[Remodeling midwifery by introducing sterilization in childbirth in the period of Republic of China].

In the period of the Republic of China, the maternal and infant mortality rates were high, most of which were caused by puerperal fever and neonatal tetanus. In this sense, Chinese traditional midwives were often regarded as "dirty". After western obstetrics was introduced into China in the late Qing Dynasty and the early period of the Republic of China,the occurrence of postpartum infection was effectively reduced with childbirth disinfection. To improve the health status of women and infants, the government of the Republic of China put in place measures to develop midwifery. The training of the traditional midwives was included in midwifery education. The delivery basket was used to help promote the new method of delivery and popularise the concept of sterilization of delivery. Thus, midwifery was remodeled and the remodeled midwives played an important role in family midwifery education.

[Cheng Zhifan and the Chinese Journal of Medical History].

Professor Cheng Zhifan (1922-2018), was a famous contemporary Chinese medical historian and medical history educator, who successively served as the deputy editor in chief, editor in chief and honorary editor in chief for the Chinese Journal of Medical History. He developed the Chinese Journal of Medical History into an important academic journal in the field of Chinese medical history. He had his 46 papers published in the Chinese Journal of Medical History. The papers published in his youth and middle age focused on the study of western medical history. In his later years, he shifted the focus of his research into the education of medical history and the comparative study of Chinese and Western medicine. He devoted his life to teaching and research of medical history, paid close attention to the Chinese Journal of Medical History and made an important contribution to the development of medical history.

[The evolution and development of palliative and hospice care].

Palliative and Hospice Care initially developed in Great Britain. It was founded by Cicely Saunders for the humane care of terminally ill cancer patients and her institution was established as the first modern hospice in England. The concept developed gradually into a systematic medical program for terminal ill patients and was subsequently been generalised worldwide. The palliative and hospice care model currently in Taiwan of China is characterised by the joint participation of the government and society. This experience and knowledge is expected to contribute to the system of palliative and hospice care in the process of being established in the mainland of China.

[Controversy and progress on whether to retain left colonic artery in radical resection of rectal cancer].

Japanese Society for Cancer of the Colon and Rectum (JSCCR) guideline 2019 recommended that lymph node dissection for advanced rectal cancer should include the lymphatic adipose tissue at the root of the inferior mesenteric vessels, but the ligation site of the inferior mesenteric artery (IMA) was not determined, and the NCCN guideline did not indicate clearly whether to retain the left colonic artery (LCA). Controversy over whether to retain LCA is no more than whether it can reduce the incidence of anastomotic complications or postoperative functional damage without affecting the patients' oncological outcome. Focusing on the above problems, this paper reviews the latest research progress. In conclusion, it is believed that the advantages of retaining LCA are supported by most studies, which can improve the blood supply of the proximal anastomosis, and technically can achieve the same range of lymph node dissection as IMA high ligation. However, whether it affects the survival of patients, reduces the incidence of anastomotic leakage, and improves the quality of life of patients, more high-quality evidence-based medical evidence is still needed.

[The progress and challenges in immunotherapy for the difficulty- to- treat liver diseases].

As a digestive organ, the liver has the functions of metabolism, synthesis, and detoxification. It is also an immune organ and plays an important role in maintaining anti-infection, autoimmune stability, and anti-tumor. In particular, the liver has unique immunological advantages. Its immune cells can maintain the liver's immune homeostasis and participate in immunoregulation. A variety of immunotherapy is used in clinical trials for the treatment of difficult and critical liver diseases. This review mainly summarizes the recent clinical trials of immunotherapy in chronic hepatitis B, cirrhosis, hepatocellular carcinoma, and autoimmune liver disease.

[Orexin-A inhibits γ-aminobutyric acid current of neonatal rat spinal cord ventral horn neurons by activating OX1R, OX2R and Ca2+-independent PKC].

