There were 240 males and 80 females in the LT3 group (75% vs 25%); 80 males and 200 females in the SCH group (28,57% vs 71.42%); the average age was 25±7.2 years, and the control group was 25.3±6.6 years old. Compared with the control group, 24hSBP, 24hDBP, insulin resistance-index, blood lipids, etc. increased in all YICH patients, especially nDBP increased significantly, P <0.05. Additionally, calculating the cumulative amount of plastic bags for 10 years, each bag is 1.6 grams, 3000 bags, the total is about 4800g. For every log unit increase in BPA, it is determined that the Z score of the plastic bag increases by 0.204 standard deviation units (P<0.003).(Table 1)
Table 1
Characteristics of the population
variable
|
LT3 (n = 320)
|
SCH (n = 280)
|
Control(n = 300)
|
P value
|
Mean age, (range)
|
25.4± 4.88
|
25.5± 6.29
|
25± 7.285
|
0.39
|
Male, n (%)
|
280 (87.5)※※
|
80 (28.57)
|
300 (50)
|
0.05
|
Married n (%)
|
218 (68.1)
|
165(58..9)
|
300(62.5)
|
0.20
|
BMI (kg/m2)
|
23.7±4.1*
|
23 ± 5.1*
|
21.1 ± 3.3
|
0.05
|
FPG ( mmol/L)
|
5.8 ± 1.24**
|
5.2 ± 0.9*
|
4.8 ± 0.8
|
0.05
|
HOMA-IR, (g/L)
|
3.5 ± 1.2**
|
3.2 ±1.3*
|
2.6 ±1.2
|
0.05
|
24hDBP (mmHg)
|
86.± 18.8**
|
82 ±9.1*
|
69 ±6.3
|
0.01
|
nDBP (mmHg)
|
86 ± 15**
|
82±11*
|
70 ±14
|
0.01
|
TG (mmol/L)
|
1.61 ± 0.8*
|
1.4 ± 0.9
|
1.27 ± 0.9
|
0.05
|
Tch (mmol/L)
|
5.23 ± 1.9**
|
4.8 ± 1.4*
|
3.8 ± 1.4
|
0.01
|
HDL-C (mmol/L)
|
0.98± 0.09*
|
1.1 ± 0.2
|
1.17 ± 0.3
|
0.06
|
LDL-C (mmol/L)
|
3.34 ± 1.1**
|
3.0 ± 0.44*
|
2.7 ± 0.74
|
0.01
|
Drinking history
|
41 (12.8)
|
30 (10.7)
|
37 (9.7)
|
0.06
|
Region,city
|
200(62.5)▲▲
|
200(62.5))▲▲
|
294(61.25)
|
0.37
|
Country
|
120(37.5)
|
80(37.5)
|
186(38.75)
|
0.30
|
Primary school
|
35 (10.9)*
|
18 (6.42)
|
20 (6.6)
|
0.06
|
Secondary School
|
275 (85.9)▲ ▲
|
250 (89.28)▲▲
|
270(90)▲▲
|
035
|
university or higher
|
10 (3.125)*
|
12(4.28)
|
10(3.33)
|
0.37
|
poor
|
20 (6.25)
|
30 (9.38)*
|
16 (5.3)
|
0.17
|
Medium
|
260(81.25.)▲
|
200(71.4)
|
252 (84)
|
0.18
|
well-off
|
40 (12.5)
|
50 (17.85)
|
32 (10.6)
|
0.05
|
Individual
|
230(71.8)▲▲
|
191(68..2)▲▲
|
220(73.3)▲▲
|
0.37
|
Cadre
|
34 (10.6)▲▲
|
33(11.78)▲▲
|
30 (10)▲▲
|
0.41
|
Doctor
|
7 (2.18)
|
6 (2.14)
|
5 (1.66)
|
0.45
|
Teacher
|
12 (3.75)
|
10 (3.57)
|
10 (3.3)
|
0.42
|
Student
|
37 (11.56)
|
40 (14.28)
|
35 (11)
|
0.35
|
Medications n (%)
|
Cytochrome C
|
300 (93.8)
|
276(98.6)
|
----
|
0.25
|
Coenzyme A
|
310 (96.9)
|
266(95)
|
----
|
0.45
|
CBPHI
|
277 (86.6)※※
|
186(66.4)
|
----
|
0.01
|
Glycerol fructose
|
276 (86.3)
|
228(81.4)
|
--
|
0.44
|
Ulinastatin
|
67 (29)※※
|
16 (5)
|
---
|
0.01
|
Naloxone
|
21 (7.5)※※
|
9 (3.2)
|
---
|
0.01
|
*P < 0.05,**P < 0.01. between ICH and controls;※p<0.05,※※p<0.01,between LT3 and SCH;▲P< 0.05,▲▲P < 0.01 . |
