[Importance and practice of standardized children's refractive development records].

The prevalence of myopia in China is increasing. The early onset and rapid progression of myopia in younger children have attracted more attention. The establishment of standardized children's refractive development records is the basis of myopic prevention and control. It would be helpful to follow the refractive status and pay more attention to the refractive development of potential myopic children, so as to reduce the prevalence of myopia. (Chin J Ophthalmol, 2021, 57: 724-726).

[Nitrate: a pioneer from the mouth to the systemic health and diseases].

Dietary nitrate which mainly comes from green leafy vegetables, is absorbed into blood circulation by the intestinal mucosa. Parotid gland is an important organ for transporting nitrate. Nitrate in blood is taken up by sialin, a nitrate transporter and concentrated in salivary glands and secreted into saliva. The salivary nitrate is partially reduced to nitrite and nitric oxide by oral bacteria, and then salivary nitrate and nitrite return into blood circulation with swallowing and intestinal mucosal absorption. As a non-classic source of nitric oxide, nitrate-nitrite-nitric oxide pathway plays an important role on physiological and pathological conditions, especially on the condition of hypoxia and ischemia. These functions include body protection, such as gastrointestinal tract, cardiovascular system, anti-inflammation, regulation of glucose/lipid metabolism, improvement of sport ability, maintaining gut microbiome hemostasis, and alleviating senility. The traditional view on nitrate as a harmful substance to human body has been proved to be lack of scientific evidence. With further research and application, as a pioneer from the mouth to the whole body, nitrate is expected to play a crucial part in human health, and prevention and treatment of systemic diseases.

Lives and Economic Loss in Brazil due to Lack of Radiotherapy Access in Cervical Cancer: A Cost-Effectiveness Analysis.

AIMS: Among all malignancies, the use of radiotherapy incurs the highest survival benefit within cervical cancers. Radiotherapy, however, remains underutilised for cervical cancers within the Brazilian public health system (BPHS). The objective of this study was to estimate the potential health and monetary benefits for universal access to radiotherapy and chemoradiotherapy (CRT) for untreated cervical cancer patients in the BPHS. MATERIALS AND METHODS: Using 2016 data on Brazilian cervical cancer incidence and availability of radiotherapy/CRT in the BPHS, the number of cancer deaths due to radiotherapy/CRT underutilisation was estimated. The incremental effectiveness was calculated by life-year gain. The indirect costs from mortality-related productivity loss (MRPL) were estimated based on life expectancy, wage and labour force participation rate. MRPL was compared with direct medical costs after being adjusted to 2016 US dollars. This study was conducted from the payer's perspective; both costs and effectiveness were discounted at a rate of 3%. The incremental cost-effectiveness ratio (ICER) was calculated to determine the cost-effectiveness of radiotherapy for cervical cancer in Brazil. One-way sensitivity analyses were carried out to assess the robustness of the model. RESULTS: The total number of life-years lost due to lack of universal access to radiotherapy and CRT per year were 27 199 and 31 627, respectively. The annual cost to match the radiotherapy gap was $10.5 million, with an additional cost of $3 million to close the CRT gap. The mean years of potential life lost per death was 20.5. The cost per life saved was $7942 for radiotherapy alone (ICER $388/life-year) and $8774 for CRT (ICER $429/life-year). MRPL due to shortage of radiotherapy and CRT were $59 million and $69 million, respectively. CONCLUSION: Providing universal access to radiotherapy/CRT for cervical cancer patients in the BPHS is highly cost-effective and should be prioritised as an impactful public health initiative.

Shifting practice in definitive chemoradiation for localized esophageal cancer.

