Effects of hepatitis B virus coinfection on anti-retroviral therapy in human immunodeficiency virus infected people / 中华传染病杂志

Objective:To investigate the influence of hepatitis B virus (HBV) combined with human immunodeficiency virus (HIV) infection on the efficacy of anti-retroviral therapy (ART).Methods:The data of 269 HIV-infected patients treated in Chongqing Public Health Medical Center from September 2016 to October 2019 were collected. The patients were divided into HIV monoinfection group and HIV/HBV coinfection group. The changes in liver function, CD4 + T lymphocyte count, and HIV RNA level between the two groups were compared when ART started and at different time points (2, 4, 8, 12, 24, 36, 48, and 96 weeks) after ART started. Statistical analysis were performed by independent sample t test, rank sum test and chi-square test. Results:A total of 145 patients with HIV monoinfection and 124 patients with HIV/HBV coinfection were collected. There were no statistically significant differences in liver function indexes (aspartate aminotransferase ( t=9.566), alanine aminotransferase ( t=-4.652) and total bilirubin ( t=-25.476)) between the two groups of patients when ART started (all P>0.05). At 24, 48 and 96 weeks after ART, the CD4 + T lymphocyte counts in the HIV monoinfection group and the HIV/HBV coinfection group were (305.9±156.9)/μL vs (266.2±172.5)/μL, (388.5±226.1)/μL vs (380.8±287.4)/μL and (369.5±191.4)/μL vs (453.6±179.6)/μL, respectively. At 48, 72 and 96 weeks after ART, the CD4 + T lymphocyte count increasing values were 121.0(-52.5, 144.5)/μL vs 156.0(-35.8, 185.8)/μL, 139.0(-116.0, 176.8)/μL vs 114.5(-59.5, 229.0)/μL and -91.0(-110.0, 153.3)/μL vs -94.0(-130.8, 114.3)/μL, respectively. The differences were all not statistically significant ( t=-0.516, -0.066 and -1.414, Z=-1.715、-0.802 and -1.602, respectively, all P>0.05). At 24, 48, and 96 weeks after ART, the HIV RNA inhibition rates in the HIV monoinfection group were 89.7%(130/145), 96.6%(140/145), and 96.6%(140/145), respectively, and those in the HIV/HBV coinfection group were 87.1%(108/124), 92.7%(115/124) and 94.4%(117/124), respectively. The differences were all not statistically significant ( χ2=0.026, 0.053 and 0.017, respectively, all P>0.05). In the second and fourth weeks after ART, the abnormal liver function rates of the HIV monoinfection group were 3.4%(5/145) and 6.2%(9/145), respectively, which were lower than those in the HIV/HBV coinfection group (21.0%(26/124) and 13.7%(17/124), respectively). The differences were both statistically significant ( χ2=20.121 and 4.309, respectively, both P<0.05). However, the abnormal liver function rates in the two group in the 8th week after ART were 10.3%(15/145) and 9.7%(12/124), respectively, and those in the 12th week were 9.0%(13/145) and 9.7%(12/124), respectively, and those in the 24th week were 9.7%(14/145) and 8.9%(11/124), respectively, and those in the 36th week were 9.7%(14/145) and 10.5%(13/124), respectively, and those in the 48th week were 8.3%(12/145) and 8.1%(10/124), respectively, and those in the 96th week were 2.8%(4/145) and 0(0/124), respectively. The differences were all not statistically significant ( χ2=0.330, 0.040, 0.049, 0.051, 0.004 and 3.472, respectively, all P>0.05). Conclusion:HBV coinfection has no adverse effect on the ART effect of HIV-infected patients.

Biosynthesis of lipase by Burkholderia cenocepacia ST8 using waste cooking oil as feedstock

