BACKGROUND:The study confirmed that adding tricalcium phosphate or pearl powder in polylactic-co-glycolic acid can complement the performance of both, which provides a good environment for cels and makes a faster and better growth of cels. OBJECTIVE:We used polylactic-co-glycolic acid as matrix, composited with pearl powder or tricalcium phosphate to prepare scaffolds by low-temperature deposition manufacturing. METHODS:Low-temperature deposition manufacturing was utilized to prepare composite scaffold of polylactic-co-glycolic acid/pearl powder or polylactic-co-glycolic acid/tricalcium phosphate at the ratio of 10:0, 5:2, 7:3 and 6:4. Microstructure, contact angle and compression modulus of elasticity of scaffolds were detected. MC3T3-E1 cels basicaly fused at 1×104/cm3 were seeded in the pure nonporous polylactic-co-glycolic acid scaffold, pure polylactic-co-glycolic acid scaffold with holes, polylactic-co-glycolic acid/pearl powder at 5:2 and polylactic-co-glycolic acid/tricalcium phosphate at 5:2 separately for 1 and 3 hours. Cel adhesion rate was detected using flow cytometry. After incubation for 1, 4 and 7 days, cel proliferation was measured using Alamar Blue method. RESULTS AND CONCLUSION:Pure polylactic-co-glycolic acid scaffold had cross-linked microporous structure, with pore size of 3-15 μm. Scaffolds ofpolylactic-co-glycolic acid/pearl powder at 5:2 or polylactic-co-glycolic acid/tricalcium phosphate at 5:2 had good continuous porous structure, with pore size of 10-25 μm. With increased content of pearl powder or tricalcium phosphate, the hydrophilicity of the composite scaffold increased. The addition of pearl powder or tricalcium phosphate could elevate compressive mechanical properties of the composite scaffold. With increased content, the mechanical property of the scaffold enhanced and then reduced. The addition of pearl powder or tricalcium phosphate improved the celular affinity of polylactic-co-glycolic acid and the biocompatibility of the scaffold. The biocompatibility of polylactic-co-glycolic acid/pearl powder scaffold at 5:2 was the best.

Objective To review the clinical characteristics and risk factors of Pseudomonas aeruginosa bloodstream infections. Methods The clinical data of P. aeruginosa bloodstream infections in the First Affiliated Hospital of Soochow University from January 2007 to December 2016 were analyzed retrospectively. Results Of the 251 patients identified, APACHE Ⅱ score on admission was 11.5±5.2. Majority (98.4％, 247/251) of the patients had fever. Leukopenia was found in 125 patients, leukocytosis in 87 patients, neutropenia in 122 patients, agranulocytosis in 113 patients, anemia in 193 patients, and hypoalbuminemia in 120 patients. Overall, 219 patients had at least one underlying disease, primarily hematological malignancy, or malignant solid tumor. Most (229) patients received invasive procedures such as deep venous catheter, urinary catheter, mechanical ventilation before blood sampling. P. aeruginosa was isolated from 108 of the 173 deep venous catheters. In addition, 130 patients received radiation or chemotherapy. Immunosuppressive agents were used in 124 patients. Among the 251 strains of P. aeruginosa, 87.3％ were susceptible to amikacin, followed by ciprofloxacin (85.7％) and cefepime (81.6％). Multidrug-resistant P. aeruginosa was isolated from 36 (14.3％) patients, and extensively drug resistant strain was isolated from 7 patients. All the 251 patients were treated withantimicrobial agents, mainly β-lactam/β-lactamase inhibitor combinations, carbapenems or fluoroquinolones. Overall, 20 (8.0％) of the 251 patients died, 37 (14.7％) refused further therapy due to worsening condition, and 194 (77.3％) improved. Binary logistic regression analysis showed that high APACHE Ⅱ score on admission, anemia and hypoalbuminemia were risk factors for poor outcome of bloodstream infectionscaused by P. aeruginosa. Conclusions P. aeruginosa bloodstream infection occurs more readily in immunocompromised patients. High APACHE Ⅱ score on admission, anemia and hypoalbuminemia are associated with poor prognosis. Appropriate empiric antimicrobial treatment as early as possible can improve the prognosis of P. aeruginosa bloodstream infection.

