Protein Containing the GGDEF Domain Affects Motility and Biofilm Formation in Vibrio cholerae and is Negatively Regulated by Fur and HapR / 生物医学与环境科学（英文）

OBJECTIVE@#This study aimed to investigate whether the VCA0560 gene acts as an active diguanylate cyclase (DGC) in Vibrio cholerae and how its transcription is regulated by Fur and HapR.@*METHODS@#The roles of VCA0560 was investigated by utilizing various phenotypic assays, including colony morphological characterization, crystal violet staining, Cyclic di-GMP (c-di-GMP) quantification, and swimming motility assay. The regulation of the VCA0560 gene by Fur and HapR was analyzed by luminescence assay, electrophoretic mobility shift assay, and DNase I footprinting.@*RESULTS@#VCA0560 gene mutation did not affect biofilm formation, motility, and c-di-GMP synthesis in V. cholerae, and its overexpression remarkably enhanced biofilm formation and intracellular c-di-GMP level but reduced motility capacity. The transcription of the VCA0560 gene was directly repressed by Fur and the master quorum sensing regulator HapR.@*CONCLUSION@#Overexpressed VCA0560 functions as an active DGC in V. cholerae, and its transcription is repressed by Fur and HapR.

Establishment and validation of a nomogram for predicting prognosis of gastric neuroendocrine neoplasms based on data from 490 cases in a single center / 南方医科大学学报

OBJECTIVE@#To develop and validate a nomogram for predicting outcomes of patients with gastric neuroendocrine neoplasms (G-NENs).@*METHODS@#We retrospectively collected the clinical data from 490 patients with the diagnosis of G-NEN at our medical center from 2000 to 2021. Log-rank test was used to analyze the overall survival (OS) of the patients. The independent risk factors affecting the prognosis of G-NEN were identified by Cox regression analysis to construct the prognostic nomogram, whose performance was evaluated using the C-index, receiver-operating characteristic (ROC) curve, area under the ROC curve (AUC), calibration curve, DCA, and AUDC.@*RESULTS@#Among the 490 G-NEN patients (mean age of 58.6±10.92 years, including 346 male and 144 female patients), 130 (26.5%) had NET G1, 54 (11.0%) had NET G2, 206 (42.0%) had NEC, and 100 (20.5%) had MiNEN. None of the patients had NET G3. The numbers of patients in stage Ⅰ-Ⅳ were 222 (45.3%), 75 (15.3%), 130 (26.5%), and 63 (12.9%), respectively. Univariate and multivariate analyses identified age, pathological grade, tumor location, depth of invasion, lymph node metastasis, distant metastasis, and F-NLR as independent risk factors affecting the survival of the patients (P < 0.05). The C-index of the prognostic nomogram was 0.829 (95% CI: 0.800-0.858), and its AUC for predicting 1-, 3- and 5-year OS were 0.883, 0.895 and 0.944, respectively. The calibration curve confirmed a good consistency between the model prediction results and the actual observations. For predicting 1-year, 3-year and 5-year OS, the TNM staging system and the nomogram had AUC of 0.033 vs 0.0218, 0.191 vs 0.148, and 0.248 vs 0.197, respectively, suggesting higher net benefit and better clinical utility of the nomogram.@*CONCLUSION@#The prognostic nomogram established in this study has good predictive performance and clinical value to facilitate prognostic evaluation of individual patients with G-NEN.

Erythropoietin promotes myocardial infarction repair in mice by improving the function of Sca-1+ stem cells / 生理学报

Myocardial infarction (MI) is one of the leading causes of death in the world. With the improvement of clinical therapy, the mortality of acute MI has been significantly reduced. However, as for the long-term impact of MI on cardiac remodeling and cardiac function, there is no effective prevention and treatment measures. Erythropoietin (EPO), a glycoprotein cytokine essential to hematopoiesis, has anti-apoptotic and pro-angiogenetic effects. Studies have shown that EPO plays a protective role in cardiomyocytes in cardiovascular diseases, such as cardiac ischemia injury and heart failure. EPO has been demonstrated to protect ischemic myocardium and improve MI repair by promoting the activation of cardiac progenitor cells (CPCs). This study aimed to investigate whether EPO can promote MI repair by enhancing the activity of stem cell antigen 1 positive stem cells (Sca-1+ SCs). Darbepoetin alpha (a long-acting EPO analog, EPOanlg) was injected into the border zone of MI in adult mice. Infarct size, cardiac remodeling and performance, cardiomyocyte apoptosis and microvessel density were measured. Lin- Sca-1+ SCs were isolated from neonatal and adult mouse hearts by magnetic sorting technology, and were used to identify the colony forming ability and the effect of EPO, respectively. The results showed that, compared to MI alone, EPOanlg reduced the infarct percentage, cardiomyocyte apoptosis ratio and left ventricular (LV) chamber dilatation, improved cardiac performance, and increased the numbers of coronary microvessels in vivo. In vitro, EPO increased the proliferation, migration and clone formation of Lin- Sca-1+ SCs likely via the EPO receptor and downstream STAT-5/p38 MAPK signaling pathways. These results suggest that EPO participates in the repair process of MI by activating Sca-1+ SCs.

