Flexible ureteroscopic lithotripsy (FURL) is one of the major minimally invasive endoscopic techniques in the management of upper urinary tract stones，but it has problems of low stone-free rate，high intraoperative intra-pelvic pressure，and high risk of postoperative infection.Since the negative pressure suction technique has been applied to FURL，it can actively suck out the stone powder and perfusion fluid during operation，thus significantly improving the immediate intraoperative stone removal rate，effectively reducing the intrarenal pelvic pressure，increasing the clarity of the operation field，and significantly improving the efficiency and safety of FURL.With the continuous progress of technology，the negative pressure suction technique has evolved from the initial simple negative pressure suction to the intelligent pressure control system integrating ‘perfusion-measurement-negative pressure'.Although this technique is now widely used in FURL，there is still optimizing space in terms of device design and operational application.This article will focus on the clinical application，technical progress and operational experience of the negative pressure suction technique in the light of domestic and international literature.

Objective To investigate the incidence,biochemical manifestations and genetic mutation features of glutaric acidemia type Ⅱ(GA-Ⅱ)in newborns in Quanzhou,Fujian province.Methods From January 2014 to December 2022,a total of 643 606 newborns were screened for inherited metabolic diseases by tandem mass spectrometry in the Quanzhou area.Suspected positive newborns with multiple acylcarnitine elevations were diagnosed by the MassARRAY assay and high-throughput sequencing technology.Results A total of 247 newborns showed multiple acylcarnitine elevations during the study period,and 19 newborns were diagnosed with GA-Ⅱ by genetic diagnosis.In addition,one newborn showed elevated levels of isovalerylcarnitine(C5),and was suspected to be isovaleric acidemia,which was confirmed with GA-Ⅱ by genetic diagnosis.Twenty newborns were eventually diagnosed with GA-Ⅱ,and the incidence of GA-Ⅱ in the study population was 1:32 180.Newborn screening results showed the concentrations of octanoylcarnitine(C8),decanoylcarnitine(C10)and dodecanylcarnitine(C12)were higher than the upper limit of the reference range,which were key indicators for screening GA-Ⅱ.Ten distinct electrontransfer flavoprotein dehydrogenase ETFDH gene mutations were found in patients with GA-Ⅱ,most of which were missense mutations.The most common ETFDH mutation was C.250G>A(p.A84T)with an allele frequency of 47.5％,followed by C.524G>A(R175H),C.998A>G(p.Y333C)and C.1657T>C(p.Y553H).Conclusion Newborn screening is an important approach for early detection of GA-Ⅱ,but patients with GA-Ⅱ may have atypical biochemical changes,and all newborns with abnormal newborn screening results should be subjected to high-throughput sequencing for genetic diagnosis.

Objective To generate and identify the Itgbl1(integrin beta-like)promoter-driven Cre knock-in mouse line.Methods Itgbll-Cre knock-in mice were generated using clustered regularly interspaced short palindromic repeats(CRISPR)/CRISPR-associated protein 9(Cas9)gene editing.The Itgbl1-Cre mice were crossed with the Cre reporter ROSALSL-tdTomato)mice to detect the expression profile of Cre activity.The tdTomato expression pattern across tissues and cell-specific markers were used to identify the cell types of Itgbl1-expressing cells and their progeny.Results and Conclusion tdTomato was specifically expressed in mucous acinar cells of the sublingual gland,pancreatic islet cells,and gastric endocrine cells.In addition,tdTomato expression was also found in some of the neurons of the retina and brain,as well as in a few cells in the serosal layer of the intestine,articular cartilage,periosteum,and bone marrow.The first Itgbl1-Cre recombinase transgenic mouse line was established,which can specifically label the mucous acinar cells of the sublingual gland.

