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Background: One of the benign tumors of the salivary glands is Warthin's Tumor (WT), which consists of cystic bilayer papillary epithelial cells accompanied by the presence of a lymphoid stroma. Several cases have been reported to turn malignant. One of the markers developed to identify tumor proteins is fibrinogen-like protein 1 (FGL1). Along with lymphocyte-activation gene 3 (LAG-3), FGL1 establishes an immune checkpoint pathway that plays a role in the mechanism of tumor immune escape. Not much has been reported regarding FGL1 expression in WT, but some studies have reported that its expression is associated with tumor growth. Purpose: This study aims to analyze the location of FGL1 expression in WT and its relation to the mechanism of tumor immune release through the interaction between FGL1 and LAG-3. Methods: Cases of WT (n = 11) and breast cancer (n = 1) were used as positive controls. All cases were stained with hematoxylin-eosin and Recombinant Anti-FGL1 antibody. The FGL1 expression was observed in the cell membrane, cytoplasm, and lymphoid stroma. The results are presented in the form of figures. Results: All cases of WT expressed FGL1 in the cell membrane, cytoplasm, and lymphoid stroma. Its expression in the cell membrane and cytoplasm is possibly related to the process of tumorigenesis and the increasing size of the lesion. Additionally, its expression is seen in the lymphoid stroma, which is closely related to immune escape by inhibiting lymphocytes against tumor cells. Conclusion: Warthin's tumor cells express FGL1, and this expression plays a role in tumor immune escape mechanisms and tumor growth.

Spray technology is an innovative salt production process technology that is able to increase seawater salinity and accelerate the salt production process. This study aims to determine the effect of variations in the amount of spray and discharge in spray technology on increasing seawater salinity. The experimental method was carried out by varying the spray and water discharge amount in spray technology according to the variables. This research has been successfully carried out to increase the salinity of synthetic seawater where to increase from the initial seawater salinity of 2.5 °Be to 24 °Be. It takes 16 hours taken in 3 days using the number of sprays as much as 5 sprays with a seawater flow rate of 0.2424 m³/hour in an evaporation pond of 15í—7 m. The use of the spray method proved effective in accelerating the rate of increase in salinity of synthetic seawater, which was tested to increase the salinity of synthetic seawater from 2.5 °Be to 12 °Be with an evaporation time in traditional methods of 15 days to only 11 hours. This can also happen because the temperature, humidity and wind speed were relatively stable when the research took place.

Tobacco sorting officers in Jember Regency are still sorting tobacco leaves manually using hand muscles which can cause Musculo Skeletal Disorders (MSDs) complaints.One of the MSDs registered at the International Labor Organization (ILO) is Carpal Tunnel Syndrome (CTS) which is a disorder resulting from compression of the median nerve in the carpal tunnel at the wrist with the main symptom being tingling, pain radiating to the fingers which can be accompanied by numbness, weakness. muscles, stiffness, and possible muscle atrophy. This study aims to determine the factors associated with CTS supported by Phalen's test. This research is expected to provide information to workers and the public regarding health problems that can be experienced by tobacco sorting workers as well as being a consideration for increasing health insurance for these workers. This research was conducted using a cross-sectional survey design at PTPN A and PT B, Jember Regency with a sample calculation using the Slovin formula and obtained 246 respondents.The data analysis technique used was univariate SPSS analysis of frequency distribution, bivariate Chi Square analysis and SEM PLS multivariate analysis. research results show that education had an effect on the symptom severity scale, age had an influence on the symptom severity scale, age had an effect on the functional status scale and age had an influence on the Phalen's test. Conclusion:Age is the dominant factor affecting the symptom severity scale, functional status scale and Phalen's test. Keywords: CTS (Carpal Tunnel Syndrome), BCTQ (Boston Carpal Tunnel Questionnaire), SSS (Symptom Severity Scale), FSS (Functional Status Scale), Phalen's Test

Background: Human Immunodeficiency Virus (HIV) infection causes Acquired Immune Deficiency Syndrome (AIDS), a collection of symptoms arising from the deteriorating immunity. The number of people living with HIV worldwide continues to increase year-by-year. Those infected with HIV need antiretroviral (ARV) therapy to suppress the amount of HIV in the body. Purpose: This study aimed to investigate the determinants of adherence in people living with HIV/AIDS (PLHIV) undergoing ARV therapy in Situbondo Regency. Methods: This study employed a quantitative analytic observational approach with a cross-sectional design. Data analysis involved both descriptive and multivariate analysis. The population for this study consisted of 328 individuals, from which 212 were selected as samples, all being PLHIV on ART as of April 2022, sourced from ARV treatment services in Situbondo district. Results: The research analysis was based on predisposing factors, measured using three indicators: work, knowledge, and belief in ARVs. Supporting aspects were measured by two factors: ownership of health insurance and adherence counselling. Reinforcing factors were measured using two indicators: family support and stigma in the community. Conclusion: The study concluded that predisposing and reinforcing factors significantly influenced PLHIV adherence to antiretroviral therapy. However, supporting factors did not show a significant influence on adherence in PLHIV undergoing antiretroviral therapy in the Situbondo District.

Background: The COVID-19 pandemic has had a major impact on the world's health system, including Indonesia. The national health system is facing challenges with increasing cases of COVID-19. With the forecasting of COVID-19 cases, it is hoped that it can be one of the references in dealing with COVID-19 and one form of mitigation in dealing with COVID-19. Purpose: This research aims to predict COVID-19 cases in East Java Province for the coming year using the Autoregressive Integrated Moving Average (ARIMA) method based on patient data from March 2020 to January 2022. Methods: This type of research is analytic. Forecasting future COVID-19 cases using the Autoregressive Integrated Moving Average (ARIMA) method based on COVID-19 data from March 2020 to January 2022. Results: Based on the results of ARIMA analysis, the best forecasting model for confirmed cases of COVID-19 is the model (1:0:1) with AIC values ​​(14.22672), SIC (14.33357), while for cured cases is the model (1:2: 3) with the value of AIC (13.93054), SIC (13.03738), and for the case of death is the model (1:2:1) with the value of AIC (10.76105) and SIC (10.86790). Conclusion: From the results of this study, it is predicted that there will be an increase in COVID-19 cases in July 2022, January 2023 and June 2023.

Background: One of the benign salivary gland tumors is Warthin’s tumor, which is a benign tumor consisting of a papillary cystic structure covered by a double epithelial layer cells and lymphoid stroma with germinal center. Several cases have reported the Warthin’s tumor transformation into a malignant tumor such as lymphoma that develops from their stromal. Expression of cytotoxic T-lymphocyte antigen 4 (CTLA-4) as part of the immune checkpoint when highly expressed leads to a more rapid development or progression of tumors. Purpose: To analyze CTLA-4 expression in Warthin’s tumors associated with the pathogenesis of its growth through an escape mechanism from immune checkpoints and analyze based on CTLA expression whether this marker has the potential to be used as immunotherapy by administering anti CTLA-4. Methods: The tissue sections slides of Warthin’s tumor (n=8) were stained with Hematoxylin Eosin and immunostained with Recombinant Anti-CTLA4 antibody [CAL49] (ab237712). The slide with positive CTLA-4 is shown as staining on the cell membrane and/or cytoplasm. Observations were carried out using Optilab. The result is presented as figures. Results: Tumor cells expressed of CTLA-4 show in cytoplasm and/or cell membranes of the epithelial and stromal components of Warthin’s lymphoid. CTLA-4 is expressed lymphoid stroma, which is associated with inhibition of T cell activity against tumor cells, while the exact mechanism of CTLA-4 expression in epithelial components is not known but is thought to induce tumorigenesis and inhibit apoptosis. Conclusion: CTLA-4 is expressed in epithelial and stromal cells of Warthin’s tumor and this expression indicates that Warthin’s tumor cell growth is through the escape mechanism of the CTLA-4 check point immune. Further research is necessary to investigate whether CTLA-4 expression in lymphoid stroma has relate to their transformation toward a malignant tumor of lymphoma.