Aims@#Every year, an estimated 25 million tons of waste oil are produced worldwide, and the generation of waste oil is one of the biggest global environmental problems. The incorporation of oil as a substrate for lipase production has been studied and shown to have a positive impact on its production. Burkholderia sp. is one of the major lipase-producing bacteria with their ability in bioremediation of oil-contaminated soil. This study aims to compare the production of lipase by Burkholderia cenocepacia ST8 using waste cooking oil and unused cooking oil as feedstock.@*Methodology and results@#The effect of different types of waste cooking oil (sunflower oil and palm oil) and concentration (1-3%) of waste cooking oil, agitation speed (100-400 rpm) and initial dissolved oxygen concentration (10-50%) on lipase production by B. cenocepacia ST8 under batch fermentation mode were investigated. The major fatty acids of which had been consumed were determined using gas chromatography. Results showed that 2% (v/v) of single used sunflower cooking oil produced the highest lipase activity of 138.86 U/mL with a productivity of 2.10 U/mL/h; agitation speed of 300 rpm produced the highest lipase activity of 183.56 U/mL with a productivity of 3.06 U/mL/h while 30% initial concentration of dissolved oxygen produced a lipase activity of 176.45 U/mL with a productivity of 2.94 U/mL/h. Oleic acid and linoleic acid were found to be the most consumed by B. cenocepacia ST8 among other fatty acids. @*Conclusion, significance and impact of study@#This study shows that 2% (v/v) single used sunflower cooking oil was the better type and optimum concentration of carbon source for the production of lipase by the fermentation of B. cenocepacia under 300 rpm and 30% initial concentration dissolved oxygen. The incorporation of 2% (v/v) single used sunflower cooking oil may be a great alternative to reduce the cost for the production of lipase as well as reducing the amount of waste oil generation.

Isolation and characterization of Lactobacillus brevis C23 with ability to secrete antimicrobial substance for the inhibition of a foodborne pathogen Listeria monocytogenes ATCC 7644

Aims@#This study aims to isolate lactic acid bacteria (LAB) from various food sources to obtain a potent strain against Listeria monocytogenes. @*Methodology and results@#A total of 68 LAB isolates were selected to evaluate their antimicrobial activity against L. monocytogenes, a foodborne pathogen and a causative agent of listeriosis. The selected isolate was identified and characterized. The isolate C23 from cabbage showed the highest antimicrobial activity against L. monocytogenes ATCC 7644 with inhibition ability of 73.94%. The isolate was closely related to Lactobacillus brevis by 16S rRNA sequencing and subsequently deposited in GenBank with an accession number of MN880215, named as L. brevis C23. The cell free supernatant (CFS) of L. brevis C23 had high tolerance in low pH and was able to withstand up to 60 °C. The proteinaceous nature of the antimicrobial agent was also confirmed through the enzymatic test. The CFS was stable on different detergents as well as bile salts. Under transmission electron microscopy (TEM), the inhibitory effect of CFS against L. monocytogenes was proven by causing cell lysis.@*Conclusion, significance and impact of study@#Bacteriocin-like inhibitory substances (BLIS) of L. brevis C23 showed very promising potential in food industrial application.

A retrospective study on primary anti-tuberculosis drug resistance in patients with acquired immunodeficiency syndrome and tuberculosis / 中华传染病杂志

Objective To investigate primary anti-tuberculosis drug resistance in patients with acquired immunodeficiency syndrome (AIDS) and tuberculosis in Chongqing area.Methods Clinical data of 119 patients with AIDS and tuberculosis were retrospectively collected.Anti-tuberculosis drug resistance rates were analyzed according to drug susceptibility testing, and their correlations with CD4+ T lymphocytes counts, initially treatment or retreatment and clinical forms of tuberculosis were also analyzed.Comparison between groups was analyzed by x2 test.Results Thirty-eight patients (31.9%) showed anti-tuberculosis drug resistance among the 119 patients with completed results of drug susceptibility testing results.The percentages of mono-resistance, poly-resistance, multi-drug resistance (MDR) and extensive drug resistance (XDR) were 11.7%, 7.6%, 6.7% and 5.9%, respectively.The resistance rate of isoniazid (22.7%, 28/119) was the highest among first-line anti-tuberculosis drugs and that of pasiniazide (11.0%, 14/119) was the highest among second-line drugs.Drug resistance rates among patients with different levels of CD4+ T lymphocytes counts did not differ significantly (the cut-off of CD4+ T lymphocytes count was 50/μL: x2=0.545, P=0.461;cut-off value was 100/μL: x2=0.652, P=0.420).Patents with milliary pulmonary tuberculosis had a significantly higher drug resistance rate (64.0%) than those with secondary pulmonary tuberculosis (27.6%).Conclusions The prevalence of anti-tuberculosis drug resistance prior to anti-tuberculosis treatment initiation is high among AIDS patients with tuberculosis in Chongqing area.Patients with milliary pulmonary tuberculosis tend to have higher anti-tuberculosis drug resistance, but drug resistance does not appear to correlate with CD4+ T lymphocytes counts.

