BACKGROUND: Previous research demonstrated that a homozygous mutation of g.136372044G>A (S12N) in caspase recruitment domain family member 9 ( CARD9 ) is critical for producing Aspergillus fumigatus -induced ( Af -induced) T helper 2 (T H 2)-mediated responses in allergic bronchopulmonary aspergillosis (ABPA). However, it remains unclear whether the CARD9S12N mutation, especially the heterozygous occurrence, predisposes the host to ABPA. METHODS: A total of 61 ABPA patients and 264 controls (including 156 healthy controls and 108 asthma patients) were recruited for sequencing the CARD9 locus to clarify whether patients with this heterozygous single-nucleotide polymorphisms are predisposed to the development of ABPA. A series of in vivo and in vitro experiments, such as quantitative real-time polymerase chain reaction, flow cytometry, and RNA isolation and quantification, were used to illuminate the involved mechanism of the disease. RESULTS: The presence of the p.S12N mutation was associated with a significant risk of ABPA in ABPA patients when compared with healthy controls and asthma patients, regardless of Aspergillus sensitivity. Relative to healthy controls without relevant allergies, the mutation of p.S12N was associated with a significant risk of ABPA (OR: 2.69 and 4.17 for GA and AA genotypes, P = 0.003 and 0.029, respectively). Compared with patients with asthma, ABPA patients had a significantly higher heterozygous mutation (GA genotype), indicating that p.S12N might be a significant ABPA-susceptibility locus ( aspergillus sensitized asthma: OR: 3.02, P = 0.009; aspergillus unsensitized asthma: OR: 2.94, P = 0.005). The mutant allele was preferentially expressed in ABPA patients with heterozygous CARD9S12N , which contributes to its functional alterations to facilitate Af -induced T H 2-mediated ABPA development. In terms of mechanism, Card9 wild-type ( Card9WT ) expression levels decreased significantly due to Af -induced decay of its messenger RNA compared to the heterozygous Card9S12N . In addition, ABPA patients with heterozygous CARD9S12N had increased Af -induced interleukin-5 production. CONCLUSION Our study provides the genetic evidence showing that the heterozygous mutation of CARD9S12N , followed by allele expression imbalance of CARD9S12N , facilitates the development of ABPA.
Humans ; Aspergillosis, Allergic Bronchopulmonary/complications* ; Aspergillus fumigatus/genetics* ; Asthma/genetics* ; Aspergillus ; Mutation/genetics* ; CARD Signaling Adaptor Proteins/genetics*

Objective:To investigate the clinicopathological features, differential diagnosis, treatment and prognosis of undifferentiated embryonal sarcoma of the liver (UESL).Methods:Five UESL cases operated on at Hunan Provincial People's Hospital from 2014 to 2021 were retrospectively analyzed. H&E and immunohistochemical staining were done for pathological observation.Results:The 5 UESL patients(two boys,three girls) were 0.5 to 15 years old, all underwent radical surgical resection. In 3 cases tumors located in right liver, 1 in left liver, 1 in both lobes. Radiographically and visually, the tumor is a large cystic solid mass, microscopically composed of myxoid stroma and undifferentiated stromal cells, with pleomorphic tumor giant cells and characteristic eosinophilic bodies. All 5 patients are now alive after surgical resection: 1 patient achieved disease-free survival of more than 91 months after surgery alone. Two patients had recurrence after surgery and received surgical resection plus chemotherapy or chemotherapy alone. They achieved survival of more than 35 and 16 months, respectively. Two patients were treated with chemotherapy or chemotherapy plus radiotherapy after surgery and survived more than 49 and 31 months without recurrence, respectively.Conclusions:UESL is a rare and highly malignant mesenchymal tumor with characteristic pathologic morphology. Radical resection is the key to the treatment for UESL, and chemotherapy and radiotherapy should be carried out after surgery.

