Preventing the Next Pandemic: The Case for Investing in Circulatory Health - A Global Coalition for Circulatory Health Position Paper.

The Coronavirus Disease 2019 (COVID-19) has had a continuous and robust impact on world health. The resulting COVID-19 pandemic has had a devastating physical, mental and fiscal impact on the millions of people living with noncommunicable diseases (NCDs). In addition to older age, people living with CVD, stroke, obesity, diabetes, kidney disease, and hypertension are at a particularly greater risk for severe forms of COVID-19 and its consequences. Meta-analysis indicates that hypertension, diabetes, chronic kidney disease, and thrombotic complications have been observed as both the most prevalent and most dangerous co-morbidities in COVID-19 patients. And despite the nearly incalculable physical, mental, emotional, and economic toll of this pandemic, forthcoming public health figures continue to place cardiovascular disease as the number one cause of death across the globe in the year 2020. The world simply cannot wait for the next pandemic to invest in NCDs. Social determinants of health cannot be addressed only through the healthcare system, but a more holistic multisectoral approach with at its basis the Sustainable Development Goals (SDGs) is needed to truly address social and economic inequalities and build more resilient systems. Yet there is reason for hope: the 2019 UN Political Declaration on UHC provides a strong framework for building more resilient health systems, with explicit calls for investment in NCDs and references to fiscal policies that put such investment firmly within reach. By further cementing the importance of addressing circulatory health in a future Framework Convention on Emergency Preparedness, WHO Member States can take concrete steps towards a pandemic-free future. As the chief representatives of the global circulatory health community and patients, the Global Coalition for Circulatory Health calls for increased support for the healthcare workforce, global vaccine equity, embracing new models of care and digital health solutions, as well as fiscal policies on unhealthy commodities to support these investments.

Salvia miltiorrhiza-derived miRNAs suppress vascular remodeling through regulating OTUD7B/KLF4/NMHC IIA axis.

Objective: Abnormal proliferation and migration of vascular smooth muscle cells (VSMCs) are essential for vascular remodeling. Natural compounds with diterpene chinone or phenolic acid structure from Salvia miltiorrhiza, an eminent medicinal herb widely used to treat cardiovascular diseases in China, can effectively attenuate vascular remodeling induced by vascular injury. However, it remains unknown whether Salvia miltiorrhiza-derived miRNAs can protect VSMCs from injury by environmental stimuli. Here, we explored the role and underlying mechanisms of Salvia miltiorrhiza-derived Sal-miR-1 and 3 in the regulation of VSMC migration and monocyte adhesion to VSMCs induced by thrombin. Methods: A mouse model for intimal hyperplasia was established by the ligation of carotid artery and the injured carotid arteries were in situ-transfected with Sal-miR-1 and 3 using F-127 pluronic gel. The vascular protective effects of Sal-miR-1 and 3 were assessed via analysis of intimal hyperplasia with pathological morphology. VSMC migration and adhesion were analyzed by the wound healing, transwell membrane assays, and time-lapse imaging experiment. Using loss- and gain-of-function approaches, Sal-miR-1 and 3 regulation of OTUD7B/KLF4/NMHC IIA axis was investigated by using luciferase assay, co-immunoprecipitation, chromatin immunoprecipitation, western blotting, etc. Results:Salvia miltiorrhiza-derived Sal-miR-1 and 3 can enter the mouse body after intragastric administration, and significantly suppress intimal hyperplasia induced by carotid artery ligation. In cultured VSMCs, these two miRNAs inhibit thrombin-induced the migration of VSMCs and monocyte adhesion to VSMCs. Mechanistically, Sal-miR-1 and 3 abrogate OTUD7B upregulation by thrombin via binding to the different sites of the OTUD7B 3'UTR. Most importantly, OTUD7B downregulation by Sal-miR-1 and 3 attenuates KLF4 protein levels via decreasing its deubiquitylation, whereas decreased KLF4 relieves its repression of transcription of NMHC IIA gene and thus increases NMHC IIA expression levels. Further, increased NMHC IIA represses VSMC migration and monocyte adhesion to VSMCs via maintaining the contractile phenotype of VSMCs. Conclusions: Our studies not only found the novel bioactive components from Salvia miltiorrhiza but also clarified the molecular mechanism underlying Sal-miR-1 and 3 inhibition of VSMC migration and monocyte adhesion to VSMCs. These results add important knowledge to the pharmacological actions and bioactive components of Salvia miltiorrhiza. Sal-miR-1 and 3-regulated OTUD7B/KLF4/NMHC IIA axis may represent a therapeutic target for vascular remodeling.

