of the 14 patients with residual stones, 9 patients underwent second-stage operation, 7 patients were stone free, and the final stone free rate was 89.7%(61/68). Conclusions Ultrasound-guided needle-perc combined with standard PCNL is safe and effective in the treatment of staghorn stone.

Objective:To introduce the preliminary experience of domestic disposable digital flexible ureteroscope (ZebraScope?)in the treatment of upper urinary calculi.Methods:The clinical data of 16 patients with upper urinary calculi treated by ZebraScope? in our hospital from February to March 2020 were retrospectively analyzed. The scope is composed of a handle and shaft, the image can be transferred through the transmission line at the end of the handle. There were 10 males and 6 females. The mean age was 42.1 years (26-63 years). 12 cases of upper ureteral calculi and 4 cases of renal calculi included. Mean diameter was 1.3cm (0.8-2.1cm). Ureteral stents were preoperatively placed in 4 patients and no pre-stent were in 12 patients. Two patients had a history of endoscopic lithotripsy. The ureteral sheath was used in 4 patients with F12/14, 10 patients with F11/13, and 2 patients with F10/12. Eight patients were treated with a stone basket. Intra-operative lithotripsy was performed using 200um optical fiber combined with holmium laser, and 6Fr ureteral stent was routinely indwelling for 2-4 weeks. The operation time, postoperative complications, hospital-in time, stone clearance rate and other related parameters were summarized and analyzed.Results:Of the 16 patients, 14 succeed and 2 patients failed and secondary operation was applied due to poor ureteral condition. The mean operative time was 55.6 minutes (32-115 minutes). The average laser emission time was 25.2 minutes (10-65 minutes). There was no image degradation and scope damage during the operation. All the patients recovered well after the operation, and no postoperative complications such as fever and pain occurred. Two patients received external physical vibration lithecbole therapy. The average hospital-in time was 1.2 days (1-3 days). One month after the operation, the calculi clearance rate was 87.5% (14/16).Conclusion:Our preliminary study found that ZebraScope? could be safe and effective in the treatment of upper urinary calculi less than 2 cm. Futhter verification is required in larger renal stones.