OBJECTIVE To provide reference for the clinically safe application of acalabrutinib by mining and analyzing the risk signals of adverse drug events （ADE）. METHODS The acalabrutinib-induced ADE reports were extracted from the U.S. FDA adverse event reporting system using the OpenVigil 2.1 platform from November 1， 2017 to March 31， 2023. The reporting odds ratio （ROR） method and composite criteria method from the Medicines and Healthcare Products Regulatory Agency （MHRA） were used for detection of ADE signals. RESULTS There were 7 869 ADE reports of acalabrutinib as the primary suspect drug and 142 ADE positive signals were detected from them， involving 20 system organ classes， which was generally consistent with the ADE recorded in the drug instruction of acalabrutinib， mainly involving general disorders and administration site conditions， various inspection， blood and lymphatic system disorders， various neurological disorders and cardiac disorders. In addition， this study identified several new potential ADE signals that were not mentioned in the drug instruction， including sudden cardiac death， pulmonary toxicity， tumor lysis syndrome， pleural effusion， dyspepsia， gastroesophageal reflux disease， bone pain， decreased blood pressure， and abnormal blood sodium， etc. CONCLUSIONS When using acalabrutinib， in addition to paying attention to the ADE recorded in its instructions， the risk of serious ADE that may lead to death， such as sudden cardiac death and pulmonary toxicity， should also be evaluated to avoid or reduce the occurrence of ADE as much as possible.

Objective To mine the adverse drug events(ADE)signal of avatrombopag,an effective drug for thrombocytopenia treatment,based on real world data in order to provide reference for its clinical safety application.Methods The OpenVigil2.1 pharmacovigilance platform was used to obtain the ADE report data of avatrombopag from May 2018 to March 2023 in the database of FDA adverse event reporting system(FAERS).The ADE signals were classified and described by the system organ class(SOC)and preferred term(PT)of the ADE terminology set in the Medical Dictionary for Regulatory Activities(MedDRA),and reporting odds ratio(ROR)and UK Medicines and Healthcare Products Regulatory Agency(MHRA)comprehensive standard were used to detect the positive ADE signals.Results A total of 1 879 ADE reports related to avatrombopag were obtained,24 SOCs were involved,and 28 positive ADE signals were detected at PT level.Among these signals,the strongest ones were renal vein thrombosis,portal vein thrombosis and graft versus host disease,while the reports accounting for the largest numbers were headache,fatigue and asthenia.There were 8 ADE signals discovered newly,that is,seasonal allergy,back disorder,musculoskeletal discomfort,flatulence,hypersomnia,rash macular,emotional disorder,and rhinorrhoea.Conclusion For clinical use of avatrombopag,clinicians should not only concern the risk of thrombosis,but also pay close attention to ADE signals such as seasonal allergy,back disorder,musculoskeletal discomfort,flatulence,hypersomnia,rash macular,emotional disorder,and rhinorrhoea that are not documented in the instructions.

Objective To investigate the clinical efficacy of mitral valve repair technique in the treatment of rheumatic mitral valve lesions. Methods The clinical data of patients diagnosed with rheumatic mitral valve lesions and undergoing mitral valve repair under extracorporeal circulation in our department from 2021 to 2022 were retrospectively analyzed. Results A total of 100 patients were collected, including 78 females and 22 males with an average age of 52 years. There were no secondary open heart or death in the whole group. Extracorporeal circulation time was 136.3±33.1 min, aortic cross-clamping time was 107.6±27.5 min, ventilator use time was 12.9±5.9 h, ICU stay was 2.6±1.4 d, and vasoactive medication use was 823.4±584.4 mg. Before and after the surgery, there were statistical differences in the left ventricular end diastolic diameter, left atrial end systolic diameter, effective mitral valve orifice area, shortening rate of left ventricular short axis, mitral E-peak blood flow velocity, mean mitral transvalvular pressure difference, mitral pressure half-time, and cardiac function graded by New York Heart Association (P＜0.05). While there was no statistical difference in left ventricular ejection fraction or left ventricular end-diastolic volume (P>0.05). Conclusion Overall repair of rheumatic mitral valve lesions can significantly improve the cardiac function and hemodynamics of the patients, and is a good choice for patients with rheumatic mitral valve lesions.