Differentiation of mild from moderate liver fibrosis with 256-slice CT perfusion imaging / 实用放射学杂志

Objective To assess the value of CT perfusion imaging in differentiation of mild from moderate liver fibrosis .Methods 18 patients with mild liver fibrosis (F1 phase) and 21 ones with moderate fibrosis (F2 and F3 phase) confirmed by liver biopsy were analyzed ,and all patients underwent the liver 256‐slice CT perfusion imaging .The differences in the CT parameters including hepatic arterial perfusion (HAP) ,portal venous perfusion (PVP) ,total liver perfusion (TLP) and time to peak (TTP) between dif‐ferent fibrosis were analyzed .ROC curve was used to evaluate the ability of perfusion indexes to distinguish mild from moderate liver fibrosis ,then the maximum Youden index was selected as a cutoff point to calculate the sensitivity and specificity .Results Compared with the mild fibrosis ,the TTP [(43 .86 ± 13 .41)s vs (37 .84 ± 9 .97)s ,P=0 .034)] in liver with moderate fibrosis was significantly increased .However ,no differences in the HAP ,PVP and TLP were found .The ROC curve analysis showed that a TTP threshold of 41 .7 s allowed discrimination of mild from moderate fibrosis with a sensitivity of 72 .7% and a specificity of 75% .Conclusion 256‐slice CT perfusion imaging can reflect the hemodynamic changes of liver fibrosis ,and the TTP may help to discriminate mild from moderate fibrosis .

Expressions of Cx26, Cx32 and Cx43 in prostate cancer and their implications / 中华男科学杂志

<p><b>OBJECTIVE</b>To investigate the expressions of Cx26, Cx32 and Cx43 in prostate cancer (PCa) and benign prostatic hyperplasia (BPH) and their roles in the development and progression of PCa in order to provide some novel evidence for the diagnosis and treatment of PCa.</p><p><b>METHODS</b>We determined the expressions of Cx26, Cx32 and Cx43 in the paraffin samples from 31 cases of PCa and 23 cases of BPH by SABC immunohistochemical staining, and analyzed the relationship of their expressions with the clinical and pathological parameters of PCa and BPH using the semiquantitative method.</p><p><b>RESULTS</b>The positive expressions of Cx26 in BPH and PCa were 82.6% and 74.2%, respectively (chi2 = 0.541, P > 0.05), those of Cx32 were 78.3% and 61.3% (chi2 = 1.763, P > 0.05), and those of Cx43 were 87.0% and 38.7% (chi2 = 12.730, P < 0.01). The staining intensities of Cx26 and Cx43 were negatively correlated with the malignant phenotype of PCa (rCx26 = -0.476, P < 0.01; rCx43 = -0.484, P < 0.01), but not the expression of Cx32 (r = -0.242, P > 0.05). The three Cxs exhibited no correlation with the age and serum PSA level of the patients (P > 0.05), nor among their expressions (P > 0.05).</p><p><b>CONCLUSION</b>Cx26, Cx32 and Cx43 are expressed in different degrees in BPH and PCa tissues. Cx43 plays a role in the occurrence and progression of PCa, and may serve as a new marker of PCa besides PSA as well as a new target in the biotherapy of PCa. Cx26 may be partially involved in the progression of PCa, but its mechanisms need to be further studied.</p>

Histological observation of implant-bone interface in immediate loading implant with platform switching / 中华口腔医学杂志

<p><b>OBJECTIVE</b>To investigate the effect of implant superstructure with platform switching to the osseointegration of implant-bone interface in immediate loading.</p><p><b>METHODS</b>The bilateral mandiblular fourth premolars of 5 beagle dogs were extracted, and 3 months later, 10 implants were implanted and the abutments were accessed immediately to form immediate loading. Using self-control, the abutment with platform switching was used in the experimental side, and the traditional abutment used in the control side. The experimental animals were sacrificed after 3 months, and non-decalcified implant-bone sections were made.</p><p><b>RESULTS</b>A favorable osseointegration of implant-bone interface in 4 animals (8 implants) was observed except for one failed case. A large number of osteoblasts and different mineralized bone were observed. In experimental side, the bone and implant-neck were nearly in the same level, but the bone around the implant-neck was significantly absorbed in control side.</p><p><b>CONCLUSIONS</b>Using different superstructure in immediate loading could affect the osseointegration of implant-neck. The platform switching technology is conducive to the keeping of implant-neck bone.</p>