Background: Pleomorphic adenoma (PA) is a benign salivary gland tumour with high incidence and recurrence after treatment. It may recur with the same appearance or develop toward malignancy, namely as carcinoma ex pleomorphic adenoma (CXPA). How this tumour can transform into a CXPA remains unclear. Purpose: The aim of this study was to analyse the possibility of pathogenesis and progressivity of PA to CXPA. Methods: Twenty-four samples of PA and three control samples of CXPA were stained with haematoxylin and eosin (HE), Mallory’s trichrome, and Periodic acid–Schiff (PAS). All of the PA cases were identified through different kinds of stroma, tumour cells types, morphologic patterns, or else through atypical appearance of the PA similar to the CXPA. Results: Twenty-four samples of PA demonstrated that the most dominant stroma was myxofibrous, and the dominant tumour cell type was plasmacytoid cells with a trabecular pattern. Additionally, in the pleomorphic histological picture of adenomas we found several patterns of malignant tumour behaviour, including pseudopodia, metaplasia and hyalinisation, and cholesterol crystals that are thought to come from fat cell necrosis derived from adipose metaplasia. Conclusions: PA displays several atypical characteristics that have the potential to develop into malignancies such as CXPA, due to capsular infiltration, necrosis, hyalinization and high mitotic activity of cells, but all these atypical characteristics that we observed still cannot be clearly classified as CXPA because they require other specific examinations.

Background: Tooth eruption begins after crown and root formation and may be delayed by gestational diabetes mellitus. Metformin can control blood glucose levels through gluconeogenesis inhibition, and consuming thymoquinone for diabetic treatment will regenerate pancreatic β cells and reduce oxidative stress. Purpose: The objective of this study is to compare the tooth eruption in rats that were born with diabetes and are being treated with either metformin or thymoquinone. Methods: This study used 48 Wistar rats (Rattus norvegicus L.), and the rat sample was divided into four groups, including rats who were born from healthy mothers, rats who were born from untreated diabetic mothers, rats who were born from diabetic mothers that were treated with metformin and rats who were born from diabetic mothers that were treated with thymoquinone. Diabetes was induced by intraperitoneal injection of a single dose of streptozotocin (40 mg/kg BB). Each rat sample was taken with simple random sampling from different mothers, and body weight, blood glucose levels and levels of tooth eruption were recorded. Eruptions of the maxillary right first molar were measured from the cusp of the tooth to the alveolar epithelial lining. Results: Based on the measurements of tooth eruption, it was found that groups A, C and D were closer to mucosa on day 1, 7 and 14 than group B. Based on statistical analysis, there were significant differences (p = 0.03) between group B and groups C and D. Conclusions: Rats born from untreated diabetic mothers have more delays in tooth eruption than those born from diabetic mothers who are treated with metformin and thymoquinone. Thymoquinone has the potential to be an alternative to metformin because it has been shown to be similarly effective.

Measures to prevent dental and oral diseases in children can be done by providing information about parts of the teeth, dental caries and the process of dental caries, as well as plaque control as an effort to prevent the occurrence of dental and oral diseases. This activity was carried out aimed at increasing understanding and knowledge of the importance of maintaining oral health in children, especially elementary school students. The knowledge that has been given is expected to be able to change the behavior of students of SDN Kranjingan III Jember, East Java-Indonesia to be able to maintain the health of their teeth and mouth properly. This can be seen through the debris index. In addition to counseling activities, other methods provided were demonstrations of how to brush teeth, demonstration of pictures and posters carried out by the service team from the Faculty of Dentistry, University of Jember. The service activities carried out can increase knowledge and improve the degree of dental and oral health of SDN Kranjingan III Jember students.

Background: Tooth loss can disrupt the mastication process. Mastication disorders limit the amount of food a person consumes, affecting nutrition. The number of functional tooth units (FTUs) can affect nutritional status, measured using the body mass index (BMI). Purpose: The purpose of this study is to analyse the effect of the number of FTUs on the BMI in the elderly. Methods: This research was conducted in four villages in the Jember Regency. The number of subjects was 189, aged 45 years and over. The number of FTUs was calculated based on the anterior and posterior teeth that have contact with the antagonist and the BMI using the BMI formula. The data was analysed using a linear regression test; the level of significance is 0.005. Results: A simple linear regression test showed that there was significant correlation between FTU and BMI (p=0.366). Conclusion: The number of FTUs affects BMI; the higher the number of FTUs, the greater the BMI.

Background: Diabetes mellitus is a metabolic disorder caused by insufficient insulin production due to pancreatic β cell destruction, whereas in gestational diabetics an increase of hormone estrogen induces insulin resistance. Oral candidiasis constitutes an opportunistic fungal infection due to a compromised immune system that is a medical condition reported by diabetics, including those suffering from gestational diabetes. Purpose: To determine the severity of oral candidiasis in female Wistar rats with type 1 and gestational diabetes mellitus. Methods: This research constituted a laboratory experiment incorporating a post test-only group control design whose subjects were female Wistar rats divided along the following lines: group 1 consisted of diabetic non-pregnant rats, group 2 contained diabetic pregnant rats induced by streptozotocin and the control group members constituted normal female rats. Diabetes induction was performed by means of 40 mg/kgBW streptozotocin administrated intraperitoneally. Diabetes mellitus was confirmed when the blood glucose level ≥ 120 mg/dL. All groups were exposed to 0.2 ml Candida albicans suspension (5x108 CFU/ml) in the oral buccal vestibule between the distal incisors and mesial maxillary first molar for three days. A swab was performed on the third day after final exposure before the samples were observed under a light microscope. Candida albicans cultivation and calculation of the resulting colonies was carried out on Sabouraud Dextrose Agar after they had been identified by means of a germ tube test. Results: The result confirmed the absence of hyphae in the control group, while in group 1 all samples contained hyphae. Moreover, group 2 featured a dense hyphae population. A chi-square test indicated a statistical significance (p

