A 65-year-old male patient was admitted for recurrent lymph node enlargement for 5 years and elevated creatinine for 6 months. This patient was diagnosed with angioimmunoblastic T-cell lymphoma 5 years ago and underwent multiple lines of anti-tumor therapy, including cytotoxic chemotherapy; epigenetic modifying drugs such as chidamide and azacitidine; the immunomodulator lenalidomide; and targeted therapy such as rituximab, a CD20-targeting antibody, and brentuximab vedotin, which targets CD30. Although the tumor was considered stable, multiple virus activation (including BK virus, JC virus, and cytomegalovirus) accompanied by the corresponding organ damage (polyomavirus nephropathy, cytomegalovirus retinitis, and progressive multifocal leukoencephalopathy) occurred during anti-tumor treatment. Anti-tumor therapy was suspended and ganciclovir was used. The serum viral load decreased and organ functions were stabilized. The purpose of this report was to raise clinicians′ awareness of opportunistic virus reactivation during anti-tumor treatment.

Purpose: The poor retention and ambiguous differentiation of stem cells (SCs) within corpus cavernosum (CC) limit the cell application in erectile dysfunction (ED). Herein, the effects and mechanism of microRNA-145 (miR-145) gene modification on modulating the traits and fate of bone marrow-derived mesenchymal stem cells (BMSCs) were investigated. Materials and Methods: The effects of miR-145 on cell apoptosis, proliferation, migration, and differentiation were determined by flow cytometry, cell counting kit-8, transwell assays and myogenic induction. Then, the age-related ED rats were recruited to four groups including phosphate buffer saline, BMSC, vector-BMSC, overexpressed-miR-145-BMSC groups. After cell transplantation, the CC were harvested and prepared to demonstrate the retention and differentiation of BMSCs by immunofluorescent staining. Then, the target of miR-145 was verified by quantitative real-time polymerase chain reaction and immunohistochemical. After that, APTO-253, as an inducer of Krüppel-like factor 4 (KLF4), was introduced for rescue experiments in corpus cavernosum smooth muscle cells (CCSMCs) under the co-culture system. Results: In vitro, miR-145 inhibited the migration and apoptosis of BMSCs and promoted the differentiation of BMSCs into smooth muscle-like cells with stronger contractility. In vivo, the amount of 5-ethynyl-2′-deoxyuridine (EdU)+cells within CC was significantly enhanced and maintained in the miR-145 gene modified BMSC group. The EdU/CD31 co-staning was detected, however, no co-staining of EdU/α-actin was observed. Furthermore, miR-145, which secreted from the gene modified BMSCs, dampened the expression of KLF4. However, the effects of miR-145 on CCSMCs could be rescued by APTO-253. Conclusions Overall, miR-145 modification prolongs the retention of the transplanted BMSCs within the CC, and this effect might be attributed to the modulation of the miR-145/KLF4 axis. Consequently, our findings offer a promising and innovative strategy to enhance the local stem cell-based treatments.

The spectrum of biopsy-confirmed kidney disease varies with regions and periods. We describe the distribution of pathological types and epidemiological characteristics of kidney diseases in Northwest China due to regional differences in geographical environment, social economy, and dietary habits. Methods: Kidney biopsy cases from 2005 to 2020 in Xijing Hospital were retrospectively analyzed. Pathological characteristics of patients in different periods were analyzed using the t test or chi-square test. Joinpoint regression was used to analyze trends in pathological types and disease spectrum. Results: A total of 10,528 eligible patients were included. Primary glomerular disease (PGD) accounted for the majority of the cases and exhibited an obvious downward trend, whereas secondary glomerular disease (SGD) showed an obvious upward trend. Among PGD, immunoglobulin A nephropathy (IgAN) remained the most common pathological type, and the detection rate of membranous nephropathy (MN) was significantly increased. Among SGD, Henoch-Schönlein purpura nephritis (HSPN) was the most common pathological type and may present a significant characteristic of Northwest China. Diabetic nephropathy (DN) exhibited the most obvious upward trend in the whole process, whereas the fastest growth since 2012 was in hypertensive nephropathy. Conclusion: The proportion of SGD increased whereas PGD declined. IgAN remained the most common PGD, and HSPN was the most common SGD. MN and DN showed the most obvious upward trend among PGD and SGD, respectively. Changes in the spectrum of kidney disease, especially the constituent ratio of SGD, pose a great challenge to public health.