Effects of all-trans retinioic acid and tazarotene on MMP-1 and TIMP-1 expression in cultured human fibroblasts after heat shock / 南方医科大学学报

<p><b>OBJECTIVE</b>To investigate the molecular mechanism of dermal damage in heat shock-induced skin aging by observing the expressions of metalloproteinase-1 (MMP-1) and tissue inhibitor of MMP-1 (TIMP-1) in retinoic acid-treated cultured human fibroblasts with heat shock.</p><p><b>METHODS</b>Cultured human fibroblasts were treated with tazarotene or all-trans-retinioic acid (at-RA) after heat shock for 30 min in 43 degrees celsius; water bath. Twenty-four hours later, MMP-1 and TIMP-1 contents in the supernatant of the cell culture medium were measured using enzyme-linked immunosorbent assay (ELISA).</p><p><b>RESULTS</b>Both tazarotene and at-RA dose-dependently reduced the expression of MMP-1 and increased the expression of TIMP-1 in cultured human fibroblasts exposed to heat shock, and tazarotene produced stronger effect than at-RA.</p><p><b>CONCLUSION</b>Retinoic acid can reduce the expression of MMP-1 and increase the expression of TIMP-1 in cultured human fibroblasts, suggesting its therapeutic potential for heat shock-induced skin aging.</p>

Two mutations of the KRT6A gene in Chinese patients with pachyonychia congenita type I / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To investigate the gene mutation in a Chinese pedigree and one sporadic case with pachyonychia congenita type I(PC-1), as well as to explore the relationship between the genotype and phenotype.</p><p><b>METHODS</b>The whole coding region of the KRT16 and KRT6A genes were amplified by long-range polymerase chain reaction (PCR). Six patients with PC-1 were studied, five of them were from a pedigree and the other one was sporadic. One unaffected member in the pedigree and 100 unrelated healthy individuals were also studied in order to exclude polymorphism. PCR products were directly sequenced to detect the mutation.</p><p><b>RESULTS</b>No mutations in the KRT16 gene were observed. All patients harbored a mutation in the KRT6A gene. All five patients in the pedigree had a mutation at codon 465 (TAC to CAC) which substitutes tyrosine (Y) by histidine (H). In the sporadic patient, codon 171 (AAC) was mutated to GAC, which changes the asparagines (N) to aspartic acid (D). No such mutations were found in the unaffected member of the pedigree and the 100 unrelated controls. The mutation of Y465H is located at the end of 2B and N171D at the beginning of 1A domain of KRT6A, both are hotspots for pathogenic keratin mutations.</p><p><b>CONCLUSION</b>The mutations Y465H and N171D of the KRT16A gene were detected in the pedigree and the sporadic case respectively. The Y465H mutation was a novel mutation, and the N171D mutation was reported recently.</p>

Alteration of tazarotene induced gene-2 expression in psoriasis vulgaris / 南方医科大学学报

<p><b>OBJECTIVE</b>To investigate the role of tazarotene induced gene-2 (TIG2) in psoriasis vulgaris.</p><p><b>METHODS</b>TIG2 protein and mRNA expressions in normal tissues, psoriatic lesions and uninvolved skin tissues were detected by immunohistochemistry and in situ hybridization, respectively.</p><p><b>RESULTS</b>TIG2 protein and mRNA were expressed in all the layers of normal and uninvolved epidermis. TIG2 expression was detected in the upper layers of the stratum spinosum of the marginal region of the psoriatic lesions, but not in the central area of the lesions. TIG2 expression was significantly lower in the basal layers of the central area of the paoriasis than that in the normal skin and uninvolved tissues (P < 0.01), and also lower in the marginal regions of the lesions (P < 0.01).The suprabasal layers of the marginal region in the lesion showed significantly lower TIG2 expression than the central area of the lesion (P < 0.01).</p><p><b>CONCLUSION</b>TIG2 may maintain the normal differentiation of epidermal keratinocytes and implicate in the pathogenesis and development of psoriasis vulgaris.</p>

