Effect of apatinib on the pharmacokinetics of tramadol and O-desmethyltramadol in rats.

Since the combination of anticancer drugs and opioids is very common, apatinib and tramadol are likely to be used in combination clinically. This study evaluated the effects of apatinib on the pharmacokinetics of tramadol and its main metabolite O-desmethyltramadol in Sprague-Dawley (SD) rats and the inhibitory effects of apatinib on tramadol in rat liver microsomes (RLMs), human liver microsomes (HLMs) and recombinant human CYP2D6.1. The samples were determined by ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). The in vivo results showed that compared with the control group, apatinib increased the AUC(0-t), AUC(0-∞) and Cmax values of tramadol and O-desmethyltramadol, and decreased the values of VZ/F and CLz/F. In addition, the MRT(0-t), MRT(0-∞) values of O-desmethyltramadol were increased. In vitro, apatinib inhibited the metabolism of tramadol by a mixed way with IC50 of 1.927 µM in RLMs, 2.039 µM in HLMs and 15.32 µM in CYP2D6.1. In summary, according to our findings, apatinib has a strong in vitro inhibitory effect on tramadol, and apatinib can increase the analgesic effect of tramadol and O-desmethyltramadol in rats.

A case of acquired thrombotic thrombocytopenic purpura induced by acute severe hepatitis E: successfully treated by plasma exchange and rituximab.

With its low morbidity and high mortality rates, thrombotic thrombocytopenic purpura (TTP) has imposed a critical physical and economic burden on both society and individuals. Thrombocytopenia commonly occurs in severe liver failure, and a variety of hepatitis viruses are known to induce immune thrombocytopenic purpura. However, TTP is extremely rare in hepatitis E virus infection. We hereby report a case of a 53-year-old male who present with TTP caused by severe hepatitis E, and the patients achieved successful recovery after treatment. Therefore, we propose considering AMAMTS13 testing as an essential and beneficial approach for accurately diagnosing and treating patients with severe hepatitis or infection with notable platelet decline.

Effect of flavonoids and CYP3A4 variants on midostaurin metabolism.

The objective of this study was to determine the effect of flavonoids on midostaurin disposition considering co-administration and metabolic enzyme gene polymorphism. Enzymatic incubation assays were performed in vitro, while in vivo experiments were conducted in Sprague-Dawley rats. The analytes were determined via UPLC-MS/MS. We found that myricetin was the most potent among the investigated 10 flavonoids in suppressing the metabolism of midostaurin, with an IC50 at a low µM level. After co-administration of midostaurin and myricetin, the plasma concentration of midostaurin's primary metabolite CGP62221 was reduced corresponding to myricetin exposure. Furthermore, CYP3A4 homologous rat protein CYP3A2 was reduced significantly in the co-administration group. Thereafter, the kinetic parameters of 23 recombinant human CYP3A4 variants were determined using midostaurin. The relative intrinsic clearance varied from 269.63% in CYP3A4.29-8.95% in CYP3A4.17. In addition, the inhibitory potency of myricetin was substantially different for CYP3A4.29 and CYP3A4.17 compared with wild type, with IC50 values of 9.85 ± 0.27 µM and 90.99 ± 16.13 µM, respectively. Collectively, our data demonstrated that flavonoids, particularly myricetin, can inhibit the metabolism of midostaurin. Additionally, CYP3A4 genetic polymorphism may contribute to stratification of midostaurin blood exposure.

[Application analysis of laparoscopic assisted microsurgical vasovasostomy in the treatment of vas deferens obstruction caused by inguinal herniorrhaphy].