Since December 2019, Corona Virus Disease (COVID-19), a new emerging infection disease occurred in Wuhan, has spread in 27 countries and regions. The clusters of many cases were reported with the epidemic progresses. We collected currently available information for 377 COVID-19 clusters (1 719 cases), excluded the hospital clusters and Hubei cases, during the period from January 1, 2020 to February 20, 2020. There were 297 family clusters (79%), case median 4; 39 clusters of dining (10%), case median 5; 23 clusters of shopping malls or supermarkets (6%), case median 13; 12 clusters of work units (3%), case median 6, and 6 clusters of transportation. We selected 325 cases to estimate the incubation period and found its range is 1 to 20 days, median was 7 days, and mode was 4 days. The analysis of the epidemic situation in a department store in China indicates that there is a possibility of patients as the source of infection during the incubation period of the epidemic. From February 5, 2020 to February 21, 2020, 634 persons were infected in the Diamond Princess Liner. All persons are susceptible to SARS-CoV-2. The older, patients during the incubation period and the worse environment may be the cause of the cases rising. The progress of the two typical outbreaks clearly demonstrates the spread of the early cases in Wuhan. Whatever happens, screening and isolating close contacts remains essential except for clinical treatment during the epidemic. Especially for the healthy people in the epidemic area, isolation is the key.

Objective A finite element analysis was conducted on the biomechanics of the locking plate and intramedullary nail fixation for the treatment of distal tibial fractures,and the resuhs were verified combined with clinical cases,so as to provide references for clinical treatment.Methods (1) Finite element analysis:the three-dimensional CT data of the lower limbs of a healthy male volunteer were used to establish a finite element model.The internal stress distribution of the tibial plateau was set to 60％ of the total load by intramedullary nail and locking plate respectively,and the tibia end was fixed effectively.400 N axial pressure load which equaled to that of adult knee joint during single axis standing was simulated.The equivalent stress and displacement of the model by different fixations were compared.(2) Clinical verification:a retrospective case control study was performed on the clinical data of 37 cases of distal tibia1 fractures treated with internal fixation from June 2015 to December 2016,including 17 cases in intramedullary nail group and 20 in locking plate group.The operation time,intraoperative blood loss,postoperative fracture healing time,and postoperative Johner-Wruhs score of patients were recorded for comprehensive assessment of recovery.Results (1) The finite element analysis results:the maximum stress value was 5.907 MPa for intramedullary nail and 5.821 MPa for locking plate model (P ＞0.05),respectively.The maximum displacement of intramedullary nail model was 2.313 mm,lower than that of locking plate fixation system (3.854 rmm) (P ＜ 0.05).(2) Clinical verification:the operation time and intraoperative blood loss of intramedullary nail were both lower than those of locking plate [(114.1 ±21.6)minutes):(129.8±21.4)minutes and (152.9 ±64.88)ml:(212.5 ±98.5)ml](P ＜0.05).The average fracture healing time was (17.7 ± 2.8)weeks for intramedullary nail and (20.6 ± 4.1) weeks for locking plate (P ＜ 0.05),respectively.In the intramedullary nail group,the Johner Wruhs score was excellent in 13 cases and good in four cases,with excellent and good rate of 100％,while in the locking plate group,nine cases were excellent,eight were good,and three were fair,with excellent and good rate of 85％ (P ＞ 0.05).Conclusions In terms of biomechanics and clinical effect,intramedullary nail fixation is superior than the medial locking plate fixation for the treatment of the distal tibial fractures.Intramedullary nail fixation can reduce surgical trauma and bone displacement after fixation and promote fracture healing.

