[Hemophagocytic lymphohistiocytosis caused by hematogenous disseminated pulmonary tuberculosis: A case report].

Hemophagocytic lymphohistiocytosis (HLH) was a life-threatening syndrome due to the uncontrolled immune activation of cytotoxic T lymphocytes, natural killer (NK) cells, and macrophages. HLH is characterized by primary and secondary causes, the early diagnosis and treatment of patients are closely related to the prognosis and clinical outcome of patients. The clinical presentation is variable but mostly includes prolonged fever, splenomegaly, coagulopathy, hypertriglyceridemia, and hemophagocytosis, none of them is specific and particular for HLH. Tuberculosis (TB) infection is one of the causes of HLH. HLH caused by TB is very rare clinically, but it has a high mortality. For patients with fever of unknown origin, HLH-related clinical manifestations sometimes present before the final diagnosis of TB, and HLH is associated with the most significant mortality rate. This article is mainly about a 28-year-old patient with HLH who suffered from severe TB infection. The patient attended a hospital with a history of 2 months of prolonged fever, 10 days booger and subcutaneous hemorrhage in lower limbs. Before this, he was in good health and denied any history of tuberculosis exposure. Combined with relevant laboratory test results (such as splenomegaly, hemoglobin, platelet count, and hypertriglyceridemia) and clinical manifestations (e.g. fever), the patient was diagnosed with hemophagocytic lymphohistiocytosis, but the etiology of HLH remained to be determined. To confirm the etiology, the patient was asked about the relevant medical history (intermittent low back pain) and was performed chest CT scan, bone marrow biopsy, and fundus photography. Finally, he was diagnosed with hemophagocytic lymphohistiocytosis caused by hematogenous disseminated pulmonary tuberculosis. In response to this, intravenous methylprednisolone and anti-tuberculosis treatment (isoniazid, pyrazinamide, moxifloxacin, and amikacin) were administered to the patient. After more than a month of treatment, the patient recovered from HLH caused by severe TB infection. Therefore, this case suggests that we should be vigilant to the patient who admitted to the hospital with fever for unknown reasons, to diagnose HLH as early as possible and clarify its cause, then perform interventions and treatment, especially HLH secondary to tuberculosis. Also, cases of atypical TB and severe TB should be carefully monitored to achieve early diagnosis and early intervention.

[Severe acute respiratory syndrome coronavirus 2 infection in renal transplant recipients: A case report].

The novel coronavirus is a newly discovered pathogen in late December 2019, and its source is currently unknown, which can lead to asymptomatic infection, new coronavirus pneumonia or serious complications, such as acute respiratory failure. Corona virus disease 2019 (COVID-19) is a new type of respiratory disease that is currently spreading all over the world and caused by this coronavirus. Its common symptoms are highly similar to those of other viruses, such as fever, cough and dyspnea. There is currently no vaccine or treatment for COVID-19. Everyone is susceptible to infection with this disease, and owing to the long-term use of immunosuppressants, the immunity of kidney transplant recipients is suppressed, and it is more likely to be infected with the disease. At present, its impact on kidney transplant recipients is unclear. This article reports the clinical features and therapeutic course of novel coronavirus infection in a patient after renal transplantation. A 37-year-old female patient who received a kidney transplant 6 months before was diagnosed with novel coronavirus pneumonia. The patient's symptoms (such as fever, chills, dry cough, muscle aches), laboratory tests (such as decreased white blood cell count, elevated liver enzymes and D-dimer, positive viral nucleic acid test), and chest CT (multiple left lower lung plaque ground glass shadow) were similar to those of non-transplanted novel coronavirus pneumonia patients. In terms of treatment, because the immunity of kidney transplant recipients has been suppressed for a long time, it is a very common strategy to suspend the use of immunosuppressive agents. Therefore, the patient immediately discontinued the immunosuppressive agent after admission, so that she could restore immunity against infection in a short time. At the same time, the use of glucocorticoids was also very important. Its immunosuppressive and anti-inflammatory effects played a large role in the treatment process.In addition, prophylactic antibiotics was needed, and nephrotoxic drugs should be used with caution. Finally, following discounting the use of immunosuppressant and a low-dose glucocorticoid-based treatment regimen, COVID-19 in this renal transplant recipient was successfully cured. The cure of this case was of great significance, and this adjuvant nonspecific antiviral therapy could provide a template for the treatment of other such patients.

