Objective To analyze the postmarketing safety characteristics of three immunomodulatory drugs(IMiDs)(thalidomide,lenalidomide and pomalidomide)in order to provide reference for clinical rational drug use.Methods The Open Vigil 2.0 tool was used to collect adverse drug event(ADE)reporting data from the U.S.Food and Drug Administration's(FDA)Adverse Event Reporting System(FAERS)between the first quarter of 2013 and the second quarter of 2022 for three IMiDs as primary suspect drugs.High frequency ADE was analyzed by mapping according to Medical Dictionary for Regulatory Activities(MedDRA terminology)25.0.The effective signals of adverse drug reactions(ADR)were screened according to the reporting odds ratio(ROR)and proportional reporting ratio(PRR)methods,and the high-intensity signals were analyzed.Results Among the top 20 ADEs,peripheral neuropathy,decreased blood count,thrombosis,skin squamous cell carcinoma and other ADEs occurred in all three drugs,but the distribution of the involved tissues and organs was different.Among the top 20 ADR signals,nearly half of the ADR signals of the 3 drugs were also in the high-frequency ADE range,among which 3 drugs showed increased human chorionic gonadotrophin,thalidomide and lenalidomide showed false positives in pregnancy tests,rectal adenocarcinoma and colorectal adenocarcinoma,and pomalidomide and lenalidomide showed decreased complete blood counts.Conclusion The overall ADE distribution of the three diamines is consistent,but there are some differences in the specific ADR signal characteristics.In clinical application,more attention should be paid to hemocytopenia,peripheral neuropathy,thrombus and second primary malignant tumors.

Objective To elucidate utilization patterns,cost and safety of Bruton's tyrosine kinase inhibitors(BTKi)in the real world.Methods A retrospective cohort was designed and constructed using real-world BTKi data from a single lymphoma center.Descriptive analysis was performed to describe the demographic and clinical characteristics of the population.Medicine utilization and cost were quantified by defined daily doses(DDDs)and defined daily dose cost(DDDc),respectively.A generalized estimating equation(GEE)was used to explore the potential influencing factors of platelet aggregation rate(PAR).Results The study cohort included 193 patients[median age,65 years;77(39.90％)women],most of whom received ibrutinib(n=109,56.48％),and 77.20％patients combined BTKi with chemotherapy or targeted therapy.The implementation of national negotiation policy had a large impact on medicine utilization and cost.The DDDs difference between the two BTKis was reduced from 18.55 to 1.41 times.The DDDc for ibrutinib decreased from 1 619.99 Yuan to 567.00 Yuan,and that for zanubrutinib from 706.25 Yuan to 340.00 Yuan was already lower than ibrutinib.Interruptions were more readily observed in patients treated with ibrutinib,and hematological toxicity was the main adverse drug event(ADE)leading to treatment interruption.Besides,the GEE model showed that combining BTKi with antiplatelet medication significantly decreases the PAR[β=-34.35％,95％confidence interval(CI):-41.60％--27.11％,P＜0.001].Compared to zanubrutinib,ibrutinib also notably reduces the PAR(β=-12.38％,95％CI:-24.50％--0.27％,P＜0.05).Conclusion After the implementation of national negotiation policy,there is no significant difference in the clinical preference for two BTKis.Compared with ibrutinib,zanubrutinib showed an advantage in terms of economic profile,treatment interruptions caused by ADE,and the effect on PAR.

