OBJECTIVE: To investigate the effect of Cyr61 on imatinib (IM) resistance in chronic myeloid leukemia (CML) and its mechanism. METHODS: Cyr61 level in cell culture supernatant was determined by enzyme-linked immunosorbent assay. The expression of Cyr61 and Bcl-xL were measured by real-time PCR and Western blot. Cell apoptosis was analyzed using an Annexin V-APC Kit. Expression of signal pathways related proteins was determined by Western blot. RESULTS: The level of Cyr61 obviously increased in K562G cells (IM resistance to CML cell line K562). Down-regulating the expression of Cyr61 decreased the resistance of K562G cells to IM and promoted IM induced apoptosis. In CML mouse model, down-regulating the expression of Cyr61 could increase the sensitivity of K562G cells to IM. The mechanism studies showed that Cyr61 mediated IM resistance in CML cells was related to the regulation of ERK1/2 pathways and apoptosis related molecule Bcl-xL by Cyr61. CONCLUSION Cyr61 plays an important role in promoting IM resistance of CML cells. Targeting Cyr61 or its related effectors pathways may be one of the ways to overcome IM resistance of CML cells.
Animals ; Humans ; Mice ; Apoptosis ; Drug Resistance, Neoplasm ; Imatinib Mesylate/pharmacology* ; K562 Cells ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive/metabolism* ; Signal Transduction

OBJECTIVE: To investigate the causes of soft tissue complications in patients with dorsal displacement distal radius fractures (DRF) after volar locking plate surgery. METHODS: From July 2016 to May 2021, 112 patients with dorsal displacement DRF were treated with volar locking plate surgery, including 45 males and 67 females. The average age was (46.24±10.08) years old, ranging from 18 to 85 years old. According to whether there were soft tissue complications after operation, they were divided into complication group (40 cases) and non complication group (72 cases). Compared with preoperation, the radial metacarpal inclination and ulnar deflection angle, wrist flexion activity and dorsal extension activity, and grip strength of patients after operation were significantly improved (P<0.05). Compared with the non complication group, the proportion of patients in the complication group whose age was>60 years, body mass index (BMI) more than 30 kg·m^-2, smoking, diabetes, fracture type C, open fracture and operation time more than 90 min was higher (P<0.05). The age, BMI, smoking, diabetes, fracture AO classification, fracture type and operation time were analyzed by multifactor Logistic regression to determine the independent risk factors affecting the occurrence of postoperative soft tissue complications of patients, establish a nomogram prediction model, and evaluate the model. RESULTS: At the latest follow-up, the excellent and good rate of wrist joint function recovery was 83.93% (94/112), and the excellent and good rate of fracture reduction was 84.82% (95/112). Multivariate Logistic regression analysis showed that age more than 60 years old, diabetes, fracture type C, open fracture and operation time more than 90 min were independent risk factors for postoperative soft tissue complications (P<0.05). The receiver operating characteristic (ROC), calibration curve and clinical decision curve of the nomogram prediction model showed discrimination, accuracy and validity were good. CONCLUSION Age more than 60 years, diabetes mellitus, fracture type C, open fracture, and operation time more than 90 min are all independent risk factors for soft tissue complications after DRF volar plate fixation. In clinical treatment, perioperative soft tissue management should be done in such patients to prevent complications.
