Reviewer’s report
Title: 
Overexpression of P-glycoprotein, MRP2, and CYP3A4 impairs intestinal
absorption of octreotide in rats with portal hypertension
Version: 
1 
Date: 
23 Jun 2019
Reviewer's report:
Sun et al provided revisions of their manuscript. However, there are still some
comments, which should be taken into account to further improove the manuscript:
ad 1a [p3, line 29-30]: please explain why recommendations on use of NSBB for
primary and secondary bleeding prophylaxis are "controversial".
ad 1a [p3, line 36]: "or cannot tolerate the propranolol therapy." -> please use the broad
term "NSBB" instead of "propranolol".
ad 2a [p5, line 9-11]: "to improve the intestinal absoption of OCT, furthermore, to
explore optimized therapeutic strategies for decreasing PH in cirrhotic patients" -> to me
these are no clear aims and do not sound pre-defined.
ad 2b [p5, line 32-43]: The authors cite the Guidelines to Care and Use of Experimental
Animals by the CCAC (https://www.ccac.ca/en/standards/guidelines/general-
guidelines.html). However these guidelines discourage the use of ether (page 135) and
recommend special equipment for the use of inhalation anesthesis (page 134) which still
has not been reported and should be reported. [see
https://www.ccac.ca/Documents/Standards/Guidelines/Experimental_Animals_Vol1.pdf].
This is of special importance when reporting hemodynamic data, which greatly depend
on adaequate anesthesia!
Authors state they tested corneal and pain reflex prior to surgery, which is good.
However this information should be also included in the paper.
The statement "All efforts were made to minimize the number of animals used" is
contradicting with the predefined sample size. I assume the authors took all efforts to
reduce the number of dropouts -> which then would lead to the question wether there
were any drop-outs and how large was their number in the respective groups?
p6, line10-13: ", which was much higher than normal value 10mmHg. It was proved that
the rats developed PH." This text is not only wrong [PH starts at 5mmHg] but also
includes bad English [proved -> proven]. I would thus suggest to omit it, as it adds no
valuable information.
ad 6 [p17, line 36-49] -> Please rephrase in better English. The text is barely
understandable.
p20, line 7-14 -> Please rephrase in better English.
Supplementary Figures showing Western Blots consist of unclear lines. They are not
labelled nor dated and lack a kDa control ladder. Please add this information.
Are the methods appropriate and well described?
If not, please specify what is required in your comments to the authors.
No
Does the work include the necessary controls?
If not, please specify which controls are required in your comments to the authors.
Yes
Are the conclusions drawn adequately supported by the data shown?
If not, please explain in your comments to the authors.
Yes
Are you able to assess any statistics in the manuscript or would you recommend an
additional statistical review?
If an additional statistical review is recommended, please specify what aspects require
further assessment in your comments to the editors.
I am able to assess the statistics
Quality of written English
Please indicate the quality of language in the manuscript:
Not suitable for publication unless extensively edited
Declaration of competing interests
Please complete a declaration of competing interests, considering the following
questions:
1
. 
Have you in the past five years received reimbursements, fees, funding, or salary
from an organisation that may in any way gain or lose financially from the
publication of this manuscript, either now or in the future?
2
. 
Do you hold any stocks or shares in an organisation that may in any way gain or
lose financially from the publication of this manuscript, either now or in the
future?
3
. 
Do you hold or are you currently applying for any patents relating to the content
of the manuscript?
4
. 
Have you received reimbursements, fees, funding, or salary from an organization
that holds or has applied for patents relating to the content of the manuscript?
5
. 
Do you have any other financial competing interests?
6
. 
Do you have any non-financial competing interests in relation to this paper?
If you can answer no to all of the above, write 'I declare that I have no competing
interests' below. If your reply is yes to any, please give details below.
I declare that I have no competing interests
I agree to the open peer review policy of the journal. I understand that my name will be
included on my report to the authors and, if the manuscript is accepted for publication,
my named report including any attachments I upload will be posted on the website along
with the authors' responses. I agree for my report to be made available under an Open
Access Creative Commons CC-BY license
(
http://creativecommons.org/licenses/by/4.0/
). I understand that any comments which I
do not wish to be included in my named report can be included as confidential
comments to the editors, which will not be published.