Salvianolic acid B inhibits Ang II-induced VSMC proliferation in vitro and intimal hyperplasia in vivo by downregulating miR-146a expression.

BACKGROUND: Salvianolic acid B (Sal B), a water-soluble compound extracted from Salvia miltiorrhiza that has been widely used to treat cardiovascular diseases for hundreds of years in China, exerts cardiovascular protection by multiple mechanisms. miR-146a is involved in vascular smooth muscle cell (VSMC) phenotypic modulation and proliferation. However, it has yet to be investigated whether the cardiovascular protective effect of Sal B is mediated by miR-146a. PURPOSE: To determine the relationship among the cardiovascular protective effect of Sal B, miR-146a expression, and VSMC proliferation. METHODS: MTS assay and cell counting were performed to evaluate the effect of Ang II, Sal B and miR-146a on VSMC proliferation. The neointima hyperplasia was assessed by hematoxylin/eosin staining. qRT-PCR was used to detect the expression of miR-146a, KLF5, cyclin D1 and PCNA. Western blot analysis was used to detect the expressions of KLF5, cyclin D1 and PCNA after miR-20b-5p was knocked down or overexpressed in VSMC. RESULTS: Sal B suppressed intimal hyperplasia induced by carotid artery ligation and decreased Ang II-induced VSMC proliferation by down-regulating the positive cell-cycle regulators KLF5 and cyclin D1. Further experiments showed that VSMC proliferation and upregulation of KLF5 and cyclin D1 induced by Ang II were accompanied by elevated miR-146a level. Furthermore, overexpression of miR-146a promoted and knockdown of miR-146a reduced Ang II-induced VSMC proliferation and ameliorated intimal hyperplasia induced by carotid artery ligation. Sal B inhibited Ang II-induced VSMC proliferation by suppressing miR-146a expression. CONCLUSION: Sal B inhibited Ang II-induced VSMC proliferation in vitro and intimal hyperplasia in vivo by downregulating miR-146a expression.

Genomewide DNA Methylation Responses in Patients with ß-Thalassemia Treated with Yisui Shengxue Granules ().

OBJECTIVE: To examine the clinical effects of Yisui Shengxue Granules () in the treatment of ß-thalassemia and explore its mechanism on DNA methylation levels. METHODS: A randomized placebo-controlled double-blinded trial was conducted. Forty patients with ß-thalassemia were recruited and distributed randomly by envelope method into an experimental group and a control group, 20 patients in each group. The patients were given Yisui Shengxue Granules in the experimental group and placebo in the control group (12 g/bag three times a day) during a 3-month intervention. Before and after 1, 2, and 3 months of treatment, peripheral intravenous blood was sampled, and blood parameters such as hemoglobin (Hb), red blood cells (RBCs), reticulocytes (Ret), and fetal hemoglobin (HbF) were analyzed. Mononuclear cells from 5 patients, who showed an obvious treatment effect, were isolated by density gradient centrifugation. DNA methylation was analyzed using an Affymetrix USA GeneChip Human Promoter 1.0 Array and Input-promoter 1.0. RESULTS: Compared with pre-treatment, there was an obvious increase in Hb and RBCs counts after 1, 2, and 3 months in the experiment group (P<0.01 or P<0.05). Meanwhile, HbF increased from the 2nd to the 3rd month (P<0.05). In the control group, Hb and RBCs showed no obvioas change. After 3-month treatment, DNA methylation results from 5 patients revealed that there were 24 hypomethylated genes and 3,685 hypermethylated genes compared with pre-treatment. Genes of insulin-like growth factor 1 receptor (IGF1R) and Janus kinase 3 (JAK3) revealed the most relations with other genes (degree: 21) and genes of 1-phosphatidylinositol-4, 5-bisphosphate phosphodiesterase gamma 2 (PLCG2) and mitogen-activated protein kinase 10 (MAPK10) showed a stronger intermediary role (betweenness centrality=0.04). CONCLUSIONS: JAK3 and MAPK10 are two key genes in bone marrow and the lymphatic system, and JAK3 is likely to be related to hematopoietic cytokines in the process of early hematopoiesis. (Registration No. NCT01549080).