ICH patients and the control were divided into two gender subgroups. The BPA level of ICH men increased significantly compared with women and the control, and there was also a difference between women and the control p <0.01 .(Figure 1 )
LT3-male nDBPcv compared with female and control, SCH male, female compared with control group, P<0.01.(Figure 2)
Compared with the female LT3 and the control, the FT3 of the male LT3 was significantly reduced, and the female SCH group TSH was significantly increased compared with the male and the control, P<0.05 .(Figure 3)
There were 600 cases of ICH, and the recent total mortality rate was 74 cases (12.3%). There were 320 cases of LT3 and 50 deaths (15%); 280 cases of SCH and 24 deaths (8.57%). The recent mortality rates of the two groups were compared in 5, 15, and 30 days.15 (4.7) vs 7(2.5),20(6.25) vs 10 (3.75),15(4.68)vs 7(2.5) P<0.01. (Figure 4)
On day 2, serum miR-338-3p significantly increased compared with the control, while miR-445 significantly decreased. P<0.01.(Figure 5)
On day 15 serum miR-338-3p significantly lowed compared with the control,while miR-451 significantly increased.P<0.01.(Figure 6)
Serum miR-338-3p decreased more significantly on day 30 compared with that on day 15 and the control, while miR-451 increased significantly. P<0.01. (Figure 7)
Compared with the control, the levels of serum BPA, various proteases, inflammatory cytokines and miR-338-3p on day 2 of LT3 and SCH increased, miR-455 decreased, and blood pressure parameters increased, P<0.05. The ratio of free testosterone in male patients to the control group was significantly lower P <0.01. In addition, there was no significant difference in serum rT3 and miR-144 levels between the two groups, P≥0.05, omitted. (Table 2)
Table 2
Comparison of serum BPA,biomarkers and BP scores in different gender subgroups.
Paramet
|
LT3
|
SCH
|
Biomarbimarker
|
Male(n=240)
|
Control(n=240)
|
Female(n=80)
|
Control(n=80)
|
Male(n=80)
|
Control(n=80)
|
Female(n=200)
|
Control(n=200)
|
BPA,b BPAng/ml
(2)
|
0.93±0.18**★★☆
|
0.52±0.14
|
0.79±0.14**
|
0.52±0.12
|
0.82±0.11**★
|
0.53±0.10
|
0.70±0.1**
|
0.53±0.1
|
MMP-9,ng/ l
|
109±11**★★ ☆
|
47 ± 8
|
99±9.5**
|
43 ± 6
|
102±8.5**
|
43 ± 6.5
|
96±7.8**
|
43 ± 6.3
|
Thrombin ng/mL
|
1.5±0.5**
|
0.65±0.1
|
1.31±0.49**
|
0.64±0.09
|
1.29±0.23 **
|
0.63±0.1
|
1.29±0.23**
|
0.66±0.12
|
miR-338-3p
|
3.1±0.9**
|
1.2±0.8
|
2.8±0.94**
|
1.23±0.85
|
2.6±0.7**
|
1.2±0.51
|
2.53±0.6**
|
1.18±0.4
|
miR-451
|
2.62±0.17**
|
3.3±0.32
|
2.7±0.2**
|
3.2±0.4
|
2.83±0.2**
|
3.3±0.5
|
2.91±0.14**
|
3.22±0.6
|
TLR-4
|
1.41±0.21**★★☆
|
0.57±0.10
|
1.1±0.2**
|
0.57±0.09
|
1.22±0.2**
|
0.53±0.1
|
1.06±0.13**
|
0.55±0.2
|
MyD88
|
1.13±0.33
**★★☆
|
0.44±0.09
|
1.1±0.25**
|
0.52±0.1
|
0.92±0.1
**
|
0.49±0.1
|
0.90±0.13
**
|
0.45±0.1
|
TRAF6
|
1.64±0.41
**★★☆
|
0.34±0.10
|
1.45±0.50
**★★☆
|
0.33±0.09
|
1.42±0.44
**★★☆
|
0.36±0.098
|
1.37±0.40
**★★☆
|
0.35±0.09
|
NF-kBP 65
|
1.21±0.2**★★☆
|
0.51±0.10
|
1.08±0.2**