Objective: To explore the clinical application value of two longitudes three transverses method in the location of the perforator of thoracodorsal artery perforator and deep wound repair. Methods: The retrospectively observational study was conducted. From December 2018 to June 2020, 17 patients with deep wounds who were admitted to the Affiliated Hospital of Zunyi Medical University met the inclusion criteria and were included in this study, including 7 males and 10 females, aged 12 to 72 years. The wound areas of patients after debridement were 7 cm×3 cm to 11 cm×7 cm. Two longitudinal lines were located through the midpoint of the armpit, the posterior superior iliac spine, and the protruding point of the sacroiliac joint, and three transverse lines were located 5, 10, and 15 cm below the midpoint of the armpit between the two longitudinal lines, i.e. two longitudes three transverses method, resulting in two trapezoidal areas. And then the thoracodorsal artery perforators in two trapezoidal areas were explored by the portable Doppler blood flow detector. On this account, a single or lobulated free thoracodorsal artery perforator flap or flap that carrying partial latissimus dorsi muscle, with an area of 7 cm×4 cm to 12 cm×8 cm was designed and harvested to repair the wound. The donor sites were all closed by suturing directly. The number and location of thoracodorsal artery perforators, and the distance from the position where the first perforator (the perforator closest to the axillary apex) exits the muscle to the lateral border of the latissimus dorsi in preoperative localization and intraoperative exploration, the diameter of thoracodorsal artery perforator measured during operation, and the flap types were recorded. The survivals of flaps and appearances of donor sites were followed up. Results: The number and location of thoracodorsal artery perforators located before operation in each patient were consistent with the results of intraoperative exploration. A total of 42 perforators were found in two trapezoidal areas, with 2 or 3 perforators each patient. The perforators were all located in two trapezoid areas, and a stable perforator (the first perforator) was located and detected in the first trapezoidal area. There were averagely 1.47 perforators in the second trapezoidal area. The position where the first perforator exits the muscle was 2.1-3.1 cm away from the lateral border of the latissimus dorsi. The diameters of thoracodorsal artery perforators were 0.4-0.6 mm. In this group, 12 cases were repaired with single thoracodorsal artery perforator flap, 3 cases with lobulated thoracodorsal artery perforator flap, and 2 cases with thoracodorsal artery perforator flap carrying partial latissimus dorsi muscle. The patients were followed up for 6 to 16 months. All the 17 flaps survived with good elasticity, blood circulation, and soft texture. Only linear scar was left in the donor area. Conclusions: The two longitudes three transverses method is helpful to locate the perforator of thoracodorsal artery perforator flap. The method is simple and reliable. The thoracodorsal artery perforator flap designed and harvested based on this method has good clinical effects in repairing deep wound, with minimal donor site damage.
Adolescent ; Adult ; Aged ; Arteries ; Child ; Female ; Humans ; Male ; Middle Aged ; Perforator Flap ; Reconstructive Surgical Procedures/methods* ; Retrospective Studies ; Skin Transplantation ; Soft Tissue Injuries/surgery* ; Treatment Outcome ; Young Adult

BACKGROUND: Psoriasis is a chronic inflammatory skin disease, affecting about 0.6% of the Chinese population. Many patients are not well controlled by conventional treatments, thus there is need for new treatment regimens. In this study, we assessed the efficacy and safety of secukinumab in Chinese patients with moderate to severe plaque psoriasis. METHODS: This study was a 52-week, multicentre, randomized, double-blind, placebo-controlled, parallel-group, Phase 3 trial. A sub-population of study participants (≥18 years) of Chinese ethnicity were randomized to receive subcutaneous injections of 300 or 150 mg secukinumab, or placebo. The co-primary endpoints were psoriasis area severity index (PASI) 75 and Investigator's Global Assessment (IGA) 0/1 at Week 12. RESULTS: A total of 441 Chinese patients were enrolled in this study. Co-primary outcomes were achieved; 300 and 150 mg secukinumab were superior to placebo as shown in the proportion of patients that achieved PASI 75 (97.7% and 87.2% vs. 3.7%, respectively; P < 0.001), and IGA 0/1 (82.3% and 69.7% vs. 2.7%; P < 0.001) at Week 12. Treatment efficacy was maintained until Week 52. There was no increase in overall adverse events with secukinumab relative to placebo throughout the 52-week period. CONCLUSION: Secukinumab is highly effective and well tolerated in Chinese patients with moderate to severe plaque psoriasis. TRIAL REGISTRATION ClinicalTrials.gov, NCT03066609; https://clinicaltrials.gov/ct2/show/record/NCT03066609.
Antibodies, Monoclonal/therapeutic use* ; Antibodies, Monoclonal, Humanized ; China ; Double-Blind Method ; Humans ; Psoriasis/drug therapy* ; Severity of Illness Index ; Treatment Outcome

