Objective To retrospectively analyze the related influencing factors of the infection oc-currence after using tofacitinib in the patients with rheumatoid arthritis.Methods The case data of 211 pa-tients with rheumatoid arthritis treated by tofacitinib in the rheumatology and immunology department of Chongqing Municipal Hospital of Traditional Chinese Medicine from January 2022 to December 2023 were col-lected.The patients were grouped according to whether infection occurred or not.After single factor test on gender,age,Chinese medicine syndromes,time of taking Chinese medicine,lung system diseases and lympho-cyte count,then the factors with statistically significant differences were included in the Logistic regression a-nalysis.Results Spleen deficiency and dampness syndrome,taking traditional Chinese medicine time 1-4 weeks,and>4-<8 weeks were the protective factors for the infection occurrence after using tofacitinib in rheumatoid arthritis(OR=0.427,95%CI:0.184-0.988,P<0.05;OR=0.233,95%CI:0.093-0.580,P<0.05;OR=0.328,95%CI:0.135-0.799,P<0.05),complicating pulmonary interstitial lesions and bronchi-ectasis were the risk factors for infection occurrence after using tofactitinib(OR=3.000,95%CI:1.306-6.894,P<0.05;OR=16.615,95%CI:1.782-154.945,P<0.05).Conclusion The risk of infection occur-rence after using tofacitinib in the patients with rheumatoid arthritis is closely correlated with Chinese medi-cine syndromes,time of taking Chinese medicine and lung system diseases.

Objective:To evaluate the clinical efficacy of percutaneous balloon pulmonary valvuloplasty (PBPV) via antegrade venous-arterial loop in neonates with critical pulmonary stenosis with intact ventricular septum (CPS-IVS).Methods:A retrospective case review was conducted. Fifteen neonates with CPS-IVS who underwent PBPV via antegrade venous-arterial loop at the Women and Children′s Hospital, Qingdao University between September 2020 and September 2023 were included. Pre-and post-operative right ventricular functional parameters, surgical complications, and follow-up outcomes were analyzed. Paired-sample t-test was used to compare changes in right ventricular systolic pressure (RVSP), percutaneous oxygen saturation (SpO 2), and echocardiographic findings pre-and post-operatively, as well as during the follow-up period. Results:Among the 15 neonates (9 males and 6 females) with CPS-IVS, the surgical age was (3.6±0.5) d. All neonates underwent successful PBPV via antegrade venous-arterial loop under general anesthesia. The immediate post-operative trans-pulmonary valve pressure gradient was (35±6) mmHg (1 mmHg=0.133 kPa), with a significant reduction in RVSP from (96±16) mmHg to (59±14) mmHg ( t=6.70, P<0.001). SpO 2 (with an inspired oxygen concentration of 0.48) increased from 0.86±0.07 pre-operatively to 0.97±0.03 post-operatively ( t=4.81, P<0.001). One month postoperatively, SpO 2 (without oxygen supplementation) normalized in all patients, with a statistically significant difference compared to pre-operative values ( t=0.16, P<0.001). Immediately postoperative, mild to moderate diastolic pulmonary valve regurgitation was observed in 8 patients, with no cases of severe regurgitation. Additionally, the severity of tricuspid valve regurgitation decreased from severe to mild-to-moderate in 6 patients. Three months postoperatively, one patient underwent a second PBPV due to an increased trans-pulmonary valve pressure gradient of 74 mmHg, which decreased to 27 mmHg immediately after the procedure, with subsequent good recovery. Over a one-year follow-up period, all 15 patients demonstrated improvements in right ventricular indices. The Z-score of the tricuspid valve annulus significantly improved from -1.9±0.8 pre-operatively to -0.4±0.1 post-operatively ( t=6.88, P<0.001). At the last follow-up, mild to moderate pulmonary valve regurgitation was observed in 3 patients, and mild tricuspid regurgitation in 2 patients, with no cases of moderate or severe regurgitation. Conclusion:Intervention via antegrade venous-arterial loop for the treatment of CPS-IVS in neonates is safe and effective.