Analysis of clinicopathological characteristics, therapeutic strategy and prognosis of 501 patients with gastric neuroendocrine neoplasms attending a single center / 中华胃肠外科杂志

Objective: To explore the clinicopathological features, treatment strategy and to analysis of prognosis-related risk factors of gastric neuroendocrine neoplasms(G-NEN). Methods: In this study, a retrospective observational study method was used to collect the clinicopathological data of patients diagnosed with G-NEN by pathological examination in the First Medical Center of PLA General Hospital from January 2000 to December 2021. The basic information of the patients, tumor pathological characteristics, and treatment methods were entered, and the treatment information and survival data after discharge were followed up and recorded. The Kaplan-Meier method was used to construct survival curves, and the log-rank test to analyze the differences in survival between groups. Cox Regression model analysis of risk factors affecting the prognosis of G-NEN patients. Results: Among the 501 cases confirmed as G-NEN, 355 were male and 146 were female, and their median age was 59 years. The cohort comprised 130 patients (25.9%) of neuroendocrine tumor (NET) G1, 54 (10.8%) of NET G2, 225 (42.9%) of neuroendocrine carcinoma (NEC), and 102 cases (20.4%) of mixed neuroendocrine-non-neuroendocrine(MiNEN). Patients NET G1 and NET G2 were mainly treated by endoscopic submucosal dissection (ESD) and endoscopic mucosal resection (EMR). The main treatment for patients with NEC/MiNEN was the same as that for gastric malignancies, namely radical gastrectomy+lymph node dissection supplemented with postoperative chemotherapy. There were significant differences in sex, age, maximum tumor diameter, tumor morphology, tumor numbers, tumor location, depth of invasion, lymph node metastasis, distant metastasis, TNM staging and expression of immunohistological markers Syn and CgA among NET, NEC, and MiNEN patients (all P<0.05). Further for NET subgroup analysis, there were significant differences between NET G1 and NET G2 in the maximum tumor diameter, tumor shape and depth of invasion(all P<0.05). 490 patients (490/501, 97.8%) were followed up with a median of 31.2 months. 163 patients had a death during follow-up (NET G1 2, NET G2 1, NEC 114, MiNEN 46). For NET G1, NET G2, NEC and MiNEN patients,the 1-year overall survival rates were 100%, 100%, 80.1% and 86.2%, respectively; the 3-year survival rates were 98.9%, 100%, 43.5% and 55.1%, respectively. The differences were statistically significant (P<0.001). Univariate analysis showed that gender, age, smoking history, alcohol history, tumor pathological grade, tumor morphology, tumor location, tumor size, lymph node metastasis, distant metastasis, and TNM stage were associated with the prognosis of G-NEN patients (all P<0.05). Multivariate analysis showed that age ≥60 years, pathological grade of NEC and MiNEN, distant metastasis, and TNM stage III-IV were independent factors influencing the survival of G-NEN patients (all P<0.05). 63 cases were stage IV at initial diagnosis. 32 of these were treated with surgery and 31 with palliative chemotherapy. Stage IV subgroup analysis showed that the 1-year survival rates were 68.1% and 46.2% in the surgical treatment and palliative chemotherapy groups, respectively, and the 3-year survival rates were 20.9% and 10.3%, respectively; the differences were statistically significant (P=0.016). Conclusions: G-NEN is a heterogeneous group of tumors. Different pathological grades of G-NEN have different clinicopathological features and prognosis. Factors such as age ≥ 60 years old, pathological grade of NEC/MiNEN, distant metastasis, stage III, IV mostly indicate poor prognosis of patients. Therefore, we should improve the ability of early diagnosis and treatment, and pay more attention to patients with advanced age and NEC/MiNEN. Although this study concluded that surgery improves the prognosis of advanced patients more than palliative chemotherapy, the value of surgical treatment for patients with stage IV G-NEN remains controversial.