I agree to the open peer review policy of the journal
Reviewer’s report
Title: 
Overexpression of P-glycoprotein, MRP2, and CYP3A4 impairs intestinal
absorption of octreotide in rats with portal hypertension
Version: 
1 
Date: 
23 Jun 2019
Reviewer's report:
Sun et al provided revisions of their manuscript. However, there are still some
comments, which should be taken into account to further improove the manuscript:
ad 1a [p3, line 29-30]: please explain why recommendations on use of NSBB for
primary and secondary bleeding prophylaxis are "controversial".
ad 1a [p3, line 36]: "or cannot tolerate the propranolol therapy." -> please use the broad
term "NSBB" instead of "propranolol".
ad 2a [p5, line 9-11]: "to improve the intestinal absoption of OCT, furthermore, to
explore optimized therapeutic strategies for decreasing PH in cirrhotic patients" -> to me
these are no clear aims and do not sound pre-defined.
ad 2b [p5, line 32-43]: The authors cite the Guidelines to Care and Use of Experimental
Animals by the CCAC (https://www.ccac.ca/en/standards/guidelines/general-
guidelines.html). However these guidelines discourage the use of ether (page 135) and
recommend special equipment for the use of inhalation anesthesis (page 134) which still
has not been reported and should be reported. [see
https://www.ccac.ca/Documents/Standards/Guidelines/Experimental_Animals_Vol1.pdf].
This is of special importance when reporting hemodynamic data, which greatly depend
on adaequate anesthesia!
Authors state they tested corneal and pain reflex prior to surgery, which is good.
However this information should be also included in the paper.
The statement "All efforts were made to minimize the number of animals used" is
contradicting with the predefined sample size. I assume the authors took all efforts to
reduce the number of dropouts -> which then would lead to the question wether there
were any drop-outs and how large was their number in the respective groups?
p6, line10-13: ", which was much higher than normal value 10mmHg. It was proved that
the rats developed PH." This text is not only wrong [PH starts at 5mmHg] but also
includes bad English [proved -> proven]. I would thus suggest to omit it, as it adds no
valuable information.
ad 6 [p17, line 36-49] -> Please rephrase in better English. The text is barely
understandable.
p20, line 7-14 -> Please rephrase in better English.
Supplementary Figures showing Western Blots consist of unclear lines. They are not
labelled nor dated and lack a kDa control ladder. Please add this information.
Are the methods appropriate and well described?
If not, please specify what is required in your comments to the authors.
No
Does the work include the necessary controls?
If not, please specify which controls are required in your comments to the authors.
Yes
Are the conclusions drawn adequately supported by the data shown?
If not, please explain in your comments to the authors.
Yes
Are you able to assess any statistics in the manuscript or would you recommend an
additional statistical review?
If an additional statistical review is recommended, please specify what aspects require
further assessment in your comments to the editors.
I am able to assess the statistics
Quality of written English
Please indicate the quality of language in the manuscript:
Not suitable for publication unless extensively edited
Declaration of competing interests
Please complete a declaration of competing interests, considering the following
questions:
1
. 
Have you in the past five years received reimbursements, fees, funding, or salary
from an organisation that may in any way gain or lose financially from the
publication of this manuscript, either now or in the future?
2
. 
Do you hold any stocks or shares in an organisation that may in any way gain or
lose financially from the publication of this manuscript, either now or in the
future?
3
. 
Do you hold or are you currently applying for any patents relating to the content
of the manuscript?
4
. 
Have you received reimbursements, fees, funding, or salary from an organization
that holds or has applied for patents relating to the content of the manuscript?
5
. 
Do you have any other financial competing interests?
6
. 
Do you have any non-financial competing interests in relation to this paper?
If you can answer no to all of the above, write 'I declare that I have no competing
interests' below. If your reply is yes to any, please give details below.
I declare that I have no competing interests
I agree to the open peer review policy of the journal. I understand that my name will be
included on my report to the authors and, if the manuscript is accepted for publication,
my named report including any attachments I upload will be posted on the website along
with the authors' responses. I agree for my report to be made available under an Open
Access Creative Commons CC-BY license
(
http://creativecommons.org/licenses/by/4.0/
). I understand that any comments which I
do not wish to be included in my named report can be included as confidential
comments to the editors, which will not be published.