OBJECTIVE: To investigate the effiicacy of laparoscopic assisted microsurgical vasovasostomy in the treatment of vas deferens obstruction caused by inguinal herniorrhaphy. METHODS: Clinical data of patients undergoing surgical treatment for deferential obstruction after inguinal hernia repair in the andrology department of the First Affiliated Hospital of Zhengzhou University from 2018 to 2022 were retrospectively analyzed, and they were divided into two groups according to different surgical methods: double mirror combined group and microscope group. The basic clinical data, intraoperative conditions, postoperative effects and complications of the two groups were compared. RESULTS: There were 14 cases in the double mirror group and 34 cases in the microscope group. There was no significant difference in age and history of groin operation between the two groups (P>0.05). The average length of hospital stay in the two-lens group was less than that in the microscope group (5.07±0.26 days vs 7.09±1.86 days, P< 0.01), and the average operation time in the two-lens group was more than that in the microscope group (211.93±58.55min vs 162.26±40.70min, P<0.01). The postoperative recurrence rate (85.7% vs 73.5%, P > 0.05) was similar between the two groups. There was no significant difference in early postoperative complications (0% vs 2.9%, P > 0.05). Only 1 patient in the microscope group experienced fat liquefaction and recovered after intensive dressing change. CONCLUSION: Laparoscope-assisted microscopy provides natural fertility opportunities for patients with vas deferens obstruction after inguinal hernia repair, reduces the difficulty of surgery and the length of hospital stay, and is a safe and effective surgical method comparable to traditional surgical methods.

Efficacy analysis of 26 cases of ejaculatory duct obstruction treated by prostatic utricle neck endoscopy.

Objective: To evaluate the safety and efficacy of transvesical incision in the treatment of ejaculatory duct obstruction. Methods: The clinical data of 26 male infertile patients with ejaculatory duct obstruction were retrospectively analysed at the First Affiliated Hospital of Zhengzhou University from June 2020 to August 2021. All patients were treated with seminal vesicle neck incision for ejaculatory duct obstruction. The general clinical characteristics, intraoperative conditions and postoperative effects on the patients were recorded, and the therapeutic effect was evaluated. Results: The ejaculatory duct was found through fenestration, and the seminal vesicle gland was smoothly entered in 25 patients (96.2%). Among them, 22 cases underwent bilateral endoscopy and three underwent unilateral endoscopy. Sperm appeared in 23 cases (88.5%) 3 months after surgery. The sperm concentration and motility postoperatively at 6 months were higher than that at 3 months postoperatively. No postoperative complications, such as epididymitis or retrograde ejaculation, occurred. Conclusion: Searching for the ejaculatory duct via the neck of the prostatic utricle, assisted by a low-energy holmium laser, is a new method for the treatment of ejaculatory duct obstruction. Microscopic vision is clear using this approach and the postoperative complications are few, which has high value for clinical application.

Analyzing the Clinical Efficacy of a Type 5 Phosphodiesterase Inhibitor Combined With Ziyin Baihuo Granules in the Treatment of Erectile Dysfunction.

The study explored the clinical efficacy of a type 5 phosphodiesterase inhibitor (PDE5i) combined with Ziyin Baihuo granules in the treatment of patients suffering from erectile dysfunction (ED) with yin deficiency and fire-hyperactivity syndrome. A total of 163 patients with erectile dysfunction were divided into observation and control groups. The observation group took tadalafil (Cialis) and Ziyin Baihuo granules orally, and the control group took only tadalafil orally, for 12 weeks. An additional 40 healthy people were selected as a normal group for comparison of the sex hormone levels before and after treatment of the participants in the erectile dysfunction group. After treatment, the symptoms of dry throat and tongue, tidal fever and night sweats, liking cold and avoiding heat, and waist pain showed significant improvement in the observation group (p < .05). Compared with before treatment, the clinical indexes of erectile function in the control group and the observation group were improved after treatment (p < .05). After treatment, Ziyin Baihuo granules combined with tadalafil restored the abnormal indexes of blood (p < .05) in the observation group. Our research shows that PDE5i combined with Ziyin Baihuo granules could effectively improve erectile function.

A Comparative Study on the Success Rates of Two Approaches for Seminal Vesiculoscopy.

