A bibliometric analysis and visualization of retinopathy of prematurity from 2001 to 2021.

OBJECTIVE: Retinopathy of prematurity (ROP) is an eye disease with the potential to cause blindness, primarily affecting premature infants with low birth weight. This study analyzed the etiology, primary location, and research advances in ROP. MATERIALS AND METHODS: We used bibliometric techniques and searched the Web of Science Core Collection for "retinopathy of prematurity." We found 4,018 original articles and reviews with 69,819 references. We analyzed the data using HistCite (12.03.17), VOSviewer (1.6.16), CiteSpace (6.1. R5), and the Bibliometrix Package (4.1.0). RESULTS: The amount of literature in this area has increased between 2001-2021. An analysis of references and journal co-citations highlights this field's most influential articles and related topics. Hellström, from the University of Gothenburg (Sweden), is the most prolific researcher; Harvard University is the most prolific research institution, and the USA is the most productive country. "Threshold ROP" and "cryotherapy" are the keywords with the highest burst strength. The future research hotspots are artificial intelligence, zone II, ROP development, ranibizumab, and type 1 retinopathy. CONCLUSIONS: This article offers a comprehensive review of the present status of ROP research, along with insights into emerging concepts and potential international collaborations in this field.

[Establishment and efficiency test of a clinical prediction model of bronchopulmonary dysplasia associated pulmonary hypertension in very premature infants].

Objective: To develop a risk prediction model for identifying bronchopulmonary dysplasia (BPD) associated pulmonary hypertension (PH) in very premature infants. Methods: This was a retrospective cohort study. The clinical data of 626 very premature infants whose gestational age <32 weeks and who suffered from BPD were collected from October 1st, 2015 to December 31st, 2021 of the Seventh Medical Center of the People's Liberation Army General Hospital as a modeling set. The clinical data of 229 very premature infants with BPD of Hunan Children's Hospital from January 1 st, 2020 to December 31st, 2021 were collected as a validation set for external verification. The very premature infants with BPD were divided into PH group and non PH group based on the echocardiogram after 36 weeks' corrected age in the modeling set and validation set, respectively. Univariate analysis was used to compare the basic clinical characteristics between groups, and collinearity exclusion was carried out between variables. The risk factors of BPD associated PH were further screened out by multivariate Logistic regression, and the risk assessment model was established based on these variables. The receiver operating characteristic (ROC) area under curve (AUC) and Hosmer-Lemeshow goodness-of-fit test were used to evaluate the model's discrimination and calibration power, respectively. And the calibration curve was used to evaluate the accuracy of the model and draw the nomogram. The bootstrap repeated sampling method was used for internal verification. Finally, decision curve analysis (DCA) to evaluate the clinical practicability of the model was used. Results: A total of 626 very premature infants with BPD were included for modeling set, including 85 very premature infants in the PH group and 541 very premature infants in the non PH group. A total of 229 very premature infants with BPD were included for validation set, including 24 very premature infants in the PH group and 205 very premature infants in the non PH group. Univariate analysis of the modeling set found that 22 variables, such as artificial conception, fetal distress, gestational age, birth weight, small for gestational age, 1 minute Apgar score ≤7, antenatal corticosteroids, placental abruption, oligohydramnios, multiple pulmonary surfactant, neonatal respiratory distress syndrome (NRDS)>stage Ⅱ, early pulmonary hypertension, moderate-severe BPD, and hemodynamically significant patent ductus arteriosus (hsPDA) all had statistically significant influence between the PH group and the non PH group (all P<0.05). Antenatal corticosteroids, fetal distress, NRDS >stage Ⅱ, hsPDA, pneumonia and days of invasive mechanical ventilation were identified as predictive variables and finally included to establish the Logistic regression model. The AUC of this model was 0.86 (95%CI 0.82-0.90), the cut-off value was 0.17, the sensitivity was 0.77, and the specificity was 0.84. Hosmer-Lemeshow goodness-of-fit test showed that P>0.05. The AUC for external validation was 0.88, and the Hosmer-Lemeshow goodness-of-fit test suggested P>0.05. Conclusions: A high sensitivity and specificity risk prediction model of PBD associated PH in very premature infants was established. This predictive model is useful for early clinical identification of infants at high risk of BPD associated PH.

[The establishment and multicenter application of internal quality control system for real-time quantitative PCR detection of BCR-ABL (P210) transcript level].

