[Effect of Liangfang Wenjing Decoction on expression of key glycolytic enzymes in uterus and ovaries of rats with coagulating cold and blood stasis syndrome].

This study aimed to investigate the relationship between coagulating cold and blood stasis syndrome and glycolysis, and observe the intervention effect of Liangfang Wenjing Decoction(LFWJD) on the expression of key glycolytic enzymes in the uterus and ovaries of rats with coagulating cold and blood stasis. The rat model of coagulating cold and blood stasis syndrome was established by ice-water bath. After modeling, the quantitative scoring of symptoms were performed, and according to the scoring results, the rats were randomly divided into a model group and LFWJD low-, medium-and high-dose groups(4.7, 9.4, 18.8 g·kg~(-1)·d~(-1)), with 10 in each group. Another 10 rats were selected as the blank group. After 4 weeks of continuous administration by gavage, the quantitative scoring of symptoms was repeated. Laser speckle flowgraphy was used to detect the changes of microcirculation in the ears and uterus of rats in each group. Hematoxylin-eosin(HE) staining was used to observe the pathological morphology of uterus and ovaries of rats in each group. The mRNA and protein expressions of pyruvate dehydrogenase kinase 1(PDK1), hexokinase 2(HK2) and lactate dehydrogenase A(LDHA) in the uterus and ovaries of rats were examined by real-time quantitative polymerase chain reaction(RT-qPCR) and Western blot, respectively. The rats in the model group showed signs of coagulating cold and blood stasis syndrome, such as curl-up, less movement, thickened veins under the tongue, and reduced blood perfusion in the microcirculation of the ears and uterus, and HE staining revealed a thinning of the endometrium with disorganized arrangement of epithelial cells and a decrease in the number of ovarian follicles. Compared with the model group, the treatment groups had alleviated coagulating cold and blood stasis, which was manifested as red tongue, reduced nail swelling, no blood stasis at the tail end as well as increased blood perfusion of the microcirculation in the ears and uterus(P<0.05 or P<0.01). Among the groups, the LFWJD medium-and high-dose groups had the most significant improvement in coagulating cold and blood stasis, with neatly arranged columnar epithelial cells in uterus, and the number of ovarian follicles was higher than that in the model group, especially mature follicles. The mRNA and protein expressions of PDK1, HK2, LDHA in uterus and ovaries were up-regulated in the model group(P<0.05 or P<0.01), while down-regulated in LFWJD medium-and high-dose groups(P<0.05 or P<0.01). The LFWJD low-dose group presented a decrease in the mRNA expressions of PDK1, HK2 and LDHA in uterus and ovaries as well as in the protein expressions of HK2 and LDHA in uterus and HK2 and PDK1 in ovaries(P<0.05 or P<0.01). The therapeutic mechanism of LFWJD against coagulating cold and blood stasis syndrome is related to the down-regulation of key glycolytic enzymes PDK1, HK2 and LDHA, and the inhibition of glycolytic activities in uterus and ovaries.

CT radiomics-based long-term survival prediction for locally advanced non-small cell lung cancer patients treated with concurrent chemoradiotherapy using features from tumor and tumor organismal environment.

BACKGROUND: Definitive concurrent chemoradiotherapy (CCRT) is the standard treatment for locally advanced non-small cell lung cancer (LANSCLC) patients, but the treatment response and survival outcomes varied among these patients. We aimed to identify pretreatment computed tomography-based radiomics features extracted from tumor and tumor organismal environment (TOE) for long-term survival prediction in these patients treated with CCRT. METHODS: A total of 298 eligible patients were randomly assigned into the training cohort and validation cohort with a ratio 2:1. An integrated feature selection and model training approach using support vector machine combined with genetic algorithm was performed to predict 3-year overall survival (OS). Patients were stratified into the high-risk and low-risk group based on the predicted survival status. Pulmonary function test and blood gas analysis indicators were associated with radiomic features. Dynamic changes of peripheral blood lymphocytes counts before and after CCRT had been documented. RESULTS: Nine features including 5 tumor-related features and 4 pulmonary features were selected in the predictive model. The areas under the receiver operating characteristic curve for the training and validation cohort were 0.965 and 0.869, and were reduced by 0.179 and 0.223 when all pulmonary features were excluded. Based on radiomics-derived stratification, the low-risk group yielded better 3-year OS (68.4% vs. 3.3%, p < 0.001) than the high-risk group. Patients in the low-risk group had better baseline FEV1/FVC% (96.3% vs. 85.9%, p = 0.046), less Grade ≥ 3 lymphopenia during CCRT (63.2% vs. 83.3%, p = 0.031), better recovery of lymphopenia from CCRT (71.4% vs. 27.8%, p < 0.001), lower incidence of Grade ≥ 2 radiation-induced pneumonitis (31.6% vs. 53.3%, p = 0.040), superior tumor remission (84.2% vs. 66.7%, p = 0.003). CONCLUSION: Pretreatment radiomics features from tumor and TOE could boost the long-term survival forecast accuracy in LANSCLC patients, and the predictive results could be utilized as an effective indicator for survival risk stratification. Low-risk patients might benefit more from radical CCRT and further adjuvant immunotherapy. TRIAL REGISTRATION: retrospectively registered.