A 56-year-old female patient was admitted to a hospital because of repeated fatigue, anorexia, fever for more than one year, recurrence for 2 months and sudden left limb twitch for 10 days. In 2017, patient was diagnosed with infective endocarditis, then underwent aortic valve replacement, valve biopsy showed Candida parapsilosis, she took medicine regularly after operation and withdrew medicine after three consecutive negative blood culture. Fever and multiple organ infarction occurred again in 2018, Candida parapsilosis was isolated again from blood culture, it is suggested that fungal endocarditis may be latent and recurrence in human body for a long time, exfoliation of vegetation may embolize various organs and lead to corresponding clinical manifestations, surgery combined with drug therapy and subsequent maintenance of antifungal therapy are extremely important to improve the prognosis of patients.

OBJECTIVE: To investigate the efficacy of autologous peripheral blood mononuclear cells in the treatment of high radial nerve injury. METHODS: From April 2011 to September 2015, 12 cases of radial nerve injury in the middle arm were treated. Preoperatively peripheral blood mononuclear cells were mobilized, and then 15 mL of mononuclear cell suspension was prepared on the operation day. Radial nerves scheduled for anastomosis were surgically explored and subjected to end-end anastomosis using outer membrane suturing under microscope. The anastomotic site of the nerve was enveloped with gelatin sponge soaked with 5 mL of autologous peripheral blood mononuclear cell suspension. The remaining 10mL of cell suspension was used for a multi-point injection into the local muscles, 0.5 mL at each point. Thereafter, the deep fascia and the incision were sutured in sequence. Postoperative antibiotic treatment was used to prevent infection for 48 hours, and upper limb immobilization lasted for 4 weeks. Performance of rehabilitation exercise was guided. During the follow-up, wrist dorsal extension and muscle strength of extensor carpi ulnaris and extensor digitorum communis were detected to evaluate the therapeutic efficacy. RESULTS AND CONCLUSION: All the patients were followed up for 15 to 36 months, with an average of 17 months. Efficacy was excellent in 9 cases, good in 2 cases, fair in 1 case and poor in 0 case. The excellent and good rate was 92%. The wrist dorsal extension could achieve the functional needs, and the thumb dorsal extension and finger extension basically met the functional requirements. It is suggested that autologous peripheral blood mononuclear cell transplantation can achieve good outcomes in the treatment of high radial nerve injury.

Objective To explore the method of WeChat medication education for patients used by pharmacists,and to investigate the effect of WeChat medication education at Peking university third hospital.Methods Totally 30 patients who used warfarin at Peking university third hospital were enrolled.A series of subscriptions concerning warfarin medication education were sent to patients and/or their caregivers by WeChat regularly.The medication knowledge score after/before the intervention were assessed.Results The score of patients' warfarin medication knowledge before intervention was (14.20 ± 1.97) points,and after that the score was (16.63 ± 1.74) points,showing an improvenent with significance (P ＜ 0.001).Questions about adverse events of warfarin were most likely to be answered by mistake and the score of relevant questions was only (0.97 ± 0.80) points and (1.07 ± 0.81) points,respectively (P ＞ 0.05) before and after intervention.Conclusion It is of great significance for pharmacists to provide warfarin medication education.It is proved effective to improve patients' recognition of warfarin medication by means of WeChat subscriptions.

BACKGROUNDAtopic dermatitis (AD) is an inflammatory skin disease characterized by chronic recurrent dermatitis with profound itching. Most patients have personal and/or family history of atopic diseases. Several criteria have been proposed for the diagnosis of AD. Although the clinical features of childhood AD have been widely studied, there has been less large-scale study on adult/adolescent AD. The aim of this study was to investigate the clinical features of adult/adolescent patients with chronic symmetrical eczema/AD and to propose Chinese diagnostic criteria for adult/adolescent AD.

