Background::Atopic dermatitis (AD) affects approximately 10% of adults worldwide. CM310 is a humanized monoclonal antibody targeting interleukin-4 receptor alpha that blocks interleukin-4 and interleukin-13 signaling. This trial aimed to evaluate the efficacy and safety of CM310 in Chinese adults with moderate-to-severe AD.Methods::This multicenter, randomized, double-blind, placebo-controlled, phase 2b trial was conducted in 21 medical institutions in China from February to November 2021. Totally 120 eligible patients were enrolled and randomized (1:1:1) to receive subcutaneous injections of 300 mg CM310, 150 mg CM310, or placebo every 2 weeks for 16 weeks, followed by an 8-week follow-up period. The primary endpoint was the proportion of patients achieving ≥75% improvement in the Eczema Area and Severity Index (EASI-75) score from baseline at week 16. Safety and pharmacodynamics were also studied.Results::At week 16, the proportion of EASI-75 responders from baseline was significantly higher in the CM310 groups (70% [28/40] for high-dose and 65% [26/40] for low-dose) than that in the placebo group (20%[8/40]). The differences in EASI-75 response rate were 50% (high vs. placebo, 95% CI 31%–69%) and 45% (low vs. placebo, 95% CI 26%–64%), with both P values <0.0001. CM310 at both doses also significantly improved the EASI score, Investigator’s Global Assessment score, daily peak pruritus Numerical Rating Scale, AD-affected body surface area, and Dermatology Life Quality Index compared with placebo. CM310 treatment reduced levels of thymus and activation-regulated chemokine, total immunoglobulin E, lactate dehydrogenase, and blood eosinophils. The incidence of treatment-emergent adverse events (TEAEs) was similar among all three groups, with the most common TEAEs reported being upper respiratory tract infection, atopic dermatitis, hyperlipidemia, and hyperuricemia. No severe adverse events were deemed to be attributed to CM310. Conclusion::CM310 at 150 mg and 300 mg every 2 weeks demonstrated significant efficacy and was well-tolerated in adults with moderate-to-severe AD.Trial Registration::ClinicalTrials.gov, NCT04805411.

Objective To monitor the antifungal resistance of clinical isolates of Candida spp.in the East China region.Methods MALDI-TOF MS or molecular methods were used to re-identify the strains collected from January 2018 to December 2022.Antifungal susceptibility testing was performed using the broth microdilution method.The susceptibility test results were interpreted according to the breakpoints of 2022 Clinical and Laboratory Standards Institute(CLSI)documents M27 M44s-Ed3 and M57s-Ed4.Results A total of 3 026 strains of Candida were collected,65.33％of which were isolated from sterile body sites,mainly from blood(38.86％)and pleural effusion/ascites(10.21％).The predominant species of Candida were Candida albicans(44.51％),followed by Candida parapsilosis complex(19.46％),Candida tropicalis(13.98％),Candida glabrata(10.34％),and other Candida species(0.79％).Candida albicans showed overall high susceptibility rates to the 10 antifungal drugs tested(the lowest rate being 93.62％).Only 2.97％of the strains showed dose-dependent susceptibility(SDD)to fluconazole.Candida parapsilosis complex had a SDD rate of 2.61％and a resistance rate of 9.42％to fluconazole,and susceptibility rates above 90％to other drugs.Candida glabrata had a SDD rate of 92.01％and a resistance rate of 7.99％to fluconazole,resistance rates of 32.27％and 48.24％to posaconazole and voriconazole non-wild-type strains(NWT),respectively,and susceptibility rates above 90％to other drugs.Candida tropicalis had resistance rates of 29.55％and 26.24％to fluconazole and voriconazole,respectively,resistance rates of 76.60％and 21.99％to posaconazole and echinocandins non-wild-type strains(NWT),and a resistance rate of 2.36％to echinocandins.Conclusions The prevalence and species distribution of Candida spp.in the East China region are consistent with previous domestic and international reports.Candida glabrata exhibits certain degree of resistance to fluconazole,while Candida tropicalis demonstrates higher resistance to triazole drugs.Additionally,echinocandins resistance has emerged in Candida albicans,Candida glabrata,Candida tropicalis,and Candida parapsilosis.