miR-29a regulates vascular neointimal hyperplasia by targeting YY1.

OBJECTIVES: The formation of vascular neointima is mainly related to impairment of the vascular endothelial barrier and abnormal proliferation and migration of smooth muscle cells. The objective of this study was to investigate whether miR-29a exerts any promoting effect on the vascular neointimal hyperplasia and if so, its mechanism. MATERIALS AND METHODS: RT-qPCR was performed to determine expression of miR-29a in vascular smooth muscle cells (VSMC) and vascular neointimal hyperplasia. To further understand its role, we restored its expression in VSMCs by transfection with miR-29a mimics or inhibitors. Effects of miR-29a on cell proliferation were also determined. RESULTS: In this study, we used two kinds of model to observe the role of miR-29a in neointimal hyperplasia induced by carotid ligation or balloon injury. The major findings were that: (i) miR-29a overexpression promoted neointimal hyperplasia induced by carotid ligation; (ii) miR-29a increased proliferation of VSMCs, one aspect of which was by targeting expression of Ying and yang 1 protein (YY1), a negative regulator of Cyclin D1. A further aspect, was by increasing expression of Krüppel-like factor 5, a positive regulator of Cyclin D1, thereby allowing formation a synergistic effect. (iii) Tongxinluo (TXL), a traditional Chinese medicine reduced neointimal formation in ligated vessels by inhibiting VSMC proliferation and migration. CONCLUSIONS: These findings provide a new molecular mechanism of TXL in decreasing neointima hyperplasia.

Tongxinluo inhibits neointimal formation by regulating the expression and post-translational modification of KLF5 in macrophages.

Neointimal hyperplasia is a common pathological characteristic in diverse vascular remodeling diseases. The inflammatory response that follows vascular injury plays an important role in intimal hyperplasia. Tongxinluo (TXL), a traditional Chinese medicine, can ameliorate neointimal formation via suppressing vascular inflammatory response induced by vascular injury. However, the mechanisms underlying anti-inflammatory and anti-intimal hyperplasia of TXL are still not fully understood. The aim of present study was to examine whether the expression and post-translational modification of KLF5 were involved in the vasoprotective effects of TXL. In vivo, TXL inhibited neointimal formation induced by carotid artery injury. In vitro, TNF-α treatment of macrophages resulted in the increased proliferation and migration, but the effects of TNF-α on macrophages were blocked by TXL treatment. Next, KLF5 expression was up-regulated by carotid artery injury in vivo, as well as by exposure of macrophages to TNF-α in vitro, whereas TXL treatment abrogated the up-regulation of KLF5 by TNF-α or vascular injury. Intimal hyperplasia was strongly reduced in macrophage-specific KLF5 knockout (KLF5ly-/-) mice, indicating that TXL inhibits intimal hyperplasia by suppression of KLF5 expression. Furthermore, besides down-regulating KLF5 expression in macrophages, TXL also regulated KLF5 stability by ubiquitination and sumoylation of KLF5. Finally, TNF-α induced KLF5 sumoylation via PI3K/Akt signaling, whereas TXL inhibited Akt phosphorylation induced by TNF-α. We conclude that the multiple ingredients in TXL may act on different targets, which in turn generates a range of actions that manifest as a comprehensively vasoprotective effect.