793 nm pump induced photo-bleaching of photo-darkened Yb(3+)-doped fibers.

We report on the strong photo-bleaching of the photo-darkening (PD) induced loss under the cladding pump of a 793 nm laser diode (LD) in double clad Yb-doped fibers. Up to 68% PD loss at 810 nm was bleached. The bleaching rates under different powers show that the higher pump power corresponds to the more bleached loss within the same time. Moreover, repeatable processes of PD and photo-bleaching were observed when alternately pumped with 915 and 793 nm LDs. Furthermore, it was found that simultaneously pumping the fiber with 915 and 793 nm LDs can suppress about 80% PD loss, compared with pumping the fiber only with 915 nm LD. The mechanism of photo-bleaching under 793 nm pump was also discussed.

A five-microRNA panel in plasma was identified as potential biomarker for early detection of gastric cancer.

BACKGROUND: Circulating microRNAs (miRNAs) have been implicated as novel biomarkers for gastric cancer (GC) diagnosis. However, the mixture of GC subtypes may have led to the inconsistent circulating miRNA profiles, and the clinical performance of circulating miRNAs has not yet been evaluated independently on early detection of GC. METHODS: A four-phase study was designed with a total of 160 cancer-free controls, 124 patients with gastric non-cardia adenocarcinoma (GNCA) and 36 patients diagnosed gastric cardia adenocarcinoma (GCA). In the discovery phase, we screened the miRNA expression profile in plasma of 40 GNCA patients (stage I) and 40 matched controls by TaqMan low density array (TLDA) chips with pooled samples. Differentially expressed miRNAs were further validated in individual sample using quantitative reverse-transcriptase PCR (qRT-PCR) in the training phase. Subsequently, in an independent validation phase, the identified miRNAs were evaluated in 48 GNCA patients (stage I) and 102 matched controls. Finally, the identified miRNAs were further assessed in an external validation phase including advanced GNCA and GCA patients. Additionally, the expression levels of identified miRNAs were measured in the media of BGC823 and MGC803 cell lines. RESULTS: Five miRNAs (miR-16, miR-25, miR-92a, miR-451 and miR-486-5p) showed consistently elevated levels in plasma of the GC patients as compared with controls, and were identified to be potential markers for GNCA with area under the receiver operating characteristic (ROC) curves (AUCs) ranging from 0.850 to 0.925 and 0.694 to 0.790 in the training and validation phases, respectively. The five-miRNA panel presented a high diagnostic accuracy for the early-stage GNCA (AUCs=0.989 and 0.812 for the training and validation phases, respectively). Three miRNAs (miR-16, miR-25 and miR-92a) were excreted into the culture media of GC cell lines. CONCLUSIONS: The five-miRNA panel in plasma may serve as a potential non-invasive biomarker in detecting the early-stage GC.

Efficacy and Safety of Preoperative Transcatheter Rectal Arterial Chemoembolisation in Patients with Locally Advanced Rectal Cancer: Results from a Prospective, Phase II PCAR Trial.