Accumulation of the delivered dose based on cone-beam CT and deformable image registration for non-small cell lung cancer treated with hypofractionated radiotherapy.

BACKGROUND: This study aimed to quantify the dosimetric differences between the planned and delivered dose to tumor and normal organs in locally advanced non-small cell lung cancer (LANSCLC) treated with hypofractionated radiotherapy (HRT), and to explore the necessity and identify optimal candidates for adaptive radiotherapy (ART). METHODS: Twenty-seven patients with stage III NSCLC were enrolled. Planned radiation dose was 51Gy in 17 fractions with cone-beam CT (CBCT) acquired at each fraction. Virtual CT was generated by deformable image registration (DIR) of the planning CT to CBCT for dose calculation and accumulation. Dosimetric parameters were compared between original and accumulated plans using Wilcoxon signed rank test. Correlations between dosimetric differences and clinical variables were analyzed using Mann-Whitney U test or Chi-square test. RESULTS: Patients had varied gross tumor volume (GTV) reduction by HRT (median reduction rate 11.1%, range - 2.9-44.0%). The V51 of planning target volume for GTV (PTV-GTV) was similar between original and accumulated plans (mean, 88.2% vs. 87.6%, p = 0.452). Only 11.1% of patients had above 5% relative decrease in V51 of PTV-GTV in accumulated plans. Compared to the original plan, limited increase (median relative increase < 5%) was observed in doses of total lung (mean dose, V20 and V30), esophagus (mean dose, maximum dose) and heart (mean dose, V30 and V40) in accumulated plans. Less than 30% of patients had above 5% relative increase of lung or heart doses. Patients with quick tumor regression or baseline obstructive pneumonitis showed more notable increase in doses to normal structures. Patients with baseline obstructive atelectasis showed notable decrease (10.3%) in dose coverage of PTV-GTV. CONCLUSIONS: LANSCLC patients treated with HRT had sufficient tumor dose coverage and acceptable normal tissue dose deviation. ART should be applied in patients with quick tumor regression and baseline obstructive pneumonitis/atelectasis to spare more normal structures.

Developing and validating an integrated gross tumor volume (GTV)-TNM stratification system for supplementing unresectable locally advanced non-small cell lung cancer treated with concurrent chemoradiotherapy.

PURPOSE: The gross tumor volume (GTV) could be an independent prognostic factor for unresectable locally advanced non-small cell lung cancer (LANSCLC). We aimed to develop and validate a novel integrated GTV-TNM stratification system to supplement LANSCLC sub-staging in patients treated with concurrent chemoradiotherapy (CCRT). METHODS: We performed a retrospective review of 340 patients with unresectable LANSCLC receiving definitive CCRT. All included patients were divided into two randomized cohorts. Then the Kaplan-Meier method and Cox regression were calculated to access the prognostic value of the integrated GTV-TNM stratification system, which was further validated by the area under the receiver operating characteristic curve (AUC) score and F1-score. RESULTS: The optimal outcome-based GTV cut-off values (70 and 180 cm3) of the modeling cohort were used to determine each patient's integrated GTV-TNM stratum in the whole cohort. Our results indicated that a lower integrated GTV-TNM stratum could had better overall survival and progression-free survival (all P < 0.001), which was recognized as an independent prognostic factor. Also, its prognostic value was robust in both the modeling and validation cohorts. Furthermore, the prognostic validity of the integrated GTV-TNM stratification system was validated by significantly improved AUC score (0.636 vs. 0.570, P = 0.027) and F1-score (0.655 vs. 0.615, P < 0.001), compared with TNM stage. CONCLUSIONS: We proposed a novel integrated GTV-TNM stratification system to supplement unresectable LANSCLC sub-staging due to its prognostic value independent of TNM stage and other clinical characteristics, suggesting that it could be considered in individual treatment decision-making process.