Clinical Effect and Mechanism of Yisui Shengxue Granules in Thalassemia Patients with Mild, Moderate, or Severe Anemia.

Yisui Shengxue granules, which is a Chinese traditional medicine, can increase hemoglobin, red blood cells, and Ret of thalassemia patients with mild, moderate, and severe anemia and thus relieve clinical anemia symptoms. Studies on mechanism found that Yisui Shengxue granules can increase the proliferation ability of hematopoietic stem cells. Emodin promoted colony forming of hematopoietic stem cells. Yisui Shengxue granules can increase the activity of GSH-PX in bone marrow blood and decreased the severity of inclusion bodies on the cytomembrane of RBCs. YSSXG attenuated anemia symptoms in patients with thalassemia mostly by increasing the proliferation of hematopoietic stem cells and decreasing the hemolysis of RBCs.

Efficacy and complications of polyethylene glycols for treatment of constipation in children: a meta-analysis.

Constipation is a common childhood complaint. In 90% to 95% of children, constipation is functional, which means that there is no objective evidence of an underlying pathological condition. Polyethylene glycol (PEG or macrogol) solution is an osmotic laxative agent that is absorbed in only trace amounts from the gastrointestinal tract and routinely used to treat chronic constipation in adults. Here, we report the results of a meta-analysis of PEG-based laxatives compared with lactulose, milk of magnesia (magnesium hydroxide), oral liquid paraffin (mineral oil), or acacia fiber, psyllium fiber, and fructose in children. This meta-analysis was conducted in accordance with PRISMA guidelines and involved searches of MEDLINE, Cochrane, EMBASE, and Google Scholar databases up to February 10, 2014, using the keywords (Constipation OR Functional Constipation OR Fecal Impaction) AND (Children) AND (Polyethylene Glycol OR Laxative). Primary efficacy outcomes included a number of stool passages/wk and percentage of patients who reported satisfactory stool consistency. Secondary safety outcomes included diarrhea, abdominal pain, nausea or vomiting, pain or straining at defecation, bloating or flatulence, hard stool consistency, poor palatability, and rectal bleeding. We identified 231 articles, 27 of which were suitable for full-text review and 10 of which were used in the meta-analysis. Patients who were treated with PEG experienced more successful disimpaction compared with those treated with non-PEG laxatives. Treatment-related adverse events were acceptable and generally well tolerated. PEG-based laxatives are effective and safe for chronic constipation and for resolving fecal impaction in children. Children's acceptance of PEG-based laxatives appears to be better than non-PEG laxatives. Optimal dosages, routes of administration, and PEG regimens should be determined in future randomized controlled studies and meta-analyses.

Tongxinluo inhibits vascular inflammation and neointimal hyperplasia through blockade of the positive feedback loop between miR-155 and TNF-α.

Tongxinluo (TXL), a traditional Chinese medicine, has multiple vasoprotective effects, including anti-inflammation. MicroRNA-155 (miR-155) is involved in vascular inflammation and atherosclerosis. However, a direct relationship between TXL and miR-155 in the development of vascular inflammation and remodeling had not yet been shown. The objective of the present study was to investigate whether TXL exerts an inhibitory effect on the vascular inflammatory response and neointimal hyperplasia by regulating miR-155 expression. Using the carotid artery ligation model in mice, we have shown that TXL dose dependently inhibited neointimal formation and reduced the vascular inflammatory response by inhibiting inflammatory cytokine production and macrophage infiltration. miR-155 was induced by carotid artery ligation, and neointimal hyperplasia was strongly reduced in miR-155(−/−) mice. In contrast, miR-155 overexpression partly reversed the inhibitory effect of TXL on neointimal hyperplasia. In bone marrow-derived macrophages, miR-155 and TNF-α formed a positive feedback loop to promote the inflammatory response, which could be blocked by TXL. Furthermore, TXL increased Akt1 protein expression and phosphorylation in TNF-α-stimulated marrow-derived macrophages, and knockdown of Akt1 abrogated the TXL-induced suppression of miR-155. In conclusion, TXL inhibits the vascular inflammatory response and neointimal hyperplasia induced by carotid artery ligation in mice. Suppression of miR-155 expression mediated by Akt1 and blockade of the feedback loop between miR-155 and TNF-α are important pathways whereby TXL exerts its vasoprotective effects.

