Sleep and hypertension.

PURPOSE: Hypertension is a global public issue, and sleep status was regarded as its risk factor; however, the results were inconsistent. This study aims to deeply investigate the correlation between sleep status and hypertension. METHODS: The electronic databases Cochrane Library, Pubmed, and Embase updated to May 31, 2019, were retrieved. Studies were selected according to the predefined screening criteria, and their qualities were assessed by using quality check scales. Based on Stata 15.1 software, the associations between sleep status and hypertension were analyzed by meta-analyses, using odds ratio and 95% confidence interval as effect indexes. Furthermore, publication bias and small study bias were evaluated using Begg and Egger's test. In addition, sensitivity analysis was conducted through ignoring one study per time and then observing its influences on the pooled results. RESULTS: A total of 54 studies (involving 1,074,207 subjects) were eligible for this meta-analysis. Six factors were included in this study. Raised blood pressure was associated with obstructive sleep apnea (OSA), oxygen desaturation index (ODI), short sleep duration, and long sleep duration. The differences in ≤ 5 h, 6 h, ≥ 9 h, and 10 h groups had statistical significances, while there was no significant difference in ≥ 8 h group. Snoring is a risk factor of hypertension (OR = 1.94, 95%CI 1.41-2.67). Subgroup analysis was conducted and results were varied. CONCLUSIONS: The hypertension risk might be reduced by treated OSA, ODI, and snoring, as well as appropriate sleep duration. More studies with large sample sizes and high qualities should be included to support the findings further.

Application of miniSTR Loci and Its Detection System for Degraded Materials in Forensic Medicine.

OBJECTIVES: To establish multiplex system of 16 miniSTR loci, and explore its application value for the degraded materials in forensic medicine. METHODS: The multiplex system of 16 miniSTR loci was established using a six-dye fluorescence labeling technology and its application value in forensic medicine was assessed. RESULTS: A six-dye fluorescence labeling miniSTR amplification kit was developed, which enabled 15 autosomal STR loci, Amelogenin locus and DYS391 to be typed simultaneously. This method showed good specificity and could provide stable and accurate typing results with a sensitivity of 50 pg. This system also provided a good test result for the normal biological sample of actual cases. CONCLUSIONS: The multiplex system of 16 miniSTR loci has application value for degraded and trace materials with the advantages of high sensitivity and database compatibility, which can be used for forensic casework.

[Recurrent bleeding following the renal artery embolization treating post-percutaneous nephrolithotomy hemorrhage: causes and countermeasure].

Objective: To explore the causes and countermeasure in recurrent bleeding following the selective renal artery embolization treating post-percutaneous nephrolithotomy hemorrhage. Methods: A total of 334 patients of severe renal hemorrhage associated with percutaneous nephrolithotomy (PCNL) from March 2011 to April 2015 were analyzed retrospectively.All the patients underwent super selective angiography and renal artery embolization.The causes of recurrent hemorrhage were analyzed and principles for diagnosis and embolization were studied. Results: The initial embolization was performed in 329 cases hospitalized in the First Affiliated Hospital of Guangzhou Medical University and 318 cases were successfully stopped bleeding with a hemostatic rate of 96.7 %(318/329). Of total 334 consecutive cases, there were 16 cases of recurrent renal hemorrhage, 11 cases were initially embolized in this hospital, and otherwise the other 5 cases were in other hospitals. Causes of recurrent hemorrhage were missed embolization of tiny pseudoaneurysm (n=12), and two cases of 12, the tiny pseudoaneurysm were feeding by accessory renal arteries, undetected arteriovenous fistula(n=2), recanalization of the embolized arteries (n=2). Conclusion: The causes of recurrent bleeding fallowing the initial selective renal artery embolization treating post-percutaneous nephrolithotomy hemorrhage are varied, and missed embolization of tiny pseudoaneurysm is the major cause of unsuccessful initial renal artery embolization. To strengthen the understanding of tiny pseudoaneurysm is helpful to improve the success rate of hemostasis.

[New progress of BRAF gene and thyroid cancer].