Plasma Epstein-Barr Virus-Deoxyribonucleic Acid Copy Number Predicts Disease Progression in Stage I-III Pulmonary Lymphoepithelioma-Like Carcinoma.

Purpose: To investigate the predictive values of plasma Epstein-Barr Virus (EBV)- deoxyribonucleic acid (DNA) copy number on disease progression and survival in stage I-III pulmonary lymphoepithelioma-like carcinoma (LELC). Patients and Methods: Patients with pathologically confirmed, initially diagnosed or locally recurrent stage I-III pulmonary LELC, who received locally radical treatment and had plasma EBV-DNA results, were retrospectively reviewed. Risk factors of progression-free survival (PFS) and overall survival (OS) were assessed, including the predictive value of pre- and post-treatment EBV-DNA levels. The EBV-DNA change during follow-up was analyzed to determine its association with tumor progression and survival. Results: A total of 102 patients were included in analysis. Eighty-eight patients had initially-diagnosed and 14 had locally recurrent disease. There were 33 patients treated with radical surgery, 55 with definite radiotherapy and 14 with both. EBV-DNA was tested pre-treatment (N = 66), post-treatment (N = 93) and/or during follow-up (N = 58). Forty-one patients had complete EBV-DNA results of all three time points. The overall 2-year PFS and OS were 66.3 and 96.0%, respectively. Pre-treatment EBV-DNA copy number > 10,000 copies/mL was a risk factor of PFS (2-year PFS, > 10,000 vs. ≤ 10,000 copies/mL, 37.2 vs. 75.1%, p = 0.007). Positive post-treatment EBV-DNA also indicated a worse PFS in univariable (2-year PFS, > 0 vs. 0 copy/mL, 25.6 vs. 76.8%, p < 0.001) and multivariable analysis (HR = 3.44, 95% CI, 1.52-7.78; p = 0.003). In the follow-up set, an increasing EBV-DNA exceeding 1,000 copies/mL strongly predicted disease progression within 3 months, with a specificity of 97.5% (95% CI: 86.8-99.6%) and was associated with impaired OS (2-year OS, > 1,000 vs. ≤ 1,000 copies/mL, 72.9 vs. 100%, p < 0.001). Conclusions: Regular testing of EBV-DNA is suggested for pulmonary LELC to predict disease progression. If EBV-DNA copy number was increasing and beyond 1,000 copies/mL during follow-up, intensive radiologic evaluations are recommended.

Risk Prediction for Locoregional Recurrence in Epidermal Growth Factor Receptor-Mutant Stage III-pN2 Lung Adenocarcinoma after Complete Resection: A Multi-center Retrospective Study.

Background: This study aimed to develop a predictive model based on the risk of locoregional recurrence (LRR) in epidermal growth factor receptor (EGFR)-mutant stage III-pN2 lung adenocarcinoma after complete resection. Methods: A total of 11,020 patients with lung surgery were screened to determine completely resected EGFR-mutant stage III-pN2 lung adenocarcinoma. Patients were excluded if they received preoperative therapy or postoperative radiation therapy (PORT). The time from surgery to LRR was recorded. Clinicopathological variables with statistical significance predicting LRR in the multivariate Cox regression were incorporated into the competing risk nomogram. Patients were then sub-grouped based on different recurrence risk as a result of the nomogram. Results: Two hundred and eighty-eight patients were enrolled, including 191 (66.3%) with unforeseen N2 (IIIA1-2), 75 (26.0%) with minimal/single station N2 (IIIA3), and 22 (7.6%) with bulky and/or multilevel N2 (IIIA4). The 2-year overall cumulative incidence of LRR was 27.2% (confidence interval [CI], 16.3%-38.0%). IIIA4 disease (hazard ratio, 2.65; CI, 1.15-6.07; P=0.022) and extranodal extension (hazard ratio, 3.33; CI, 1.76-6.30; P<0.001) were independent risk factors for LRR and were incorporated into the nomogram. Based on the nomogram, patients who did not have any risk factor (low-risk) had a significantly lower predicted 2-year incidence of LRR than those with any of the risk factors (high-risk; 4.6% vs 21.9%, P<0.001). Conclusions: Pre-treatment bulky/multilevel N2 and pathological extranodal extension are risk factors for locoregional recurrence in EGFR-mutant stage III-pN2 lung adenocarcinoma. Intensive adjuvant therapies and active follow-up should be considered in patients with any of the risk factors.

