OBJECTIVE: To investigate the clinical effect and adverse reactions of dapoxetine hydrochloride versus paroxetine in the treatment of primary premature ejaculation by cross-comparison. METHODS: Based on the clinic-visit time, we equally randomized 148 patients with primary premature ejaculation into groups A and B for a cross-comparison test, the former treated with paroxetine at 20 mg once nightly and the latter with dapoxetine hydrochloride at 30 mg on demand, both for 6 successive weeks, during which we observed the therapeutic effects and adverse reactions. Following 4 weeks of drug discontinuance, we administered dapoxetine hydrochloride at 30 mg on demand for group A and paroxetine at 20 mg once nightly for group B, both for another 6 successive weeks, followed by observation and comparison of the therapeutic effects and adverse reactions. RESULTS: There were no statistically significant differences in the initial characteristics of the two groups of patients (P > 0.05). Compared with the baseline, the mean intra-vaginal ejaculation latency time (IELT) was dramatically improved after treatment in both groups A (4.43 min) and B (7.12 min), increased by 3.99% and 6.72%, respectively (P<0.001). The patients treated with paroxetine showed significantly longer IELT than those taking dapoxetine hydrochloride in both groups (P<0.001). Findings of the Premature Ejaculation Profile (PEP) and spouses' conditions indicated significant improvement after treatment in the average scores of the four indicators of PEP, that is, perceived control over ejaculation, ejaculation-related personal distress, satisfaction with sexual intercourse and ejaculation-related interpersonal difficulty, as well as in the overall experience and partner's satisfaction and orgasm frequency. Adverse reactions to medication were found in 20.8% of the cases in group A and 9.7% in group B, but none was serious. Preference survey following drug withdrawal revealed a preference for paroxetine (61.9%) over dapoxetine (26.8%), and that only a few of the patients thought of the two drugs as comparable or both ineffective. CONCLUSION In term of overall effectiveness, paroxetine was superior to dapoxetine in the treatment of primary premature ejaculation. And the patients obviously preferred the former to the latter, which might be partly attributed to the higher price of dapoxetine.
Humans ; Benzylamines/therapeutic use* ; Male ; Premature Ejaculation/drug therapy* ; Naphthalenes/therapeutic use* ; Paroxetine/therapeutic use* ; Adult ; Treatment Outcome ; Middle Aged ; Young Adult ; Selective Serotonin Reuptake Inhibitors/therapeutic use*