It is noteworthy that the incidence of thyroid cancer around the world has increased significantly in recent decades, raising an imperative need to research its pathogenesis, diagnosis and treatment. Up to now, fine needle aspiration biopsy (FNAB) of thyroid has been acknowledged to discriminate benign from malignant thyroid nodules with the highest sensitivity and specificity. However, 10% to 40% thyroid nodules cannot be discriminated by FNAB. Therefore, it is vitally important to look for highly-correlated tumor makers in molecule level. BRAF mutation is a focus in thyroid cancer research, and some studies showed that this mutation is essential to the onset and development of thyroid cancer, especially papillary thyroid cancer. Joint detection of BRAF mutation could improve diagnostic sensitivity of thyroid cancer, which is crucial for thyroid cancer diagnosis and classification. As for treatment, the discovery of target gene enabled molecule therapy for thyroid cancer, raising hopes for patients with thyroid cancer that refractory to conventional treatments. Currently, many molecule therapeutics relating to BRAF has already undergone clinical trials. It is believed that further research on BRAF-thyroid cancer relationship could create a new field for diagnosis and treatment of thyroid cancer, and set a mode for discovering others molecule markers.

[Drug-resistant gene polymorphisms in Plasmodium falciparum isolated from Bioko Island, Equatorial Guinea in 2018 and 2019].

OBJECTIVE: To investigate the genetic polymorphisms of Plasmodium falciparum multidrug resistance protein 1 (PfMDR1), chloroquine resistance transporter (PfCRT) and Kelch 13 (PfK13) genes in Bioko Island, Equatorial Guinea, so as to provide insights into the development of the malaria control strategy in local areas. METHODS: A total of 85 peripheral blood samples were collected from patients with Plasmodium falciparum infections in Bioko Island, Equatorial Guinea in 2018 and 2019, and genomic DNA was extracted. The PfMDR1, PfCRT and PfK13 genes were amplified using a nested PCR assay. The amplification products were sequenced, and the gene sequences were aligned. RESULTS: There were no mutations associated with artemisinin resistance in PfK13 gene in Bioko Island, Equatorial Guinea, while drug-resistant mutations were detected in PfMDR1 and PfCRT genes, and the proportions of PfMDR1_N86Y, PfMDR1_Y184F and PfCRT_K76T mutations were 35.29% (30/85), 72.94% (62/85) and 24.71% (21/85), respectively. CONCLUSIONS: There are mutations in PfMDR1, PfCRT and PfK13 genes in P. falciparum isolates from Bioko Island, Equatorial Guinea.

Targeted inhibition of platelet-derived growth factor receptor-beta subunit in hepatic stellate cells ameliorates hepatic fibrosis in rats.

The activation of hepatic stellate cells (HSCs) is the key event of the pathogenesis of hepatic fibrosis. Platelet-derived growth factor (PDGF) is the most potent mitogen for HSCs, and PDGF receptor-beta subunit (PDGFR-beta) is required for the proliferation of HSCs induced by PDGF. In this study, a high gene-silencing-efficacy PDGFR-beta small interference RNA (siRNA) was synthesized that could suppress the PDGFR-beta expression and inhibit the activation and proliferation but could not induce the apoptosis of HSCs in vitro. To avoid the side effect of nonspecific interference of PDGFR-beta, we constructed an HSCs-specific short hairpin RNA (shRNA) expression plasmid in which PDGFR-beta shRNA was driven by a glial fibrillary acidic protein (GFAP) promoter. The double-staining immunofluorescence examination indicated that GFAP promoter could target the transgene expression into HSCs in carbon tetrachloride induced acute injured rat's liver and bile duct ligation (BDL)-induced chronic injured rat's liver. Furthermore, HSCs-specific PDGFR-beta shRNA could relieve liver injury and hepatic fibrosis in the rat's model induced by BDL. This study demonstrates that PDGFR-beta siRNA may be presented as an antifibrogenic agent. The application of HSCs-specific RNA interference induced by the GFAP promoter might supply a new powerful tool for cell-specific gene therapy of hepatic fibrogenesis.

MOTS-c improves osteoporosis by promoting osteogenic differentiation of bone marrow mesenchymal stem cells via TGF-ß/Smad pathway.