BACKGROUND:Macropore morphology of a composite scaffold prepared by the three-dimensional printing technique is of great importance in determining the physicochemical and biological properties of tissue engineering scaffolds.OBJECTIVE:To fabricate strontium-containing mesoporous (Sr-MBG) bioactive glass (PCL) scaffolds by the three-dimensional printing technique, and to explore the effect of these scaffolds on MC3T3-E1 proliferation and osteogenic differentiation, thereby to find out the optimal macropore morphology.METHODS: Sr-MBG/PCL composite scaffolds were fabricated by the three-dimensional printing technique. The angles between fibrous latitudes and longitudes were set to 45°, 60° and 90°. Then the proliferation and alkaline phosphatase activity of MC3T3-E1 cells on the scaffolds were tested.RESULTS AND CONCLUSION: Cell counting kit-8 results showed that MC3T3-E1 cells could proliferate on all the three kinds of scaffolds. The proliferation rate of MC3T3-E1 cells on the 45° Sr-MBG/PCL scaffolds was just slightly higher than that on the 60° and 90° Sr-MBG/PCL scaffolds at days 1 and 4 (P > 0.05), but there was a significant increase at day 7 (P < 0.05). The 45° Sr-MBG/PCL scaffolds exhibited a significant increase in alkaline phosphatase activity of MC3T3-E1 cells compared to the 60° and 90° Sr-MBG/PCL scaffolds at day 14 (P < 0.05), while there was no significant difference among three groups at day 21 (P > 0.05). These results indicate that the 45° Sr-MBG/PCL scaffold is more suitable to promote the proliferation and osteogenic differentiation of the MC3T3 cells than the 60° and 90° Sr-MBG/PCL scaffolds.

BACKGROUND: Three-dimensional (3D) printing technique has showed unparalleled advantages in the field of tissue engineering scaffold preparation because of its outstanding merits of convenience, efficiency, controllability and ability to construct complex shapes.OBJECTIVE: To fabricate Fe-containing mesoporous calcium-silicate (MCS) /poly (3-hydroxybutyrate-co-3-hydroxyhexanoate) (PHBHHx) composite scaffolds using the 3D printing technique and to test the characterization and cellular biocompatibility of the composite scaffolds.METHODS: Four groups of Fe-containing MCS/PHBHHx composite scaffolds were fabricated using 3D printing technique. The molar percentage of Fe in these four groups was 0%, 5%, 10%, 15%, respectively and they were marked as 0Fe-MCS/PHBHHx, 5Fe-MCS/PHBHHx, 10Fe-MCS/PHBHHx and 15Fe-MCS/PHBHHx. The scanning electron microscopy was used to observe the microstructure of the scaffolds after being soaked in the simulated body fluid.Osteoblast cell lines MC3T3-E1 were seeded on these four groups of scaffolds as well. Cell counting kit-8 method was adopted to test the cell proliferation at 1, 3, 7 days of culture. Intracellular alkaline phosphatase activity was tested at 7 and 14 days of culture.RESULTS AND CONCLUSION: (1) Compared with the scaffolds with no soaking process, spherical particles were formed on the scaffolds because of mineralization after soaking 3 days in the simulated body fluid. (2) At 1 day of culture,there was no difference in cell proliferation among the four groups. At 3 days of culture, the proliferation rate of the 15Fe-MCS/PHBHHx scaffold was remarkably higher than that of the rest three groups (P < 0.05). At 7 days of culture,the proliferation rate was significantly higher in the 10Fe-MCS/PHBHH and 15Fe-MCS/PHBHHx scaffolds than the 0Fe-MCS/PHBHH scaffold (P < 0.05), as well as significantly higher in the 15Fe-MCS/PHBHHx scaffold than the 10Fe-MCS/PHBHH scaffold (P < 0.05). (3) At 7 days of culture, no difference in alkaline phosphatase activity could be found among these four groups of scaffolds; however, at 14 days, the 5Fe-MCS/PHBHHx, 10Fe-MCS/PHBHHx and 15Fe-MCS/PHBHHx scaffolds exhibited an enhanced alkaline phosphatase activity compared with the 0Fe-MCS/PHBHHx scaffold. Meanwhile, the 15Fe-MCS/PHBHHx showed the highest alkaline phosphatase activity.These findings indicate that the MCS/PHBHH scaffolds containing Fe could promote the proliferation and osteogenic differentiation of the MC3T3-E1 cells.