Objective To investigate the preventive effect of highly effective antiretroviral therapy (HARRT) combined with SMZ-TMP on opportunistic infection (OIs) in patients with HIV/AIDS. Methods The 6-month follow-up data of 170 AIDS patients in the Department of Infectious Diseases of Nantong Third People's Hospital were analyzed retrospectively. All patients received HARRT. According to whether SMZ-TMP was used for OIs preventive treatment, the patients were divided into a prevention group (n=47) and a non-prevention group (n=123). The demographic data such as gender, age, occupation and education level of the two groups were collected. The incidence of OIs in the 12-month follow-up period of the two groups was analyzed and compared, and the single factor unconditional logistic regression analysis and multi factor unconditional logistic regression analysis were carried out for AIDS patients taking SMZ-TMP. Results The proportion of prophylactic use of SMZ-TMP in 170 AIDS patients was only 27.65%, and the incidence of OIs in the prevention group was 31.91%, which was significantly lower than that in the non-prevention group (57.72%) (χ²=9.062, P<0.05). Among the 15 patients with OIs in the prevention group, the proportion of patients with one, two to three and more than three types of OIs accounted for 64.71%, 23.53% and 4.26%, respectively, while those in the non prevention group were 30.99%, 38.03% and 30.98%, respectively. There was a significant difference in the composition ratio between the two groups (χ²=7.419, P<0.05). The incidences of bacterial pneumonia, tuberculosis, extrapulmonary tuberculosis, PCP and fungal stomatitis in the prevention group were 18.89%, 10.64%, 4.26%, 6.38% and 4.26%, respectively, which were significantly lower than those in the non-prevention group (30.89%, 25.20%, 16.26%, 18.70% and 18.70%, respectively) (χ²=4.473, 4.322, 4.350, 3.982, 5.656, P<0.05). Univariate and multivariate unconditional logistic regression analysis showed that the benefits of SMZ-TMP, doctors' detailed recommendation of SMZ-TMP and higher education level were all influencing factors (95% CI: 135.79-3748.36, 107.43-2954.67, 1.873-25.94). Conclusion Prophylactic use of SMZ-TMP significantly reduced the incidence of AIDS related OIs, but the proportion of SMZ-TMP use was relatively low. It is necessary to take relevant measures according to the influencing factors of taking SMZ-TMP to improve the use rate of SMZ-TMP in AIDS patients.

Objective:To assess the translation activity of circ-PTPN22, and to investigate its relationship with systemic lupus erythematosus (SLE) .Methods:From May 10, 2019 to September 30, 2019, whole blood samples were collected from 6 female patients with SLE and 9 healthy female controls in the Department of Rheumatology and Immunology, Integrated Traditional Chinese and Western Medicine, and Physical Examination Center of Southwest Hospital, respectively. Peripheral blood mononuclear cells (PBMCs) were isolated from these blood samples, and PBMCs from 3 cases of SLE and 3 healthy controls were sorted into T, B and NK cells by using magnetic beads. The circ-PTPN22 internal ribosomal entry site (IRES) sequence and protein sequence translated from it were predicted in the circRNADb database, rabbit anti-circ-PTPN22pro polyclonal antibodies were prepared against the specific amino acid sequence at the circ-PTPN22 splice site, and Western blot analysis was performed to determine the protein expression of circ-PTPN22pro in PBMCs and T, B and NK cell subsets of the healthy controls and patients with SLE. Cultured Jurkat cells were divided into 4 groups to be transfected with recombinant lentiviral vectors carrying circ-PTPN22-FLAG, circ-PTPN22-NC-FLAG, circ-PTPN22-shRNA-FLAG, circ-PTPN22-shRNA-NC-FLAG respectively, with the normally cultured cells as the cell control group. Then, Western blot analysis was performed to determine the protein expression of circ-PTPN22pro in Jurkat cells, flow cytometry to evaluate the effect of circ-PTPN22 on cell activation and apoptosis. Statistical analysis was carried out by using two-way repeated measures analysis of variance and two-independent-sample t test. Results:Based on the circRNADb database, circ-PTPN22 was predicted to have a translation ability, and Western blot analysis showed that the relative molecular mass of circ-PTPN22pro was 20 000. Forty-eight hours after transfection, circ-PTPN22pro expression was significantly higher in the circ-PTPN22-FLAG group than in the circ-PTPN22-NC-FLAG group and cell control group. At 24, 48 and 72 hours after transfection, the interleukin 2 (IL-2) expression was significantly lower in the circ-PTPN22 group (22.20% ± 8.92%, 31.10% ± 5.88%, 53.20% ± 10.25%, respectively) than in the circ-PTPN22-NC Group (30.90% ± 11.00%, 51.23% ± 10.70%, 69.67% ± 9.00%, respectively; F = 284.881, P = 0.003) , but significantly higher in the circ-PTPN22-shRNA group (35.57% ± 8.79%, 78.10% ± 10.08%, 88.63% ± 3.89%, respectively) than in the circ-PTPN22-shRNA-NC group (26.73% ± 4.92%, 41.03% ± 10.45%, 41.33% ± 4.96%, respectively; F = 293.818, P = 0.003) . After 48, 72 and 96 hours after transfection, the apoptosis rate was significantly higher in the circ-PTPN22 group than in the circ-PTPN22-NC group ( F = 81.287, P = 0.012) , as well as in the circ-PTPN22-shRNA group than in the circ-PTPN22-shRNA-NC group ( F = 111.813, P = 0.009) . The SLE group showed decreased (almost no) circ-PTPN22pro expression in PBMCs compared with the healthy control group. The circ-PTPN22pro expression in T and B cells was significantly lower in the SLE group than in the healthy control group ( t = 3.047, 4.806, both P <0.05) , and there was no significant difference in the circ-PTPN22pro expression in NK cells between the two groups ( t = 0.582, P > 0.05) . Conclusions:Circ-PTPN22 can be translated into circ-PTPN22pro protein, and can inhibit the activation of Jurkat cells. The circ-PTPN22pro expression is lower in PBMCs of the SLE patients than in those of the healthy controls, suggesting that circ-PTPN22 may be related to the occurrence and development of SLE.

