Objective To investigate the value of one-stage lymphatics-venous anastomosis in radical mastectomy of breast cancer to prevent post-mastectomy upper limb lymphedema.Methods Ninety patients requiring radical mastectomy of breast cancer in Tangshan Tumor Hospital Affiliated to North China University of Science and Technology from March 2010 to May 2013 were collected as the objects.They were divided into the control group (45 cases) and the treatment group (45 cases) using block randomized grouping (concealment of allocation).Both groups underwent radical mastectomy of breast cancer, and the treatment group was treated with one-stage lymphatics-venous anastomosis on the basis of radical mastectomy.The operation times, amount of bleeding, hospitalization times, postoperative complications and the numbers of axillary lymph node dissection of the patients in the two groups were compared, and the postoperative upper limb lymphedema incidence rates of the patients in the two groups were compared.Results The operative times of the patients in the treatment group and the control group were (152.82 ± 18.76) min and (78.92 ± 10.33) min respectively, and amount of bleeding were (416.64 ± 94.65) ml and (250.84 ± 63.17) ml, with statistical significances (t =-20.39, P =0.00;t =-4.48, P =0.00).The average hospitalization times of the patients in the treatment group and the control group were (14.91 ± 5.44) d and (13.45 ± 2.36) d respectively, the numbers of axillary lymph node dissection were 14.63 ± 3.37 and 14.37 ± 3.18, the numbers of postoperative complications occurred were 9 cases (20.00％) and 5 cases (11.11％), with no statistical significances (t =-0.47, P =0.64;t =0.75, P =0.46;x2 =1.35, P =0.38).Compared with the control group, the treatment group has lower incidence of upper extremity lymphedema (13.95％ vs.40.91％) and lower swelling degree, with statistical significance (x2 =8.48, P =0.03).Conclusion One-stage lymphatics-venous anastomosis in radical masteetomy of breast cancer can effectively transfer lymph diversion to the venous circulation and reduce the incidence of limb lymphedema, which has significant preventive effect.

Two cases of frontal fibrosing alopecia (FFA) were reported.Case 1,a 44-year-old woman,presented with progressive recession of the frontotemporal hairline for 4 years and multiple skincolored facial papules for 2 years.Skin examination showed that the frontotemporal hairline was receded,the local skin was smooth and thin,and a few remaining fine hairs could be seen.Additionally,eyebrows,axillary and pubic hairs were partly shed,and plenty of millet-sized skin-colored papules were diffusedly distributed on the frontotemporal region and bilateral mandibular angles.Dermatoscopy showed reduced hair follicular openings,different hair shaft diameters,cicatricial white patches and perifollicular erythema.Case 2,a 55-year-old woman,presented with progressive frontotemporal hair loss for 2 years.Skin examination revealed the recession of bilateral frontotemporal hairline and partial loss of eyebrows,axillary and pubic hairs.Histopathological examinations of the 2 patients both revealed perifollicular infiltration of lymphocytes,liquefaction degeneration of basal cells and perifollicular lamellar fibrosis.Clinical manifestations and histopathological features of the 2 patients both confirmed the diagnosis of FFA.

Objective To induce the mutation of HPV-16 E7 in two zinc-binding motifs near the C terminus by polymerase chain reaction (PCR) and evaluate the effect of this mutation on the antigen-specific immunity of HPV-16 E7. Methods HPV-16 E7 fragment was amplified by PCR and cloned into pGEM-3zf vector. Two site mutations at 58 and 91 animo acid sites in the open reading frame of HPV-16 E7 were induced by PCR, and then the molecular clones of HPV-16 E7 wild type (pcDNA3.1/E7) and mutant (pcDNA3.1/ME7) were successfully reconstructed. Western blot and immunofluorescence were used to detect the expression of E7 protein. Results Intracellular fluorescence signals were observed in the cells transfected with pcDNA3.1/E7 and pcDNA3.1/ME7 24 hours after transfection, but the signals in the cells transfected with pcDNA3.1/ME7 disappeared 48 hours after tansfection. Twenty-four and 48 hours after transfection with pcDNA3.1/ME7, E7 protein was not detected by Western blot. Conclusions The stability of HPV-16 E7 protein is reduced by mutations (C58G, C91G) near two zinc-binding motifs. It is suggested that the zinc-binding motifs near the C terminus of HPV-16 E7 may be important for maintaining the stability of E7 protein.

OBJECTIVETo identify the genetic etiology in a Chinese patient with neurofibromatosis type 1 (NF-1).

METHODSAll coding exons and the flanking sequences of neurofibromin 1 (NF1) gene from the patient were captured, individually barcoded and subjected to HiSeq2000 high-throughput sequencing. Suspected mutation was validated in the nuclear family members with Sanger sequencing.

RESULTSA novel indel mutation, c.789_790delAGinsT, was identified in the exon 8 of the NF1 gene in the patient but not in her asymptomatic parents. The mutation was predicted to have caused shifting of the reading frame and a premature downstream stop codon (p.K263Nfs*18). Two known polymorphisms, c.888+108 C>T (rs2953000) and c.888+118 G>T (rs2952999), was detected in the flanking of the indel mutation in the patient and her father. Sequencing chromatogram for the family indicates that above changes are located on the same chromosome.

CONCLUSIONThe c.789_790delAGinsT, as a de novo mutation occurring on the paternally derived chromosome, is most likely to be causative for the disease. Compared with Sanger sequencing, targeted next-generation sequencing is more efficient and can dramatically reduce the cost for the genetic testing of NF-1.