Taking 12-N-p-chlorobenzyl sophoridinol 2 as a lead, a series of novel sophoridinic derivatives with various 3'-substituents at the 11-side chain were synthesized and evaluated for their anticancer activity from sophoridine (1), a natural antitumor medicine. Among them, the sophoridinic ketones 5a-b, alkenes 7a-b and sophoridinic amines 14a-b displayed reasonable antiproliferative activity with IC50 values ranging from 3.8 to 5.4 μmol/L. Especially, compounds 5a and 7b exhibited an equipotency in both adriamycin (AMD)-susceptible and resistant MCF-7 breast carcinoma cells, indicating a different mechanism from AMD. The primary mechanism of action of 5a was to arrest the cell cycle at the G0/G1 phase, consistent with that of parent compound 1. Thus, we consider 12-chlorobenzyl sophoridinic derivatives with a tricyclic scaffold to be a new class of promising antitumor agents with an advantage of inhibiting drug-resistant cancer cells.

BACKGROUND: Compared with the metal screws, absorbable screws have more obvious advantages, such as does not have to conduct internal fixation removal, non-metal ic components, no influence on the magnetic resonance imaging of patients after implantation, relatively simple operations, namely dril ing-tapping-screws fixation, more in line with the principles of minimal y invasive in orthopedics. OBJECTIVE: To investigate the biomechanical characteristics of absorbable screw fixation in repair of simple lateral mal eolus fractures by means of finite element technology. METHODS: The three-dimensional model of simple lateral mal eolus fractures and absorbable screw model were established, and then fixed according to standard orthopedic surgical techniques. The reference load when the load bearing of fibulotalar joint reaching the peak value in a normal adult gait cycle was loaded. The stress distribution and displacement of fibula and absorbable screws were analyzed. RESULTS AND CONCLUSION: There were total y 38 542 units, 8 790 nodes in the single screw fixation model. When the articular facet of lateral mal eolus loading 300 N, the maximum stress of screws was 89.35 MPa, the maximum displacement was 0.5 mm, the maximum displacement of the distal fracture was 0.5 mm. When the articular facet of lateral mal eolus loading 450 N, the maximum stress of screws was 152.58 MPa, the maximum displacement was 0.59 mm, the maximum displacement of the distal fracture was 0.77 mm. There were total y 43 115 units, 9 496 nodes in the double screws fixation model. When the articular facet of lateral mal eolus loading 300 N, the maximum stress of screws was 38 MPa, the maximum displacement was 0.44 mm, the maximum displacement of the distal fracture was 0.44 mm. When the articular facet of lateral mal eolus loading 450 N, the maximum stress of screws was 66.68 MPa, the maximum displacement was 0.48 mm, the maximum displacement of the distal fracture was 0.49 mm. The experiment verified the biomechanical feasibility of absorbable screw fixation in repair of simple lateral mal eolus fractures. For simple involving only the lower lateral fibular fracture, absorbable screw fixation is entirely feasible, and usual y requires at least two screws to maintain the stability of the articular surface of the reset.

Retinoblastoma is the most common pediatric retinal tumor initiated by biallelic inactivation of the retinoblastoma gene ( RB1 ) , affecting roughly 1 in 15000 children with 1100 new cases each year.In China, RB remains a potentially devastating disease while lack of early diagnosis and aggressive treatment strategies.Moreover, RB patients individually show a variety of drug response to regular systemic chemotherapy since intensive chemotherapy and long-term follow-up are not as readily available.The majority of patients with advanced diseases require enucleation which affects the future quality of children life.Recent studies showed that alterations in genomics and epigenomics of RB play very important roles in RB progress and therapy.We thereby review current understanding changes of genomics and epigenomics in RB as potential prognostic and therapeutic targets.

With the recent understanding of cancer biology, physiopathology, and cancer genetics& genomics, new treatments and methodologies are constantly developed, including on the development and application of molecular targeted drugs for cancer therapy have been widespread concerned.Antibody-based drugs targeting over-expressed oncogenes or other functional proteins in cancer with its high specificity, less side-effects and significant clinical efficacy became rapidly the hot-spot of anti-tumor drug research.Currently, there are already more than 20 of anti-tumor antibody-based drugs approved for clinical application, and achieved remarkable results.This article summarizes the development and current situation of monoclonal antibody-based drug research for cancer therapy, as well as their anti-tumor mechanism of action.At the same time summarizes the new advances in cancer research in the field of monoclonal antibody drugs made,and its prospects as well as shortcomings were outlined.