Objective: The study aims to establish a perfect BCR-ABL (P210) internal quality control system and ensure the long-term stability and comparability of the detection results between laboratories and to popularize and apply it in the three hospitals. Methods: The Qilu Hospital of Shandong University (H1) prepared a set of the BCR-ABL (P210) quality control substances to establish and improve internal quality control system. We went to other three participating hospitals (H2, H3, and H4) to inspect quality control before the measurement. In addition, we mailed 25 sets of quality control substances to each of the hospital for detection. The slope and intercept of the standard curve of each hospital and the detection results were analyzed and statistically judged using the Levey-Jennings quality control chart combined with the Westgard multirule theory. Then, we made a quality control evaluation. Results: ①An internal quality control system for the BCR-ABL (P210) transcript levels monitoring was successfully established for the quality inspection before the measurement, statistical judgment during the measurement, and evaluation after the measurement. ② Both the slope and intercept of the standard curve of the four hospitals was under control. ③The multicenter quality control substance judgment results were as follows: for H1 hospital, two times of "1(2s)" warning were found in the middle-level quality control substance, which was judged as being under control; for H2 hospital, one time of "1(2s)" warning was found for each quality control substance, which was judged as being "2(2s)" out of control; for H3 hospital, its high-level quality control substance violated the "1(3s)" rule, and low-level quality control substance appeared "1(2s)" warning, which was judged as "1(3s)" out of control; and all quality control substances were under control in H4 hospital. ④The quality control evaluation and correction were as follows: two hospitals were under control, and the other two hospitals had an "out of control." We found out the reason for the out of control and corrected them. ⑤The comparisons of the original values of the multicenter quality control substance were as follows: there were statistical differences in the results of high-level quality control substance among the four hospitals, and no significant difference was found in the results of the medium-level and low-level quality control substance. ⑥The comparisons of the IS values of the multicenter quality control substance were as follows: the IS values of the three quality control substance in H2 and H3 hospitals were significantly higher than those of H1 hospital, and H2 hospital was significantly higher than H3 hospital. Conclusion: A perfect and stable internal quality control system for the BCR-ABL (P210) transcripts has been established, which can effectively ensure the accuracy and stability of the clinical detection results. This internal quality control system has been successfully popularized and applied in other hospitals.

Budesonide and Poractant Alfa prevent bronchopulmonary dysplasia via triggering SIRT1 signaling pathway.

OBJECTIVE: This study aimed to evaluate effect of budesonide combining Poractant Alfa on preventing bronchopulmonary dysplasia (BPD). PATIENTS AND METHODS: A total of 120 preterm infants were involved. pH value, partial pressure of oxygen (PO2), and blood gas analysis were evaluated. Peripheral blood was collected and mononuclear cells were isolated. Reactive oxygen species (ROS) in peripheral blood mononuclear cells (PBMCs) were detected with laser confocal. Sirtuin 1 (SIRT1) in PBMCs was detected using immunofluorescence. SIRT1 and small ubiquitin-like modifier (SUMO)-specific protease 1 (SENP1) were detected with Western blot. RESULTS: Compared with group B, pH value and PO2 were improved significantly in group C and D (p<0.01). Compared with group B, oxygen inhalation duration, rate of having a respirator assisted ventilation, and using pulmonary surfactant (PS) again, and BPD incidence were significantly decreased in other groups (p<0.05). BPD incidence in group D was less than group C (χ2=4.00, p<0.05). Compared with control group, ROS level of neonatal respiratory distress syndrome (NRDS) group was significantly increased, SENP1 was increased, and SIRT1 was decreased in SIRT1 group. Compared with NRDS, when budesonide combined with Poractant Alfa, ROS decreased, SENP1 decreased, SIRT1 nuclear pulp shuttling rate reduced, nuclear SIRT1 increased (p<0.01). Compared with control, ROS level of NRDS group was significantly increased, SENP1 increased, and SIRT1 in nucleus decreased (p<0.05). Compared with NRDS group, when treated with budesonide and Poractant Alfa, ROS levels decreased, SENP1 decreased, nuclear SIRT1 increased (p<0.01). CONCLUSIONS: Budesonide combining Poractant Alfa can prevent BPD in preterm infants by activating the SIRT1 signaling pathway.

Long noncoding RNA ABHD11-AS1 predicts the prognosis of pancreatic cancer patients and serves as a promoter by activating the PI3K-AKT pathway.