The purposes of this study are to study the pathogenesis of oral cancer and to see the role play of oncogenes, onco-suppressor genes in cancer growth and their mutation type. There are many predisposing factors which may influence the development ofcancer. The factors are divided intrinsic (hereditary) and extrinsic factors (bacteria, viruses, fungi, chemical, drugs, radiation, trauma, heat, cold and nutrition). These agents may act individually, in combination with other carcinogen (co-carcinogen) or in combination with other agents that do not in themselves causes cancer (promoters), but that help the carcinogens to mutate or depress cells, but in the mechanism still enigma. Oncogenes oncosuppressor genes are normal genes in human. Oncogenes functions are as growth factor (e.g. sis), growth factor receptor (e.g. erbB1), signal transducer (e.g. ras) or nuclear factor (e.g. myc, jun). Tumor (oral cancer) will be arises if oncogenes and onco-suppressor genes function are disturbed by some carcinogen and these genes have mutation, deletion, amplification or translocation. That was also related to the loss or inactivation of onco-suppressor genes such as p53, so that causes the loss of the normal growth regulation/strait control that associated with tumorigenesis.DOI: 10.14693/jdi.v15i2.66

Background: It is known that oral squamous epithelial dysplasia (SED) and carcinoma in-situ (CIS) are precancerous lesion and it could transform to squamous cell carcinoma (SCC). We had reported p53-Protein Over-Expression and Gene Mutational of Oral CIS, such as basaloid, verrucous, and acanthothic/atrophic types, but demarcated between SED to CIS and CIS to SCC and how their transformation is still unclear. It is considered that their molecular behavior related one another. Purpose: To understand the molecular behavior of them we examined p53 exon 5-8 gene mutation and their protein expression in the sequential cases. Methods: Using 10 cases formalin–fixed paraffin sections that composed SED appearance, CIS and SCC in the same case were subjected to P53 immunohistochemistry. Then all cases were subjected to p53 gene mutations analysis. By laser capturing microdissection dysplasia part, CIS part and SCC part were cutted, and followed by direct sequencing of PCR product for exon 5-8. Result: SED p53-protein over-expression in some cells, and the expression was increased to CIS and SCC. Mutational analysis for p53 gene showed that 60% of p53 gene mutation in CIS also found in SCC, therefore SCC had additional mutation in other exon of p53 gene. While no particular mutations were found in SED part of all cases. Conclusion: Carcinoma in-situ is a squamous cell carcinoma eventhough not invasive yet, but squamous epithelial dysplasia is an early step to malignancy. It needs other genes examination to know any genes are involved in the precancerous to cancer transformation process.

We had been reported histological types of oral carcinoma in-situ (oral CIS), such as basaloid, verrucous, and acanthothic/ atrophic types. We considered that they have different histological appearance influenced by molecular behavior. To understand the molecular behavior of them we examined p53 exon 4–8 gene mutation and their protein expression. Using 35 cases formalin-fixed paraffin sections of oral CIS and 10 cases of mild and moderate squamous epithelial displasia (SED) as a control were subjected to p53 immunohistochemistry. In the next step all cases were subjected to p53 gene mutations analysis by laser capturing microdissection and direct sequencing of PCR product for exon 4–8. Showed that p53-protein over-expression were found in basal layer of SED and the p53 protein over-expression were confined in the whole layer of CIS-basaloid type, basal and parabasal layers of CIS-verrucous type, and sporadically in the basal layer of CIS-acanthothic type. Mutational analysis for p53 gene showed 43% of total cases of CIS had p53 gene mutation therefore CIS-basaloid type had mutations more frequently than the other types and mutation in exon 8 more dominant than other exons, which had some common mutation at codons 196, 248, 282, 291, and 306, while no particular mutations were found in control (SED).Our criteria to diagnose several types of oral carcinoma in-situ by p53 protein expression and mutational analysis could be used to understand molecular behavior of CIS.

The purposes of this study are to study the pathogenesis of oral cancer and to see the role play of oncogenes, onco-suppressor genes in cancer growth and their mutation type. There are many predisposing factors which may influence the development of cancer. The factors are divided intrinsic (hereditary) and extrinsic factors (bacteria, viruses, fungi, chemical, drugs, radiation, trauma, heat, cold and nutrition). These agents may act individually, in combination with other carcinogen (co-carcinogen) or in combination with other agents that do not in themselves causes cancer (promoters), but that help the carcinogens to mutate or depress cells, but in the mechanism still enigma. Oncogenes onco-suppressor genes are normal genes in human. Oncogenes functions are as growth factor (e.g. sis), growth factor receptor (e.g. erbB1), signal transducer (e.g. ras) or nuclear factor (e.g. myc, jun). Tumor (oral cancer) will be arises if oncogenes and onco-suppressor genes function are disturbed by some carcinogen and these genes have mutation, deletion, amplification or translocation. That was also related to the loss or inactivation of onco-suppressor genes such as p53, so that causes the loss of the normal growth regulation/strait control that associated with tumorigenesis. Keywords: oncogenes, onco-suppressor genes, pathogenesis, carcinoma

The patient is a 10-month and 21-day-old girl who began to show developmental delays at 3 months of age, with severe language developmental disorders, stereotyped movements, and easily provoked laughter. Physical examination revealed fair skin and a flattened occiput. At 10 months of age, a video electroencephalogram suggested atypical absence seizures, with migrating slow-wave activity observed during the interictal period. Whole exome sequencing of three family members indicated a novel mutation in the AP2M1 gene, c.508C>T (p.R170W), in the patient. A total of six cases of autosomal dominant intellectual developmental disorder 60 with seizures associated with mutations in the AP2M1 gene have been reported both domestically and internationally (including this study). The main clinical features included developmental delays (6 cases), language developmental disorders (5 cases), stereotyped movements (3 cases), a tendency to smile (1 case), and atypical absence seizures (4 cases). Interictal electroencephalograms showed widespread spike waves and spike-slow wave discharges (5 cases), and migrating slow-wave activity (1 case). The c.508C>T (p.R170W) mutation may be a hotspot for mutations in the AP2M1 gene, and its clinical features are similar to those of Angelman syndrome.

Alzheimer's disease (AD) is a progressive and fatal neurodegenerative disease. The prevalent features of AD pathogenesis are the appearance of β-amyloid (Aβ) plaques and neurofibrillary tangles, which cause microglial activation, synaptic deficiency, and neuronal loss. Microglia accompanies AD pathological processes and is also linked to cognitive deficits. Purinergic signaling has been shown to play a complex and tight interplay with the chemotaxis, phagocytosis, and production of pro-inflammatory factors in microglia, which is an important mechanism for regulating microglia activation. Here, we review recent evidence for interactions between AD, microglia, and purinergic signaling and find that the purinergic P2 receptors pertinently expressed on microglia are the ionotropic receptors P2X4 and P2X7, and the subtypes of P2YRs expressed by microglia are metabotropic receptors P2Y 2 , P2Y 6 , P2Y 12 , and P2Y 13 . The adenosine P1 receptors expressed in microglia include A 1 R, A 2A R, and A 2B R. Among them, the activation of P2X4, P2X7, and adenosine A 1 , A 2A receptors expressed in microglia can aggravate the pathological process of AD, whereas P2Y 2 , P2Y 6 , P2Y 12 , and P2Y 13 receptors expressed by microglia can induce neuroprotective effects. However, A 1 R activation also has a strong neuroprotective effect and has a significant anti-inflammatory effect in chronic neuroinflammation. These receptors regulate a variety of pathophysiological processes in AD, including APP processing, Aβ production, tau phosphorylation, neuroinflammation, synaptic dysfunction, and mitochondrial dysfunction. This review also provides key pharmacological advances in purinergic signaling receptors., (© 2024. The Author(s), under exclusive licence to Springer Nature B.V.)