BACKGROUND: The efficacy of carboplatin-paclitaxel in the trimodality setting was demonstrated in the cross trial. Because of better tolerance, that regimen has been adopted as an alternative for patients receiving definitive chemoradiation (dcrt). The purpose of our study was to compare outcomes in patients with localized esophageal and gastroesophageal junction (gej) cancer who received dcrt using either platinum-5-fluorouracil (5fu) or carboplatin-paclitaxel. METHODS: Medical records and outcomes for all patients diagnosed with localized carcinoma of the esophagus and gej at our centre between 2008 and 2015 were reviewed. All patients who underwent dcrt using cisplatin-5fu, carboplatin-5fu, or carboplatin-paclitaxel were included. RESULTS: The 73 identified patients (34 cisplatin-5fu, 13 carboplatin-5fu, 26 carboplatin-paclitaxel) were all prescribed concomitant radiotherapy of 50 Gy in 25 daily fractions. The diagnosis was adenocarcinoma in 64% and squamous cell carcinoma in 36%. Median overall survival (os) duration for the cisplatin-5fu group was 28 months [95% confidence interval (ci): 19 to 41 months], with a 3-year os rate of 44%, in contrast to the 15 months (95% ci: 11 to 17 months) and 15% in the carboplatin-paclitaxel group (log-rank p = 0.0047). Median os duration for the carboplatin-5fu group was 17 months (95% ci: 11 to 68 months) with a 3-year os rate of 31%. Adjusting for patient and disease factors, better os durations and rates were associated with cisplatin-5fu (hazard ratio: 0.34; p = 0.0016) and carboplatin-5fu (hazard ratio: 0.55; p = 0.20) than with carboplatin-paclitaxel. CONCLUSIONS: In a dcrt regimen, a better os is associated with cisplatin-5fu than with carboplatin-paclitaxel. Clinical trials to determine optimal chemotherapy regimens are warranted for patients who are not suitable for surgery.

From Nitrate to Nitric Oxide: The Role of Salivary Glands and Oral Bacteria.

The salivary glands and oral bacteria play an essential role in the conversion process from nitrate (NO3-) and nitrite (NO2-) to nitric oxide (NO) in the human body. NO is, at present, recognized as a multifarious messenger molecule with important vascular and metabolic functions. Besides the endogenous L-arginine pathway, which is catalyzed by complex NO synthases, nitrate in food contributes to the main extrinsic generation of NO through a series of sequential steps (NO3--NO2--NO pathway). Up to 25% of nitrate in circulation is actively taken up by the salivary glands, and as a result, its concentration in saliva can increase 10- to 20-fold. However, the mechanism has not been clearly illustrated until recently, when sialin was identified as an electrogenic 2NO3-/H+ transporter in the plasma membrane of salivary acinar cells. Subsequently, the oral bacterial species located at the posterior part of the tongue reduce nitrate to nitrite, as catalyzed by nitrate reductase enzymes. These bacteria use nitrate and nitrite as final electron acceptors in their respiration and meanwhile help the host to convert nitrate to NO as the first step. This review describes the role of salivary glands and oral bacteria in the metabolism of nitrate and in the maintenance of NO homeostasis. The potential therapeutic applications of oral inorganic nitrate and nitrite are also discussed.

Dose reduction of cone beam CT scanning for the entire oral and maxillofacial regions with thyroid collars.

OBJECTIVE: The aim of this study was to evaluate the influence of thyroid collars on radiation dose during cone beam CT (CBCT) scanning. METHODS: Average tissue-absorbed dose for a NewTom 9000 CBCT scanner (Quantitative Radiology, Verona, Italy) was measured using thermoluminescent dosemeter chips in a phantom. The scans were carried out with and without thyroid collars. Effective organ dose and total effective dose were derived using International Commission on Radiological Protection 2007 recommendations. RESULTS: The effective organ doses for the thyroid gland and oesophagus were 31.0 µSv and 2.4 µSv, respectively, during CBCT scanning without a collar around the neck. When the thyroid collars were used loosely around the neck, no effective organ dose reduction was observed. When one thyroid collar was used tightly on the front of the neck, the effective organ dose for the thyroid gland and oesophagus were reduced to 15.9 µSv (48.7% reduction) and 1.4 µSv (41.7% reduction), respectively. Similar organ dose reduction (46.5% and 41.7%) was achieved when CBCT scanning was performed with two collars tightly on the front and back of the neck. However, the differences to the total effective dose were not significant among the scans with and without collars around the neck (p = 0.775). CONCLUSIONS: Thyroid collars can effectively reduce the radiation dose to the thyroid and oesophagus if used appropriately.

[Studies on the expression of the recombinant human GM-CSF/IL-3 fusion protein].

A human granulocyte-macrophage colony stimulating factor (GM-CSF)/interleukin-3(IL-3) fusion gene with a short linker between the GM-CSF and IL-3 gene has been successfully constructed and expressed in E. coli under the control of T7 promoter. The recombinant fusion protein was expressed as inclusion bodies after the IPTG induction. The yield of the GM-CSF/IL-3 fusion protein was over 30% of the total cellular proteins. Western-blotting results showed that the fusion protein could specifically combined with GM-CSF antibody and IL-3 antibody. The biological activity was detected by the GM-CSF and IL-3 dependent cell line TF-1. After solubilizing with 8 mol/L urea and renaturing with dialysis against Tris. HCl solution, the refolded fusion protein showed obvious activities to maintain the growth of TF-1 cell.