Investigating the loco-regional control of simultaneous integrated boost intensity-modulated radiotherapy with different radiation fraction sizes for locally advanced non-small-cell lung cancer: clinical outcomes and the application of an extended LQ/TCP model.

BACKGROUND: To investigate the loco-regional progression-free survival (LPFS) of intensity-modulated radiotherapy (IMRT) with different fraction sizes for locally advanced non-small-cell lung cancer (LANSCLC), and to apply a new radiobiological model for tumor control probability (TCP). METHODS: One hundred and three LANSCLC patients treated with concurrent radiochemotherapy were retrospectively analyzed. Factors potentially predictive of LPFS were assessed in the univariate and multivariate analysis. Patients were divided into group A (2.0 ≤ fraction size<2.2Gy), B (2.2 ≤ fraction size<2.5Gy), and C (2.5 ≤ fraction size≤3.1Gy) according to the tertiles of fraction size. A novel LQRG/TCP model, incorporating four "R"s of radiobiology and Gompertzian tumor growth, was developed to predict LPFS and compared with the classical LQ/TCP model. RESULTS: With a median follow-up of 22.1 months, the median LPFS was 23.8 months. Fraction size was independently prognostic of LPFS. The median LPFS of group A, B and C was 13.8, 35.7 months and not reached, respectively. Using the new LQRG/TCP model, the average absolute and relative fitting errors for LPFS were 6.9 and 19.6% for group A, 5.5 and 8.8% for group B, 6.6 and 9.5% for group C, compared with 9.5 and 29.4% for group A, 16.6 and 36.7% for group B, 24.8 and 39.1% for group C using the conventional LQ/TCP model. CONCLUSIONS: Hypo-fractionated IMRT could be an effective approach for dose intensification in LANSCLC. Compared with conventional LQ model, the LQRG model showed a better performance in predicting follow-up time dependent LPFS.

Intensity-Modulated Radiotherapy versus Three-Dimensional Conformal Radiotherapy in Definitive Chemoradiotherapy for Cervical Esophageal Squamous Cell Carcinoma: Comparison of Survival Outcomes and Toxicities.

PURPOSE: The purpose of this study was to compare the survival and toxicities in cervical esophageal squamous cell carcinoma (CESCC) treated by concurrent chemoradiothrapy with either three-dimensional conformal radiotherapy (3D-CRT) or intensity-modulated radiotherapy (IMRT) techniques. MATERIALS AND METHODS: A total of 112 consecutive CESCC patients were retrospectively reviewed. 3D-CRT and IMRT groups had been analyzed by propensity score matching method, with sex, age, Karnofsky performance status, induction chemotherapy, and tumor stage well matched. The Kaplan-Meier method and Cox proportional hazards model were used for overall survival (OS) and progression-free survival (PFS). Toxicities were compared between two groups by Fisher exact test. RESULTS: With a median follow-up time of 34.9 months, the 3-year OS (p=0.927) and PFS (p=0.859) rate was 49.6% and 45.8% in 3D-CRT group, compared with 54.4% and 42.8% in IMRT group. The rates of grade ≥ 3 esophagitis, grade ≥ 2 pneumonitis, esophageal stricture, and hemorrhage were comparable between two groups, while the rate of tracheostomy dependence was much higher in IMRT group than 3D-CRT group (14.3% vs.1.8%, p=0.032). Radiotherapy technique (hazard ratio [HR], 0.09; 95% confidence interval [CI], 0.01 to 0.79) and pretreatment hoarseness (HR, 0.12; 95% CI 0.02 to 0.70) were independently prognostic of tracheostomy dependence. CONCLUSION: No survival benefits had been observed while comparing IMRT versus 3D-CRT in CESCC patients. IMRT with fraction dose escalation and pretreatment hoarseness were considered to be associated with a higher risk for tracheostomy dependence. Radiation dose escalation beyond 60 Gy should be taken into account carefully when using IMRT with hypofractionated regimen.