Objectives: To investigate the differences in clinical characteristics among children on prolonged mechanical ventilation (PMV) due to different primary diseases., Methods: A retrospective analysis was performed on the clinical data of 59 pediatric patients requiring PMV from July 2017 to September 2022. According to the primary disease, they were divided into respiratory disease (RD) group, central nervous system (CNS) group, neuromuscular disease (NMD) group, and other disease group. The four groups were compared in terms of general information, treatment, and outcome., Results: There were significant differences among the four groups in age, body weight, Pediatric Logistic Organ Dysfunction-2 (PELOD-2) score, Pediatric Risk of Mortality III (PRISM Ⅲ) score, analgesic and sedative treatment, nutrition supply, rehabilitation treatment, tracheotomy, successful ventilator weaning, and outcomes ( P <0.05). Compared with the RD group, the CNS group and the other disease group had a significantly higher age and a significantly higher proportion of children receiving rehabilitation treatment, and the CNS group had a significantly higher proportion of children receiving tracheotomy ( P <0.008). Compared with the other disease group, the CNS group and the NMD group had significantly lower PELOD-2 and PRISM III scores, and the CNS group had a significantly higher proportion of children with successful ventilator weaning and a significantly higher proportion of children who were improved and discharged ( P <0.008)., Conclusions: There are differences in clinical characteristics among children receiving PMV due to different etiologies. Most children in the RD group have a younger age, and children in the CNS group have a relatively good prognosis.

CAPZA2 encodes the α2 subunit of CAPZA, which is vital for actin polymerization and depolymerization in humans. However, understanding of diseases associated with CAPZA2 remains limited. To date, only three cases have been documented with neurodevelopmental abnormalities such as delayed motor development, speech delay, intellectual disability, hypotonia, and a history of seizures. In this study, we document a patient who exhibited seizures, mild intellectual disability, and impaired motor development yet did not demonstrate speech delay or hypotonia. The patient also suffered from recurrent instances of respiratory infections, gastrointestinal and allergic diseases. A novel de novo splicing variant c.219+1 G > A was detected in the CAPZA2 gene through whole-exome sequencing. This variant led to exon 4 skipping in mRNA splicing, confirmed by RT-PCR and Sanger sequencing. To our knowledge, this is the third study on human CAPZA2 defects, documenting the fourth unambiguously diagnosed case. Furthermore, this splicing mutation type is reported here for the first time. Our research offers additional support for the existence of a CAPZA2-related non-syndromic neurodevelopmental disorder. Our findings augment our understanding of the phenotypic range associated with CAPZA2 deficiency and enrich the knowledge of the mutational spectrum of the CAPZA2 gene., (© 2024. The Author(s), under exclusive licence to The Japan Society of Human Genetics.)

Objectives: To explore the risk factors associated with cow's milk protein allergy (CMPA) in infants., Methods: This study was a multicenter prospective nested case-control study conducted in seven medical centers in Beijing, China. Infants aged 0-12 months were included, with 200 cases of CMPA infants and 799 control infants without CMPA. Univariate and multivariate logistic regression analyses were used to investigate the risk factors for the occurrence of CMPA., Results: Univariate logistic regression analysis showed that preterm birth, low birth weight, birth from the first pregnancy, firstborn, spring birth, summer birth, mixed/artificial feeding, and parental history of allergic diseases were associated with an increased risk of CMPA in infants ( P <0.05). Multivariate logistic regression analysis revealed that firstborn ( OR =1.89, 95% CI : 1.14-3.13), spring birth ( OR =3.42, 95% CI : 1.70-6.58), summer birth ( OR =2.29, 95% CI : 1.22-4.27), mixed/artificial feeding ( OR =1.57, 95% CI : 1.10-2.26), parental history of allergies ( OR =2.13, 95% CI : 1.51-3.02), and both parents having allergies ( OR =3.15, 95% CI : 1.78-5.56) were risk factors for CMPA in infants ( P <0.05)., Conclusions: Firstborn, spring birth, summer birth, mixed/artificial feeding, and a family history of allergies are associated with an increased risk of CMPA in infants.

Background: The Diabetic Retinopathy Extended Screening Study (DRESS) aims to develop and validate a new DR/diabetic macular edema (DME) risk stratification model in patients with Type 2 diabetes (DM) to identify low-risk groups who can be safely assigned to biennial or triennial screening intervals. We describe the study methodology, participants' baseline characteristics, and preliminary DR progression rates at the first annual follow-up., Methods: DRESS is a 3-year ongoing longitudinal study of patients with T2DM and no or mild non-proliferative DR (NPDR, non-referable) who underwent teleophthalmic screening under the Singapore integrated Diabetic Retinopathy Programme (SiDRP) at four SingHealth Polyclinics. Patients with referable DR/DME (> mild NPDR) or ungradable fundus images were excluded. Sociodemographic, lifestyle, medical and clinical information was obtained from medical records and interviewer-administered questionnaires at baseline. These data are extracted from medical records at 12, 24 and 36 months post-enrollment. Baseline descriptive characteristics stratified by DR severity at baseline and rates of progression to referable DR at 12-month follow-up were calculated., Results: Of 5,840 eligible patients, 78.3% (n = 4,570, median [interquartile range [IQR] age 61.0 [55-67] years; 54.7% male; 68.0% Chinese) completed the baseline assessment. At baseline, 97.4% and 2.6% had none and mild NPDR (worse eye), respectively. Most participants had hypertension (79.2%) and dyslipidemia (92.8%); and almost half were obese (43.4%, BMI ≥ 27.5 kg/m 2 ). Participants without DR (vs mild DR) reported shorter DM duration, and had lower haemoglobin A1c, triglycerides and urine albumin/creatinine ratio (all p < 0.05). To date, we have extracted 41.8% (n = 1909) of the 12-month follow-up data. Of these, 99.7% (n = 1,904) did not progress to referable DR. Those who progressed to referable DR status (0.3%) had no DR at baseline., Conclusions: In our prospective study of patients with T2DM and non-referable DR attending polyclinics, we found extremely low annual DR progression rates. These preliminary results suggest that extending screening intervals beyond 12 months may be viable and safe for most participants, although our 3-year follow up data are needed to substantiate this claim and develop the risk stratification model to identify low-risk patients with T2DM who can be assigned biennial or triennial screening intervals., (© 2024. The Author(s).)

Abstract: Recent research has revealed that aerobic glycolysis has a strong correlation with sepsis-associated pulmonary fibrosis (PF). However, at present, the mechanism and pathogenesis remain unclear. We aimed to test the hypothesis that the adenosine monophosphate-activated protein kinase (AMPK) activation and suppression of hypoxia-inducible factor 1α (HIF-1α)-induced aerobic glycolysis play a central role in septic pulmonary fibrogenesis. Cellular experiments demonstrated that lipopolysaccharide increased fibroblast activation through AMPK inactivation, HIF-1α induction, alongside an augmentation of aerobic glycolysis. By contrast, the effects were reversed by AMPK activation or HIF-1α inhibition. In addition, pretreatment with metformin, which is an AMPK activator, suppresses HIF-1α expression and alleviates PF associated with sepsis, which is caused by aerobic glycolysis, in mice. Hypoxia-inducible factor 1α knockdown demonstrated similar protective effects in vivo . Our research implies that targeting AMPK activation and HIF-1α-induced aerobic glycolysis with metformin might be a practical and useful therapeutic alternative for sepsis-associated PF., Competing Interests: The authors report no conflict of interests., (Copyright © 2023 by the Shock Society.)