Objective:To investigate the feasibility,safety and effectiveness of robot-assisted laparo-scopic buccal mucosa graft ureteroplasty in the treatment of complex long proximal ureteral stricture.Methods:The clinical data of 20 patients with proximal ureteral stricture undergoing robot-assisted lapa-roscopic buccal mucosa graft ureteroplasty admitted to the Department of Urology,Peking University First Hospital and Beijing Jiangong Hospital from July 2022 to January 2023 were prospectively collected and analyzed.Intraoperative conditions,postoperative complications and follow-up data were also recorded and analyzed.Results:The operations under robot-assisted laparoscopy were performed successfully in all the 20 patients without conversion to traditional laparoscopic surgery or open surgery.The study in-cluded 14 males and 6 females with a mean age of(41±11)years(range:19 to 60 years)and a mean body mass index of(24.3±3.6)kg/m2(range:18.2 to 31.8 kg/m2).There were 9 cases on the left side and 11 cases on the right side.The strictures of all the patients were located in the proximal segment of the ureter(including the ureteropelvic junction).The mean preoperative serum creatinine was(92.2±23.3)μmol/L(range:49.2 to 138.9 μmol/L),and the mean length of ureteral stricture was(2.8±0.9)cm(range:1.0 to 4.0 cm).Ten patients had previously undergone unsuccessful reconstructive surgery.During the operation,12 patients received posteriorly augmented anastomosis with ventral onlay.The mean length of the buccal mucosa graft harvested during the operation was(3.1±0.6)cm(range:2.0 to 4.3 cm),and the median width was 1.5 cm(range:1.0 to 2.0 cm).The omentum flap was used to wrap the reconstructed ureteral segment in all the 20 cases.The median operative time was 154 min(range:113 to 300 min),and the median estimated blood loss was 45 mL(range:0 to 100 mL).The median postoperative hospital stay was 4 d(range:4 to 14 d).The mean postoperative follow-up time was(15.0±1.7)months(range:12.5 to 17.9 months),and the surgical success rate was 100.0％in this study.After surgery,11 patients reported mild discomfort at the oral donor site,2 patients deve-loped urinary tract infection,and no postoperative complications were reported in the other 7 patients.The mean serum creatinine was(90.9±23.9)μmol/L(range:60.0 to 153.0 μmol/L)six months after surgery.Conclusion:Robot-assisted laparoscopic buccal mucosa graft ureteroplasty for the treatment of complex long proximal ureteral stricture has satisfactory efficacy without severe complications,which has shown good feasibility,safety and effectiveness.However,large sample studies and long-term follow-up are still needed to evaluate its long-term efficacy.

Objective:To evaluate the effect of virtual reality arthroscopic simulation system combined with case-based learning (CBL) in orthopedic clinical teaching.Methods:From January 2021 to June 2022, a total of 36 residents who took the standardized residency training at Department of Articular Orthopedics in The Third Affiliated Hospital of Soochow University were enrolled in this study. They were randomized into an experimental group and a control group, with 18 trainees in each group. The experimental group adopted the virtual reality arthroscopic simulation system combined with CBL teaching mode, while the control group adopted simple endoscopic simulation training box with traditional teaching mode. Theoretical and practical tests and questionnaire survey were carried out to evaluate the teaching effects in two groups. SPSS 22.0 was performed to conduct t-test on the measurement data between the two groups. Results:The theoretical and practical test scores of the experimental group [(89.39±3.09) and (82.72±4.28)] were better than those of the control group [(86.22±4.43) and (76.61±5.65)], with statistically significant differences ( t= 2.49, P=0.018; t=3.66, P=0.001). The questionnaire survey showed that the experimental group was better than the control group in creating novel forms of courses [(4.94±0.24) vs. (4.11±0.58), t=5.62, P<0.001], simulating more real scenes [(4.83±0.38) vs. (3.78±0.43), t=7.80, P<0.001], inspiring learning interests [(4.78±0.43) vs. (4.00±0.59), t=4.51, P<0.001], improving practical skills [(4.83±0.38) vs. (3.83±0.51), t=6.61, P<0.001], and building career confidence [(4.50±0.62) vs. (3.06±0.54), t=7.47, P<0.001], with statistically significant differences (all P<0.001). Conclusions:The virtual reality arthroscopic simulation system combined with CBL teaching mode can better simulate the real clinical scenes, help inspire the interest of learning and quickly improve practical skills, thereby improving the effect of orthopedic clinical teaching.