Objective:To build an investigator-initiated clinical research process management indicator system based on the theory of Hazard Analysis and Critical Control Point(HACCP).Methods:A plan was developed according to HACCP principles, and 23 experts were invited to form an expert advisory group. Literature research, panel discussion, and Delphi method were used to collect clinical research process management indicators, and the weight of each indicator was calculated via Analytic Hierarchy Process(AHP).Results:Two rounds of expert consultation were carried out with a high positive coefficient and a high expert authority level, and finally formed 3 primary indicators and 14 secondary indicators. The primary indicators were project establishment, project process management, and project implementation assessment, with weights of 0.142 8, 0.714 4, and 0.142 8, respectively.Conclusions:This study established a clinical research process management system based on HACCP theory from 3 dimensions: project establishment, project process management, and project implementation assessment, carried out precise management of clinical research according to the weights of secondary indicators, focusing on the content of indicators with great weight, and provided an important reference for the management of investigator-initiated clinical research.

Objective:To analyze the time cost in the start-up stages of clinical trials and to investigate the influencing factors of the initiation efficiency.Methods:We retrospectively analyzed time-cost of the review and approval of drug clinical trials initiated in Beijing Hospital from January 2020 to June 2021.The contract signing time and trial starting time of drug clinical trials in different situations were compared.Results:The mean time to sign the contract in our hospital was 19(11~26) days, and the mean time to start experiment was 235(175~317) days. There was no significant difference in the contract signature time between clinical trials with different stages, different sponsors, different types of drugs and whether to be the leading site ( P>0.05). Compared with other phases, phase Ⅲ drug trials took the longest time to start, and the mean initiation time of clinical trials initiated by foreign pharmaceutical companies was 136 days longer than that initiated by domestic pharmaceutical companies ( P<0.05). Conclusions:Clinical trial institutions should optimize the project management process, better organize the contract review and ethics review, encourage the sponsor to use our template document. Every department may set up a GCP contact to be responsible for clinical trials; The sponsor should improve the efficiency of internal circulation and communication, submit the review materials as soon as possible according to the requirements of the institution, and establish a good communication and feedback mechanism between both sides, may shorten the start-up time of clinical trials and improve the initiation efficiency.

Objective:To analyze whether the sample of elderly subjects in clinical trials of prostate cancer drugs is representative.Methods:From the level of trial design, the age distribution of subjects in clinical trials of prostate cancer drugs for elderly patients from January 2019 to December 2021 was inquired on the platform of drug clinical trial registration and information disclosure.From the actual enrollment level, the prostate cancer drug clinical trials initiated and completed by a hospital from January 2010 to June 2022 were collected.The age information of subjects in all centers was collected for multicenter trials with a summary report, and the age data of subjects in the center was collected for trials without a summary report or single-center trials.The average age of prostate cancer onset and the incidence of prostate cancer in different age groups were compared with the Chinese Cancer Registry System, so as to compare whether the two were consistent.Results:Most of the trials(72.1%、44/61)did not set upper age limit at the protocol design level.Phase Ⅲ and phase Ⅳ trials did not set an upper age limit for enrolled subjects in the protocol.From the actual enrollment level, a total of 19 studies were included in this study, with 1 402 subjects, and the average age of subjects was 67.1±8.6 years old, which was significantly different from the average age of prostate cancer in China and Beijing(all P<0.001). The age group with the largest number of participants was 60-64 years old(34.2%、479/1 402). The population aged ≥75 years was the least(21.5%, 301/1 402), which was different from the high incidence age group of prostate cancer in China in 2017(421.77/100 000). Conclusions:Clinical trials of prostate cancer drugs are designed to cover all age groups of elderly patients, but the actual sample representation of the enrolled elderly subjects is insufficient.Under the premise of protecting the safety of subjects, the trial population who are matched for the average age of prostate cancer onset and the incidence of prostate cancer in age groups, should be gradually increased.