Analysis of hemagglutinin-neuraminidase gene characteristics of human parainfluenza virus type 3 among children with acute respiratory tract infection in Qingdao city / 中华预防医学杂志

The purpose was to discuss the infection status of human parainfluenza virus type 3 (HPIV-3) in children with acute respiratory tract infection(ARTI) in Qingdao, Shandong province, and to analyze the gene characteristics of HPIV-3 hemagglutinin-neuraminidase protein (HN). This study was a cross-sectional study. A total of 1 674 throat swab samples were collected randomly from children with ARTI, in the three hospitals (Qingdao Women and Children's Hospital, West Coast Branch of Affiliated Hospital of Qingdao University, Laoshan Branch of Affiliated Hospital of Qingdao University) from January 2018 to December 2019. Multiplex real-time fluorescence RT-PCR was performed to screen HPIV-3 positive specimens. For HPIV-3 positive specimens, nested PCR was used to amplify the full-length HN gene of HPIV-3. The HN gene was sequenced and compared with the representative strains of HPIV-3 in GenBank, and the phylogenetic tree was established. As results, this study collected 1 674 samples, in which there were 90 HPIV-3 positive samples showed and the detection rate was 5.37%. Among positive specimens, the number of samples from children under 6 years old was 88, accounting for 97.78%. HPIV-3 positive cases were mainly distributed in spring and summer. The full-length sequences of 44 HPIV-3 HN genes were obtained by nested PCR method. Sequence alignment and evolutionary analysis showed that the HPIV-3HN gene belonged to the C3a and C3b branches of C3 genotype, with 30 strains of subtype C3a and 14 strains of subtype C3b. The nucleotide and amino acid homology of the amplified 44 strains of the HPIV-3 HN gene in Qingdao were 97.0%-100.0% and 98.5%-100.0%, respectively. In conclusion, from 2018 to 2019, the C3a and C3b branches of HPIV-3 C3 genotype were circulating prevalent in Qingdao, Shandong province. HN gene variation rate was low, but showed certain regional characteristics in evolution.

Iron Overload and the Risk of Diabetes in the General Population: Results of the Chinese Health and Nutrition Survey Cohort Study

Background@#Recent studies have found that there are significant associations between body iron status and the development of diabetes. In the present study, we aimed to analyze the association among iron overload (IO), insulin resistance (IR), and diabetes in Chinese adults, and to explore the sex difference. @*Methods@#Men and women (age >19 years) who participated in the Chinese Health and Nutrition Survey and did not have diabetes at baseline were followed between 2009 and 2015 (n=5,779). Over a mean of 6 years, 75 participants were diagnosed with incident diabetes. Logistic regression was used to assess the risk factors associated with IO. Cox proportional hazard regression was used to estimate the risk of incident diabetes and to determine whether the risk differed among subgroups. Causal mediation analysis (CMA) was used to explore the mechanism linking IO and diabetes. @*Results@#According to sex-stratified multivariable-adjusted Cox proportional hazards regression, IO increased the risk of incident diabetes. Women with IO had a higher risk of diabetes than men. Subgroup analysis with respect to age showed that the association between IO and diabetes was stronger in older women and younger men (P<0.001). CMA showed that liver injury (alanine transaminase) and lipid metabolism abnormalities (triglyceride, apolipoprotein B) contributed to the association between IO and diabetes. @*Conclusion@#IO is associated with diabetes and this association is sex-specific. IO may indirectly induce IR via liver injury and lipid metabolism abnormalities, resulting in diabetes.

Mesoderm products and PPDO lines jointly improve the effects of periorbital rejuvenation / 中华医学美学美容杂志

Objective:To observe the clinical effect of injecting hyaluronic acid fillers and Poly (p-dioxanone) (PPDO) absorption line in improving periorbital aging.Methods:From May 2017 to May 2019, 104 patients aged 20-55 (36±5) years were treated with combination of injection and PPDO; a score scale was developed based on the tear ditch aging, and beauty seekers were divided into two groups, 48 in mild and 56 in moderate, and followed up for 6-12 months after treatment.Results:Immediately postoperative satisfaction in the mild group was significantly higher than that in the moderate group, and ideal within 6 months. For 6 months after surgery, satifactoty score was (7.48±1.29) in the mild group and (6.32±1.03) in the moderate group; the treatment effect decreased over time.Conclusions:Based on the rheological characteristics of sodium hyaluronic acid gel and the anatomical characteristics of tear ditch formation, multi-point injection filling technique combined with small line to treat light and moderate orbital aging can achieve good clinical results.