OBJECTIVE To prepare Lonicerae japonicae flavonoids liposome membrane （LFLM）， and to study the mechanism of its anti-methicillin-resistant Staphylococcus aureus （MRSA）. METHODS L. japonicae flavonoids liposome （LFL） were prepared by ethanol injection with phospholipids and cholesterol as carriers. LFLM was prepared by loading LFL in mixed membranes of chitosan and polyvinyl alcohol. The particle size of LFL， polydispersity index （PDI） and release rate of LFLM were measured. A control group， LFLM low-concentration group （2.5 mg/mL）， LFLM-medium concentration group （5 mg/mL）， LFLM high-concentration group （10 mg/mL）， positive group （10 μg/mL vancomycin）， and combination therapy group （10 mg/mL LFLM and 10 μg/mL vancomycin） were set up. The effects of LFLM on MRSA colony formation and survival as well as the formation of MRSA biofilm were evaluated. The contents of K+， Mg2+， lactic dehydrogenase （LDH）， and alkaline phosphatase （AKP） in the supernatant of MRSA were determined. mRNA expressions of mecA and mecR1 in MRSA were determined. RESULTS The particle size of LFL was （80.91±3.96） nm， and the PDI was 0.26±0.07. The release rate of LFLM was 55% within 12 h and 73% within 36 h. Compared with the control group， the number of MRSA colony formation decreased significantly in LFLM medium-concentration and high-concentration groups， and the positive group （P＜0.05）. The ratio of dead to live bacteria， biofilm inhibition rate， and the contents of K+， Mg2+， LDH and AKP were increased significantly （P＜0.05）， while the mRNA expressions of mecA and mecR1 were decreased significantly （P＜0.05）. The combination of LFLM and vancomycin further enhanced the anti-MRSA effect. CONCLUSIONS LFLM is prepared successfully in the study and has good drug release characteristics. LFLM can exert anti-MRSA activity by promoting cell wall and membrane damage， and suppressing the mRNA expression of mecA and mecR1.

Objective:To investigate the effects of antibacterial absorbable suture closure in the repair of small range of bone defect wounds due to deep sternal wound infection after median thoracotomy.Methods:This study was a retrospective non-randomized clinical controlled study. A total of 32 patients (20 males and 12 females, aged (58±11) years) who met the inclusion criteria and underwent closure with antibacterial absorbable sutures (hereinafter referred to as direct closure surgery) admitted to Guangdong Provincial People's Hospital of Southern Medical University (hereinafter referred to as our hospital) from October 2017 to December 2021 were included in direct closure group. A total of 39 patients (27 males and 12 females, aged (59±11) years) who met the inclusion criteria and received bilateral pectoralis major muscle flap packing repair admitted to our hospital from January 2015 to January 2020, were included in muscle flap packing group. In the two groups, sternal infected wounds were thoroughly debrided during stage Ⅰ surgery, followed by wound repair during stage Ⅱ surgery. The width of sternal cross-section defects after debridement was less than 1 cm for patients in the two groups. For patients in direct closure group, stage Ⅱ wound repair involved intermittent sutures to the anterior sternal plate or full-thickness sternum with a total of 6 or 7 double sternal sutures. Relevant data including the duration of the stage Ⅱ wound repair surgery and the volume of blood loss during surgery, length of hospital stay, and bacterial wound infection of patients in the two groups were recorded. The postoperative complications and wound healing of patients in the two groups were recorded. During follow-up, the wound infection or recurrence of patients in the two groups and the sternal healing of patients in direct closure group were observed.Results:Compared with those in muscle flap packing group, the duration of stage Ⅱ wound repair surgery and length of hospital stay of patients in direct closure group were significantly shorter (with t values of 13.61 and 6.25, respectively, P<0.05), and there was no statistically significant difference in intraoperative blood loss volume of the stage Ⅱ wound repair surgery between the two groups ( P>0.05). The main bacterial infection in the two groups was Staphylococcus. In direct closure group, one patient had exudation in the wound two weeks post-operation, however the wound healed well after two weeks of conservative dressing changes; the wounds of the other patients healed well. In muscle flap packing group, 5 patients had postoperative complications, of which one patient died, and the wounds of 4 patients healed after dressing change or reoperation; the wounds of the other patients healed well. There was no statistically significant difference in complication incidence of patients between the two groups ( P>0.05). During the follow-up of 22-45 months, there was no re-infection or recurrence in the wound of patients in direct closure group and surviving patients in muscle flap packing group, the sternum of patients in the direct closure group achieved anatomical union. Conclusions:Direct closure surgery can not only effectively repair sternal cross-sectional defects with width below 1 cm due to deep sternal wound infections after median thoracotomy, but can also significantly shorten the operation time and duration of hospitalization.