Purpose To explore the application value of contrast enhancement boost(CE-Boost)technique in image quality of tumors and their feeding arteries in preoperative evaluation of renal cancer patients.Materials and Methods A total of 36 renal cancer patients in People's Hospital Affiliated to Shandong First Medical University from August 2022 to May 2023 with pathologically confirmed were retrospective collected.All patients underwent renal enhanced CT.The cortical phase images were post-processed using the CE-Boost technique to obtain CE-Boost images.The cortical phase images were set as group A and the CE-Boost images were set as group B.The CT value and image noise(SD)of abdominal aorta,renal artery,tumor and its adjacent renal cortex,and SD of the vertical spinal muscle on both sides of the spine of two groups were measured and recorded,and then the signal-to-noise ratio and contrast-to-noise ratio of tumor,abdominal aorta and renal artery were calculated.The image quality of the tumor,tumor feeding artery and renal artery was scored on 4 points by 2 doctors with double-blind method.Results The signal-to-noise ratio,contrast-to-noise ratio and CT value of group B were significantly higher than those of group A(t=-27.385--5.267,all P<0.05).The SD of tumor,abdominal aorta,right and left renal artery were not significantly different between group A and B(t=-1.849-0.993,all P>0.05).The subjective score of tumor in group A and B were no significant difference(Z=-1.490,P=0.136).However,the subjective score of tumor feeding arteries and renal arteries were significantly higher in group B than in group A(Z=-3.512,P=0.000;Z=-2.127,P=0.033).Conclusion The CT CE-Boost technique can improve the image quality of renal enhanced CT and provide visualization of tumor feeding arteries.

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 characterize the knee gait maps of ordinary people, athletes and patients with anterior cruciate ligament (ACL) injury when walking on a level ground in order to identify potential kinematic indicators for early identification of ACL injury.Methods:From December 2021 to March 2022, 39 ordinary college students (normal group) and 39 college athletes (athlete group) were recruited in Southern Medical University, and 26 patients with ACL injury (patient group) were recruited at the Department of Orthopedics, Guangdong Provincial People＇s Hospital. The normal group consisted of 20 males and 19 females with a median age of 19 (18, 21) years; the athlete group consisted of 22 males and 17 females with a median age of 19 (18, 20) years; the patient group consisted of 23 males and 3 females with a median age of 20 (19, 20) years. A portable knee joint motion capture system was used to collect the knee gait maps of the subjects walking at a speed of 3 km/h on a treadmill. The knee varus and valgus angles, internal and external rotation angles, flexion and extension angles during the movement, and anteroposterior, medial-lateral superior-inferior displacements of the tibia relative to the femur were compared between the 3 groups.Results:There was no significant difference in the general data among the 3 groups except for gender, showing they were comparable ( P>0.05). There were significant differences in the varus and valgus angles during the whole gait cycle (1% to 100%), internal and external rotation angles during the weight-bearing response period (9% to 10%), flexion and extension angles during the stance phase and swing phase (1% to 27%, 29% to 100%), anteroposterior displacements during the weight-bearing reaction phase (1% to 3%) and at the end of the swing phase (96% to 98%), superior-inferior displacements at the middle support phase (15% to 19%), the end of the support phase (29% to 33%, 36% to 43%) and the swing phase (68% to 94%), and medial-lateral displacements at the middle stance phase and the middle swing phase (12% to 82%) among the 3 groups ( P<0.05). The maximum varus and valgus angles (-10.89°±4.55°, -12.20°±4.38°) of the subjects in the normal group and the athlete group were significantly greater than those in the patient group (-5.44°±3.72°) ( P<0.05). The medial-lateral displacement at the middle support phase [3.69 (0.13, 7.25) mm] of the subjects in the normal group was significantly larger than those in the athlete group and the patient group [-0.59 (-6.65, 5.24) mm, 0.96 (-1.54, 3.89) mm] ( P<0.05). Conclusions:The gait of college athletes is significantly different from that of ordinary college students and that of patients with ACL injury. Indexes like the varus and valgus angles and the medial-lateral displacement may be used as potential indictors for early identification of ACL injury.