AIMS: The PCAR study aimed to assess the efficacy and safety of preoperative transcatheter rectal arterial chemoembolisation (TRACE) in patients with locally advanced rectal cancer (LARC). MATERIALS AND METHODS: This was a single-centre, prospective, phase II trial conducted in China. Eligible patients were adults aged 18 years and older with histologically confirmed stage II or III rectal carcinoma and an Eastern Cooperative Oncology Group performance status of 0-1. Patients received TRACE with oxaliplatin, followed by radiotherapy with a cumulative dose of 45 Gy (1.8 Gy/time/day, five times a week for 5 weeks) and received oral S1 capsules twice daily (7 days a week for 4 weeks). Patients underwent total mesorectal excision 4-8 weeks after the completion of chemoradiotherapy, followed by mFOLFOX6 or CAPOX regimens for 4-6 months. The hypothesis of this study was that adding TRACE to preoperative neoadjuvant chemoradiotherapy would improve tumour regression and prognosis. The primary end point was the pathological complete response rate; secondary end points included the major pathological response rate, anal preservation rate, 5-year disease-free survival (DFS), 5-year overall survival and treatment-related adverse events. RESULTS: In total, 111 LARC patients received TRACE and subsequent scheduled treatment plans. The pathological complete response and major pathological response rates were 20.72% and 48.65%, respectively. The 5-year DFS and 5-year overall survival were 61.89% (95% confidence interval 51.45-74.45) and 74.80% (95% confidence interval 65.05-86.01), respectively. Grade 3-4 toxicities were reported in 29 patients (26.13%). The postoperative complication rate was 21.62%, without serious surgical complications. Multivariate Cox regression analysis showed that ypN stage (hazard ratio = 4.242, 95% confidence interval 2.101-8.564, P = 0.00017) and perineural invasion (hazard ratio = 2.319, 95% confidence interval 1.058-5.084, P = 0.0487) were independent risk factors associated with DFS, whereas ypN stage (hazard ratio = 3.164, 95% confidence interval 1.347-7.432, P = 0.0101), perineural invasion (hazard ratio = 4.118, 95% confidence interval 1.664-10.188, P = 0.0134) and serum carbohydrate antigen 199 (CA199; hazard ratio = 4.142, 95% confidence interval 1.290-13.306, P = 0.0344) were independent predictors for overall survival. CONCLUSION: The current study provides evidence that adding TRACE to neoadjuvant chemoradiotherapy can improve the pathological remission rate in LARC patients with acceptable toxicity. Given its promising effectiveness and safe profile, incorporating TRACE into the standard treatment strategy for patients with LARC should be considered.

Alteration of the microRNA expression profile in human osteosarcoma cells transfected with APE1 siRNA.

Apurinic/apyrimidinic endonuclease1 (APE1), which has the dual functions of DNA repair and redox regulation, is considered to be a promising potential target in cancer treatment. Microarray and qRT-PCR were used to confirm the change of miRNA followed by analysis with comprehensive bioinformatics-based analysis. Both microarray and qRT-PCR demonstrated that 13 microRNAs (miRNAs) were significantly changed (>2-fold) in APE1 knockdown HOS cells; seven of them (hsa-miR-451, hsa-miR-1290, hsa-miR-765, hsa-miR-483-5p, hsa-miR-513a-5p, hsa-miR-129-5p and hsa-miR-31) were up-regulated and the other six (hsa-miR-29b, hsa-miR-197, has-let-7b, hsa-miR-324-5p, hsa-let-7i and hsa-miR-484) were down-regulated. Furthermore, pathway analysis showed that these miRNAs and their target genes affected by the expression of APE1 were involved in pathways relating to developmental processes, regulation of cellular processes, cell signaling (such as TGF-ß, Wnt, MAPK and the p53 signaling pathway) and cancers. There are putative binding sites of NF-κB, p53, HIF-1α, AP-1, PEBP2, ATF, NF-Y, Pax-2,CREB and c-Myb in the promoters of several down regulated miRNAs, indicating that APE1 may regulate miRNAs via transcription factors. Our data suggest that our understanding of the biological functions of APE1 will inevitably expand due to the novel pathways that APE1 uses to regulate gene expression through miRNAs.

Botryomycosis presenting as nasal cutaneous fistulas caused by Prevotella melaninogenica.