Monomorphic epitheliotropic intestinal T-cell lymphoma: a clinicopathological analysis of twelve cases / 中华病理学杂志

Objective@#To investigate the clinicopathological features, diagnosis and differential diagnosis of monomorphic epitheliotropic intestinal T-cell lymphoma (MEITL).@*Methods@#A total of 12 specimens were collected, which were surgically resected and verified as MEITL by postoperative pathology, immumohistochemical staining and gene rearrangement at the First Affiliated Hospital of Nanjing Medical University from 2012 to 2018, and all of these had complete clinical and pathological data. The MEITL cases were reviewed to compare the clinicopathological characteristics, including morphologic and immunophenotypic features and followed up by telephone and clinic visit.@*Results@#All the cases were diagnosed with MEITL. There were 8 males and 4 females. Male to female ratio was 2∶1, at a median age of 54 years. The sites of involvement included jejunum (4 cases), ileum (5 cases), duodenum (1 case), ileocecal junction (1 case) and rectum (1 case). The neoplastic cells were monotonous of small to intermediate cells in size with round to slightly irregular nuclei in 11 cases. The immunophenotyping showed that CD3 (12/12), CD8 (11/12), CD43 (11/12), CD56 (11/12), TIA-1 (12/12) were positive; CD5 (12/12), Gran B (9/12), and perforin (7/12) were negative. Two cases aberrantly expressed the B-cell marker CD20. A high proliferation index was demonstrated by Ki-67 immunostaining. In situ hybridization for EBER was all negative(12/12). The whole exome sequencing(WES) mutational landscape of MEITL was remarkably homogeneous, showing significantly enriched clusters among histone modifier genes, JAK-STAT and MAPK-signal pathways. Histonelysine N-methytransferase SETD2 gene was mutated in 2/4 tumors. All the patients analyzed harbored at least one mutation in the JAK-STAT signal pathway, including STAT5B (2/4), JAK3 (3/4) and STAT5A (2/4). Furthermore, frequent alterations (TP53) were observed in the MAPK pathway in 3/4 of MEITL cases. The CNV analysis derived from WES data identified multiple regions of frequent gains and losses. In particular, gains in 1q, 7q and 9q, and recurrent losses involving 7p and 8p were observed.@*Conclusions@#MEITL is a rare and aggressive type of extranodal T-cell lymphoma. The differential diagnosis of MEITL includes EATL, extranodal NT/T-cell lymphoma and other types of PTCL. Diagnosis should be correlated to clinical symptoms while the final diagnosis is mainly based on the pathological features, immunophenotypes and genetic testing.

Effectiveness and Safety Evaluation of Qixiong Zhongzi Decoction () in Idiopathic Asthenozoospermia Treatment: A Randomized Controlled Trial / 中国结合医学杂志

OBJECTIVE@#To evaluate the clinical effectiveness and safety of the Chinese medicine (CM) Qixiong Zhongzi Decoction (, QZD) in the treatment of patients with idiopathic asthenozoospermia.@*METHODS@#A total number of 66 patients with idiopathic asthenozoospermia were included and randomly divided into treatment and control groups by SAS-generated code from January 2015 to August 2016, 33 patients in each group. Patients in the treatment group were administered with 150 mL of QZD twice a day, whereas those in the control group were given 1 g of levocarnitine oral liquid twice a day. The two groups received the indicated medication for 12 weeks and were then followed up for 4 weeks. The primary outcome was sperm motility, and the secondary therapeutic indices were sperm volume, density, pregnancy probability, and CM syndrome score. The comparison between groups was carried out at 4, 8 and 12 weeks, respectively. The safety was determined before and after treatment.@*RESULTS@#(1) Drop-off: 5 cases (7.58%) were lost after treatment (2 from the treatment group and 3 from the control group). (2) Primary outcomes: after 8- and 12-week treatment, the progressive sperms in the two groups were significantly higher than the baseline (all P0.05), however, the CM syndrome score of the treatment group significantly declined compared with baseline level at each time points (all P<0.05). (4) Safety: no obvious side reactions were found during the treatment in both groups.@*CONCLUSION@#QZD could improve the progressive and non-progressive grade sperm in the treatment of idiopathic asthenozoospermia. It is safe with no obvious side effects.

Effect of Naoxintong capsule on blood lipids and hemorheology in the treatment of type 2 diabetes mellitus patients complicated with cerebral infarction with Qi deficiency and blood stasis type / 中国基层医药