ObjectiveTo clarify the differences in the efficacy and mechanism of different processed products of Atractylodes chinensis rhizoma by the pharmacodynamics and metabolomics studies of raw， bran-fried and rice water-processed products on rats with spleen deficiency. MethodSixty male SD rats were randomly divided into blank group， model group， raw product group（3.75 g·kg^-1）， bran-fried product group（3.75 g·kg^-1）， rice water-processed product group（3.75 g·kg^-1） and Shenling Baizhusan group（6.7 g·kg^-1）， with 10 rats in each group. The method of excessive fatigue+improper diet was used to establish a spleen deficiency model in rats. After the end of modeling， except for the blank and model groups， each dosing group was given the corresponding drug suspension， the immune organ coefficients of each group of rats were examined， the levels of interleukin-6（IL-6）， tumor necrosis factor-α（TNF-α）， immunoglobulin G（IgG）， amylase（AMS）， motilin（MTL）， gastrin（GAS）， Na⁺-K⁺-adenosine triphosphatase（ATPase）， aquaporin 2（AQP2）， AQP3 and AQP8 in rats were measured by enzyme-linked immunosorbent assay（ELISA）. Ultra high performance liquid chromatography-quadrupole-time-of-flight tandem mass spectrometry（UPLC-Q-TOF-MS） combined with orthogonal partial least squares-discriminant analysis（OPLS-DA） were used to search for biomarkers in the plasma samples of spleen-deficient rats by using two criteria［P<0.05 and variable importance in the projection（VIP） value>1］， and to compare the different modulatory effects of the three decoction pieces on the splenic-deficient biomarkers， and metabolic pathway analysis was conducted through the Kyoto Encyclopedia of Genes and Genomes（KEGG） database. ResultCompared with the blank group， the thymus index and spleen index of rats in the model group were significantly decreased（P<0.05）， the levels of IL-6， TNF-α， IgG and AQP2 were significantly increased（P<0.05）， the levels of AMS， GAS， MTL， AQP3， AQP8 and Na⁺-K⁺-ATPase were significantly decreased（P<0.05）. Compared with the model group， raw products， bran-fried products and rice water-processed products all increased thymus index and spleen index（P<0.05）， decreased IL-6， TNF-α， IgG and AQP2 levels（P<0.05）， and increased AMS， GAS， MTL， AQP3， AQP8 and Na⁺-K⁺-ATPase levels to different degrees. A total of 176 differential metabolites were screened in the model group compared with the blank group， of which 75， 72 and 84 biomarkers were called back by the raw products， bran-fried products and rice water-processed products， respectively（P<0.05， P<0.01）. Raw products of A. chinensis rhizoma mainly affected glycine， serine and threonine metabolism. Bran-fried products mainly affected alanine， aspartate and glutamate metabolism， D-arginine and D-ornithine metabolism. Rice water-processed products mainly affected glycine， serine and threonine metabolism， alanine， aspartate and glutamate metabolism， citrate cycle， thiamine metabolism， D-arginine and D-ornithine metabolism. ConclusionRaw products， bran-fried products and rice water-processed products of A. chinensis rhizoma all have good spleen strengthening effects， among which the effects of bran-fried products and rice water-processed products were stronger. Meanwhile， raw products has the strongest dryness， followed by bran-fried products， and the weakest dryness of rice water-processed products. The three decoction pieces are able to significantly modulate metabolic abnormalities in spleen-deficient rats， and the mechanism may be related to amino acid metabolism such as glycine， serine and threonine metabolism as well as alanine， aspartate and glutamate metabolism.

Immunological evasion is one of the defining characteristics of cancers, as the immune modification of an immune checkpoint (IC) confers immune evasion capabilities to tumor cells. Multiple ICs, such as programmed cell death protein-1 (PD-1) and cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4), can bind to their respective receptors and reduce tumor immunity in a variety of ways, including blocking immune cell activation signals. IC blockade (ICB) therapies targeting these checkpoint molecules have demonstrated significant clinical benefits. This is because antibody-based IC inhibitors and a variety of specific small molecule inhibitors can inhibit key oncogenic signaling pathways and induce durable tumor remission in patients with a variety of cancers. Deciphering the roles and regulatory mechanisms of these IC molecules will provide crucial theoretical guidance for clinical treatment. In this review, we summarize the current knowledge on the functional and regulatory mechanisms of these IC molecules at multiple levels, including epigenetic regulation, transcriptional regulation, and post-translational modifications. In addition, we provide a summary of the medications targeting various nodes in the regulatory pathway, and highlight the potential of newly identified IC molecules, focusing on their potential implications for cancer diagnostics and immunotherapy.
Apoptosis Regulatory Proteins ; CTLA-4 Antigen/therapeutic use* ; Epigenesis, Genetic ; Humans ; Immunotherapy ; Neoplasms/therapy* ; Programmed Cell Death 1 Receptor/therapeutic use*