Background: Fibrosis is a heavy burden on the global healthcare system. Recently, an increasing number of studies have demonstrated that Extracellular vesicles play an important role in intercellular communication under both physiological and pathological conditions. This study aimed to explore the role of extracellular vesicles' in fibrosis using bibliometric methods., Methods: Original articles and reviews related to extracellular vesicles and fibrosis were obtained from the Web of Science Core Collection database on November 9, 2022. VOSviewer was used to obtain general information, including co-institution, co-authorship, and co-occurrence visualization maps. The CiteSpace software was used to analyze citation bursts of keywords and references, a timeline view of the top clusters of keywords and cited articles, and the dual map. R package "bibliometrix" was used to analyze annual production, citation per year, collaboration network between countries/regions, thematic evolution map, and historiography network., Results: In total, 3376 articles related to extracellular vesicles and fibrosis published from 2013 to 2022 were included in this study, with China and the United States being the top contributors. Shanghai Jiao Tong University has the highest number of publications. The main collaborators were Giovanni Camussi, Stefania Bruno, Marta Tepparo, and Cristina Grange. Journals related to molecular, biology, genetics, health, immunology, and medicine tended to publish literature on extracellular vesicles and fibrosis. "Recovery," "heterogeneity," "degradation," "inflammation," and "mesenchymal stem cells" are the keywords in this research field. Literature on extracellular vesicles and fibrosis associated with several diseases, including "kidney disease," "rheumatoid arthritis," and "skin regeneration" may be the latest hot research field., Conclusions: This study provides a comprehensive perspective on extracellular vesicles and fibrosis through a bibliometric analysis of articles published between 2013 and 2022. We identified the most influential countries, institutions, authors, and journals. We provide information on recent research frontiers and trends for scholars interested in the field of extracellular vesicles and fibrosis. Their role in biological processes has great potential to initiate a new upsurge in future research., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)

Objective: To investigate the clinical phenotype and gene variation conditions in neonatal intrahepatic cholestasis caused by citrin deficiency (NICCD), so as to provide a basis for genetic counseling and clinical diagnosis and treatment of the family. Methods: 11 cases of neonatal intrahepatic cholestasis who visited the Children's Hospital Affiliated to Zhengzhou University between February 2019 and March 2021 were selected as the study subjects. High-throughput sequencing technology was used to detect the gene variation condition in 11 neonatal patients and 100 normal control neonates. The suspicious loci and family members were verified by Sanger sequencing and QPCR technology. Results: All 11 children with NICCD had different degrees of jaundice and liver damage symptoms, combined with coagulation dysfunction and anemia ( n = 7), cardiac malformation ( n = 2), elevated myocardial enzymes ( n = 4), hyperlipidemia ( n = 1), hyperkalemia ( n = 1), persistent diarrhea ( n = 3), developmental delay ( n = 1). A total of 10 different types of SLC25A13 gene mutations were detected in 11 cases, including three frameshift mutations, two splicing changes, two missense mutations, one intron insertion, one nonsense mutation, and one heterozygous deletion. After reviewing literature and databases, c.1878delG(p.I627Sfs*73) and exon11 deletion were novel mutations that had not been reported at home or abroad. Conclusion: The clinical features of NICCD are non-specific, and genetic testing aids in the early and accurate diagnosis of the disease, providing an important basis for clinical treatment and genetic counseling for family members. In addition, the detection of novel mutation sites has enriched the SLC25A13 gene variation spectrum.

Canine brucellosis is primarily caused by Brucella canis , but other Brucella species can also cause the disease. Identifying sequences specific to B. canis and establishing PCR assays that can distinguish between B. canis and other Brucella species is essential to determine the etiology of canine brucellosis and the source of infection and to achieve effective control. We analyzed the gaps and SNPs of genomes I and II from B. canis strain RM6/66 and B. melitensis strain 16M using the Mauve genome alignment software, and the specificity of each of these differential regions was analyzed by BLAST. A 132 bp specific sequence was found between the DK60&#95;915 (glycosyl hydrolase 108 family protein) and DK60&#95;917 (aldose 1-epimerase) loci in B. canis chromosome 1. Further comparative analysis revealed that this is a reverse complement sequence between B. canis and other Brucella species. Then, three primers were designed based on the sequence that could detect B. canis with a 310 bp amplification product or other Brucella species with a 413 bp product. The PCR based on these primers had reasonable specificity and a sensitivity of 100 copies of Brucella DNA. The detection results for the blood samples of the aborted dogs showed a favorable accordance with the Bruce-ladder multiplex PCR assay. In conclusion, we found a specific reverse complement sequence between B. canis and other Brucella and developed a PCR method that allows a more comprehensive identification of the pathogen involved in canine brucellosis. These findings provide an effective means for preventing and controlling brucellosis., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Ye, Yang, Li, Hao, Zhang, Mei, Zhang, Du, Yv, Liu and Chen.)

The succession of microbiota is closely associated with several essential factors, including race, sex, health condition, lifestyle, postmortem interval, etc., and it has great potential application value in forensic medicine. This paper summarizes recent studies on the forensic applications of the microbiome, including individual identification, geographical feature identification, origin identification of the tissue or body fluid, and postmortem interval estimation, and introduces the current machine learning algorithms for microbiology research based on next-generation sequencing data. In addition, the current problems facing forensic microbiomics such as the extraction and preservation of samples, construction of standardization and database, ethical review and practical applicability are discussed. Future multi-omics studies are expected to explore micro ecosystems from a comprehensive and dynamic perspective, to promote the development of forensic microbiomics application.