[The influences of lactose as an inducer on the expression of the recombinant proteins in Escherichia coli BL21 (DE3)].

The possibility of using lactose as an inducer to substitute the common inducer IPTG in the fermentation process of the recombinant microorganism was deeply investigated. The influences of culture conditions such as lactose concentration, growth medium composition, the point of induction and the duration of the induction phase on the expression of the recombinant protein were analyzed and studied in detail. In the following experiments, lactose was then used in the high cell density culture process of E. coli BL21 (DE3)(pFu). The final cell density (OD600) was over 40. The expression level of recombinant protein was about 15% of the total cellular protein. Both the culture density and foreign protein expression level were lower than those induced by IPTG. However, because of the potential toxicity to human beings and the high cost of IPTG, the use of lactose might provide an alternative means of inducing foreign protein expression. This would be more attractive in industrial scale productions of recombinant proteins. The results confirmed that lactose could be used as an inducer in the fermentation process.

Preparation and cDNA sequence analysis of two novel monoclonal antibodies against magaininII.

By using intrasplenic immunization and the conventional B lymphocyte hybridoma technique, we have established two novel hybridoma cell lines stably secreting specific monoclonal antibodies (MAbs) to magaininII, termed as 2D1 and 3F8, respectively. The two cell lines were then subjected to RNA extraction and the VH and VL segments were obtained by reverse transcription of RNA followed by polymerase chain reaction (RT-PCR) and characterized by nucleotide sequence analysis. The VH segments of 2D1 and 3F8 belong to the VH5 family and the VL segments of 2D1 and 3F8 belong to VK10 and VK1 groups, respectively. The two MAbs utilize different VL segments and have disparities in their HCDR3 regions, which may contribute to the different epitope recognition of the two antibodies.

Immunization with T cell receptor V beta chain peptides deletes pathogenic T cells and prevents the induction of collagen-induced arthritis in mice.

Collagen-induced arthritis (CIA) in susceptible strains of mice is an animal model of T cell-mediated inflammatory polyarthritis. Analysis of T cell receptor (TCR) V beta gene usage in cells isolated from arthritic joints of BUB/BnJ (BUB) mice (H-2q, TCR V beta a) showed that TCR V beta chain gene usage was limited to TCR V beta 3 and V beta 10 gene families. All of the BUB mice immunized with a mixture of TCR V beta 3 and TCR V beta 10 peptides, but not with control TCR V beta 14 peptide, were refractory to the induction of CIA. Immunization with TCR V beta 3 and V beta 10 peptides completely blocked the development of clinical and subclinical inflammation, formation of pannus and synovial hyperplasia, and the erosion of cartilage and bone. Further studies revealed that preimmunization of BUB mice with V beta 10 peptide alone was sufficient to render the mice resistant to CIA. Analysis of TCR V beta chain gene expression in lymph node cells from arthritic and arthritis-protected mice showed the expression of TCR V beta 10 subfamily in all of the arthritic mice, but not in arthritis-protected mice. Immunization with TCR V beta peptides did not diminish the humoral responses to chicken type-II collagen and also elicited significant levels of anti-V beta 3 and anti-V beta 10 peptide antibodies. Antibodies cross-reactive with mouse chicken type-II collagen were detected in both the arthritic and arthritis-protected mice. Adoptive transfer of serum from arthritis-protected BUB mice significantly delayed the onset (P < 0.005) of arthritis in recipient BUB mice. In contrast, mice injected with serum from arthritic mice had early onset of arthritis. These results demonstrate that immunization of BUB mice with TCR V beta chain peptides elicited antibodies reactive with the self-TCR and prevented the induction of collagen-induced arthritis by eliminating or downregulating pathogenic T cells and consequently blocking the development of humoral immune response. These findings may have clinical applications in treating human autoimmune diseases characterized by common TCR gene usage.

Limited heterogeneity in T-cell receptor V beta chain gene expression in arthritic joints of BUB/BnJ (H-2q) mice--a T-cell receptor V beta a strain.