OBJECTIVE: To investigate the effect of orexin-A on the functionality of ionotropic γ-aminobutyric acid (GABA) receptors in spinal cord ventral horn neurons and its mechanisms. OBJECTIVE: The spinal cord containing the lumbosacral enlargement was isolated from neonatal SD rats (7-12 days old) and sliced. The slices were digested with papain (in 0.18 g/30 mL artificial cerebrospinal fluid) for 40-60 min, and the ventral horn neurons were separated acutely using fire-polished Pasteur pipettes. After the cells adhered to the bottom of Petri dishes, patch-clamp experiments combined with pharmacological methods were performed to test the effects of orexin-A on GABA currents of the neurons treated with SB334867 (a selective OX1R antagonist), TCSOX229 (a selective OX2R antagonist), Bis-Ⅳ (a PKC inhibitor), PMA (a PKC agonist), Rp-cAMP (a PKA inhibitor), or BAPTA (Ca2+ chelator). OBJECTIVE: The isolated neurons maintained good morphologies with diverse shapes of cell body and long protrusions. Treatment with orexin-A significantly inhibited the amplitude of GABA-induced current (P < 0.001, n=49) with an inhibition rate of (67.48±12.50)%. SB334867 and TCSOX229, when applied simultaneously, completely abolished the suppressive effect of orexin-A on the GABA currents (P=0.93, n=6), and their separate use partially relieved the suppressive effect of orexin-A (P=0.001, n=8; P=0.02, n=8). The application of Bis-Ⅳ also abolished the suppressive effect of orexin-A on GABA currents (P=0.31, n=5). PMA mimicked the effect of orexin-A in these neurons and significantly inhibited GABA currents with an inhibition rate of (60.79±10.94)%, and the application of orexin-A did not cause further suppression of GABA currents in PMA-treated neurons (P=0.15, n=6). Orexin-A was still capable of suppressing GABA currents in Rp-cAMP-treated neurons (P=0.001, n=5). The extracellular Ca2+-free solution (P=0.004, n=8) or the presence of BAPTA (P=0.04, n=7) did not significantly affect the inhibitory effect of orexin-A on GABA currents. OBJECTIVE: Orexin-A inhibits GABA currents in the ventral horn neurons of rat spinal cord probably by activating OX1R, OX2R and Ca2+-independent PKC.

[Reminiscing the pioneers of modern nursing during Covid-19 epidemic: 200th anniversary of Florence Nightingale's birth].

Before Florence Nightingale, nurses lacked special skills and training. The nursing mainly relied on nurse's religious passion and feelings to carry out nursing activities, and some vulgar and ignorant women took care of the job. Nightingale, who well-educated, born in an aristocratic family, devoted herself to nursing career despite the opposition of her family. She travelled around the world to investigate the hospital and nursing status. Nightingale practiced her concept of nursing work in the Crimean war. After the investigation of the wounded soldiers, she pointed out that the high mortality rate of British soldiers was related to poor nursing. She put forward suggestions to strengthen military nursing education; then she established modern nursing education institutions and created a new nursing education model, which was the beginning of modern nursing career.

HSP90 stabilizes B-cell receptor kinases in a multi-client interactome: PU-H71 induces CLL apoptosis in a cytoprotective microenvironment.

Chronic lymphocytic leukemia (CLL) is characterized by the accumulation of B cells in the hematopoietic system and lymphoid tissues. Although inhibitors targeting the B-cell receptor (BCR) pathway have been successful in the treatment of the disease, the underlying mechanisms leading to BCR over-activity in CLL are not fully understood. In this study, we found that HSP90, a highly conserved molecular chaperone, is overexpressed in CLL compared with resting B cells. HSP90 overexpression is accompanied by the overexpression of several BCR kinases including LYN, spleen tyrosine kinase, Bruton tyrosine kinase and AKT. Chemical and immune-precipitation demonstrated that these BCR constituents are present in a multi-client chaperone complex with HSP90. Inhibition of HSP90 with PU-H71 destabilized the BCR kinases and caused apoptosis of CLL cells through the mitochondrial apoptotic pathway. Further, PU-H71 induced apoptosis in the presence of stromal co-culture or cytoprotective survival signals. Finally, genetic knockdown of HSP90 and its client AKT, but not BTK, reduced CLL viability. Overall, our study suggests that the chaperone function of HSP90 contributes to the over-activity of the BCR signaling in CLL and inhibition of HSP90 has the potential to achieve a multi-targeting effect. Thus, HSP90 inhibition may be explored to prevent or overcome drug resistance to single targeting agents.