Botryomycosis is an uncommon chronic suppurative granulomatous bacterial infection that can affect the skin and viscera. Clinically, lesions typically consist of small tender nodules from which draining sinuses may develop to expel a purulent discharge. Histopathological features include characteristic aggregation of microorganisms (grain) within the inflammatory infiltrate. The commonest causative organisms are Staphylococcus aureus and Pseudomonas aeruginosa, of others. Botryomycosis resulting from Prevotella melaninogenica has not been reported previously. We report the case of a middle-aged patient with botryomycosis presenting as nasal cutaneous fistulas caused by P. melaninogenica, which was successfully treated with surgical intervention combined with systemic antibiotic treatment.

Gender representation on editorial boards of leading oncology journals.

BACKGROUND: There has historically been women underrepresentation on editorial boards of peer-reviewed medical journals. High-ranked oncology journals showcase cancer-related scientific work at the forefront of the discipline. There is urgent need to investigate gender representation on editorial boards at leading oncology journals. MATERIALS AND METHODS: Sixty high-ranked oncology journals based on impact factor calculated by the Journal Citation Reports (JCR) 2021 from Web of Science/Clarivate Analytics were identified. Gender-related information of editorial boards was obtained from each journal's website. The gender of each member of the editorial team was confirmed by an internet search for picture and/or gender-specific pronoun from journal or personal profile. Fisher's exact tests and analysis of variance were used to analyze categorical and continuous variables, respectively. Significance was set at P < 0.05. RESULTS: Among 4898 members on editorial boards of top oncology journals with the highest impact factor, 1177 were women. Women made up 24% (1177 of 4898) of members on editorial boards in top oncology journals, and there was significantly less women board members than men (P < 0.0001). The mean female composition of editorial boards of oncology journals was 27% (range from 4% to 100%). Among 71 editors-in-chief of the top oncology journals, 14 (20%) were women. There was a positive correlation between the presence of women in journal editorial leadership and the percentage of women on editorial boards (rs = 0.340, P = 0.008). The underrepresentation of women on oncology journal editorial boards was significantly different among quartiles of journal impact factor. There was no significant correlation between women's representation on journal editorial boards (%) and journal impact factors (rs = 0.226, P = 0.086). CONCLUSIONS: The results demonstrated that there are gender disparities among editorial leadership at high-impact oncology journals. There are cultural and structural barriers and prejudices to gender parity and diversity on editorial boards of oncology journals.

[Hyperoside protects mouse spermatocytes GC-2 cells from oxidative damage by activating the Keap1/Nrf2/HO-1 pathway].

OBJECTIVE: To study the protective effect of hyperoside (Hyp) against ydrogen peroxide (H2O2)- induced oxidative damage in mouse spermatocytes GC-2 cells and explore the role of the Keap1/Nrf2/HO-1 pathway in this protective mechanism. METHODS: GC-2 cells were treated with 2.5 mmol/L azaacetylcysteine (NAC), 50, 100, and 200 µmol/L hyperoside, or the culture medium for 48 h before exposure to H2O2 (150 µmol/L) for 2 h. CCK-8 assay was used to detect the changes in cell viability, and cell apoptosis was analyzed using flow cytometry. Enzyme-linked immunosorbent assay (ELISA) was used to detect the levels of superoxide dismutase (SOD), glutathione peroxidase (GSH-PX), catalase (CAT) activity and malondialdehyde (MDA) in the culture medium. Western blotting and RT-qPCR were used to detect the protein and mRNA expression levels of nuclear factor erythroid 2-related factor2 (Nrf2), Kelch-like ECH-associated protein 1 (Keap1), and heme oxygenase-1 (HO-1); the nuclear translocation of Nrf2 was detected using immunofluorescence assay. RESULTS: Exposure to H2O2 significantly lowered the proliferation rate, reduced the activities of SOD, GSH and CAT, and obviously increased MDA content, cell apoptosis rate, and the expressions of Keap1 and Nrf2 mRNA and Keap1 protein in GC-2 cells (P < 0.05 or 0.01). Treatment of the cells prior to H2O2 exposure with either NAC or 200 µmol/L hyperoside significantly increased the cell proliferation rate, enhanced the activities of SOD, GSH-PX and CAT, and lowered MDA content and cell apoptosis rate (P < 0.05). Treatment with 200 µmol/L hyperoside significantly decreased the mRNA and protein expressions of Keap1 and increased the expressions of HO-1 mRNA and the protein expressions of Nrf2 and HO-1 (P < 0.05 or 0.01). Hyperoside also caused obvious nuclear translocation of Nrf2 in the cells (P < 0.05). CONCLUSION: Hyperoside protects GC-2 cells against H2O2- induced oxidative damage possibly by activation of the Keap1/Nrf2/HO-1 signaling pathway.

