ObjectiveBased on ultra-performance liquid chromatography-quadrupole-electrostatic field orbitrap high resolution mass spectrometry（UPLC-Q-Orbitrap-MS）， the chemical constituents of Qili Qiangxin capsules was identified， and their distribution in vivo was analyzed. MethodsUPLC-Q-Orbitrap-MS was used to detect the sample solution of Qili Qiangxin capsules， as well as the serum， brain， heart， lung， spleen， liver and kidney tissues of mice after oral administration. Using the Thermo Xcalibur 2.2 software， the compound information database was constructed， and the molecular formulas of compounds corresponding to the quasi-molecular ions were fitted. Based on the information of retention time， accurate relative molecular mass and fragments， the compounds and their distribution in vivo were analyzed by comparing with the data of reference substances and literature. ResultsA total of 233 compounds， including 70 terpenoids， 60 flavonoids， 23 organic acids， 17 alkaloids， 20 steroids， 7 coumarins and 36 others， were identified or predicted from Qili Qiangxin capsules， 73 of which were identified matching with standard substances. Tissue distribution results showed that 71， 17， 38， 33， 32， 58 and 43 migrating components were detected in blood， brain， heart， lung， spleen， liver and kidney， respectively. Thirty-seven components were absorbed into the blood and heart， including quinic acid， benzoylaconitine benzoylmesaconine and so on. Fourteen components were absorbed into the blood and six tissues， including calycosin， methylnissolin， formononetin， alisol B， alisol A and so on. ConclusionThis study comprehensively analyzes the chemical components of Qili Qiangxin capsules and their distribution in vivo. Among them， astragaloside Ⅳ， salvianolic acid B， ginsenoside Rb₁， ginsenoside Rb₃， ginsenoside Rd， ginsenoside Rg₃， calycosin-7-glucoside， and sinapine may be the important components for the treatment of heart failure， which can provide useful reference for its quality control and research on pharmacodynamic material basis.

In cases where a tracheal injury exceeds half the length of the adult trachea or one-third of the length of the child trachea, it becomes difficult to perform end-to-end anastomosis after tracheal resection due to excessive tension at the anastomosis site. In such cases, tracheal replacement therapy is required. Advances in tissue engineering technology have led to the development of tissue engineering tracheal substitutes, which have promising applications. Hydrogels, which are highly hydrated and possess a good three-dimensional network structure, biocompatibility, low immunogenicity, biodegradability, and modifiability, have had wide applications in the field of tissue engineering. This article provides a review of the characteristics, advantages, disadvantages, and effects of various hydrogels commonly used in tissue engineering trachea in recent years. Additionally, the article discusses and offers prospects for the future application of hydrogels in the field of tissue engineering trachea.

ObjectiveTo qualitatively analyze the chemical constituents and their tissue distribution in Lujiao formula based on ultra performance liquid chromatography-quadrupole-electrostatic field orbitrap high resolution mass spectrometry（UPLC-Q-Orbitrap-MS）. MethodThe separation was performed on an ACQUITY UPLC^® BEH C₁₈ column（2.1 mm×100 mm， 1.7 μm） with the mobile phase of 0.1% formic acid aqueous solution（A）-methanol（B） in a gradient elution（0-2 min， 4%B； 2-6 min 4%-12%B； 6-38 min， 12%-70%B； 38-38.5 min， 70%B； 38.5-39 min， 70%-95%B； 39-43 min， 95%B； 43-43.1 min， 95%-4%B； 43.1-45 min， 4%B）， the flow rate was 0.3 mL·min^-1 with the column temperature of 40 ℃ and the injection volume of 5 µL. The data were acquired by an electrospray ionization（ESI） in the full scanning mode of positive and negative ions， the scanning rang was set at m/z 100-1 500， the collision energies were 10， 20， 40 eV. Retention time， precise relative molecular mass and secondary mass spectrometry fragment ions were used to identify the compounds in Lujiao formula and analyze their tissue distribution， combing with self-established database and comparing with standard substances and published literature data. ResultA total of 260 compounds， including 156 flavonoids， 43 terpenoids， 18 coumarins， 13 organic acids， 7 phenylethanoids， 7 alkaloids and 16 others， were identified or hypothesized from Lujiao formula， 68 of which were identified by comparison with standard substances. And the results of tissue distribution showed that 100， 143， 129 and 126 prototype components were detected in blood， heart， liver and kidney， respectively. ConclusionThe chemical composition of Lujiao formula and their tissue distribution were systematic analyzed， which can provide reference for the quality control， clinical application， pharmacokinetics and pharmacodynamic material basis of Lujiao formula and its medicinal materials.