Objective:To evaluate the clinical efficacy of percutaneous balloon pulmonary valvuloplasty (PBPV) via antegrade venous-arterial loop in neonates with critical pulmonary stenosis with intact ventricular septum (CPS-IVS).Methods:A retrospective case review was conducted. Fifteen neonates with CPS-IVS who underwent PBPV via antegrade venous-arterial loop at the Women and Children′s Hospital, Qingdao University between September 2020 and September 2023 were included. Pre-and post-operative right ventricular functional parameters, surgical complications, and follow-up outcomes were analyzed. Paired-sample t-test was used to compare changes in right ventricular systolic pressure (RVSP), percutaneous oxygen saturation (SpO 2), and echocardiographic findings pre-and post-operatively, as well as during the follow-up period. Results:Among the 15 neonates (9 males and 6 females) with CPS-IVS, the surgical age was (3.6±0.5) d. All neonates underwent successful PBPV via antegrade venous-arterial loop under general anesthesia. The immediate post-operative trans-pulmonary valve pressure gradient was (35±6) mmHg (1 mmHg=0.133 kPa), with a significant reduction in RVSP from (96±16) mmHg to (59±14) mmHg ( t=6.70, P<0.001). SpO 2 (with an inspired oxygen concentration of 0.48) increased from 0.86±0.07 pre-operatively to 0.97±0.03 post-operatively ( t=4.81, P<0.001). One month postoperatively, SpO 2 (without oxygen supplementation) normalized in all patients, with a statistically significant difference compared to pre-operative values ( t=0.16, P<0.001). Immediately postoperative, mild to moderate diastolic pulmonary valve regurgitation was observed in 8 patients, with no cases of severe regurgitation. Additionally, the severity of tricuspid valve regurgitation decreased from severe to mild-to-moderate in 6 patients. Three months postoperatively, one patient underwent a second PBPV due to an increased trans-pulmonary valve pressure gradient of 74 mmHg, which decreased to 27 mmHg immediately after the procedure, with subsequent good recovery. Over a one-year follow-up period, all 15 patients demonstrated improvements in right ventricular indices. The Z-score of the tricuspid valve annulus significantly improved from -1.9±0.8 pre-operatively to -0.4±0.1 post-operatively ( t=6.88, P<0.001). At the last follow-up, mild to moderate pulmonary valve regurgitation was observed in 3 patients, and mild tricuspid regurgitation in 2 patients, with no cases of moderate or severe regurgitation. Conclusion:Intervention via antegrade venous-arterial loop for the treatment of CPS-IVS in neonates is safe and effective.

ABSTRACT To consider the cultivation of children's drug clinical research professionals guided by post competence. METHODS The current research status of post competency for clinical research professionals was analyzed, the necessity of constructing a post competency model for children's drug clinical research professionals was discussed, the post competency elements of children's drug clinical research professionals was analyzed, a hierarchical and systematic training goal for children's drug clinical research professionals was set. RESULTS The post competency model for children's drug clinical research professionals needs to be urgently established. CONCLUSION Building a post competency model for children's drug clinical research professionals is an important path for cultivating clinical research professionals in children's drugs.

OBJECTIVE To introduce the construction of undergraduate specialty of clinical pharmacy based on the concept of outcome-based education （OBE），and to provide new idea and enlightenment for the construction of undergraduate specialty of clinical pharmacy in Chinese universities. METHODS Through the establishment and construction of training objectives and graduation requirements ，teaching reform was designed and implemented ，and the construction of teaching support system and teaching quality assurance system were completed. RESULTS The clinical pharmacy department of our university established the training direction of clinical pharmacy talents under the guidance of post competence ，including clarifying the training needs of undergraduate talents based on the overall requirements of national undergraduate education ；defining the social and industrial needs of clinical pharmacy talents based on the normative documents or concepts of clinical pharmacy ；clarifying the post and ability needs of clinical pharmacy talents based on the investigation of graduates and clinical pharmacists ；clarifying the development needs of clinical pharmacy based on the current situation and trends at home and abroad ；forming characteristic training objectives combined with the regional characteristics and school positioning ， so as to construct training objectives and graduation requirements. The OBE concept was introduced into the undergraduate teaching reform of clinical pharmacy ；the pharmacy talent training direction were established under the guidance of post competence ；the training system was designed by reverse design method；a training mode of both innovation and practical ability was built so as to promote teaching reform ，strengthen the construction of grass-roots teaching organizations and teaching staff ， and improve the construction of teaching quality assurance system. CONCLUSIONS The undergraduate training mode of clinical pharmacy specialty based on the concept of OBE is helpful to improve students ’personal comprehensive quality and professional knowledge and skills. The established undergraduate training model of clinical pharmacy specialty is in line with the modern educational concept and social needs ，and provides theoretical basis and practical experience for the training mode of clinical pharmacy professionals.