[Incidence of gastric cancer and risk factors in Suzhou cohort].

Objective: To describe gastric cancer incidence in Suzhou cohort, explore the environmental risk factors of gastric cancer in Suzhou, and provide appropriate suggestions for gastric cancer prevention and control. Methods: The participants were from the Suzhou cohort of China Kadoorie Biobank. Baseline survey was conducted from 2004 to 2008, followed by long-term follow-up until December 31, 2013. After the exclusion of those who had been previously diagnosed with peptic ulcer and malignant tumor reported at baseline survey and gastric cancer within six months after enrollment, a total of 50,136 participants were included. Cox proportional risk models were used to identify risk factors of gastric cancer and their hazard ratios in Suzhou. The effect modifications of gender on the association between risk factors and gastric cancer were analyzed. Results: In the follow-up of 7.19 years (median), 374 gastric cancers cases occurred. The standardized incidence was 94.57 per 100 000 person-years. Multivariate Cox proportional risk model analysis found that age (10 years old as a age group, HR=2.20, 95%CI: 1.92-2.53, P<0.001), current smoking (HR=1.84, 95%CI: 1.10-3.07 P=0.020), consumption of preserved vegetables weekly (HR=2.28, 95%CI: 1.28-4.07, P=0.005) and daily (HR=2.05, 95%CI: 1.16-3.61, P=0.013) were risk factors for gastric cancer. Female (HR=0.44, 95%CI: 0.25-0.76, P=0.003) and refrigerator use (10 years as a limit, HR=0.85, 95%CI: 0.74-0.97, P=0.016) were protective factors for gastric cancer. Further analysis showed that there was heterogeneity between males and females in the association between refrigerator use years and the incidence of gastric cancer (P=0.009), and there was an interaction effect between gender and refrigerator use on the incidence of gastric cancer (P=0.010). Conclusions: The incidence of gastric cancer in Suzhou cohort was high. The risk factors of gastric cancer varied. There was a synergistic interaction effect between gender and refrigerator use years on the incidence of gastric cancer.

Microneedles in clinical practice--an exploratory study into the opinions of healthcare professionals and the public.

PURPOSE: Microneedles are being developed to administer vaccines and therapeutics to and through skin. To date there has been no qualitative or quantitative research into public and health professionals' views on this new delivery technique. METHODS: Focus groups (n=7) comprising public and healthcare professionals were convened to capture the perceived advantages for, and concerns with, microneedles. Discussions were audio-recorded and transcribed. Transcript analysis identified themes that were explored using a questionnaire identifying consensus or otherwise. RESULTS: Participants identified many potential benefits of the microneedle delivery system, including reduced pain, tissue damage and risk of transmitting infections compared with conventional injections, as well as potential for self-administration (subject to safeguards such as an indicator to confirm dose delivery). Delayed onset, cost, accurate and reliable dosing and the potential for misuse were raised as concerns. A range of potential clinical applications was suggested. The public (100%) and professional (74%) participants were positive overall about microneedle technology. CONCLUSIONS: This exploratory research study captured the views of the eventual end-users of microneedle technology. Microneedle researchers should now reflect on their research and development activities in the context of stakeholder engagement in order to facilitate the transfer of this new technology 'from bench to bedside.'