Hepatitis B virus core protein (HBc) has become a hot spot in drug carrier protein research due to its natural particle self-assembly ability and ease of modification. The truncation of the C-terminal polyarginine domain (CTD, aa 151-183) of HBc does not affect the self-assembly of the particles. However, it does affect the internal and external charges of the particles, which may subsequently affect drug encapsulation. Thus, the truncated C-terminal polyarginine domain (CTD) of HBc and the inserted RGD peptide were selected to construct and express three HBc variants (RH) encapsulated with ICG (RH/ICG) with different C-terminal lengths to compare the stability and drug activity of their nanoformulations. RH160/ICG was found to have a great advantages in encapsulation efficiency and biological imaging. Compared with other HBc variants, RH160/ICG significantly improved encapsulation efficiency, up to 32.77%±1.23%. Cytotoxicity and hemolysis assays further demonstrated the good biocompatibility of RH160/ICG. Cell uptake and in vivo imaging experiments in mice showed that RH160/ICG could efficiently deliver ICG in tumor cells and tumor sites with good imaging effect. This research provides a new direction for further expanding the diagnosis and treatment application of ICG and development of HBc-based nanoparticle drug carrier platform.
Animals ; Hepatitis B/drug therapy* ; Hepatitis B Core Antigens ; Indocyanine Green/chemistry* ; Mice ; Nanoparticles/chemistry* ; Viral Core Proteins