This study aimed to compare the success rates of two approaches for seminal vesiculoscopy: through the interior of the prostatic utricle and through the neck of the prostatic utricle. The patients were divided into two groups based on the seminal vesiculoscopy used. Group A was an interior of the prostatic utricle group (152 cases), and group B was a neck of the prostatic utricle group (146 cases). The general clinical data, intraoperative conditions and surgical results of the two groups were compared. Compared with group A, group B had a higher surgical success rate (94.5% vs. 62.5%, p < .001), a shorter operation time (33 min vs. 45 min, p < .001), less blood loss (0.5 ml vs. 2 ml, p < .001), a higher pain relief rate (86.6% vs. 52.3%, p < .001), a higher remission rate of haemospermia (82.2% vs. 58.5%, p = .011), a lower recurrence rate of pain (10.4% vs. 35.4%, p < .001), a lower recurrence rate of haemospermia (15.6% vs. 37.7%, p = .014), a higher symptom remission rate of the lower urinary tract (90.9% vs. 50.0%, p = .030), a higher remission rate of scrotal moisture (84.6% vs. 45.5%, p = .042) and a higher remission rate of frequent spermatorrhea (80.0% vs. 55.6%, p = .033). Seminal vesiculoscopy undertaken through the neck of the prostatic utricle has the characteristics of high success rate, short operation time and good surgical effect and is worthy of promotion and application.

Development and Validation of a UHPLC-MS/MS Method for Quantitation of Almonertinib in Rat Plasma: Application to an in vivo Interaction Study Between Paxlovid and Almonertinib.

Almonertinib was approved for the first-line treatment of advanced NSCLC patients with EGFR-TKI-sensitive genetic mutations by National Medical Products Administration (NMPA) in 2021.The purpose of this study was to establish and validate a fast, accurate, stable and facile ultra-performance liquid chromatography-tandem mass spectrometry method for the quantification of almonertinib in rat plasma, it was employed to explore the effect of Paxlovid on the pharmacokinetics of almonertinib in rats. Zanubrutinib was used as an internal standard (IS), and the plasma samples were prepared by the protein precipitation method using acetonitrile. Chromatographic separation was carried out on a Shimadzu LC-20AT ultra-performance liquid chromatography system using a Shim-pack velox C18 (2.1× 50 mm, 2.7 µM) column. The mobile phase consisted of methanol and 0.1% formic acid-water. Mass spectrum analysis was executed using Shimadzu 8040 Triple quadrupole mass spectrometry. The precursor and product ions of the analyte and internal standard were detected in multiple reaction monitoring (MRM) mode. The typical fragment ions were m/z 526.20 → 72.10 for almonertinib and m/z 472.15 → 290.00 for zanubrutinib (IS). The method was validated to have good linearity for quantifying almonertinib in rat plasma from 0.1-1000 ng/ml (R2 = 0.999), and the LLOQ was 0.1 ng/ml. The validity of this method was sufficiently verified for selectivity, specificity, extraction recovery, matrix effect, accuracy, precision and stability. The validated UHPLC-MS/MS method was successfully applied to the drug interaction study of almonertinib with Paxlovid in rats. Paxlovid significantly inhibits the metabolism of almonertinib and increased the exposure of almonertinib. This study can help us to understand the metabolic profile of almonertinib better, and further human trials should be conducted to validate the results.

Endothelial GABBR2 Regulates Post-ischemic Angiogenesis by Inhibiting the Glycolysis Pathway.