We have earlier shown that T-cells in arthritic joints and LNs of B10.Q mice (H-2q, TCR V beta b) use a restricted number of TCR V beta chain genes (V beta 6, 8, 9). In the present study, we have investigated the TCR V beta chain gene expression in arthritic joints and LN of BUB/BnJ mice (H-2q, TCR V beta a). Mice were immunized with [table: see text] chicken type-II collagen, and arthritic joints and draining LNs were removed at the onset of arthritis and the TCR V beta chain gene expression was studied by PCR. A restricted usage of TCR V beta was observed in both the tissues. A dominant usage of TCR V beta 4, 7, and 15 was found in the LNs while TCR V beta 3 and 10 were predominantly expressed in arthritic joints in the majority of the arthritic mice (5/7). Our results indicate that (a) in H-2q mice with CIA there is a restricted usage of TCR V beta chain genes regardless of the TCR V beta genotype; and (b) in the absence of TCR V beta 8 and 9, TCR V beta 3 and 10 are predominantly used by joint-infiltrating T-cells.

Restricted expression of T cell receptor V beta and lymphokine genes in arthritic joints of a TCR V beta a (H-2q) mouse strain-BUB/BnJ-with collagen-induced arthritis.

Type II collagen-induced arthritis (CIA) is an animal model of inflammatory polyarthritis with clinical and pathological features resembling rheumatoid arthritis (RA). We compared the expression of T cell receptor (TCR) V beta genes in T cells isolated from the inflamed joints, draining lymph nodes and the spleens of BUB/BnJ (H-2q) mice (BUB) during the early phase of CIA. We also investigated the profiles of cytokine gene expression in T cells obtained from the same tissues. We found that the expression of TCR V beta s, in arthritic joints of mice, during the early phase of the disease was limited to TCR V beta 3 and 10 gene families. In contrast, TCR V beta 4, 7, and 15 were predominant in the draining lymph nodes (LNs) and TCR V beta 2, 6, and 14 were predominant in the spleens of arthritic mice. Molecular cloning and sequence analysis revealed that the T cell populations in the arthritic joints were oligoclonal as determined by the limited N-D-N region diversity observed in the sequenced clones. These results demonstrate, for the first time, that (1) joint infiltrating T cells in TCR V beta a genotype mice use a restricted repertoire of TCR V beta genes; (2) there was oligoclonal expansion of infiltrating T cells in arthritic joints in mice with collagen-induced arthritis. Our results on cytokine gene expression in the arthritic joints of BUB mice indicate that Th-1-like T cell derived cytokines may be the predominant cytokines in the arthritic joints as illustrated by the presence of transcripts for IL-2 and IFN-gamma but not IL-4. In summary, our results provide evidence that T cells with restricted specificities, and more specificially, Th-1 type T cells, are crucial in the early phase of collagen induced arthritis in mice.

BUB/BnJ (H-2q) is a TCR deletion mutant mouse strain (TCR V beta a, KJ16-) that is susceptible to type II collagen-induced arthritis.

Type II collagen-induced arthritis (CIA) in mice is an animal model of autoimmune inflammatory arthritis. Arthritis is induced in susceptible strains of mice (H-2q and H-2r) after immunization with heterologous or autologous type II collagen in CFA. Induction of CIA is T cell dependent and a restricted usage of TCR V beta genes has been found in the arthritic joints and lymph nodes of mice with CIA. However, genes within the MHC are not the only determinants of susceptibility to CIA as SWR/j, AU/ssJ (both H-2q) and RIIIS/J(H-2r) mice are resistant to the induction of CIA. These strains of mice are TCR V beta chain genes deletion mutants (TCR V beta a and TCR V beta c haplotypes) and it was hypothesized that these mice are resistant to CIA because of the absence of a particular set of V beta TCR genes that are genomically deleted in these strains of mice. We now show that BUB/BnJ mice (H-2q) are T cell subsets deficient because of the genomic deletion of TCR V beta 5, 8, 9, 11, 12, and 13 sub-families. Our data demonstrate that despite the deficiency in T cell subsets from genomic deletion of TCR V beta genes, BUB mice are highly susceptible to the development of CIA. These results indicate that genomic deletion of certain TCR V beta genes alone is not in itself sufficient to confer resistance to CIA. These results further suggest that other unknown gene(s) must also contribute to the induction of CIA.

Potentially amyloidogenic, carboxyl-terminal derivatives of the amyloid protein precursor.