Spinal protein kinase Mζ contributes to the maintenance of peripheral inflammation-primed persistent nociceptive sensitization after plantar incision.

BACKGROUND: Previous studies suggest that persistent post-surgical pain (PPSP) is correlated with preoperative pain status and amplification of central sensitization. Protein kinase Mζ (PKMζ) is an essential substrate of the late long-term potentiation underlying central sensitization, which is one mechanism of pain memory formation. However, the potential contributions of spinal PKMζ to PPSP, a condition in which preoperative pain is prevalent, are not known. METHODS: Here, a modified 'hyperalgesia priming' model was established to simulate the clinical situation. This model used intraplantar injections of carrageenan (Car) as priming stimuli to elicit persistent nociceptive sensitization after plantar incision in rats. Upon treatment with PKMζ inhibitor ZIP, Scr-ZIP or protein kinase Cs (PKCs) inhibitor NPC-15437, altered behaviour and spinal PKMζ/PKCs expression were observed. RESULTS: A long-lasting hypersensitivity induced by Car-priming was identified and precipitated by subsequent plantar incision in this 'two-hit' paradigm. Post-treatment with ZIP, but not Scr-ZIP and NPC-15437, after the resolution of Car-priming selectively relieved hypersensitivity. In contrast, pre-priming NPC-15437 treatment only prevented Car-induced initial transient hyperalgesia. Immunoassays showed a significant decrease in spinal PKMζ expression after plantar incision with post-priming ZIP treatment as compared with Scr-ZIP and NPC-15437, but no notable differences in PKCs expression were observed. CONCLUSIONS: Spinal PKCs solely contribute to the initial induction of persistent pain, whereas PKMζ plays an essential role in spinal plasticity storage. PKMζ is responsible for the maintenance of peripheral inflammation-primed PPSP. Therefore, spinal PKMζ may be a therapeutic target to prevent surgery-induced chronic pain in patients with preoperative pain.

Photodynamic therapy inhibits the formation of hypertrophic scars in rabbit ears by regulating metalloproteinases and tissue inhibitor of metalloproteinase-1.

BACKGROUND: Hypertrophic scarring (HS) is a chronic skin condition, and inhibition of normal fibroblast ageing plays an important role in its pathogenesis. Photodynamic therapy (PDT) is known to inhibit synthesis of collagen proliferation in blood vessels and fibroblasts in scar tissue, with no significant adverse reactions reported. AIM: To investigate the effect of PDT in the rabbit ear model of HS, and the specific mechanism of action of PDT. METHODS: We assessed the clinical and histopathological appearance of rabbit ears with HS with and without PDT. In addition, mRNA levels of matrix metalloproteinase (MMP)-2, MMP-3, MMP-9 and tissue inhibitor of metalloproteinase (TIMP)-1, and concentration of ß-galactose were all measured to confirm cell senescence. RESULTS: Our data indicate that PDT can accelerate fibroblast ageing by increasing the ratio of MMPs to TIMP, in addition to promoting degradation of collagen and extracellular matrix, thereby inhibiting HS formation. These effects lasted for up to 60 days, and induced no significant adverse local or systemic reactions. The efficacy of the treatment can be maximized by applying an appropriately high concentration of aminolaevulinic acid. CONCLUSIONS: PDT can induce senescence in fibroblasts, and may constitute a useful treatment for pathological scarring.