Expressions of fibrillin-1, elastin and matrix metalloproteinase-1 and -9 in chronic actinic dermatitis in elderly patients / 南方医科大学学报

<p><b>UNLABELLED</b>To investigate the expressions of fibrillin-1, elastin and matrix metalloproteinase-1 and -9 (MMP-1, 9) in chronic actinic dermatitis in elderly patients and explore the pathogenesis of the disease.</p><p><b>METHODS</b>Twenty-three patients with chronic actinic dermatitis were examined for the expressions of fibrillin-1, elastin, MMP-1, and MMP-9 with immunohistochemistry in the skin lesions. Image analysis was carried out to measure MMP-1 and MMP-9 expressions semi-quantitatively.</p><p><b>RESULTS</b>In the skin lesions of patients with chronic actinic dermatitis, elastin expression was obviously reduced or absent in the papillary dermis. The elastic fibers were disorderly arranged in the reticular dermis with local aggregation in some regions. Obvious fibrillin-1 deposition was found in the reticular dermis. Increased expressions of MMP-1, but not that of MMP-9, was found in the skin lesions of the patients.</p><p><b>CONCLUSION</b>Elastin and fibrillin-1 deposition can be found in the skin lesions in patients with chronic actinic dermatitis, suggesting the association of increased MMP-1 expression with the elastic tissue degeneration in the lesions. MMP-9 does not exhibit an obvious association with the pathogenesis of chronic actinic dermatitis in elderly patients.</p>

Analysis of the difference in proteome expression between yeast form and mould form of Penicillium marneffei using SELDI technique / 南方医科大学学报

<p><b>OBJECTIVE</b>To compare the difference in protome expression between yeast form and mould form of Penicillium marneffei.</p><p><b>METHODS</b>Surface enhanced laser desorption/ionization (SELDI) time-of-flight mass spectra were performed to compare the expressed proteins between yeast form and mould form of Penicillium marneffei. Protein profiling was read by PBSIIC ProteinChip Reader and the proteome database was analyzed by Proteinchip Software 3.2.0.</p><p><b>RESULTS</b>Seventy-five distinct proteins were found in the yeast form and mould form of Penicillium marneffei, in which 10 proteins were up-regulated in yeast form and 3 in mould form. The proteins 2900 and 3151 were only expressed in the yeast form and the proteins 13,151 and 13,285 only in mould form.</p><p><b>CONCLUSION</b>SELDI technique can identify the difference of the expressed low-molecular-mass proteins between the mould form and yeast form of Penicillium marneffei.</p>

Endoluminal therapy for bilateral malignant ureteric obstruction / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To evaluate the endourological technique in the treatment of bilateral malignant ureteric obstruction.</p><p><b>METHODS</b>The data of 43 patients (totally, 70 cases) with bilateral malignant ureteric obstruction treated with endoluminal therapy were reviewed retrospectively. Of 70 cases, 38 were treated by retrograde double-J stenting, 24 by minimally invasive percutaneous nephrotomy (MPCN) and 8 by antegrade double-J stenting.</p><p><b>RESULTS</b>All patients were followed up for an average of 12 months. The retrograde double-J stenting, MPCN and antegrade double-J stenting was successfully performed in 50.0% (19/38), 100.0% (24/24) and 62.5% (5/8), respectively. Technical failures in placing retrograde double-J stent were too difficult to identify the ureteric orifice (13/38) or failing to cross the obstruction site because of severe extraluminal compression (6/38). Failure in placing antegrade double-J stent was due to severe extraluminal compression (3/8). Dislodgment of nephrostomy tubes (11/19) was the major factor which limited the application of MPCN.</p><p><b>CONCLUSION</b>It is safe and effective to treat malignant ureteric obstruction with endourological technique, and suggested initially with retrograde double-J stenting. If malignant ureteric orifice occlusion or a severe extraluminal compression is showed in the imaging, MPCN or antegrade double-J stenting may be selected according to the site and the extent of obstruction.</p>