Objective: To investigate the effect and mechanism of polysaccharide of atractylodes macrocephala (PAM) on the growth of colon cancer cells in mice bearing in-situ colon cancer transplantation tumor. Methods: 1×107 colon cancer HT-29 cells labeled with luciferase were injected into colon serosa of the mice to establish the in-situ colon cancer transplantation tumor model. When the tumor volume reached 230 mm3, the mice were given 30 mg/kg PAM (PAM group) or equal volume of normal saline (Control group) by gavage for 10 consecutive days. The effect of PAM on the growth of colon cancer cells in mice was tested by in vivo tumor imaging technology. The expressions of MHCII and IL-12 in granulocytes, dendritic cells and macrophages, the activation of lymphocytes, and IFN-γ expression in CD4+ and CD8+ cells of tumor tissues were detected by Flow cytometry. Results: PAM significantly inhibited the growth of colon cancer cells in mice bearing in-situ colon cancer transplantation tumor (P<0.01). PAM activated immune cells though increasing the expression levels of MHCII and IL-12 in dendritic cells and macrophages (both P<0.01). PAM significantly increased the frequency of CD8+ cells, NK cells, CD44+/NK cells and CD44+/CD4+ cells in tumor tissues and the number of CD8+ cells and NK cells per unit volume (all P<0.01). PAM significantly increased the IFN-γ secretion of CD4+ and CD8+ cells (both P<0.01), too. Conclusion: PAM inhibits the growth of colon cancer by activating immune cells in tumor tissues of mice bearing in-situ colon cancer transplantation tumor.

OBJECTIVETo investigate the epidemiological characteristics of human infections with avian influenza A (H7N9) in China and to provide scientific evidence for the adjustment of preventive strategy and control measures.

METHODSDemographic and epidemiologic information on human cases were collected from both reported data of field epidemiological investigation and the reporting system for infectious diseases.

RESULTSA total of 433 cases including 163 deaths were reported in mainland China before June 4, 2014. Two obvious epidemic peaks were noticed, in March to April, 2013 and January to February, 2014. Confirmed cases emerged in 14 areas of China. Five provinces, including Zhejiang, Guangdong, Jiangsu, Shanghai, and Hunan, reported about 85% of the total cases. Median age of the confirmed cases was 58 years (range, 1-91), with 70% as males. Of the 418 cases with available data, 87% had ever exposed to live poultry or contaminated environments. 14 clusters were identified but human to human transmission could not be ruled out in 9 clusters.

CONCLUSIONHuman infections with avian influenza A (H7N9) virus showed the characteristics of obvious seasonal distribution, with certain regional clusters. The majority of confirmed cases were among the elderly, with more males seen than the females. Data showed that main source of infection was live poultry and the live poultry market had played a significant role in the transmission of the virus.

Adaptation, Psychological ; Aged ; Animals ; China ; epidemiology ; Demography ; Environmental Pollution ; Female ; Humans ; Influenza A Virus, H7N9 Subtype ; Influenza, Human ; epidemiology ; prevention & control ; transmission ; Male ; Meat ; Poultry ; Research Design

Aim To investigate the effect of dihydro-myricetin (DMY) on the insulin resistance in 3T3-L1 adipocytes and its mechanism. Methods The differ-entiated adipocytes were treated with 1 μmol · L-1 dexamethasone ( dex ) for 7 days to induce insulin re-sistance. With or without insulin, DMY (1 × 10 -6 ~ 1 × 10 -8 mol·L-1 ) was exposed to the normal and in-sulin-resistant 3 T3-L1 adipocytes for 48 hour and 72 hour, respectively. Rosiglitazone ( 1 × 10 -6 mol · L-1 ) was used as a positive control. The glucose up-take was evaluated by glucose consumption. The mR-NA expressions of glucose transporter 4 ( GLUT4 ) , protein kinase B ( PKB/Akt) and adiponectin were de-termined by RT-PCR analysis. Results DMY ( 5 × 10 -7 ~ 1 × 10 -8 mol·L-1 ) concentration-dependently increased the glucose uptake in insulin-resistant 3 T3-L1 adipocytes, similar to rosiglitazone. However, DMY did not affect the glucose consumption in normal 3T3-L1 cells. After treatment of DMY to insulin-resist-ant 3T3-L1 adipocytes for 72 hours, the expressions of GLUT4 , Akt2 and adiponectin mRNA were markedly increased, compared with the dexamethasone-treated group. Conclusion DMY could improve the insulin resistance in 3T3-L1 adipocytes, which is related to in-creasing the mRNA expression of GLUT4 , Akt2 and adiponectin.