OBJECTIVE: To explore whether MOTS-c could improve osteoporosis by promoting osteogenic differentiation of rat bone mesenchymal stem cells (BMSCs) via transforming growth factor-ß (TGF-ß)/Smad pathway. MATERIALS AND METHODS: Rat BMSCs were isolated and cultured, followed by osteogenic and lipid differentiation. CCK-8 (cell counting kit-8) assay was performed to detect the highest treatment dose of MOTS-c that did not affect cell proliferation. Expressions of osteogenesis-related genes (ALP, Bglap, and Runx2) were detected by qRT-PCR (quantitative Real-Time Polymerase Chain Reaction) and Western blot, respectively. Alizarin red staining and alkaline phosphatase (ALP) cytochemical staining were carried out to evaluate the effect of MOTS-c on BMSCs osteogenesis. TGF-ß/Smad pathway-related genes (TGF-ß1, TGF-ß2, and Smad7) in BMSCs treated with MOTS-c were detected. Finally, TGF-ß1 was knocked down to investigate the regulatory effect of MOTS-c on BMSCs osteogenesis. RESULTS: BMSCs exhibited an elongated morphology and was identified with a high purity by flow cytometry. After osteogenic differentiation, alizarin red staining and ALP staining were all positive. MOTS-c treatment could remarkably stimulate the formation of calcified nodules in BMSCs. Besides, TGF-ß/Smad pathway-related genes were significantly upregulated after BMSCs were treated with MOTS-c. Promoted osteogenesis by MOTS-c treatment was reversed by the TGF-ß1 knockdown. CONCLUSIONS: MOTS-c promotes cell differentiation of BMSCs to osteoblasts via TGF-ß/Smad pathway.

[Langerhans cell histiocytosis of the thyroid: a case report].

Langerhans cell histiocytosis (LCH) is a rare monoclonal disease,its clinical presentation is highly variable because it can affect multiple organs, such as lung, bone, skin, lymph nodes, hypothalamopituitary axis, and other multiple sites. LCH involving the thyroid gland is extremely rare, here we reported a rare case of LCH involving thyroid, presenting as painless thyroid goiters.

Baicalin can attenuate the inhibitory effects of mifepristone on Wnt pathway during peri-implantation period in mice.

Wnts are considered as important factors in uterus developmental process and embryo implantation. Baicalin has been demonstrated to possess tocolytic properties. In order to investigate the effect of baicalin on the Wnt signaling pathway during the peri-implantation, pregnant Kuming mice were randomly divided into four groups: control group, baicalin group administered with 40mg/kg BW of baicalin through an intragastric gavage on day 2 to 7 of the pregnancy (Pd2-Pd7), mifepristone group treated with 4mg/kg BW of mifepristone, an abortifacient agent, via subcutaneous administration on Pd4, and baicalin+mifepristone group treated with their combination. The concentrations of the implantation-related steroid hormones (progesterone and estradiol) in the blood serum were measured with RIA. The gene and protein expression levels of the important molecules of the Wnt pathway (Wnt4, LRP6, Dkk1 and ß-catenin) in the endometrium were detected with RT-PCR and western blot, respectively. The results showed that baicalin decreased (P<0.05) the estradiol levels on Pd4-Pd8 and increased (P<0.05) the progesterone levels on Pd3-Pd8. Mifepristone increased (P<0.05) the estradiol levels on Pd5-Pd8 and decreased (P<0.05) the progesterone levels on Pd6-Pd8. Compared with the control group, baicalin increased the gene and protein expression levels of Wnt4, LRP6 and ß-catenin (P<0.05) and decreased the gene and protein expression levels of Dkk1 (P<0.05) during the middle-to-late stage of the experiment in mice uterine tissue. Baicalin alleviated the mifepristone-induced increase or decrease in the serum levels of progesterone and estradiol, and the gene or protein expression levels of Wnt4, LRP6 and ß-catenin. The tocolytic properties tocolysis of baicalin may be realized through regulating the levels of estrogen/progesterone and the important components of canonical Wnt signaling pathway during the embryo implantation process intervened with the subcutaneous administration of mifepristone in the mice.

Long-term observation after radiotherapy for nasopharyngeal carcinoma (NPC).