Purpose: Angiogenesis post-ischemia plays an essential role in preventing ischemic damage to tissue by improving the blood recovery. Determining the regulatory mechanism of ischemic angiogenesis, therefore, could provide effective therapeutics for ischemic injury. Materials and Methods: The RNA sequencing (RNA-seq) database was used to predict the association of gamma-aminobutyric acid type B receptor subunit 2 (GABBR2) with endothelial-specific expression. The role of GABBR2 in angiogenesis was verified in vitro by downregulating GABBR2 in human umbilical vein endothelial cells (HUVECs) with lentiviral vectors. Besides, the in vivo effect of GABBR2 on the blood recovery of an ischemic hindlimb was demonstrated by establishing a hindlimb ischemia model in normal and GABBR2 adenoviral vector-infected mice. Then, the mobilization of endothelial progenitor cells (EPCs) in peripheral blood post-ischemia was determined by flow cytometry. Finally, the XF analyzer and Western blot were used to determine the effect of GABBR2 on endothelial metabolism. Results: The RNA-seq results indicated a strong association between GABBR2 and endothelial revascularization, and the upregulation of GABBR2 was detected in both hypoxia-treated HUVECs and ischemic mouse hindlimb. Hypoxia treatment for 6 h increased the proliferation, migration, and tube formation of HUVECs, which were inhibited by GABBR2 knockdown. Additionally, GABBR2 downregulation significantly decreased the blood flow recovery of mouse ischemic hindlimb. The expressions of the EPC markers CD34+ and CD133+ significantly decreased in the peripheral blood in hindlimb post-ischemia. Mechanically, glycolysis-dominated metabolism of HUVECs was compromised by GABBR2 knockdown. Evidences of the decreased expressions of HKII, PFKFB3, and PKM1 also supported the compromised glycolysis induced by GABBR2 downregulation. Conclusion: Our study demonstrated that GABBR2 regulated angiogenesis post-ischemia by inhibiting the glycolysis pathway.

Inhibitory effect of resveratrol on the pharmacokinetics of ticagrelor in vivo and in vitro.

This study was to evaluate the effect of resveratrol on the pharmacokinetics of ticagrelor in rats and the metabolism of ticagrelor in human cytochrome P450 (CYP) 3A4 (CYP3A4) and liver microsomes. Eighteen Sprague-Dawley rats were randomly divided into three groups: group A (control group), group B (50 mg/kg resveratrol), and group C (150 mg/kg resveratrol). After 30 min administration of resveratrol, a single dose of ticagrelor (18 mg/kg) was administered orally. The in vitro experiment was performed to examine the influence of resveratrol on ticagrelor metabolism in CYP3A4*1, human, and rat liver microsomes. Serial biological samples were assayed by validated ultra high-performance liquid chromatography - tandem mass spectrometer methods. For the in vivo study, the area under the concentration-time curve and mean peak plasma concentrations of ticagrelor in group B and C appeared to be significantly higher than the control group, while volume of distribution in terminal phase and apparent clearance of ticagrelor in group B and C were significantly decreased. For the in vitro study, resveratrol exhibited an inhibitory effect on CYP3A4*1, human and rat liver microsomes. The half-maximal inhibitory concentration values of resveratrol were 56.75 µM, 69.07 µM, and 14.22 µM, respectively. Our results indicated that resveratrol had an inhibitory effect on the metabolism of ticagrelor in vitro and in vivo. Further research should focus on the clinical combination of resveratrol with ticagrelor, and ticagrelor plasma concentration should be monitored to avoid the occurrence of adverse reaction.

[Blood biochemical indexes in ED patients with kidney deficiency or non-kidney deficiency: A comparative analysis of 156 cases].