Objective To establish an intestinal organoid-based assay to investigate the radiation mitigation effect of epiregulin in vitro. Methods Intestinal crypts were released from tissue incubated with EDTA. Intestinal crypts seeded in 3D matrigel were irradiated at 24 h after plating. The radiation mitigation effect of epiregulin was evaluated by measuring the survival rate, size and budding numbers of the organoid after irradiation, and the basic FGF was used as a positive control of epiregulin. Results Radiation-induced lethality and dose-dependent survival curve of the intestinal organoid were consistent with in vivo data. Treatment with epiregulin (400 ng/ml) at 24 h post-radiation significantly increased survival rate of 8 Gy X-ray irradiated intestinal organoid in comparison with non-treated group [(12.56 ± 1.02)％vs. (4.73 ± 0.38)％, t=12.43,P<0.05]. Conclusions Epiregulin has radiation mitigation effect on intestinal organoid and could serve as a potential medical countermeasure to mitigate gastrointestinal toxicity.

Child ; Dose-Response Relationship, Drug ; Drug Dosage Calculations ; Humans ; Precision Medicine

In the application of therapeutic antibodies, large molecular weight of antibodies is always a problem that prevents them from penetrating into tissues or binding to antigenic determinants. To overcome this problem, we investigated the function of the heavy chain variable domain of a monoclonal anti-VEGF human IgM antibody derived from the Five-Feature Translocus Mice. We cloned the cDNA of the heavy chain variable domain, which was then inserted into pET28a vector and expressed in Escherichia coli. After purification and renaturation of the denatured recombinant protein, we obtained a 16 kDa antibody fragment, which is named as rhVVH. By immunoassaying its VEGF-binding capability in vitro, we proved that rhVVH retains this activity as the complete IgM. Importantly, rhVVH is shown to inhibit the HUVEC cell proliferation in a concentration-dependent manner. Our results indicate that the single heavy chain variable domain might inherit part of the biological function of the complete IgM antibody, which provided a valuable potential in further research on antibody miniaturisation.
Amino Acid Sequence ; Animals ; Base Sequence ; Cloning, Molecular ; Escherichia coli ; genetics ; metabolism ; Humans ; Immunoglobulin Heavy Chains ; biosynthesis ; genetics ; Immunoglobulin Variable Region ; biosynthesis ; genetics ; Mice ; Molecular Sequence Data ; Recombinant Proteins ; biosynthesis ; genetics ; Single-Chain Antibodies ; biosynthesis ; genetics ; Vascular Endothelial Growth Factor A ; genetics ; metabolism

The constant iv. of aconitine can induce the varied arrhythmias in mice. Taurine 100mg/kg iv. or Quinidine 5 mg/kg iv. can delays the onset time of arrhythmias, and increases the dose of aconitine, respectively .But no effects were seen in mice pretreated with taurine 50mg/kg or quinidine 2.5mg/kg. However their combination can significantly decrease the incident of ventricular fibrillation and delay the onset time of death. Our results suggested that taurine, quinidine and their combination are effective on arrhythmias induced by aconitine in mice.

The effect of Taurine ( Tau)on 45Ca influx of isolated left ventricular muscles in rats has been investigated. The 45Ca influx of the preparations untreated with Tau, are affected by the concentrations of calcium in KH solution. when the concentration of calcium is 0.62; 1.25; and 1.87mmol/L respectively, the 45Ca influx is 1.02? 0.25; 1.37?0.14 and 1.45?0.14 ?mol/g wet tissue, respectively. After adding Tau, the situations above were changed significantly. It was shown that is 1.11 ? 0.11, 1.45?0.12, and 1.48 ? 0.09 ?mol/g wet tissue in low Ca2?; 1.19?0.07, 1.14 ? 0.23, and 0.97?0.24 ?mol/g wet tissue in normal Ca2?; and 1.12?0.05,0.58?0.18 and 0.53?0.10 ?mol/g wet tissue in high Ca2? treated with Tau 10, 20, and 40 mmol/L, respectively. The results show that the varied ,Ca2? concentrations in KH solution can affect 45Ca influx of cardiac muscles, but Taurine has a bisphasic modulation o,f calcium influx in the same tissue. The effects of modulating calcium may play an important role for anti-arrhythmic mechanism of Taurine.