Objective:To explore the demand and actual supply of community-based care services for the elderly residents and the factors that affecting care mode for them in the context of rapid urbanization and population aging in China.Methods:Based on the cross-sectional data of the seventh China Longitudinal Survey on Health and Longevity(CLHLS)(2018), 15 854 elderly residents aged 60 and above were selected as the research population.Logistic regression method was used to analyze the patterns of community-based care services and their influencing factors.Results:Among 15 854 elderly residents, 6 912(43.60%)were male and 8 942(56.40%)were female.The results of activities of daily living(ADL)evaluation showed that 11 109 elderly residents could take care of themselves completely, and 3 889 elderly residents were disabled.The disability rate was 25.93%.The proportion of social services that elderly town dwellers expect the community to provide is higher than those living in cities and rural areas in terms of daily care, spiritual care, providing health care knowledge, and dealing with neighborhood disputes.From the perspective of social services actually provided by the community, in addition to providing home-based care, the proportion of community services available to the elderly living in towns and rural areas are similar, but significantly lower than the proportion of social services provided for elderly city dwellers.Age, marital status, residence, cultural differences, health status, source of life and living preference had significant impacts on the choice of care demand patterns.Those of older age( OR=2.29, 95% CI: 1.04-5.03 for 70-79 years old; OR=2.94, 95% CI: 1.38-6.25 for elderly 80 years old or above), having no spouse( OR=3.50, 95% CI: 2.49-4.92), and with higher levels of disability( OR=4.24, 95% CI: 3.12-5.77 for mild disability; OR=7.54, 95% CI: 5.19-10.95 for moderate disability; OR=10.50, 95% CI: 7.59-14.53 for severe disability)are more inclined to choose socialized care. Conclusions:In the process of rapid urbanization in China, the demands for care services of elderly living in towns has increased, but the actual care services provided for them by the communities are yet to be improved.Moreover, elderly town dwellers are still inclined to family care, the same as those of elderly rural dwellers.

Objective:The Clinical Research Coordinator (CRC) is responsible for transcribing and verifying clinical trial data, and making recommendations to research institutions and sponsors on clinical trial data through analyzing and discussing data problems found in CRC work assessment, thereby improving the quality of clinical trials.Methods:Based on the ALOCA+ Principle, this study analyzed the data problems found in CRC assessment based on clinical trial quality conducted in a grade A tertiary hospital in Beijing from November 2018 to December 2021, and discussed improvement measures for clinical trial data problems.Results:Among the clinical trial data problems, data integrity is the most prominent, followed by accuracy.Conclusions:Research institutions and sponsors should improve the data management system and SOP, strengthen the training for clinical trial participants, optimize a trial plan and process design, strengthen supervision and inspection, and establish a risk-based quality control system, etc., so as to make clinical trial data conform to the international ALOCA+ principle and make clinical trial results accurate and reliable.

Objective: To explore the accuracy in localizing occult insulinomas with Glucagon-like peptide-1 receptor(GLP-1R) PET-CT with ⁶⁸Ga-exendin-4. Methods: In this prospective cohort study, patients with biochemically proven endogenous hyperinsulinemic hypoglycemia and negative contrast-enhanced CT with pancreatic perfusion scans were enrolled consecutively at Department of Nuclear Medicine, Peking Union Medical College Hospital from February 2014 to June 2018.There were 37 males and 32 females, with age of (43.2±17.9)years. ⁶⁸Ga-exendin-4 PET-CT, MRI and endoscopic ultrasound(EUS) were done before elective surgery. Sensitivity, specificity, accuracy, positive predictive value(PPV) and negative predictive value(NPV) of the above imaging modalities were calculated. Results: A total of 69 patients were recruited. Thirty-two patients were diagnosed with insulinomas at histology. Four patients with positive ⁶⁸Ga-exendin-4 PET-CT findings did not undergo surgery so far. Twenty-eight patients were proven to be noninsulinoma induced hyperinsulinemic hypoglycemia. Five patients were unknown of etiology of hypoglycemia. The sensitivity, specificity, accuracy, PPV and NPV of ⁶⁸Ga-exendin-4 in localizing occult insulinomas were 96.9%(31/32), 100%(30/30), 98.3%(59/60), 100%(29/29), 96.8%(30/31), respectively.The sensitivity, specificity, accuracy, PPV and NPV of MRI were 74.1%(20/27), 9/11, 76.3%(29/38), 90.9%(20/22), 9/16, respectively. The sensitivity, specificity, accuracy, PPV and NPV of EUS were 75.0% (15/20), 2/2, 77.3%(17/22), 15/15, and 2/7. Conclusion ⁶⁸Ga-exendin-4 PET-CT has a high sensitivity, specificity and accuracy for detection of occult insulinoma, which shows superiority to MRI and EUS.