Objective To investigate the clinical efficacy and safety of the combination PP(Pemetrexed+Cisplatin)regimen of sindilizumab(Sintilimab)+bevacizumab(Bevacizumab)in advanced non-squamous non-small cell lung cancer(NSCLC)with disease progression after treatment with epidermal growth factor receptor(EGFR)tyrosine kinase inhibitors.Methods Patients with advanced non-squamous NSCLC with disease progression after receiving EGFR tyrosine kinase inhibitor treatment from January 2019 to January 2022 were retrospectively selected from The Third Affiliated Hospital of Zhejiang University of Traditional Chinese Medicine.According to the different treatment modalities,patients were divided into the pemetrexed+cisplatin treatment group(Chemotherapy)group and the pemetrexed+cisplatin+si ndilizumab+bevacizumab treatment(Sintilimab+Bevacizumab)group.Progression-free survival(PFS),overall survival(OS),objective response rate(ORR)and disease control rate(DCR)were compared between the two groups and the occurrence of adverse reactions was assessed.Results A total of 107 patients were enrolled in the study,53 in the Sintilimab+Bevacizumab group and 54 in the Chemotherapy group.The median PFS and median OS were significantly higher in the Sintilimab+Bevacizumab group than in the Chemotherapy group(P＜0.05).The median PFS and median OS in the Sintilimab+Bevacizumab group were significantly higher than in the Chemotherapy group.Bevacizumab group had no statistically significant difference in ORR with Chemotherapy group(P＞0.05),while DCR was significantly higher than Chemotherapy group(P＜0.05).The main adverse reactions were similar in both groups with the most common adverse events being anemia and neutrophils decrease.Conclusion Sintilimab+Bevacizumab combined with PP regimen treatment improved DCR and prolonged PFS and OS in patients with advanced non-squamous NSCLC whose disease progressed after EGFR tyrosine kinase inhibitor treatment.

Objective To analyze the current development of researches on biomarkers for predicting the efficacy of immunotherapy in non-small cell lung cancer and to provide reference for subsequent studies. Methods Studies on biomarkers for predicting the efficacy of immunotherapy for non-small cell lung cancer indexed in the Web of Science Core Collection from 2017 to 2021 were searched by computer. The annual distribution, journals, authors, countries, institutions, and keywords of studies were visualized and analyzed by CiteSpace. Results A total of 426 studies were collected, including 298 articles and 128 reviews. The average number of published studies was about 85, and increased year by year. PD-L1 expression, tumor mutational burden, tumor microenvironment and liquid biopsy were hot keywords in this field. Conclusion In the future, combination of biomarkers in the liquid biopsy and tumor microenvironment with radiomics analysis will be the research hotspot and frontier in this field for more accurate assessment with tumor-related signatures such as lymphocytic immune status and characteristics of tumor lesions in non-small cell lung cancer patients.

Objective To analyze the current research application status and hotspots of nanoparticles in the treatment of non-small cell lung cancer (NSCLC) and predict the future development trend. Methods The Web of Science database was searched for literatures on nanoparticles use in the treatment of NSCLC from inception to November 2022. CiteSpace, VOSviewer and literature measurement analysis online platform (https://bibliometric.com/) were used for the visual analysis of the number of documents, source journals, authors, organizations, countries and keywords. Results A total of 742 English literatures were included. The results showed that the number of published literatures increased year by year from 2011 and reached the peak in 2020. Researches on nanoparticles and NSCLC treatment were mainly concentrated in China, the United States, India and Japan. China is a major research country in this field, but it lacked cooperation with other countries and related institutions. Among numerous research institutions, the Chinese Academy of Sciences was the authoritative and backbone force in this research field, with the number of published literatures ranking first and the research achievements outstanding. The keyword analysis found that "poly lactic-co-glycolic acid nanoparticles (PLGA NPs)" and "photothermal therapy" had become the latest breakout words since 2018. Moreover, the occurrence frequency of related keywords such as "drug delivery" increased significantly, indicating that the application of PLGA NPs in photothermal therapy might be the current research hotspot and future development trend of NSCLC treatment. Conclusion Currently, the domestic research on the treatment of nanoparticles and NSCLC is in a leading position in the world. The organic combination of nanoparticles with different materials and other NSCLC therapies is expected to improve the prognosis of NSCLC patients. In the future, attempts to develop nanoparticles with different sources and structures and combined with photothermal therapy for the treatment of NSCLC may become a research hotspot of nanoparticles in the treatment of NSCLC.