Objective To observe the effect of Naoxintong capsule on blood lipid and hemorheology in the treatment of type 2 diabetes mellitus patients complicated with cerebral infarction with Qi deficiency and blood stasis type.Methods From February 2015 to February 2017,96 type 2 diabetes mellitus patients complicated with cerebral infarction with Qi deficiency and blood stasis type who treated in the Traditional Chinese Medicine Hospital of Tongxiang were selected in the research.The patients were randomly divided into two groups according to the digital table,with 48 cases in each group.The control group was treated with routine treatment scheme,while the observation group was added Naoxintong capsule.The blood lipids and hemorheology data before and after treatment were compared between the two groups.Results After treatment,the levels of LDL-C,TG,TC and HDL-C in the observation group were (1.8 ± 0.3) mmol/L,(0.9 ± 0.4) mmol/L,(2.1 ± 0.4) mmol/L,(1.6 ± 0.7) mmol/L,respectively,which were lower than those in the control group [(2.2 ± 0.4) mmol/L,(1.2 ± 0.6) mmol/L,(2.3 ± 0.3)mmol/L,(1.3 ±0.4) mmol/L] (t =5.54,2.88,3.18,2.58,all P ＜0.05).The HCT,ESR,EEP,Fig in the observation group were (41.5 ± 1.3) ％,(16.5 ± 2.1) mm/h,(292.1 ± 18.3) s,(7.6 ± 0.4) g/L,respectively,which were lower than those in the control group[(45.6 ± 1.4)％,(21.1 ± 3.2)mm/h,(332.3 ± 19.2)s,(8.2 ± 0.3) g/L] (t =14.87,8.33,10.50,8.31,all P ＜ 0.05).Conclusion Naoxintong capsule is effective in the treatment of type 2 diabetes mellitus patients complicated with cerebral infarction with Qi deficiency and blood stasis type,and can effectively improve the related indicators of blood lipids and hemorhelogy and stabilize the carotid artery plaque,it is worthy of clinical application.

Antioxidant Mechanism of Xiaojin Pill () for Treatment of Peyronie's Disease in Rats Based on Matrix Metalloproteinases / 中国结合医学杂志

OBJECTIVE@#To evaluate the effects of Xiaojin Pill () in the treatment of Peyronie's disease (PD) in a rat model.@*METHODS@#Twenty-four male Sprague-Dawley rats were randomly divided into four groups with 6 in each: sham operation, PD model, vehicle control and Xiaojin Pill groups. The rats in the sham operation group received penile tunica albsginea (TA) injection with 50 μL vehicle, while the rats in the other 3 groups received 50 μL penile TA injection of 50 μg transforming growth factor (TGF)-β1. Forty-two days after the injection, rats in the vehicle control and Xiaojin Pill groups received 0.5 mL water and Xiaojin Pill solution (107 mg/kg of body weight), respectively by gavage for 28 days, while those in the sham operation and PD model groups did not receive any intervention. After intervention, the expressions of matrix metalloproteinase 2/9 (MMP2/9), nitric oxidesynthase (NOS), superoxide dismutase (SOD) and malondialdehyde (MDA) were measured.@*RESULTS@#Rats in the PD model and vehicle control groups presented obvious fibrosis in corpus cavernosum (CC) and demonstrated a significantly increased expressions of MMP2 and MMP9 in the CC compared with the sham operation group (all P<0.01). In contrast, the expressions of MMP2 and MMP9 in the Xiaojin Pill group were significantly down-regulated (both P<0.01). In addition, the levels of NOS and MDA in CC were significantly increased while the activity of SOD was decreased in the PD model and vehicle control groups compared with the sham operation group (all P<0.01). After Xiaojin Pill treatment, the levels of MDA, NOS and SOD appeared to be corrected (all P<0.01).@*CONCLUSIONS@#Xiaojin Pill could reduce fibrosis in the CC by decreasing the expressions of MMPs, NOS and MDA, and by increasing the activity of SOD. Therefore, Xiaojin Pill might be a therapeutic option for PD.

Regional Differences of the Urinary Proteomes in Healthy Chinese Individuals / 中国医学科学杂志(英文版)

Objective Urine is a promising biomarker source for clinical proteomics studies. Regional physiological differences are common in multi-center clinical studies. In this study, we investigate whether significant differences are present in the urinary proteomes of individuals from different regions in China. Methods In this study, morning urine samples were collected from healthy urban residents in three regions of China (Haikou, Xi'an and Xining) and urinary proteins were preserved using a membrane-based method (Urimem). The urine proteomes of 27 normal samples were analyzed using LC-MS/MS and compared among three regions. Functional annotation of the differential proteins among the three areas was analyzed using the DAVID online database, and pathway enrichment of the differential urinary proteins was analyzed using KEGG. Results We identified 1898 proteins from Urimem samples using label-free proteome quantification, of which 56 urine proteins were differentially expressed among the three regions ( < 0.05). Hierarchical clustering analysis showed that inter-regional differences caused less significant changes in the urine proteome than inter-sex differences. After gender stratification, 16 differential proteins were identified in male samples and 84 differential proteins were identified in female samples. Among these differential proteins, several proteins have been previously reported as urinary disease biomarkers. Conclusions Urimem will facilitate urinary protein storage for large-scale urine sample collection. Regional differences are a confounding factor influencing the urine proteome and should be considered in future multi-center biomarker studies.