Patients with severe trauma require an extremely timely treatment and transfusion plays an irreplaceable role in the emergency treatment of such patients. An increasing number of evidence-based medicinal evidences and clinical practices suggest that patients with severe traumatic bleeding benefit from early transfusion of low-titer group O whole blood or hemostatic resuscitation with red blood cells, plasma and platelet of a balanced ratio. However, the current domestic mode of blood supply cannot fully meet the requirements of timely and effective blood transfusion for emergency treatment of patients with severe trauma in clinical practice. In order to solve the key problems in blood supply and blood transfusion strategies for emergency treatment of severe trauma, Branch of Clinical Transfusion Medicine of Chinese Medical Association, Group for Trauma Emergency Care and Multiple Injuries of Trauma Branch of Chinese Medical Association, Young Scholar Group of Disaster Medicine Branch of Chinese Medical Association organized domestic experts of blood transfusion medicine and trauma treatment to jointly formulate Chinese expert consensus on blood support mode and blood transfusion strategies for emergency treatment of severe trauma patients ( version 2024). Based on the evidence-based medical evidence and Delphi method of expert consultation and voting, 10 recommendations were put forward from two aspects of blood support mode and transfusion strategies, aiming to provide a reference for transfusion resuscitation in the emergency treatment of severe trauma and further improve the success rate of treatment of patients with severe trauma.

OBJECTIVE: To explore the pathogenesis of erythrocytosis by detecting the key enzymes of glucose metabolism and glucose transporter in bone marrow erythrocytes of chronic mountain sickness (CMS), and analyzing its correlation with hemoglobin. METHODS: Twenty CMS patients hospitalized in Qinghai Provincial People's Hospital from January 2019 to December 2020 were selected as CMS group. Twenty males with leukocyte count > 3.5×10⁹/L who had accepted bone marrow aspiration and had normal result were taken as control group. The mRNA and protein expression of key enzymes and glucose transporter in glucose metabolism in bone marrow CD71⁺ erythrocytes were detected by real time qPCR and Western blot, respectively. Glucose, lactic acid and 2,3-diphosphoglycerate in the bone marrow supernatant and serum were tested by ELISA. The mRNA and protein expression of key enzymes and glucose transporter, glucose, lactic acid and 2,3-diphosphoglycerate of the two groups were compared. Pearson correlation was used to analyze the correlation between key enzymes, glucose transporter in glucose metabolism in bone marrow CD71⁺ erythrocytes and hemoglobin. RESULTS: The expression of HK2, GLUT1 and GLUT2 mRNA in the CMS group were higher than those in the control group (P<0.001), while the expression of HK1, OGDH and COX5B mRNA were not different. The expression of HK2, GLUT1 and GLUT2 protein in the CMS group were higher than those in the control group (P<0.05). The levels of glucose and lactic acid in the bone marrow supernatant and serum in the CMS group were not different from those in the control group, while the level of 2,3-diphosphoglycerate was higher (P<0.001). Both HK2 and GLUT2 proteins were positively correlated with hemoglobin (r=0.511, 0.717). CONCLUSION CMS patients may increase glycolysis by increasing the expression of HK2, and promote the utilization of glucose through high expression of GLUT1 and GLUT2 to meet the need of energy supply.
Male ; Humans ; Altitude Sickness/metabolism* ; Glucose Transporter Type 1 ; 2,3-Diphosphoglycerate ; Hemoglobins ; Chronic Disease ; RNA, Messenger ; Phenotype ; Glucose