Despite the advancement of treatments, adults with relapsed/refractory (R/R) B-lineage acute lymphoblastic leukemia (B-ALL) have poor prognosis, with an expected five-year overall survival (OS) rate of 10%‒20% (Nguyen et al., 2008; Oriol et al., 2010). Extramedullary relapse of B-ALL is regarded as a high-risk factor generally associated with poor survival, occurring in about 15% to 20% of all relapsed patients (Ding et al., 2017; Sun et al., 2018). The central nervous system (CNS) and the testes are the most common sites of extramedullary relapse of B-ALL. In addition, extramedullary leukemia can appear in the skin, eyes, breasts, bones, muscles, and abdominal organs. The prognosis of relapsed extramedullary B-ALL after allogeneic hematopoietic stem cell transplantation (allo-HSCT) is extremely poor (Spyridonidis et al., 2012; Dahlberg et al., 2019). Conventional chemotherapy or radiation is often ineffective in such patients. At present, there are no optimal treatment strategies for treating extramedullary leukemia after allo-HSCT.
Adult ; Antigens, CD19 ; Hematopoietic Stem Cell Transplantation ; Humans ; Immunotherapy, Adoptive/adverse effects* ; Precursor Cell Lymphoblastic Leukemia-Lymphoma/therapy* ; Receptors, Chimeric Antigen ; Recurrence

Objective:To study whether early leukocytosis after total joint arthroplasty (TJA) requires further workup to exclude infection by observing changes in peripheral blood white blood cell (WBC) count after TJA.Methods:This study included the 294 patients (infection-free group) who had undergone primary hip or knee TJA from June 2019 to June 2020 but reported no periprosthetic joint infection (PJI) within one month after surgery and the 31 patients (infection group) who had undergone the same TJA but reported infection within one month after surgery from May 2012 to June 2020 at Department of Joint Surgery, The First Affiliated Hospital to Xinjiang Medical University. Peripheral blood WBC counts were measured and recorded before surgery and 1 to 5 days after surgery. Differences were compared between time points and multiple linear regression analysis was used to screen the factors associated with early postoperative leukocytosis. The receiver operating characteristic (ROC) curve was used to evaluate the predictive value of WBC for early PJI.Results:The peripheral WBC level in the infection-free group showed a trend of increasing at first and then decreasing. It reached the peak on day 2 after surgery, increasing by 8.08×10 9/L±2.33×10 9/L compared to pre-surgery, and then began to decrease to a level slightly higher than the preoperative value on day 5 after surgery. The changes in WBC count in the first 2 days after surgery ranged from 6.24×10 9/L to 26.32×10 9/L. The incidence of leukocytosis in the first 5 days after surgery was 95.6% (281/294). The factors associated with postoperative leukocytosis included preoperative WBC count and bilateral surgery. For every increase of 1.00×10 9/L in preoperative WBC count, the postoperative WBC value increased by an average of 0.98×10 9/L [ β=0.984, 95% confidence interval (95% CI): 0.821-1.148, P<0.001]. The postoperative WBC count in the patients undergoing bilateral surgery increased by an average of 1.03×10 9/L compared with that in the patients undergoing unilateral surgery ( β=1.026, 95% CI: 0.565-1.486, P<0.001). The area under the curve (AUC) for prediction of early PJI by absolute WBC count difference (the absolute difference between the maximum postoperative WBC value and the baseline) was 0.655 (95% CI: 0.546-0.764, P<0.05), providing a threshold of 7.96×10 9/L, a sensitivity of 57.5% and a specificity of 74.2%. Conclusions:Leukocytosis is a common phenomenon after TJA, indicating a normal physiological response to surgery. The preoperative WBC count is a predictor for postoperative leukocytosis. In the absence of abnormal clinical symptoms or signs, there is no need for further workup to check infection if the postoperative WBC does not deviate from its changing range and trend.