Molecular mechanism of yisui shengxue granule, a complex chinese medicine, on thalassemia patients suffering from hemolysis and anemia of erythrocytes.

The objective of this study was to investigate the therapeutic biological mechanism of Yisui Shengxue Granule (YSSXG), a complex Chinese medicine, on the hemolysis and anemia of erythrocytes from patient with thalassemia disease. Sixteen patients with thalassemia (8 cases of α-thalassemia and 8 cases of ß-thalassemia) disease were collected and treated with YSSXG for 3 months. The improvements of blood parameter demonstrated that YSSXG had a positive clinical effect on patients with thalassemia disease. For patients with α-thalassemia disease, RT-PCR showed that YSSXG upregulated the relative mRNA expression level of α-globin to ß-globin and downregulated DNMT1, DNMT3a, and DNMT3b mRNA compared with pretreatment. Western blotting showed that YSSXG downregulated the expression of DNMT1 and DNMT3a. For patients with ß-thalassemia disease, the relative expression level of (A) γ-globin to α-globin had an increasing trend and the level of BCL11A mRNA expression obviously increased. For all patients, RT-PCR showed that YSSXG upregulated mRNA expression of SPTA1 and SPTB. Activities of SOD and GSH-Px significantly increased and MDA obviously reduced on erythrocyte and blood serum after YSSXG treatment. TEM showed that YSSXG decreased the content of inclusion bodies. Activities of Na(+)K(+)-ATPtase and T-ATPtase of erythrocyte increased significantly after YSSXG treatment. This study provides the basis for mechanisms of YSSXG on thalassemia suffering with hemolysis and anemia of erythrocytes from patient.

[Impact of clinicopathological features and extent of lymph node dissection on the prognosis in early gastric cancer patients].

OBJECTIVE: To explore the impact of clinicopathological features and extent of lymph node dissection on the prognosis in early gastric cancer (EGC) patients. METHODS: A total of 142 EGC cases screened from database of gastric cancer of Sun Yat-sen University, from Aug. 1994 to Jan. 2010, were included in this study. According to the lymph node metastasis status, they were divided into lymph node negative (n = 116) and lymph node positive (n = 26) groups. The clinicopathological features of the two groups and the impact of extent of lymph node dissection on the prognosis were analyzed. RESULTS: There were no significant differences in age, gender, tumor size and location, Borrmann typing, WHO TNM staging, histological typing, and CEA value between the two groups (P > 0.05). The TNM stages in the lymph node positive group were higher than that in the lymph node negative group (P < 0.001). Between the cases who underwent D1 (n = 21) and D2 (n = 121) dissection, there were no significant differences in postoperative hospital days, blood transfusion volume, and operation time (P > 0.05). The median numbers of LN dissected in D1 and D2 cases were 4 (0 to 16) and 20 (12 to 30), with a significant difference (P = 0.000), but the number of positive LN without significant difference (P = 0.502). The postoperative complication rates were 9.5% in the D1 and 3.3% in the D2 dissection groups, without a significant difference (P = 0.128). The median survival time of the lymph node negative and positive groups was 156 vs. 96 months (P = 0.010). In cases who received D2 and D1 lymph node dissection, the median survival time (MST) was 156 vs. 96 months (P = 0.0022). In the lymph node positive group, D2 dissection prolonged survival time significantly than D1 dissection (96 vs. 27months) (P = 0.001). Cox regression analysis showed that the extent of lymph node dissection and LN metastasis were independent prognostic factors for EGC patients. CONCLUSIONS: It is not able to accurately assess the LN metastasis status preoperatively according to the routine clinicopathological features. For the patients with unknown LN metastasis status, D2 dissection should be the first choice. Comparing with D1 dissection, the morbidity of D2 dissection are not increased, but survival time is prolonged.