OBJECTIVE: Accumulating evidence showed aberrant expressions of long non-coding RNAs (lncRNAs) strongly correlated to the development of cancers, including pancreatic cancer (PC). Whether lncRNA ABHD11-AS1 (ABHD11-AS1) is involved in PC remains to be elucidated. Thus, we aimed to evaluate the effects of ABHD11-AS1 on PC and the underlying molecular mechanism. PATIENTS AND METHODS: RT-PCR was used to detect the expression level of ABHD11-AS1 in both PC tissue and cell lines. Then, the correlation of ABHD11-AS1 expression with clinicopathological features and prognosis was studied. Cell proliferation, apoptosis, migration and invasion abilities were detected by MTT, flow cytometry, and transwell assays. We further investigated the effect of abnormal ABHD11-AS1 expression through the PI3K/AKT and EMT pathway by Western blot assays in treated PC cells. RESULTS: We found that the expression of ABHD11-AS1 was significantly increased in both PC tissues and cell lines. The clinical analysis revealed that a high level of ABHD11-AS1 expression was correlated with distant metastasis, TNM stage, and tumor differentiation. The Kaplan-Meier analysis showed that high ABHD11-AS1 expression levels predicted poorer survival. Moreover, univariate and multivariate analyses confirmed that the expression of ABHD11-AS1 was an independent and significant factor associated with poor overall survival rates. Loss-of-function experiments showed that the knockdown of ABHD11-AS1 suppressed PC cell proliferation, migration, invasion, and EMT in vitro. Mechanistically, the knockdown of ABHD11-AS1 decreased phospho(p) AKT and phospho(p) PI3K expression, but did not affect the AKT and PI3K expression in PC cells CONCLUSIONS: This study suggested that ABHD11-AS1 may potentially function as a valuable prognostic biomarker and a therapeutic target for PC patients.

Paeoniflorin attenuates postoperative pain by suppressing Matrix Metalloproteinase-9/2 in mice.

BACKGROUND: Recent studies have implicated that matrix metalloproteinase (MMP)-9 and MMP-2 play key roles in neuropathic pain due to their facilitation of inflammatory cytokine maturation and induction of neuroinflammation. However, the role of MMP-9/2 in postoperative pain is still unclear. We previously suggested that the natural compound paeoniflorin inhibited microglia activation induced by morphine treatment. In the present study, we demonstrated that paeoniflorin could alleviate postoperative pain via specific inhibition of matrix metalloproteinases (MMPs). METHODS: Mice received a plantar incision surgery and their mechanical allodynia was assessed with von Frey filaments. The activity of MMP-9/2 was determined by gelatin zymography. Cell signalling was assayed by western blot and immunohistochemistry. RESULTS: The expression of MMP-9/2 was significantly increased in mice spinal cords with plantar incision surgery. Paeoniflorin remarkably suppressed the activity of MMP-9/2 and relieved plantar incision-induced mechanical allodynia. Interestingly, the administration of paeoniflorin blocked the maturation of interleukin-1ß, which is a critical substrate of MMPs. Thereafter, paeoniflorin markedly suppressed microglia activation, inhibited the phosphorylation of p38 mitogen-activated protein kinase (MAPK) and the expression of neuronal c-Fos. CONCLUSION: These results indicated that MMP-9/2 activation in spinal microglia plays a key role in incision-induced mechanical allodynia in mice. Moreover, utilizing paeniflorin blockage of the microglia MMP-9/2 activity might represent a valuable alternative for treating postoperative pain. SIGNIFICANCE: Our results provided direct evidence for the first time that paeoniflorin can inhibit plantar incision-induced microglia TLR4/MMP-9/2/IL-1ß signalling pathway and suppress postoperative pain. Thus, regulation of microglia MMP-9/2 may provide a new strategy for ameliorating postoperative pain.

Genetic Polymorphisms of 21 STR Loci in Hunan Province-based Han Population.