Female ; Male ; Humans ; Adult ; Middle Aged ; Adolescent ; Young Adult ; Aged ; Aged, 80 and over ; Wrist Fractures ; Fractures, Open ; Risk Factors ; Wrist Joint/surgery* ; Metacarpal Bones

OBJECTIVE: To investigate the mechanism by which Chinese medicine Shengmai Yin (SMY) reverses epithelial-mesenchymal transition (EMT) through lipocalin-2 (LCN2) in nasopharyngeal carcinoma (NPC) cells CNE-2R. METHODS: Morphological changes in EMT in CNE-2R cells were observed under a microscope, and the expressions of EMT markers were detected using quantitative real-time PCR (RT-qPCR) and Western blot assays. Through the Gene Expression Omnibus dataset and text mining, LCN2 was found to be highly related to radiation resistance and EMT in NPC. The expressions of LCN2 and EMT markers following SMY treatment (50 and 100 µ g/mL) were detected by RT-qPCR and Western blot assays in vitro. Cell proliferation, migration, and invasion abilities were measured using colony formation, wound healing, and transwell invasion assays, respectively. The inhibitory effect of SMY in vivo was determined by observing a zebrafish xenograft model with a fluorescent label. RESULTS: The CNE-2R cells showed EMT transition and high expression of LCN2, and the use of SMY (5, 10 and 20 µ g/mL) reduced the expression of LCN2 and reversed the EMT in the CNE-2R cells. Compared to that of the CNE-2R group, the proliferation, migration, and invasion abilities of SMY high-concentration group were weakened (P<0.05). Moreover, SMY mediated tumor growth and metastasis in a dose-dependent manner in a zebrafish xenograft model, which was consistent with the in vitro results. CONCLUSIONS SMY can reverse the EMT process of CNE-2R cells, which may be related to its inhibition of LCN2 expression. Therefore, LCN2 may be a potential diagnostic marker and therapeutic target in patients with NPC.
Animals ; Humans ; Nasopharyngeal Carcinoma/genetics* ; Epithelial-Mesenchymal Transition ; Zebrafish ; Cell Proliferation ; Cell Line, Tumor ; Nasopharyngeal Neoplasms/radiotherapy* ; Cell Movement ; Gene Expression Regulation, Neoplastic

Objective:To investigate the clinicopathologic features and differential diagnosis of ureteral fibroepithelial polyps.Methods:The clinicopathologic features and prognosis of ureteral fibroepithelial polyps with complete data retrieved from the pathology database of the Institute of Urology, Peking University from January 2013 to December 2021 were collected and analyzed. All HE staining sections were reviewed by a senior urologic pathologist. Immunohistochemical analysis was done in some cases for differential diagnosis. The clinical, imaging and outcome data were collected, and discussed together with relevant literature.Results:There were 45 patients with complete clinicopathologic data, including 34 males and 11 females (male: female=3.1∶1.0), with a median age of 36 (range 13-80) years. Preoperative diagnosis included polyp in 23 cases, tumor in 19 cases and calculi in 3 cases. The main clinical symptoms were hematuria (13 cases), low back and abdominal pain (9 cases) and no symptoms (9 cases). There were 29 cases of multiple polyps, 16 cases of single polyp; 32 cases were on the left side, 13 cases were on the right side; 29 cases of upper polyps, 9 cases of middle polyps, and 6 cases of lower polyps. Twenty-seven patients had no related urologic history, 10 patients had history of urolithiasis, and the rest had history of stents, strictures or tumors. Local ureteral resection and anastomosis were the most common treatment (20 cases), followed by ureteroscopic polypectomy (12 cases). The patients were followed up from the pathological diagnosis to the cut-off time: 4 cases were lost to follow-up, and the remaining 34 cases were followed up for 3 to 85 (mean 60 months). One case had polyp recurrence after 3 months, and the other case had polyp recurrence after 2 years. Fibroepithelial polyps had a variety of gross manifestations, ranging from elongated polyps or small papillary and polypoid to large papillary masses. Microscopically, they were divided into type 1, type 2 and type 3, and the type 3 was the most common type (28 cases). In this study, there were 41 cases of simple fibroepithelial polyp, 2 cases of malignant transformation of polyps into urothelial carcinoma, one case of polyps with urothelial carcinoma, and one case of polyp with surface urothelial carcinoma in situ; the stroma showed myofibroblastic proliferation.Conclusions:The clinical manifestations and morphologic characteristics of ureteral fibroepithelial polyps are diverse. The three microscopic types are easily confused with many benign and malignant ureteral diseases, such as inflammatory polyps, adenocystitis, papilloma, etc. Awareness of the key differentiation points and judicious use of immunohistochemistry will be helpful for the diagnosis and differential diagnosis.