Gankyrin promotes breast cancer cell metastasis by regulating Rac1 activity.

Tumor metastasis is responsible for most cancer patients' deaths. Understanding the mechanism of metastasis is crucial for improving the cure rate for cancer. Here, we report that Gankyrin, a chaperone of ubiquitin-proteasome, has an essential role in breast cancer metastasis. We find that Gankyrin is highly overexpressed in human breast cancers and the expression correlates strongly with lymph node metastasis. Knocking down Gankyrin expression in highly metastatic human breast cancer cells significantly decreases cancer cell migration and invasion. Furthermore, we demonstrate that depletion of Gankyrin inhibits intrinsic Rac1 activity and induces large focal adhesions. Overexpression of Gankyrin accelerates focal adhesion turnover and increases cell migration. Notably, reduction of Gankyrin expression in mouse mammary tumor cell significantly decreases tumor metastasis to lung in animal models. Therefore, our findings suggest that Gankyrin is crucial for breast cancer metastasis and highlight the potential of Gankyrin as a therapeutic target for tumor metastasis.

Anterior visual pathway assessment by magnetic resonance imaging in normal-pressure glaucoma.

PURPOSE: To analyze the axonal architecture of the optic nerve in patients with normal-pressure glaucoma and determine whether these parameters correlate with the disease severity. METHODS: Using magnetic resonance (MRI) imaging (1.5-Tesla unit) and diffusion tensor (DT) MRI, we measured the optic nerve diameter, optic chiasm height and lateral geniculate nucleus (LGN) volume in patients with normal-pressure glaucoma and an age-matched control group. The retinal nerve fibre layer thickness (RNFL) was determined by optical coherence tomography (OCT). RESULTS: The study included 30 patients with normal-pressure glaucoma and 30 age-matched control subjects. Optic nerve diameter (p < 0.001), optic chiasm height (p < 0.001) and LGN volume (p = 0.02) were significantly smaller in the glaucoma group than in the control group and were significantly correlated with RNFL thickness and perimetric loss. In the control group, the parameters significantly (p < 0.05) decreased with age. The DT-MRI-derived fractional anisotropy for the optic nerve was significantly lower (p < 0.001), and the DT-MRI-derived mean diffusivity (p < 0.001), radial diffusivity (λ(⊥) ; p < 0.001) and axial diffusivity (λ(||) ; p = 0.009) for the optic nerve were significantly higher in the glaucoma group and significantly correlated with RNFL thickness and mean perimetric defect. CONCLUSIONS: Patients with normal-pressure glaucoma show an age-adjusted reduced optic nerve diameter, optic chiasm height and LGN volume as measured by MRI, correlating with a reduced RNFL thickness and increased perimetric loss. MRI may be applied to examine the optic nerve in patients with glaucoma with opaque optic media.

Study on energy transfer and energy migration of Ca2Gd8(SiO4)6O2:Dy3+ phosphor films.

Being a kind of rare-earth-metal silicate with oxidapatite structure, Ca2R8(SiO4)6O2 (R = Y, Gd, La) is a promising material doped with rare earth, and widely used as phosphors. In this thesis, Ca2Gd8(SiO4)6O2:Dy3+ films were prepared by the sol-gel method. X-ray diffraction (XRD), atomic force microscopy (AFM), photoluminescence (PL) spectra, and lifetimes were used to characterize the resulting films. AFM study indicated that the phosphor films consisted of 120 nm homogeneous particles. By combining the model of Burshtein for donor-donor migration and the V-F-B model for donor-acceptor energy transfer, the experimental luminescence decay curve of 6P(J) state of Gd3+ was re-simulated. It is found that concentration quenching of Gd3+ can be due to the result of the joint action of donor-donor (Gd3+-Gd3+) energy migration and donor-acceptor (Gd3+-Dy3+) energy transfer.

Magnetic properties in Co and Mn-doped ZnO powders and thin films.