Adult ; Amino Acid Sequence ; Base Sequence ; Female ; Humans ; Molecular Sequence Data ; Neurofibromatosis 1 ; enzymology ; genetics ; Neurofibromin 1 ; genetics ; metabolism ; Point Mutation

Lateral epicondylitis is a common clinical disease with characteristics of lateral elbow pain, insidious onset and easy recurrence, which can cause forearm pain and decreased wrist strength, seriously affecting patients′ daily life and work. Although there are various treatment methods for lateral epicondylitis with different effects, standard treatments are still lacking nowadays. Platelet-rich plasma (PRP) has good effects on bone and tendon repair, and is now widely used in the treatment of lateral epicondylitis. However, there is a lack of a unified understanding of the technology and specifications of PRP in the treatment of lateral epicondylitis. Therefore, the Sports Medicine Branch of the Chinese Medical Association and Physical Medicine and Rehabilitation Branch of the Chinese Medical Association organized experts in the fields of sports medicine and rehabilitation medicine in China to formulate the "clinical expert consensus on platelet-rich plasma treatment for lateral epicondylitis (2022 version)", and proposed suggestions based on evidence-based medicine mainly from the concept, epidemiology and pathophysiology of lateral epicondylitis, symptoms, signs and imaging manifestations of lateral epicondylitis, PRP concept and application component requirements, quality control of PRP preparation technology, indications and contraindications of PRP in the treatment of lateral epicondylitis, PRP injection in the treatment of lateral epicondylitis, application of PRP in the operation of lateral epicondylitis, related problems after PRP treatment of lateral epicondylitis, evaluation of the results after PRP treatment of lateral epicondylitis, and health and economic evaluation of PRP treatment of lateral epicondylitis, so as to provide guidance for clinical diagnosis and treatment.

Cough variant asthma （CVA） is a chronic respiratory disease with cough as its main symptom. The occurrence of CVA is closely related to non-specific airway inflammation， and its pathogenesis involves environmental， genetic， immune， and other factors. In recent years， the advantages of traditional Chinese medicine （TCM） in the treatment of CVA have attracted the attention of experts and scholars in China and abroad， especially its prominent role in regulating immune balance， relieving cough symptoms in CVA patients， and reducing recurrence. T Helper cells 1 （Th1）， T helper cells 2 （Th2）， T helper cells 17 （Th17）， and regulatory T cells （Treg） are derived from CD4⁺ T cells. Immune imbalance of Th1/Th2 and Th17/Treg is a new hotspot in the pathogenesis of CVA and a potential key target in the treatment of CVA by TCM. Th cell subsets are in dynamic balance under physiological conditions， maintaining respiratory immune homeostasis in which pro-inflammatory cytokines and anti-inflammatory cytokines are balanced. Immature helper T cells （Th0） can be differentiated into Th1， Th2， Th17， Treg， and other cell subsets due to cytokine types in the microenvironment in the stage of CVA maturation. The proliferation of Th2 cells leads to eosinophilic airway inflammation. Excessive differentiation of Th17 cells induces neutrophil airway inflammation. Th1/Th2 and Th17/Treg cells are mutually restricted in number and function， and the immune imbalance of Th1/Th2 and Th17/Treg is easy to aggravate the generation of inflammatory response. Restoring immune balance is particularly important for the airway anti-inflammatory therapy of CVA. In this paper， the imbalance of Th1/Th2 and Th17/Treg and the pathogenesis of CVA were systematically expounded. Meanwhile， the latest research on the regulation of immune imbalance by TCM compound， single TCM， and its effective ingredients in the treatment of CVA was reviewed. It provides ideas and references for revealing the scientific connotation of TCM regulating immune balance therapy of CVA， as well as the development of clinical treatment and basic research of CVA.

Mutations or inactivation of parkin, an E3 ubiquitin ligase, are associated with familial form or sporadic Parkinson's disease (PD), respectively, which manifested with the selective vulnerability of neuronal cells in substantia nigra (SN) and striatum (STR) regions. However, the underlying molecular mechanism linking parkin with the etiology of PD remains elusive. Here we report that p62, a critical regulator for protein quality control, inclusion body formation, selective autophagy and diverse signaling pathways, is a new substrate of parkin. P62 levels were increased in the SN and STR regions, but not in other brain regions in parkin knockout mice. Parkin directly interacts with and ubiquitinates p62 at the K13 to promote proteasomal degradation of p62 even in the absence of ATG5. Pathogenic mutations, knockdown of parkin or mutation of p62 at K13 prevented the degradation of p62. We further showed that parkin deficiency mice have pronounced loss of tyrosine hydroxylase positive neurons and have worse performance in motor test when treated with 6-hydroxydopamine hydrochloride in aged mice. These results suggest that, in addition to their critical role in regulating autophagy, p62 are subjected to parkin mediated proteasomal degradation and implicate that the dysregulation of parkin/p62 axis may involve in the selective vulnerability of neuronal cells during the onset of PD pathogenesis.
Adaptor Proteins, Signal Transducing ; chemistry ; metabolism ; Animals ; HEK293 Cells ; Heat-Shock Proteins ; chemistry ; metabolism ; Humans ; Lysine ; metabolism ; Mice ; Neurons ; metabolism ; pathology ; Oxidopamine ; pharmacology ; Parkinson Disease ; metabolism ; pathology ; Proteasome Endopeptidase Complex ; metabolism ; Protein Stability ; Proteolysis ; drug effects ; Sequestosome-1 Protein ; Ubiquitin-Protein Ligases ; metabolism ; Ubiquitination ; drug effects