Objective:To investigate the epidemiological characteristics, diagnosis, treat-ment and prognosis of gallbladder cancer in China from 2010 to 2017.Methods:The single disease retrospective registration cohort study was conducted. Based on the concept of the real world study, the clinicopathological data, from multicenter retrospective clinical data database of gallbladder cancer of Chinese Research Group of Gallbladder Cancer (CRGGC), of 6 159 patients with gallbladder cancer who were admitted to 42 hospitals from January 2010 to December 2017 were collected. Observation indicators: (1) case resources; (2) age and sex distribution; (3) diagnosis; (4) surgical treatment and prognosis; (5) multimodality therapy and prognosis. The follow-up data of the 42 hospitals were collected and analyzed by the CRGGC. The main outcome indicator was the overall survival time from date of operation for surgical patients or date of diagnosis for non-surgical patients to the end of outcome event or the last follow-up. Measurement data with normal distribu-tion were represented as Mean±SD, and comparison between groups was conducted using the t test. Measurement data with skewed distribution were represented as M( Q1, Q3) or M(range), and com-parison between groups was conducted using the U test. Count data were described as absolute numbers or percentages, and comparison between groups was conducted using the chi-square test. Univariate analysis was performed using the Logistic forced regression model, and variables with P<0.1 in the univariate analysis were included for multivariate analysis. Multivariate analysis was performed using the Logistic stepwise regression model. The life table method was used to calculate survival rates and the Kaplan-Meier method was used to draw survival curves. Log-rank test was used for survival analysis. Results:(1) Case resources: of the 42 hospitals, there were 35 class A of tertiary hospitals and 7 class B of tertiary hospitals, 16 hospitals with high admission of gallbladder cancer and 26 hospitals with low admission of gallbladder cancer, respectively. Geographical distribution of the 42 hospitals: there were 9 hospitals in central China, 5 hospitals in northeast China, 22 hospitals in eastern China and 6 hospitals in western China. Geographical distribution of the 6 159 patients: there were 2 154 cases(34.973%) from central China, 705 cases(11.447%) from northeast China, 1 969 cases(31.969%) from eastern China and 1 331 cases(21.611%) from western China. The total average number of cases undergoing diagnosis and treatment in hospitals of the 6 159 patients was 18.3±4.5 per year, in which the average number of cases undergoing diagnosis and treatment in hospitals of 4 974 patients(80.760%) from hospitals with high admission of gallbladder cancer was 38.8±8.9 per year and the average number of cases undergoing diagnosis and treatment in hospitals of 1 185 patients(19.240%) from hospitals with low admission of gallbladder cancer was 5.7±1.9 per year. (2) Age and sex distribution: the age of 6 159 patients diagnosed as gallbladder cancer was 64(56,71) years, in which the age of 2 247 male patients(36.483%) diagnosed as gallbladder cancer was 64(58,71)years and the age of 3 912 female patients(63.517%) diagnosed as gallbladder cancer was 63(55,71)years. The sex ratio of female to male was 1.74:1. Of 6 159 patients, 3 886 cases(63.095%) were diagnosed as gallbladder cancer at 56 to 75 years old. There was a significant difference on age at diagnosis between male and female patients ( Z=-3.99, P<0.001). (3) Diagnosis: of 6 159 patients, 2 503 cases(40.640%) were initially diagnosed as gallbladder cancer and 3 656 cases(59.360%) were initially diagnosed as non-gallbladder cancer. There were 2 110 patients(34.259%) not undergoing surgical treatment, of which 200 cases(9.479%) were initially diagnosed as gallbladder cancer and 1 910 cases(90.521%) were initially diagnosed as non-gallbladder cancer. There were 4 049 patients(65.741%) undergoing surgical treatment, of which 2 303 cases(56.878%) were initially diagnosed as gallbladder