OBJECTIVES: To investigate the genetic polymorphisms of 21 short tandem repeat （STR） loci （D3S1358, D13S317, D7S820, D16S539, Penta E, D2S441, TPOX, TH01, D2S1338, CSF1PO, Penta D, D10S1248, D19S433, vWA, D21S11, D18S51, D6S1043, D8S1179, D5S818, D12S391 and FGA）. METHODS: A total of 560 blood samples were collected from unrelated healthy individuals of Han population in Hunan Province. Chelex-100 extraction method was applied to the extraction of genomic DNA, and an AGCU EX22 Kit and 9700 STR amplification was used in amplification reactions. The products were separated and analyzed on 310 Genetic Analyzer. RESULTS: A total of 248 alleles were observed, the allelic frequencies ranging from 0.001 to 0.518. Observation of genotype distributions for each locus showed no deviations from Hardy-Weinberg equilibrium except Penta E （P=0.023）. The combined power of discrimination, combined power of exclusion, and combined matching probability of the 21 STR loci were approximately 0.999 999 999 999 999 999 999 999 8, 0.999 999 998, and 1.36×10⁻²5, respectively. CONCLUSIONS: The 21 STR loci show high polymorphisms in the Han population, which can provide valuable data and a theoretical basis for forensic individual identification and paternity testing.

Cryopreservation of gemmae of Marchantia polymorpha L. (Marchantiophyta, Marchantiaceae) without prior pretreatment.

BACKGROUND: Successful cryopreservation of gametophytic material of bryophytes requires pretreatment with sucrose or abscisic acid. Compared to gametophyte materials, spore and gemmae cryopreservation may be more efficient, simple and stable systems for storing large amounts of genetic diversity of bryophytes within a small space. However, there has still been no attempt at cryopreserving bryophyte gemmae. OBJECTIVE: The aim of this study is to determine whether bryophyte gemmae with differing levels of desiccation tolerance could survive and germinate after cryopreservation without prior encapsulation and pretreatment. MATERIALS AND METHODS: Gemmae of Marchantia polymorpha L. were dried with silica gel for different times and then rapidly cooled in liquid nitrogen. RESULTS: The germination level of fresh gemmae was 95 % After 3 h predrying and 1 d in LN, germination was 68 % and was still up to 59 % after storage for 75 days. CONCLUSION: We conclude that the natural desiccation tolerance of bryophyte gemmae permits cryopreservation without prior pretreatment other than drying.

Spouses' experience of caregiving for cancer patients: a literature review.

BACKGROUND: The spouse is generally the primary informal caregiver for cancer patients. Many studies have explored the experience of caregiving for cancer patients, but it is unclear whether there are gender differences in the spousal caring experience for cancer patients. AIM: This review describes the recent published research on the stress process of spousal caregiving experience for cancer patients, and aims to identify any gender differences in the caregiving experience. METHODS: Electronic, manual and author's searches were conducted. Articles included were published in English and Chinese, from January 2000 to March 2012. Study population is couples coping with cancer. Focus is on caregiving experience for spouse with cancer, and findings include both male and female spousal caregivers in quantitative studies. The databases searched included MEDLINE, CINAHL, Science Citation Index Expanded, Scopus, PsycINFO and the China Academic Journal Full-text Database. The key search terms used were 'cancer' or 'oncology' or 'carcinoma' AND 'caregiver' or 'caregiving' or 'carer' AND 'gender differences' or 'gender' AND 'spouse' or 'couple' or 'partner'. Spousal caregiving experiences of cancer patients were explored by adopting the 'stress process' of the Cancer Family Caregiving Experience Model from the gender perspective. RESULTS: Twenty-five articles were identified and included in this review. It was revealed that female spousal caregivers perceived higher level negative experience in caregiving, such as lower mental health, lower physical health, poorer health-related quality of life, lower life satisfaction and decreased marital satisfaction than male spousal caregivers. However, female spousal caregivers are more likely to experience personal growth than male spousal caregivers. CONCLUSION: This review identified that female spousal caregivers for cancer patients had higher levels of negative experience in caregiving. A better understanding of the spousal caregiving experience will provide healthcare professionals with the information needed to develop interventions to support and prepare spousal caregivers to care for their loved ones with cancer.

Hypoxia decreased chemosensitivity of breast cancer cell line MCF-7 to paclitaxel through cyclin B1.