Background: The coronavirus disease 2019 (COVID-19) becomes a worldwide public health threat. Increasing evidence proves that COVID-19-induced acute injuries could be reversed by a couple of therapies. After that, post-COVID-19 fibrosis (PCF), a sequela of "Long COVID," earns rapidly emerging concerns. PCF is associated with deteriorative lung function and worse quality of life. But the process of PCF remains speculative. Therefore, we aim to conduct a bibliometric analysis to explore the overall structure, hotspots, and trend topics of PCF., Materials and Methods: A comprehensive search was performed in the Web of Science core database to collect literature on PCF. Search syntax included COVID-19 relevant terms: "COVID 19," "COVID-19 Virus Disease," "COVID-19 Virus Infection," "Coronavirus Disease-19," "2019 Novel Coronavirus Disease," "2019 Novel Coronavirus Infection," "SARS Coronavirus 2 Infection," "COVID-19 Pandemic," "Coronavirus," "2019-nCoV," and "SARS-CoV-2"; and fibrosis relevant terms: "Fibrosis," "Fibroses," and "Cirrhosis." Articles in English were included. Totally 1,088 publications were enrolled. Searching results were subsequentially exported and collected for the bibliometric analysis. National, organizational, and individual level data were analyzed and visualized through biblioshiny package in the R, VOSviewer software, the CiteSpace software, and the Graphical Clustering Toolkit (gCLUTO) software, respectively., Results: The intrinsic structure and development in the field of PCF were investigated in the present bibliometric analysis. The topmost keywords were "COVID-19" (occurrences, 636) surrounded by "SARS-CoV-2" (occurrences, 242), "coronavirus" (occurrences, 123), "fibrosis" (occurrences, 120), and "pneumonia" (occurrences, 94). The epidemiology, physiopathology, diagnosis, and therapy of PCF were extensively studied. After this, based on dynamic analysis of keywords, hot topics sharply changed from "Wuhan," "inflammation," and "cytokine storm" to "quality of life" and "infection" through burst detection; from "acute respiratory syndrome," "cystic-fibrosis" and "fibrosis" to "infection," "COVID-19," "quality-of-life" through thematic evolution; from "enzyme" to "post COVID." Similarly, co-cited references analysis showed that topics of references with most citations shift from "pulmonary pathology" (cluster 0) to "COVID-19 vaccination" (cluster 6). Additionally, the overview of contributors, impact, and collaboration was revealed. Summarily, the USA stood out as the most prolific, influential, and collaborative country. The Udice French Research University, Imperial College London, Harvard University, and the University of Washington represented the largest volume of publications, citations, H -index, and co-authorships, respectively. Dana Albon was the most productive and cited author with the strongest co-authorship link strength. Journal of Cystic Fibrosis topped the list of prolific and influential journals., Conclusion: Outcomes gained from this study assisted professionals in better realizing PCF and would guide future practices. Epidemiology, pathogenesis, and therapeutics were study hotspots in the early phase of PCF research. As the spread of the COVID-19 pandemic and progress in this field, recent attention shifted to the quality of life of patients and post-COVID comorbidities. Nevertheless, COVID-19 relevant infection and vaccination were speculated to be research trends with current and future interest. International cooperation as well as in-depth laboratory experiments were encouraged to promote further explorations in the field of PCF., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Zhong, Zhou, Mei, Tang, Feng, He, Xu and Xing.)

Background: A tertiary-hospital-based retrospective study (2011-2019) was conducted to determine the mediating role of hypertensive disorders of pregnancy and abnormal placentations between advanced maternal age and adverse neonatal outcomes., Methods: Data from a tertiary-hospital-based retrospective study (n= 23051) was used and conducted regression-based mediation analysis to assess the mediating role of hypertensive disorders of pregnancy and abnormal placentation between the advanced maternal age and adverse neonatal outcomes., Results: After adjusting for confounding factors, the indirect effect of advanced maternal age on preterm births, perinatal mortality, and low birth weight mediated by hypertensive disorders of pregnancy was [aOR 4.95 (95% CI: 4.05, 5.85)], [aOR 2.82 (95% CI: 1.78, 3.86)], and [aOR 5.90 (95% CI: 4.93, 6.87)], respectively. The indirect effect of advanced maternal age on preterm births and low birth weight mediated by abnormal placentation was [aOR 6.83 (95% CI: 5.70, 7.97)] and [aOR 4.18 (95% CI: 3.26, 5.11)]. About, 23%, 37%, and 17% of the effect of advanced maternal age on preterm births, perinatal mortality, and low birth weight was mediated by hypertensive disorders of pregnancy, respectively. Furthermore, abnormal placentation mediates the association between advanced maternal age and preterm births by 18% and low birth weight by 23%., Conclusion: Hypertensive disorders of pregnancy and abnormal placentation partially mediate the association between advanced maternal age and adverse neonatal outcomes., Competing Interests: Conflict of interest All the authors declare no conflict of interest., (Copyright © 2022 Li et al. Published by Tehran University of Medical Sciences.)

Objectives: To compare the sociodemography, disease characteristics and hypertension self-care profiles and to determine the factors influencing Hypertension Self-Care Profiles (HTN-SCP) in two populations in primary care settings from Singapore and Malaysia., Design: Cross-sectional, cross national., Setting: Multi-centre, primary care clinics Malaysia and Singapore., Participants: 1123 adults with hypertension enrolled and analysed., Primary and Secondary Outcome Measures: Comparison between sociodemography, disease characteristics and the mean scores of HTN-SCP domains (behaviour, motivation and self-efficacy) and the factors influencing hypertension self-care., Results: 1123 adults with hypertension attending primary care clinics in Malaysia and Singapore were involved. The participants' mean age was 63.6 years (SD 9.7) in Singapore and 60.4 (SD 9.1) in Malaysia. Most of the participants in Singapore had tertiary education (22.3%) compared with Malaysia (13.0%), p<0.001. A higher proportion of participants from Singapore had controlled blood pressure (74.6%) compared with Malaysia (33.8%), p<0.001. The mean total score of HTN-SCP was significantly higher among Singapore participants compared with Malaysia participants 190 (SD 28) versus 184 (SD 23) (p<0.001). Similarly, the mean score for motivation domain 67 (SD 10) versus 65 (SD 9), followed by self-efficacy score 65 (SD 11) versus 62 (SD 9) and behaviour score (58 SD 9 vs 56 SD 9) were higher among Singapore participants. In both countries, the factors which influenced higher HTN-SCP mean scores across all domains were being Indian and had tertiary education., Conclusions: The study population in Singapore had a higher HTN-SCP mean score compared with Malaysia. The common factors influencing higher HTN-SCP mean scores at both study sites were ethnicity and level of education. Future intervention to improve self-care among people with hypertension may need to be tailored to their behaviour, motivation and self-efficacy levels., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Oral anticoagulant therapy use in patients with atrial fibrillation (AF) remains suboptimal in Singapore, despite the availability of both warfarin and non-vitamin K antagonist oral anticoagulants (NOACs). Primary care physicians' (PCP) decision-making to initiate and select appropriate anticoagulant medication is pivotal in reducing complications among patients with AF. This study explored the factors influencing PCPs' decision-making in anticoagulant initiation and anticoagulant switch for patients with non-valvular AF., Method: The study design is qualitative research based on the theoretical framework of the Generalist Wheel of Knowledge, Understanding and Inquiry. In-depth interviews or focus group discussions were conducted with 27 PCPs in general practice in urban Singapore. The audio-recordings were transcribed and coded to identify themes, which are framed according to the "clinician", "patient", "medical condition and treatment" and "healthcare system and policy" domains., Results: Personal training and experience with anticoagulant therapy; understanding patient risk-stratification; AF detection during clinical practice; medication cost; clinical support services for anticoagulation monitoring and constraints in existing care model influenced PCPs in their anticoagulant prescription. PCPs preferred to seek guidance from cardiologists in managing patients with newly diagnosed AF and attempted to engage their patients in decision-making regarding anticoagulant therapy. Some PCPs perceived sub-specialized primary care clinics focusing on AF co-management with cardiologists as an ideal setting for initiation and maintenance of anticoagulant therapy., Conclusions: PCPs are influenced by multiple interrelated factors while making decisions on anticoagulant initiation and anticoagulant switch for patients with AF. Their proposed care model to address the barriers awaits feasibility and acceptance assessment in future research.