Effect of acupuncture on blood pressure variability in elderly patients with cerebral infarction complicated with essential hypertension / 中国针灸

OBJECTIVE@#To observe the therapeutic effect of acupuncture on blood pressure variability (BPV) in elderly patients with cerebral infarction complicated with essential hypertension.@*METHODS@#Seventy-six elderly patients with cerebral infraction complicated with essential hypertension were randomized into an observation group and a control group, 38 cases in each group. acupuncture and nifedipin were given in the control group. On the basis treatment in the control group, the and acupuncture was applied at Renying (ST 9), Hegu (LI 4), Quchi (LI 11), Zusanli (ST 36) and Taichong (LR 3) in the observation group for 30 min. The treatment was given once a day, 5 times a week for 8 weeks. The 24-hour ambulatory blood pressure was monitored in the two groups. The changes of blood pressure and blood pressure variability were observed before and after 8 weeks of treatment, and the occurrence of adverse reactions during the treatment were recorded.@*RESULTS@#The mean systolic blood pressure (SBP), diastolic blood pressure (DBP), daytime SBP, DBP, nighttime SBP and DBP were reduced in the two groups after 8 weeks of treatment (0.05).@*CONCLUSION@# and acupuncture method can effectively control the blood pressure and blood pressure variability in the elderly patients with cerebral infraction complicated with essential hypertension.

Qiaoshao Prescription improves premature ejaculation in male rats by increasing the content of 5-hydroxytryptamine / 中华男科学杂志

<p><b>Objective</b>To observe the intervention effect of Qiaoshao Prescription (QSP) on premature ejaculation (PE) induced by 8-OH-DPAT in male rats and explore its possible action mechanism.</p><p><b>METHODS</b>Seventy-two male Wistar rats were equally randomized into six groups, blank control, PE model control, low-, medium- and high-dose QSP, and dapoxetine. The PE model was established by injection of 8-OH-DPAT into the subarachnoid space of the lumbosacral spinal cord. Four weeks after modeling, the rats in the blank control and PE model control groups with gavaged with normal saline at 10 ml/kg/d, those in the low-, medium- and high-dose QSP groups with QSP at 5, 10 and 20 g/kg/d respectively once a day, and those in the dapoxetine group with dapoxetine hydrochloride at 300 mg/kg at 3 hours before mating. Forty-five female Wistar rats were injected subcutaneously with 20 μg estradiol benzoate after removal of bilateral ovaries to induce estrous estrus. Two and 4 weeks later, the male rats were mated with the female ones for 30 minutes per time and meanwhile observed for the mating behavior of the males, including mounting latency (ML), intromission latency (IL), ejaculation latency (EL), mounting frequency (MF), intromission frequency (IF), and ejaculation frequency (EF). After the 4th week of mating, the hypothalamus of the animals was isolated and weighed, and the content of 5-hydroxytryptamine (5-HT) was measured.</p><p><b>RESULTS</b>Compared with the blank control group, the PE model controls showed significantly decreased content of 5-HT in the hypothalamus(1 257.1 vs 923.4 ng/g, P<0.05), ML (［11.22 ± 3.60］ vs ［8.69 ± 2.48］ s, P<0.05), IL (［22.33 ± 2.45］ vs ［12.08±1.39］ s, P<0.05), MF (［13.28 ± 3.24］ vs ［7.53 ± 1.84］ times, P<0.05), and EL (［712.35 ± 36.77］ vs ［502.35 ± 46.72］ s, P<0.05). In comparison with the PE model controls, the rats of the QSP and dapoxetine groups exhibited remarkably increased content of 5-HT (P<0.05) and prolonged EL (P<0.05).</p><p><b>CONCLUSIONS</b>Qiaoshao Prescription can prolong EL in PE rats, which might be associated with the increased content of 5-HT in the hypothalamus. Further studies, however, are needed on its underlying mechanisms.</p>

Establishment of a rat model of premature ejaculation with 8-OH-DPAT / 中华男科学杂志

Objective@#To explore the feasibility and practicability of establishing a rat model of premature ejaculation (PE) by injection of 8-OH-DPAT into the subarachnoid space of the lumbosacral spinal cord segments.@*METHODS@#Twenty-four male Wistar rats were equally randomized into a PE model and a blank control group. The PE model was established by injection of 8-OH-DPAT in 10 ml normal saline at 0.8 mg per kg of the body weight per day into the subarachnoid space of the lumbosacral spinal cord segments and the control rats were injected with the same volume of normal saline only, both for 4 weeks. Another 24 female Wistar rats were injected subcutaneously with benzoic acid estradiol at 20 μg to induce estrus at 36 hours before mated with the male animals. At 2 and 4 weeks, the male rats were mated with the female ones for 30 minutes each time and meanwhile observed for their mating behavior indicators, such as mount latency, intromission latency, ejaculation latency, mount frequency, intromission frequency, and ejaculation frequency.@*RESULTS@#Compared with the controls, the PE model rats showed a significantly lower ejaculation latency (［712.35 ± 36.77］ vs ［502.35 ± 46.72］ s, P0.05).@*CONCLUSIONS@#A rat model of premature ejaculation was successfully established by injection of 8-OH-DPAT into the subarachnoid space of the lumbosacral spinal cord segments, which is of great significance for further study of the mechanism of premature ejaculation.