OBJECTIVE: To analyze the blood biochemical characteristics of the ED patients with different types of kidney deficiency or non-kidney deficiency. METHODS: We reviewed the clinical data on 156 ED patients treated in our Department of Andrology from May to July 2018 and, according to the traditional Chinese medicine (TCM) syndromes, divided them into four groups: kidney-yang deficiency (n = 48), kidney-yin deficiency (n = 34), kidney-yin+yang deficiency (n = 36) and non-kidney deficiency control (n = 38). We obtained and compared their blood biochemical indexes, including the levels of testosterone (T), estradiol (E2), cortisol (CORT), thyroid stimulating hormone (TSH), free thyroxine (FT4), free triiodothyronine (FT3), nitric oxide (NO), total nitric oxide synthase (tNOS), and inducible nitric oxide synthase (iNOS). RESULTS: There were no statistically significant differences in the mean age, course of disease, IIEF-5 score and erection hardness score (EHS) among the four groups of patients. Pairwise comparison showed that, compared with the non-kidney deficiency controls, the patients in the kidney-yin deficiency group exhibited a dramatically higher level of CORT (ï¼»87.97 ± 45.59ï¼½ vs ï¼»121.78 ± 41.87ï¼½ µg/L, P = 0.002) and those in the kidney-yang deficiency group a remarkably lower level of FT3 (ï¼»5.44 ± 0.38ï¼½ vs ï¼»5.11 ± 0.54ï¼½ pmol/L, P = 0.008). The iNOS level was significantly higher in the kidney-yin deficiency group (14.42 ± 2.49 U/ml) than in either the control (12.71 ± 2.58 U/ml) (P = 0.039) or the kidney-yang deficiency group (13.05 ± 2.17 U/ml) (P =0.049). CONCLUSIONS: ED patients with different types of kidney deficiency syndromes have different blood biochemical indexes, which may help clarify the biological basis of the TCM syndromes of kidney deficiency in ED patients.

Association between dietary fiber and endometrial cancer: a meta-analysis.

To explore a potential relationship between dietary fiber consumption and risk of endometrial cancer (EC), eligible studies published up to 30 June 2018 were retrieved via computer searches and manual review of references. Random-effects models were used to calculate summary relative risk (RR) estimates based on contrasting high- and low-fiber intake values. Sensitivity analysis was conducted, and heterogeneity among study results was explored through stratified analyses by study design, geographic region, Newcastle-Ottawa Scale (NOS) score, impact factor, and adjustment for several confounders (age, body mass index, smoking, energy intake, and education). We extracted data from 16 studies (involving 6,563 cases). There was a significant association between dietary fiber intake and EC (RR = 0.86, 95% confidence interval [CI]: 0.78, 0.93). In stratified analysis, this trend was more pronounced in the case-control studies, and in studies conducted in the Americas and Asia. The relationship was further confirmed after adjusting for education level (RR = 0.74; 95% CI: 0.60, 0.88) and age (RR = 0.70; 95% CI: 0.57, 0.83), and NOS scores of 6 (RR = 0.81; 95% CI: 0.67, 0.95) and 7 (RR = 0.75; 95% CI: 0.62, 0.88). In conclusion, our meta-analysis revealed an inverse association between dietary fiber consumption and EC risk. Further efforts should be made to confirm these findings.

Plasma osteopontin acts as a prognostic marker in acute intracerebral hemorrhage patients.

BACKGROUND: Osteopontin (OPN), a matricellular protein, is greatly generated from brain tissues after acute brain injury. We determine the relationship between plasma OPN concentrations and outcome after acute intracerebral hemorrhage (ICH) in a clinical setting. METHODS: In this prospective, observational study enrolling 162 ICH patients and 162 healthy controls, hemorrhagic severity was assessed using National Institutes of Health Stroke Scale (NIHSS) scores and hematoma volumes, a poor outcome was defined as modified Rankin Scale >2 at poststroke 90 days, and early neurologic deterioration (END) was defined as an increase of ≥4 points in the NIHSS score or death at 24 h from symptoms onset. RESULTS: Plasma OPN concentrations were significantly higher in patients than in controls (median value, 1287.6 vs. 405.7 pmol/l; P < 0.001). OPN concentrations were strongly correlated with admission NIHSS scores (r value = 0.520) and hematoma volumes (r value = 0.468). Areas under receiver operating characteristic curve for poor outcome and END were 0.811 and 0.753 respectively. Plasma OPN emerged as an independent predictor of functional outcome and END, with odds ratio values of 3.897 and 6.004 respectively. CONCLUSIONS: Plasma OPN could serve as a useful prognostic biomarker in ICH.