Abstract: Traditional forensic identification relies on forensic experts to manually extract information and provide identification opinions based on medicine, biology and other fields of knowledge combined with personal work experience, which is not only time-consuming and require great effort, but also affected by subjective factors that are difficult to overcome. In the era of big data, the booming development of artificial intelligence brings new ideas to forensic medicine. In recent years, forensic researchers at home and abroad have conducted many studies based on artificial intelligence technology, such as face recognition, age and gender identification, DNA analysis, postmortem interval estimation, injury and cause of death identification, showing the feasibility and advantages of using artificial intelligence technology to solve forensic identification problems. As a new means of technology that has adapted to the development of the times, artificial intelligence has brought new vitality to forensic medicine, but at the same time also some new challenges. How to deal with these challenges scientifically and form a new mode of 'artificial intelligence plus forensic medicine' with artificial intelligence and forensic medicine developing collaboratively is a new direction for the development of forensic medicine in the era of big data., Competing Interests: The authors of this article and the planning committee members and staff have no relevant financial relationships with commercial interests to disclose., (Copyright© by the Editorial Department of Journal of Forensic Medicine.)

Abstract: Objective To explore the genetic background and structure of Urumqi Mongolians, the previously developed 39-AIM-InDels panel for ancestry inference was utilized in the present study. Methods The blood samples of 145 unrelated healthy Urumqi Mongolian individuals were collected and genotyped. The compositions of ancestry information of Urumqi Mongolians were studied with 17 different populations from three continents （East Asia, Europe and Africa） as reference populations. Then, multiple population genetics and bioinformatics analysis methods were applied, the Fst and DA values between matched populations were compared and analyzed, PCA analysis was performed and a phylogenetic tree was constructed. The proportions of ancestry information components of Urumqi Mongolians were analyzed with Structure software, etc. Results The ancestry information components of Urumqi Mongolian group in different intercontinental populations accounted for 89%, 7%, and 3% of East Asian, European, and African populations, respectively. Compared with other intercontinental populations, Urumqi Mongolian group and East Asian populations have lower Fst and DA values, and they were in the same cluster in PCA analysis as well. In a phylogenetic tree, the Urumqi Mongolian group was in the same branch as East Asian populations. Conclusion Urumqi Mongolian group had relatively close genetic relationships with East Asian populations, and the proportion of its East Asian ancestry was about 89%., Competing Interests: The authors of this article and the planning committee members and staff have no relevant financial relationships with commercial interests to disclose., (Copyright© by the Editorial Department of Journal of Forensic Medicine.)

Genomic full length sequence of HLA-A*24:20:01:01, was identified by cloning and sequencing from a Chinese donor., (© 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Tubulin beta eight class VIII (TUBB8) is a subtype of β-tubulin that only exists in primates. Mutations in the TUBB8 gene have been proven to cause oocyte maturation arrest. The aim of this study was to identify the new types of mutations in TUBB8. Six women (families) with oocyte maturation arrest and 100 healthy controls were recruited. The sequence of the TUBB8 gene was amplified and analyzed by Sanger sequencing, which revealed a de novo heterozygous variant c.292G > A (p.G98R) of TUBB8 in one affected individual. This TUBB8 variant was absent in the 100 fertile females and was predicted to be highly damaging to the function of the TUBB8 protein by SIFT and PolyPhen-2. This novel variant extends the spectrum of TUBB8 mutations and the presence of a TUBB8 mutation is being considered to be indicative of a poor prognosis for the success of assisted reproductive treatment.

Polygonatum is a genus of the perennial herb family Liliaceae, with great potential in food, medicine and other field. In this study, genetic diversity and cluster structure analysis of 6 species in Polygonatum were investigated the molecular marker technique of simple sequence repeat (SSR). A total of 49 SSR makers were used to study genetic diversity and population structure within 60 germplasm resources which obtained from 38 counties and cities in 14 provinces of China. A total of 211 alleles were identified and the number of alleles ranged from 2 to 10, with an average of 4.306 1 alleles per SSR. The range of polymorphism information content (PIC) varied from 0.731 8 to 0.031 7, with the average of 0.309 6. The cluster analysis classified 60 germplasm resources into four defined groups at the genetic distance value of 0.26, among which most species with relatives were clustered into the same group. Extraordinarily, there were 6 germplasm resources clustered into other species, indicating that the classification of inter-genus and geographical distribution was crossed in Polygonatum. The genetic diversity index of the 4 geographical populations from high to low was: Western region, Central China, Southern China, Eastern China. The population structure analysis, also indicating divided the entire collection into four groups, which was similar to the assignment pattern of cluster structure analysis. These results suggested that the Polygonatum germplasm resources used in this study is rich in relatively high genetic diversity with large variation range, relatively fuzzy boundaries of species. It appeared the phenomenon that there is a difference decreases between the alternate leaf system and the rotation leaf system. The genetic diversity in the western region was higher than that in other regions, and the western region may be the origin center of the genus Polygonatum., Competing Interests: The authors of this article and the planning committee members and staff have no relevant financial relationships with commercial interests to disclose., (Copyright© by the Chinese Pharmaceutical Association.)

A novel HLA-G allele, HLA-G*01:01:01:07, was identified in a Chinese patient with Posner-Schlossman syndrome., (© 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Wnt-induced secreted protein-1 (WISP1) is an extracellular matrix protein that has been reported in cancer researches. Our previous studies on WISP1 implied it could be a harmful mediator in septic mice. However, its role in liver ischemia reperfusion (I/R) injury is unknown. This study investigated the effects of WISP1 on liver I/R damage. Male C57BL/6 wild-type mice were used to undergo 60 min segmental (70%) ischemia. WISP1 expression was measured after indicated time points of reperfusion. Anti-WISP1 antibody was injected intraperitoneally to mice. Toll-like receptor 4 (TLR4) knockout mice and TIR-domain-containing adaptor inducing interferon-β (TRIF) knockout mice were adopted in this study. WISP1 was significantly enhanced after 6 h of reperfusion when compared with sham treated mice and significantly decreased either by TLR4 knockout mice or TRIF knockout mice. Anti-WISP1 antibody significantly decreased serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), pathological changes and pro-inflammatory cytokine levels in the mice following I/R. Furthermore, significantly increased serum transaminase levels were found in C57 wild-type mice treated with recombinant WISP1 protein, but not found in TLR4 knockout or TRIF knockout mice subjected to liver I/R. Taken together, WISP1 might contribute to hepatic ischemia reperfusion injury in mice and possibly depends on TLR4/TRIF signaling.

Objective: To study the changes of minimal residual disease (MRD) in children with B cell acute lymphoblastic leukemia (B-ALL) of different genetic abnormalities., Methods: Between February 2004 and April 2013, 271 newly diagnosed B-ALL pediatric patients who had finished the induction chemotherapy were enrolled in the study. The characteristics of changes in MRD in patients with different genetic abnormalities on the 15th day and at the end of the induction therapy were analyzed., Results: On the 15th day of the induction chemotherapy, the MRD positive proportion in patients with hyperdiploid was higher on all the three cut-off levels of MRD≥0.1%, 1% and 10% compared to patients without hyperdiploid (P<0.05), but there was no significant difference in the MRD positive proportion on the three levels of MRD between the TEL-AML1-positive and TEL-AML1-negative groups (P>0.05). On the end of induction chemotherapy, there was no significant difference in the MRD positive proportion on the three levels of MRD between the patients with and without hyperdiploid (P>0.05), neither between the BCR-ABL-positive and negative groups. The MRD positive proportion in TEL-AML1-negative patients was significantly higher than in TEL-AML1-positive patients on all three levels of MRD (P<0.05). The MRD positive proportion on two levels of MRD≥0.01% and 0.1% in E2A-PBX1-negative patients was significantly higher than in E2A-PBX1-positive patients (P<0.05)., Conclusions: Children with B-ALL of different genetic abnormalities have different MRD levels during, and at the end of, induction therapy. The prognostic significance of MRD may be related to the genetic abnormalities.