Efficacy and safety of traditional Chinese medicine combined with sildenafil in the treatment of ED in Chinese men： A real-world study / 中华男科学杂志

Objective@#To make a real-world study on the efficacy and safety of traditional Chinese medicine (TCM) combined with sildenafil in the treatment of erectile dysfunction (ED) that failed to respond to TCM medication.@*METHODS@#This study included 1 038 ED patients with the International Index of Erectile Function-5 (IIEF-5) scores ≤21 and improvement <30% after 4 weeks of TCM medication, differentially diagnosed with kidney-yang or kidney-yin deficiency syndrome. We administered TCM combined with sildenafil (Viagra, Pfizer Pharmaceutical Co., Ltd) at 100 mg 1 hour before sexual intercourse. After 2 and 4 weeks of medication, we recorded the scores in IIEF-5, erection hardness, Sexual Encounter Profile question 2 (SEP-2: whether vaginal penetration is successful), SEP-3 (whether sexual intercourse is successful), and TCM Syndromes Scale as well as the indexes of routine blood, urine, liver function, and renal function of the patients, and compared them with those obtained before treatment.@*RESULTS@#No serious adverse reactions were observed in any of the patients. Compared with the baseline, the patients achieved significantly increased IIEF-5 scores after 2 and 4 weeks of medication (15.01 ± 2.25 vs 16.96 ± 2.55 and 19.41 ± 2.82, P <0.05), penileelectionhardness remarkably improved at 4 weeks (3.36% vs 44.58%, P<0.05), and the positive answers to SEP-2 and SEP-3 both markedly increased at 2 (38.11% vs 90.49%, P<0.05; 22.01% vs 63.77% , P<0.05) and 4 weeks (38.11% vs 96.95% , P<0.05; 22.01% vs 89.73%, P<0.05).@*CONCLUSIONS@#TCM combined with sildenafil is safe and effective in the treatment of ED in Chinese men, which can significantly improve the IIEF-5 score and erection hardness of the patients.

Efficacy and safety of Qiaoshao Formula () on patients with lifelong premature ejaculation of Gan (Liver) depression and Shen (Kidney) deficiency syndrome: A randomized controlled trial / 中国结合医学杂志

<p><b>OBJECTIVE</b>To observe the effificacy and safety of Qiaoshao Formula (, QSF) on patients with lifelong premature ejaculation (LPE) of Gan (Liver) depression and Shen (Kidney) defificiency syndrome.</p><p><b>METHODS</b>A total of 60 LPE patients were randomly divided into treatment (QSF) and control (dapoxetine) groups. The treatment group received QSF twice a day and the control group received dapoxetine 1 to 2 h prior to planned sexual intercourse for 4 weeks. The outcomes included intra-vaginal ejaculation latency time (IELT), premature ejaculation diagnostic tool (PEDT), clinical global impression of change (CGIC), scores of Chinese medicine symptoms (CMSS), sex life satisfaction (SLS) and adverse events (AEs).</p><p><b>RESULTS</b>In the treated group, the median IELT was 3 min vs. 1.5 min before and after treatment (P<0.05). PEDT in the treated group was reduced to 11.76±1.68 from 15.83±2.30 after treatment (P<0.05). Besides, patient's SLS was improved from 1.30±0.05 to 6.30±0.04 (P<0.05), and spouse's SLS was increased from 1.30±0.to 6.10±0.06 (P<0.05); CMSS was decrease from 14.86±3.02 to 9.62±2.87 (P<0.05). In addition, no significant AE was observed in both groups.</p><p><b>CONCLUSION</b>QSF may be effective and safe on LPE patients with Gan depression and Shen defificiency syndrome.</p>

Involvement of Hfq in stress response and transcriptional regulation of virulence genes and stress-responsive genes in Vibrio cholera / 中华微生物学和免疫学杂志