Zn0.86Co0.14O powder and thin films were prepared by standard solid-state reaction processes and radio-frequency (RF) magnetron sputtering. Magnetic measurements indicate that the powder is paramagnetic for temperatures above 3 K, while the thin films annealed in vacuum are ferromagnetic at room temperature. The saturated magnetization was found to be about 0.6 microB/Co, while the coercive force was found to be 200 Oe at room temperature. The very similar results were also obtained in Zn0.96Mn0.04O powder and thin films. Such different results for the powder and thin films indicate that growth conditions and defects play an important role in producing ferromagnetism.

KDBI: Kinetic Data of Bio-molecular Interactions database.

Understanding of cellular processes and underlying molecular events requires knowledge about different aspects of molecular interactions, networks of molecules and pathways in addition to the sequence, structure and function of individual molecules involved. Databases of interacting molecules, pathways and related chemical reaction equations have been developed. The kinetic data for these interactions, which is important for mechanistic investigation, quantitative study and simulation of cellular processes and events, is not provided in the existing databases. We introduce a new database of Kinetic Data of Bio-molecular Interactions (KDBI) aimed at providing experimentally determined kinetic data of protein-protein, protein-RNA, protein-DNA, protein-ligand, RNA-ligand, DNA-ligand binding or reaction events described in the literature. KDBI contains information about binding or reaction event, participating molecules (name, synonyms, molecular formula, classification, SWISS-PROT AC or CAS number), binding or reaction equation, kinetic data and related references. The kinetic data is in terms of one or a combination of the following quantities as given in the literature of a particular event: association/dissociation or on/off rate constant, first/second/third/. order rate constant, equilibrium rate constant, catalytic rate constant, equilibrium association/dissociation constant, inhibition constant and binding affinity constant. Each entry can be retrieved through protein or nucleic acid or ligand name, SWISS-PROT AC number, ligand CAS number and full-text search of a binding or reaction event. KDBI currently contains 8273 entries of biomolecular binding or reaction events involving 1380 proteins, 143 nucleic acids and 1395 small molecules. Hyperlinks are provided for accessing references in Medline and available 3D structures in PDB and NDB. This database can be accessed at http://xin.cz3.nus.edu.sg/group/kdbi/kdbi.asp.

Protection of xenogeneic cells from human complement-mediated lysis by the expression of human DAF, CD59 and MCP.

CD59 and membrane cofactor protein (MCP, CD46) are widely expressed cell surface glycoproteins that protect host cells from the effect of homologous complement attack. cDNAs encoding human CD59 and MCP cloned from Chinese human embryo were separately transfected into NIH/3T3 cells resulting in the expression of human CD59 and MCP protein on the cell surface. The functional properties of expressed proteins were studied. When the transfected cells were exposed to human serum as a source of complement and naturally occurring anti-mouse antibody, they were resistant to human complement-mediated cell killing. However, the cells remained sensitive to rabbit and guinea pig complement. Human CD59 and MCP can only protect NIH/3T3 cells from human complement-mediated lysis. These results demonstrated that complement inhibitory activity of these proteins is species-selective. The cDNAs of CD59 and MCP were also separately transfected into the endothelial cells (ECs) of the pigs transgenic for the human DAF gene to investigate a putative synergistic action. The ECs expressing both DAF and MCP proteins or both DAF and CD59 proteins exhibited more protection against cytolysis by human serum compared to the cells with only DAF expressed alone.

[Clinical medicine of the western medicine in the 18th century].

The 18th century is an important turning point not only in human history, but also in medical history. G. B. Morgagni was an Italian who founded the organic pathology in the 18th century, which was a bridge between basic medicine and clinical medicine of western medicine. H. Boerhaave called for "paying attention to the development of clinical medicine", and under this situation, western clinical medicine was attached importance and developed again in the 18th century. However, at the same time, the mechanical materialism was also infiltrated into western clinical medicine.