Objective:To analyze the effects of DHT on the proliferation and migration of endothelial progenitor cells (EPCs) and the role of RhoA/ROCK pathway in this process.Methods:Early EPCs were isolated from peripheral blood of healthy adults, and cultured in serum-free EBM-2 medium for 24 h before incubation with various concentrations of DHT (1, 10, and 100 nmol/L). EPCs proliferative and migrative capacities were measured. The adherent cells were collected and randomLy divided into: control group, DHT group, C3 exoenzyme+DHT, Y-27632+DHT group. EPCs proliferation and migration were assayed by MTT assay and modified Boyden chamber assay respectively.Results:DHT significantly increased the proliferation and migration ability of EPCs in a dose- and time-dependent manner, maximum at 10 nmol/L, 24 h ( P<0.05). C3 exoenzyme [(0.22±0.02) vs (0.26±0.05), P>0.05] and Y-27632 [(0.21±0.04) vs (0.26±0.05), P>0.05] can attenuate the proliferative capacities of EPCs induced by DHT compared with the DHT group, but there was no statistical significance. The influence of DHT on EPCs migrative capacities can be abolished by C3 exoenzyme [(35.26±4.27) vs (46.92±5.46), P<0.05] and Y-27632 [(33.61±5.33) vs (46.92±5.46), P<0.01]. C3 exoenzyme [(116.75±7.42) vs (156.80± 21.74), P<0.05] and Y-27632 [(121.73±5.33) vs (156.80 ±21.74), P<0.01] could noticeably attenuate DHT-induced EPCs secretion of VEGF respectively. Conclusions:DHT can modulate EPCs proliferation, migration and the RhoA/ROCK pathway plays an important role in this process.

TSCI have dyskinesia and sensory disturbance that can cause various life-threaten complications. The patients with traumatic spinal cord injury (TSCI), seriously affecting the quality of life of patients. Based on the epidemiology of TSCI and domestic and foreign literatures as well as expert investigations, this expert consensus reviews the definition, injury classification, rehabilitation assessment, rehabilitation strategies and rehabilitation measures of TSCI so as to provide early standardized rehabilitation treatment methods for TSCI.

This article reported a case of malignant pheochromocytoma and paraganglioma with cranial metastasis. The patient was a 25-year-old man. At the age of 10, he was diagnosed with retroperitoneal paraganglioma. He received radiotherapy after partial resection of the tumor. At the age of 15, when he consulted for headache and hypertension, a space occupying lesion was found on the right adrenal without further diagnosis and treatment. His headache and hypertension were aggravated at the age of 25. Then he visited our medical center and diagnosed with right adrenal pheochromocytoma. He undertook an operation to remove the right adrenal lesion, and his blood pressured could be controlled in the normal range with oral antihypertensive medication. One year after the surgery, a cranial lesion with positive 131I-metaiodobenzylguanidine imaging was found following the increase of norepinephrine and dopamine in both blood and urine. The diagnosis of malignant pheochromocytoma with cranial metastasis was confirmed. The cranial lesion was treated with cyberknife therapy for 4 times, and the lesion was slightly reduced. Four year after the removal of right adrenal tumor, he developed multiple bone metastasis in the right ribs and left ilium, and then he received 131I-metaiodobenzylguanidine radiotherapy. Additionally, the results of gene test indicated a pathogenic mutation of SDHB. During the follow-up period of one year after the treatment, his blood pressure fluctuated to about 140/90mmHg with 10mg of phenoxybenzamine once a day. The case is a malignant pheochromocytoma with multiple bone metastasis characterized by a long course with an ideal prognosis in a way. Consequently, we suggested the diagnostic pathway with genetic testing based on clinical phenotype to approach more timely diagnosis and reasonable evaluation of the prognosis in pheochromocytoma and paraganglioma. Furthermore, clinicians should pay more attention to the long-term surveillance.