Objective:To prepare anti-human IgE nanobody by phage display technology,and to establish a method for hyper-sensitivity detection of cat dander specific IgE antibody.Methods:Allergen bio-information of cat was searched in WHO/IUIS Allergen Database.After synthesizing sequence,recombinant cat dander allergenic protein Fel d 1 was expressed and purified in prokaryotic ex-pression system.Human IgE was used to immunize Bactrian camel and RNA were extracted from lymphocyte to construct phage dis-play library.Library capacity,diversity and insertion rate were analyzed,anti-human IgE nanobody were obtained by screening and identification.A magnetic particle chemical method for cat dander specific IgE antibody detection was established using recombinant allergen-coupled magnetic particles and acridine ester-labeled nanobodies.Results:Capacity of phage display library was 1.88×108 cfu/ml,insertion rate was 93.6%,and purity of nanobody was>95%.Linear range of the method based on nanobody was 0.1～100 U/ml,who was consistent with ImmunoCAP detection system by clinical data.Conclusion:Nanobody-based cat dander specific IgE antibody hypersensitivity assay is successfully prepared,providing a technical basis for auxiliary diagnosis of cat allergic diseases.

Objective:To explore the clinical outcomes of locking compression plating (LCP) in the treatment of periprosthetic fracture (PPF) of the distal femur in the aged patients.Methods:A retrospective study was performed to analyze the 31 aged patients who had been treated at Department of Orthopedic Surgery, The Affiliated Hospital to Nantong University for PPF of the distal femur with LCP between June 2012 and May 2023. There were 27 females and 4 males with an age of (80.2±6.1) years. According to the Unified Classification System (UCS), 18 PPFs were classified as type Ⅴ.3B1 and 6 PPFs as type Ⅴ.3B2 after total knee arthroplasty and 7 PPFs as type Ⅳ.3C after total hip arthroplasty. The patients were fixated with a lateral single plate in 25 cases, and with lateral and medial dual plates in 6 cases. The surgical time, intraoperative blood loss, hospitalization time, postoperative weight-bearing time, fracture healing time, and knee joint function and complications during follow-up were recorded.Results:For the 25 patients undergoing fixation with a lateral single plate, the surgical time was (58.7±7.9) minutes, the intraoperative blood loss (78.0±15.1) mL, the hospitalization time (6.9±1.6) days, the postoperative weight-bearing time (5.9±1.4) days, and the follow-up time 37 (15, 51) months. For the 6 patients undergoing fixation with lateral and medial dual plates, the surgical time was (186.6±9.8) minutes, the intraoperative blood loss (1,256.7±231.2) mL, the hospitalization time (17.8±3.3) days, the postoperative weight-bearing time (3.6±0.6) days, and the follow-up time 17 (16, 21) months. The fracture healing time was (14.9±2.0) and (18.7±2.6) weeks, respectively, for patients fixed with single and double steel plates. By the scoring criteria of the American Hospital for Special Surgery (HSS), the knee joint function was evaluated at the last follow-up as excellent in 10 cases and as good in 15 cases for the 25 patients undergoing fixation with a lateral single plate, and as good for all the 6 patients undergoing fixation with lateral and medial dual plates. No patient experienced such complications as incision infection, bone nonunion, or internal fixation failure during the follow-up period.Conclusions:LCP fixation can achieve satisfactory outcomes in the treatment of PPF of the distal femur in the aged patients. As fixation with a single lateral femoral plate is suitable for most of the aged patients with PPF of the distal femur, it can be used as the first choice. Fixation with dual plates can provide stronger stability, but its indications should be strictly controlled.

OBJECTIVE To compare the efficacy of Danning tablet， taurosodeoxycholic acid and ursodeoxycholic acid in preventing the recurrence of choledocholithiasis after endoscopic retrograde cholangiopancreatography （ERCP）. METHODS The clinical data of 153 patients who underwent ERCP choledocholithotomy from January 2017 to January 2020 in Nantong First People’s Hospital were retrospectively analyzed. According to the different drug treatment received after surgery， patients were divided into three groups， namely， Danning tablet group （group A， 49 cases）， tauroursodeoxycholic acid group （group B， 44 cases） and ursodeoxycholic acid group （group C， 60 cases）. The above groups of drugs are all single-use， starting from 2 weeks after surgery for a course of 180 days. The effects of bile component indicators [total bilirubin （Tbil）， direct bilirubin （Dbil）， alkaline phosphatase （ALP）， glutamyltransferase （GGT）]， lipid metabolism indicators [total cholesterol （TC）， triglyceride （TG）， low-density lipoprotein （LDL）， high-density lipoprotein （HDL）]， the occurrence of clinical symptoms （abdominal pain， bloating， nausea， and poor appetite） at 6 months after ERCP， and the recurrence of choledocholithiasis at 6， 12， 18 and 24 months after surgery were compared among 3 groups. RESULTS Compared with before surgery， the serum levels of Tbil， Dbil， ALP， GGT， TC， TG and LDL were significantly reduced （P＜0.05）， while serum HDL levels were significantly increased （P＜0.05） in the three groups at 6 months after surgery. The proportion of patients who experienced abdominal pain， bloating， nausea， and poor appetite at 6 months after surgery was significantly reduced （P＜0.05）. The Tbil levels of groups A and B were significantly lower than those of group C （P＜0.05）， while the Dbil and ALP levels of group A were significantly lower than those of groups B and C （P＜0.05）； however， there was no statistically significant difference in GGT levels among the 3 groups （P＞0.05）. Compared with groups A and C， the levels of four lipid metabolism indicators in group B were significantly improved （P＜0.05）； the proportion of patients with abdominal pain， bloating， and poor appetite in group A was significantly lower than groups B and C （P＜0.05）， but there was no statistically significant difference in the proportion of patients with nausea among the 3 groups （P＞0.05）. At 6，12 and 18 months after surgery， there was no statistically significant difference in the rate of choledocholithiasis recurrence among the 3 groups （P＞0.05）； at 24 months after surgery， the rate of choledocholithiasis recurrence in group A （2.04%） was significantly lower than group B （15.91%） and group C （15.00%） （P＜0.05）. CONCLUSIONS Compared with tauroursodeoxycholic acid and ursodeoxycholic acid， the application of Danning tablet after ERCP is more beneficial to reduce the secretion of bile acid， prevent the recurrence of gallstones， and improve clinical symptoms， but tauroursodeoxycholic acid can significantly accelerate the lipid metabolism of patients compared with the other two drugs.