OBJECTIVES: To realize the dynamic visualization of forensic odontology based on the bibliometrics methods, and capture the research hotspots and identify the future development trend. METHODS: Literature articles published from January 1995 to December 2020 were searched according to specific subject words in the core data set of Web of Science. The visualization analysis of publishing country, institution, discipline, author, co-cited journal and keywords was performed by CiteSpace 5.7.R5W software. RESULTS: The annual analysis of publications showed an upward trend of forensic odontology research literature year by year, with the number of annual publications more than 110 in the last five years. Developed countries were the main source of contributions and the average centrality was greater than 0.2. The research of forensic odontology involved multiple disciplines, including stomatology, biology, computer science and medical imaging, with a distinct interdisciplinary feature. A total of 115 nodes were obtained by keyword cluster analysis. The principal line of forensic odontology mainly included individual identification and age estimation and the emergence of hotspots was closely related to new technologies. Population-based odontology investigation, improvement of traditional dental age estimation method and dental age estimation based on new technology were popular research in forensic odontology. CONCLUSIONS Developing countries urgently need to increase the focus on related research. It may be an important direction for the development of forensic odontology to establish and enrich the regional dental database, develop new odontology identification technology combined with frontier and high-end technology, and develop the identification program based on advanced information technology.
Forensic Medicine ; Software ; Bibliometrics

Objective:To investigate molecules involved in the occurrence of pruritus in patients with mycosis fungoides (MF) .Methods:Totally, 522 patients with MF were enrolled from Peking University First Hospital from October 2009 to August 2021, and the incidence of pruritus was calculated. The patients were grouped according to whether they suffered from pruritus or not. RNA sequencing data on biopsied skin lesions of 49 patients were analyzed to identify differentially expressed genes between patients with pruritus and those without; enzyme-linked immunosorbent assay and immunohistochemical techniques were performed to determine the protein expression of CC chemokine ligand 17 (CCL17) in serum samples from 88 MF patients, and in tissue samples from 81 MF patients, respectively; flow cytometry was conducted to detect markers for T lymphocyte activation and differentiation in peripheral blood samples from 46 MF patients to identify peripheral blood lymphocyte subsets associated with pruritus. Statistical analysis was carried out by using chi-square test, Mann-Whitney U test, and Spearman correlation analysis. Results:Among the 522 patients with MF, 305 were males and 217 were females; 347 were diagnosed with early-stage MF, and 175 with advanced MF. The incidence of pruritus was 67.2% (351/522) in the patients with MF, and significantly higher in the patients with advanced MF (81.7%, 143/175) than in those with early-stage MF (59.9%, 208/347; χ2 = 25.03, P < 0.001) . RNA sequencing showed that CCL17 mRNA expression was significantly higher in the MF patients with pruritus than in those without (fold change = 10.09, P < 0.001) . The serum CCL17 concentration was significantly elevated in the patients with pruritus (1 017.05[377.12, 4 831.80] pg/ml) compared with those without (361.66 [180.47, 500.08] pg/ml; Z = -4.57, P < 0.001) , and correlated with pruritus scores ( r = 0.57, P = 0.010) . In both early and advanced stages of MF, the serum CCL17 concentration was significantly higher in the patients with pruritus than in those without ( Z = -3.68, P < 0.001; Z = -2.54, P = 0.011, respectively) . Immunohistochemical staining revealed that there was no significant difference in the relative quantification value of CCL17 between the patients with pruritus and those without ( Z = -1.84, P = 0.066) . The percentage of CD3 +CD4 +CD26 -CCR4 + malignant T cells significantly increased in the MF patients with pruritus than in those without ( Z = -2.03, P = 0.043) , and was positively correlated with serum CCL17 concentrations ( r = 0.49, P < 0.001) . Conclusions:Both CCL17 mRNA expression in lesional tissues and serum CCL17 concentrations increased in MF patients with pruritus, and CCL17 was associated with the occurrence of pruritus. CCL17 may be involved in the occurrence of pruritus through the recruitment of CD3 +CD4 +CD26 -CCR4 + malignant T cells.