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.

Comparison of hyper- and hypofractionated radiation schemes with IMRT technique in small cell lung cancer: Clinical outcomes and the introduction of extended LQ and TCP models.

PURPOSE: To evaluate the outcomes of 45 Gy/15 fractions/once-daily and 45 Gy/30 fractions/twice-daily radiation schemes utilizing intensity-modulated radiation therapy (IMRT) in extensive stage small cell lung cancer (SCLC), and to build up a new radiobiological model for tumor control probability (TCP) considering multiple biological effects. METHODS: Fifty-eight consecutive patients diagnosed with extensive stage SCLC, treated with chemotherapy and chest irradiation, were retrospectively reviewed. Thirty-seven received hyperfractionated IMRT (Hyper-IMRT, 45 Gy/30 fractions/twice-daily) and 21 received hypofractionated IMRT (Hypo-IMRT, 45 Gy/15 fractions/once-daily). Local progression-free survival (LPFS) and overall survival (OS) were calculated and compared. An extended linear-quadratic (LQ) model, LQRG, incorporating cell repair, redistribution, reoxygenation, regrowth and Gompertzian tumor growth was created based on the clinical data. The TCP model was reformulated to predict LPFS. The classical LQ and TCP models were compared with the new models. Akaike information criterion (AIC) was used to assess the quality of the models. RESULTS: The 2-year LPFS (34.1% vs 27.9%, p = 0.44) and OS (76.9% vs 76.9%, p = 0.26) were similar between Hyper- and Hypo-IMRT patients. According to the LQRG model, the α/ß calculated was 9.2 (95% confidence interval: 8.7-9.9) Gy after optimization. The average absolute and relative fitting errors for LPFS were 9.1% and 18.7% for Hyper-IMRT, and 8.8% and 16.2% for Hypo-IMRT of the new TCP model, compared with 29.1% and 62.3% for Hyper-IMRT, and 30.7% and 65.3% for Hypo-IMRT of the classical model. CONCLUSIONS: Hypo- and Hyper-IMRT resulted in comparable local control in the chest irradiation of extensive stage SCLC. The LQRG model has better performance in predicting the TCP (or LPFS) of the two schemes.

Differential expression profiles of long noncoding RNAs in synchronous multiple and solitary primary esophageal squamous cell carcinomas: A microarray analysis.

As a unique subtype of esophageal cancer, synchronous multiple primary esophageal squamous cell carcinomas (ESCCs) mostly occur in Asian patients with alcohol and/or tobacco abuse, or with a family history of cancer. Multiple ESCCs are associated with poor clinical outcomes. Growing evidence has addressed that long noncoding RNAs (lncRNAs) are involved in the carcinogenesis of various malignancies. We compared the lncRNA and messenger RNA (mRNA) profiles between solitary and multiple ESCC tissues through microarray analysis, aiming at studying their different mechanisms in tumor development. As a result, in multiple ESCCs, a total of 5257 lncRNAs and 3371 mRNAs were consistently differentially expressed compared with solitary ESCC, including 2986 upregulated and 2271 downregulated lncRNAs, and 2313 upregulated, and 1058 downregulated mRNAs. We validated the results in four differentially expressed lncRNAs using quantitative real-time polymerase chain reaction. There were 38 and 20 pathways significantly related to up- and downregulated transcripts. The pathways associated with mostly enriched up- and downregulated mRNAs were hsa01200 (carbon metabolism) and hsa05221 (acute myeloid leukemia- homo sapiens [human]). Gene ontology analysis suggested that upregulated and downregulated mRNAs were mainly enriched in bounding membrane of organelle involved in the cellular component and positive regulation of transport involved in the biological process. Further analysis identified 189 differentially expressed paired antisense lncRNAs and relative sense mRNA, as well as 2134 differentially expressed long intergenic noncoding RNAs and their adjacent mRNA pairs. In conclusion, the aberrantly expressed lncRNAs might play a role in the carcinogenesis of multiple ESCCs and could be candidates as diagnostic biomarkers and therapeutic targets.

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.

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.

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>

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>

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>