One thousand one hundred twenty-seven cases of nasopharyngeal carcinoma were treated with routine radiotherapy from October 1969 to March 1976, of which 436 cases have survived for more than 5 years, 323 cases have survived for over 10 years. The follow-up rate was 98.4%. The present paper analyzes the factors involved in these 436 cases. All patients were treated with tele60Co unit, and in the neck some cases were treated with orthovoltage therapy. The total dose to the primary lesion was 60-75 Gy in 6-8 weeks and in a few cases over 80 Gy were needed, and 50 Gy were applied bilateral cervical lymphatic chain. In this series of cases the 10-year overall survival rate was 28.7%, with Stage I being 66.7%, Stage II 46.5%, Stage III 28.0%, and Stage IV 18.6%, respectively. Statistically, 68 cases died of cardiovascular and other diseases and should be eliminated for net survival calculations. Therefore, we could obtain an actual 10-year survival rate of 30.5%. However, it should be noted that most of these cases were advanced, with Stage III, IV accounting for 82.3%, thus at Stage I, II the 10-year survival rate was 48%, while at Stage III, IV rate was down to 24.5%, which was statistically significant (p less than 0.01). Local and cervical recurrence as well as distant spread of diseases, for these cases started from the fifth to the tenth year after radiotherapy, the mortality caused by the above-mentioned three sites together was 76.9%. According to these findings, we propose that follow-up after radiotherapy in NPC exceeds 10-years. Of the 323 NPC cases, 10 were nasopharyngeal local recurrence which were re-irradiated, accounting for 3.1%. This paper shows that the 3-year survival rate in the local recurrence which were re-irradiated was 34.5%, the 5-year survival rate was 14.8%, and the 10-year survival rate was 11.5%. The failure after re-irradiation was caused by local recurrence and metastasis with a mortality of 83.6%. These results emphasize that the success of initial irradiation is important.

Development and localization of enkephalin and substance P in the nucleus of tractus solitarius in the medulla oblongata of human fetuses.

The presence of enkephalin and substance P-positive neurons and fibers were studied by immunohistochemistry (peroxidase-antiperoxidase or avidin-biotin-peroxidase complex methods) in 26 human fetuses ranging from 11 weeks of gestation to 40 weeks of gestation. Enkephalin-positive neurons were localized in the commissural, medial and intermediate subnuclei as early as 11-12 weeks' gestation. Positive enkephalin fibers were localized around 12 weeks' gestation and in many subnuclei, notably the medial, commissural, intermediate, ventrolateral, ventral and dorsolateral subnuclei. Substance P-positive neurons were localized in the commissural and medial subnuclei around gestation age 13 weeks. Positive substance P fibers appeared even earlier, around 11 weeks of gestation in many subnuclei, notably the medial, intermediate, ventral, ventrolateral and dorsolateral subnuclei. Increase in both enkephalin- and substance P-positive fibers was evident in the later stages of development (e.g. around 26 weeks of gestation). The importance of the early appearance of enkephalin and substance P neurons and fibers of the pain pathways in the major subnuclei connecting with the cardiovascular, gastrointestinal and respiratory functions in the human has to be stressed.

Inhibitory effect of Ginkgo biloba extract on the expression of inducible nitric oxide synthase in endothelial cells.

Excessive production of nitric oxide (NO) may have cytotoxic effects through the formation of peroxynitrite with superoxide. The extract of Ginkgo biloba leaves (EGb) has been demonstrated to be a potent scavenger of free radicals. Although EGb has been shown recently to inhibit NO production in macrophages, its effect on NO production in endothelial cells is largely unknown. The objective of this study was to elucidate the mechanism by which EGb affects NO production in a human endothelial cell line (ECV304). After cells were incubated with EGb (10-100 microg/mL) for 2 or 4 hr, the amounts of NO metabolites released by the cells were quantitated, and cellular NOS activities were determined following the conversion of [3H]arginine to [3H]citrulline. NOS protein expression was determined by western immunoblotting analysis. mRNA levels were examined by reverse transcription-polymerase chain reaction (RT-PCR) analysis. EGb (50 microg/mL) caused a 30% reduction of NO metabolites released by endothelial cells. Following EGb treatment, cellular inducible NO synthase (iNOS) activity was reduced by 28% with a concomitant reduction in the levels of iNOS protein mass and mRNA. There was no change in the activity or protein mass of constitutive NO synthase in these cells. EGb inhibited NO production by attenuating the level of iNOS mRNA in ECV304 cells. Selective inhibition of iNOS by EGb may be therapeutically relevant in modulating NO production in endothelial cells.

The first epidemic of dengue hemorrhagic fever in the People's Republic of China.