Objective:To investigate the perioperative total blood loss of robot-assisted total knee arthroplasty (TKA).Methods:A total of 60 patients with knee osteoarthritis who underwent initial unilateral TKA in Peking Union Medical College Hospital from February to June 2022 were retrospectively analyzed. According to whether they received robot-assisted surgery, they were divided into robot-assisted group and traditional surgery group. In the robot-assisted group, there were 32 patients, including 6 males and 26 females, aged 70.22±5.88 years (range, 57 to 79 years). Left side 14 cases, right side 18 cases; grade of Kellgren-Lawrence: 1 case of grade Ⅱ, 14 cases of grade Ⅲ, 17 cases of grade Ⅳ. In the traditional surgery group, there were 28 patients, including 5 males and 23 females, aged 68.61±6.79 years (range, 57 to 87 years). Left side 16 cases, right side 12 cases; grade of Kellgren-Lawrence: 2 cases of grade Ⅱ, 12 cases of grade Ⅲ, 14 cases of grade Ⅳ. There was no significant difference in baseline data between the two groups ( P>0.05). Postoperative hemoglobin, hematocrit, and their decreased values were recorded in the two groups, and perioperative range of motion (ROM) of knee and Hospital for Special Surgery (HSS) scores were compared between the two groups. Results:All patients successfully completed the surgery and were followed up, with a follow-up time of 9.93±0.83 months (range, 8-11 months) in the robotic-assisted group and 9.59±0.97 months (range, 8-11 months) in the traditional surgery group. The application time of tourniquet in the robot-assisted group was 96.19±10.21 min, which was higher than that in the traditional surgery group (62.68±16.54 min), and the difference was statistically significant ( t=9.57, P<0.001). The total perioperative blood loss in the robot-assisted group was 534.59(411.85, 859.26) ml, which was higher than 411.32(313.42, 613.52) ml in the traditional surgery group, and the difference was statistically significant ( Z=-2.37, P=0.018). There were no significant differences in hemoglobin or hematocrit between the two groups at day 1 and 3 after surgery ( P>0.05). The hemoglobin decrease value in the robotic-assisted group was 19.63±9.73 g/L, which was greater than 14.71±5.84 g/L in the traditional surgery group, and the difference was statistically significant ( t=2.40, P=0.020). The decrease value of hematocrit in the robot-assisted group was 5.77%±3.14%, which was greater than 4.09%±1.57% in the traditional operation group ( t=2.56, P=0.013). At the last follow-up, knee ROM of the two groups were 123.03°±5.91° and 125.82°±6.59°, respectively, which were higher than the preoperative values of 95.69°±11.64° and 90.29°±23.08°. Postoperative HSS scores were 89.50±4.19 points and 90.70±4.34 points, which were higher than 62.58±10.52 points and 61.09±12.66 points before operation, the differences were statistically significant ( P<0.05), and there was no significant difference between groups ( P>0.05). There were 6 cases of postoperative deep vein thrombosis of the lower extremities in the robot-assisted group and 2 cases in the traditional surgery group, and the difference was not statistically significant (χ 2=0.88, P=0.348). Conclusion:Compared with traditional TKA, robotic-assisted TKA increased perioperative blood loss, and there was no difference in postoperative knee function between the two groups.

With the increasing understanding of the complex interaction between the tumor microenvironment and immune therapy, the role of immune checkpoint inhibitors in the treatment of head and neck squamous cell carcinoma (HNSCC) has gained significant attention. Immune checkpoint inhibitors targeting programmed death-1 (PD-1) and programmed death-ligand 1 (PD-L1) , cytotoxic T-lymphocyte-associated protein-4 (CTLA-4) , and T cell immunoglobulin domain and mucin domain-3 (TIM-3) , such as pembrolizumab, durvalumab, tremelimumab, ipilimumab, and LY3321367, have been applied in numerous clinical trials as monotherapies and combination therapies for the treatment of recurrent or metastatic HNSCC. Further research into the efficacy and safety of these immune checkpoint inhibitors in clinical trials may provide more effective strategies for the treatment of patients with recurrent or metastatic HNSCC.