Objective:To investigate the combination of internal fixation for periprosthetic fractures of the proximal femur (PFFF) after hip arthroplasty.Methods:The data of 58 patients with periprosthetic fractures after hip arthroplasty from May 2008 to March 2022 were retrospectively analyzed, including 31 males and 27 females. The average age was 75.5±18.2 years (range, 35-95 years). There were 39 total hip arthroplasty and 19 hemiarthroplasty; 37 biological prosthesis and 21 cemented prosthesis. Intraoperative periprosthetic fractures occurred in 6 cases and 52 cases postoperatively. Unified classification system (UCS): UCS IV.3A1 type 2 cases, 3A2 type 1 case, 3B1.1 type 19 cases, 3B2.1 type 25 cases, 3B3 type 2 cases, 3C type 9 cases. Fracture site: 3 cases in zone A (greater trochanter), 46 cases in zone B (around the femoral stem), and 9 cases in zone C (distal to the tip of the femoral stem. Internal fixation is composed of primary and secondary fixation, the main fixation method was the cerclage of steel wire or titanium cable, locking compression plate, and locking attachment plate fixation. The secondary fixation method was the cerclage of titanium cable, which was required to cover three zones A, B and C to form an overall balanced fixation. The modified Harris hip scores (mHHS), plate length, working length and screw number of different internal fixation combinations were compared.Results:The follow-up time was 54.2±21.6 months (range, 11-86 months). All patients showed signs of fracture healing at 10.2±1.5 weeks (range, 7-13 weeks) after operation, and bony union was observed at 19.6±1.3 weeks (range, 17-22 weeks) after operation. No delayed union or nonunion was observed. After operation, one case had a stress fracture and was revised with double-plate internal fixation; one case had a failed internal fixation and was revised with double-plate internal fixation and a large allograft bone graft. The mHHS score of UCSIV.3B2.1 group (80.3±4.6) was the lowest at 6 months after operation, and the difference between the groups of different types was statistically significant ( F=256.72, P<0.001). The score of simple internal fixation group (91.6±4.2) was higher than that of revision combined with internal fixation group (81.9±4.1), and the difference was statistically significant ( t=8.32, P<0.001). The plate length and working length were 24.9±2.5 cm and 12.6±1.7 cm for UCS IV.3B1.1, 25.4±2.6 cm and 13.6±1.8 cm for 3B2.1 and 28.1±2.5 cm and 4.9±1.9 cm for 3C, respectively ( F=5.33, P=0.005; F=6.78, P<0.001). The number of screws in zone A was significant difference among different UCS types ( F=52.67, P<0.001); UCS IV.3B1.1 (6.5±2.3) and 3B2.1 (6.7±2.2) were more than 3B3 (3.5±1.5) and 3C (3.7±1.6). The number of screws in zone B was significant difference among different UCS types ( F=42.15, P<0.001); The number of UCS IV.3B1.1 (2.3±1.6) and 3B2.1 (2.8±1.9) were significantly more than that of 3B3 (1.0±0.5) and 3C (1.2±0.6). The number of screws in zone C was significant differences among different UCS types ( F=39.62, P<0.001); The number of UCS IV.3B1.1 (3.8±1.9) and 3B2.1 (3.9±1.7) were more than that of 3B3 (2.0±0.5), the difference was statistically significant ( P<0.05). Conclusion:The function of hip after simple internal fixation of proximal femoral periprosthetic fractures was better than that of those who underwent revision at the same time; the number of screws of UCSIV.B1 and B2 is more than that of B3.