The first epidemic of dengue in China associated with significant severe and fatal hemorrhagic disease which met the World Health Organization case definition occurred on Hainan Island in 1985-1986. The epidemic began in Zhan County in September 1985, spread throughout the coastal areas, and ultimately involved 13 counties and cities of the island in 1986. The mosquito vector was Aedes aegypti. The morbidity associated with dengue infection on Hainan Island was 1,913 per 100,000 residents, with a case fatality rate of 0.25%. Severe disease was more prevalent in the 10-29-year-old age group. Principal clinical features in laboratory-confirmed cases were fever, osteoarthralgia, hemorrhage and/or shock, and thrombocytopenia. Complications such as acute intravascular hemolysis, diffuse intravascular coagulation, hemoconcentration, pleural effusion, altered mentality, and pneumonia were also observed. One hundred twenty-five isolates of dengue 2 virus were recovered from acute-phase serum samples from 278 patients, and 5 strains of this same virus serotype were isolated from 5 pools of adult Ae. aegypti.

Expression of p53 in oesophageal squamous cell carcinoma in Hong Kong Chinese.

We studied p53 overexpression in a series of 99 primary oesophageal squamous cell carcinomas (28 well-differentiated, 42 moderately-differentiated and 29 poorly-differentiated squamous cell carcinomas) from Chinese patients using the p53 protein specific mouse monoclonal antibody DO-7 on paraffin sections. The p53 protein was detected in 30% (30 cases) of the tumours. A significantly higher positive rate was noted in the poorly-differentiated tumours (11% for the well-differentiated, 31% for the moderately-differentiated and 48% for the poorly-differentiated tumours). In addition, strong positive p53 staining was identified only in the less differentiated tumour cells in the periphery of the tumour cell nests in all the cases and the expression was weaker in the better differentiated foci. The central keratinizing areas and the immediately adjacent tumour cells were always negative for p53. The adjacent normal oesophageal mucosa was all negative for p53 protein but the non-invasive dysplastic epithelium next to the tumours could also be strongly positive for p53 protein (four out of 14 cases in which the dysplastic epithelium adjacent to the tumour was adequately sampled). In two out of these four cases, the dysplastic epithelium showed staining for p53; even the adjacent invasive tumour was negative for p53. It is concluded that there is a strong relationship between p53 overexpression and tumour cell differentiation in oesophageal squamous carcinoma and overexpression of p53 can occur in non-invasive tumour cells.

Pathological changes in human malignant carcinoma treated with high-intensity focused ultrasound.

The purpose of this study was to investigate the pathologic changes of extracorporeal ablation of human malignant tumors with high-intensity focused ultrasound (HIFU). HIFU treatment was performed in the 164 patients with liver cancer, breast cancer, malignant bone tumor, soft tissue sarcoma and other malignant tumors at focal peak intensities from 5000 W x cm(-2) to 20,000 W x cm(-2), with operating frequencies of 0.8 to 3.2 MHz. To explore the pathologic impact of extracorporeal HIFU, 30 patients with malignant carcinoma underwent surgical removal after HIFU treatment. Pathologic findings showed that the treated tissues demonstrated homogeneous coagulative necrosis with an irreversible tumor cell death and severe damage to tumor blood vessels at the level of microsvasculature within the HIFU-targeted region. Thermolesions to intervening tissue were never observed. The treated region had a sharp border comprising only several cell layers between the treated and untreated areas. The repair of lesions had the processes of necrotic tissue absorption and granulation tissue replacement. It is concluded that extracorporeal treatment of human solid malignancies with HIFU could be safe, effective and feasible. As a noninvasive therapy, HIFU would be used clinically to treat patients with solid malignancies.

Expression of the p53 gene in trophoblastic cells in hydatidiform moles and normal human placentas.

In this study we compared the expression of p53 in six early placentas and eight hydatidiform moles using Northern blotting. A higher expression of p53 in hydatidiform moles as compared to normal placentas of comparable gestational age was observed. Immunohistochemical studies did not detect mutant protein of p53 in the hydatidiform moles. DNA sequencing was performed on four of the hydatidiform moles with increased expression of p53, but no mutations could be detected. The possible role of p53 in the pathogenesis of hydatidiform mole is discussed.

HDV (delta factor) infection complicated with subacute fulminant hepatitis B. A morphological and immunohistochemical observation.