cancer and 1 746 cases(43.122%) were initial diagnosed as non-gallbladder cancer. Of the 1 746 patients who were initially diagnosed as non-gallbladder cancer, there were 774 cases(19.116%) diagnosed as gallbladder cancer during operation and 972 cases(24.006%) diagnosed as gallbladder cancer after operation. Of 6 159 patients, there were 2 521 cases(40.932%), 2 335 cases(37.912%) and 1 114 cases(18.087%) undergoing ultrasound, computed tomography (CT) or magnetic resonance imaging (MRI) examination before initial diagnosis, respec-tively, and there were 3 259 cases(52.914%), 3 172 cases(51.502%) and 4 016 cases(65.205%) undergoing serum carcinoembryonic antigen, CA19-9 or CA125 examination before initially diagnosis, respectively. One patient may underwent multiple examinations. Results of univariate analysis showed that geographical distribution of hospitals (eastern China or western China), age ≥72 years, gallbladder cancer annual admission of hospitals, whether undergoing ultrasound, CT, MRI, serum carcinoembryonic antigen, CA19-9 or CA125 examination before initially diagnosis were related factors influencing initial diagnosis of gallbladder cancer patients ( odds ratio=1.45, 1.98, 0.69, 0.68, 2.43, 0.41, 1.63, 0.41, 0.39, 0.42, 95% confidence interval as 1.21-1.74, 1.64-2.40, 0.59-0.80, 0.60-0.78, 2.19-2.70, 0.37-0.45, 1.43-1.86, 0.37-0.45, 0.35-0.43, 0.38-0.47, P<0.05). Results of multivariate analysis showed that geographical distribution of hospitals (eastern China or western China), sex, age ≥72 years, gallbladder cancer annual admission of hospitals and cases undergoing ultrasound, CT, serum CA19-9 examination before initially diagnosis were indepen-dent influencing factors influencing initial diagnosis of gallbladder cancer patients ( odds ratio=1.36, 1.42, 0.89, 0.67, 1.85, 1.56, 1.57, 0.39, 95% confidence interval as 1.13-1.64, 1.16-1.73, 0.79-0.99, 0.57-0.78, 1.60-2.14, 1.38-1.77, 1.38-1.79, 0.35-0.43, P<0.05). (4) Surgical treatment and prognosis. Of the 4 049 patients undergoing surgical treatment, there were 2 447 cases(60.435%) with complete pathological staging data and follow-up data. Cases with pathological staging as stage 0, stage Ⅰ, stage Ⅱ, stage Ⅲa, stage Ⅲb, stage Ⅳa and stage Ⅳb were 85(3.474%), 201(8.214%), 71(2.902%), 890(36.371%), 382(15.611%), 33(1.348%) and 785(32.080%), respectively. The median follow-up time and median postoperative overall survival time of the 2 447 cases were 55.75 months (95% confidence interval as 52.78-58.35) and 23.46 months (95% confidence interval as 21.23-25.71), respectively. There was a significant difference in the overall survival between cases with pathological staging as stage 0, stage Ⅰ, stage Ⅱ, stage Ⅲa, stage Ⅲb, stage Ⅳa and stage Ⅳb ( χ2=512.47, P<0.001). Of the 4 049 patients undergoing surgical treatment, there were 2 988 cases(73.796%) with resectable tumor, 177 cases(4.371%) with unresectable tumor and 884 cases(21.833%) with tumor unassessable for resectabi-lity. Of the 2 988 cases with resectable tumor, there were 2 036 cases(68.139%) undergoing radical resection, 504 cases(16.867%) undergoing non-radical resection and 448 cases(14.994%) with operation unassessable for curative effect. Of the 2 447 cases with complete pathological staging data and follow-up data who underwent surgical treatment, there were 53 cases(2.166%) with unresectable tumor, 300 cases(12.260%) with resectable tumor and receiving non-radical resection, 1 441 cases(58.888%) with resectable tumor and receiving radical resection, 653 cases(26.686%) with resectable tumor and receiving operation unassessable for curative effect. There were 733 cases not undergoing surgical treatment with complete pathological staging data and follow-up data. There was a significant difference in the overall survival between cases not undergoing surgical treatment, cases undergoing surgical treatment for unresectable tumor, cases undergoing non-radical resection for resectable tumor and cases undergoing radical resection for resectable tumor ( χ2=121.04, P<0.001). (5) Multimodality therapy and prognosis: of 6 