Effect of Yisui Shengxue Granule () on the oxidative damage of erythrocytes from patients with hemoglobin H disease.

OBJECTIVE: To investigate the effect of Yisui Shengxue Granule (, YSSXG), a complex Chinese medicine, on the oxidative damage of erythrocytes from patients with hemoglobin H (HbH) disease. METHODS: Twenty-two patients with HbH disease and 22 healthy volunteers were observed. YSSXG was given to patients with HbH disease for 3 months. Before and after the 3-month treatment, blood parameters [hemoglobin (Hb), red blood cells (RBCs), and reticulocyte percent (Ret)] were examined; inclusion bodies in erythrocytes were observed by transmission electron microscopy (TEM); activities of antioxidant defense enzymes [superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), and catalase (Cat)] and erythrocyte membrane malondialdehyde (MDA) concentrations were determined. RESULTS: In patients with HbH disease, measured values of RBC and Hb obtained from the first to the third months after treatment with YSSXG were significantly higher than before treatment (P<0.01). Measured values of Ret from the second to the third months after treatment were significantly lower than before treatment (P<0.05 and P<0.01, respectively). Prior to treatment with YSSXG, TEM images of RBCs showed the presence of numerous inclusion bodies. After treatment with YSSXG, the amount and volume of inclusion bodies decreased. Treatment with YSSXG also led to a significant increase in SOD activity (P<0.01), a decrease in Cat activity (P<0.01), and no significant differences in GSHPx activity (P>0.05) or MDA concentration (P>0.05). However, compared with the healthy counterparts, SOD, GSH-Px, and Cat activities presented at high levels (P<0.01) both before and after treatment. CONCLUSIONS: YSSXG could improve the degree of hemolysis and anemia in patients with HbH disease. The mechanism may be related to its antioxidative effects, which could elevate the activity of total SOD in erythrocytes and efficiently inhibit the oxidative precipitation of ß-globin chains.

Chemical composition of volatile oils from the pericarps of Indian sandalwood (Santalum album) by different extraction methods.

The chemical composition of volatile compounds from pericarp oils of Indian sandalwood, Santalum album L., isolated by hydrodistillation and solvent extraction, were analyzed by GC and GC-MS. The pericarps yielded 2.6 and 5.0% volatile oil by hydrodistillation and n-hexane extraction, and they were colorless and yellow in color, respectively. A total of 66 volatile components were detected. The most prominent compounds were palmitic and oleic acids, representing about 40-70% of the total oil. Many fragrant constituents and biologically active components, such as alpha- and beta-santalol, cedrol, esters, aldehydes, phytosterols, and squalene were present in the pericarp oils. This is the first report of the volatile composition of the pericarps of any Santalum species.

[Evaluation of heart and liver iron deposition status in patients with ß- thalassemia intermedia and major with MRI T2* technique].

OBJECTIVE: To study the status of iron deposition in patients with ß-thalassemia intermedia and major in mainland China. METHODS: The status of transfusion and chelation was examined in 39 patients with ß-thalassemia intermedia or major. Serum ferritin levels were measured. MRI T2* technique was used to detect cardiac and hepatic iron deposition. RESULTS: Serum ferritin levels ranged from the minimum of 1500 ng/mL up to a maximum of 11491 ng/mL. From liver MRI T2* measurement, 15 cases had severe hepatic iron deposition (38%) and moderate deposition was found in 15 cases (38%), mild in 7 cases (18%), and normal in 2 cases (5%). Heart MRI T2* showed severe heart iron deposition in 7 cases (18%), mild in 5 cases (13%), and normal in 27 cases (69%). One case had cardiac arrhythmia. Four cases were over 20 years of age, and presented with gonadal function hypoplasia. The majority of patients did not receive regular transfusion and they had delayed, suboptimal chelation due to financial problems. Serum ferritin level was closely related with timing and dosage of chelation. CONCLUSIONS: In patients with ß-thalassemia who do not receive early regular transfusion and iron chelation therapy, iron deposition may occur at an early age. Important organs and tissue functional lesions and related complications also result. Relevant agencies and family members should be aware of this trend and develop appropriate strategies to improve the medical condition and quality of life of patients with this disorder.