Objective:To study the effects of reactive oxygen species (ROS)-responsive antibacterial microneedles (MNs) on the full-thickness skin defect wounds with bacterial colonization in diabetic mice.Methods:Experimental research methods were adopted. The ROS-responsive crosslinker N1-(4-boronobenzyl)-N3-(4-boronophenyl)-N1, N1, N3, N3-tetramethylpropane-1,3-diaminium (TSPBA) was first synthesized, and then the polyvinyl alcohol (PVA)-TSPBA MNs, PVA-ε-polylysine (ε-PL)-TSPBA MNs, PVA-TSPBA-sodium hyaluronate (SH) MNs, and PVA-ε-PL-TSPBA-SH MNs were prepared by mixing corresponding ingredients, respectively. The PVA-TSPBA MNs were placed in pure phosphate buffer solution (PBS) and PBS containing hydrogen peroxide, respectively. The degradation of MNs immersed for 0 (immediately), 3, 7, and 10 days was observed to indicate their ROS responsiveness. The standard strains of Staphylococcus aureus ( S. aureus) and Escherichia coli (E. coli) cultured in Luria-Bertani medium containing hydrogen peroxide were divided according to the random number table (the same grouping method below) into blank control group (without any treatment, the same below) and 0 g/L ε-PL group, 1.0 g/L ε-PL group, 5.0 g/L ε-PL group, and 10.0 g/L ε-PL group with which PVA-ε-PL-TSPBA MNs containing the corresponding concentration of ε-PL were co-cultured, respectively. Bacterial growth was observed after 24 h of culture, and the relative survival rate of bacteria was calculated ( n=3). The mouse fibroblast cell line 3T3 cells at logarithmic growth stage (the same growth stage below) were divided into blank control group and 0 g/L ε-PL group, 1.0 g /L ε-PL group, 5.0 g /L ε-PL group, and 10.0 g /L ε-PL group in which cells were cultured in medium with the extract from PVA-ε-PL-TSPBA MNs containing the corresponding concentration of ε-PL, respectively. Cell growth was observed after 24 h of culture by optical microscopy, and the relative survival rate of cells was detected and calculated by cell counting kit 8 (CCK-8) assay to indicate the cytotoxicity ( n=6). Both PVA-TSPBA MNs and PVA-TSPBA-SH MNs were taken, the morphology of the two kinds of MNs was observed by optical microscopy, and the mechanical properties of the two kinds of MNs were tested by microcomputer controlled electronic universal testing machine (denoted as critical force, n=6). Six male BALB/c mice aged 6-8 weeks (the same gender and age below) were divided into PVA-TSPBA group and PVA-TSPBA-SH group, with 3 mice in each group. After pressing the skin on the back of mice vertically with the corresponding MNs for 1 minute, the skin condition was observed at 0, 10, and 20 min after pressing. Another batch of 3T3 cells were divided into blank control group, 0 g/L ε-PL group and simple 5.0 g/L ε-PL group which were cultured with the extract of PVA-ε-PL-TSPBA MNs containing the corresponding concentration of ε-PL, and 5.0 g/L ε-PL+SH group which were cultured with the extract of PVA-ε-PL-TSPBA-SH MNs with 5.0 g/L ε-PL. The CCK-8 assay was performed to detect and calculate the relative survival rate of cells cultured for 24, 48, and 72 h to indicate the cell proliferation activity ( n=6). Eighteen BALB/c mice were induced into diabetic mice model by high-sugar and high-fat diet combined with streptozotocin injection and then divided into sterile dressing group, 0 g/L ε-PL+SH group, and 5.0 g/L ε-PL+SH group, with 6 mice in each group. A full-thickness skin defect wound was made on the back of each mouse, and S. aureus solution was added to make a full-thickness skin defect wound with bacterial colonization model for diabetic mouse. The wounds of mice in 0 g/L ε-PL+SH group and 5.0 g/L ε-PL+SH group were covered with PVA-ε-PL-TSPBA-SH MNs with the corresponding concentration of ε-PL, and the wounds of mice in the 3 groups were all covered with sterile surgical dressings. The wound healing was observed on post injury day (PID) 0, 3, 7, and 12, and the wound healing rate on PID 3, 7, and 12 was calculated. On PID 12, the skin tissue of the wound and the wound margin were stained with hematoxylin and eosin to observe the growth of new epithelium and the infiltration of inflammatory cells. Data were statistically analyzed with one-way analysis of variance, analysis of variance for repeated measurement, Mann-Whitney U test, and Bonferroni test. Results:With the extension of the immersion time, the PVA-TSPBA MNs in PBS containing hydrogen peroxide gradually dissolved and completely degraded after 10 days of immersion. The PVA-TSPBA MNs in pure PBS only swelled but did not dissolve. After 24 h of culture, there was no growth of S. aureus in 5.0 g/L ε-PL group or 10.0 g/L ε-PL group, and there was no growth of E. coli in 10.0 g/L ε-PL group. The relative survival rate of S. aureus was significantly lower in 1.0 g/L ε-PL group, 5.0 g/L ε-PL group, and 10.0 g/L ε-PL group than in blank control group ( P<0.05 or P<0.01). The relative survival rate of E. coli was significantly lower in 5.0 g/L ε-PL group and 10.0 g/L ε-PL group than in blank control group ( P<0.01). After 24 h of culture, the cells in blank control group, 0 g/L ε-PL group, 1.0 g/L ε-PL group, 5.0 g/L ε-PL group, and 10.0 g/L ε-PL group all grew well, and the relative survival rate of cells was similar among the groups ( P>0.05). The needle bodies of PVA-TSPBA MNs and PVA-TSPBA-SH MNs were both quadrangular pyramid-shaped and neatly arranged, and the needle bodies of PVA-TSPBA-SH MNs was more three-dimensional and more angular. The critical force of PVA-TSPBA-SH MNs was significantly higher than that of PVA-TSPBA MNs ( Z=3.317, P<0.01). The MNs in PVA-TSPBA+SH group penetrated the skin of mice at 0 min after pressing, and the pinholes partially disappeared after 10 min and completely disappeared after 20 min, while the MNs in PVA-TSPBA group failed to penetrate the skin of mice. After 24, 48, and 72 h of culture, the proliferation activity of the cells in 5.0 g/L ε-PL+SH group was significantly higher than that of blank control group ( P<0.05 or P<0.01). In sterile dressing group, the wounds of mice healed slowly and exuded more. The wound healing speed of mice in 0 g/L ε-PL+SH group was similar to that of sterile dressing group in the early stage but was faster than that of sterile dressing group in the later stage, with moderate exudation. The wound healing of mice in 5.0 g/L ε-PL+SH group was faster than that in the other two groups, with less exudation. The wound healing rates of mice in 5.0 g/L ε-PL+SH group were (40.6±4.2)%, (64.3±4.1)%, and (95.8±2.4)% on PID 3, 7, and 12, which were significantly higher than (20.4±2.7)%, (38.9±2.2)%, and (59.1±6.2)% in sterile dressing group and (21.6±2.6)%, (44.0±1.7)%, and (82.2±5.3)% in 0 g/L ε-PL+SH group ( P<0.01). The wound healing rates of mice in 0 g/L ε-PL+SH group on PID 7 and 12 were significantly higher than those in sterile dressing group ( P<0.05 or P<0.01). On PID 12, the wounds of mice in 5.0 g/L ε-PL+SH group were almost completely epithelialized with less inflammatory cell infiltration, the wounds of mice in 0 g/L ε-PL+SH group were partially epithelialized with a large number of inflammatory cell infiltration, and no obvious epithelialization but a large number of inflammatory cell infiltration was found in the wounds of mice in sterile dressing group. Conclusions:The composite MNs prepared by TSPBA, PVA, ε-PL, and SH can successfully penetrate mouse skin and slowly respond to ROS in the wound to resolve and release antibacterial substances, inhibit bacterial colonization, and promote the repair of full-thickness skin defect wounds with bacterial colonization in diabetic mice.