Evaluation of Antibiotic Supply Decisions by Community Pharmacists in Thailand: A Vignette Study.

In Thailand, antibiotics are available lawfully from community pharmacies without a prescription. Inappropriate supply of antibiotics from Thai community pharmacies to the public for common, self-limiting diseases has been reported. The study aimed to evaluate the appropriateness of antibiotics selected by community pharmacists in Thailand in response to vignettes. A cross-sectional survey of community pharmacists across Thailand was conducted using a self-administered questionnaire including nine case vignettes with three conditions, namely upper respiratory infections (URIs), acute diarrhoea and simple wounds. A total of 208 questionnaires were completed and analysed (20.8% response rate). In response to vignettes relating to URIs, 50.8% of pharmacist recommendations were not in accordance with antibiotic guidelines. Inappropriate recommendations for diarrhoea and wound cases were 20.8% and 16.7%, respectively. A higher proportion of younger pharmacists, those with less experience, Pharm. D. graduate pharmacists, employee pharmacists and those pharmacists who worked in a chain pharmacy were more likely to recommend appropriate antibiotic treatment in response to the vignettes (p < 0.05). These findings will be useful to promote educational interventions for community pharmacists regarding common infectious disease management in order to improve appropriate antibiotic use.

[Timing of food introduction to the infant diet and risk of food allergy: a systematic review and Meta-analysis].

Objective: To evaluate the relationship between the timing of complementary feeding for infants and the occurrence of food allergy. Methods: The PubMed, Cochrane Library, China National Knowledge Infrastructure (CNKI), and WanFang Data database were searched for randomized controlled trials (RCTs) about the effects of early introduction of complementary foods in infants on the occurrence of food allergy. Papers published from the establishment of the databases to December 31, 2019 were extracted. The quality of the selected literature was evaluated using the risk-of-bias (ROB) tools in the Cochrane Handbook, and the RevMan 5.3 software was used for meta-analysis. For the complementary food analyzed in a few reports in literature, a systematic review was conducted. Results: A total of 8 RCTs were extracted, and the systematic review and Meta-analysis were carried out according to food types. The results of Meta-analysis showed that compared with late introduction (after 6 months of age), early introduction (before 6 months of age) of eggs (RR=0.60, 95%CI 0.46-0.79) could reduce the risk of egg allergy in infants. The subgroup analysis of the six studies about eggs demonstrated that in infants with a prior or family history of allergic diseases, the introduction of eggs before 6 months of age was associated with reduced risk of egg allergy (RR=0.55, 95%CI 0.40-0.75), and the introduction of raw eggs (RR=0.67, 95%CI 0.49-0.93) and small amount of eggs (equivalent to weekly protein 0-4 g) (RR=0.55, 95%CI 0.36-0.85) before 6 months of age were also associated with reduced risk of egg allergy. In addition, egg supplementation during 4-6 months of age reduced the occurrence of egg allergy compared with supplementation before 4 months of age (RR=0.58, 95%CI 0.43-0.78). The systematic review found no conclusive relationship between early peanut introduction and peanut allergy, nor the correlation between early cow's milk protein introduction and cow's milk protein allergy (P>0.05). Conclusion: Early introduction (before 6 months of age) of eggs in infants' complementary foods can prevent infant egg allergy, but the limitations of the study need to be considered.

A genetic map of melon highly enriched with fruit quality QTLs and EST markers, including sugar and carotenoid metabolism genes.