A case report of concomitant paroxysmal nocturnal hemoglobinuria and heterozygous ß-thalassemia.

Paroxysmal nocturnal hemoglobinuria (PNH) is a rare clonal blood disorder that presents chronic intravascular hemolysis. PNH concomitant with inherited hemolytic anemia has been rarely reported. Here, we report an interesting PNH patient who was misdiagnosed with iron deficiency anemia due to concomitant heterozygous ß-thalassemia. The patient experienced dizziness, fatigue, and restricted physical activity for the previous 3 years. Thalassemia gene analysis revealed heterozygous ß-thalassemia. Iron staining of the bone marrow demonstrated the absence of stainable iron and sideroblasts. The patient was diagnosed with iron deficiency anemia. Iron supplementation treatment was performed, but the anemia remained unresolved. The patient became transfusion dependent 1 year later and was admitted to our hospital in March 2010. Flow cytometry of the patient's peripheral blood demonstrated that 7.9% and 11.9% of the erythrocytes were CD59 and CD55 deficient, respectively. The patient was finally diagnosed with concomitant PNH and heterozygous ß-thalassemia.

[A family survey of syndromes of traditional Chinese medicine in patients with beta-thalassemia].

OBJECTIVE: To explore the relationship between syndromes of traditional Chinese medicine (TCM) and genetic background in patients with beta-thalassemia. METHODS: TCM syndromes were surveyed in the selected 78 patients with beta-thalassemia intermedia including 120 parents. The gene mutations were detected separately. The frequency and score of TCM syndromes between the offspring and their parents in different family types were analyzed, and the differences were compared. RESULTS: The 73 families were divided into two family types by hereditary characteristics. Family type one meant that genotypes of one of the parents were normal, while the offspring genotypes were heterozygous and were exactly the same as another parent. In the 22 families of type one, the heterozygous offspring manifested 6 high-frequency symptoms and signs such as spontaneous perspiration, dry mouth and dry throat, pale or sallow complexion, tidal fever and night sweating, lassitude and pale fingernails. The heterozygous parents manifested 5 high-frequency symptoms and signs such as lassitude in loins and knees, dizziness, aversion to cold and cold limbs, tinnitus, dry mouth and dry throat. The normal parents manifested 3 high-frequency symptoms and signs such as lassitude in loins and knees, dizziness, and spontaneous perspiration. TCM syndrome score in the heterozygous offspring was higher than that in the heterozygous and normal parents, but there was no significant difference (P>0.05). Family type two meant that genotypes of both parents were heterozygous, while the offspring genotypes were heterogenic duplex heterozygotes. In the 51 families of type two, the offspring manifested 9 high-frequency symptoms and signs such as pale or sallow complexion, spontaneous perspiration, dry mouth and dry throat, pale fingernails, tidal fever and night sweating, lassitude, frequent attack of common cold, dysphoria with feverish sensation in chest, and yellow discoloration of the skin and sclera. The parents manifested 3 high-frequency symptoms and signs such as lassitude in loins and knees, dizziness, aversion to cold and cold limbs. TCM syndrome score in the offspring was significant higher than that in the parents (P<0.01). CONCLUSION: In the two family types, TCM syndrome in the offspring is of yin-blood deficiency, while the syndrome of the parents is of kidney deficiency. The differences of TCM syndromes between the offspring and the parents may have some relations to the type of mutant genes and genetically modified ingredients. This research provides scientific evidence to TCM syndrome differentiation treatment of thalassemia.