Effect of bovine lactoferrin as a novel therapeutic agent in a rat model of sepsis-induced acute lung injury.

Sepsis is a serious clinical condition resulting from severe infection. High rates of mortality and tissue damage have been reported in intensive care unit (ICU) patients with sepsis. Bovine lactoferrin (BLF) is a well-known 80-kDa glycoprotein in the transferrin family that inhibits sepsis in low-birth-weight neonates. The present study investigated the protective effects of BLF in a rat model of sepsis-induced acute lung injury (ALI). The wet/dry ratio, lipid peroxidation, antioxidant markers, total protein, total cell count, inflammatory markers and myeloperoxidase (MPO) levels were assessed. Histopathological analysis was also carried out. BLF treatment reduced the wet/dry ratio of lung tissue by 30.7% and 61.3%, and lipid peroxidation by 22.3% and 67%, at concentrations of 100 and 200 mg/kg, respectively. Superoxide dismutase (SOD), reduced glutathione (GSH), glutathione peroxidase (Gpx) and catalase were increased by more than 50% under treatment with 200 mg/kg BLF. Inflammatory markers, neutrophils, lymphocytes and total cell count were reduced by more than 50% under treatment with 200 mg/kg BLF. BLF treatment significantly reduced MPO activity, by 28.2% and 74.3%, at concentrations of 100 and 200 mg/kg, respectively. Neutrophilic infiltration and edema were observed in control rats. However, BLF treatment restored intestinal microvilli to the normal range and reduced inflammatory cell invasion. Collectively, these results suggest that BLF is an effective therapeutic agent against sepsis-induced ALI.

Erratum: MiR-4295 promotes cell growth in bladder cancer by targeting BTG1.

[This corrects the article on p. 4892 in vol. 8, PMID: 27904689.].

WITHDRAWN: MiR-6838 Promotes Growth and Invasion in Bladder Cancer Via Suppression of Rb.

Ahead of Print article withdrawn by publisher..

An in vitro Vascular Model for Studying the Impact of Different Blood Oxygen Saturation on Main Pulmonary Artery Pressure Changes / 中国循环杂志

Objective: To establish an in vitro vascular model to study the impact of different blood oxygen (O2) saturation on main pulmonary artery pressure changes in order to further explore the mechanism of pulmonary hypertension. Methods: 20 New Zealand white rabbits were randomly divided into 4 groups: Normal control group and 3 experimental groups as High O2 (90％-100％)saturation group, Middle O2 (65％-75％)saturation group and Low O2 (40％-50％) saturation group, n=5 in each group. The in vitro pulmonary artery segments were treated with fresh heparinized rabbit blood and connected to extracorporeal circulation system for 48h at perfusion pressure at 40 mmHg; the condition of O2 saturation was regulated by membrane oxygenator. Pathological morphology was compared among different groups. Results:The bypass time in all 3 groups was 48h and the pressure was stably controlled at 40 mmHg. Blood O2 contents in High O2 saturation group, Middle O2 saturation group and Low O2 saturation group were (97.94±1.01) ％, (72.14±12.85) ％and (43.83±8.71) ％ respectively, P<0.05. Pathological analysis indicated that compared with Normal control group, 3 experimental groups had increased thickness in pulmonary artery wall; upon O2 saturation decreasing, the elastic fibers in pulmonary artery became increasing and more thickening accordingly. Conclusion: We established an in vitro vascular model to study the impact of different blood O2 saturation on main pulmonary artery pressure changes in experimental rabbits.