159 patients, there were 541 cases(8.784%) under-going postoperative adjuvant chemotherapy and advanced chemotherapy, 76 cases(1.234%) under-going radiotherapy. There were 1 170 advanced gallbladder cancer (pathological staging ≥stage Ⅲa) patients undergoing radical resection, including 126 cases(10.769%) with post-operative adjuvant chemotherapy and 1 044 cases(89.231%) without postoperative adjuvant chemo-therapy. There was no significant difference in the overall survival between cases with post-operative adjuvant chemotherapy and cases without postoperative adjuvant chemotherapy ( χ2=0.23, P=0.629). There were 658 patients with pathological staging as stage Ⅲa who underwent radical resection, including 66 cases(10.030%) with postoperative adjuvant chemotherapy and 592 cases(89.970%) without postoperative adjuvant chemotherapy. There was no significant difference in the overall survival between cases with postoperative adjuvant chemotherapy and cases without postoperative adjuvant chemotherapy ( χ2=0.05, P=0.817). There were 512 patients with pathological staging ≥stage Ⅲb who underwent radical resection, including 60 cases(11.719%) with postoperative adjuvant chemotherapy and 452 cases(88.281%) without postoperative adjuvant chemotherapy. There was no significant difference in the overall survival between cases with postoperative adjuvant chemo-therapy and cases without post-operative adjuvant chemo-therapy ( χ2=1.50, P=0.220). Conclusions:There are more women than men with gallbladder cancer in China and more than half of patients are diagnosed at the age of 56 to 75 years. Cases undergoing ultrasound, CT, serum CA19-9 examination before initial diagnosis are independent influencing factors influencing initial diagnosis of gallbladder cancer patients. Preoperative resectability evaluation can improve the therapy strategy and patient prognosis. Adjuvant chemotherapy for gallbladder cancer is not standardized and in low proportion in China.

Polyhydroxyalkanoates (PHAs) are polymers obtained by esterification of hydroxy fatty acid monomers. Due to similar mechanical characteristics of traditional petroleum-based plastics, 100% biodegradability and biocompatibility, PHAs are considered to be one of the most potential green materials. However, the application and promotion of PHAs as a green and environmentally friendly material are difficult because of the high production costs. This article focuses on the current methods to reduce production cost of PHAs effectively, such as cell morphology regulation, metabolic pathway construction, economic carbon source utilization and open fermentation technology development. Despite most research results are still limited in laboratory, the research methods and directions provide theoretical guidance for the industrial production of economic PHAs.
Fermentation ; Industry ; Petroleum ; Plastics ; Polyhydroxyalkanoates

Dammarane-type triterpenoid saponins are regarded as the main active constituents of Gynostemma longipes C.Y.Wu. By using MCI and silica gel column chromatography, as well as preparative HPLC, we isolated four new dammarane-type triterpenoid saponins from the polar saponin fraction of G. longipes C.Y.Wu. Their structures were determined by comprehensive analyses of NMR and MS data and identified as (20S)-3β,20,21-trihydroxydammar-19-oxo-24-ene-3-O-{[α-L-rhamnopyranosyl(1→2)]-[β-D-xylopyranosyl(1→3)]-α-L-arabinopyranosyl}-21-O-β-D-glucopyranosyl(1→6)-β-D-glucopyranoside (1), (20S)-3β,20,21-trihydroxydammar-24-ene-19-oxo-3-O-[α-L-rhamnopyranosyl(1→2)]-[β-D-xylopyranosyl(1→3)]-α-L-arabinopyranosyl-21-O-α-L-rhamnopyranosyl(1→6)-β-D-glucopyranoside (2), (20S)-3β,19,20,21-terahydroxydammar-24-ene-3-O-{[α-L-rhamnopyranosyl(1→2)]-[β-D-xylopyranosyl(1→3)]-α-L-arabinopyranosyl}-21-O-[β-D-glucopyranosyl(1→6)]-β-D-glucopyranoside (3), (20S)-3β,20,21-trihydroxydammar-24-ene-3-O-{[α-L-rhamnopyranosyl(1→2)]-[β-D-glucopyranosyl(1→3)]-β-D-glucopyranosyl}-21-O-[β-D-glucopyranosyl(1→6)]-β-D-glucopyranoside (4). Compounds 1-4 are new dammarane-type triterpenoid saponins which contain five glycosyl residues.