A genetic map of melon enriched for fruit traits was constructed, using a recombinant inbred (RI) population developed from a cross between representatives of the two subspecies of Cucumis melo L.: PI 414723 (subspecies agrestis) and 'Dulce' (subspecies melo). Phenotyping of 99 RI lines was conducted over three seasons in two locations in Israel and the US. The map includes 668 DNA markers (386 SSRs, 76 SNPs, six INDELs and 200 AFLPs), of which 160 were newly developed from fruit ESTs. These ESTs include candidate genes encoding for enzymes of sugar and carotenoid metabolic pathways that were cloned from melon cDNA or identified through mining of the International Cucurbit Genomics Initiative database (http://www.icugi.org/). The map covers 1,222 cM with an average of 2.672 cM between markers. In addition, a skeleton physical map was initiated and 29 melon BACs harboring fruit ESTs were localized to the 12 linkage groups of the map. Altogether, 44 fruit QTLs were identified: 25 confirming QTLs described using other populations and 19 newly described QTLs. The map includes QTLs for fruit sugar content, particularly sucrose, the major sugar affecting sweetness in melon fruit. Six QTLs interacting in an additive manner account for nearly all the difference in sugar content between the two genotypes. Three QTLs for fruit flesh color and carotenoid content were identified. Interestingly, no clear colocalization of QTLs for either sugar or carotenoid content was observed with over 40 genes encoding for enzymes involved in their metabolism. The RI population described here provides a useful resource for further genomics and metabolomics studies in melon, as well as useful markers for breeding for fruit quality.

Eleven themes of patient-centred professionalism in community pharmacy: innovative approaches to consulting.

OBJECTIVES: The study aimed to clarify patient-centred professionalism within and across community pharmacy settings; position that knowledge in a modern-day environment, accessing the opinions and experiences of patients and professionals; inform the literature on the value of consultation workshops within this context; and develop a template of positive and challenging exemplars of patient-centred professionalism within these contexts. METHODS: Thirty-nine study participants contributed to extended consultation workshops. Sessions were supported by bio-photographic data of healthcare practices across a range of different settings, and a final forum event. KEY FINDINGS: Thematic analysis of qualitative data, supported by the Nominal Group Work technique, led to a template containing 11 themes of positive and challenging aspects of patient-centred professionalism: safety, professional characteristics, relationships with patients, confidentiality and privacy, accessibility, training, professional pressures, services, environment, changing professional roles and patient characteristics. Themes, while descriptive and rich, highlight difficulties in defining this notion, which is both nuanced and ambiguous. While study participants were interested in the everyday examples of practice and interaction, they were strongly influenced by their different agendas and experiences. Patients, for example, wanted a quick and efficient dispensing service, where their needs and expectations came first. Pharmacists, on the other hand, found that pressing patient demands and overarching company policies led to professional anxiety that distracted them from what they perceived to be the defining aspect of their professionalism, dispensary work. CONCLUSIONS: The study outcomes indicate, in line with international literature, that while proud of supporting patients, many pharmacists feel demoralised, torn between pressing public and professional demands and the expectations of advice-giving in unfamiliar, formal situations within nondescript, corporate workspaces.

3,4-O-Isopropyl-idene-2-C-methyl-d-galactonolactone.

X-ray crystallography unequivocally confirmed the stereochemistry of the 2-C-methyl group in the title mol-ecule, C(10)H(16)O(6), in which the 1,5-lactone ring exists in a boat conformation. The use of d-galactose in the synthesis determined the absolute stereochemistry. The crystal exists as O-H⋯O hydrogen-bonded layers in the ab plane, with each mol-ecule acting as a donor and acceptor for two hydrogen bonds.

STAT3 gene polymorphism in chronic obstructive pulmonary disease.