I agree to the open peer review policy of the journal
Please review this paper.
user
Reviewer’s report
Title: 
Overexpression of P-glycoprotein, MRP2, and CYP3A4 impairs intestinal
absorption of octreotide in rats with portal hypertension
Version: 
1 
Date: 
23 Jun 2019
Reviewer's report:
Sun et al provided revisions of their manuscript. However, there are still some
comments, which should be taken into account to further improove the manuscript:
ad 1a [p3, line 29-30]: please explain why recommendations on use of NSBB for
primary and secondary bleeding prophylaxis are "controversial".
ad 1a [p3, line 36]: "or cannot tolerate the propranolol therapy." -> please use the broad
term "NSBB" instead of "propranolol".
ad 2a [p5, line 9-11]: "to improve the intestinal absoption of OCT, furthermore, to
explore optimized therapeutic strategies for decreasing PH in cirrhotic patients" -> to me
these are no clear aims and do not sound pre-defined.
ad 2b [p5, line 32-43]: The authors cite the Guidelines to Care and Use of Experimental
Animals by the CCAC (https://www.ccac.ca/en/standards/guidelines/general-
guidelines.html). However these guidelines discourage the use of ether (page 135) and
recommend special equipment for the use of inhalation anesthesis (page 134) which still
has not been reported and should be reported. [see
https://www.ccac.ca/Documents/Standards/Guidelines/Experimental_Animals_Vol1.pdf].
This is of special importance when reporting hemodynamic data, which greatly depend
on adaequate anesthesia!
Authors state they tested corneal and pain reflex prior to surgery, which is good.
However this information should be also included in the paper.
The statement "All efforts were made to minimize the number of animals used" is
contradicting with the predefined sample size. I assume the authors took all efforts to
reduce the number of dropouts -> which then would lead to the question wether there
were any drop-outs and how large was their number in the respective groups?
p6, line10-13: ", which was much higher than normal value 10mmHg. It was proved that
the rats developed PH." This text is not only wrong [PH starts at 5mmHg] but also
includes bad English [proved -> proven]. I would thus suggest to omit it, as it adds no
valuable information.
ad 6 [p17, line 36-49] -> Please rephrase in better English. The text is barely
understandable.
p20, line 7-14 -> Please rephrase in better English.
Supplementary Figures showing Western Blots consist of unclear lines. They are not
labelled nor dated and lack a kDa control ladder. Please add this information.
Are the methods appropriate and well described?
If not, please specify what is required in your comments to the authors.
No
Does the work include the necessary controls?
If not, please specify which controls are required in your comments to the authors.
Yes
Are the conclusions drawn adequately supported by the data shown?
If not, please explain in your comments to the authors.
Yes
Are you able to assess any statistics in the manuscript or would you recommend an
additional statistical review?
If an additional statistical review is recommended, please specify what aspects require
further assessment in your comments to the editors.
I am able to assess the statistics
Quality of written English
Please indicate the quality of language in the manuscript:
Not suitable for publication unless extensively edited
Declaration of competing interests
Please complete a declaration of competing interests, considering the following
questions:
1
. 
Have you in the past five years received reimbursements, fees, funding, or salary
from an organisation that may in any way gain or lose financially from the
publication of this manuscript, either now or in the future?
2
. 
Do you hold any stocks or shares in an organisation that may in any way gain or
lose financially from the publication of this manuscript, either now or in the
future?
3
. 
Do you hold or are you currently applying for any patents relating to the content
of the manuscript?
4
. 
Have you received reimbursements, fees, funding, or salary from an organization
that holds or has applied for patents relating to the content of the manuscript?
5
. 
Do you have any other financial competing interests?
6
. 
Do you have any non-financial competing interests in relation to this paper?
If you can answer no to all of the above, write 'I declare that I have no competing
interests' below. If your reply is yes to any, please give details below.
I declare that I have no competing interests
I agree to the open peer review policy of the journal. I understand that my name will be
included on my report to the authors and, if the manuscript is accepted for publication,
my named report including any attachments I upload will be posted on the website along
with the authors' responses. I agree for my report to be made available under an Open
Access Creative Commons CC-BY license
(
http://creativecommons.org/licenses/by/4.0/
). I understand that any comments which I
do not wish to be included in my named report can be included as confidential
comments to the editors, which will not be published.
I agree to the open peer review policy of the journal
assistant