METHODSA hospital-based study was performed. Forty-two dermatological centers participated in this study. Adult and adolescent patients (12 years and over) with chronic symmetrical eczema or AD were included in this study. Questionnaires were completed by both patients and investigators. The valid questionnaires were analyzed using EpiData 3.1 and SPSS 17.0 software.

RESULTSA total of 2662 valid questionnaires were collected (1369 male and 1293 female). Of all 2662 patients, 2062 (77.5%) patients had the disease after 12 years old, while only 600 (22.5%) patients had the disease before 12 years old, suggesting late-onset eczema/AD is common. Two thousand one hundred and thirty-nine (80.4%) patients had the disease for more than 6 months. One thousand one hundred and forty-four (43.0%) patients had a personal and/or family history of atopic diseases. One thousand five hundred and forty-eight (58.2%) patients had an elevated total serum IgE and/or eosinophilia and/or positive allergen-specific IgE. Based on these clinical and laboratory features, we proposed Chinese criteria for adult/adolescent AD. Of all 2662 patients, 60.3% were satisfied with our criteria, while only 48.2% satisfied with Hanifin Rajka criteria and 32.7% satisfied with Williams criteria, suggesting a good sensitivity of our criteria in adult/adolescent AD patients.

CONCLUSIONLate-onset of eczema or AD is common. The clinical manifestations of AD are heterogeneous. We have proposed Chinese diagnostic criteria for adolescent and adult AD, which are simple and sensitive for diagnosis of adult/adolescent AD.

Adolescent ; Adult ; Dermatitis, Atopic ; diagnosis ; immunology ; Eczema ; diagnosis ; Female ; Humans ; Immunoglobulin E ; blood ; Male ; Middle Aged ; Retrospective Studies ; Surveys and Questionnaires

OBJECTIVETo explore the CD phenotypic, protein expression and pluripotent differentiation of human hypertrophic scar fibroblasts cultured in vitro, so as to study the mechanisms of scar formation.

METHODSFibroblasts were isolated and cultured from human hypertrophic scar of 3 cases. The cells morphology was observed by inverted microscope, and the growing state of the third passage was detected by the cell counting meter of Vi-CELL. The cell surface markers CD105, CD14, CD73, CD34, CD44, CD45 and CD90 were identified by flow cytometry. The expression of CK19, Oct-4, Nanog and vimentin was detected by immunocytochemistry, and the expression of alpha-smooth muscle actin(alpha-SMA) was tested by immunofluorescence. The differentiated potential of fibroblasts of the third passage into adipogenic, osteogenic and chondrogenic lineages was assayed.

RESULTSThe primary passage fibroblasts showed the shape of spindle shaped or irregular polygon with a radiated or circinate of growing arrangement. The growth curve showed the cells growth was slow on the first and second day, and quick during the third to fifth day, which reached platform stage on the sixth or seventh day. The fibroblasts highly expressed mesenchymal stem cell surface markers-CD73, CD105, CD44, CD90, but not expressed hematopoietic stem cell surface markers-CD14, CD34, CD45 by flow cytometry. And positive expression of vimentin, Oct-4 and negative expression of CK19 were detected by Immunocytochemistry. Positive expression of alpha-SMA was also detected by immunofluorescence. Multidirectional differentiation induction indicated that the third passage cells could differentiate into adipogenic, osteogenic and chondrogenic lineages.

CONCLUSIONSHuman hypertrophic scar-derived fibroblasts show the biologic characteristics of mesenchymal stem cells, which may play an important role in wound healing and hypertrophic scar formation.

Adolescent ; Antigens, CD ; metabolism ; Cell Differentiation ; physiology ; Cells, Cultured ; Cicatrix, Hypertrophic ; pathology ; Female ; Fibroblasts ; cytology ; metabolism ; Humans ; Male ; Mesenchymal Stromal Cells ; cytology ; metabolism ; Phenotype ; Young Adult