OBJECTIVE: To explore the pathogenesis of two fetuses from one family affected with Joubert syndrome (JS). METHODS: Whole exome sequencing was employed to screen potential mutations in both fetuses. Suspected mutations were verified by Sanger sequencing. Impact of intronic mutations on DNA transcription was validated by cDNA analysis. RESULTS: Two novel TCTN1 mutations, c.342-8A>G and c.1494+1G>A, were identified in exons 2 and 12, respectively.cDNA analysis confirmed the pathogenic nature of both mutations with interference of normal splicing resulting in production of truncated proteins. CONCLUSION The genetic etiology of the family affected with JS has been identified.Above findings have enriched the mutation spectrum of TCTN1gene and facilitated understanding of the genotype-phenotype correlation of JS.
Abnormalities, Multiple ; diagnosis ; genetics ; Cerebellum ; abnormalities ; Eye Abnormalities ; diagnosis ; genetics ; Humans ; Kidney Diseases, Cystic ; diagnosis ; genetics ; Membrane Proteins ; genetics ; Mutation ; Pedigree ; Retina ; abnormalities ; Whole Exome Sequencing

OBJECTIVE: To explore the genetic cause for a patient with intellectual disability, short stature and multiple congenital anomalies, and to correlate the result with the clinical phenotype. METHODS: Routine karyotyping analysis was carried out on GTG-banded metaphase chromosomes. Single nucleotide polymorphism (SNP) microarray was used to detect microdeletions or microduplications in the patient. Fluorescence in situ hybridization (FISH) was used to ascertain the origin of aberrant chromosomes. RESULTS: The karyotype of the patient was 46,XY,der(18), while both of his parents had a normal karyotype. SNP array identified a 1.23 Mb deletion at 18p11.32-pter (chr18: 136 227-1 370 501, hg19) and a 33.76 Mb duplication at 18q21.1-qter (chr18: 44 250 359-78 013 728, hg19) in the patient. Above finding was confirmed by dual-color FISH with one color for 18p and another for 18q. The patient presented with some common features of 18p deletion and 18q duplication including intellectual disability and growth retardation, in addition with some features of 18p deletion including pectus excavatum, short stature and growth hormone (GH) deficiency. The patient showed progressive improvement of stature with GH therapy. Comparison of patients with previously reported dup(18q)+del(18p) recombinations suggested that, even for patients with similar breakpoints, their phenotypes have ranged from normal to severe and there were no consistent findings. CONCLUSION As aberrations involving double chromosomal segments often result in phenotypic variability, it has been difficult to correlate the genotype of our patient with his phenotype.
Abnormalities, Multiple ; Chromosome Deletion ; Chromosomes, Human, Pair 18 ; Genotype ; Humans ; In Situ Hybridization, Fluorescence ; Karyotyping ; Monosomy ; Phenotype ; Trisomy