|
0.50±0.08
|
1.0±0.2**
|
0.48±0.1
|
0.86±0.1**
|
0.50±0.2
|
FT3,pg/ml
|
0.74±0.2**☆☆
|
4.8± 0.8
|
0.86±0.5**☆
|
4.8±0.9
|
4.17±0.7
|
4.33±0.6
|
4.2±0.5
|
4.8± 1.0
|
FT4,pmol/l
|
24± 7.2
|
30 ± 9.2
|
26± 9.0
|
31 ± 9.2
|
28 ± 8.6
|
28.5 ± 6.1
|
26±12.2
|
31± 9
|
T3, nmol/l
|
1.67 ± 1.0
|
2.0± 0.6
|
1.65 ± 0.9
|
2.0± 0.6
|
2.1 ± 0.5
|
2.2± 0.4
|
1.69 ± 1.0
|
2.1± 0.7
|
T4, nmol/l
|
66 ± 19.7*
|
85±11.4
|
68 ± 17.7*
|
85±12
|
78± 10.7
|
86±14
|
79± 19
|
85±11
|
TSH,µIU/ml
|
3.6 ± 0.4
|
3.7± 0.7
|
3.8 ± 0.6
|
3.7± 0.9
|
12.9±2.18**
|
3.91± 0.9
|
9.6±0.7**
|
3.7± 0.5
|
FT(nmol/L)
|
0.13±0.0※※
|
021±0.05
|
0.20±0.06
|
0.21±0.05
|
0.15±0.05*
|
0.20±0.5
|
0.19±0.02
|
021±0.04
|
TT(nmol/L)
|
4.9±1.5**
|
17±4.6
|
16±4.2
|
17±4.6
|
7±1.4*
|
16±3.5
|
15±4.5
|
17±4.6
|
24hDBPCV
|
0.17(0.12-0.19)**
|
0.11(0.08-0.12)
|
0.16(0.12-0.19)**
|
0.10(0.08-0.11)
|
0.14(0.07-0.15)*
|
0.09(0.06-0.10)
|
0.13(0.1-0.16)*
|
0.09(0.07-0.11)
|
nDBPCV
|
0.16(0.09-0.19)**★☆
|
0.05(0.02-0.08)
|
0.14(0.08-0.17)**
|
0.05(0.02-007)
|
0.13(0.07-0.5)**
|
0.04(0.02-0.06)
|
0.11(0.06-0.14)**
|
0.04(0.02-0.05)
|
5 days,n %
Death rate
|
6 ( 1.875)★★☆☆
|
-
|
3 (0.937)
|
-
|
3 (1.07)
|
-
|
2(0.714)
|
-
|
*P < 0.05; **P < 0.01. between ICH and controls;★p<0.05,★★p<0.01; between male and female;☆p<0.05,☆☆p<0.01; between LT3 and SCH. |
Compared with the control, the serum BPA and protease in the LT3 and SCH groups at 15 and 30 days tended to decrease; on the contrary, the level of miR-338-3p decreased, the level of miR-455 increased, and the blood pressure parameters increased. In particular, nDBPCV was more Obviously, P <0.01. (Table 3)
Table 3
Comparison of serum bisphenol A, biomarkers and death rate in different subgroups.
15 day
|
LT3
|
SCH
|
Bioma bi biomarer
|
Male
(n=240)
|
Control
(n=240)
|
Female
(n=80)
|
Control
(n=80)
|
Male
(n=80)
|
Control
(n=80)
|
Female
(n=200)
|
Control
(n=200)
|
BPA,b BPAng/ml
(2)
|
0.89±0.15**★★
|
0.52±0.14
|
0.74±0.11**
|
0.52±0.12
|
0.78±0.1**
|
0.53±0.10
|
0.70±0.12**
|
0.53±0.1
|
MiR-338-3p
|
1.7±0.37*
|
1.21±0.2
|
1.41±0.59*
|
1.22±0.55
|
1.25±0.56
|
1.22±0.49
|
1.22±0.46
|
1.21±0.49
|
MiR-451
|
3.4±0.19*
|
3.25±0.31
|
3.6±0.19*
|
3.3±0.3
|
3.5±0.19
|
3.24±0.32
|
3.45±0.19
|
3.3±0.30
|
Death rate
n, %
|
4(1.25)★★
|
-
|
2 (0.625)☆☆
|
-
|
3 (1.07)★★
|
-
|
1(0.357)
|
-
|
30 days
|
BPA,b BPAng/ml
(2)
|
0.89±0.14**★★
|
0.52±0.12
|
0.70±0.10**
|
0.52±0.11
|
0.73±0.12**
|
0.53±0.10
|
0.66±0.10**
|
0.53±0.1
|
MiR-338-3p
|
1.42±0.3*
|
1.21±0.2
|
1.28±0.59*
|
1.23±0.55
|
1.24±0.56
|
1.22±0.49
|
1.217±0.4
|
1.21±0.42
|
MiR-451
|
3.6±0.19
|
3.28±0.27
|
3.7±0.18
|
3.26±0.31
|
3.8±0.19
|
3.24±0.34
|
3.9±0.19
|
3.3±0.35
|
Death rate
n, %
|
20 (6.25)★★☆☆
|
-
|
8 (1.56)
|
-
|
7 (2.5)
|
-
|
6 (2.14)
|
-
|
*P < 0.05; **P < 0.01. between ICH and controls;★p<0.05,★★p<0.01; between male and female;☆p<0.05,☆☆p
<0.01; between LT3 and SCH.