Objective: The aim of the study is to analyze the effects of vestibular spontaneous nystagmus(SN) on the smooth pursuit function of visual ocularmotor system. Methods: A total of 46 patients with acute unilateral peripheral vestibular syndrome with SN (26 cases of vestibular neuritis, 6 cases of Ramsay Hunt Syndrome (RHS) with vertigo, 14 cases of sudden deafness with vertigo) were included in this work. In the study group, the results of SPT and SN test with videonystagmography(VNG) were also reviewed. Taking SPT parameters, the influence of SN intensity on SPT gain, asymmetry and waveform and their correlation were analyzed.SPSS19.0 software was used for statistical analysis. Results: Among the 46 patients, there were 36 cases of SN pointing to the healthy side(SN intensity range of 2.68°/s-32.53°/s), and 10 cases of SN pointing to the affected side (SN intensity range of 2.66°/s-16.54°/s). SN intensity was divided into 3 groups, including light(0.50°/s-5.00°/s), medium(5.01°/s-10.00°/s) and strong(>10.01°/s), accounting for 14 cases(30.4%), 18 cases(39.1%) and 14 cases(30.4%), respectively. The differences of the gain of SPT to the fast phase and slow phase direction in the overall groups and light, medium and strong groups of SN intensity respectively were statistically significant(t_total=13.338, t_light=6.184, t_medium=8.436, t_strong=8.477, all of P<0.001). The difference of SPT gain in SN fast phase direction between groups with different SN intensity was statistically significant(F=9.639, P<0.001),there was no statistically significant difference in SPT gain between the groups on the SN slow phase direction(F=1.137, P=0.330).The SN intensity significantly negatively correlated with the SPT gain of the fast phase direction of SN (r=-0.433, P=0.003), that was, the SPT gain on the fast phase direction of SN decreased with the increase of SN intensity. There was no significant correlation between SN intensity and the gain of SPT on the slow phase direction of SN (r=-0.061, P=0.687). SPT waveform analysis showed that type I, type II and type III accounted for 8 cases(17.4%), 21 cases(45.6%) and 17 cases(37.0%), respectively. The corresponding mean values of SN intensity were (3.71±0.69)°/s, (7.44±1.88)°/s, (20.04±5.53)°/s, respectively, without type IV wave. The intensity of SN was positively correlated with the asymmetric value of the gain of SPT left and right(r=0.450,P=0.002). That was, with the increase of SN strength, the asymmetric value also increased, and the worse the asymmetry of the gain of SPT left and right pursuit was, the worse the SPT waveform was. Conclusion: SPT gain, asymmetry and SPT waveforms are all affected by SN, and the greater the intensity of SN, the greater the influence on the three. When SN is strong, type III waves may occur, suggesting that acute peripheral vestibular syndrome can also affect the visual ocularmotor systems.