Increasing dietary fish intake has contributed to decreasing mortality from CHD among the older population in Hong Kong.

OBJECTIVE: To test whether change in the frequency of fish intake at population level would affect the trends of death from CHD and how many CHD events could be prevented in Hong Kong, a population among those with the highest fish consumption and the lowest CHD mortality in the world. DESIGN: Time trends analysis with data from repeated dietary surveys and death registration. SETTING: Hong Kong SAR, People's Republic of China. SUBJECTS: A total of 3096 men and women aged 40-69 years who participated in territory-wide surveys in 1995 or 2003 were included in the analysis of changes in dietary fish intake; all adults aged 40-69 years in Hong Kong were included in the analysis of time trends of CHD mortality. RESULTS: Over the period, the frequency of fish intake increased and CHD mortality decreased significantly in the population age group of 50-69 years, while in the age group of 40-49 years little change in both fish intake and CHD mortality was observed. It was estimated that 240 CHD deaths (or 29 % of the total) were avoided among the population aged 40-69 years in 2003, as more than half of the population consumed fish every day in Hong Kong. CONCLUSIONS: The time trend of CHD mortality was inversely related to the trend of fish intake. The frequency of fish intake may have a substantial impact on the population for the prevention of CHD deaths in Hong Kong.

Observations on after-effect duration of kidney-nourishing and marrow-replenishing therapy on 58 cases of Mediterranean anemia.

OBJECTIVE: To observe the after-effect duration of kidney-nourishing and marrow-replenishing therapy on Mediterranean anemia. METHODS: To observe the kidney-nourishing and marrow-replenishing therapy on 58 cases of Mediterranean anemia and the influence of various relative factors on the after-effect duration. RESULTS: The after-effect duration on 58 cases varied from 3-6 months, about 4 months on average, and was not influenced by sex, clinical types, genetic types, types of Mediterranean anemia and other factors. CONCLUSION: Kidney-nourishing and marrow-replenishing therapy used to treat Mediterranean anemia can not only produce good therapeutic effect during treatment but also keep after effect lasting for about 4 months, indicating that the therapy used to treat Mediterranean anemia has good clinical after effect.

[Clinical observation of Yisui Shengxue Granule in treating 25 patients with hemoglobin H disease].

OBJECTIVE: To investigate the clinical efficacy and safety of Yisui Shengxue Granule (YSSXG), a compound traditional Chinese herbal medicine for reinforcing kidney and nourishing blood, in treating hemoglobin H (HbH) disease. METHODS: YSSXG was given orally to 25 patients with HbH disease in Guangxi Zhuang Autonomous Region (high incidence area for HbH disease in China) for 3 months as one therapeutic course, 3 times a day, 10 g YSSXG was given each time (dose of YSSXG for children should be reduced properly), and blood transfusion was not given to HbH patients during the course of treatment. The levels of hemoglobin (Hb), red blood cell (RBC), HbH and reticulocyte (Ret) were observed before and after YSSXG treatment, and side effects were observed during the course of treatment. Meanwhile, the genotype was examined, and the clinical efficacy of YSSXG in treating HbH patients with different genotype was evaluated. RESULTS: The levels of Hb, RBC and Ret were obviously increased after YSSXG treatment from the first month to the end of treatment (P<0.01). After YSSXG treatment, the levels of Hb, RBC, Ret in 12 HbH patients with gene deletion were elevated (P<0.05, P<0.01), and the levels of Hb and Ret in 13 HbH patients with gene non-deletion were increased obviously (P<0.05, P<0.01). The total response rate was 84% after 3-month treatment, and there was no statistical difference in clinical efficacy between gene deletion HbH patients and non-deletion HbH patients. No adverse effect was observed during the course of treatment. CONCLUSION: YSSXG is effective and safe for treatment of HbH disease. YSSXG can improve the levels of Hb, RBC and Ret in HbH patients, especially in gene deletion HbH patients.