  Objective  To understand the current status of surgical treatment for hemophilia osteoarthropathy (HO) in China.  Methods  Using an online questionnaire, select domestic hospitals that partici-pated in the compilation of the 'Guideline for perioperative management of hemophilia patients undergoing orthopaedic surgery in China ', in addition to members of the National Joint Surgery Group, and the Orthopedic Branch of the Chinese Medical Association for targeted investigation and analysis.  Results  A total of 17 domestic hospitals were included, all of which were general hospitals. Hospitals that started HO surgery treatment before 2000 accounted for 35.29%. A total of 3057 surgical cases of HO were reported by those hospitals. The most commonly performed surgical procedures were hip and knee joint replacement. The most commonly used coagulation factor replacement regimen was recombinant coagulation factor preparation. Ten hospitals reported finding patients with transfusion-related infectious diseases. Bleeding and hematoma formation were the most frequently reported surgical complications. Excessive length of hospital stay and high economic costs were the most frequently reported problems.  Conclusions  Surgical treatment for HO in 17 hospitals is mainly carried out in some large comprehensive medical centers in the eastern region. Compared with the patient base, the popularity and number of surgeries are still relatively insufficient. It is necessary to further standardize the treatment system by standardizing factor replacement and strengthening rehabilitation to improve surgical treatment outcomes.

Objective To explore the effect of peripheral blood markers on the efficacy and prognosis of patients with advanced esophageal cancer treated with immune checkpoint inhibitors (ICIs). Methods The case data of 61 patients with advanced esophageal cancer who met the inclusion criteria were collected. Data on clinical indicators and peripheral blood markers as well as objective response rate (ORR) and progression-free-survival (PFS) were obtained. Results The median PFS of the included patients was 7.10 months (95%CI: 5.12-9.07). The ORR of patients with baseline lactate dehydrogenase (LDH) < 201 was better than that of patients with LDH≥201 (P < 0.05). Univariate analysis showed that baseline LDH0 < 201, neutrophil to lymphocyte ratio (NLR) < 3.9, platelet-to-lymphocyte ratio (PLR) < 240.3, and LDH1 < 249.0 two weeks after ICI treatment were significantly associated with significant improvement in PFS (P < 0.05). In multivariate analysis, patients with NLR0 < 3.9 had longer PFS (P < 0.05). Conclusion LDH0 < 201, NLR0 < 3.9, PLR0 < 240.3, and LDH1 < 249.0 are positively correlated with the prognosis of patients with advanced esophageal cancer treated with ICIs.

Objective To investigate the impact of PD1-TCF1+CD8+ stem-like memory T cells on immunotherapy prognosis and tertiary lymphoid structure in tumors. Methods Pathological tissue sections were collected from 33 patients treated with immunotherapy, 18 cases of NSCLC and 15 cases of ESCC. The expression of PD1-TCF1+CD8+T cells was detected through quantitative analysis by multiplex immunofluorescence. Survival curves were described by the Kaplan-Meier method. Pearson's correlation test was used for correlation analysis. Results The high levels of PD1-TCF1+CD8+T cells had a better PFS in NSCLC and ESCC cohorts. In the NSCLC cohort, high levels of PD1-TCF1+CD8+ T cells were significantly and positively correlated with the number (P=0.0151) and size (P=0.0007) of TLSs. Conclusion In patients with NSCLC and ESCCs, high PD1-TCF1+CD8+ stem-like memory T cell expression indicates improved prognosis and immune response and is associated with the formation of TLSs in the tumor microenvironment of NSCLC.