The practice of hybridization has greatly contributed to the increase in crop productivity. A major component that exploits heterosis in crops is the cytoplasmic male sterility (CMS)/nucleus-controlled fertility restoration (Rf) system. Through positional cloning, it is shown that heterozygous alleles (RsRf3-1/RsRf3-2) encoding pentatricopeptide repeat (PPR) proteins are responsible for restoring fertility to cytoplasmic male-sterile radish (Raphanus sativus L.). Furthermore, it was found that heterozygous alleles (RsRf3-1/RsRf3-2) show higher expression and RNA polymerase II occupancy in the CMS cytoplasmic background compared with their homozygous alleles (RsRf3-1/RsRf3-1 or RsRf3-2/RsRf3-2). These data provide new insights into the molecular mechanism of fertility restoration to cytoplasmic male-sterile plants and illustrate a case of overdominance.

Magnesium fructose-1,6-diphosphate is a novel agent of antimyocardial ischaemia. In the present study, the subchronic toxicity of magnesium fructose-1,6-diphosphate was investigated after 13-week repeated intravenous administration in beagle dogs. The animals received doses of 0, 75, 150 and 300 mg/kg/day (three males and three females for each dose). During the study period, clinical signs, mortality, body weights, food consumption, electrocardiogram, urinalysis, haematology, clinical biochemistry, macroscopic findings, organ weights and histopathology were examined. The administration of magnesium fructose-1,6-diphosphate resulted in increased incidence of clinical signs, including salivation and emesis. These effects were transient and were noted in almost all dogs given 300 mg/kg/day and occasionally noted in the 150 mg/kg/day dose-treated animals. Serum magnesium in the 150 mg/kg/day and 300 mg/kg/day dose-treated animals was significantly increased after 6- and 13-week administration, but recovered at the end of a 2-week recovery period. At 6 weeks, a statistically significant decrease in serum electrolytes, including sodium and potassium, was observed in the treatment groups. There were no other treatment-related findings. Under the conditions of the present study, magnesium fructose-1,6-diphosphate did not show any evidence of target organ toxicity. The no-observed-adverse-effect level for 13-week intravenous administration of magnesium fructose-1,6-diphosphate to beagle dogs was considered 75 mg/kg/day based on observations of clinical signs and serum electrolytes.

In this study, we have investigated a new fertility restorer (Rf) locus for cytoplasmic male sterility (CMS) in radish. We have obtained a CMS-Rf system consisting of sterile line '9802A1', maintainer line '9802B1' and restorer line '9802H'. F(1) plants from cross between sterile line '9802A1' and restorer line '9802H' were all male fertile, self pollination of F(1) plants produced an F(2) segregating population consisting of 600 individuals. The segregating population was found to fit a segregation ratio 3:1 for male fertile and sterile types, indicating that male fertility is restored by a single dominant gene (termed Rfo2) in the CMS-Rf system. Based on the DNA sequence of Rfo/Rfk1 (AJ535623), just one full length gene in the sterile line '9802A1', in the restorer line '9802H' and in the male fertile line '2006H', was cloned, respectively. The three sequences correspond to the same gene with two alleles: Rfob in '9802H' and rfob in '9802A1' and '2006H'. These two alleles differ from Rfo/Rfk1 and rfk1 (AJ535624) alleles by two synonymous base substitutions, respectively. Based on the differences between the Rfob and rfob genes, one PCR-based marker was developed, and designated Marker 1, which is identical to the corresponding region of Rfob by sequence analysis. In the F(2) segregating population described above, the Marker 1 was present in 5 sterile plants and in 453 fertile plants, absent in 4 fertile plants and in 138 sterile plants, and was found to fit a segregation ratio 3:1 indicating that Rfob was single copy in '9802H'. Linkage analysis showed that the Rfo2 locus for our CMS-Rf system was distant from the Rfo locus by about 1.6 cM. The sterile line '9802A1' was pollinated by the male fertile line '2006H' and the resulting F(1) plants were all male fertile. These results indicated that the male fertility of radish CMS can be restored by a new Rf locus, which linked tightly to the Rfo locus.

Objective: To study the clinical effect of "Jin's three-needling" in the treatment of generalized anxiety disorder., Methods: Fifty-eight patients with generalized anxiety were randomly assigned to two groups equally, the medication group treated with anti-anxiety drugs and the acupuncture group with "Jin's three-needling". The treatment course was 6 weeks. The clinical effects were evaluated with Hamilton anxiety scale (HAMA), clinical global impression (CGI), and treatment emergent symptom scale (TESS) before treatment and at the end of 2nd, 4th, 6th week of the treatment course. The concentration of 5-hydroxytryptamine (5-HT) in platelet, and plasma levels of corticosterone (CS) and adrenocorticotropic hormone (ACTH) were measured with high performance liquid chromatography-electrochemical detection (HPLC-ED) method before and after treatment., Results: The clinical effects in the two groups were equivalent, while the adverse reaction found in the acupuncture group was less than that in the medication group (P < 0.05). The platelet concentration of 5-HT and plasma ACTH level decreased significantly in both groups after treatment with insignificant difference between the group (P < 0.05). The plasma CS level had no obvious change in the two groups after treatment as compared with that before treatment respectively., Conclusion: "Jin's three-needling" shows similar curative effect on generalized anxiety to routine Western medicine but with less adverse reaction, which may be realized through regulating the platelet 5-HT concentration and plasma ACTH level.

A putative sulfate transporter gene, RSultr3.2A, was identified from radish (Raphanus sativus L.). The RSultr3.2A gene encodes a polypeptide of 651 amino acids with a calculated molecular mass of 71701 Da. The deduced amino acid sequence preserves the common motifs of the sulfate transporters and exhibits a high degree of homology to other plant sulfate transporters. RSultr3.2A was not induced by sulfur starvation and was expressed in roots, stems, leaves, flowers and young pods, suggesting a possible need for the nonregulated and constitutive sulfate transport system of the plant. The RSultr3.2A is a single copy gene in the radish genome. A genomic sequence information corresponding to RSultr3.2A cDNA was found by PCR and sequencing. Comparison of cDNA and genomic sequences revealed that the coding sequence of RSultr3.2A consisted of 12 exons. In addition, another cDNA (RSultr3.2B) from radish young pods was found. As compared with RSultr3.2A, RSultr3.2B encodes a 499 amino acid protein with modifications in the carboxy-terminus. Sequence analysis suggested an occasional donor splicing site mutation (GT to TT) in the RSultr3.2A gene from radish young pods leading to the truncated cDNA RSultr3.2B.