An in vitro Vascular Model for Studying the Impact of Different Blood Oxygen Saturation on Main Pulmonary Artery Pressure Changes / 中国循环杂志

Objective: To establish an in vitro vascular model to study the impact of different blood oxygen (O2) saturation on main pulmonary artery pressure changes in order to further explore the mechanism of pulmonary hypertension. Methods: 20 New Zealand white rabbits were randomly divided into 4 groups: Normal control group and 3 experimental groups as High O2 (90％-100％)saturation group, Middle O2 (65％-75％)saturation group and Low O2 (40％-50％) saturation group, n=5 in each group. The in vitro pulmonary artery segments were treated with fresh heparinized rabbit blood and connected to extracorporeal circulation system for 48h at perfusion pressure at 40 mmHg; the condition of O2 saturation was regulated by membrane oxygenator. Pathological morphology was compared among different groups. Results:The bypass time in all 3 groups was 48h and the pressure was stably controlled at 40 mmHg. Blood O2 contents in High O2 saturation group, Middle O2 saturation group and Low O2 saturation group were (97.94±1.01) ％, (72.14±12.85) ％and (43.83±8.71) ％ respectively, P<0.05. Pathological analysis indicated that compared with Normal control group, 3 experimental groups had increased thickness in pulmonary artery wall; upon O2 saturation decreasing, the elastic fibers in pulmonary artery became increasing and more thickening accordingly. Conclusion: We established an in vitro vascular model to study the impact of different blood O2 saturation on main pulmonary artery pressure changes in experimental rabbits.

MiR-4295 promotes cell growth in bladder cancer by targeting BTG1.

microRNAs (miRNAs) have been demonstrated to contribute to tumor progression and metastasis, and have been proposed to be key regulators of diverse biological processes. In this study, we report that miR-4295 is deregulated in bladder cancer tissues and cell lines. To characterize the role of miR-4295 in bladder cancer cells, we performed functional assays. The overexpression of miR-4295 significantly promoted bladder cancer cell proliferation, colony formation, and migration. Moreover, its downregulation induced cell cycle arrest and apoptosis of bladder cancer cells. Furthermore, a luciferase reporter assay and rescue experiment indicated that miR-4295 directly targets BTG1 by binding its 3'UTR. In conclusion, these results demonstrate that miR-4295 acts as an oncogene and may be a potential biomarker for bladder cancer diagnosis and treatment.

Transient receptor potential melastatin-2 and temperature participate in the process of CD38-regulated oxytocin secretion.

In recent studies, oxytocin showed potential for the treatment of mental diseases. CD38 is essential for oxytocin release, and hence plays a critical role in social behavior. CD38 catalyzes ß-NAD into cyclic ADP ribose (cADPR), which could elevate the intracellular Ca by Ca-permeable channels for oxytocin secretion. The temperature-sensitive cation channel, transient receptor potential melastatin-2 (TRPM2), is a cation-nonselective cation and has been shown to affect oxytocin indirectly. The aim of the present study was to verify the participation of temperature and TRPM2 in CD38-regulated oxytocin release. The crude membranes were prepared to isolate the nerve terminals from the posterior pituitary. At 34°C, 37°C, and 39°C, agonists (ß-NAD, ADPR, cADPR) and antagonists (8-Br-cADPR, 2-APB) were used to stimulate the nerve terminals. Oxytocin releases were investigated by enzyme-linked immunosorbent assay. In addition, the expression of TRPM2 and CD38 in the hypothalamus and pituitary was detected by western blotting and quantitative PCR. CD38 agonists (ß-NAD, cADPR) and antagonist (8-Br-cADPR) could increase or reduce the oxytocin release, respectively. TRPM2 agonist (ADPR) and antagonist (2-APB) alone could also regulate oxytocin release. Furthermore, temperature could increase agonist stimulation and attenuate the antagonist inhibition on oxytocin release. In addition, CD38 and TRPM2 were expressed in the hypothalamus and pituitary at both the mRNA and the protein level. TRPM2 in pituitary nerve terminals plays a role in oxytocin release. Temperature- enhanced oxytocin release by CD38 and TRPM2. TRPM2 might be involved in the process of CD38-regulated oxytocin release.