Serum BPA is positively correlated with biomarker, 24hDBPCV, and was negatively correlated LT3 and niR-451.(Table 4)
The increase of nSBP and nDBP were used as dependent variables, and age, gender, BMI and BPA were used as independent variables. The results of multiple linear regression showed that cumulative BPA exposure was an independent factor affecting of nSBP and nDBP.(Table 5)
The relationship between BPA, thrombin and miRNA expression risk factors: draw a BPA ROS curve, the area under the curve is 0.744 (95% CI 0.624-0.894), the maximum Uden index is 0.426, the sensitivity is 75.4%, and the specificity is 67.4%, corresponding to a cut-off value of 1.567. Adjusting for confounding factors such as gender, age, and marital status, the risk of BPA in ICH patients is 5.12 times that of the general population. (Table 6)
Table 4
Linear correlation analysis of serum BPA,ABP and biomarkers in YICH.
Variables
|
Rvalue
|
Pvalue
|
Variables
|
R value
|
P value
|
BPA
|
and
|
YAP
|
-0.61
|
<0.01
|
CX43
|
and
|
TSH(in female)
|
0.52
|
<0.01
|
BPA
|
and
|
miR-451
|
-052
|
<0.01
|
CX43
|
and
|
NFκB65
|
0.55
|
<0.01
|
BPA
|
and
|
miR-388-3p
|
0.46
|
<0.01
|
MMP-9
|
and
|
FT(in male)
|
-0.45
|
<0.01
|
BPA
|
and
|
FT3
|
-0.51
|
<0.01
|
BPA
|
and
|
24hDBPCV
|
0.48
|
<0.01
|
Table 5
Multiple linear regression analysis of nSBP and nDBP increase (n=600)
D variable I variable B SE β t value P value
|
nSBP
|
constant
|
16.432
|
1.939
|
----
|
7.482
|
< 0.01
|
|
BPA
|
1.935
|
0.448
|
0.229
|
3.452
|
< 0.05
|
nDBP
|
constant
|
18.449
|
2.439
|
----
|
8.442
|
< 0.01
|
|
BPA
|
2.335
|
0.398
|
0.286
|
4.452
|
< 0.01
|
Table 6
Logistic regression analysis of serum bisphenol A level,blood lipid and risk factors (n=280 )
Independent variable B SE X2 value P value OR 95%CI
|
BPA
|
2.86
|
0.613
|
9.89
|
0.003
|
7.413 (0.624-0.931)
|
Thrombin
|
2.41
|
0.514
|
8.99
|
0.002
|
5.114(0.891-1.614)
|
miR-338-3p
|
1.618
|
0.412
|
12.007
|
0.001
|
4.170 (1.861-9.431)
|
BMI stratification normal
|
|
Thin
|
-0.214
|
0.891
|
0.059
|
0.124
|
6.784 (0.129-4.718)
|
Overweight, obese
|
1.090
|
0.412
|
6.410
|
0.011
|
2.803 ( 1.247-6.313)
|
Insulin resistance index
|
1.214
|
0.539
|
7.140
|
0.009
|
3.143 (1.349-8.726 )
|
High triglycerides
|
1.225
|
0.397
|
5.765
|
0.02
|
2.56 (1.19-4.976)
|
High Tch
|
1.231
|
0.497
|
6.476
|
0.01
|
2.948 (1.241-5.736)
|
Increase BPA levels (none = 0, yes = 1) and miR-451 (none = 0, yes = 1), nDBPCV (none = 0, yes = 1), binding and interaction analysis. The results of the cross-health analysis showed that after adjusting for factors such as gender, age, and marital status. Nocturnal hypertension and the low expression of miR144/451 and the presence of elevated serum BPA are significantly different from the BPA levels of patients with non-nocturnal hypertension, and there is a risk of ICH. The results of interaction analysis showed that there is a multiplicative and additive interaction between whether serum BPA is related to nocturnal hypertension (U = 4.19, P <0.05) and whether miR-451 is under-expressed (U = 6.16, P <0.05)(Table 7)
Table 7
Effect of BPA level on the coefficient of variation of night blood pressure (n=280)
-BPA miR-451 nDBPCV NBP OR MI AI
(n) (n) (n) (95%CI)
|
No
|
No
|
No
|
240
|
1.947(0.175-29.987)
|
0.0134
|
RERI:3.12(0.912-3.123)
|
No
|
No
|
No
|
1
|
0.765 (0.32-0.915
|
|
AP:5.13 ( 0.723-1.346)
|
Yes
|
160
|
240
|
0
|
4.997(1.845-9.365)
|
|
S:1.715(0.541-15.57)
|
Yes
|
140
|
240
|
0
|
19.778(1.879-245.667)
|
|
|