OBJECTIVE: To study the trend of surgical type, surgical procedure and etiological distribution of upper urinary tract repair in recent 10 years. METHODS: The preoperative and perioperative variables and follow-up data of upper urinary tract reconstruction surgery in RECUTTER (Reconstruction of Urinary Tract: Technology, Epidemiology and Result) database from 2010 to 2021 were searched, collected and analyzed. The surgical type, surgical procedure, duration of hospitalization, time of operation, incidence of short-term complications, and proportion of the patients undergoing reoperations were compared between the two groups of 2010-2017 period and 2018-2021 period. RESULTS: A total of 1 072 patients were included in the RECUTTER database. Congenital factors and iatrogenic injuries were the main causes of upper urinary tract repair. Among them, 129 (12.0%) patients had open operation, 403 (37.6%) patients had laparoscopic surgery, 322 (30.0%) patients had robot-assisted laparoscopic surgery and 218 (20.3%) patients had endourological procedure. In the last decade, the total number of surgeries showed a noticeable increasing annual trend and the proportion of robot-assisted laparoscopic surgery in 2018-2021 was significantly higher than that in 2010-2017 (P < 0.001). The 1 072 patients included 124 (11.6%) cases of ileal ureter replacements, 440 (41.1%) cases of pyeloplasty, 229 (21.4%) cases of balloon dilation, 109 (10.2%) cases of ureteral reimplantation, 49 (4.6%) cases of boari flap-Psoas hitch surgery, 60 (5.6%) cases of uretero-ureteral anastomosis, 61 (5.7%) cases of lingual mucosal onlay graft ureteroplasty or appendiceal onlay flap ureteroplasty. Pyeloplasty and balloon dilatation had been the main types of surgery, while the proportion of lingual mucosal onlay graft ureteroplasty plus appendiceal onlay flap ureteroplasty had increased significantly in recent years (P < 0.05). In addition, the time of operation was significantly increased (P < 0.05) after 2018, which was considered to be related to the sharp increase in the proportion of robot-assisted laparoscopic surgery. We found that minimally invasive surgery (endourological procedure and robot-assisted laparoscopic surgery) as an independent risk factor (P=0.050, OR=0.472) could reduce the incidence of short-term post-operative complications. CONCLUSION We have justified the value of the RECUTTER database, created by the Institute of Urology, Peking University in data support for clinical research work, and provided valuable experience for the construction of other multi-center databases at home and abroad. In recent 10 years, we have observed that, in upper urinary tract reconstruction surgery, the surgery type tends to be minimally invasive and the surgery procedure tends to be complicated, suggesting the superiority of robot-assisted laparoscopic surgery.
Humans ; Laparoscopy/methods* ; Retrospective Studies ; Robotic Surgical Procedures ; Treatment Outcome ; Ureter/surgery* ; Ureteral Obstruction/surgery* ; Urologic Surgical Procedures/methods*