In 75 patients with subacute fulminant hepatitis B (SAFH), HDAg positive liver cells were observed in 14 cases (18.67%) by direct enzyme labelled method. It was found further that HDV (delta factor) infection was an important cause in producing massive necrosis of liver cells and superinfection of HDV with hepatitis B was identified as one of the causes of SAFH. This experiment also showed that the number of HDAg positive cells was in direct proportion to the area of liver necrosis. No obvious lymphocytic infiltrations and cytotoxic phenomena around the necrotic foci and HDAg positive cells could be found, while the cytoplasmic type HDAg positive cells showed distinct degeneration or even atrophy. Hence it was suggested that HDV could be a direct pathogenesis. No obvious characteristic changes in morphology of HDV infection could be found.

[Analysis of residue and regression of metastatic cervical lymph nodes in NPC after radiotherapy].

Follow up results of residue and regression of metastatic cervical lymph nodes in NPC after radiotherapy are presented. All the 453 cases have been followed for more than five years. According to WHO's criteria, the relative 5 year survival rate was 43.9%. 389 of 453 had had lymph node metastases in the neck at the beginning of treatment. At the end of radiation, immediate regression rate of lymph nodes was 53.2%, which was related to lymph node size before radiotherapy. Five year survival rate of those whose lymph node metastases disappeared completely was 48.8% (group 1). There were 182 cases with residual nodes at the conclusion of radiation (140 recorded in detail). The regression rate of nodes was 96.4% (135/140) and the 5 year survival rate of these 140 patients was 40.0% (group 2). There is no significant difference and the long term results are similar in the two groups. Total recurrence rate in the neck was 4.4%: 5.3% in group 1 and 3.8% in group 2 (P greater than 0.05). The treatment results of the local cervical lesions are the same, too. In 182 cases with residual lesions, 121 with 147 clinically evaluable residual nodes, 0.5 approximately 3 cm in diameter, were followed. The regression time of these residual nodes was 2.5 approximately 2.7 months as to geometric mean (the regressive confidence limit 95%). To sum up, according to the routine cervical target dose, some nodes remaining at the of radiation seem to require no boost dose in order to avoid delayed radiation complications. But the residual nodes which recur during follow up would require a prompt retreatment.

[Studies on uranium mobilization agents. IV. Synthesis of N, N'-bis-[N-carboxymethyl-(2,3-dihydroxy-5-carbomethoxy) benzylaminoacetyl]-alpha, omega-diamines].

In continuation of searching for effective antidotes against uranium intoxication, a series of N,N'-bis-[N-carboxymethyl-(2,3-dihydroxy-5-carbomethoxy) benzylaminoacetyl]-alpha, omega-diamines was synthesized by reacting 2,3-dihydroxy-5-carbomethoxybenzylamine diacetic acid with diamines of different chain lengths. Their effects on the elimination of uranyl nitrate from rats were tested. Most of them were found to be more effective than the reported uranium chelating agents as Tiron and Phosphicine and compound IIa was shown to be the most promising. The results of pharmacological studies will be published elsewhere.

[Effects of guan-fu base a on experimental cardiac arrhythmias and myocardial contractility].

Guan-fu base A (GFA) is a terpenoid alkaloid isolated from the tuber of Aconitum coreanum in our institute. GFA (20-30 mg.L-1) reduced the ventricular tachycardia (VT) and ventricular fibrillation (VF) rate induced by K(+)-free and high Ca2+ solution in Langendorf heart of rats. Pretreatment of conscious rats with GFA 2.5-10 mg.kg-1 iv, increased the amount of beiwutine necessary to produce arrhythmias. Ouabain-induced VT in conscious dogs was reverted to sinus rhythm in 1-2 min by iv GFA 9-10 mg.kg-1. GFA 10-20 mg.kg-1 iv was also found to be effective in protecting anesthetized dogs from atrial fibrillation induced by topical application of ACh. GFA 10 mg.kg-1 iv obviously decreased heart rate and prolonged the P-R interval, but slightly affected the myocardial contractility in anesthetized dogs. GFA showed no obvious effect on stroke volume and cardiac output in conscious dogs. In conclusion, GFA showed therapeutic and prophylactic effect on different models of experimental arrhythmias without causing marked effect on myocardial contractility.