Objective To characterize Hfq-dependent phenotypes in stress response and to dissect Hfq-dependent transcription of virulence genes and stress-responsive genes in Vibrio cholera.Methods The hfq null mutant strain (△hfq) and the complemented mutant strain (△hfq/pUC18-hfq) were constructed from the wild-type Vibrio cholera.Comparisons on the motility,biofilm formation,growth under various oxygen-supplying conditions,outer membrane resistance,and sensitivity to oxidative stress were analyzed between the wild type strain and the mutant strains.Reverse-transcript fluorescence quantitative PCR (RT-qPCR) was used to determine the transcriptional levels of target genes in the above mentioned strains.Results △hfq and △hfq/pUC18-hfq strains were successfully constructed.The motility,outer membrane resistance and sensitivity to oxidative stress were reduced,but biofilm formation was enhanced in the hfq null mutant strain.RT-qPCR testified that Hfq had regulation effects on gene transcription for forming falagellum,extracellular polysaccharide,outer membrane protein and oxidative stress in Vibrio cholera.Conclusion As a RNA chaperone,Hfq could affect Vibrio cholera in its biofilm formation,resistance to oxidative stress and antibiotics resistance through regulating the transcription of multiple metabolic genes and virulence genes,which indicates that Hfq,combined with other regulators,may play a key role in the complex regulation of metabolic genes and virulence genes.

Treatment of oligospermia/asthenozoospermia patients by three different Chinese medical principles: a randomized control clinical study / 中国中西医结合杂志

<p><b>OBJECTIVE</b>To assess the efficacy and safety of three different Chinese medical principles in treating patients with male infertility (oligospermia/asthenozoospermia).</p><p><b>METHODS</b>Totally 128 patients with male infertility were classified into 3 groups, i.e., Shen-essence deficiency syndrome, Pi-Shen deficiency syndrome, Shen-deficiency blood-stasis syndrome. They were assigned to the Chinese medical treatment group (96 cases) and the Western medical treatment group (32 cases) by stratified randomization in the ratio of 3: 1. Those in the Chinese medical treatment group were treated with Chinese drugs for Shen invigorating and blood activating, Shen invigorating and Pi supplementing, Shen-qi benefiting. Those in the Western medical treatment group were treated with Clomifene (at the daily dose of 25 mg per day, once daily). Three months consisted of one therapeutic course. The parameters of semen, the pregnancy rate, and adverse reactions were observed.</p><p><b>RESULTS</b>Totally 24 patients dropped out in the two group, 17 in the Chinese medical treatment group (9 patients of Shen deficiency blood stasis syndrome, 5 of Shen-Pi deficiency syndrome, and 3 of Shen-essence deficiency syndrome) and 7 in the Western medical treatment group. Compared with before treatment, there was no statistical difference in the improvement of semen amount at 3 months after treatment between the two groups (P > 0.05). There was statistical difference in the improvement of semen density, class A semen, class A +B semen, and 1-h activity ratio (P < 0.05). The improvement was most obvious in Shen deficiency blood stasis syndrome, followed by Shen-Pi deficiency syndrome and Shen-essence deficiency syndrome. The improvement was the weakest in the Western medical treatment group. There was no statistical difference in the improvement of semen amount, semen density, class A semen, or 1-h activity ratio at 3 months after treatment between the two groups (P > 0.05). Best effect was obtained in improving class A + B semen quality in patients of Shen deficiency blood stasis syndrome, showing statistical difference when compared with the other two syndrome types and the Western medical treatment group (P < 0.05, P < 0.01). No obvious adverse reaction occurred in the two groups during the treatment course.</p><p><b>CONCLUSION</b>Shen invigorating and blood activating method could improve the semen density and semen activities, and it was superior to other therapeutic methods.</p>

Use of rich BHI medium instead of synthetic TMH medium for gene regulation study in Yersinia pestis / 生物医学与环境科学（英文）

<p><b>OBJECTIVE</b>This study is to verify the use of rich BHI medium to substitute synthetic media for gene regulation studies in Yersinia pestis.</p><p><b>METHODS</b>The transcriptional regulation of rovA by PhoP or via temperature upshift, and that of pla by CRP were investigated when Y. pestis was cultured in BHI. After cultivation under 26 °C, and with temperature shifting from 26 to 37 °C, the wild-type (WT) strain or its phoP or crp null mutant (ΔphoP or Δcrp, respectively) was subject to RNA isolation, and then the promoter activity of rovA or pla in the above strains was detected by the primer extension assay. The rovA promoter-proximal region was cloned into the pRW50 containing a promoterless lacZ gene. The recombinant LacZ reporter plasmid was transformed into WT and ΔphoP to measure the promoter activity of rovA in these two strains with the β-Galactosidase enzyme assay system.</p><p><b>RESULTS</b>When Y. pestis was cultured in BHI, the transcription of rovA was inhibited by PhoP and upon temperature upshift while that of pla was stimulated by CRP.</p><p><b>CONCLUSION</b>The rich BHI medium without the need for modification to be introduced into the relevant stimulating conditions (which are essential to triggering relevant gene regulatory cascades), can be used in lieu of synthetic TMH media to cultivate Y. pestis for gene regulation studies.</p>