The 39- to 43-amino acid amyloid beta protein (beta AP), which is deposited as amyloid in Alzheimer's disease, is encoded as an internal peptide that begins 99 residues from the carboxyl terminus of a 695- to 770-amino acid glycoprotein referred to as the amyloid beta protein precursor (beta APP). To clarify the processing that produces amyloid, carboxyl-terminal derivatives of the beta APP were analyzed. This analysis showed that the beta APP is normally processed into a complex set of 8- to 12-kilodalton carboxyl-terminal derivatives. The two largest derivatives in human brain have the entire beta AP at or near their amino terminus and are likely to be intermediates in the pathway leading to amyloid deposition.

Phenotypic plasticity in adult sympathetic neurons: changes in neuropeptide expression in organ culture.

Vasoactive intestinal peptide (VIP)-like immunoreactivity is present at low levels in the superior cervical ganglion of the adult rat, where immunostained neural processes, but only an occasional immunostained cell body, are found. However, when ganglia are maintained for 24 or 48 hr in organ culture, their content of VIP-like immunoreactivity increases 6- or 31-fold, respectively. When examined at 24 hr, the increase in VIP-like immunoreactivity is totally blocked by an inhibitor of RNA or protein synthesis. Many neuronal cell bodies and processes with immunoreactivity for VIP and the related peptide histidine isoleucine amide (PHI) are seen in cultured ganglia. In addition, VIP/PHI mRNA is abundant in cultured ganglia but only barely detectable in ganglia prior to culture. Under the same culture conditions, neuropeptide Y-like immunoreactivity increases to a small extent, and tyrosine hydroxylase activity and total ganglion protein remain unchanged. These results support the idea that adult sympathetic neurons exhibit plasticity in neuropeptide expression and that this plasticity, in the case of VIP, depends on changes in gene expression.

Delayed response, preoperative overtraining, and prefrontal lesions in the rat.

An earlier study in this laboratory found that preoperative overtraining improved retention of a delayed alternation task after prefrontal lesions in the rat. In this study, however, it was found that preoperative overtraining did not improve performance of the rat in a delayed response task following prefrontal lesions. These results support the hypothesis that preoperative overtraining can improve postoperative performance only when postoperative recovery is ordinarily present, as it is with delayed alternation. but not with delayed response, in the prefrontal rat. This suggests that effects of preoperative overtraining and postoperative recovery may be mediated by similar mechanisms. It further suggests that a shift of function, which seems to account for postoperative recovery, may occur in some parts of the normal adult brain as a result of overtraining.

Effects of a purified cecropin D from a Chinese silk moth on growth, function and differentiation of murine hemopoietic cells.

The effects of cecropin D, a small basic peptide isolated from a Chinese oak silk moth, on the functions or differentiation of mammalian hemopoietic cells are described in the present paper. This peptide suppressed lectin-induced DNA synthesis of murine splenocytes in a dose-dependent manner without any significant cytotoxic effects. It also exhibited inhibitory effects on antibody production in lipopolysaccharide-stimulated lymphocytes and on colony formation of hemopoietic progenitor cells in plasma clots culture. These results indicate that cecropin D can regulate growth, function and differentiation of murine hemopoietic cells. The biological significance of this finding is discussed from the comparative immunological point of view.

Purification of a lectin from the hemolymph of Chinese oak silk moth (Antheraea pernyi) pupae.

A lectin with affinity to galactose was purified to homogeneity from the hemolymph of diapausing pupae of the Chinese oak silk moth, Anteraea pernyi. The molecular mass of this lectin was 380,000 and it formed an oligomeric structure of a subunit with a molecular mass of 38,000. The hemagglutinating activity in the hemolymph was found to increase with time after immunization with E. coli. Studies with antibody against the purified lectin showed that increase in the hemagglutinating activity was due to the same lectin, suggesting that the amount of the lectin increased in response to intrusion of foreign substances. The function of this lectin in the defence mechanism is discussed.

Interaction between liposomes and sarcotoxin IA, a potent antibacterial protein of Sarcophaga peregrina (flesh fly).

The direct interaction between phospholipids and sarcotoxin IA, a potent bactericidal protein of Sarcophaga peregrina, was studied using authentic sarcotoxin IA, its synthetic derivatives, and various liposomes. Results showed that sarcotoxin IA interacted with liposomes constituted from acidic phospholipids, resulting in the release of glucose trapped in these liposomes. The amidated carboxyl-terminal of this protein was found to be important for this interaction. Liposomes constituted from total phospholipids of Escherichia coli became less susceptible to sarcotoxin IA with an increase in their cholesterol content. Since bacterial membranes do not contain cholesterol, this finding may partly explain the selective toxicity of sarcotoxin I to bacteria.