Hypoxia, frequently found in the center of solid tumors, may lead to enhance the production of key factor in cell survival, invasion, angiogenesis and loss of apoptosis. The low oxygen tension in hypoxic tumors is also known to interfere with the efficacy of chemotherapy, but the underlying mechanisms are not very clear. Paclitaxel (PTX) is an active agent used in breast cancer chemotherapy, which disturbs microtubule dynamics and impairs the transition of cells from metaphase to anaphase in mitosis, leading to cell death by apoptosis. In the present study, we try to determine whether hypoxia can decrease the chemosensitivity of human breast carcinoma cells to PTX and elucidate the underlying mechanism. We found that hypoxia could decrease PTX-induced cell death and G(2)/M arrest. Furthermore, our results showed that hypoxia inhibit PTX-induced soluble tubulin polymerized. In addition, we also found hypoxia could suppress PTX-induced cell cycle protein-cyclin B1 expression in MCF-7 cells. To further investigate whether the inhibitory effect of hypoxia on PTX-induced cell death is mediated by decreasing levels of cyclin B1, cyclin B1-transfected MCF-7 cells were used under hypoxic condition. The data showed that the hypoxia-based decreasing chemosensitivity of breast cancer cells to PTX was reversed by cyclin B1. We also found that overexpression of cyclin B1 could significantly increase the sensitivity of MCF-7 cells to PTX by stimulating soluble polymerized tubulin. Overall, hypoxia decreases cyclin B1, which could in turn reverse hypoxia-induced decreasing chemosensitivity to PTX in breast cancer cell line MCF-7.

Yizhi capsule for vascular dementia.

BACKGROUND: Vascular dementia (VD) is a syndrome or diagnosis that has different causes and clinical manifestations relating to several different vascular mechanisms and changes in the brain. Some traditional Chinese herbal medicines were developed for treating VD. DH: Yizhi capsule is one such herbal concoction which is reported to improve clinical symptoms significantly. The efficacy and adverse effects of Yizhi capsule need to be reviewed systematically and assessed critically to inform clinical practice and guide the continued search for new treatment regimens. OBJECTIVES: To assess the effectiveness and possible adverse events of 'Yizhi capsule' in treating vascular dementia. SEARCH STRATEGY: The Cochrane Dementia and Cognitive Improvement Group's Specialised Register was searched on 18 September 2006 using the terms yi-zhi, "yi zhi" and yizhi. This database contains trial references from major health care databases and ongoing trial database and is up to date. In addition the review authors searched a variety of Chinese databases. SELECTION CRITERIA: Randomised, placebo controlled trials in which patients with vascular dementia were treated with 'Yizhi capsule' were included. DATA COLLECTION AND ANALYSIS: Two authors independently assessed trial quality and extracted data. We telephoned study authors for missing information as to whether treatment allocation was randomised and other methodological details. MAIN RESULTS: No studies were found that met the inclusion criteria. We identified nine references to trials which included the term 'Yizhi capsule' in the description of the interventions. Two study authors were contacted by telephone and we discovered that the allocation methods they had used were not actually randomised. Four references were describing the same study. Three studies were excluded because 'positive drugs' were used as a control. AUTHORS' CONCLUSIONS: There is no evidence from randomised controlled trials to support or proscribe against the use of 'Yizhi capsule' as a treatment for vascular dementia.

[Depressive effect of tetrandrine on collagen synthesis in vascular smooth muscle cells].

AIM: To clarify whether collagen deposition and collagen synthesis are increased in renovascular hypertensive rats (RHR) and whether these are affected by treatment with tetrandrine (Tet). METHODS: Collagen deposition was detected by electron microscope and evaluated by the amount of hydroxyproline in aorta of sham-operated rats (Sham), renovascular hypertensive rats (RHR), and Tet treated RHR. The aortic vascular smooth muscle cells (AVSMCs) were isolated and cultured. The collagen synthesis in cultured AVSMCs was detected by [3H]-proline incorporation. RESULTS: The ultrastructure of aorta suggests that AVSMCs in RHR had been transferred from contractile phenotype to synthetic phenotype. Compared with sham-operated rats, the hydroxyproline content in aorta was increased by 36.6% in RHR, while it was reduced by 18.7% in Tet treated RHR (P < 0.01, vs RHR). Tet (0.1-10 mumol.L-1) treatment in vitro induced a concentration dependent depression [3H]-proline incorperation stimulated by NE or Ang II in AVSMCs from either Sham or RHR. CONCLUSION: The depressive effects of tetrandrine on collagen synthesis and deposition in arteries may contribute to the regression of vascular remodeling.

Isolation and complete nucleotide sequence of a Chinese Sindbis-like virus.