Humans ; Nystagmus, Pathologic ; Pursuit, Smooth ; Vertigo ; Vestibular Diseases ; Vestibular Function Tests ; Vestibular Neuronitis

Objective:To analyze the feasibility of applying transcutaneous electrical nerve stimulator and high-frequency ultrasound in superficial nerve positioning for detection anatomical location in the area of lateral lip of the iliac crest by lateral cutaneous branch of subcostal nerve(LCSN). The significance of using the nerve as a free sensory superficial circumflex iliac artery perforator flap was discussed.Methods:The data of patients who underwent the repair of defects on limbs with free perforator flap or composite flap of superficial iliac circumflex artery carrying sensory nerve and the volunteers who agreed to have the location of the LCSN measured between October, 2018 and October, 2020 were collected. The LCSN were located by percutaneous electrical nerve stimulation and ultrasound, and the patients were measured and located during surgery. Using Passing-Bablok regression and Bland-Altman graph to evaluated the consistency between transcutaneous electrical nerve stimulation, ultrasound and the surgical positioning.Results:A total of 43 subjects, including 22 patients and 21 volunteers, were selected for locating the LCSN. Thirty-nine males and 4 females, with an average age of 39 years old and an average BMI of 24.08. The operation time of percutaneous nerve electrical stimulation was(6±1) min, and the detection distance was(80.7±5.9) mm. The high-frequency ultrasound was(23±4) min, and the distance was(81.2± 6.6) mm. The average operation time of surgical measured distance was(80.9±8.2)(65-100) mm, the diameter of nerve was(2.3±0.8)(1.0-4.0) mm, and the operation time was(5±1) min. A 95% CI of Passing-Bablok regression intercept and slope of operation, percutaneous electrical nerve stimulation and ultrasoundincluded 0 and 1, respectively. The points on Bland-Altman plot were distributed on both sides, and 95% CI of total mean difference, total intercept and slope included 0. Therefore, it was can be considered that the application of percutaneous electrical nerve stimulation and ultrasound in LCSN localization has good consistency.Conclusion:The location point of the LCSN crossing the iliac crest which detected by transcutaneous electrical nerve stimulation and high-frequency ultrasound detection was close to the measurement taken during the operation. It was also showed that both of them can be used for preoperative locationing of the sensory branch of the sensory nerve flap, optimizing the design of the flap, shortening the operation time, and reducing the unnecessary injury in operation.

BACKGROUND: Albuvirtide is a once-weekly injectable human immunodeficiency virus (HIV)-1 fusion inhibitor. We present interim data for a phase 3 trial assessing the safety and efficacy of albuvirtide plus lopinavir-ritonavir in HIV-1-infected adults already treated with antiretroviral drugs. METHODS: We carried out a 48-week, randomized, controlled, open-label non-inferiority trial at 12 sites in China. Adults on the World Health Organization (WHO)-recommended first-line treatment for >6 months with a plasma viral load >1000 copies/mL were enrolled and randomly assigned (1:1) to receive albuvirtide (once weekly) plus ritonavir-boosted lopinavir (ABT group) or the WHO-recommended second-line treatment (NRTI group). The primary endpoint was the proportion of patients with a plasma viral load below 50 copies/mL at 48 weeks. Non-inferiority was prespecified with a margin of 12%. RESULTS: At the time of analysis, week 24 data were available for 83 and 92 patients, and week 48 data were available for 46 and 50 patients in the albuvirtide and NRTI groups, respectively. At 48 weeks, 80.4% of patients in the ABT group and 66.0% of those in the NRTI group had HIV-1 RNA levels below 50 copies/mL, meeting the criteria for non-inferiority. For the per-protocol population, the superiority of albuvirtide over NRTI was demonstrated. The frequency of grade 3 to 4 adverse events was similar in the two groups; the most common adverse events were diarrhea, upper respiratory tract infections, and grade 3 to 4 increases in triglyceride concentration. Renal function was significantly more impaired at 12 weeks in the patients of the NRTI group who received tenofovir disoproxil fumarate than in those of the ABT group. CONCLUSIONS: The TALENT study is the first phase 3 trial of an injectable long-acting HIV drug. This interim analysis indicates that once-weekly albuvirtide in combination with ritonavir-boosted lopinavir is well tolerated and non-inferior to the WHO-recommended second-line regimen in patients with first-line treatment failure. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT02369965; https://www.clinicaltrials.gov.Chinese Clinical Trial Registry No. ChiCTR-TRC-14004276; http://www.chictr.org.cn/enindex.aspx.
Adult ; Anti-HIV Agents/adverse effects* ; Antiretroviral Therapy, Highly Active ; China ; Drug Therapy, Combination ; HIV Infections/drug therapy* ; HIV-1 ; Humans ; Maleimides ; Peptides ; Ritonavir/therapeutic use* ; Treatment Outcome ; Viral Load