Objective: To analyze the status of personnel in occupational disease prevention and treatment institutions in Hunan Province, China, from 1996 to 2015, to predict staff composition using grey model (GM) (1, 1) , and to provide a scientific basis and reference for optimizing human resource planning of occupational disease prevention and treatment in other provinces and regions and promoting the service capacity of the institutions. Methods: The data of the staff in occupational disease prevention and treatment institutions in Hunan Province, China, from 1996 to 2015 were obtained from the established basic information management system. The descriptive analysis method was used to analyze the dynamic changes in number and composition of the staff and the GM (1, 1) was used to predict the staff composition. Results: The numbers of the staff members in 1996 and 2015 in occupational disease prevention and treatment institutions in Hunan Province, China were 1591 and 1429, respectively. In the twenty years, the main education level of the staff transformed from "technical secondary school education and non-academic qualifications" to "bachelor degree or above and college degree"; the main major of the staff transformed from "other majors" to "public health and clinical medicine"; the proportion of the staff members without professional titles changed from >1/3 to 5%; and the proportions of the staff members with senior, intermediate, and junior professional titles were steadily rising. GM prediction showed that the proportions of highly educated staff members in 2018 and 2020 would be up to 41.00% and 45.61%, respectively; and the proportions of the staff members with a major in public health in 2018 and 2020 would be up to 44.15% and 46.60%, respectively. Conclusion The staff in occupational disease prevention and treatment institutions in Hunan Province, China, in the twenty years have slight changes in staff size and great improvement in staff quality, which is beneficial to sustainable development of the occupational disease prevention and treatment undertakings. The education level and major will be further optimized in the next five years.

OBJECTIVETo identify a rare subtype of the ABO blood group system and explore its molecular basis.

METHODSBased on a standard serological assay, ABO subtype and haplotype were analyzed through PCR amplification of the 7 exons and adjacent introns of the ABO gene and TA clone sequencing.

RESULTSForward typing showed a B type, while reverse typing demonstrated an extremely weak anti-B on routine gel analysis, which indicated a forward and reverse typing discrepancy. Absorption-elution testing confirmed that there was no A antigen on the surface of patient's red blood cells. Sequencing of the ABO gene showed a G>A exchange at position 523 in exon 7, which resulted in a Val to Met substitution at codon 175. Clone sequencing of the amplificons of the ABO gene showed an ABO* Bw14/O01 heterozygote genotype.

CONCLUSIONMolecular method is useful for the identification of ambiguous blood groups. A 523G>A substitution of the ABO gene resulting in a Bw14 subtype probably underlies the weak B phenotype noted in the patient.

With the continuously exploration,in recent years,further understanding of anatomical characteristics of the cervical pedicle brings great breakthrough in cervical pedicle screw implantation.In addition,pedicle screw implantation in cervical spine is considered as a technique with high safety and reliability,which can be widely used in cervical trauma fracture,cervical instability,degenerative,inflammatory,benign or malignant tumor,deformity and other neck diseases.Because of the tremendous differences between upper cervical spine (C1,C2) and lower cervical spine (C3-7) in anatomical morphology,cervical pedicle screw implantation in C1 and C2 differs from in lower cervical spine.Due to the similar structure of C3-7,pedicle screw implantation methods are based on the same principle and sharing a few points in common.The pedicle screw technique can be classified in two groups according to the practice methods:navigation technology and manual placement of cervical pedicle screw.Navigation nailing is considered as reliable,easy handing,and with clear operative vision,however,with disadvantages as complex procedures,highly cost operation equipment,and risk in navigation draft.Therefore,manual placement of pedicle screw is more reasonable and practical comparing with the former.In this study,it analyzed anatomical characteristics of lower cervical pedicle and the measurement of pedicle structure,discussed technique of manual placement of pedicle screw in lower cervical spine and biomechanical study of pedicle screw,and summed up the comparison of the advantages and disadvantages of current representative manual placement technology.