OBJECTIVE: The aim of this study was to explore the correlation between rs8069115, rs41289087, and rs11079042 polymorphisms of the signal transducer and activator of transcription 3 (STAT3) gene and chronic obstructive pulmonary disease (COPD). PATIENTS AND METHODS: A total of 200 patients diagnosed with COPD were enrolled in the disease group. Meanwhile, 200 normal subjects were selected as the control group. Peripheral blood was collected from subjects in the disease group and control group. Subsequently, nucleated cells were isolated for determination of STAT3 gene polymorphisms. Quantitative Polymerase Chain Reaction (qPCR) was utilized to detect the expression level of STAT3. Samples from 12 patients with differences in STAT3 haplotypes and 12 cases with no difference were collected and treated with transcriptome sequencing to analyze pathways enriched with differentially expressed genes. RESULTS: There were statistically significant differences in allele distributions at rs8069115 between the disease group and control group (p=0.000), and the allele frequency of G was higher in disease group. Genotype distributions of rs8069115 (p=0.000) and rs41289087 (p=0.000) of the STAT3 gene in disease group were significantly different in comparison with the control group. The frequency of rs8069115 GG genotype was remarkably higher, while the frequency of rs41289087 TG genotype was lower in the disease group (p<0.05). In addition, compared with the control group, the distributions of the dominant model (p=0.002) and recessive model (p=0.004) of rs8069115 of the STAT3 gene were markedly different in the disease group. A significantly higher frequency of dominant model GG+GA and lower frequency of recessive model GA+AA were observed at rs8069115 in the disease group (p<0.05). Moreover, the haplotype distributions of AGC (p=0.002), ATC (p=0.001), GTA (p=0.010), and GTC (p=0.035) at rs8069115, rs41289087, and rs11079042 were different between the disease group and control group. Besides, rs8069115 locus and rs11079042 locus were linked to each other (D'=0.523). There was a remarkable association between rs11079042 polymorphism of the STAT3 gene and gene expression (p<0.05). STAT3 was highly expressed in patients with genotype CC (p<0.05). Furthermore, changes in transcriptome levels among different haplotype populations (haplotype with different distributions vs. haplotype with no difference in distribution) were analyzed. The results demonstrated that multiple pathways, such as ECM-receptor interactions, cell cycle checkpoints, and protein processing were notably enriched (p<0.05). CONCLUSIONS: According to our results, we confirmed that the polymorphisms (rs8069115, rs41289087, and rs11079042) of STAT3 gene are noticeably correlated with the occurrence and progression of COPD.

Expression and bioactivities of endothelin-1 in gingiva during cyclosporine A treatment.

BACKGROUND AND OBJECTIVE: This study aimed to evaluate the expression and bioactivities of endothelin-1 (ET-1) in gingiva during cyclosporine A (CsA) treatment. MATERIAL AND METHODS: After establishing edentulous ridges, experimental rats were fed 30 mg/kg/day CsA while control animals received mineral oil for 4 weeks, after which a reverse transcription-polymerase chain reaction (RT-PCR) and/or immunohistochemistry was used to examine the expression of ET-1, its receptors, proliferating cell nuclear antigen (PCNA) and inducible nitric oxide synthase (iNOS) in gingivae. The roles of the endothelin receptors A and B (ET(A) and ET(B)) in CsA-enhanced expression of PCNA and iNOS were examined in cultured human gingival fibroblasts pretreated with receptor antagonists, by immunocytochemistry and RT-PCR, respectively. RESULTS: The mRNA expression of ET-1, ET(A) and ET(B), as well as of PCNA and iNOS, was significantly greater in edentulous gingiva that received CsA compared with control gingiva. Immunohistochemistry revealed more cells positively stained for ET-1 and its receptors in the tissues of CsA-treated rats than in those of control rats. In fibroblast cultures, enhanced mRNA expression of ET-1, ET(A) and ET(B) was observed after CsA treatment at the concentrations of 10 and 100 ng/mL. Cyclosporine A-enhanced PCNA expression was somewhat reduced by blockade of ET(A), but not ET(B), whereas iNOS expression was somewhat reduced by blockade of ET(B). CONCLUSION: Based on the present findings, we suggest that: (1) CsA upregulates the gingival expression of ET-1 and its receptors; and (2) ET(A) and ET(B) have different bioactivities, ET(A) being involved in cell proliferation and ET(B) being associated with iNOS expression.