Objective To analyze the median urinary iodine(MUI)level in normal pregnant women based on World HeMth Organization(WHO) recommended criterion,and to provide the MUI reference values for monitoring and evaluating iodine nutrition during pregnancy and related studies.Methods Total 604 normal pregnant and 192 non-pregnant women(as a comparison)were selected from a cross-sectional survey.These women were all healthy,iodine sufficient,with normal thyroid function,and negative anti-thyroid antibodies.The iodine content in drinking water,edible salt,and urine was determined by standard methods,and serum TSH,FT4,FT3,thyroid peroxidaseantibody(TPOAb),and thyroglobulin antibody(TgAb)were measured using chemiluminescent immunoassay.Resuits (1)The iodine in drinking water was 3.0μg/L indicating such small amount of iodine could be neglected for daily iodine intake.(2)All women consumed iodized salt with the median iodine in salt of 31.7 mg/kg.The daily iodine intake of at least 240 μg could be roughly estimated if an average of 10 g salt was taken per person per day and further subtracted by 20%iodine lost during cooking,which could meet the iodine needs during pregnancy.(3)The MUI of 173.1μg/L was calculated from 604 pregnant women having 174.5,167.0,and 180.7 μg/L during the first,second,and third trimesters,respectively,reaching the optimal level of 150-249 μg/L recommended by WHO for pregnant women.However,our data showed relatively lower levels,not reaching 200μg/L.The MUI of 240.2μg/L was calculated from 192 non-pregnant women,reaching the level of"above requirement"(200-299μg/L) recommended by WHO for adults.(4)All women were euthyroid and antibody-negative,but the TSH level in pregnant women was lower than that in non-pregnant women,in particular during the first trimester,while FT4 and FT3 were considerably decreased compared with the non-pregnant(with an exception of FT4 in the first trimester),and both gradually declined with the gestational age.Conclusions The optimal MUI level of 150-249 μg/,L recommended by WHO can be applied to pregnant Chinese women,but our data provided a relatively low range of 150-200μ/L throughout pregnancy.The higher MUI of 240.2μg/L in non-pregnant women indicated that iodized salt with different contents should be supplied on market to meet the requirement of different groups of population.

Objective To set up the trimester-specific reference ranges of thyroid hormones for normal pregnant women to provide reference criteria for diagnosis, treatment and monitoring or screening of thyroid disease during pregnancy and related research. Methods A cross-sectional survey was conducted in pregnant and non-pregnant women in iodine sufficient areas. A total of 505 normal pregnant women and 153 normal non-pregnant women (as control) were selected for establishing trimester-specific reference ranges of thyroid hormones after rigorous screening through the survey questionnaire and laboratory tests. Thyroid hormones were measured by Bayer automated chemiluminescence immunoassay, and the reference range of each hormone was calculated as median (the 50th percentile value) and two-sided limits (the 2.5th and 97.5th percentile values). Results All women investigated were in iodine sufficient status within optimal urine iodine level. The serum TSH level during the 1st trimester was obviously declined compared with that in the non-pregnant individuals (P < 0.01), and started to rise during the 2nd trimester, but was still not restored to non-pregnant level until the 3rd trimester. Serum FT4 and FT3 levels gradually decreased from the 2nd trimester to the 3rd (P < 0.01), and the TT4 and TT3 levels were markedly elevated since early pregnancy (P < 0.01) and reached peak levels at the 2nd trimester approximately making up to 1.5 times of those in the non-pregnant individuals. Conclusion The thyroid hormone levels during pregnancy differ completely from those of the non-pregnant individuals, and also differ during different gestation periods. Therefore, to establish trimester-specific reference data of thyroid hormones during normal pregnancy may be important for clinical practice.