Infection with alphaviruses is common in the Chinese population. Here we report the isolation of a Sindbis-like virus from a pool of Anopheles mosquitoes collected in Xinjiang, China during an arbovirus survey. This virus, designated XJ-160, rapidly produced cytopathic effects on mosquito and hamster cells. In addition, it was lethal to neonatal mice if inoculated intracerebrally. Serologically, XJ-160 reacted with and was neutralized by an anti-Sindbis antibody. Anti-XJ-160 antibodies were found in several cohorts of Chinese subjects. The complete 11626-base nucleotide sequence of XJ-160 was determined. XJ-160 has diverged significantly from the prototype Sindbis virus, with an 18% difference in nucleotide sequence and an 8.6% difference in amino acids; there are 11 deletions and 2 insertions, involving 99 nucleotides in total. XJ-160 is most closely linked to Kyzylagach virus isolated in Azerbaijan. Both belong to the African/European genetic lineage of Sindbis virus, albeit more distantly related to other members.

Restraint stress changes heart sensitivity to arrhythmogenic drugs.

AIM: To study the effects of acute restraint stress on ventricular electric stability (VES) and its mechanisms of action. METHODS: VES was evaluated both in vivo and in vitro by the changes of arrhythmogenic responses to icv or ip aconitine in rats and iv BaCl2 or adrenaline in rabbits following restraint stress for different durations. Pretreatments and the assay of heart-specific enzymes were made. RESULTS: The heart sensitivity to these drugs was promoted after stress for 2 h, but obtunded after stress for 8 h (the latency of ventricular arrhythmia to icv aconitine was shortened from 4.1 +/- 0.9 min in control rats to 2.9 +/- 0.9 min after stress for 2 h, P < 0.05; but prolonged to 9.3 +/- 3.8 min after stress for 8 h, P < 0.05). In Langendorff heart, the changes of VES induced by stress were similar to those in vivo, but to lesser degree. Pretreatment with adrenalectomy inhibited the descending phase of VES, while pretreatment with both aminophylline and vagotomy remarkably depressed the ascending phase at 8 h. In addition, the serum activities of lactate dehydrogenase (LDH), creatine kinase (CK), and aspartate aminotransferase and their isozymes, LDH1 and CK-MB, were elevated at 2 h, and rose continuously at 8 h. CONCLUSION: Acute restraint stress causes biphasic changes of VES. The initial decrease of VES was related to adrenal catecholamine release, whereas the following increase of VES was ascribed to adaptive decrease of cAMP and vagal activation. The changes of VES did not always parallel the injury of heart.

[Effects of calcium antagonists on withdrawal of beta-receptor blockers in rats during left ventricular hypertrophy].

The hemodynamic changes of metoprolol (Met, 50 mg.kg-1.d-1, po, 3 wk) withdrawal for 1 day and the effects of nifedipine (Nif) and m-nifedipine (m-Nif) on these changes were observed in pressure overload hypertrophy in rats by abdominal aortic constriction for 4 wk. Both Nif and m-Nif (10 mg.kg-1.d-1, respectively, po, 3 wk) significantly attenuated the increase of MAP (from 14.3 +/- 2.3 to 12.9 +/- 2.3 and 11.3 +/- 2.4 kPa, respectively, n = 6-7, P < 0.05) and decrease the abnormal development of systolic function of left ventricle after Met withdrawal. Radioreceptor assay indicates that Nif and m-Nif can prevent the up-regulation of myocardium beta-receptors in left ventricular hypertrophy and large dose of Met exposure for a long time. These results suggest that calcium antagonists administered with beta-blockers can prevent beta-receptor blocker withdrawal syndrome.

Frequency-dependent depression of Vmax in K(+)-depolarized guinea pig papillary muscle by tetrandrine.

The effect of tetrandrine (Tet), a calcium antagonist, on the maximal upstroke velocity (Vmax) of depolarization in K(+)-depolarized guinea pig papillary muscles was studied by standard microelectrode method with computer. The results showed that: (1) the resting block of Tet on Vmax was concentration dependent; (2) the drug (50 or 100 mumol.L-1) caused a marked frequency-dependent block of Vmax, which accounted for 65 +/- 8% of total block at a concentration of 100 mumol.L-1 and the pacing frequency of 0.3 Hz; (3) the recovery kinetics of Vmax could be characterized as a biexponential function, of which the second phase was prolonged by the drug; (4) compared with verapamil, nitrendipine, and diltiazem, the above-mentioned effects of Tet on Vmax were similar to those of diltiazem. These results suggest that Tet can block calcium channel in both frequency-dependent and frequency-independent manner, mainly the former.