Localization and differentiation of hair follicle stem cells / 中国医学科学院学报

<p><b>OBJECTIVE</b>To identify the localization of hair follicles stem cell (HFSC) in different stages of hair and explore the differentiating capacity of HFSC into epidermis in vitro.</p><p><b>METHODS</b>HFSC were detected by K19 immunostaining in normal human skin. Then, the isolated HFSC through enzyme digestion were seeded on dermal equivalent (DE) and cultured between the air-liquid interfaces for 14 days. Skin-equivalents was harvested and used for evaluation.</p><p><b>RESULTS</b>HFSC mainly located in outer root sheet in hair follicle and human anagen hair follicles containing two distinct reservoirs for K19-positive cells located in the bulge and bulb of the follicle. These two reservoirs fused in line of outer root sheets during the catagen-telogen transition phase and individualized again in the newly forming anagen hair follicle. Based on DE, growing HFSC built a multilayered and confined epidermis.</p><p><b>CONCLUSION</b>HFSC located in outer root sheets can promote hair cycle and differentiate into epidermis in vitro.</p>

Inhibition of promyelocytic leukemia gene by tazarotene in hyperproliferative epidermis of psoriasis / 南方医科大学学报

<p><b>OBJECTIVE</b>To investigate the mechanism of tazarotene against active psoriasis vulgaris.</p><p><b>METHODS</b>A randomized, controlled trial was conducted in 43 patients with active psoriasis vulgaris, who were divided into tazarotene and control groups. Promyelocytic leukemia (PML) mRNA in active psoriatic lesions before and 14 days after tazarotene treatment was detected by in situ hybridization.</p><p><b>RESULTS</b>PML mRNA expression was detected not only in the basal layer (86.96%), but also in the suprabasal layers of the epidermis in the manner of focal expression (78.26%). After tazarotene treatment, virtually no PML mRNA expression could be detected in the psoriatic lesions (8.69% in the basal layer and 4.35% in the suprabasal layers). PML mRNA expression in the control group underwent no obvious changes during the observation.</p><p><b>CONCLUSIONS</b>Tazarotene may inhibit abnormal proliferation of keratinocytes through down-regulating PML gene expression in active psoriatic epidermis.</p>

Effects of bradykinin on the proliferation, apoptosis and differentiation of human keratinocytes / 中华烧伤杂志

<p><b>OBJECTIVE</b>To investigate the effects of bradykinin (BK) on the proliferation, apoptosis and differentiation of human keratinocyte (HKC) and the underlying mechanisms.</p><p><b>METHODS</b>HKCs were cultured together with 1 x 10(-4) - 1 x 10(-9) mol/L of BK. With methyl thiotetrazole (MTT) and trypan blue staining it was shown that the BK in dose of 1 x 10(-4) mol/L possessed most powerful inhibitory effect, and the survival rate of HKC was 69.3%. Therefore, BK was employed in the dose of 1 x 10(-4) mol/L in the following studies. When the growth of HKCs reached the logarithmic phase, BK in the concentration of 1 x 10(-4) mol/L was added, and it was categorized as the test group (E). HKCs without BK served as the control group (C). The cell cycle and apoptosis were detected by flow cytometry after being cultured for 24 and 48 hours. The change in intracellular calcium [Ca(2+)](i) was determined by means of laser scanning confocal microscopy with calcium fluorescence probe Fluo-3/AM technique. The expression of HKC differentiation labeling protein keratin10 (K10) and involucrin were detected with Strept Avidin-Biotin Complex (SABC) immunocytochemical assay.</p><p><b>RESULTS</b>The cell ratio in G0/G1 phase in E group increased by 34.57% while in S phase decreased by 58.91% in reference to that in C group. The G1/S phase switching of HKCs was obviously inhibited by BK, and apoptosis was stimulated (apoptotic rate of 15.34% in E group vs 5.60% in C group, P < 0.05). The [Ca(2+)](i) increased transiently in HKCs by 163.0% in E group after 3 minutes of BK activation and decreased thereafter in reference to that in C group. The K10 expression in HKC was down-regulated in E group with positive cell rate of 2.20%, which was lower than that of C group (6.89%, P < 0.05).</p><p><b>CONCLUSION</b>The cell cycle process of HKC could be inhibited by high concentration of BK with increased apoptosis and an increase in [Ca(2+)](i), which might be the mechanism of inhibition of growth of HKC in vitro. Furthermore, the epithelial regeneration and HKC differentiation can also be inhibited by BK.</p>